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Sample records for ectosylvian sulcus siv

  1. Corticothalamic and corticotectal somatosensory projections from the anterior ectosylvian sulcus (SIV cortex) in neonatal cats: an anatomical demonstration with HRP and 3H-leucine

    International Nuclear Information System (INIS)

    McHaffie, J.G.; Kruger, L.; Clemo, H.R.; Stein, B.E.

    1988-01-01

    Corticothalamic and corticotectal projections from the anterior ectosylvian sulcus (AES) in neonatal cats were studied with anterograde and retrograde neuroanatomical techniques. When the injection site was relatively restricted to the sulcal walls and fundus of the rostral AES (i.e., the SIV cortex), heavy ipsilateral thalamic label was observed in the medial subdivision of the posterior group, in the suprageniculate nucleus, and in the external medullary lamina. No terminal label was seen in the contralateral thalamus although the contralateral homotopic cortex was heavily labeled. Within the ventrobasal complex (VB), dense axonal label was observed in fascicles that traversed VB, but only light terminal label was observed within VB itself. However, in cases where the tracer spread into adjacent SII, terminal label in VB was pronounced. Similarly, when the injection site extended into auditory cortex, terminal label was observed in the lateral and intermediate subdivisions of the posterior group. Rostral AES injections produced distinct, predominantly ipsilateral, terminal label in the superior colliculus that was distributed in two tiers: a discontinuous band in the stratum griseum intermedium and a more diffuse band in stratum griseum profundum. Caudally, dense terminal label was seen in the intercollicular zone and dorsolateral periaqueductal gray. When the injection site did not include rostral AES, no label was observed in the superior colliculus. Horseradish peroxidase injections into the superior colliculus of neonates produced retrogradely labeled neurons throughout the AES, but none was found on the crown of the gyrus where SII is located. Thus, the neonatal corticotectal somatosensory projection arises exclusively from AES and parallels that found in adults

  2. The Earthquake‐Source Inversion Validation (SIV) Project

    KAUST Repository

    Mai, Paul Martin

    2016-04-27

    Finite-fault earthquake source inversions infer the (time-dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, multiple source models for the same earthquake, obtained by different research teams, often exhibit remarkable dissimilarities. To address the uncertainties in earthquake-source inversion methods and to understand strengths and weaknesses of the various approaches used, the Source Inversion Validation (SIV) project conducts a set of forward-modeling exercises and inversion benchmarks. In this article, we describe the SIV strategy, the initial benchmarks, and current SIV results. Furthermore, we apply statistical tools for quantitative waveform comparison and for investigating source-model (dis)similarities that enable us to rank the solutions, and to identify particularly promising source inversion approaches. All SIV exercises (with related data and descriptions) and statistical comparison tools are available via an online collaboration platform, and we encourage source modelers to use the SIV benchmarks for developing and testing new methods. We envision that the SIV efforts will lead to new developments for tackling the earthquake-source imaging problem.

  3. The Earthquake‐Source Inversion Validation (SIV) Project

    KAUST Repository

    Mai, Paul Martin; Schorlemmer, Danijel; Page, Morgan; Ampuero, Jean‐Paul; Asano, Kimiyuki; Causse, Mathieu; Custodio, Susana; Fan, Wenyuan; Festa, Gaetano; Galis, Martin; Gallovic, Frantisek; Imperatori, Walter; Kä ser, Martin; Malytskyy, Dmytro; Okuwaki, Ryo; Pollitz, Fred; Passone, Luca; Razafindrakoto, Hoby; Sekiguchi, Haruko; Song, Seok Goo; Somala, Surendra N.; Thingbaijam, Kiran Kumar; Twardzik, Cedric; van Driel, Martin; Vyas, Jagdish Chandra; Wang, Rongjiang; Yagi, Yuji; Zielke, Olaf

    2016-01-01

    Finite-fault earthquake source inversions infer the (time-dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, multiple source models for the same earthquake, obtained by different research teams, often exhibit remarkable dissimilarities. To address the uncertainties in earthquake-source inversion methods and to understand strengths and weaknesses of the various approaches used, the Source Inversion Validation (SIV) project conducts a set of forward-modeling exercises and inversion benchmarks. In this article, we describe the SIV strategy, the initial benchmarks, and current SIV results. Furthermore, we apply statistical tools for quantitative waveform comparison and for investigating source-model (dis)similarities that enable us to rank the solutions, and to identify particularly promising source inversion approaches. All SIV exercises (with related data and descriptions) and statistical comparison tools are available via an online collaboration platform, and we encourage source modelers to use the SIV benchmarks for developing and testing new methods. We envision that the SIV efforts will lead to new developments for tackling the earthquake-source imaging problem.

  4. The Earthquake‐Source Inversion Validation (SIV) Project

    Science.gov (United States)

    Mai, P. Martin; Schorlemmer, Danijel; Page, Morgan T.; Ampuero, Jean-Paul; Asano, Kimiyuki; Causse, Mathieu; Custodio, Susana; Fan, Wenyuan; Festa, Gaetano; Galis, Martin; Gallovic, Frantisek; Imperatori, Walter; Käser, Martin; Malytskyy, Dmytro; Okuwaki, Ryo; Pollitz, Fred; Passone, Luca; Razafindrakoto, Hoby N. T.; Sekiguchi, Haruko; Song, Seok Goo; Somala, Surendra N.; Thingbaijam, Kiran K. S.; Twardzik, Cedric; van Driel, Martin; Vyas, Jagdish C.; Wang, Rongjiang; Yagi, Yuji; Zielke, Olaf

    2016-01-01

    Finite‐fault earthquake source inversions infer the (time‐dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, multiple source models for the same earthquake, obtained by different research teams, often exhibit remarkable dissimilarities. To address the uncertainties in earthquake‐source inversion methods and to understand strengths and weaknesses of the various approaches used, the Source Inversion Validation (SIV) project conducts a set of forward‐modeling exercises and inversion benchmarks. In this article, we describe the SIV strategy, the initial benchmarks, and current SIV results. Furthermore, we apply statistical tools for quantitative waveform comparison and for investigating source‐model (dis)similarities that enable us to rank the solutions, and to identify particularly promising source inversion approaches. All SIV exercises (with related data and descriptions) and statistical comparison tools are available via an online collaboration platform, and we encourage source modelers to use the SIV benchmarks for developing and testing new methods. We envision that the SIV efforts will lead to new developments for tackling the earthquake‐source imaging problem.

  5. Stability of the Gorilla Microbiome Despite SIV Infection

    OpenAIRE

    Moeller, Andrew H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H.; Ochman, Howard

    2015-01-01

    Simian Immunodeficiency Viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in fecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. He...

  6. Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines.

    NARCIS (Netherlands)

    J.L. Heeney (Jonathan); P. de Vries (Petra); R. Dubbes (Rob); W. Koornstra (Willem); H. Niphuis; P. ten Haaft (Peter); J. Boes (Jolande); M.E.M. Dings (Marlinda); B. Morein (Bror); A.D.M.E. Osterhaus (Albert)

    1992-01-01

    textabstractThis study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8)

  7. Visualisation of Rouviere's Sulcus during Laparoscopic Cholecystectomy.

    Science.gov (United States)

    Thapa, P B; Maharjan, D K; Tamang, T Y; Shrestha, S K

    2015-01-01

    Safe dissection of Calot's Triangle is important during the performance of laparascopic cholucystectomy. The purpose of the study is to determine the frequency of demonstrable Rouviere's sulcus in patients with symptomatic gall stones and its role in safe dissection in Calot's triangle. This is a prospective descriptive study design done in Department of surgery, Kathmandu Medical College Teaching Hospital from Jan 2013 to Jan 2015. Patients who were posted for laparoscopic cholecystectomy were included. During laparoscopy, Rouviere's sulcus was noted in the operative note and classified according to following: Type I: Open type was defined as a cleft in which the right hepatic pedicle was visualized and the sulcus was opened throughout its length. Type II: if the sulcus was open only at its lateral end. Type III If the sulcus was open only at its medial end. Type IV: Fused type was defined as one in which the pedicle was not visualized.  A total of 200 patients underwent laparoscopic cholecystectomy during period of 2 years. Out of which Rouviere's sulcus was visualized in 150 patients (75 %).Type I (open type) was commoner in 54%, type II in 12%, Type III in 9% and type IV (fused type) in 25%. Rouviere's Sulcus is an important extra biliary land mark for safe dissection of Calot's triangle during laparoscopic cholecystectomy.  Rouviere's Sulcus, Laparoscopic cholecystectomy, Bile duct injury.

  8. Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Emily R Roberts

    2016-12-01

    Full Text Available Poor maintenance of cytotoxic factor expression among HIV-specific CD8+ T cells, in part caused by dysregulated expression of the transcription factor T-bet, is associated with HIV disease progression. However, the precise evolution and context in which CD8+ T cell cytotoxic functions become dysregulated in HIV infection remain unclear. Using the rhesus macaque (RM SIV infection model, we evaluated the kinetics of SIV-specific CD8+ T cell cytolytic factor expression in peripheral blood, lymph node, spleen, and gut mucosa from early acute infection through chronic infection. We identified rapid acquisition of perforin and granzyme B expression in SIV-specific CD8+ T cells in blood, secondary lymphoid tissues and gut mucosa that collapsed rapidly during the transition to chronic infection. The evolution of this expression profile was linked to low expression of T-bet and occurred independent of epitope specificity, viral escape patterns and tissue origin. Importantly, during acute infection SIV-specific CD8+ T cells that maintained T-bet expression retained the ability to express granzyme B after stimulation, but this relationship was lost in chronic infection. Together, these data demonstrate the loss of cytolytic machinery in SIV-specific CD8+ T cells in blood and at tissue sites of viral reservoir and active replication during the transition from acute to chronic infection. This phenomenon occurs despite persistent high levels of viremia suggesting that an inability to maintain properly regulated cytotoxic T cell responses in all tissue sites enables HIV/SIV to avoid immune clearance, establish persistent viral reservoirs in lymphoid tissues and gut mucosa, and lead ultimately to immunopathogenesis and death.

  9. Useful signs for identification of the central sulcus in MRI

    International Nuclear Information System (INIS)

    Carrasco, E.; Domitrovic, L.; Ypa, P.; Gandarillas Baldelomar, B.; Fuentes, F.; Arcos, A.

    2011-01-01

    Objective. To describe the frequency of appearance of the central sulcus localizing signs in magnetic resonance images (MRI). Material and method. The MRI of 60 adult patients (18-83 years) of both sexes (34 women / 26 men) with normal brains were studied. Axial T1 and T2 images were performed on a Phillips 1.5 tesla resonator. On the MRI we looked the following signs: union between the superior frontal sulcus and the precentral sulcus, sigmoidal hook, pars bracket, bifid post central sulcus, union between the intraparietal sulcus and the post central sulcus and, central sulcus reaching the midline. Mean frequencies were calculated. Results. The posterior part of the superior frontal sulcus joined the precentral sulcus in 95% of the cases. Sigmoidal hook sign was seen in 96.66% of the cases. Pars bracket sign was present in 95% of the observations. Bifid postcentral sulcus sign was seen in 65 % of cases. The postcentral gyrus was thinner than the precentral gyrus in 98.33% of the cases. Intraparietal sulcus joined with the postcentral gyrus in 88.33% of the cases. The central sulcus reached the midline in 86.66% of the observations. Conclusion. The signs described had a high frequency: they were found in 89.28% of the MRI studied. (authors)

  10. Visualisation of Rouviere’s Sulcus during Laparoscopic Cholecystectomy

    Directory of Open Access Journals (Sweden)

    Prabin Bikram Thapa

    2015-09-01

    Full Text Available Introduction: Safe dissection of Calot’s Triangle is important during the performance of laparascopic cholucystectomy. The purpose of the study is to determine the frequency of demonstrable Rouviere’s sulcus in patients with symptomatic gall stones and its role in safe dissection in Calot’s triangle. Methods: This is a prospective descriptive study design done in Department of surgery, Kathmandu Medical College Teaching Hospital from Jan 2013 to Jan 2015. Patients who were posted for laparoscopic cholecystectomy were included. During laparoscopy, Rouviere’s sulcus was noted in the operative note and classified according to following: Type I: Open type was defined as a cleft in which the right hepatic pedicle was visualized and the sulcus was opened throughout its length. Type II: if the sulcus was open only at its lateral end. Type III If the sulcus was open only at its medial end. Type IV: Fused type was defined as one in which the pedicle was not visualized. Results: A total of 200 patients underwent laparoscopic cholecystectomy during period of 2 years. Out of which Rouviere’s sulcus was visualized in 150 patients (75 %.Type I (open type was commoner in 54%, type II in 12%, Type III in 9% and type IV (fused type in 25%. Conclusions: Rouviere’s Sulcus is an important extra biliary land mark for safe dissection of Calot’s triangle during laparoscopic cholecystectomy. Keywords: Rouviere’s Sulcus, laparoscopic cholecystectomy, bile duct injury.

  11. Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Hongzhao Li

    Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

  12. Stability of the Gorilla Microbiome Despite SIV Infection

    Science.gov (United States)

    Moeller, Andrew H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H.; Ochman, Howard

    2015-01-01

    Simian Immunodeficiency Viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in fecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1 infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune-system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority. PMID:25545295

  13. Enhanced cellular immune response against SIV Gag induced by immunization with DNA vaccines expressing assembly and release-defective SIV Gag proteins

    International Nuclear Information System (INIS)

    Bu Zhigao; Ye Ling; Compans, Richard W.; Yang Chinglai

    2003-01-01

    Codon-optimized genes were synthesized for the SIVmac239 Gag, a mutant Gag with mutations in the major homology region, and a chimeric Gag containing a protein destruction signal at the N-terminus of Gag. The mutant and chimeric Gag were expressed at levels comparable to that observed for the wild-type Gag protein but their stability and release into the medium were found to be significantly reduced. Immunization of mice with DNA vectors encoding the mutant or chimeric Gag induced fourfold higher levels of anti-SIV Gag CD4 T cell responses than the DNA vector encoding the wild-type SIV Gag. Moreover, anti-SIV Gag CD8 T cell responses induced by DNA vectors encoding the mutant or chimeric Gag were found to be 5- to 10-fold higher than those induced by the DNA construct for the wild-type Gag. These results indicate that mutations disrupting assembly and/or stability of the SIV Gag protein effectively enhance its immunogenicity when expressed from DNA vaccines

  14. HIV/SIV infection primes monocytes and dendritic cells for apoptosis.

    Directory of Open Access Journals (Sweden)

    Mireille Laforge

    2011-06-01

    Full Text Available Subversion or exacerbation of antigen-presenting cells (APC death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs. We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14(+ from SIV(+RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV(+RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV(+RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection.

  15. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A; Mangus, Lisa M; Abreu, Celina M; Gama, Lucio; Witwer, Kenneth W; Adams, Robert J; Zink, M Christine; Clements, Janice E; Mankowski, Joseph L

    2018-04-01

    Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

  16. The Earthquake Source Inversion Validation (SIV) - Project: Summary, Status, Outlook

    Science.gov (United States)

    Mai, P. M.

    2017-12-01

    Finite-fault earthquake source inversions infer the (time-dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, this kinematic source inversion is ill-posed and returns non-unique solutions, as seen for instance in multiple source models for the same earthquake, obtained by different research teams, that often exhibit remarkable dissimilarities. To address the uncertainties in earthquake-source inversions and to understand strengths and weaknesses of various methods, the Source Inversion Validation (SIV) project developed a set of forward-modeling exercises and inversion benchmarks. Several research teams then use these validation exercises to test their codes and methods, but also to develop and benchmark new approaches. In this presentation I will summarize the SIV strategy, the existing benchmark exercises and corresponding results. Using various waveform-misfit criteria and newly developed statistical comparison tools to quantify source-model (dis)similarities, the SIV platforms is able to rank solutions and identify particularly promising source inversion approaches. Existing SIV exercises (with related data and descriptions) and all computational tools remain available via the open online collaboration platform; additional exercises and benchmark tests will be uploaded once they are fully developed. I encourage source modelers to use the SIV benchmarks for developing and testing new methods. The SIV efforts have already led to several promising new techniques for tackling the earthquake-source imaging problem. I expect that future SIV benchmarks will provide further innovations and insights into earthquake source kinematics that will ultimately help to better understand the dynamics of the rupture process.

  17. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

    Directory of Open Access Journals (Sweden)

    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  18. Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

    International Nuclear Information System (INIS)

    Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

    2013-01-01

    Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication

  19. Simian Immunodeficiency Virus (SIV-Specific Chimeric Antigen Receptor-T Cells Engineered to Target B Cell Follicles and Suppress SIV Replication

    Directory of Open Access Journals (Sweden)

    Kumudhini Preethi Haran

    2018-03-01

    Full Text Available There is a need to develop improved methods to treat and potentially cure HIV infection. During chronic HIV infection, replication is concentrated within T follicular helper cells (Tfh located within B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated levels of simian immunodeficiency virus (SIV-specific CTL in B cell follicles are linked to both decreased levels of viral replication in follicles and decreased plasma viral loads. These findings provide the rationale to develop a strategy for targeting follicular viral-producing (Tfh cells using antiviral chimeric antigen receptor (CAR T cells co-expressing the follicular homing chemokine receptor CXCR5. We hypothesize that antiviral CAR/CXCR5-expressing T cells, when infused into an SIV-infected animal or an HIV-infected individual, will home to B cell follicles, suppress viral replication, and lead to long-term durable remission of SIV and HIV. To begin to test this hypothesis, we engineered gammaretroviral transduction vectors for co-expression of a bispecific anti-SIV CAR and rhesus macaque CXCR5. Viral suppression by CAR/CXCR5-transduced T cells was measured in vitro, and CXCR5-mediated migration was evaluated using both an in vitro transwell migration assay, as well as a novel ex vivo tissue migration assay. The functionality of the CAR/CXCR5 T cells was demonstrated through their potent suppression of SIVmac239 and SIVE660 replication in in vitro and migration to the ligand CXCL13 in vitro, and concentration in B cell follicles in tissues ex vivo. These novel antiviral immunotherapy products have the potential to provide long-term durable remission (functional cure of HIV and SIV infections.

  20. Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

    Science.gov (United States)

    Malkevitch, Nina V; Patterson, L Jean; Aldrich, M Kristine; Wu, Yichen; Venzon, David; Florese, Ruth H; Kalyanaraman, V S; Pal, Ranajit; Lee, Eun Mi; Zhao, Jun; Cristillo, Anthony; Robert-Guroff, Marjorie

    2006-09-15

    Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained protection against re-challenge.

  1. Loading the Saturn I S-IV Stage into Pregnant Guppy

    Science.gov (United States)

    1965-01-01

    The photograph shows the loading operation of the Saturn I S-IV stage (second stage) into the Pregnant Guppy at the Redstone Airfield, Huntsville, Alabama. The Pregnant Guppy was a Boeing B-377 Stratocruiser modified to transport various stages of Saturn launch vehicles. The modification project called for lengthening the fuselage to accommodate the S-IV stage. After the flight test of that modification, phase two called for the enlargement of the plane's cabin section to approximately double its normal volume. The fuselage separated just aft of the wing's trailing edge to load and unload the S-IV and other cargoes.

  2. Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication.

    Science.gov (United States)

    Pallikkuth, Suresh; Mohan, Mahesh

    2015-12-01

    This commentary highlights new findings from a recent study identifying adipose tissue as a potential HIV reservoir and a major site of inflammation during chronic human/simian immunodeficiency virus (HIV/SIV) infection. A concise discussion about upcoming challenges and new research avenues for reducing chronic adipose inflammation during HIV/SIV infection is presented. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Deep and shallow forms of the sulcus for extensor carpi ulnaris.

    OpenAIRE

    Nakashima, T; Hojo, T; Furukawa, H

    1993-01-01

    Anatomical variations in the sulcus for the tendon of extensor carpi ulnaris were studied in 240 upper limbs. The sulcus lies between the head and the styloid process on the dorsal surface of the distal end of the ulna. This groove has deep and shallow forms and, rarely, a flat form. The sulcus was classified into 4 grades according to its depth. Grade I, a deep sulcus, was found in 51.3%. Grades II and III are shallow, but the styloid process in grade II is more prominent than in grade III. ...

  4. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

    Directory of Open Access Journals (Sweden)

    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  5. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

    Directory of Open Access Journals (Sweden)

    Kevin R McCarthy

    Full Text Available In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm. Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac and pig-tailed macaques (SIVmne have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

  6. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

    Science.gov (United States)

    McCarthy, Kevin R; Johnson, Welkin E; Kirmaier, Andrea

    2016-01-01

    In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV) from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm). Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac) and pig-tailed macaques (SIVmne) have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa) were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

  7. Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication.

    Science.gov (United States)

    McBrien, Julia Bergild; Kumar, Nitasha A; Silvestri, Guido

    2018-02-10

    In this article, we summarize the role of CD8 + T cells during natural and antiretroviral therapy (ART)-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8 + T cell-based HIV cure strategies. Evidence suggests that CD8 + T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8 + T cells is responsible for control of viremia. However, it has been proposed that CD8 + T cells also use non-cytolytic mechanisms to control SIV infection. More recently, CD8 + T cells were shown to be required to fully suppress virus production in ART-treated SIV-infected macaques, suggesting that CD8 + T cells are involved in the control of virus transcription in latently infected cells that persist under ART. A better understanding of the complex antiviral activities of CD8 + T cells during HIV/SIV infection will pave the way for immune interventions aimed at harnessing these functions to target the HIV reservoir. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Sensitive method for the determination of different S(IV) species in cloud and fog water.

    Science.gov (United States)

    Lammel, G

    1996-08-01

    Suppressed ion chromatography has been applied to the determination of S(IV) species in cloud and fog water in the range 0.012-2.4 mg S(IV)-S/L. The samples have been preserved prior to storage and S(IV) species have been determined as hydroxy methanesulfonate (HMS) together with the low molecular weight carboxylic acid anions, formate and acetate. Samples have been divided and treated differently such that total S(IV) as well as the non-oxidizable fraction of S(IV) (as given by the reactivity with H(2)O(2), added in surplus) could be determined. The difference between the two corresponds to the S(IV) fraction subjected to oxididation, which is of paramount interest in cloud and fogwater chemistry.

  9. Effect of voice therapy in sulcus vocalis: A single case study

    Directory of Open Access Journals (Sweden)

    R. Rajasudhakar

    2016-02-01

    Full Text Available Background: Sulcus vocalis is a structural deformity of the vocal ligament. It is the focal invagination of the epithelium deeply attaching to the vocal ligament. There is a dearth of literature on the outcome of voice therapy in sulcus vocalis condition.Objective: The primary objective of this study was to document voice characteristics of sulcus vocalis and the secondary objective was to establish the efficacy of voice therapy in a patient with sulcus vocalis.Method: A trial of voice therapy was given to the client who was diagnosed as having sulcus vocalis. Boon’s facilitation techniques were used in voice therapy along with other techniques such as breath holding and push and pull approach prior to surgery. Acoustic, aerodynamic, perceptual, quantitative measures of voice quality and self-rating measurements were performed before and after voice therapy.Results: Improvement was noticed in 10/10 acoustic, 4/4 aerodynamic, perceptual, dysphonia severity index and voice handicap index scores, which hinted that voice therapy can be an option critically for clients with sulcus vocalis in the initial stage.Conclusion: Voice therapy showed promising improvement in the study and it must be recommended as the initial treatment option before any surgical management.

  10. Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

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    Félicien Moukambi

    2015-12-01

    Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

  11. Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge.

    Science.gov (United States)

    Demberg, Thorsten; Boyer, Jean D; Malkevich, Nina; Patterson, L Jean; Venzon, David; Summers, Ebonita L; Kalisz, Irene; Kalyanaraman, V S; Lee, Eun Mi; Weiner, David B; Robert-Guroff, Marjorie

    2008-11-01

    Previously, combination DNA/nonreplicating adenovirus (Ad)- or poxvirus-vectored vaccines have strongly protected against SHIV(89.6P), DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components. Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA. After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein. Four control macaques received control DNA plasmids, empty Ad vector, and adjuvant. All vaccine components were immunogenic, but the cytokine DNAs had little effect. Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group. Other immune responses were indistinguishable between groups. Overall, no protection against intrarectal challenge with SIV(mac251) was observed, although immunized non-Mamu-A*01 macaques as a group exhibited a statistically significant 1-log decline in acute viremia compared to non-Mamu-A*01 controls. Possible factors contributing to the poor outcome include administration of cytokine DNAs to sites different from the Ad recombinants (intramuscular and intratracheal, respectively), too few DNA priming immunizations, a suboptimal DNA delivery method, failure to ensure delivery of SIV and cytokine plasmids to the same cell, and instability and short half-life of the IL-15 component. Future experiments should address these issues to determine if this combination approach is able to control a virulent SIV challenge.

  12. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

    International Nuclear Information System (INIS)

    Devitt, Gerard; Emerson, Vanessa; Holtkotte, Denise; Pfeiffer, Tanya; Pisch, Thorsten; Bosch, Valerie

    2007-01-01

    Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767 stop , which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752 N750K ) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752 N750K exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses

  13. High-throughput profiling of anti-glycan humoral responses to SIV vaccination and challenge.

    Directory of Open Access Journals (Sweden)

    Christopher T Campbell

    Full Text Available Recent progress toward an HIV vaccine highlights both the potential of vaccines to end the AIDS pandemic and the need to boost efficacy by incorporating additional vaccine strategies. Although many aspects of the immune response can contribute to vaccine efficacy, the key factors have not been defined fully yet. A particular area that may yield new insights is anti-glycan immune responses, such as those against the glycan shield that HIV uses to evade the immune system. In this study, we used glycan microarray technology to evaluate anti-glycan antibody responses induced by SIV vaccination and infection in a non-human primate model of HIV infection. This comprehensive profiling of circulating anti-glycan antibodies found changes in anti-glycan antibody levels after both vaccination with the Ad5hr-SIV vaccine and SIV infection. Notably, SIV infection produced generalized declines in anti-glycan IgM antibodies in a number of animals. Additionally, some infected animals generated antibodies to the Tn antigen, which is a cryptic tumor-associated antigen exposed by premature termination of O-linked glycans; however, the Ad5hr-SIV vaccine did not induce anti-Tn IgG antibodies. Overall, this study demonstrates the potential contributions that glycan microarrays can make for HIV vaccine development.

  14. SULCUS TEMPERATURE DISTRIBUTIONS IN THE ABSENCE AND PRESENCE OF ORAL HYGIENE

    NARCIS (Netherlands)

    PERDOK, JF; LUKACOVIC, M; MAJETI, S; ARENDS, J; BUSSCHER, HJ

    In this study we investigated the possibility of using sulcus temperature measurements as an early indicator for the beginning of gingival inflammation. Sulcus temperature distributions over the arches appeared to obey a quadratic polynomial. With a test group of 10 volunteers, all dental students,

  15. Low dose rectal inoculation of rhesus macaques by SIV SME660 or SIV MAC251 recapitulates human mucosal infection by HIV-1

    Energy Technology Data Exchange (ETDEWEB)

    Koraber, Bette [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory; Hraber, Peter [Los Alamos National Laboratory; Giorgi, E [Los Alamos National Laboratory; Bhattacharya, T [Los Alamos National Laboratory

    2009-01-01

    Recently, we developed a novel approach to the identification of transmitted or early founder HIV -1 genomes in acutely infected humans based on single genome amplification and sequencing. Here we tested this approach in 18 acutely infected Indian rhesus macaques to determine the molecular features of SIV transmission. Animals were inoculated intrarectally (IR) or intravenously (IV) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV -1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA one to five weeks after infection. IR inoculation was followed by productive infection by one or few viruses (median 1; range 1-5) that diversified randomly with near star-like phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or few nuc1eotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder virus( es). IV infection was approximately 10,000-fold more efficient than IR infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV -1.

  16. Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIV(mac251).

    Science.gov (United States)

    Zhou, Qifeng; Hidajat, Rachmat; Peng, Bo; Venzon, David; Aldrich, M Kristine; Richardson, Ersell; Lee, Eun Mi; Kalyanaraman, V S; Grimes, George; Gómez-Román, V Raúl; Summers, L Ebonita; Malkevich, Nina; Robert-Guroff, Marjorie

    2007-11-19

    Oral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp120 protein. Cellular immune responses in PBMC were stronger and more frequent after I/O administration. Both groups developed mucosal immunity, including memory cells in bronchial alveolar lavage, and gut-homing receptors on PBMC. Following intrarectal SIV(mac251) challenge, both groups exhibited equivalent, significant protection and robust post-challenge cellular immunity. Our results illustrate the promise of oral replication-competent Ad-recombinant vaccines. Pre-challenge PBMC ELISPOT and proliferative responses did not predict protection in the O/O group, highlighting the need for simple, non-invasive methods to reliably assess mucosal immunity.

  17. Curved planar reformation images for identification of the central sulcus of affected hemispheres. Comparison with functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Nishimoto, Hideaki; Inoue, Takashi

    2006-01-01

    The aim of the present study was to evaluate the curved planar reformation (CPR) for identification of the central sulcus on affected hemispheres. Thirty four patients with an intracranial lesion adjacent to the central sulcus underwent functional magnetic resonance imaging (fMRI). fMRI was performed with a 3.0 Tesla scanner during repetitive opening and closing of each hand. The central sulcus was defined as the nearest sulcus to the highest activation spots. Three-dimensional magnetic resonance imaging date sets were processed using the CPR method to create brain surface reformatted images. We evaluated five anatomical features widely used for clinical identification of the central sulcus: 1, termination of the superior frontal sulcus in the precentral sulcus; 2, the intraparietal sulcus joining the postcentral sulcus; 3, the precentral gyros thicker than the postcentral gyrus; 4, inverted omega-shape of the precentral gyrus; and 5, the central sulcus as an isolated sulcus. fMRI and CPR coincided in defining the central sulcus in 34 hemispheres of patients. Applicability of each of the five signs was 61.8, 73.5, 58.8, 50.0 and 67.6%, respectively. The present study indicates that the CPR method successfully defined the central sulcus in most patients with brain tumors. For identification of the central sulcus, the CPR method will be recommended. (author)

  18. Control of viremia and prevention of AIDS following immunotherapy of SIV-infected macaques with peptide-pulsed blood.

    Directory of Open Access Journals (Sweden)

    Robert De Rose

    2008-05-01

    Full Text Available Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIV(mac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably approximately 10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.

  19. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

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    Sandrine Peruchon

    Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

  20. DMPD: Monocyte/macrophage traffic in HIV and SIV encephalitis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960230 Monocyte/macrophage traffic in HIV and SIV encephalitis. Kim WK, Corey S, ...Alvarez X, Williams K. J Leukoc Biol. 2003 Nov;74(5):650-6. Epub 2003 Aug 11. (.png) (.svg) (.html) (.csml) Show Monocyte/macrophage... traffic in HIV and SIV encephalitis. PubmedID 12960230 Title Monocyte/macrophage tr

  1. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  2. A brief history of the discovery of natural simian immunodeficiency virus (SIV) infections in captive sooty mangabey monkeys.

    Science.gov (United States)

    Gormus, Bobby J; Martin, Louis N; Baskin, Gary B

    2004-01-01

    Experimental leprosy studies using Mycobacterium leprae inoculum isolated from a sooty mangabey monkey (SMM) resulted in the accidental discovery that SMM's asymptomatically carry simian immunodeficiency virus (SIV) that is pathogenic in macaques. We showed that the SMM virus, SIVDelta, was antigenically related to SIVmac, which had been identified in macaques, and to the human immunodeficiency virus (HIV). Similar asymptomatic natural SIV infections had been reported in African green monkeys (AGM). Our results together with observations of others led us to propose that both SIVmac and SIVDelta originated in SMM and that SIV emerged in humans as a result of early African nonhuman primate SIV trans-species infections in humans.

  3. Influence of NO2 and metal ions on oxidation of aqueous-phase S(IV in atmospheric concentrations

    Directory of Open Access Journals (Sweden)

    Cláudia R. Martins

    2008-06-01

    Full Text Available An investigation was made of the influence of atmospheric concentrations (15 or 130 ppbv of NO2 on the aqueous-phase oxidation rate of S(IV in the presence and absence of Fe(III, Mn(II and Cr(VI metal ions under controlled experimental conditions (pH, T, concentration of reactants, etc.. The reaction rate in the presence of the NO2 flow was slower than the reaction rate using only clean air with an initial S(IV concentration of 10-4 mol/L. NO2 appears to react with S(IV, producing a kind of inhibitor that slows down the reaction. Conversely, tenfold lower concentrations of S(IV ([S(IV]º = 10-5 mol/L caused a faster reaction in the presence of NO2 than the reaction using purified air. Under these conditions, therefore, the equilibrium shifts to sulfate formation. With the addition of Fe(III, Mn(II or Cr(VI in the presence of a NO2 flow, the reaction occurred faster under all the conditions in which S(IV oxidation was investigated.A reação de oxidação de S(IV em fase aquosa foi estudada em laboratório em presença de NO2 dos íons metálicos Fe(III, Mn(II, e Cr(VI sob condições experimentais controladas (pH, T, concentração dos reagentes, etc.. Na presença de corrente de ar com NO2 (15 ou 130 ppbv a reação de oxidação de S(IV ocorreu mais lentamente do que na presença de ar purificado, para uma concentração inicial de S(IV de 10-4 mol/L. Ao contrário, para concentração inicial de S(IV dez vezes menor ([S(IV]° = 10-5 mol/L a reação ocorreu mais rapidamente na presença de NO2. A explicação está relacionada com o equilíbrio envolvendo a formação de espécies intermediárias de longa vida, que impedem o prosseguimento da reação, porém a depender das concentrações relativas de S(IV e NO2, essas espécies se decompõem deslocando o equilíbrio no sentido de formação de sulfato. A adição dos íons Fe(III, Mn(II ou Cr(VI em presença de corrente de ar com NO2 indicou atividade catalítica para esses íons, em todas

  4. Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

    Science.gov (United States)

    Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

    2016-03-01

    Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

  5. Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.

    Science.gov (United States)

    Ault, Alida; Tennant, Sharon M; Gorres, J Patrick; Eckhaus, Michael; Sandler, Netanya G; Roque, Annelys; Livio, Sofie; Bao, Saran; Foulds, Kathryn E; Kao, Shing-Fen; Roederer, Mario; Schmidlein, Patrick; Boyd, Mary Adetinuke; Pasetti, Marcela F; Douek, Daniel C; Estes, Jacob D; Nabel, Gary J; Levine, Myron M; Rao, Srinivas S

    2013-12-02

    Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuated Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-type S. typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-type S. typhimurium induces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques. Copyright © 2013. Published by Elsevier Ltd.

  6. An "escape clock" for estimating the turnover of SIV DNA in resting CD4⁺ T cells.

    Directory of Open Access Journals (Sweden)

    Jeanette Reece

    Full Text Available Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most studies suggest that cells with latently integrated HIV decay very slowly under therapy. However, it is much more difficult to study the turnover and persistence of HIV DNA during active infection. We have developed an "escape clock" approach for measuring the turnover of HIV DNA in resting CD4+ T cells. This approach studies the replacement of wild-type (WT SIV DNA present in early infection by CTL escape mutant (EM strains during later infection. Using a strain-specific real time PCR assay, we quantified the relative amounts of WT and EM strains in plasma SIV RNA and cellular SIV DNA. Thus we can track the formation and turnover of SIV DNA in sorted resting CD4+ T cells. We studied serial plasma and PBMC samples from 20 SIV-infected Mane-A*10 positive pigtail macaques that have a signature Gag CTL escape mutation. In animals with low viral load, WT virus laid down early in infection is extremely stable, and the decay of this WT species is very slow, consistent with findings in subjects on anti-retroviral medications. However, during active, high level infection, most SIV DNA in resting cells was turning over rapidly, suggesting a large pool of short-lived DNA produced by recent infection events. Our results suggest that, in order to reduce the formation of a stable population of SIV DNA, it will be important either to intervene very early or intervene during active replication.

  7. Evaluación de la estructura factorial del Cuestionario de Valores Interpersonales (SIV

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    César Merino Soto

    2013-09-01

    Full Text Available El artículo evalúa la estructura factorial bajo los efectos del método ipsativo de respuesta, estudiados en el nivel de las subescalas del Cuestionario de Valores Interpersonales de Gordon (SIV, y las relaciones entre ellas, en una muestra de adolescentes entre 15 y 17 años de ambos sexos y procedentes de un colegio privado y estatal, representativos de los niveles socioeconómicos medio y bajo. Aunque el SIV ha sido una herramienta extensamente utilizada, no se reportado previamente un análisis de su estructura factorial en muestras Latinoamericanas. Mediante el análisis de componentes principales y el análisis factorial con un enfoque confirmatorio, se han identificado relaciones bipolares entre Independencia y Benevolencia, y Soporte y Conformidad. Se obtuvo también la confirmación del modelo de valores interpersonales propuesto por L. V. Gordon. En el análisis se consideró un aspecto que artificialmente puede haber influido en el patrón de correlaciones entre los componentes, esto es el método ipsativo de las preguntas del SIV. Finalmente, se discute sobre las medidas ipsativas y sus consecuencias en la interpretación de sus resultados. The present study evaluates the factorial structure, in the level of the subscales, of the Survey of Interpersonal Values (SIV, and the relationships among them, in a sample of adolescents between 15 and 17 years old of both sexes and from a private and public school, representative of low and middle socioeconomic levels. Although the SIV has been a widely used tool, there is no report of an analysis of its factorial structure in Latin-American samples. By means of the principal components analysis and the factorial analysis with a confirmatory approach, bipolar relationships have been identified between Independence and Benevolence, and Support and Conformity. The confirmation of the pattern of interpersonal values proposed by L. V. Gordon was also accomplished. An aspect considered in the

  8. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.

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    Benjamin B Policicchio

    2016-09-01

    Full Text Available Viruses that persist despite seemingly effective antiretroviral treatment (ART and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control

  9. Analysis of the functional compatibility of SIV capsid sequences in the context of the FIV gag precursor.

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    César A Ovejero

    Full Text Available The formation of immature lentiviral particles is dependent on the multimerization of the Gag polyprotein at the plasma membrane of the infected cells. One key player in the virus assembly process is the capsid (CA domain of Gag, which establishes the protein-protein interactions that give rise to the hexagonal lattice of Gag molecules in the immature virion. To gain a better understanding of the functional equivalence between the CA proteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively, we generated a series of chimeric FIV Gag proteins in which the CA-coding region was partially or totally replaced by its SIV counterpart. All the FIV Gag chimeras were found to be assembly-defective; however, all of them are able to interact with wild-type SIV Gag and be recruited into extracellular virus-like particles, regardless of the SIV CA sequences present in the chimeric FIV Gag. The results presented here markedly contrast with our previous findings showing that chimeric SIVs carrying FIV CA-derived sequences are assembly-competent. Overall, our data support the notion that although the SIV and FIV CA proteins share 51% amino acid sequence similarity and exhibit a similar organization, i.e., an N-terminal domain joined by a flexible linker to a C-terminal domain, their functional exchange between these different lentiviruses is strictly dependent on the context of the recipient Gag precursor.

  10. Sulcus depth reproduction with polyvinyl siloxane impression material: effects of hydrophilicity and impression temperature.

    Science.gov (United States)

    Takahashi, Hidekazu; Finger, Werner J; Kurokawa, Rie; Furukawa, Masae; Komatsu, Masashi

    2010-03-01

    To determine the sulcus penetration ability of hydrophilic and hydrophobic polyvinyl siloxane (PVS) impression materials by impression technique, temperature, and sulcus width. Hydrophilic Flexitime (FLE; Heraeus Kulzer) and its hydrophobic counterpart (EXP) without surfactant were investigated, using light (L), monophase (M), and heavy (H) consistencies. A truncated steel cone surrounded by a 2-mm-deep and 50-, 100-, or 200-microm-wide sulcus, simulating the gingival tissue with agar, served as the test model. Impressions were made with single-mix (L or M) and double-mix (LM or LH) techniques at 23 degrees C and 37 degrees C, respectively. The reproduced sulcus heights were measured with a 3D laser scanner. Data were analyzed by ANOVA and Tukey HSD (P 1.9 mm); FLE-M, -LM, and-LH reproductions were shorter with narrow sulci. Reproductions of 50- and 100-microm sulci with EXP-L were shallower than with FLE-L. The shortest reproduction was, however, greater than 1.6 mm. In spite of some significant differences found in sulcus-reproducing ability with hydrophilic and hydrophobic impression materials applied at different impression-making temperatures and with different techniques, the practical relevance is limited.

  11. The effect of handedness on the shape of the central sulcus

    DEFF Research Database (Denmark)

    Sun, Zhong Yi; Klöppel, Stefan; Rivière, Denis

    2012-01-01

    Sinistrals differ from dextrals in the size of certain cortical folds. For instance, handedness has an impact on central sulcus surface area: the sulcus is larger in the dominant left hemisphere of dextrals and vice versa for sinistrals. However, the impact of handedness on the shape of the centr...... an accumulated record of both innate biases and early developmental experience. Characterizing normal variation of cortical morphology provides a means of systematically correlating behavior with cortical development....

  12. Epithelium-innate immune cell axis in mucosal responses to SIV.

    Science.gov (United States)

    Shang, L; Duan, L; Perkey, K E; Wietgrefe, S; Zupancic, M; Smith, A J; Southern, P J; Johnson, R P; Haase, A T

    2017-03-01

    In the SIV (simian immunodeficiency virus)-rhesus macaque model of HIV-1 (human immunodeficiency virus type I) transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T-cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T-cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T-cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment, and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.

  13. Role of Monocyte/Macrophages during HIV/SIV Infection in Adult and Pediatric Acquired Immune Deficiency Syndrome

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    Kristen M. Merino

    2017-12-01

    Full Text Available Monocytes/macrophages are a diverse group of cells that act as first responders in innate immunity and then as mediators for adaptive immunity to help clear infections. In performing these functions, however, the macrophage inflammatory responses can also contribute to pathogenesis. Various monocyte and tissue macrophage subsets have been associated with inflammatory disorders and tissue pathogeneses such as occur during HIV infection. Non-human primate research of simian immunodeficiency virus (SIV has been invaluable in better understanding the pathogenesis of HIV infection. The question of HIV/SIV-infected macrophages serving as a viral reservoir has become significant for achieving a cure. In the rhesus macaque model, SIV-infected macrophages have been shown to promote pathogenesis in several tissues resulting in cardiovascular, metabolic, and neurological diseases. Results from human studies illustrated that alveolar macrophages could be an important HIV reservoir and humanized myeloid-only mice supported productive HIV infection and viral persistence in macrophages during ART treatment. Depletion of CD4+ T cells is considered the primary cause for terminal progression, but it was reported that increasing monocyte turnover was a significantly better predictor in SIV-infected adult macaques. Notably, pediatric cases of HIV/SIV exhibit faster and more severe disease progression than adults, yet neonates have fewer target T cells and generally lack the hallmark CD4+ T cell depletion typical of adult infections. Current data show that the baseline blood monocyte turnover rate was significantly higher in neonatal macaques compared to adults and this remained high with disease progression. In this review, we discuss recent data exploring the contribution of monocytes and macrophages to HIV/SIV infection and progression. Furthermore, we highlight the need to further investigate their role in pediatric cases of infection.

  14. Plasmon resonance enhanced temperature-dependent photoluminescence of Si-V centers in diamond

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Shaoheng [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China); Song, Jie; Wang, Qiliang; Liu, Junsong; Li, Hongdong, E-mail: hdli@jlu.edu.cn [State Key Laboratory of Superhard Materials, Jilin University, Changchun 130012 (China); Zhang, Baolin [State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China)

    2015-11-23

    Temperature dependent optical property of diamond has been considered as a very important factor for realizing high performance diamond-based optoelectronic devices. The photoluminescence feature of the zero phonon line of silicon-vacancy (Si-V) centers in Si-doped chemical vapor deposited single crystal diamond (SCD) with localized surface plasmon resonance (LSPR) induced by gold nanoparticles has been studied at temperatures ranging from liquid nitrogen temperature to 473 K, as compared with that of the SCD counterpart in absence of the LSPR. It is found that with LSPR the emission intensities of Si-V centers are significantly enhanced by factors of tens and the magnitudes of the redshift (width) of the emissions become smaller (narrower), in comparison with those of normal emissions without plasmon resonance. More interestingly, these strong Si-V emissions appear remarkably at temperatures up to 473 K, while the spectral feature was not reported in previous studies on the intrinsic Si-doped diamonds when temperatures are higher than room temperature. These findings would lead to reaching high performance diamond-based devices, such as single photon emitter, quantum cryptography, biomarker, and so forth, working under high temperature conditions.

  15. Immunological alterations and associated diseases in mandrills (Mandrillus sphinx) naturally co-infected with SIV and STLV.

    Science.gov (United States)

    Souquière, Sandrine; Makuwa, Maria; Sallé, Bettina; Lepelletier, Yves; Mortreux, Franck; Hermine, Olivier; Kazanji, Mirdad

    2014-04-01

    Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2.

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    Bin Jia

    2009-05-01

    Full Text Available Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host-cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIV(smm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIV(mac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIV(smm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts.

  17. Experimental Oral Herpes Simplex Virus-1 (HSV-1 Co-infection in Simian Immunodeficiency Virus (SIV-Infected Rhesus Macaques

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    Meropi Aravantinou

    2017-12-01

    Full Text Available Herpes simplex virus 1 and 2 (HSV-1/2 similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

  18. A field study on chemistry, S(IV) oxidation rates and vertical transport during fog conditions

    Science.gov (United States)

    Joos, F.; Baltensperger, U.

    An extensive fog study was carried out in the central plateu of Switzerland. Ninety-seven fog samples were collected along with aerosol filter and cascade impactor samples, and measurements of O 3, SO 2, NO, NO x, PAN, temperature, and wind speed and direction. Maximum levels in fogwater were 4.3, 4.4., 0.033, 1.7, 0.5, 0.024 and 9.2 mmol ℓ -1 for Cl -, NO 3-, NO 2-, SO 42-, S(IV), oxalate and NH 4+, respectively. pH varied between 2.9 and 7.1. Sixteen additional elements were determined in the fog samples by ICP. The sum of the concentrations of SO 42- and S(IV) agreed very with the total sulfur concentration as determined by ICP. A substantial excess of S(IV) (up to 0.2 mmol ℓ -1) compared to Henry and acid-base equilibrium calculations was found, which can probably be attributed to complex formations with aldehydes. S(IV) oxidation rates of up to 650 nmol ℓ -1 s -1 with ozone and of up to 100 nmol ℓ -1 s -1 with NO 2 were calculated. S(IV) oxidation due to PAN, NO 2- and Fe(III) was of minor importance. A substantial fraction of the major ions was present in the intersitial aerosol (aerosol particles < 4 μm) even during fog conditions. High correlations were found for NH 4+, NO 32-. From their ratios in the fog water and the aerosol (< 4 μm) it could be concluded that at least 40% of NO 3- and 20% of NH 4+ in fog water was due to gas phase scavenging. Increasing concentrations in fog water were found during fog dissipation. Concentrations decreased with increasing height. A vertical transport model including turbulent diffusion and droplet sedimentation is introduced, which matches the experimental data of this vertical profile.

  19. Is the omega sign a reliable landmark for the neurosurgical team? An anatomical study about the central sulcus region

    Directory of Open Access Journals (Sweden)

    Thiago Rodrigues

    2015-11-01

    Full Text Available ABSTRACTThe central sulcus region is an eloquent area situated between the frontal and parietal lobes. During neurosurgical procedures, it is sometimes difficult to understand the cortical anatomy of this region.Objective Find alternative ways to anatomically navigate in this region during neurosurgical procedures.Method We analyzed eighty two human hemispheres using a surgical microscope and completed a review of the literature about central sulcus region.Results In 68/82 hemispheres, the central sulcus did not reach the posterior ramus of the lateral sulcus. A knob on the second curve of the precentral gyrus was reliably identified in only 64/82 hemispheres.Conclusion The morphometric data presented in this article can be useful as supplementary method to identify the central sulcus region landmarks.

  20. Oxidation of S(IV) in Seawater by Pulsed High Voltage Discharge Plasma with TiO2/Ti Electrode as Catalyst

    Science.gov (United States)

    Gong, Jianying; Zhang, Xingwang; Wang, Xiaoping; Lei, Lecheng

    2013-12-01

    Oxidation of S(IV) to S(VI) in the effluent of a flue gas desulfurization(FGD) system is very critical for industrial applications of seawater FGD. This paper reports a pulsed corona discharge oxidation process combined with a TiO2 photocatalyst to convert S(IV) to S(VI) in artificial seawater. Experimental results show that the oxidation of S(IV) in artificial seawater is enhanced in the pulsed discharge plasma process through the application of TiO2 coating electrodes. The oxidation rate of S(IV) using Ti metal as a ground electrode is about 2.0×10-4 mol · L-1 · min-1, the oxidation rate using TiO2/Ti electrode prepared by annealing at 500°C in air is 4.5×10-4 mol · L-1 · min-1, an increase with a factor 2.25. The annealing temperature for preparing TiO2/Ti electrode has a strong effect on the oxidation of S(IV) in artificial seawater. The results of in-situ emission spectroscopic analysis show that chemically active species (i.e. hydroxyl radicals and oxygen radicals) are produced in the pulsed discharge plasma process. Compared with the traditional air oxidation process and the sole plasma-induced oxidation process, the combined application of TiO2 photocatalysts and a pulsed high-voltage electrical discharge process is useful in enhancing the energy and conversion efficiency of S(IV) for the seawater FGD system.

  1. Innate Lymphoid Cells in HIV/SIV Infections.

    Science.gov (United States)

    Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith

    2017-01-01

    Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  2. Innate Lymphoid Cells in HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Spandan V. Shah

    2017-12-01

    Full Text Available Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  3. Sulcus reproduction with elastomeric impression materials: a new in vitro testing method.

    Science.gov (United States)

    Finger, Werner J; Kurokawa, Rie; Takahashi, Hidekazu; Komatsu, Masashi

    2008-12-01

    Aim of this study was to investigate the depth reproduction of differently wide sulci with elastomeric impression materials by single- and double-mix techniques using a tooth and sulcus model, simulating clinical conditions. Impressions with one vinyl polysiloxane (VPS; FLE), two polyethers (PE; IMP and P2), and one hybrid VPS/PE elastomer (FUS) were taken from a truncated steel cone with a circumferential 2 mm deep sulcus, 50, 100 or 200 microm wide. The "root surface" was in steel and the "periodontal tissue" in reversible hydrocolloid. Single-mix impressions were taken with light-body (L) or monophase (M) pastes, double-mix impressions with L as syringe and M or heavy-body (H) as tray materials (n=8). Sulcus reproduction was determined by 3D laser topography of impressions at eight locations, 45 degrees apart. Statistical data analysis by ANOVA and multiple comparison tests (pimpression materials only: FLE=IMP>FUS=P2. At 50 and 100 microm width, significant differences were found between materials (IMP>FUS=FLE>P2) and techniques (L+H=L+M>M>L). The sulcus model is considered useful for screening evaluation of elastomeric impression materials ability to reproduce narrow sulci. All tested materials and techniques reproduced 200 microm wide sulci to almost nominal depth. Irrespective of the impression technique used, IMP showed the best penetration ability in 50 and 100 microm sulci. Double-mix techniques are more suitable to reproduce narrow sulci than single-mix techniques.

  4. Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

    Science.gov (United States)

    Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

    2013-01-01

    The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

  5. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Feng, Youjun; Qi, Jianxun; Zhang, Huimin; Wang, Jinzi; Liu, Jinhua; Jiang, Fan; Gao, Feng

    2005-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β 2 m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides

  6. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Youjun [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Qi, Jianxun [Graduate School, Chinese Academy of Sciences, Beijing (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Zhang, Huimin; Wang, Jinzi [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Liu, Jinhua [College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Jiang, Fan [Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Gao, Feng, E-mail: gaofeng@im.ac.cn [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

    2006-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β{sub 2}m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides.

  7. Nonlinear dynamic-based analysis of severe dysphonia in patients with vocal fold scar and sulcus vocalis

    Science.gov (United States)

    Choi, Seong Hee; Zhang, Yu; Jiang, Jack J.; Bless, Diane M.; Welham, Nathan V.

    2011-01-01

    Objective The primary goal of this study was to evaluate a nonlinear dynamic approach to the acoustic analysis of dysphonia associated with vocal fold scar and sulcus vocalis. Study Design Case-control study. Methods Acoustic voice samples from scar/sulcus patients and age/sex-matched controls were analyzed using correlation dimension (D2) and phase plots, time-domain based perturbation indices (jitter, shimmer, signal-to-noise ratio [SNR]), and an auditory-perceptual rating scheme. Signal typing was performed to identify samples with bifurcations and aperiodicity. Results Type 2 and 3 acoustic signals were highly represented in the scar/sulcus patient group. When data were analyzed irrespective of signal type, all perceptual and acoustic indices successfully distinguished scar/sulcus patients from controls. Removal of type 2 and 3 signals eliminated the previously identified differences between experimental groups for all acoustic indices except D2. The strongest perceptual-acoustic correlation in our dataset was observed for SNR; the weakest correlation was observed for D2. Conclusions These findings suggest that D2 is inferior to time-domain based perturbation measures for the analysis of dysphonia associated with scar/sulcus; however, time-domain based algorithms are inherently susceptible to inflation under highly aperiodic (i.e., type 2 and 3) signal conditions. Auditory-perceptual analysis, unhindered by signal aperiodicity, is therefore a robust strategy for distinguishing scar/sulcus patient voices from normal voices. Future acoustic analysis research in this area should consider alternative (e.g., frequency- and quefrency-domain based) measures alongside additional nonlinear approaches. PMID:22516315

  8. Revisiting a quarter of a century of simian immunodeficiency virus (SIV-associated cardiovascular diseases at the German Primate Center

    Directory of Open Access Journals (Sweden)

    M. Mietsch

    2017-06-01

    Full Text Available Human immunodeficiency virus (HIV comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV-infected rhesus macaque (Macaca mulatta represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear. We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data. The main findings included myocarditis (12.8 %, endocarditis (9.7 %, and arteriopathy (10.3 % in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, p < 0. 0001 and p = 0. 0016, respectively. Further investigations of the interaction between coagulation markers, proinflammatory cytokines, and biomarkers associated with endothelial dysfunction (e.g., D-dimers and histological data (vascular wall structure may unravel the mechanisms underlying HIV/SIV-associated CV comorbidities.

  9. HIV vaccine research and discovery in the nonhuman primates model: a unified theory in acquisition prevention and control of SIV infection.

    Science.gov (United States)

    Lynch, Rebecca M; Yamamoto, Takuya; McDermott, Adrian B

    2013-07-01

    Here we highlight the latest advances in HIV vaccine concepts that will expand our knowledge on how to elicit effective acquisition-prevention and/or control of simian immunodeficiency virus (SIV) replication in the nonhuman primate (NHP) model. In the context of the promising analyses from the RV144 Thai Trial and the effective control of SIV replication exerted by rhCMV-(SIV) elicited EM CD8 T cells, the HIV field has recently shifted toward vaccine concepts that combine protection from acquisition with effective control of SIV replication. Current studies in the NHP model have demonstrated the efficacy of HIV-neutralizing antibodies via passive transfer, the potential importance of the CD4 Tfh subset, the ability to effectively model the RV144 vaccine trial and the capacity of an Ad26 prime and modified vaccinia Ankara virus boost to elicit Env-specific antibody and cellular responses that both limit acquisition and control heterologous SIVmac251 challenge. The latest work in the NHP model suggests that the next generation HIV-1 vaccines should aim to provoke a comprehensive adaptive immune response for both prevention of SIV acquisition as well as control of replication in breakthrough infection.

  10. Imaging the femoral sulcus with ultrasound, CT, and MRI: reliability and generalizability in patients with patellar instability

    Energy Technology Data Exchange (ETDEWEB)

    Toms, Andoni P.; Cahir, John [Norfolk and Norwich University Hospital, Departments of Radiology, Norwich, Norfolk (United Kingdom); Swift, Louise [University of East Anglia, School of Medicine, Health Policy and Practice, Norwich, Norfolk (United Kingdom); Donell, Simon T. [Norfolk and Norwich University Hospital, Institute of Orthopedics, Norwich, Norfolk (United Kingdom)

    2009-04-15

    Recent advances in surgical intervention for patellar instability have led to a need for long-term radiological monitoring. The aim of this study is to determine whether or not magnetic resonance imaging (MRI) or ultrasound (US) can replace computed tomography (CT) as the standard of care for the evaluation of the femoral sulcus. This was a prospective study comparing the reliability of CT, magnetic resonance (MR), and US for measuring the femoral sulcus in patients with patellar instability. Twenty-four patients were recruited to undergo a CT, MR, and US examination of each knee. Two observers independently measured femoral sulcus angles from subchondral bone and hyaline cartilage on two occasions. Intraclass correlations and generalizability coefficients were calculated to measure the reliability of each of the techniques. Thereafter, two observers measured the femoral sulcus angle from ultrasound images recorded by two independent operators to estimate interobserver and interoperator reliability. Forty-seven knees were examined with CT and US and 44 with MRI. The sulcus angle was consistently smaller when measured from subchondral bone compared to cartilage (5-7 ). Interobserver reliability for CT, MR, and US measurements from subchondral bone were 0.87, 0.80, and 0.82 and from cartilage 0.80, 0.81, and 0.50. Generalizability coefficients of measurements from subchondral bone for CT, MR, and US were 0.87, 0.76, and 0.81 and for cartilage 0.76, 0.73, and 0.05. Most of the variability in the US occurred at image acquisition rather than measurement. In patients with patellar instability, CT and MR are reliable techniques for measuring the femoral sulcus angle but US, particularly of the articular cartilage, is not. MR is therefore the most suitable tool for longitudinal studies of the femoral sulcus. (orig.)

  11. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

    Science.gov (United States)

    Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

  12. Altered immune responses in rhesus macaques co-infected with SIV and Plasmodium cynomolgi: an animal model for coincident AIDS and relapsing malaria.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Koehler

    2009-09-01

    Full Text Available Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens.Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response.These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions.

  13. Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.

    Science.gov (United States)

    Zhang, Xinsheng; Wallace, Olivia; Wright, Kevin J; Backer, Martin; Coleman, John W; Koehnke, Rebecca; Frenk, Esther; Domi, Arban; Chiuchiolo, Maria J; DeStefano, Joanne; Narpala, Sandeep; Powell, Rebecca; Morrow, Gavin; Boggiano, Cesar; Zamb, Timothy J; Richter King, C; Parks, Christopher L

    2013-11-01

    We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination. © 2013 Elsevier Inc. All rights reserved.

  14. The influence of sulcus width on simulated electric fields induced by transcranial magnetic stimulation

    Science.gov (United States)

    Janssen, A. M.; Rampersad, S. M.; Lucka, F.; Lanfer, B.; Lew, S.; Aydin, Ü.; Wolters, C. H.; Stegeman, D. F.; Oostendorp, T. F.

    2013-07-01

    Volume conduction models can help in acquiring knowledge about the distribution of the electric field induced by transcranial magnetic stimulation. One aspect of a detailed model is an accurate description of the cortical surface geometry. Since its estimation is difficult, it is important to know how accurate the geometry has to be represented. Previous studies only looked at the differences caused by neglecting the complete boundary between cerebrospinal fluid (CSF) and grey matter (Thielscher et al 2011 NeuroImage 54 234-43, Bijsterbosch et al 2012 Med. Biol. Eng. Comput. 50 671-81), or by resizing the whole brain (Wagner et al 2008 Exp. Brain Res. 186 539-50). However, due to the high conductive properties of the CSF, it can be expected that alterations in sulcus width can already have a significant effect on the distribution of the electric field. To answer this question, the sulcus width of a highly realistic head model, based on T1-, T2- and diffusion-weighted magnetic resonance images, was altered systematically. This study shows that alterations in the sulcus width do not cause large differences in the majority of the electric field values. However, considerable overestimation of sulcus width produces an overestimation of the calculated field strength, also at locations distant from the target location.

  15. Dual Endotemponade for Extensive Long-standing Cyclodialysis Using Sulcus-fixated Cionni Ring and PCIOL.

    Science.gov (United States)

    Gupta, Shikha; Sagar, Pradeep; Gogia, Varun; Khokhar, Sudarshan; Dada, Tanuj

    2016-03-01

    A young patient presented with visual acuity of hand movements only, unrecordable intraocular pressure, and total cataract after trauma 12 months ago. She reported failure to improve with conservative therapy as well as a direct cycloplexy elsewhere. After cleft localization on preoperative gonioscopy, ultrasound biomicroscopy (UBM), and intraoperative gonioscopy, a partial-thickness scleral flap was fashioned at the site of maximum cleft height. Following phacoaspiration, a multipiece intraocular lens was implanted in the sulcus; its haptics aligned to the axis with maximum height of cyclodialysis. A Cionni ring placed in sulcus was sutured to sclera under the flap to provide additional tamponading effect. Postoperative UBM and gonioscopy confirmed cleft closure. Normalization of intraocular pressure was found on repeated follow-ups till 1 year (12 to 14 mm Hg). UBM showed increase in sulcus diameter, and "double indentation sign" on the ciliary body.

  16. Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells

    Science.gov (United States)

    Milush, Jeffrey M.; Mir, Kiran D.; Sundaravaradan, Vasudha; Gordon, Shari N.; Engram, Jessica; Cano, Christopher A.; Reeves, Jacqueline D.; Anton, Elizabeth; O’Neill, Eduardo; Butler, Eboneé; Hancock, Kathy; Cole, Kelly S.; Brenchley, Jason M.; Else, James G.; Silvestri, Guido; Sodora, Donald L.

    2011-01-01

    SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3+CD4–CD8– T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4+ T cells to SIV-negative animals resulted in rapid loss of CD4+ T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell–like helper functions upon SIV-induced CD4+ T cell depletion in this species. PMID:21317533

  17. Radiology of the paraglenoid sulcus

    International Nuclear Information System (INIS)

    Schemmer, D.; White, P.G.; Friedman, L.

    1995-01-01

    The paraglenoid sulcus is a variable groove in the ilium adjacent to the inferior end of the sacroiliac joint. This study investigates the hypothesis that the groove is due to resorption at the insertion of the anterior sacroiliac ligament in response to stress. The anatomical relationships of the groove are shown with plain films, arteriography and computed tomography. Relationship to parity was tested in 70 adult female subjects; a statistically significant relationship was found, with deep grooves occurring only in parous women. An association with osteitis condensans ilii was also demonstrated. Relationship to lumbosacral posture was tested in 102 adult females, and an association with increased lumbar lordosis was found. These findings are consistent with our initial hypothesis. (orig.)

  18. Radiology of the paraglenoid sulcus

    Energy Technology Data Exchange (ETDEWEB)

    Schemmer, D [McMaster Univ. Medical Centre, Hamilton, ON (Canada); White, P G [Dept. of Radiology, McMaster Univ. Medical Centre, Hamilton, ON (Canada); Friedman, L [Dept. of Radiology, McMaster Univ. Medical Centre, Hamilton, ON (Canada)

    1995-04-01

    The paraglenoid sulcus is a variable groove in the ilium adjacent to the inferior end of the sacroiliac joint. This study investigates the hypothesis that the groove is due to resorption at the insertion of the anterior sacroiliac ligament in response to stress. The anatomical relationships of the groove are shown with plain films, arteriography and computed tomography. Relationship to parity was tested in 70 adult female subjects; a statistically significant relationship was found, with deep grooves occurring only in parous women. An association with osteitis condensans ilii was also demonstrated. Relationship to lumbosacral posture was tested in 102 adult females, and an association with increased lumbar lordosis was found. These findings are consistent with our initial hypothesis. (orig.)

  19. Low dose rectal inoculation of rhesus macaques by SIV smE660 or SIVmac251 recapitulates

    Energy Technology Data Exchange (ETDEWEB)

    Hraber, Peter [Los Alamos National Laboratory; Giorgi, Elena E [Los Alamos National Laboratory; Keele, Brandon [UNIV OF ALABAMA; Li, Hui [UNIV OF ALABAMA; Learn, Gerald [UNIV OF ALABAMA

    2008-01-01

    We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1--5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1--5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.

  20. The influence of sulcus width on simulated electric fields induced by transcranial magnetic stimulation

    International Nuclear Information System (INIS)

    Janssen, A M; Rampersad, S M; Stegeman, D F; Oostendorp, T F; Lucka, F; Lanfer, B; Aydin, Ü; Wolters, C H; Lew, S

    2013-01-01

    Volume conduction models can help in acquiring knowledge about the distribution of the electric field induced by transcranial magnetic stimulation. One aspect of a detailed model is an accurate description of the cortical surface geometry. Since its estimation is difficult, it is important to know how accurate the geometry has to be represented. Previous studies only looked at the differences caused by neglecting the complete boundary between cerebrospinal fluid (CSF) and grey matter (Thielscher et al 2011 NeuroImage 54 234–43, Bijsterbosch et al 2012 Med. Biol. Eng. Comput. 50 671–81), or by resizing the whole brain (Wagner et al 2008 Exp. Brain Res. 186 539–50). However, due to the high conductive properties of the CSF, it can be expected that alterations in sulcus width can already have a significant effect on the distribution of the electric field. To answer this question, the sulcus width of a highly realistic head model, based on T1-, T2- and diffusion-weighted magnetic resonance images, was altered systematically. This study shows that alterations in the sulcus width do not cause large differences in the majority of the electric field values. However, considerable overestimation of sulcus width produces an overestimation of the calculated field strength, also at locations distant from the target location. (paper)

  1. Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection.

    Directory of Open Access Journals (Sweden)

    Haiying Li

    2014-12-01

    Full Text Available HIV/SIV infections break down the integrity of the gastrointestinal mucosa and lead to chronic immune activation and associated disease progression. Innate lymphoid cells (ILCs, distinguishable by high expression of NKp44 and RORγt, play key roles in mucosal defense and homeostasis, but are depleted from gastrointestinal (GI tract large bowel during chronic SIV infection. However, less is known about the kinetics of ILC loss, or if it occurs systemically. In acute SIV infection, we found a massive, up to 8-fold, loss of NKp44+ILCs in all mucosae as early as day 6 post-infection, which was sustained through chronic disease. Interestingly, no loss of ILCs was observed in mucosa-draining lymph nodes. In contrast, classical NK cells were not depleted either from gut or draining lymph nodes. Both ILCs and NK cells exhibited significantly increased levels of apoptosis as measured by increased Annexin-V expression, but while classical NK cells also showed increased proliferation, ILCs did not. Interestingly, ILCs, which are normally noncytolytic, dramatically upregulated cytotoxic functions in acute and chronic infection and acquired a polyfunctional phenotype secreting IFN-γ, MIP1-β, and TNF-α, but decreased production of the prototypical cytokine, IL-17. Classical NK cells had less dramatic functional change, but upregulated perforin expression and increased cytotoxic potential. Finally, we show that numerical and functional loss of ILCs was due to increased apoptosis and ROR γt suppression induced by inflammatory cytokines in the gut milieu. Herein we demonstrate the first evidence for acute, systemic, and permanent loss of mucosal ILCs during SIV infection associated with reduction of IL-17. The massive reduction of ILCs involves apoptosis without compensatory de novo development/proliferation, but the full mechanism of depletion and the impact of functional change so early in infection remain unclear.

  2. Temporalis Fascia Transplantation for Sulcus Vocalis and Vocal Fold Scar: Long-Term Outcomes.

    Science.gov (United States)

    Karle, William E; Helman, Samuel N; Cooper, Amy; Zhang, Yuan; Pitman, Michael J

    2018-04-01

    Sulcus vocalis and vocal fold scar involve derangement of the superficial lamina propria of the vocal fold, which results in significant dysphonia. Many options exist for treatment, most of which have unsatisfactory and unpredictable outcomes. Autologous transplantation of temporalis fascia into the vocal fold (ATFV) has the potential to be a better treatment option, but long-term outcomes have not been well studied. Retrospective chart review and patient survey. Twenty-one patients diagnosed with vocal fold scar or sulcus vocalis and treated with ATFV with at least 1-year follow-up were included. Voice Handicap Index 10 (VHI-10) questionnaires were collected preoperatively and 6 months postoperatively. Patients were reached at the time of the study to complete another VHI-10 and a Likert scale survey. The mean decrease in VHI-10 scores between preoperation and 6 months postoperation was 8.35 ( P vocal fold for the treatment of vocal fold scar and sulcus vocalis is a safe surgery with good long-term outcomes and high patient satisfaction.

  3. INFRAORBITAL SULCUS: A STUDY IN 100 SKULLS

    OpenAIRE

    Roshni; . Jayanthi; Shubha

    2014-01-01

    INTRODUCTION: A study was done on 100 intact, unsexed human skulls in the Department of Anatomy, KIMS, Bangalore, to observe and record the presence of a groove in the lateral wall of the orbit, synonymous with infra orbital sulcus. This entity has been described by the fortieth edition of Gray’s text book of Anatomy to extend from the lateral end of superior orbital fissure to the orbital floor. It sometimes contains an anastomosis between middle meningeal artery and infr...

  4. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    Directory of Open Access Journals (Sweden)

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  5. Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection

    DEFF Research Database (Denmark)

    Muenchhoff, Maximilian; Adland, Emily; Karimanzira, Owen

    2016-01-01

    nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved...

  6. Distinct phenotype, longitudinal changes of numbers and cell-associated virus in blood dendritic cells in SIV-infected CD8-lymphocyte depleted macaques.

    Directory of Open Access Journals (Sweden)

    Caroline Soulas

    Full Text Available Loss of circulating CD123+ plasmacytoid dendritic cells (pDCs during HIV infection is well established. However, changes of myeloid DCs (mDCs are ambiguous since they are studied as a homogeneous CD11c+ population despite phenotypic and functional heterogeneity. Heterogeneity of CD11c+ mDCs in primates is poorly described in HIV and SIV infection. Using multiparametric flow cytometry, we monitored longitudinally cell number and cell-associated virus of CD123+ pDCs and non-overlapping subsets of CD1c+ and CD16+ mDCs in SIV-infected CD8-depleted rhesus macaques. The numbers of all three DC subsets were significantly decreased by 8 days post-infection. Whereas CD123+ pDCs were persistently depleted, numbers of CD1c+ and CD16+ mDCs rebounded. Numbers of CD1c+ mDCs significantly increased by 3 weeks post-infection while numbers of CD16+ mDCs remained closer to pre-infection levels. We found similar changes in the numbers of all three DC subsets in CD8 depleted animals as we found in animals that were SIV infected animals that were not CD8 lymphocyte depleted. CD16+ mDCs and CD123+ pDCs but not CD1c+ mDCs were significantly decreased terminally with AIDS. All DC subsets harbored SIV RNA as early as 8 days and then throughout infection. However, SIV DNA was only detected in CD123+ pDCs and only at 40 days post-infection consistent with SIV RNA, at least in mDCs, being surface-bound. Altogether our data demonstrate that SIV infection differently affects CD1c+ and CD16+ mDCs where CD16+ but not CD1c+ mDCs are depleted and might be differentially regulated in terminal AIDS. Finally, our data underline the importance of studying CD1c+ and CD16+ mDCs as discrete populations, and not as total CD11c+ mDCs.

  7. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  8. Fragmentation of SIV-gag vaccine induces broader T cell responses.

    Directory of Open Access Journals (Sweden)

    Adel Benlahrech

    Full Text Available High mutation rates of human immunodeficiency virus (HIV allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.three vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Fragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise

  9. A model for predicting sulcus-to-sulcus diameter in posterior chamber phakic intraocular lens candidates: correlation between ocular biometric parameters.

    Science.gov (United States)

    Ghoreishi, Mohammad; Abdi-Shahshahani, Mehdi; Peyman, Alireza; Pourazizi, Mohsen

    2018-02-21

    The aim of this study was to determine the correlation between ocular biometric parameters and sulcus-to-sulcus (STS) diameter. This was a cross-sectional study of preoperative ocular biometry data of patients who were candidates for phakic intraocular lens (IOL) surgery. Subjects underwent ocular biometry analysis, including refraction error evaluation using an autorefractor and Orbscan topography for white-to-white (WTW) corneal diameter and measurement. Pentacam was used to perform WTW corneal diameter and measurements of minimum and maximum keratometry (K). Measurements of STS and angle-to-angle (ATA) were obtained using a 50-MHz B-mode ultrasound device. Anterior optical coherence tomography was performed for anterior chamber depth measurement. Pearson's correlation test and stepwise linear regression analysis were used to find a model to predict STS. Fifty-eight eyes of 58 patients were enrolled. Mean age ± standard deviation of sample was 28.95 ± 6.04 years. The Pearson's correlation coefficient between STS with WTW, ATA, mean K was 0.383, 0.492, and - 0.353, respectively, which was statistically significant (all P correlation of STS with WTW and mean K and potential of direct and essay measurement of WTW and mean K, it seems that current IOL sizing protocols could be estimating with WTW and mean K.

  10. Spatially Controlled Fabrication of Brightly Fluorescent Nanodiamond-Array with Enhanced Far-Red Si-V Luminescence

    Science.gov (United States)

    Singh, Sonal; Thomas, Vinoy; Martyshkin, Dmitry; Kozlovskaya, Veronika; Kharlampieva, Eugenia

    2014-01-01

    We demonstrate a novel approach to precise pattern fluorescent nanodiamond-arrays with enhanced far-red intense photostable luminescence from silicon-vacancy (Si-V) defect centers. The precision-patterned pre-growth seeding of nanodiamonds is achieved by scanning probe “Dip-Pen” nanolithography technique using electrostatically-driven transfer of nanodiamonds from “inked” cantilevers to a UV-treated hydrophilic SiO2 substrate. The enhanced emission from nanodiamond-dots in the far-red is achieved by incorporating Si-V defect centers in subsequent chemical vapor deposition treatment. The development of a suitable nanodiamond ink, mechanism of ink transport, and effect of humidity, dwell time on nanodiamond patterning are investigated. The precision-patterning of as-printed (pre-CVD) arrays with dot diameter and dot height as small as 735 nm ± 27 nm, 61 nm ± 3 nm, respectively and CVD-treated fluorescent ND-arrays with consistently patterned dots having diameter and height as small as 820 nm ± 20 nm, 245 nm ± 23 nm, respectively using 1 s dwell time and 30% RH is successfully achieved. We anticipate that the far-red intense photostable luminescence (~738 nm) observed from Si-V defect centers integrated in spatially arranged nanodiamonds could be beneficial for the development of the next generation fluorescent based devices and applications. PMID:24394286

  11. Gene expression of Lactobacillus plantarum and the commensal microbiota in the ileum of healthy and early SIV-infected rhesus macaques

    Science.gov (United States)

    Golomb, Benjamin L.; Hirao, Lauren A.; Dandekar, Satya; Marco, Maria L.

    2016-01-01

    Chronic HIV infection results in impairment of gut-associated lymphoid tissue leading to systemic immune activation. We previously showed that in early SIV-infected rhesus macaques intestinal dysfunction is initiated with the induction of the IL-1β pathway in the small intestine and reversed by treatment with an exogenous Lactobacillus plantarum strain. Here, we provide evidence that the transcriptomes of L. plantarum and ileal microbiota are not altered shortly after SIV infection. L. plantarum adapts to the small intestine by expressing genes required for tolerating oxidative stress, modifying cell surface composition, and consumption of host glycans. The ileal microbiota of L. plantarum-containing healthy and SIV+ rhesus macaques also transcribed genes for host glycan metabolism as well as for cobalamin biosynthesis. Expression of these pathways by bacteria were proposed but not previously demonstrated in the mammalian small intestine. PMID:27102350

  12. Stochastic inequalities and applications to dynamics analysis of a novel SIVS epidemic model with jumps

    Directory of Open Access Journals (Sweden)

    Xiaona Leng

    2017-06-01

    Full Text Available Abstract This paper proposes a new nonlinear stochastic SIVS epidemic model with double epidemic hypothesis and Lévy jumps. The main purpose of this paper is to investigate the threshold dynamics of the stochastic SIVS epidemic model. By using the technique of a series of stochastic inequalities, we obtain sufficient conditions for the persistence in mean and extinction of the stochastic system and the threshold which governs the extinction and the spread of the epidemic diseases. Finally, this paper describes the results of numerical simulations investigating the dynamical effects of stochastic disturbance. Our results significantly improve and generalize the corresponding results in recent literatures. The developed theoretical methods and stochastic inequalities technique can be used to investigate the high-dimensional nonlinear stochastic differential systems.

  13. Decreased number of CD4+ and CD8+ T cells that express the interleukin-7 receptor in blood and tissues of SIV-infected macaques

    International Nuclear Information System (INIS)

    Moniuszko, Marcin; Edghill-Smith, Yvette; Venzon, David; Stevceva, Liljana; Nacsa, Janos; Tryniszewska, Elzbieta; Tsai, Wen-Po; Franchini, Genoveffa

    2006-01-01

    Acute HIV/SIV (human/simian immunodeficiency virus) infection results in severe CD4 + T cell depletion in lymphoid compartments. During the chronic phase of infection, CD4 + T cell numbers rebound in blood but remain low in the gut-associated lymphoid tissue (GALT), even when viral replication is suppressed by antiretroviral therapy (ART). Thus, strategies to repopulate lymphoid compartments may ameliorate the clinical outcome of HIV/SIV infection. Interleukin (IL)-7 is a key cytokine for the maintenance of homeostatic proliferation of T cells. In HIV/SIV infection, IL-7 expression is increased, likely to compensate for T cell loss, suggesting that supraphysiological administration of IL-7 could provide additional benefit. However, the ability of T cells to respond to IL-7 is dependent on the level of expression of the IL-7 receptor (IL-7R) in T cells in various body compartments. In here, we investigated the proportion of IL-7R + T cells in blood, spleen, gut, and genitourinary tract of healthy and SIV-infected macaques with various degrees of CD4 + T cell depletion. We found that the percentage of T cells expressing IL-7R was significantly lower in both CD4 + and CD8 + T cell subsets in SIV-infected macaques than in healthy animals and this decrease directly correlated with the CD4 + T cell number. Importantly, the proportion of CD4 + and CD8 + T cells expressing IL-7R in blood paralleled that found in tissues. IL-7R + T cells within the SIV-specific CD8 + T cells varied and were lowest in most tissues of viremic macaques, likely reflecting continuous antigen stimulation of effector cells

  14. Opacification of the C-flex 570C intraocular lens after sulcus fixation.

    Science.gov (United States)

    Daigle, Patrick; Carbonneau, Marjorie

    2017-09-08

    To report a case of diffuse intraocular lens (IOL) opacification in a patient who started complaining of blurred vision in his left eye over the course of three years after having phacoemulsification surgery combined with capsular bag fixation of a C-flex 570C IOL. The IOL had been repositioned in the ciliary sulcus following its subluxation. An IOL exchange was performed, and the explanted IOL was sent for histopathological analysis. Scanning electron microscopy identified multiple crystalline-like deposits on both sides of the IOL. The optic was more extensively involved than the haptics. Energy-dispersive X-ray spectroscopy confirmed the predominance of calcium within the deposits. The breakdown of the blood-aqueous barrier seems to be a key component of this calcification process. Ciliary sulcus fixation is not a suitable option for C-flex 570C IOLs.

  15. A Multiplex Microsphere-Based Immunoassay Increases the Sensitivity of SIV-Specific Antibody Detection in Serum Samples and Mucosal Specimens Collected from Rhesus Macaques Infected with SIVmac239.

    Science.gov (United States)

    Powell, Rebecca L R; Ouellette, Ian; Lindsay, Ross W; Parks, Christopher L; King, C Richter; McDermott, Adrian B; Morrow, Gavin

    2013-06-01

    Results from recent HIV-1 vaccine studies have indicated that high serum antibody (Ab) titers may not be necessary for Ab-mediated protection, and that Abs localized to mucosal sites might be critical for preventing infection. Enzyme-linked immunosorbent assay (ELISA) has been used for decades as the gold standard for Ab measurement, though recently, highly sensitive microsphere-based assays have become available, with potential utility for improved detection of Abs. In this study, we assessed the Bio-Plex(®) Suspension Array System for the detection of simian immunodeficiency virus (SIV)-specific Abs in rhesus macaques (RMs) chronically infected with SIV, whose serum or mucosal SIV-specific Ab titers were negative by ELISA. We developed a SIVmac239-specific 4-plex bead array for the simultaneous detection of Abs binding to Env, Gag, Pol, and Nef. The 4-plex assay was used to quantify SIV-specific serum IgG and rectal swab IgA titers from control (SIV-naive) and SIVmac239-infected RMs. The Bio-Plex assay specifically detected anti-SIV Abs in specimens from SIV-infected animals for all four analytes when compared to SIV-naive control samples (p≤0.04). Furthermore, in 70% of Env and 79% of Gag ELISA-negative serum samples, specific Ab was detected using the Bio-Plex assay. Similarly, 71% of Env and 48% of Gag ELISA-negative rectal swab samples were identified as positive using the Bio-Plex assay. Importantly, assay specificity (i.e., probability of true positives) was comparable to ELISA (94%-100%). The results reported here indicate that microsphere-based methods provide a substantial improvement over ELISA for the detection of Ab responses, aid in detecting specific Abs when analyzing samples containing low levels of Abs, such as during the early stages of a vaccine trial, and may be valuable in attempts to link protective efficacy of vaccines with induced Ab responses.

  16. ACVP-02: Plasma SIV/SHIV RNA Viral Load Measurements through the AIDS and Cancer Virus Program Quantitative Molecular Diagnostics Core | Frederick National Laboratory for Cancer Research

    Science.gov (United States)

    The SIV plasma viral load assay performed by the Quantitative Molecular Diagnostics Core (QMDC) utilizes reagents specifically designed to detect and accurately quantify the full range of SIV/SHIV viral variants and clones in common usage in the rese

  17. 'Omics investigations of HIV and SIV pathogenesis and innate immunity.

    Science.gov (United States)

    Palermo, Robert E; Fuller, Deborah H

    2013-01-01

    In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics

  18. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

    Directory of Open Access Journals (Sweden)

    Iskra Tuero

    2015-08-01

    Full Text Available Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC

  19. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

    Science.gov (United States)

    Tuero, Iskra; Mohanram, Venkatramanan; Musich, Thomas; Miller, Leia; Vargas-Inchaustegui, Diego A; Demberg, Thorsten; Venzon, David; Kalisz, Irene; Kalyanaraman, V S; Pal, Ranajit; Ferrari, Maria Grazia; LaBranche, Celia; Montefiori, David C; Rao, Mangala; Vaccari, Monica; Franchini, Genoveffa; Barnett, Susan W; Robert-Guroff, Marjorie

    2015-08-01

    Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males) was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males) received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC) in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized) remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC and ADCP

  20. Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

    Directory of Open Access Journals (Sweden)

    Strasak Alexander

    2009-06-01

    Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

  1. Assessment of a new hydrophilic acrylic supplementary IOL for sulcus fixation in pseudophakic cadaver eyes

    Science.gov (United States)

    Reiter, N; Werner, L; Guan, J; Li, J; Tsaousis, K T; Mamalis, N; Srinivasan, S

    2017-01-01

    Purpose Management of refractive errors after cataract surgery includes spectacles or contact lens, secondary laser vision correction, intraocular lens (IOL) exchange, or piggyback lens implantation. We evaluated for the first time a single-piece hydrophilic acrylic IOL designed for supplementary sulcus fixation in postmortem pseudophakic human eyes. Methods Pseudophakic human cadaver eyes were imaged by anterior segment optical coherence tomography (AS-OCT) to assess position of the primary IOL. Eyes were prepared as per the Miyake-Apple technique. The supplementary IOL (Medicontur A4 Addon IOL family) was then inserted into the ciliary sulcus. AS-OCT and photographs from anterior and posterior views were used to assess IOL centration, tilt, and interlenticular distance from the primary IOL. Results Data were obtained from 12 eyes having primary IOLs of varying materials and designs in the bag and representing different sizes of eyes and severity of Soemmering's ring formation. The A4 Addon IOL was successfully inserted into the ciliary sulcus and was well centered in all cases. Four cases of tilt were observed on AS-OCT: three with mild tilt due to pre-existing zonular dehiscence, and one due to a localized area of Soemmering's ring formation. Interlenticular distance ranged from 0.34 to 1.24 mm and was not dependent on severity of Soemmering's ring or type of primary IOL. Conclusions The A4 Addon IOL was designed for sulcus fixation as a supplementary lens, with a large diameter, a square-shaped optic, four smooth loop haptics, and a convex–concave optical surface. It exhibited appropriate centration and interlenticular distance with different primary in-the-bag IOLs. PMID:28106890

  2. Spatially controlled fabrication of a bright fluorescent nanodiamond-array with enhanced far-red Si-V luminescence.

    Science.gov (United States)

    Singh, Sonal; Thomas, Vinoy; Martyshkin, Dmitry; Kozlovskaya, Veronika; Kharlampieva, Eugenia; Catledge, Shane A

    2014-01-31

    We demonstrate a novel approach to precisely pattern fluorescent nanodiamond-arrays with enhanced far-red intense photostable luminescence from silicon-vacancy (Si-V) defect centers. The precision-patterned pre-growth seeding of nanodiamonds is achieved by a scanning probe 'dip-pen' nanolithography technique using electrostatically driven transfer of nanodiamonds from 'inked' cantilevers to a UV-treated hydrophilic SiO2 substrate. The enhanced emission from nanodiamond dots in the far-red is achieved by incorporating Si-V defect centers in a subsequent chemical vapor deposition treatment. The development of a suitable nanodiamond ink and mechanism of ink transport, and the effect of humidity and dwell time on nanodiamond patterning are investigated. The precision patterning of as-printed (pre-CVD) arrays with dot diameter and dot height as small as 735 nm ± 27 nm and 61 nm ± 3 nm, respectively, and CVD-treated fluorescent ND-arrays with consistently patterned dots having diameter and height as small as 820 nm ± 20 nm and, 245 nm ± 23 nm, respectively, using 1 s dwell time and 30% RH is successfully achieved. We anticipate that the far-red intense photostable luminescence (~738 nm) observed from Si-V defect centers integrated in spatially arranged nanodiamonds could be beneficial for the development of next generation fluorescence-based devices and applications.

  3. Determining the Structure of an Unliganded and Fully Glycosylated SIV gp120 Envelope Glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Bing; Vogan, Erik M.; Gong, Haiyun; Skehel, John J.; Wiley, Don C.; Harrison, Stephen C. (Harvard-Med); (NIMR)

    2010-07-13

    HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 {angstrom} resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

  4. Simple Mathematical Models Do Not Accurately Predict Early SIV Dynamics

    Directory of Open Access Journals (Sweden)

    Cecilia Noecker

    2015-03-01

    Full Text Available Upon infection of a new host, human immunodeficiency virus (HIV replicates in the mucosal tissues and is generally undetectable in circulation for 1–2 weeks post-infection. Several interventions against HIV including vaccines and antiretroviral prophylaxis target virus replication at this earliest stage of infection. Mathematical models have been used to understand how HIV spreads from mucosal tissues systemically and what impact vaccination and/or antiretroviral prophylaxis has on viral eradication. Because predictions of such models have been rarely compared to experimental data, it remains unclear which processes included in these models are critical for predicting early HIV dynamics. Here we modified the “standard” mathematical model of HIV infection to include two populations of infected cells: cells that are actively producing the virus and cells that are transitioning into virus production mode. We evaluated the effects of several poorly known parameters on infection outcomes in this model and compared model predictions to experimental data on infection of non-human primates with variable doses of simian immunodifficiency virus (SIV. First, we found that the mode of virus production by infected cells (budding vs. bursting has a minimal impact on the early virus dynamics for a wide range of model parameters, as long as the parameters are constrained to provide the observed rate of SIV load increase in the blood of infected animals. Interestingly and in contrast with previous results, we found that the bursting mode of virus production generally results in a higher probability of viral extinction than the budding mode of virus production. Second, this mathematical model was not able to accurately describe the change in experimentally determined probability of host infection with increasing viral doses. Third and finally, the model was also unable to accurately explain the decline in the time to virus detection with increasing viral

  5. Şemseddin Sivȃsȋ’nin Tasavvufȋ Tecrübesinde Rizȃ-yı Bȃrȋ Düşüncesi

    Directory of Open Access Journals (Sweden)

    Kadir Özköse

    2015-12-01

    Full Text Available Halvetiyyenin dört ana kolundan biri olan Şemsiyyenin pȋri konumundaki Şemseddin Sivȃsȋ’nin eserlerinden hareketle hazırladığımız bu makale Şemseddin Sivȃsȋ’nin sȗfȋ tecrübesini okumaya dönük bir çalışmadır. Mensur ve manzum eserlerinin herbirinde Şemseddin Sivȃsȋ ana tema olarak Allah’ın rızasını merkeze almıştır. İlahi rızanın her zaman gündemde olmasını, kulluğun ilahi rıza ekseninde gerçekleşmesini istemiştir. Lutfun da hoş kahrın da hoş anlayışına bağlı olan Şemseddin Sivȃsȋ ilahi takdire boyun eğmiş, ne varlığa sevinmeyi ne de yokluktan yerinmeyi öngörmüştür. Rıza halinin kemalini o, mücahede eğitimne, sabır ve sebat gayretine, tevazu duygusuna, ihlas hassasiyetine ve zikir diriliğine bağlamıştır. Makalemizde Şemseddin Sivȃsȋ’nin rızanın ehemmiyetine ve rıza makamına ulaşmayı sağlayan teel ölçütlere dikkat çekmeye çalıştık.

  6. Spatially controlled fabrication of a bright fluorescent nanodiamond-array with enhanced far-red Si-V luminescence

    International Nuclear Information System (INIS)

    Singh, Sonal; Thomas, Vinoy; Kharlampieva, Eugenia; Catledge, Shane A; Martyshkin, Dmitry; Kozlovskaya, Veronika

    2014-01-01

    We demonstrate a novel approach to precisely pattern fluorescent nanodiamond-arrays with enhanced far-red intense photostable luminescence from silicon-vacancy (Si-V) defect centers. The precision-patterned pre-growth seeding of nanodiamonds is achieved by a scanning probe ‘dip-pen’ nanolithography technique using electrostatically driven transfer of nanodiamonds from ‘inked’ cantilevers to a UV-treated hydrophilic SiO 2 substrate. The enhanced emission from nanodiamond dots in the far-red is achieved by incorporating Si-V defect centers in a subsequent chemical vapor deposition treatment. The development of a suitable nanodiamond ink and mechanism of ink transport, and the effect of humidity and dwell time on nanodiamond patterning are investigated. The precision patterning of as-printed (pre-CVD) arrays with dot diameter and dot height as small as 735 nm ± 27 nm and 61 nm ± 3 nm, respectively, and CVD-treated fluorescent ND-arrays with consistently patterned dots having diameter and height as small as 820 nm ± 20 nm and, 245 nm ± 23 nm, respectively, using 1 s dwell time and 30% RH is successfully achieved. We anticipate that the far-red intense photostable luminescence (∼738 nm) observed from Si-V defect centers integrated in spatially arranged nanodiamonds could be beneficial for the development of next generation fluorescence-based devices and applications. (paper)

  7. Upper midbrain profile sign and cingulate sulcus sign. MRI findings on sagittal images in idiopathic normal-pressure hydrocephalus, Alzheimer's disease, and progressive supranuclear palsy

    International Nuclear Information System (INIS)

    Adachi, Michito; Ohshima, Fumi; Kawanami, Toru; Kato, Takeo

    2006-01-01

    On magnetic resonance imaging (MRI) sagittal sections, we sometimes encounter abnormal aspects of the superior profile of the midbrain and the cingulate sulcus in patients with dementia. In this preliminary study, we refer to these findings as the ''upper midbrain profile sign'' and the cingulate sulcus sign.'' We prospectively evaluated the usefulness of these signs for the diagnosis of idiopathic normal-pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). We evaluated the upper midbrain profile sign and the cingulate sulcus sign on MRI sagittal images obtained from 21 people with headaches but no neurological deficit (controls), 10 iNPH patients, 11 AD patients, and 5 PSP patients. The upper midbrain profile sign indicated a concave shape to the superior profile of the midbrain on mid-sagittal images, and the cingulate sulcus sign indicated a narrow, tight aspect of the posterior part of the cingulate sulcus on paramedian-sagittal images. These signs were never seen in any images from the controls. The upper midbrain profile sign was seen in 7 of 10 patients with iNPH, 5 of 11 with AD, and 3 of 5 with PSP. The cingulate sulcus sign was seen in all 10 patients with iNPH but was never seen in any patient with AD or PSP. The upper midbrain profile sign could support a diagnosis of PSP but cannot discriminate among iNPH, AD, and PSP. In contrast, the cingulate sulcus sign has a very high sensitivity for iNPH and should facilitate the distinction of iNPH from other dementias. In the clinical setting, it is momentous to evaluate these signs easily by one simple MRI sequence. (author)

  8. Altered regional homogeneity of brain spontaneous signals in SIV infected rhesus macaque model.

    Science.gov (United States)

    Zhao, Jing; Jing, Bin; Chen, Feng; Liu, Jiaojiao; Wang, Yuanyuan; Li, Hongjun

    2017-04-01

    Regional homogeneity (ReHo), a measurement from resting-state functional magnetic imaging (rs-fMRI) to reflect local synchronization of brain activities, has been widely explored in previous studies of neurological diseases. SIV infected model for detecting the neurological changes with progression was studied. In the study, six rhesus macaques infected by simian immunodeficiency virus (SIV) were scanned by resting-state fMRI at the following time points: before SIV inoculation (baseline), 12weeks and 24weeks post inoculation (12wpi, 24wpi). Meanwhile, the immunological parameters including serum percentage of CD4+ T cell, CD4/CD8 ratio and absolute CD4+ T cell number were measured and analyzed. In comparison of baseline, significant decreased ReHo was found in the left superior frontal gyrus, left superior temporal gyrus, left hippocampus, right precuneus, left angular gyrus, and bilateral occipital gyrus; in contrast increased ReHo in putamen at 12wpi. Moreover, at the time of 24wpi, decreased ReHo was observed in the right postcentral gyrus, left precentral gyrus, posterior cingulated gyrus and thalamus, while ReHo was increased in the left putamen, hippocampus, left anterior cingulated cortex and precentral cortex. The correlation analysis revealed that ReHo in the superior frontal gyrus showed negative association with CD4/CD8 ratio and positive with absolute CD4+ T cell number. The correlation analysis showed that percentage of CD4+ was correlated with the ReHo values in right middle frontal gyrus, bilateral thalamus and amygdala positively; negative relationship with left putamen, left superior frontal gyrus, left superior and middle temporal gyrus. The study first indicates that hippocampus, putamen, frontal and occipital lobe were impaired by using rs-fMRI and correlated with immunological parameters. Thus, ReHo value can be utilized as a noninvasive biomarker of spontaneous brain activity changes caused by the progression of neurological impairments

  9. Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry.

    Directory of Open Access Journals (Sweden)

    Rachid Sougrat

    2007-05-01

    Full Text Available The envelope glycoproteins of primate lentiviruses, including human and simian immunodeficiency viruses (HIV and SIV, are heterodimers of a transmembrane glycoprotein (usually gp41, and a surface glycoprotein (gp120, which binds CD4 on target cells to initiate viral entry. We have used electron tomography to determine the three-dimensional architectures of purified SIV virions in isolation and in contact with CD4+ target cells. The trimeric viral envelope glycoprotein surface spikes are heterogeneous in appearance and typically approximately 120 A long and approximately 120 A wide at the distal end. Docking of SIV or HIV-1 on the T cell surface occurs via a neck-shaped contact region that is approximately 400 A wide and consistently consists of a closely spaced cluster of five to seven rod-shaped features, each approximately 100 A long and approximately 100 A wide. This distinctive structure is not observed when viruses are incubated with T lymphocytes in the presence of anti-CD4 antibodies, the CCR5 antagonist TAK779, or the peptide entry inhibitor SIVmac251 C34. For virions bound to cells, few trimers were observed away from this cluster at the virion-cell interface, even in cases where virus preparations showing as many as 70 envelope glycoprotein trimers per virus particle were used. This contact zone, which we term the "entry claw", provides a spatial context to understand the molecular mechanisms of viral entry. Determination of the molecular composition and structure of the entry claw may facilitate the identification of improved drugs for the inhibition of HIV-1 entry.

  10. Viral CTL escape mutants are generated in lymph nodes and subsequently become fixed in plasma and rectal mucosa during acute SIV infection of macaques.

    Directory of Open Access Journals (Sweden)

    Thomas H Vanderford

    2011-05-01

    Full Text Available SIV(mac239 infection of rhesus macaques (RMs results in AIDS despite the generation of a strong antiviral cytotoxic T lymphocyte (CTL response, possibly due to the emergence of viral escape mutants that prevent recognition of infected cells by CTLs. To determine the anatomic origin of these SIV mutants, we longitudinally assessed the presence of CTL escape variants in two MamuA*01-restricted immunodominant epitopes (Tat-SL8 and Gag-CM9 in the plasma, PBMCs, lymph nodes (LN, and rectal biopsies (RB of fifteen SIV(mac239-infected RMs. As expected, Gag-CM9 did not exhibit signs of escape before day 84 post infection. In contrast, Tat-SL8 escape mutants were apparent in all tissues by day 14 post infection. Interestingly LNs and plasma exhibited the highest level of escape at day 14 and day 28 post infection, respectively, with the rate of escape in the RB remaining lower throughout the acute infection. The possibility that CTL escape occurs in LNs before RBs is confirmed by the observation that the specific mutants found at high frequency in LNs at day 14 post infection became dominant at day 28 post infection in plasma, PBMC, and RB. Finally, the frequency of escape mutants in plasma at day 28 post infection correlated strongly with the level Tat-SL8-specific CD8 T cells in the LN and PBMC at day 14 post infection. These results indicate that LNs represent the primary source of CTL escape mutants during the acute phase of SIV(mac239 infection, suggesting that LNs are the main anatomic sites of virus replication and/or the tissues in which CTL pressure is most effective in selecting SIV escape variants.

  11. Mucosal vaccination with heterologous viral vectored vaccine targeting subdominant SIV accessory antigens strongly inhibits early viral replication

    DEFF Research Database (Denmark)

    Xu, Huanbin; Andersson, Anne-Marie Carola; Ragonnaud, Emeline

    2017-01-01

    Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat...

  12. Characterization of Vocal Fold Vibration in Sulcus Vocalis Using High-Speed Digital Imaging

    Science.gov (United States)

    Yamauchi, Akihito; Yokonishi, Hisayuki; Imagawa, Hiroshi; Sakakibara, Ken-Ichi; Nito, Takaharu; Tayama, Niro; Yamasoba, Tatsuya

    2017-01-01

    Purpose: The aim of the present study was to qualitatively and quantitatively characterize vocal fold vibrations in sulcus vocalis by high-speed digital imaging (HSDI) and to clarify the correlations between HSDI-derived parameters and traditional vocal parameters. Method: HSDI was performed in 20 vocally healthy subjects (8 men and 12 women) and…

  13. Attenuation of Pathogenic Immune Responses during Infection with Human and Simian Immunodeficiency Virus (HIV/SIV) by the Tetracycline Derivative Minocycline

    Science.gov (United States)

    Drewes, Julia L.; Szeto, Gregory L.; Engle, Elizabeth L.; Liao, Zhaohao; Shearer, Gene M.; Zink, M. Christine; Graham, David R.

    2014-01-01

    HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo. PMID:24732038

  14. The Source Inversion Validation (SIV) Initiative: A Collaborative Study on Uncertainty Quantification in Earthquake Source Inversions

    Science.gov (United States)

    Mai, P. M.; Schorlemmer, D.; Page, M.

    2012-04-01

    Earthquake source inversions image the spatio-temporal rupture evolution on one or more fault planes using seismic and/or geodetic data. Such studies are critically important for earthquake seismology in general, and for advancing seismic hazard analysis in particular, as they reveal earthquake source complexity and help (i) to investigate earthquake mechanics; (ii) to develop spontaneous dynamic rupture models; (iii) to build models for generating rupture realizations for ground-motion simulations. In applications (i - iii), the underlying finite-fault source models are regarded as "data" (input information), but their uncertainties are essentially unknown. After all, source models are obtained from solving an inherently ill-posed inverse problem to which many a priori assumptions and uncertain observations are applied. The Source Inversion Validation (SIV) project is a collaborative effort to better understand the variability between rupture models for a single earthquake (as manifested in the finite-source rupture model database) and to develop robust uncertainty quantification for earthquake source inversions. The SIV project highlights the need to develop a long-standing and rigorous testing platform to examine the current state-of-the-art in earthquake source inversion, and to develop and test novel source inversion approaches. We will review the current status of the SIV project, and report the findings and conclusions of the recent workshops. We will briefly discuss several source-inversion methods, how they treat uncertainties in data, and assess the posterior model uncertainty. Case studies include initial forward-modeling tests on Green's function calculations, and inversion results for synthetic data from spontaneous dynamic crack-like strike-slip earthquake on steeply dipping fault, embedded in a layered crustal velocity-density structure.

  15. [Endoscopically controlled optimization of trans-scleral suture fixation of posterior chamber lenses in the ciliary sulcus].

    Science.gov (United States)

    Althaus, C; Sundmacher, R

    1993-08-01

    Two technical difficulties have to be overcome in transscleral suture fixation of posterior chamber intraocular lenses (PCL) in the ciliary sulcus: first, exact needle penetration through the sulcus, and second, exact positioning of the PCL haptics in the sulcus. Incongruence of the two may lead to long-term complications by compression or even strangulation of ciliary processes. Intraocular endoscopy was used intraoperatively to visualize the site of needle penetration and the final location of the haptics in patients. It turned out that with our previously described standard techniques the precision was far less than anticipated. Thus, new technical ways had to be sought to improve the precision of positioning. In secondary implantation without perforating keratoplasty we achieved the best results when the needle was passed ab externo before opening the eye and before anterior vitrectomy, taking advantage of a precisely prepared sclerocorneal zone. Passing the needle ab externo in an already hypotonic eyeball gives much less precise results. In combination with perforating keratoplasty with an open-sky approach, needle penetration ab interno is reliable. Correct positioning of the PCL haptics is at least as difficult as correct needle penetration, a fact which up to now has mostly been ignored. In 33 consecutively operated eyes the technique of implantation and PCL design was varied under endoscopical control.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Immune targeting of PD-1hi expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

    International Nuclear Information System (INIS)

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine; Venzon, David; Brocca-Cofano, Egidio; DiPasquale, Janet; Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit; Sui, Yongjun; Berzofsky, Jay A.; Liu, Linda; Langermann, Solomon; Robert-Guroff, Marjorie

    2013-01-01

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1 hi expressing T cells and Tregs in PBMCs, and PD-1 hi Tregs in lymph nodes. It transiently decreased expression of Ki67 and α 4 β 7 in PBMC CD4 + and CD8 + Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1 hi cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1 hi cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1 hi cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire

  17. The cortical representation of sensory inputs arising from bone.

    Science.gov (United States)

    Ivanusic, Jason J; Sahai, Vineet; Mahns, David A

    2009-05-07

    In the present study, we show that sensory information from bone reaches the discriminative areas of the somatosensory cortices by electrically stimulating the nerve to the cat humerus and recording evoked potentials on the surface of the primary (SI) and secondary (SII) somatosensory cortex. The SI focus was located over the rostral part of the postcruciate cortex, caudal to the lateral aspect of the cruciate sulcus. The SII focus was identified on the anterior ectosylvian gyrus, lateral to the suprasylvian sulcus. These foci were located adjacent to, or within areas that responded to stimulation of the median, ulnar and/or musculocutaneous nerves. The latency (6-11 ms) to onset of cortical responses in SI and SII were indistinguishable (unpaired t-test; P>0.05), and were consistent with activation of A delta fibers in the peripheral nerve. The amplitudes of the cortical responses were graded as a function of stimulus intensity, and may reflect a mechanism for intensity coding. We did not observe long latency cortical responses (50-300 ms) that would be consistent with C fiber activation in the peripheral nerve, and provide evidence that this may be attributable to inhibition of cortical responsiveness following the initial A delta response. Our finding of discrete, short latency evoked potentials (presumably of A delta origin) in the primary and secondary somatosensory cortices, following stimulation of a nerve innervating bone, may reflect a mechanism for the discriminative component of bone pain.

  18. The Secretion of IL-22 from Mucosal NKp44+ NK Cells Is Associated with Microbial Translocation and Virus Infection in SIV/SHIV-Infected Chinese Macaques

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2014-01-01

    Full Text Available Microbial translocation (MT causes systemic immune activation in chronic human immunodeficiency virus (HIV infection. The role of a novel subtype of innate lymphoid cells, the NKp44+ NK cells, in HIV/simian immunodeficiency virus- (SIV- induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV- infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44+ NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44+ NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44+ NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44+ NK cells and interleukin-22 (IL-22 secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44+ NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

  19. The relation between chondromalacia patella and meniscal tear and the sulcus angle/ trochlear depth ratio as a powerful predictor.

    Science.gov (United States)

    Resorlu, Hatice; Zateri, Coskun; Nusran, Gurdal; Goksel, Ferdi; Aylanc, Nilufer

    2017-01-01

    To investigate the relation between chondromalacia patella and the sulcus angle/trochlear depth ratio as a marker of trochlear morphology. In addition, we also planned to show the relationship between meniscus damage, subcutaneous adipose tissue thickness as a marker of obesity, patellar tilt angle and chondromalacia patella. Patients with trauma, rheumatologic disease, a history of knee surgery and patellar variations such as patella alba and patella baja were excluded. Magnetic resonance images of the knees of 200 patients were evaluated. Trochlear morphology from standardized levels, patellar tilt angle, lateral/medial facet ratio, subcutaneous adipose tissue thickness from 3 locations and meniscus injury were assessed by two specialist radiologists. Retropatellar cartilage was normal in 108 patients (54%) at radiological evaluation, while chondromalacia patella was determined in 92 (46%) cases. Trochlear sulcus angle and prepatellar subcutaneous adipose tissue thickness were significantly high in patients with chondromalacia patella, while trochlear depth and lateral patellar tilt angle were low. The trochlear sulcus angle/trochlear depth ratio was also high in chondromalacia patella and was identified as an independent risk factor at regression analysis. Additionally, medial meniscal tear was observed in 35 patients (38%) in the chondromalacia patella group and in 27 patients (25%) in the normal group, the difference being statistically significant (P = 0.033). An increased trochlear sulcus angle/trochlear depth ratio is a significant predictor of chondromalacia patella. Medial meniscus injury is more prevalent in patients with chondromalacia patella in association with impairment in knee biomechanics and the degenerative process.

  20. Ahmed glaucoma valve implantation with tube insertion through the ciliary sulcus in pseudophakic/aphakic eyes.

    Science.gov (United States)

    Eslami, Yadolla; Mohammadi, Massood; Fakhraie, Ghasem; Zarei, Reza; Moghimi, Sasan

    2014-02-01

    To report the efficacy and safety of Ahmed glaucoma valve (AGV) insertion into the ciliary sulcus in pseudophakic/aphakic patients. A chart review was done on patients with uncontrolled glaucoma, who underwent AGV implantation with tube inserted into the ciliary sulcus. Baseline intraocular pressure (IOP) and number of medications were compared with that of postoperative follow-up visits. Surgical success was defined as last IOP glaucoma control, and without loss of light perception. Postoperative complications were recorded. Twenty-three eyes of 23 patients were recruited with the mean follow-up of 9 months (range, 3 to 24 mo). The mean (SD) age of patients was 49.9 (16.9) years (range, 22 to 80 years). The mean (SD) IOP (mm Hg) was reduced from 37.9 (12.4) before surgery to 16.2 (3.6) at the last follow-up visit (P<0.001). The mean (SD) number of medications was reduced from 3.3 (0.9) preoperatively to 1 (1.1) at the last follow-up (P<0.001). Success rate was 18/23 (78.6%). Complications included endophthalmitis in 1 eye, tube exposure in 1 diabetic patient, and vitreous tube occlusion in 1 eye. No case of corneal decompensation or graft failure was seen during follow-up. Ciliary sulcus placement of the tube of AGV effectively reduces IOP and medication use in short term. It has the potential to lower corneal complications of anterior chamber tube insertion and avoids the need for pars plana vitrectomy and tube insertion in patients at higher risk of corneal decompensation.

  1. The far lateral transpontomedullary sulcus approach to pontine cavernous malformations: technical report and surgical results.

    Science.gov (United States)

    Abla, Adib A; Benet, Arnau; Lawton, Michael T

    2014-09-01

    Pontine cavernous malformations (CMs) located on a peripheral pontine surface or the fourth ventricular floor are resectable lesions, but those deep within the pons away from a pial surface are typically observed. However, the anterior bulge of the pons formed by the brachium pontis creates a unique entry point for access to deep pontine lesions from below, working upward through the pontomedullary sulcus. We developed a transpontomedullary sulcus (TPMS) approach to these lesions. The TPMS approach used the far lateral craniotomy and upper vagoaccessory triangle to define the surgical corridor. The entry point was above the olive, lateral to the pyramidal tracts and cranial nerve (CN) VI, above the preolivary sulcus and CN XII, and medial to CNs VII and VIII and CNs IX through XI. Four patients underwent this approach. All presented with hemorrhage and CN VI palsies. All pontine CMs were resected completely. Three patients were improved or unchanged, with good outcomes (modified Rankin Scale score ≤2) in all patients. The central pons remains difficult territory to access, and new surgical corridors are needed. The bulging underbelly of the pons allows access to pontine lesions deep to the pial surface from below. The far lateral TPMS approach is a novel and more direct alternative to the retrosigmoid transmiddle cerebellar peduncle approach. Unlike the retrosigmoid approach, the TPMS approach requires minimal parenchymal transgression and uses a brainstem entry point medial to most lower CNs. Favorable results demonstrate the feasibility of resecting pontine CMs that might have been previously deemed unresectable.

  2. Kunstimuuseumi Kumu püsiväljapanek = Permanent exhibition at the Kumu Art Museum of Estonia

    Index Scriptorium Estoniae

    2007-01-01

    siväljapanekute "Eesti kunsti klassika 18. sajandi algusest kuni 1944. aastani" (kujundus Liina Siib) ja "Eesti kunst 1945-1991" (kujundus Terje Kallast ja Urmas Luure) näitusekujundusest, kujundajatest, nende tähtsamad tööd näituse kujundajatena. 8 värv. vaadet, fotod L. Siibist ja T. Kallastist

  3. Semiautomated volumetric response evaluation as an imaging biomarker in superior sulcus tumors

    International Nuclear Information System (INIS)

    Vos, C.G.; Paul, M.A.; Dahele, M.; Soernsen de Koste, J.R. van; Senan, S.; Bahce, I.; Smit, E.F.; Thunnissen, E.; Hartemink, K.J.

    2014-01-01

    Volumetric response to therapy has been suggested as a biomarker for patient-centered outcomes. The primary aim of this pilot study was to investigate whether the volumetric response to induction chemoradiotherapy was associated with pathological complete response (pCR) or survival in patients with superior sulcus tumors managed with trimodality therapy. The secondary aim was to evaluate a semiautomated method for serial volume assessment. In this retrospective study, treatment outcomes were obtained from a departmental database. The tumor was delineated on the computed tomography (CT) scan used for radiotherapy planning, which was typically performed during the first cycle of chemotherapy. These contours were transferred to the post-chemoradiotherapy diagnostic CT scan using deformable image registration (DIR) with/without manual editing. CT scans from 30 eligible patients were analyzed. Median follow-up was 51 months. Neither absolute nor relative reduction in tumor volume following chemoradiotherapy correlated with pCR or 2-year survival. The tumor volumes determined by DIR alone and DIR + manual editing correlated to a high degree (R 2 = 0.99, P < 0.01). Volumetric response to induction chemoradiotherapy was not correlated with pCR or survival in patients with superior sulcus tumors managed with trimodality therapy. DIR-based contour propagation merits further evaluation as a tool for serial volumetric assessment. (orig.)

  4. Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

    Science.gov (United States)

    Campbell, Jennifer H.; Burdo, Tricia H.; Autissier, Patrick; Bombardier, Jeffrey P.; Westmoreland, Susan V.; Soulas, Caroline; González, R. Gilberto; Ratai, Eva-Maria; Williams, Kenneth C.

    2011-01-01

    Background Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline's functions are not well defined. Methods Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. PMID:21494695

  5. "Walk the Rim, Feel the Bone" Technique in Superior Sulcus Filling.

    Science.gov (United States)

    Looi, Audrey L G; Yong, Kai-Ling

    2015-12-01

    Superior sulcus filler injection is a nonsurgical method to rejuvenate the upper face. Blindness and stroke are devastating complications of facial filler injection. This study describes an injection technique that minimizes the risk of blindness and includes a case study demonstrating the cosmetic benefits of this procedure. To avoid retrograde injection of filler embolus into the ophthalmic artery, we advocate a "'walk the rim, feel the bone" approach. Small boluses of hyaluronic acid filler are given in preperiosteal plane, avoiding the superior orbital foramen.

  6. Long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses in children: An ultrasound biomicroscopy study.

    Directory of Open Access Journals (Sweden)

    Yun-E Zhao

    Full Text Available To evaluate the long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses (IOLs in children after pediatric cataract surgery.IOL was implanted in the ciliary sulcus in 21 eyes of 14 children, and in the capsular bag in 19 eyes of 12 children for the treatment of pediatric cataract in an institutional setting. Ultrasound biomicroscopy (UBM was performed. Main outcome measures included IOL decentration, IOL tilt, anterior chamber depth (ACD, angle-opening distance at 500 μm (AOD500, trabecular-iris angle (TIA, best-corrected visual acuity (BCVA, intraocular pressure (IOP, and incidence of postoperative complications.The mean follow-up period was 6.81 ± 1.82 years. Comparing to the capsular bag fixation group, the ciliary sulcus fixation group had higher vertical IOL decentration, horizontal IOL tilt, and vertical IOL tilt (p = 0.02, 0.01,0.01, respectively, higher incidence of iris-IOL contact and peripheral anterior synechia (p = 0.001, 0.03, respectively, smaller ACD, AOD500, and TIA (p = 0.02, 0.03, 0.04, respectively, higher mean IOP (17.10 ±6.06 mmHg vs.14.15± 4.74 mmHg, p = 0.01, and higher incidence of secondary glaucoma (28.57% vs. 10.53%, p = 0.007.There was no significant difference between the two groups with regard to the BCVA, refractive errors, incidence of myopic shift, nystagmus, strabismus, and visual axis opacity.Ciliary sulcus fixation of IOLs in pediatric eyes may increase IOL malposition and crowding of the anterior segment, and may associate with a higher risk of secondary glaucoma compared to capsular bag fixation of IOLs.

  7. Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

    Science.gov (United States)

    Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S Munir; Fenizia, Claudio; Lifson, Jeffrey D; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David; Franchini, Genoveffa

    2013-02-01

    The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+) T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV(mac251) acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells that express high levels of α(4)β(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

  8. Pigment dispersion and chronic intraocular pressure elevation after sulcus placement of 3-piece acrylic intraocular lens.

    Science.gov (United States)

    Almond, M Camille; Wu, Michael C; Chen, Philip P

    2009-12-01

    A 55-year-old man had phacoemulsification and implantation of a 3-piece acrylic intraocular lens (IOL) (AcrySof MA60AC) in the right eye. One month postoperatively, the intraocular pressure (IOP) was 48 mm Hg and peripheral transillumination defects were noted in the iris circumferentially, with the IOL optic edge visible as a silhouette. Gonioscopy showed dense pigmentation of the trabecular meshwork in the right eye, but in the left eye, only mild trabecular meshwork pigment was seen, along with a concave peripheral iris insertion. At 21 months, the right eye required 3 medications for IOP control. While pigment dispersion has been widely reported after placement of 1-piece acrylic IOLs in the ciliary sulcus, we conclude that in susceptible individuals with a concave peripheral iris insertion, pigment dispersion can occur with sulcus placement of a 3-piece acrylic model despite its thinner optic and angulated haptics.

  9. Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model.

    Science.gov (United States)

    Nomura, Takushi; Yamamoto, Hiroyuki; Takahashi, Naofumi; Naruse, Taeko K; Kimura, Akinori; Matano, Tetsuro

    2014-07-25

    Virus-specific CD8(+) T-cell responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. Multiple studies on HIV-infected individuals and SIV-infected macaques have indicated association of several major histocompatibility complex class I (MHC-I) genotypes with lower viral loads and delayed AIDS progression. Understanding of the viral control mechanism associated with these MHC-I genotypes would contribute to the development of intervention strategy for HIV control. We have previously reported a rhesus MHC-I haplotype, 90-120-Ia, associated with lower viral loads after SIVmac239 infection. Gag206-216 and Gag241-249 epitope-specific CD8(+) T-cell responses have been shown to play a central role in the reduction of viral loads, whereas the effect of Nef-specific CD8(+) T-cell responses induced in all the 90-120-Ia(+) macaques on SIV replication remains unknown. Here, we identified three CD8(+) T-cell epitopes, Nef9-19, Nef89-97, and Nef193-203, associated with 90-120-Ia. Nef9-19 and Nef193-203 epitope-specific CD8(+) T-cell responses frequently selected for mutations resulting in viral escape from recognition by these CD8(+) T cells, indicating that these CD8(+) T cells exert strong suppressive pressure on SIV replication. Results would be useful for elucidation of the viral control mechanism associated with 90-120-Ia. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia A.

    2016-04-23

    Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  11. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Venzon, David [Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Brocca-Cofano, Egidio; DiPasquale, Janet [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit [Advanced Bioscience Laboratories Inc., Rockville, MD 20850 (United States); Sui, Yongjun; Berzofsky, Jay A. [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Liu, Linda; Langermann, Solomon [Amplimmune Inc., Gaithersburg, MD 20878 (United States); Robert-Guroff, Marjorie, E-mail: guroffm@mail.nih.gov [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-15

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{sup hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.

  12. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia A.; Bustamante, Eduardo A.; Bortell, Nikki; Morsey, Brenda; Fox, Howard S.; Ravasi, Timothy; Marcondes, Maria Cecilia Garibaldi

    2016-01-01

    /function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model

  13. Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN

    NARCIS (Netherlands)

    Geijtenbeek, T. B.; Koopman, G.; van Duijnhoven, G. C.; van Vliet, S. J.; van Schijndel, A. C.; Engering, A.; Heeney, J. L.; van Kooyk, Y.

    2001-01-01

    Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a

  14. Management of sulcus-fixated single-piece intraocular lens-induced pigmentary glaucoma with 3-piece IOL exchange.

    Science.gov (United States)

    Rabie, Hossein Mohammad; Esfandiari, Hamed; Rikhtegar, Mohammad Hassan; Hekmat, Vahid

    2018-02-01

    To describe our experience with exchanging sulcus-fixated single-piece intraocular lens (IOL) with 3-piece IOLs for management of pigmentary glaucoma. In this retrospective study, records of patients who underwent sulcus-fixated single-piece IOL exchanged with 3-piece IOLs were retrieved, and demographic and baseline data of patients, type of IOL, pre- and post-IOL exchange BCVA, IOP, number of anti-glaucoma medications, and optic nerve head examination were documented. Baseline and final examinations were analyzed and compared. Mean age of the patients was 59 ± 10 years, and 5 (41.6%) were female. Mean interval between primary cataract extraction operation and IOL exchange was 17 ± 5 months. Nine patients received in sulcus implantation of Alcon SA60AT, and three patients had SN60WF model at the end of primary surgery. BCVA changed insignificantly from 0.06 ± 0.06 logMAR to 0.06 ± 0.06 after IOL exchange. (P = 0.22) IOP was controlled in 8 cases (66.6%), but four cases (33.3%) needed glaucoma surgery to further control glaucoma condition. IOP decreased significantly from preoperative 17 ± 3 to 14 ± 1 mmHg postoperatively. Patients with advanced age and higher baseline IOP were more likely to undergo glaucoma surgery after IOL exchange. (P = 0.07 and 0.00, respectively). single-piece IOL exchange with 3-piece IOL dramatically decreases pigment release and reduces IOP. Those with advanced age and higher IOP are less likely to respond to IOL exchange and may need glaucoma surgery to control high intraocular pressure.

  15. Pneumopericardium and Deep Sulcus Sign After Blunt Chest Trauma

    Directory of Open Access Journals (Sweden)

    Taner Tarladacalisir

    2014-12-01

    Full Text Available Pneumopericardium is defined as air between the leaves of the pericardium, which is usually self-limited. In tension pneumopericardium, however, rapid fluid resuscitation and haemodynamic monitoring followed by pericardial fenestration and drainage should be performed. A 49-year-old male falling from height was brought to the emergency room. On chest X-ray in supine position, a deep sulcus sign and subcutaneous emphysema with multiple rib fractures were detected. At computerized tomography, pericardial free air, right pneumothorax and subcutaneous emphysema were detected. A tube thoracostomy was applied to the patient. During follow-up with cardiac enzymes in the intensive care unit, no tension pneumopericardium developed, and subcutaneous emphysema regressed. A control computerized tomography scan showed a complete regression in the pneumopericardium on the tenth day.

  16. Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

    Science.gov (United States)

    Adnan, Sama; Reeves, R Keith; Gillis, Jacqueline; Wong, Fay E; Yu, Yi; Camp, Jeremy V; Li, Qingsheng; Connole, Michelle; Li, Yuan; Piatak, Michael; Lifson, Jeffrey D; Li, Wenjun; Keele, Brandon F; Kozlowski, Pamela A; Desrosiers, Ronald C; Haase, Ashley T; Johnson, R Paul

    2016-12-01

    Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

  17. Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA on SIV-infected Chinese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Binhua Ling

    Full Text Available Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM treated with intensive combination antiretroviral therapy (cART and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA.SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

  18. Surgical Outcomes of Deep Superior Sulcus Augmentation Using Acellular Human Dermal Matrix in Anophthalmic or Phthisis Socket.

    Science.gov (United States)

    Cho, Won-Kyung; Jung, Su-Kyung; Paik, Ji-Sun; Yang, Suk-Woo

    2016-07-01

    Patients with anophthalmic or phthisis socket suffer from cosmetic problems. To resolve those problems, the authors present the surgical outcomes of deep superior sulcus (DSS) augmentation using acellular dermal matrix in patients with anophthalmic or phthisis socket. The authors retrospectively reviewed anophthalmic or phthisis patients who underwent surgery for DSS augmentation using acellular dermal matrix. To evaluate surgical outcomes, the authors focused on 3 aspects: the possibility of wearing contact prosthesis, the degree of correction of the DSS, and any surgical complications. The degree of correction of DSS was classified as excellent: restoration of superior sulcus enough to remove sunken sulcus shadow; fair: gain of correction effect but sunken shadow remained; or fail: no effect of correction at all. Ten eyes of 10 patients were included. There was a mean 21.3 ± 37.1-month period from evisceration or enucleation to the operation for DSS augmentation. All patients could wear contact prosthesis after the operation (100%). The degree of correction was excellent in 8 patients (80%) and fair in 2. Three of 10 (30%) showed complications: eyelid entropion, upper eyelid multiple creases, and spontaneous wound dehiscence followed by inflammation after stitch removal. Uneven skin surface and paresthesia in the forehead area of the affected eye may be observed after surgery. The overall surgical outcomes were favorable, showing an excellent degree of correction of DSS and low surgical complication rates. This procedure is effective for patients who have DSS in the absence or atrophy of the eyeball.

  19. Attention to emotion modulates fMRI activity in human right superior temporal sulcus.

    Science.gov (United States)

    Narumoto, J; Okada, T; Sadato, N; Fukui, K; Yonekura, Y

    2001-10-01

    A parallel neural network has been proposed for processing various types of information conveyed by faces including emotion. Using functional magnetic resonance imaging (fMRI), we tested the effect of the explicit attention to the emotional expression of the faces on the neuronal activity of the face-responsive regions. Delayed match to sample procedure was adopted. Subjects were required to match the visually presented pictures with regard to the contour of the face pictures, facial identity, and emotional expressions by valence (happy and fearful expressions) and arousal (fearful and sad expressions). Contour matching of the non-face scrambled pictures was used as a control condition. The face-responsive regions that responded more to faces than to non-face stimuli were the bilateral lateral fusiform gyrus (LFG), the right superior temporal sulcus (STS), and the bilateral intraparietal sulcus (IPS). In these regions, general attention to the face enhanced the activities of the bilateral LFG, the right STS, and the left IPS compared with attention to the contour of the facial image. Selective attention to facial emotion specifically enhanced the activity of the right STS compared with attention to the face per se. The results suggest that the right STS region plays a special role in facial emotion recognition within distributed face-processing systems. This finding may support the notion that the STS is involved in social perception.

  20. Partial protection of SIV-infected rhesus monkeys against superinfection with a heterologous SIV isolate

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory

    2009-01-01

    Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virus for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.

  1. Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

    Directory of Open Access Journals (Sweden)

    Sama Adnan

    2016-12-01

    Full Text Available Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

  2. The relation of sulcus nervi radialis with the fracture line of humerus fracture and radial nerve injury

    DEFF Research Database (Denmark)

    Ozden, Hilmi; Demir, Ahmet; Guven, Gul

    2008-01-01

    PURPOSE: Radial nerve is closely in contact with the bone in sulcus nervi radialis (SNR). Location of SNR shows ethnic differences. Radial nerve is a big problem in humerus fractures and its surgery. In this study, we aimed to examine if humerus fractures of this region increases the probability...

  3. Solving intraocular lens-related pigment dispersion syndrome with repositioning of primary sulcus implanted single-piece IOL in the capsular bag.

    Science.gov (United States)

    Kohnen, Thomas; Kook, Daniel

    2009-08-01

    We describe 2 cases of pigment dispersion syndrome (PDS) after uneventful phacoemulsification and implantation of a posterior chamber single-piece intraocular lens (IOL) with a sharp-edge design. In both cases, several days after IOL implantation, marked pigment dispersion was seen on the iris and in the trabecular meshwork, associated with an elevation in intraocular pressure (IOP). Thorough examination showed that the implanted IOL was in the ciliary sulcus. After surgical repositioning of both IOLs in the capsular bag, the pigment dispersion regressed and the IOP returned to normal limits. The 2 cases suggest that particularly in PDS patients, an IOL with an anterior sharp-edge design should be implanted in the capsular bag. Implantation in the ciliary sulcus should be avoided.

  4. A phase I/II exploratory clinical trial for intracordal injection of recombinant hepatocyte growth factor for vocal fold scar and sulcus.

    Science.gov (United States)

    Hirano, Shigeru; Kawamoto, Atsuhiko; Tateya, Ichiro; Mizuta, Masanobu; Kishimoto, Yo; Hiwatashi, Nao; Kawai, Yoshitaka; Tsuji, Takuya; Suzuki, Ryo; Kaneko, Mami; Naito, Yasushi; Kagimura, Tatsuo; Nakamura, Tatsuo; Kanemaru, Shin-Ichi

    2018-04-01

    Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 μg of HGF per vocal fold; Step II received 3 μg of HGF; and Step III received 10 μg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Prevalence of the acetabular sublabral sulcus at MR arthrography in patients under 17 years of age: does it exist?

    Energy Technology Data Exchange (ETDEWEB)

    Magerkurth, Olaf [University of Michigan, Department of Radiology, Ann Arbor, MI (United States); Hospital Baden, Department of Radiology, Baden (Switzerland); Jacobson, Jon A.; Morag, Yoav; Fessell, David [University of Michigan, Department of Radiology, Ann Arbor, MI (United States); Bedi, Asheesh; Sekiya, Jon K. [University of Michigan, Department of Orthopedic Surgery, Ann Arbor, MI (United States)

    2015-04-18

    To retrospectively determine characteristics of contrast-filled acetabular labral clefts in patients under the age of 17 years at MR arthrography (Mra) correlated with arthroscopy, which may impact the thinking regarding the existence of a sublabral sulcus. After IRB approval, 41 patients under the age of 17 who had MRa were identified. The following observations of contrast-filled clefts were assessed: (1) presence/absence, (2) location, (3) depth, (4) abnormal signal within the labrum and (5) shape (linear, gaping, complex). Fisher's exact and the Wilcoxon matched-pairs signed-rank test were performed. Interreader agreement was calculated with Cohen's k. Reader 1 found clefts in 41 %. Depth was less than half in 6 %, more than half in 65 % and full thickness in 29 %. Shape was linear in 53 %, gaping in 18 % and complex in 29 %. Signal changes occurred in 88 %. Reader 2 found clefts in 29 %. Depth was less than half in 17 %, more than half in 58 % and full thickness in 25 %. Shape was linear in 50 %, gaping in 42 % and complex in 17 %. Signal changes occurred in 50 %. None of the clefts fulfilled the criteria for a sublabral sulcus at MRa and arthroscopy. None of the clefts found in our subjects under the age of 17 years met the MRa and arthroscopy criteria for a sublabral sulcus, which supports the theory that such clefts represent labral tears. (orig.)

  6. [Human interaction, social cognition, and the superior temporal sulcus].

    Science.gov (United States)

    Brunelle, Francis; Saitovitch, Anna; Boddaert, Nathalie; Grevent, David; Cambier, Jean; Lelord, Gilbert; Samson, Yves; Zilbovicius, Monica

    2013-01-01

    Human beings are social animals. This ability to live together is ensured by cognitive functions, the neuroanatomical bases of which are starting to be unraveled by MRI-based studies. The regions and network engaged in this process are known as the "social brain ". The core of this network is the superior temporal sulcus (STS), which integrates sensory and emotional inputs. Modeling studies of healthy volunteers have shown the role of the STS.in recognizing others as biological beings, as well as facial and eye-gaze recognition, intentionality and emotions. This cognitive capacity has been described as the "theory of mind ". Pathological models such as autism, in which the main clinical abnormality is altered social abilities and communication, have confirmed the role of the STS in the social brain. Conceptualisation of this empathic capacity has been described as "meta cognition ", which forms the basis of human social organizationand culture.

  7. The effect of photodynamic therapy on pathogenic bacteria around peri-implant sulcus and in the cavity between abutment and implant after healing phase: A prospective clinical study.

    Science.gov (United States)

    Zhou, Lin-Yi; Shi, Jun-Yu; Zhu, Yu; Qian, Shu-Jiao; Lai, Hong-Chang; Gu, Ying-Xin

    2018-05-14

    To compare levels of pathogens from peri-implant sulcus versus abutment screw cavities after photodynamic therapy. Twenty patients were included. Photodynamic therapy (PDT) was applied both in sulcus and cavities after sampling following suprastructures loading, and repeated after 2 weeks. Two samples each containing four paper points were collected for each implant at baseline, 2 weeks, 3 months: (i) peri-implant sulcus and (ii) abutment screw cavities. Seventy-five percent ethanol was applied in another 20 patients as the control group in the same way. qPCR was used to quantify periodontal pathogens: Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mutans. PDT showed a better bacterial reduction than ethanol. P. g. and F. n. were most frequently detected, while less for S. m. P. gingivalis' proportion from both sites was significantly higher than the other two bacteria (P abutment screw cavities were always less than those from peri-implant sulcus and was significantly lower for total bacteria at 3 months (P abutment screw cavities significantly reduced at 3 months compared to baseline (P abutment screw cavities in the long run, suggesting PDT an effective way sterilizing inner surface of oral implant suprastrutures. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  8. Supplementary Material for: Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia

    2016-01-01

    Abstract Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  9. Organic contaminants degradation from the S(IV) autoxidation process catalyzed by ferrous-manganous ions: A noticeable Mn(III) oxidation process.

    Science.gov (United States)

    Zhang, Jiaming; Ma, Jun; Song, Haoran; Sun, Shaofang; Zhang, Zhongxiang; Yang, Tao

    2018-04-15

    Remarkable atrazine degradation in the S(IV) autoxidation process catalyzed by Fe 2+ -Mn 2+ (Fe 2+ /Mn 2+ /sulfite) was demonstrated in this study. Competitive kinetic experiments, alcohol inhibiting methods and electron spin resonance (ESR) experiments proved that sulfur radicals were not the major oxidation species. Mn(III) was demonstrated to be the primary active species in the Fe 2+ /Mn 2+ /sulfite process based on the comparison of oxidation selectivity. Moreover, the inhibiting effect of the Mn(III) hydrolysis and the S(IV) autoxidation in the presence of organic contaminants indicated the existence of three Mn(III) consumption routes in the Fe 2+ /Mn 2+ /sulfite process. The absence of hydroxyl radical and sulfate radical was interpreted by the competitive dynamics method. The oxidation capacity of the Fe 2+ /Mn 2+ /sulfite was independent of the initial pH (4.0-6.0) because the fast decay of S(IV) decreased initial pH below 4.0 rapidly. The rate of ATZ degradation was independent of the dissolved oxygen (DO) because that the major DO consumption process was not the rate determining step during the production of SO 5 •- . Phosphate and bicarbonate were confirmed to have greater inhibitory effects than other environmental factors because of their strong pH buffering capacity and complexing capacity for Fe 3+ . The proposed acetylation degradation pathway of ATZ showed the application of the Fe 2+ /Mn 2+ /sulfite process in the research of contaminants degradation pathways. This work investigated the characteristics of the Fe 2+ /Mn 2+ /sulfite process in the presence of organic contaminants, which might promote the development of Mn(III) oxidation technology. Copyright © 2018. Published by Elsevier Ltd.

  10. Supplementary Material for: Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia; Bustamante, Eduardo; Bortell, Nikki; Morsey, Brenda; Fox, Howard; Ravasi, Timothy; Marcondes, Maria

    2016-01-01

    /function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model

  11. Photoluminescence excitation spectroscopy of SiV- and GeV- color center in diamond

    Science.gov (United States)

    Häußler, Stefan; Thiering, Gergő; Dietrich, Andreas; Waasem, Niklas; Teraji, Tokuyuki; Isoya, Junichi; Iwasaki, Takayuki; Hatano, Mutsuko; Jelezko, Fedor; Gali, Adam; Kubanek, Alexander

    2017-06-01

    Color centers in diamond are important quantum emitters for a broad range of applications ranging from quantum sensing to quantum optics. Understanding the internal energy level structure is of fundamental importance for future applications. We experimentally investigate the level structure of an ensemble of few negatively charged silicon-vacancy (SiV-) and germanium-vacancy (GeV-) centers in bulk diamond at room temperature by photoluminescence (PL) and excitation (PLE) spectroscopy over a broad wavelength range from 460 to 650 {nm} and perform power-dependent saturation measurements. For SiV- our experimental results confirm the presence of a higher energy transition at ˜ 2.31 {eV}. By comparison with detailed theoretical simulations of the imaginary dielectric function we interpret the transition as a dipole-allowed transition from {}2{E}g-state to {}2{A}2u-state where the corresponding a 2u -level lies deeply inside the diamond valence band. Therefore, the transition is broadened by the diamond band. At higher excitation power of 10 {mW} we indicate signs of a parity-conserving transition at ˜ 2.03 {eV} supported by saturation measurements. For GeV- we demonstrate that the PLE spectrum is in good agreement with the mirror image of the PL spectrum of the zero-phonon line. Experimentally we do not observe a higher lying energy level up to a transition wavelength of 460 {nm}. The observed PL spectra are identical, independent of excitation wavelength, suggesting a rapid decay to {}2{E}u excited state and followed by optical transition to {}2{E}g ground state. Our investigations convey important insights for future quantum optics and quantum sensing experiments based on SiV--center and GeV--center in diamond.

  12. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

    2003-01-01

    To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

  13. Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

    Science.gov (United States)

    Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

    2012-11-26

    Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (Pnow hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. "Eesti taluarhitektuur. Püsiv ja muutuv : Eesti Vabaõhumuuseumi näitus = Estonian farm architecture. Enduring and changing : an Estonian Open Air Museum exhibition / Heiki Pärdi

    Index Scriptorium Estoniae

    Pärdi, Heiki, 1951-

    2015-01-01

    Eesti Vabaõhumuuseumi näitus "Eesti taluarhitektuur. Püsiv ja muutuv". Näituse autor Heiki Pärdi, kuraator Elo Lutsepp, kujundaja Jan Skolimowski (KAMP Arhitektid). 2014. aasta Kultuurkapitali Arhitektuuripreemia kandidaat

  15. Graded representations of emotional expressions in the left superior temporal sulcus

    Directory of Open Access Journals (Sweden)

    Christopher P Said

    2010-03-01

    Full Text Available Perceptual categorization is a fundamental cognitive process that gives meaning to an often graded sensory environment. Previous research has subdivided the visual pathway into posterior regions that processes the physical properties of a stimulus, and frontal regions that process more abstract properties such as category information. The superior temporal sulcus (STS is known to be involved in face and emotion perception, but the nature of its processing remains unknown. Here, we used targeted fMRI measurements of the STS to investigate whether its representations of facial expressions are categorical or noncategorical. Multivoxel pattern analysis showed that even though subjects were performing a categorization task, the left STS contained graded, noncategorical representations. In the right STS, representations showed evidence for both stimulus-related gradations and a categorical boundary.

  16. Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail

    Directory of Open Access Journals (Sweden)

    Takeo eKuwata

    2013-05-01

    Full Text Available The role of antibodies in protecting the host from human immunodeficiency virus type 1 (HIV-1 infection is of considerable interest, particularly because the RV144 trial results suggest that antibodies contribute to protection. Although infection of nonhuman primates with simian immunodeficiency virus (SIV is commonly used as an animal model of HIV-1 infection, the viral epitopes that elicit potent and broad neutralizing antibodies to SIV have not been identified. We isolated a monoclonal antibody (MAb B404 that potently and broadly neutralizes various SIV strains. B404 targets a conformational epitope comprising the V3 and V4 loops of Env that intensely exposed when Env binds CD4. B404-resistant variants were obtained by passaging viruses in the presence of increasing concentration of B404 in PM1/CCR5 cells. Genetic analysis revealed that the Q733stop mutation, which truncates the cytoplasmic tail of gp41, was the first major substitution in Env during passage. The maximal inhibition by B404 and other MAbs were significantly decreased against a recombinant virus with a gp41 truncation compared with the parental SIVmac316. This indicates that the gp41 truncation was associated with resistance to antibody-mediated neutralization. The infectivities of the recombinant virus with the gp41 truncation were 7900-fold, 1000-fold, and 140-fold higher than those of SIVmac316 in PM1, PM1/CCR5, and TZM-bl cells, respectively. Immunoblotting analysis revealed that the gp41 truncation enhanced the incorporation of Env into virions. The effect of the gp41 truncation on infectivity was not obvious in the HSC-F macaque cell line, although the resistance of viruses harboring the gp41 truncation to neutralization was maintained. These results suggest that viruses with a truncated gp41 cytoplasmic tail were selected by increased infectivity in human cells and by acquiring resistance to neutralizing antibody.

  17. On the scavenging of SO2 by large and small rain drops. 5. A wind tunnel and theoretical study of the desorption of SO2 from water drops containing S(IV)

    International Nuclear Information System (INIS)

    Mitra, S.K.; Hannemann, A.U.

    1993-01-01

    An experimental and theoretical study has been carried out to investigate the fate of desorption of SO 2 from water drops falling at terminal velocity in air. The experiments were carried out in the Mainz vertical wind tunnel in which water drops of various sizes containing S(IV) in various concentrations were freely suspended in the vertical airstream of the tunnel. The results were compared with the predictions of theoretical models, and with the experiments of Walcek et al. This comparison shows that the predictions of the diffusion model of Kronig and Brink in the formulation given by Walcek and Pruppacher agree well with the experimental results. In contrast, the predictions of the diffusion model which assumes complete internal mixing inside a drop agrees with the experimental results only if the concentration of S(IV) inside the drop is less than that equivalent of an equilibrium SO 2 concentration of 15 ppbv. At larger concentrations, the theoretical predictions of the model for complete internal mixing progressively deviate from the experimental results. It is further shown that Barrie's double film model can be used to interpret the resistance to diffusion inside a drop in terms of a diffusion boundary layer inside the drop which increases in thickness with decreasing concentration of S(IV). Applying our results to the desorption of SO 2 from small and large rain drops falling below an assumed cloud base, shows that for typical contents of S(IV) inside the drops substantial amounts of SO 2 will desorb from these drops unless H 2 O 2 is present in the surrounding air

  18. What causes an icy fault to slip? Investigating strike-slip failure conditions on Ganymede at Dardanus and Tiamat Sulcus.

    Science.gov (United States)

    Cameron, M. E.; Smith-Konter, B. R.; Burkhard, L. M.; Collins, G. C.; Seifert, F.; Pappalardo, R. T.

    2015-12-01

    Ganymede exhibits two geologically distinct terrains known as dark and light (grooved) terrain. The mechanism for a transition from dark to light terrain remains unclear; however, inferences of strike-slip faulting and distributed shear zones suggest that strike-slip tectonism may be important to the structural development of Ganymede's surface and in this transition. Here we investigate the role of tidal stresses on Ganymede in the formation and evolution of strike-slip structures in both dark and grooved terrains. Using numerical code SatStress, we calculate both diurnal and non-synchronous rotation (NSR) tidal stresses at Ganymede's surface. Specifically, we investigate the role of fault friction and orbital eccentricity in the development of ~45 km of right-lateral offset at Dardanus Sulcus and a possible case of study with a detailed morphological mapping of strike-slip morphologies (en echelon structures, strike-slip duplexes, laterally offset pre-existing features, and possible strained craters) at Nun Sulcus and several other locations. These structures serve as example regions to provide improved constraints for global stress mechanisms responsible for strike-slip fault evolution on Ganymede.

  19. Intraoperative definition of bottom-of-sulcus dysplasia using intraoperative ultrasound and single depth electrode recording - A technical note.

    Science.gov (United States)

    Miller, Dorothea; Carney, Patrick; Archer, John S; Fitt, Gregory J; Jackson, Graeme D; Bulluss, Kristian J

    2018-02-01

    Bottom of sulcus dysplasias (BOSDs) are localized focal cortical dysplasias (FCDs) centred on the bottom of a sulcus that can be highly epileptogenic, but difficult to delineate intraoperatively. We report on a patient with refractory epilepsy due to a BOSD, successfully resected with the aid of a multimodal surgical approach using neuronavigation based on MRI and PET, intraoperative ultrasound (iUS) and electrocorticography (ECoG) using depth electrodes. The lesion could be visualized on iUS showing an increase in echogenicity at the grey-white matter junction. IUS demonstrated the position of the depth electrode in relation to the lesion. Depth electrode recording showed almost continuous spiking. Thus, intraoperative imaging and electrophysiology helped confirm the exact location of the lesion. Post-resection ultrasound demonstrated the extent of the resection and depth electrode recording did not show any epileptiform activity. Thus, both techniques helped assess completeness of resection. The patient has been seizure free since surgery. Using a multimodal approach including iUS and ECoG is a helpful adjunct in surgery for BOSD and may improve seizure outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Viral RNA levels and env variants in semen and tissues of mature male rhesus macaques infected with SIV by penile inoculation.

    Directory of Open Access Journals (Sweden)

    Francis Fieni

    Full Text Available HIV is shed in semen but the anatomic site of virus entry into the genital secretions is unknown. We determined viral RNA (vRNA levels and the envelope gene sequence in the SIVmac 251 viral populations in the genital tract and semen of 5 adult male rhesus monkeys (Macaca mulatta that were infected after experimental penile SIV infection. Paired blood and semen samples were collected from 1-9 weeks after infection and the monkeys were necropsied eleven weeks after infection. The axillary lymph nodes, testes, epididymis, prostate, and seminal vesicles were collected and vRNA levels and single-genome analysis of the SIVmac251 env variants was performed. At the time of semen collection, blood vRNA levels were between 3.09 and 7.85 log10 vRNA copies/ml plasma. SIV RNA was found in the axillary lymph nodes of all five monkeys and in 3 of 5 monkeys, all tissues examined were vRNA positive. In these 3 monkeys, vRNA levels (log10 SIVgag copies/ug of total tissue RNA in the axillary lymph node (6.48 ± 0.50 were significantly higher than in the genital tract tissues: testis (3.67 ± 2.16; p<0.05, epididymis (3.08 ± 1.19; p<0.0001, prostate (3.36 ± 1.30; p<0.01, and seminal vesicle (2.67 ± 1.50; p<0.0001. Comparison of the SIVmac251 env viral populations in blood plasma, systemic lymph node, and genital tract tissues was performed in two of the macaques. Visual inspection of the Neighbor-Joining phylograms revealed that in both animals, all the sequences were generally distributed evenly among all tissue compartments. Importantly, viral populations in the genital tissues were not distinct from those in the systemic tissues. Our findings demonstrate striking similarity in the viral populations in the blood and male genital tract tissues within 3 months of penile SIV transmission.

  1. Cortical thickness difference across the central sulcus visualized in the presence of vasogenic edema

    Energy Technology Data Exchange (ETDEWEB)

    Togao, Osamu [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582 (Japan)], E-mail: togao@dr.hosp.kyushu-u.ac.jp; Yoshiura, Takashi; Mihara, Futoshi; Noguchi, Tomoyuki; Hiwatashi, Akio; Yamashita, Koji; Yoshitake, Tadamasa; Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582 (Japan)

    2008-05-15

    Purpose: To confirm the cortical thickness difference across the central sulcus (CS) visualized in the presence of vasogenic edema on MRI. Materials and methods: T2-weighted images of 70 cerebral hemispheres showing vasogenic edema infiltrating into subcortical white matter around the CS were studied retrospectively. Two neuroradiologists measured the cortical thickness of the anterior and posterior banks of the CS, precentral sulci (PrCS), and postcentral sulci (PoCS). Additionally, we compared the cortical thickness of the anterior and posterior banks of each sulcus visually using a grading scale. Results: On T2-weighted images, the cerebral cortex was highlighted by a high signal-intensity vasogenic edema in the adjacent white matter, and its thickness was readily measurable. The unique cortical thickness difference between the anterior and posterior banks of the CS were confirmed with measurements of 2.67 and 1.48 mm (p < 0.0001). The cortical measurements across other cerebral sulci were 2.04 and 1.95 mm (NS) for the PrCS, and 1.67 and 1.77 mm (NS) for the PoCS. The cortical thickness ratios were 1.86 for the CS, 1.05 for the PrCS, and 0.96 for the PoCS. On visual evaluation, the anterior bank of the CS was thicker than the posterior bank in 93% (65/70). For the PrCS and PoCS, the thickness of the anterior and posterior banks appeared to be equal in over 70% of the patients. Conclusion: A prominent cortical thickness difference across the CS in the presence of vasogenic edema was confirmed. This finding is considered to facilitate the identification of the CS in patients with brain tumors.

  2. Cortical thickness difference across the central sulcus visualized in the presence of vasogenic edema

    International Nuclear Information System (INIS)

    Togao, Osamu; Yoshiura, Takashi; Mihara, Futoshi; Noguchi, Tomoyuki; Hiwatashi, Akio; Yamashita, Koji; Yoshitake, Tadamasa; Honda, Hiroshi

    2008-01-01

    Purpose: To confirm the cortical thickness difference across the central sulcus (CS) visualized in the presence of vasogenic edema on MRI. Materials and methods: T2-weighted images of 70 cerebral hemispheres showing vasogenic edema infiltrating into subcortical white matter around the CS were studied retrospectively. Two neuroradiologists measured the cortical thickness of the anterior and posterior banks of the CS, precentral sulci (PrCS), and postcentral sulci (PoCS). Additionally, we compared the cortical thickness of the anterior and posterior banks of each sulcus visually using a grading scale. Results: On T2-weighted images, the cerebral cortex was highlighted by a high signal-intensity vasogenic edema in the adjacent white matter, and its thickness was readily measurable. The unique cortical thickness difference between the anterior and posterior banks of the CS were confirmed with measurements of 2.67 and 1.48 mm (p < 0.0001). The cortical measurements across other cerebral sulci were 2.04 and 1.95 mm (NS) for the PrCS, and 1.67 and 1.77 mm (NS) for the PoCS. The cortical thickness ratios were 1.86 for the CS, 1.05 for the PrCS, and 0.96 for the PoCS. On visual evaluation, the anterior bank of the CS was thicker than the posterior bank in 93% (65/70). For the PrCS and PoCS, the thickness of the anterior and posterior banks appeared to be equal in over 70% of the patients. Conclusion: A prominent cortical thickness difference across the CS in the presence of vasogenic edema was confirmed. This finding is considered to facilitate the identification of the CS in patients with brain tumors

  3. Laser iridotomy to treat uveitis-glaucoma-hyphema syndrome secondary to reverse pupillary block in sulcus-placed intraocular lenses: Case series.

    Science.gov (United States)

    Singh, Harmanjit; Modabber, Milad; Safran, Steven G; Ahmed, Iqbal Ike K

    2015-10-01

    To present cases of uveitis-glaucoma-hyphema (UGH) syndrome due to reverse pupillary block in sulcus-placed posterior chamber intraocular lenses (PC IOLs) that were managed with laser peripheral iridotomy (LPI). Community-based subspecialty clinics. Retrospective interventional case series. A chart review of patients with a sulcus-placed PC IOLs presenting with UGH syndrome and reverse pupillary block with posterior iris bowing as diagnosed by gonioscopy and anterior segment optical coherence tomography was carried out. Laser peripheral iridotomy was performed in the eyes included in the study. The main outcome measure was clinical resolution of UGH syndrome. The study included 6 eyes of 6 patients with a mean age of 59.8 years (range 43.0 to 66.0 years) who presented with unilateral UGH syndrome a mean of 28.7 months (range 0.3 to 84.0 months) after PC IOL implantation. All patients were previously myopic, with 5 (83.3%) having a history of vitrectomy. The mean axial length was 27.0 mm ± 1.4 (SD). An LPI was used to treat the reverse pupillary block with resultant improvement in iris profile and resolution of UGH syndrome in all eyes. The mean intraocular pressure decreased from 30.5 ± 10.0 mm Hg on 0.5 ± 0.8 glaucoma medications to 15.5 ± 3.2 mm Hg postoperatively on 0.7 ± 1.2 medications. The UGH syndrome due to reverse pupillary block occurred after sulcus-placed PC IOLs in susceptible patients, those with axial myopia, and post-vitrectomized eyes. The cases were managed with LPIs. Dr. Ahmed is a consultant to Alcon Laboratories, Inc. and Abbott Medical Optics, Inc. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  4. [Identification of the central sulcus using magnetoencephalography and neuronavigator].

    Science.gov (United States)

    Watanabe, E; Mayanagi, Y; Kaneko, Y

    1993-11-01

    The brain-generated currents that produce potentials measured by the electroencephalogram also produce magnetic fields which can be measured by the magnetoencephalogram (MEG), N 20 compatible evoked field after median nerve stimulation is known to be generated in primary sensory cortex. Using MEG with 37 channel SQUIDs, a current dipole is back traced which corresponds to the sensory cortex. When the dipole is projected onto the MRI of the same patient, the primary sensory cortex is precisely identified in the MRI images. These data were used as the key images for navigator enabling a surgeon identify the central cortex in the surgical field. Seven patients with peri-central mass lesion (3 meningiomas, 1 metastatic tumors, 1 angiomas, 2 gliomas) underwent surgery under MEG-navigator method. In every case, the central sulcus and motor cortex were easily identified on the cortex and the tumor was removed as far as possible preserving the motor strip. There were no postoperative worsening of the motor paresis and no other complications were noticed. The method which combines the MEG functional mapping and navigator was considered to be a powerful tool in surgery of the pericentral mass lesions.

  5. The effect of cyclosporin-A on the oral microflora at gingival sulcus of the ferret.

    Science.gov (United States)

    Fischer, R G; Edwardsson, S; Klinge, B; Attström, R

    1996-09-01

    The effect of cyclosporin-A (CyA) on the dentogingival flora of ferrets with healthy and experimentally induced periodontal breakdown was studied. Five animals were given 10 mg/kg/d CyA. At the start of the experiments (day 0), ligatures were placed around 4 teeth in the right upper and lower jaws; corresponding contralateral teeth on the left side served as control. On days 0 and 28 (end of the experiment), microbiological samples were collected from the gingival sulcus of the experimental and the control teeth and from closely located gingival mucosa membrane. The samples were subjected to viable counts and to darkfield microscopic analyses. On day 0, facultative anaerobic rods, mainly Pasteurella spp, Alcaligenes spp, Corynebacterium spp. and Rothia spp dominated in the viable counts. No anaerobic bacteria were detected in the viable counts. On day 28 spirochetes increased in the experimental gingival sulcus samples and anaerobic bacteria appeared in most of the samples and constituted 40-60% of the total cultivable flora; Fusobacterium necrophorum and Eubacterium spp. predominated in the samples from the experimental sites. The results of the present study were compared with those of our previous investigation of ferrets not medicated with cyclosporin but also subject to experimental ligature periodontitis. Eubacterium spp. were absent in the animals not treated with cyclosporin, while this species was frequently present in the immunosuppressed ferrets. The results indicate that the presence of the large numbers of gram negative rods and of anaerobic bacteria may have enhanced the inflammatory process and further provoked the gingival overgrowth observed.

  6. Where syntax meets math: Right Intraparietal Sulcus activation in response to grammatical number agreement violations

    Science.gov (United States)

    Carreiras, Manuel; Carr, Lindsay; Barber, Horacio A.; Hernandez, Arturo

    2009-01-01

    Previous research has shown that the processing of words referring to actions activated motor areas. Here we show activation of the right intraparietal sulcus, an area that has been associated with quantity processing, when participants are asked to read pairs of words with number agreement violations as opposed to phrases with gender agreement violations or with no violation. In addition, we show activation in the left premotor and left inferior frontal areas when either gender or number agreement is violated. We argue that number violation automatically activates processes linked to quantity processing which are not directly related to language mechanisms. PMID:19800410

  7. Small Intestinal Submucosa Implantation for the Possible Treatment of Vocal Fold Scar, Sulcus, and Superficial Lamina Propria Atrophy.

    Science.gov (United States)

    Pitman, Michael J; Cabin, Jonathan A; Iacob, Codrin E

    2016-02-01

    Evaluate the histologic effects of grafting porcine-derived small intestinal submucosa (SIS) into the vocal fold superficial lamina propria (SLP) layer for the potential treatment of vocal fold scar, sulcus and superficial lamina propria atrophy. Small intestinal submucosa was implanted into the right vocal fold SLP of 6 mongrel dogs. The left vocal fold served as a sham surgical control. At 2, 4, and 6 weeks postoperative, bilateral vocal fold specimens were evaluated histologically. At 2 and 4 weeks, respectively, SIS-implanted vocal folds demonstrated moderate and mild inflammation and acute and chronic inflammation. At 6 weeks, inflammation was minimal and chronic. The 6-week specimens showed copious amounts of newly generated hyaluronic acid (HA) within the graft. There was no reactive fibrosis at 6 weeks. In the canine model, SIS appears safe for SLP grafting. Inflammation is similar to that of sham surgery. Small intestinal submucosa results in newly generated HA without concomitant fibrosis. Small intestinal submucosa has potential to be used in treatment of disorders with SLP, including vocal fold scar, sulcus, and atrophy. Studies evaluating the effect of SIS implantation on vocal fold function, as well as the ultimate fate of the graft, are required. © The Author(s) 2015.

  8. Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges.

    Science.gov (United States)

    Lakhashe, Samir K; Velu, Vijayakumar; Sciaranghella, Gaia; Siddappa, Nagadenahalli B; Dipasquale, Janet M; Hemashettar, Girish; Yoon, John K; Rasmussen, Robert A; Yang, Feng; Lee, Sandra J; Montefiori, David C; Novembre, Francis J; Villinger, François; Amara, Rama Rao; Kahn, Maria; Hu, Shiu-Lok; Li, Sufen; Li, Zhongxia; Frankel, Fred R; Robert-Guroff, Marjorie; Johnson, Welkin E; Lieberman, Judy; Ruprecht, Ruth M

    2011-08-05

    We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus > 90%; these RM also had strong SIV Gag-specific proliferation of CD8⁺ T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4β7-expressing CD4⁺ T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Posterior superior temporal sulcus responses predict perceived pleasantness of skin stroking

    Directory of Open Access Journals (Sweden)

    Monika Davidovic

    2016-09-01

    Full Text Available Love and affection is expressed through a range of physically intimate gestures, including caresses. Recent studies suggest that posterior temporal lobe areas typically associated with visual processing of social cues also respond to interpersonal touch. Here, we asked whether these areas are selective to caress-like skin stroking. We collected functional magnetic resonance imaging (fMRI data from 23 healthy participants and compared brain responses to skin stroking and vibration. We did not find any significant differences between stroking and vibration in the posterior temporal lobe; however, right posterior superior temporal sulcus (pSTS responses predicted healthy participant's perceived pleasantness of skin stroking, but not vibration. These findings link right pSTS responses to individual variability in perceived pleasantness of caress-like tactile stimuli. We speculate that the right pSTS may play a role in the translation of tactile stimuli into positively valenced, socially relevant interpersonal touch and that this system may be affected in disorders associated with impaired attachment.

  10. The Spatial Distribution of Thermal Emission from Baghdad Sulcus, Enceladus, at 100 meter Scales

    Science.gov (United States)

    Spencer, John R.; Gorius, N. J. P.; Howett, C. J. A.; Jennings, D. E.; Albright, S. A.

    2012-10-01

    The Cassini Composite Infrared Spectrometer (CIRS) has been observing endogenic thermal emission from the south pole of Enceladus since 2005. Best spatial resolution from conventional scans is about 1km, usually from distances > 2000 km. When Cassini is closer to Enceladus, the spacecraft cannot rotate fast enough to track the surface, and the 5 seconds required to obtain a CIRS spectrum produces many kilometers of smear. However, higher-resolution mapping can be done from much closer range by exploiting the 20 msec sampling of the CIRS raw interferograms. On April 14th 2012, Cassini made a gravity pass of Enceladus at a range of 74 km. Spacecraft orientation was inertially fixed, and chosen so that the active tiger stripe Baghdad Sulcus passed through the CIRS and VIMS fields of view during the flyby. In the 7 to 17 µm region, CIRS uses linear arrays of ten detectors with IFOV of 0.29 mrad, which were oriented roughly perpendicular to the groundtrack and operated in pairs, giving five cross-track spatial resolution elements, each 43 meters wide. Along-track spatial resolution, defined by the 20 msec interferogram sampling time and the flyby speed of 7.5 km/sec, was 150 meters. At longer wavelengths, CIRS obtained a single-detector scan with a spatial resolution of 300 meters. The brief passage of the intense tiger stripe thermal emission through the field of view produced complex spikes in the CIRS interferograms. Though spectra cannot be reconstructed, we can use knowledge of the interferogram temporal response to reconstruct the time history of the incoming radiation and thus its spatial distribution. The resulting image will map tiger stripe thermal emission along a small part of Baghdad Sulcus at about ten times the spatial resolution of the best previous Cassini thermal images.

  11. Técnica do retalho pediculado para correção do sulco vocal The pediculated flap technique to sulcus vocalis repairing

    Directory of Open Access Journals (Sweden)

    Marcos Grellet

    Full Text Available Introdução: técnica do retalho pediculado de mucosa para reparar o sulco vocal permite o aparecimento da onda mucosa nessa região. A presença do sulco vocal traz como conseqüência rouquidão, soprosidade e aspereza. Outros sintomas podem estar presentes como fadiga ao falar, queimação ou ardor. Objetivo: provocar o aparecimento de onda mucosa com técnica cirúrgica. Forma de estudo: clínico retrospectivo. Material e método: Foram operados 3 pacientes para auxiliar no deslocamento do epitélio escamoso estratificado e da camada superficial da prega vocal aderidos ao ligamento vocal injetamos pequena quantidade de dexametasona. Obtemos o retalho pediculado descolando retalho de mucosa da prega vocal. Resultados: No pós-operatório, a videoestroboscopia mostra uniformidade do revestimento da cobertura da prega vocal na região do sulco vocal. Nos pacientes operados observamos a presença da onda mucosa nessa região e a coaptação das pregas vocais é satisfatória, no caso de sulco unilateral. A análise subjetiva e objetiva da voz apresenta resultados normais a partir de um ano da cirurgia. Os sintomas, esforço e fadiga ao falar, ardor e queimação, desapareceram nesse período. Para sulco bilateral operamos inicialmente o sulco de uma prega vocal com melhora dos índices acústicos utilizados, embora não atingisse valores normais em todos os parâmetros avaliados no curto período de evolução (30 dias de pós-operatório após realizarmos a correção cirúrgica do sulco da outra prega vocal. Conclusão: A técnica microfonocirúrgica de retalho pediculado de mucosa para correção do sulco vocal mostrou resultados amplamente favoráveis para reabilitação da voz nos três pacientes apresentados.Introduction: the pedicullate flap technique to repair sulcus vocalis allows the appearing of the mucous wave in this region. Sulcus vocalis cause hoarseness, breathing and roughness. Other symptoms can happen during the speech like

  12. Complex assembly, crystallization and preliminary X-ray crystallographic studies of rhesus macaque MHC Mamu-A*01 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Chu, Fuliang; Lou, Zhiyong; Gao, Bin; Bell, John I.; Rao, Zihe; Gao, George F.

    2005-01-01

    Crystallization of the first rhesus macaque MHC class I complex. Simian immunodeficiency virus (SIV) infection in rhesus macaques has been used as the best model for the study of human immunodeficiency virus (HIV) infection in humans, especially in the cytotoxic T-lymphocyte (CTL) response. However, the structure of rhesus macaque (or any other monkey model) major histocompatibility complex class I (MHC I) presenting a specific peptide (the ligand for CTL) has not yet been elucidated. Here, using in vitro refolding, the preparation of the complex of the rhesus macaque MHC I allele (Mamu-A*01) with human β 2 m and an immunodominant peptide, CTPYDINQM (Gag-CM9), derived from SIV Gag protein is reported. The complex (45 kDa) was crystallized; the crystal belongs to space group I422, with unit-cell parameters a = b = 183.8, c = 155.2 Å. The crystal contains two molecules in the asymmetric unit and diffracts X-rays to 2.8 Å resolution. The structure is being solved by molecular replacement and this is the first attempt to determined the crystal structure of a peptide–nonhuman primate MHC complex

  13. Superior Intraparietal Sulcus Controls the Variability of Visual Working Memory Precision.

    Science.gov (United States)

    Galeano Weber, Elena M; Peters, Benjamin; Hahn, Tim; Bledowski, Christoph; Fiebach, Christian J

    2016-05-18

    Limitations of working memory (WM) capacity depend strongly on the cognitive resources that are available for maintaining WM contents in an activated state. Increasing the number of items to be maintained in WM was shown to reduce the precision of WM and to increase the variability of WM precision over time. Although WM precision was recently associated with neural codes particularly in early sensory cortex, we have so far no understanding of the neural bases underlying the variability of WM precision, and how WM precision is preserved under high load. To fill this gap, we combined human fMRI with computational modeling of behavioral performance in a delayed color-estimation WM task. Behavioral results replicate a reduction of WM precision and an increase of precision variability under high loads (5 > 3 > 1 colors). Load-dependent BOLD signals in primary visual cortex (V1) and superior intraparietal sulcus (IPS), measured during the WM task at 2-4 s after sample onset, were modulated by individual differences in load-related changes in the variability of WM precision. Although stronger load-related BOLD increase in superior IPS was related to lower increases in precision variability, thus stabilizing WM performance, the reverse was observed for V1. Finally, the detrimental effect of load on behavioral precision and precision variability was accompanied by a load-related decline in the accuracy of decoding the memory stimuli (colors) from left superior IPS. We suggest that the superior IPS may contribute to stabilizing visual WM performance by reducing the variability of memory precision in the face of higher load. This study investigates the neural bases of capacity limitations in visual working memory by combining fMRI with cognitive modeling of behavioral performance, in human participants. It provides evidence that the superior intraparietal sulcus (IPS) is a critical brain region that influences the variability of visual working memory precision between and

  14. Bringing transcranial mapping into shape: Sulcus-aligned mapping captures motor somatotopy in human primary motor hand area

    DEFF Research Database (Denmark)

    Raffin, Estelle; Pellegrino, Giovanni; Di Lazzaro, Vincenzo

    2015-01-01

    Motor representations express some degree of somatotopy in human primary motor hand area (M1HAND), but within-M1HAND corticomotor somatotopy has been difficult to study with transcranial magnetic stimulation (TMS). Here we introduce a “linear” TMS mapping approach based on the individual shape...... of the central sulcus to obtain mediolateral corticomotor excitability profiles of the abductor digiti minimi (ADM) and first dorsal interosseus (FDI) muscles. In thirteen young volunteers, we used stereotactic neuronavigation to stimulate the right M1HAND with a small eight-shaped coil at 120% of FDI resting...

  15. Visualizing the Immune System: Providing Key Insights into HIV/SIV Infections

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    Jacob D. Estes

    2018-03-01

    Full Text Available Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens. Particularly in HIV/SIV disease, imaging technologies are of great importance in the investigation of the local interplay between the virus and host cells, with respect to understanding viral dynamics and persistence, immune responses (i.e., adaptive and innate inflammatory responses, tissue structure and pathologies, and changes to the surrounding milieu and function of immune cells. Merging imaging platforms with other cutting-edge technologies could lead to novel findings regarding the phenotype, function, and molecular signatures of particular immune cell targets, further promoting the development of new antiviral treatments and vaccination strategies.

  16. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

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    Mickaël J Ploquin

    2016-08-01

    Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

  17. Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

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    Natalia Guerra-Pérez

    Full Text Available Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques, while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.

  18. [Application of 3D virtual reality technology with multi-modality fusion in resection of glioma located in central sulcus region].

    Science.gov (United States)

    Chen, T N; Yin, X T; Li, X G; Zhao, J; Wang, L; Mu, N; Ma, K; Huo, K; Liu, D; Gao, B Y; Feng, H; Li, F

    2018-05-08

    Objective: To explore the clinical and teaching application value of virtual reality technology in preoperative planning and intraoperative guide of glioma located in central sulcus region. Method: Ten patients with glioma in the central sulcus region were proposed to surgical treatment. The neuro-imaging data, including CT, CTA, DSA, MRI, fMRI were input to 3dgo sczhry workstation for image fusion and 3D reconstruction. Spatial relationships between the lesions and the surrounding structures on the virtual reality image were obtained. These images were applied to the operative approach design, operation process simulation, intraoperative auxiliary decision and the training of specialist physician. Results: Intraoperative founding of 10 patients were highly consistent with preoperative simulation with virtual reality technology. Preoperative 3D reconstruction virtual reality images improved the feasibility of operation planning and operation accuracy. This technology had not only shown the advantages for neurological function protection and lesion resection during surgery, but also improved the training efficiency and effectiveness of dedicated physician by turning the abstract comprehension to virtual reality. Conclusion: Image fusion and 3D reconstruction based virtual reality technology in glioma resection is helpful for formulating the operation plan, improving the operation safety, increasing the total resection rate, and facilitating the teaching and training of the specialist physician.

  19. Somatotopic organization of cortical fields in the lateral sulcus of Homo sapiens: evidence for SII and PV.

    Science.gov (United States)

    Disbrow, E; Roberts, T; Krubitzer, L

    2000-02-28

    The human somatosensory cortex in the Sylvian fissure was examined using functional magnetic resonance imaging to describe the number and internal organization of cortical fields present. Somatic stimuli were applied to the lips, face, hand, trunk, and foot of 18 human subjects. Activity patterns were transposed onto three-dimensional magnetic resonance images of the brain so that the location of activity associated with the different stimuli could be related to specific regions of the cortex. There were several consistent findings. First, there were three regions of activity in the lateral sulcus associated with stimulation of the contralateral body. The most consistent locus of activation was on the upper bank of the lateral sulcus, continuing onto the operculum. The other two areas, one rostral and one caudal to this large central area, were smaller and were activated less consistently. Second, when activity patterns in the large central area resulting from stimulation of all body parts were considered, this region appeared to contain two fields that corresponded in location and somatotopic organization to the second somatosensory area (SII) and the parietal ventral area (PV). Finally, patterns of activation within SII and PV were somewhat variable across subjects. Repeated within-subject stimulus presentation indicated that differences across subjects were not due to inconsistent stimulus presentation. Comparisons with other mammals suggest that some features of organization are found only in primates. It is hypothesized that these features may be associated with manual dexterity and coordination of the hands, a characteristic generally restricted to the primate lineage.

  20. DOES THE INFERIOR FRONTAL SULCUS PLAY A FUNCTIONAL ROLE IN DECEPTION? A NEURONAVIGATED THETA-BURST TRANSCRANIAL MAGNETIC STIMULATION STUDY

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    Bruno eVerschuere

    2012-10-01

    Full Text Available Background. By definition, lying involves withholding the truth. Response inhibition may therefore be the cognitive function at the heart of deception. Neuroimaging research has shown that the same brain region that is activated during response inhibition tasks, namely the inferior frontal region, is also activated during deception paradigms. This led to the hypothesis that the inferior frontal region is the neural substrate critically involved in withholding the truth. Objective. We critically examine the functional necessity of the inferior frontal region in withholding the truth during deception. Method. We experimentally manipulated the neural activity level in right inferior frontal sulcus (IFS by means of neuronavigated continuous theta burst stimulation (cTBS. Individual structural magnetic resonance brain images (MRI were used to allow precise stimulation in each participant. Twenty-six participants answered autobiographical questions truthfully or deceptively before and after sham and real cTBS. Results. Deception was reliably associated with more errors, longer and more variable response times than truth telling. Despite the potential role of IFS in deception as suggested by neuroimaging data, the cTBS-induced disruption of right IFS did not affect response times or error rates, when compared to sham stimulation. Conclusions. The present findings do not support the hypothesis that the right inferior frontal sulcus is critically involved in deception.

  1. The non-lemniscal auditory cortex in ferrets: convergence of corticotectal inputs in the superior colliculus

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    Victoria M Bajo

    2010-05-01

    Full Text Available Descending cortical inputs to the superior colliculus (SC contribute to the unisensory response properties of the neurons found there and are critical for multisensory integration. However, little is known about the relative contribution of different auditory cortical areas to this projection or the distribution of their terminals in the SC. We characterized this projection in the ferret by injecting tracers in the SC and auditory cortex. Large pyramidal neurons were labeled in layer V of different parts of the ectosylvian gyrus after tracer injections in the SC. Those cells were most numerous in the anterior ectosylvian gyrus (AEG, and particularly in the anterior ventral field, which receives both auditory and visual inputs. Labeling was also found in the posterior ectosylvian gyrus (PEG, predominantly in the tonotopically-organized posterior suprasylvian field. Profuse anterograde labeling was present in the SC following tracer injections at the site of acoustically-responsive neurons in the AEG or PEG, with terminal fields being both more prominent and clustered for inputs originating from the AEG. Terminals from both cortical areas were located throughout the intermediate and deep layers, but were most concentrated in the posterior half of the SC, where peripheral stimulus locations are represented. No inputs were identified from primary auditory cortical areas, although some labeling was found in the surrounding sulci. Our findings suggest that higher level auditory cortical areas, including those involved in multisensory processing, may modulate SC function via their projections into its deeper layers.

  2. HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells

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    John Zaunders

    2017-04-01

    Full Text Available BackgroundT follicular helper (Tfh cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4+ T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells.MethodologyTfh and other CD4+ T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV+ subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay.ResultsPhylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV+ subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5+PD-1intermediate(int+ memory CD4+ T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1int cells survive, carry SIV provirus, and differentiate into PD-1hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5+ Tfh and pre-Tfh cells from human tonsils.ConclusionThe major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population

  3. Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA

    International Nuclear Information System (INIS)

    Buckley, Kathleen A.; Li Peilin; Khimani, Anis H.; Hofmann-Lehmann, Regina; Liska, Vladimir; Anderson, Daniel C.; McClure, Harold M.; Ruprecht, Ruth M.

    2003-01-01

    The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVΔ3 (the live attenuated vaccine strain derived from SIVmac239), or SIVΔ3+ (a pathogenic progeny virus that had evolved from SIVΔ3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVΔ3, and SIVΔ3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression

  4. Pigment dispersion syndrome and pigmentary glaucoma after secondary sulcus transscleral fixation of single-piece foldable posterior chamber intraocular lenses in Chinese aphakic patients.

    Science.gov (United States)

    Tong, Nianting; Liu, Fuling; Zhang, Ting; Wang, Liangyu; Zhou, Zhanyu; Gong, Huimin; Yuan, Fuxiang

    2017-05-01

    To describe secondary pigment dispersion syndrome (PDS) and pigmentary glaucoma after secondary sulcus transscleral fixation of 1-piece hydrophobic acrylic foldable posterior chamber intraocular lenses (PC IOLs) in aphakic patients in a Chinese population. Department of Ophthalmology, Qingdao Municipal Hospital, Qingdao, China. Retrospective case series. This chart review included eyes that had secondary sulcus transscleral fixation of a 1-piece hydrophobic acrylic foldable PC IOL (Tecnis ZCB00) between March 2011 and March 2014. The patients' demographic data, clinical data, postoperative complications, intervals between initial surgery and the onset of PDS, pigmentary glaucoma occurrences, and findings on slitlamp biomicroscopy, gonioscopy, and ultrasound biomicroscopy (UBM) were recorded. The study comprised 23 consecutive eyes of 21 patients. Seventeen eyes of 16 patients were diagnosed with PDS, and 7 eyes of 6 patients were diagnosed with pigmentary glaucoma. The slitlamp examination and UBM showed that the location between the IOL optic and the posterior surface of the iris was very close. Slitlamp examination of the anterior chamber angle using a gonioscope showed dense pigment deposition on the IOL surfaces. A reverse pupillary block was found in 10 eyes of 9 patients. Other postoperative complications included intraocular hemorrhage, pupillary capture of the IOL optic, IOL tilt, IOL decentration, IOL dislocation, and suture erosion. The 1-piece hydrophobic acrylic foldable PC IOL was not suitable for sulcus transscleral fixation because of a high incidence of PDS and pigmentary glaucoma after surgery in a Chinese population. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  5. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

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    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  6. The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid

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    Aiken Christopher

    2004-06-01

    Full Text Available Abstract Background Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast, SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB, we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4+ T cells. Results Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to DSB, but the mutant virus replicated with reduced efficiency. Conversely, replication of an SIV mutant containing three amino acid substitutions in the CA-SP1 cleavage site was highly sensitive to DSB, and the mutations resulted in delayed cleavage of the CA-SP1 junction in the presence of the drug. Conclusions These results demonstrate that the CA-SP1 junction in Pr55Gag represents the primary viral target of DSB. They further suggest that the therapeutic application of DSB will be accompanied by emergence of mutant viruses that are highly resistant to the drug but which exhibit reduced fitness relative to wild type HIV-1.

  7. Multisensory speech perception without the left superior temporal sulcus.

    Science.gov (United States)

    Baum, Sarah H; Martin, Randi C; Hamilton, A Cris; Beauchamp, Michael S

    2012-09-01

    Converging evidence suggests that the left superior temporal sulcus (STS) is a critical site for multisensory integration of auditory and visual information during speech perception. We report a patient, SJ, who suffered a stroke that damaged the left tempo-parietal area, resulting in mild anomic aphasia. Structural MRI showed complete destruction of the left middle and posterior STS, as well as damage to adjacent areas in the temporal and parietal lobes. Surprisingly, SJ demonstrated preserved multisensory integration measured with two independent tests. First, she perceived the McGurk effect, an illusion that requires integration of auditory and visual speech. Second, her perception of morphed audiovisual speech with ambiguous auditory or visual information was significantly influenced by the opposing modality. To understand the neural basis for this preserved multisensory integration, blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine brain responses to audiovisual speech in SJ and 23 healthy age-matched controls. In controls, bilateral STS activity was observed. In SJ, no activity was observed in the damaged left STS but in the right STS, more cortex was active in SJ than in any of the normal controls. Further, the amplitude of the BOLD response in right STS response to McGurk stimuli was significantly greater in SJ than in controls. The simplest explanation of these results is a reorganization of SJ's cortical language networks such that the right STS now subserves multisensory integration of speech. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Specialization of the Right Intraparietal Sulcus for Processing Mathematics During Development.

    Science.gov (United States)

    Schel, Margot A; Klingberg, Torkel

    2017-09-01

    Mathematical ability, especially perception of numbers and performance of arithmetics, is known to rely on the activation of intraparietal sulcus (IPS). However, reasoning ability and working memory, 2 highly associated abilities also activate partly overlapping regions. Most studies aimed at localizing mathematical function have used group averages, where individual variability is averaged out, thus confounding the anatomical specificity when localizing cognitive functions. Here, we analyze the functional anatomy of the intraparietal cortex by using individual analysis of subregions of IPS based on how they are structurally connected to frontal, parietal, and occipital cortex. Analysis of cortical thickness showed that the right anterior IPS, defined by its connections to the frontal lobe, was associated with both visuospatial working memory, and mathematics in 6-year-old children. This region specialized during development to be specifically related to mathematics, but not visuospatial working memory in adolescents and adults. This could be an example of interactive specialization, where interacting with the environment in combination with interactions between cortical regions leads from a more general role of right anterior IPS in spatial processing, to a specialization of this region for mathematics. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Cytoarchitectonic identification and probabilistic mapping of two distinct areas within the anterior ventral bank of the human intraparietal sulcus

    Science.gov (United States)

    Choi, Hi-Jae; Zilles, Karl; Mohlberg, Hartmut; Schleicher, Axel; Fink, Gereon R.; Armstrong, Este; Amunts, Katrin

    2008-01-01

    Anatomical studies in the macaque cortex and functional imaging studies in humans have demonstrated the existence of different cortical areas within the IntraParietal Sulcus (IPS). Such functional segregation, however, does not correlate with presently available architectonic maps of the human brain. This is particularly true for the classical Brodmann map, which is still widely used as an anatomical reference in functional imaging studies. The aim of this cytoarchitectonic mapping study was to use previously defined algorithms to determine whether consistent regions and borders can be found within the cortex of the anterior IPS in a population of ten postmortem human brains. Two areas, the human IntraParietal area 1 (hIP1) and the human IntraParietal area 2 (hIP2), were delineated in serial histological sections of the anterior, lateral bank of the human IPS. The region hIP1 is located posterior and medial to hIP2, and the former is always within the depths of the IPS. The latter, on the other hand, sometimes reaches the free surface of the superior parietal lobule. The delineations were registered to standard reference space, and probabilistic maps were calculated, thereby quantifying the intersubject variability in location and extent of both areas. In the future, they can be a tool in analyzing structure – function relationships and a basis for determining degrees of homology in the IPS among anthropoid primates. We conclude that the human intraparietal sulcus has a finer grained parcellation than shown in Brodmann’s map. PMID:16432904

  10. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

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    Martin Cranage

    2008-08-01

    Full Text Available The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model.A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6 or had

  11. Imaging lymphoid tissues in nonhuman primates to understand SIV pathogenesis and persistence.

    Science.gov (United States)

    Deleage, Claire; Turkbey, Baris; Estes, Jacob D

    2016-08-01

    CD4+ T cells are the primary HIV-1 target cell, with the vast majority of these cells residing within lymphoid tissue compartments throughout the body. Predictably, HIV-1 infection, replication, localization, reservoir establishment and persistence, as well as associated host immune and inflammatory responses and disease pathology principally take place within the tissues of the immune system. By virture of the fact that the virus-host struggle is played out within lymphoid and additional tissues compartments in HIV-1 infected individuals it is critical to understand HIV-1 infection and disease within these relevant tissue sites; however, there are obvious limitations to studying these dynamic processes in humans. Nonhuman primate (NHP) research has provided a vital bridge between basic and preclinical research and clinical studies, with experimental SIV infection of NHP models offering unique opportunities to understand key processes of HIV-1 infection and disease that are either not practically feasible or ethical in HIV-1 infected humans. In this review we will discuss current approaches to studying the tissue based immunopathogenesis of AIDS virus infection in NHPs, including both analyses of tissues obtained at biopsy or necropsy and complementary non-invasive imaging approaches that may have practical utility in monitoring HIV-1 disease in the clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A novel CD4-conjugated ultraviolet light-activated photocatalyst inactivates HIV-1 and SIV efficiently.

    Science.gov (United States)

    Yamaguchi, Koushi; Sugiyama, Takahiro; Kato, Shinji; Kondo, Yoichi; Ageyama, Naohide; Kanekiyo, Masaru; Iwata, Misao; Koyanagi, Yoshio; Yamamoto, Naoki; Honda, Mitsuo

    2008-08-01

    In this study, we found that the electric potential derived from the redox reaction of ultraviolet (UV)-illuminated CD4-conjugated titanium dioxide (TiO2) inactivated a wide range of high-titered primary HIV-1 isolates, regardless of virus co-receptor usage or genetic clade. In vitro incubation of HIV-1 isolates with CD4-conjugated TiO2 (CD4-TiO2) followed by UV illumination led to inhibition of viral infectivity in both H9 cells and peripheral blood mononuclear cells as well as to the complete inactivation of plasma virions from HIV-1-infected individuals. Treatment with a newly established extra-corporeal circulation system with the photocatalyst in rhesus macaques completely inactivated plasma virus in the system and effectively reduced the infectious plasma viral load. Furthermore, plasma viremia and infectious viral loads were controlled following a second therapeutic photocatalyst treatment during primary SIV(mac239) infection of macaques. Our findings suggest that this therapeutic immunophysical strategy may help control human immunodeficiency viral infection in vivo.

  13. Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion

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    Durand-Gasselin Lucie

    2010-09-01

    Full Text Available Abstract Background HIV reservoirs are rapidly established after infection, and the effect of HAART initiated very early during acute infection on HIV reservoirs remains poorly documented, particularly in tissue known to actively replicate the virus. In this context, we used the model of experimental infection of macaques with pathogenic SIV to assess in different tissues: (i the effect of a short term HAART initiated at different stages during acute infection on viral dissemination and replication, and (ii the local concentration of antiviral drugs. Results Here, we show that early treatment with AZT/3TC/IDV initiated either within 4 hours after intravenous infection of macaques with SIVmac251 (as a post exposure prophylaxis or before viremia peak (7 days post-infection [pi], had a strong impact on SIV production and dissemination in all tissues but did not prevent infection. When treatment was initiated after the viremia peak (14 days pi or during early chronic infection (150 days pi, significant viral replication persists in the peripheral lymph nodes and the spleen of treated macaques despite a strong effect of treatment on viremia and gut associated lymphoid tissues. In these animals, the level of virus persistence in tissues was inversely correlated with local concentrations of 3TC: high concentrations of 3TC were measured in the gut whereas low concentrations were observed in the secondary lymphoid tissues. IDV, like 3TC, showed much higher concentration in the colon than in the spleen. AZT concentration was below the quantification threshold in all tissues studied. Conclusions Our results suggest that limited antiviral drug diffusion in secondary lymphoid tissues may allow persistent viral replication in these tissues and could represent an obstacle to HIV prevention and eradication.

  14. Gram-positive bacteria as an antigen topically applied into gingival sulcus of immunized rat accelerates periodontal destruction.

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    Nagano, F; Kaneko, T; Yoshinaga, Y; Ukai, T; Kuramoto, A; Nakatsu, S; Oshino, K; Ichimura, I; Hara, Y

    2013-08-01

    Periodontitis is generally accepted to relate to gram-negative bacteria, and the host defense system influences its onset and progression. However, little is known about the relation between gram-positive bacteria and periodontitis. In this study, we topically applied gram-positive and gram-negative bacterial suspensions to the gingival sulcus in rats after immunization, and then histopathologically examined their influence on periodontal destruction. Rats previously immunized with heat-treated and sonicated Staphylococcus aureus or Aggregatibacter actinomycetemcomitans were used as immunized groups. The non-immunized group received only sterile phosphate-buffered saline. In each animal, S. aureus or A. actinomycetemcomitans suspension was applied topically to the palatal gingival sulcus of first molars every 24 h for 10 d. Blood samples were collected and the serum level of anti-S. aureus or anti-A. actinomycetemcomitans immunoglobulin G (IgG) antibodies was determined by enzyme-linked immunosorbent assay. The first molar regions were resected and observed histopathologically. Osteoclasts were stained with tartrate-resistant acid phosphatase (TRAP). The formation of immune complexes was confirmed by immunohistological staining of C1qB. Serum levels of anti-S. aureus and anti-A. actinomycetemcomitans IgG antibodies in the immunized groups were significantly higher than those in the non-immunized groups were. The loss of attachment, increase in apical migration of the junctional epithelium, and decreases in alveolar bone level and number of TRAP-positive multinuclear cells in each immunized group were significantly greater than in each non-immunized group. The presence of C1qB was observed in the junctional epithelium and adjacent connective tissue in the immunized groups. Heat-treated and sonicated S. aureus and A. actinomycetemcomitans induced attachment loss in rats immunized with their suspensions. Our results suggest that not only gram-negative but also gram

  15. Mouth and Voice: A Relationship between Visual and Auditory Preference in the Human Superior Temporal Sulcus.

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    Zhu, Lin L; Beauchamp, Michael S

    2017-03-08

    Cortex in and around the human posterior superior temporal sulcus (pSTS) is known to be critical for speech perception. The pSTS responds to both the visual modality (especially biological motion) and the auditory modality (especially human voices). Using fMRI in single subjects with no spatial smoothing, we show that visual and auditory selectivity are linked. Regions of the pSTS were identified that preferred visually presented moving mouths (presented in isolation or as part of a whole face) or moving eyes. Mouth-preferring regions responded strongly to voices and showed a significant preference for vocal compared with nonvocal sounds. In contrast, eye-preferring regions did not respond to either vocal or nonvocal sounds. The converse was also true: regions of the pSTS that showed a significant response to speech or preferred vocal to nonvocal sounds responded more strongly to visually presented mouths than eyes. These findings can be explained by environmental statistics. In natural environments, humans see visual mouth movements at the same time as they hear voices, while there is no auditory accompaniment to visual eye movements. The strength of a voxel's preference for visual mouth movements was strongly correlated with the magnitude of its auditory speech response and its preference for vocal sounds, suggesting that visual and auditory speech features are coded together in small populations of neurons within the pSTS. SIGNIFICANCE STATEMENT Humans interacting face to face make use of auditory cues from the talker's voice and visual cues from the talker's mouth to understand speech. The human posterior superior temporal sulcus (pSTS), a brain region known to be important for speech perception, is complex, with some regions responding to specific visual stimuli and others to specific auditory stimuli. Using BOLD fMRI, we show that the natural statistics of human speech, in which voices co-occur with mouth movements, are reflected in the neural architecture of

  16. New analytical methodology for analysing S(IV) species at low pH solutions by one stage titration method (bichromatometry) with a clear colour change. Could potentially replace the state-of-art-method iodometry at low pH analysis due higher accuracy.

    Science.gov (United States)

    Santasalo-Aarnio, Annukka; Galfi, Istvan; Virtanen, Jorma; Gasik, Michael M

    2017-01-01

    A new, faster and more reliable analytical methodology for S(IV) species analysis at low pH solutions by bichromatometry is proposed. For decades the state of the art methodology has been iodometry that is still well justified method for neutral solutions, thus at low pH media possess various side reactions increasing inaccuracy. In contrast, the new methodology has no side reactions at low pH media, requires only one titration step and provides a clear color change if S(IV) species are present in the solution. The method is validated using model solutions with known concentrations and applied to analyses of gaseous SO2 from purged solution in low pH media samples. The results indicate that bichromatometry can accurately analyze SO2 from liquid samples having pH even below 0 relevant to metallurgical industrial processes.

  17. Hybrid video-assisted and limited open (VALO) resection of superior sulcus tumors.

    Science.gov (United States)

    Nun, Alon Ben; Simansky, David; Rokah, Merav; Zeitlin, Nona; Avi, Roni Ben; Soudack, Michalle; Golan, Nir; Apel, Sarit; Bar, Jair; Yelin, Alon

    2016-06-01

    To compare the postoperative recovery of patients with superior sulcus tumors (Pancoast tumors) following conventional open surgery vs. a hybrid video-assisted and limited open approach (VALO). The subjects of this retrospective study were 20 patients we operated on to resect a Pancoast tumor. All patients received induction chemo-radiation followed by surgery, performed via either a conventional thoracotomy approach (n = 10) or the hybrid VALO approach (n = 10). In the hybrid VALO group, lobectomy and internal chest wall preparation were performed using a video technique, with rib resection and specimen removal through a limited incision. There was no mortality in either group. Two patients from the thoracotomy group required mechanical ventilation, but there was no major morbidity in the hybrid VALO group. The operative times were similar for the two procedures. The average length of hospital stay was shorter and the average pain scores were significantly lower in the hybrid VALO group. The incidence of chronic pain was 10 % in the hybrid VALO group vs. 50 % in the thoracotomy group. Hybrid VALO resection of Pancoast tumors is feasible and safe, resulting in faster patient recovery and a significantly lower incidence of severe chronic pain than open thoracotomy. We conclude that centers experienced with video-assisted lobectomy should consider hybrid VALO surgery as the procedure of choice for Pancoast tumors.

  18. [Lens exchange for subluxation of posterior chamber lenses implanted in the capsular bag or in the ciliary sulcus].

    Science.gov (United States)

    Stürmer, J

    2013-04-01

    There are an increasing number of patients with decreased vision due to dislocated posterior chamber lenses, with pseudoexfoliation being the main risk factor. Various techniques for refixation of the subluxated posterior chamber IOL have been described. Experience with our technique of IOL-explantation, anterior vitrectomy and implantation of an Artisan anterior chamber lens are presented. In a retrospective study design all lens exchanges with implantation of an Artisan anterior chamber lens performed between 2003 and 2012 are analyzed. The study included 65 eyes of 61 patients (age 79.6 ± 9.2 years: 43-98). The majority of eyes (46/65; 70.8%) had Sundown Syndrome (late in-the-bag intraocular lens dislocation), in 19 eyes the posterior chamber lens was implanted primary or secondary into the ciliary sulcus. In the 46 eyes with Sundown Syndrome cataract surgery with implantation of a posterior chamber lens in the capsular bag was performed 7.4 ± 3.7 (1-22) years before subluxation within the bag. Pseudoexfoliation was the main risk factor in 42/46 (91.2%) of these eyes. A capsular tension ring (CTR) was implanted during cataract surgery in 34/46 (73.9%) eyes. The 34 IOLs with a CTR luxated significantly earlier (p IOLs without a CTR (6.6 ± 3.6 years; median 5.8 vs. 9.4 ± 3.1 years; median 9.2). The average visual gain was 0.2 logMAR in the group of luxated capsular bag lenses and 0.12 logMAR in the group of luxated sulcus lenses. Postoperative IOP decompensation was seen in 17/65 (26.2%) eyes (requiring IOP-lowering surgery in 8 eyes), 7 eyes developed corneal decompensation, 5 eyes had central retinal vein occlusion and one eye developed postoperative endophthalmitis. Lens exchange with implantation of an Artisan anterior chamber lens has become a routine procedure to improve vision in patients with subluxated IOLs. Postoperative IOP decompensation and vascular problems are the major complications. Georg Thieme Verlag KG Stuttgart · New York.

  19. Glutamate Concentration in the Superior Temporal Sulcus Relates to Neuroticism in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Johanna Balz

    2018-05-01

    Full Text Available Clinical studies suggest aberrant neurotransmitter concentrations in the brains of patients with schizophrenia (SCZ. Numerous studies have indicated deviant glutamate concentrations in SCZ, although the findings are inconsistent. Moreover, alterations in glutamate concentrations could be linked to personality traits in SCZ. Here, we examined the relationships between personality dimensions and glutamate concentrations in a voxel encompassing the occipital cortex (OCC and another voxel encompassing the left superior temporal sulcus (STS. We used proton magnetic resonance spectroscopy to examine glutamate concentrations in the OCC and the STS in 19 SCZ and 21 non-psychiatric healthy control (HC participants. Personality dimensions neuroticism, extraversion, openness, agreeableness and conscientiousness were assessed using the NEO-FFI questionnaire. SCZ compared to HC showed higher glutamate concentrations in the STS, reduced extraversion scores, and enhanced neuroticism scores. No group differences were observed for the other personality traits and for glutamate concentrations in the OCC. For the SCZ group, glutamate concentrations in STS were negatively correlated with the neuroticism scores [r = -0.537, p = 0.018] but this was not found in HC [r(19 = 0.011, p = 0.962]. No other significant correlations were found. Our study showed an inverse relationship between glutamate concentrations in the STS and neuroticism scores in SCZ. Elevated glutamate in the STS might serve as a compensatory mechanism that enables patients with enhanced concentrations to control and prevent the expression of neuroticism.

  20. Auditory, Visual and Audiovisual Speech Processing Streams in Superior Temporal Sulcus.

    Science.gov (United States)

    Venezia, Jonathan H; Vaden, Kenneth I; Rong, Feng; Maddox, Dale; Saberi, Kourosh; Hickok, Gregory

    2017-01-01

    The human superior temporal sulcus (STS) is responsive to visual and auditory information, including sounds and facial cues during speech recognition. We investigated the functional organization of STS with respect to modality-specific and multimodal speech representations. Twenty younger adult participants were instructed to perform an oddball detection task and were presented with auditory, visual, and audiovisual speech stimuli, as well as auditory and visual nonspeech control stimuli in a block fMRI design. Consistent with a hypothesized anterior-posterior processing gradient in STS, auditory, visual and audiovisual stimuli produced the largest BOLD effects in anterior, posterior and middle STS (mSTS), respectively, based on whole-brain, linear mixed effects and principal component analyses. Notably, the mSTS exhibited preferential responses to multisensory stimulation, as well as speech compared to nonspeech. Within the mid-posterior and mSTS regions, response preferences changed gradually from visual, to multisensory, to auditory moving posterior to anterior. Post hoc analysis of visual regions in the posterior STS revealed that a single subregion bordering the mSTS was insensitive to differences in low-level motion kinematics yet distinguished between visual speech and nonspeech based on multi-voxel activation patterns. These results suggest that auditory and visual speech representations are elaborated gradually within anterior and posterior processing streams, respectively, and may be integrated within the mSTS, which is sensitive to more abstract speech information within and across presentation modalities. The spatial organization of STS is consistent with processing streams that are hypothesized to synthesize perceptual speech representations from sensory signals that provide convergent information from visual and auditory modalities.

  1. Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag.

    Science.gov (United States)

    Coleman, John W; Wright, Kevin J; Wallace, Olivia L; Sharma, Palka; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Zamb, Timothy P; Zhang, Xinsheng; Parks, Christopher L

    2015-03-01

    Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Hand preference and magnetic resonance imaging asymmetries of the central sulcus.

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    Foundas, A L; Hong, K; Leonard, C M; Heilman, K M

    1998-04-01

    Hand preference is perhaps the most evident behavioral asymmetry observed in humans. Anatomic brain asymmetries that may be associated with hand preference have not been extensively studied, and no clear relationship between asymmetries of the motor system and hand preference have been established. Therefore, using volumetric magnetic resonance imaging methodologies, the surface area of the hand representation was measured along the length of the central sulcus in 15 consistent right- and 15 left-handers matched for age and gender. There was a significant leftward asymmetry of the motor hand area of the precentral gyrus in the right-handers, but no directional asymmetry was found in the left-handers. When asymmetry quotients were computed to determine the distribution of interhemispheric asymmetries, the left motor bank was greater than the right motor bank in 9 of 15 right-handers, the right motor bank was greater than the left motor bank in 3 of 15 right-handers, and the motor banks were equal in 3 of 15 right-handers. In contrast, among left-handers, the left motor bank was greater than the right motor bank in 5 of 15, the right motor bank was greater than the left motor bank in 5 of 15, and the motor banks were equal in 5 of 15. Although no direct measure of motor dexterity and skill was performed, these data suggest that anatomic asymmetries of the motor hand area may be related to hand preference because of the differences in right-handers and left-handers. Furthermore, the predominant leftward asymmetry in right-handers and the random distribution of asymmetries in the left-handers support Annett's right-shift theory. It is unclear, however, whether these asymmetries are the result of preferential hand use or are a reflection of a biologic preference to use one limb over the other.

  3. Formation and function of a new pollen aperture pattern in angiosperms: The proximal sulcus of Tillandsia leiboldiana (Bromeliaceae).

    Science.gov (United States)

    Albert, Béatrice; Matamoro-Vidal, Alexis; Raquin, Christian; Nadot, Sophie

    2010-02-01

    Pollen grains are generally surrounded by an extremely resistant wall interrupted in places by apertures that play a key role in reproduction; pollen tube growth is initiated at these sites. The shift from a proximal to distal aperture location is a striking innovation in seed plant reproduction. Reversals to proximal aperture position have only very rarely been described in angiosperms. The genus Tillandsia belongs to the Bromeliaceae family, and its aperture pattern has been described as distal monosulcate, the most widespread aperture patterns recorded in monocots and basal angiosperms. Here we report developmental and functional elements to demonstrate that the sulcate aperture in Tillandsia leiboldiana is not distal as previously described but proximal. Postmeitotic tetrad observation indicates unambiguously the proximal position of the sulcus, and in vitro germination of pollen grains confirms that the aperture is functional. This is the first report of a sulcate proximal aperture with proximal germination. The observation of microsporogenesis reveals specific features in the patterns of callose thickenings in postmeiotic tetrads.

  4. Activity in the superior temporal sulcus highlights learning competence in an interaction game.

    Science.gov (United States)

    Haruno, Masahiko; Kawato, Mitsuo

    2009-04-08

    During behavioral adaptation through interaction with human and nonhuman agents, marked individual differences are seen in both real-life situations and games. However, the underlying neural mechanism is not well understood. We conducted a neuroimaging experiment in which subjects maximized monetary rewards by learning in a prisoner's dilemma game with two computer agents: agent A, a tit-for-tat player who repeats the subject's previous action, and agent B, a simple stochastic cooperator oblivious to the subject's action. Approximately 1/3 of the subjects (group I) learned optimally in relation to both A and B, while another 1/3 (group II) did so only for B. Post-experiment interviews indicated that group I exploited the agent strategies more often than group II. Significant differences in learning-related brain activity between the two groups were only found in the superior temporal sulcus (STS) for both A and B. Furthermore, the learning performance of each group I subject was predictable based on this STS activity, but not in the group II subjects. This differential activity could not be attributed to a behavioral difference since it persisted in relation to agent B for which the two groups behaved similarly. In sharp contrast, the brain structures for reward processing were recruited similarly by both groups. These results suggest that STS provides knowledge of the other agent's strategies for association between action and reward and highlights learning competence during interactive reinforcement learning.

  5. Immunogenicity in pig-tailed macaques of poliovirus replicons expressing HIV-1 and SIV antigens and protection against SHIV-89.6P disease

    International Nuclear Information System (INIS)

    Fultz, Patricia N.; Stallworth, Jackie; Porter, Donna; Novak, Miroslav; Anderson, Marie J.; Morrow, Casey D.

    2003-01-01

    In the search for an effective vaccine against the human immunodeficiency virus (HIV), novel ways to deliver viral antigens are being evaluated. One such approach is the use of nonreplicating viral vectors encoding HIV and/or SIV genes that are expressed after infection of host cells. Nonreplicating poliovirus vectors, termed replicons, that expressed HIV-1/HXB2 and SIVmac239 gag and various HIV-1 env genes from different clades were tested for immunogenicity and protective efficacy against intravenous challenge of pig-tailed macaques with SHIV-89.6P. To maximize both cellular and humoral immune responses, a prime-boost regimen was used. Initially, macaques were immunized four times over 35 weeks by either the intranasal and intrarectal or the intramuscular (im) route with mixtures of poliovirus replicons expressing HIV-1 gag and multiple env genes. Immunization with replicons alone induced both serum antibodies and lymphocyte proliferative responses. After boosting with purified Env protein, neutralizing antibodies to SHIV-89.6P were induced in four of five immunized animals. In a second experiment, four macaques were immunized im three times over 27 weeks with replicons expressing the SIVmac239 gag and HIV-1/HXB2 env genes. All immunized animals were then boosted twice with purified HIV-1-89.6 rgp140-Env and SIVmac239 p55-Gag proteins. Four control animals received only the two protein inoculations. Immunized and control animals were then challenged intravenously with the pathogenic SHIV-89.6P. After challenge the animals were monitored for virus isolation from peripheral blood mononuclear cells and plasma viremia and for changes in virus-specific antibody titers. Naieve pig-tailed macaques experienced rapid loss of CD4 + T cells and died between 38 and 62 weeks after infection. In contrast, macaques immunized with replicons and proteins rapidly cleared plasma virus and did not experience sustained loss of CD4 + lymphocytes. Furthermore, two of the four macaques

  6. Inefficient Nef-mediated downmodulation of CD3 and MHC-I correlates with loss of CD4+T cells in natural SIV infection.

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    Michael Schindler

    2008-07-01

    Full Text Available Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect SIVsmm-infected sooty mangabeys (SMs against the loss of CD4+ T cells. However, the mechanisms underlying this protective effect remain unclear. To further assess the role of Nef in nonpathogenic SIV infection, we cloned nef alleles from 11 SIVsmm-infected SMs with high (>500 and 15 animals with low (<500 CD4+ T-cells/microl in bulk into proviral HIV-1 IRES/eGFP constructs and analyzed their effects on the phenotype, activation, and apoptosis of primary T cells. We found that not only efficient Nef-mediated downmodulation of TCR-CD3 but also of MHC-I correlated with preserved CD4+ T cell counts, as well as with high numbers of Ki67+CD4+ and CD8+CD28+ T cells and reduced CD95 expression by CD4+ T cells. Moreover, effective MHC-I downregulation correlated with low proportions of effector and high percentages of naïve and memory CD8+ T cells. We found that T cells infected with viruses expressing Nef alleles from the CD4low SM group expressed significantly higher levels of the CD69, interleukin (IL-2 and programmed death (PD-1 receptors than those expressing Nefs from the CD4high group. SIVsmm Nef alleles that were less active in downmodulating TCR-CD3 were also less potent in suppressing the activation of virally infected T cells and subsequent cell death. However, only nef alleles from a single animal with very low CD4+ T cell counts rendered T cells hyper-responsive to activation, similar to those of HIV-1. Our data suggest that Nef may protect the natural hosts of SIV against the loss of CD4+ T cells by at least two mechanisms: (i downmodulation of TCR-CD3 to prevent activation-induced cell death and to suppress the induction of PD-1 that may impair T cell function and survival, and (ii downmodulation of MHC-I to reduce CTL lysis of virally infected CD4+ T cells and/or bystander CD8+ T cell activation.

  7. In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain

    Directory of Open Access Journals (Sweden)

    Joo Chan-Gyu

    2009-06-01

    Full Text Available Abstract Background In vivo proton magnetic resonance spectroscopy (1H-MRS studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. Results Changes in the N-acetylaspartate (NAA, choline (Cho, myo-inositol (MI, creatine (Cr and glutamine/glutamate (Glx resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi. At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions. Conclusion These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.

  8. Lateralization for dynamic facial expressions in human superior temporal sulcus.

    Science.gov (United States)

    De Winter, François-Laurent; Zhu, Qi; Van den Stock, Jan; Nelissen, Koen; Peeters, Ronald; de Gelder, Beatrice; Vanduffel, Wim; Vandenbulcke, Mathieu

    2015-02-01

    Most face processing studies in humans show stronger activation in the right compared to the left hemisphere. Evidence is largely based on studies with static stimuli focusing on the fusiform face area (FFA). Hence, the pattern of lateralization for dynamic faces is less clear. Furthermore, it is unclear whether this property is common to human and non-human primates due to predisposing processing strategies in the right hemisphere or that alternatively left sided specialization for language in humans could be the driving force behind this phenomenon. We aimed to address both issues by studying lateralization for dynamic facial expressions in monkeys and humans. Therefore, we conducted an event-related fMRI experiment in three macaques and twenty right handed humans. We presented human and monkey dynamic facial expressions (chewing and fear) as well as scrambled versions to both species. We studied lateralization in independently defined face-responsive and face-selective regions by calculating a weighted lateralization index (LIwm) using a bootstrapping method. In order to examine if lateralization in humans is related to language, we performed a separate fMRI experiment in ten human volunteers including a 'speech' expression (one syllable non-word) and its scrambled version. Both within face-responsive and selective regions, we found consistent lateralization for dynamic faces (chewing and fear) versus scrambled versions in the right human posterior superior temporal sulcus (pSTS), but not in FFA nor in ventral temporal cortex. Conversely, in monkeys no consistent pattern of lateralization for dynamic facial expressions was observed. Finally, LIwms based on the contrast between different types of dynamic facial expressions (relative to scrambled versions) revealed left-sided lateralization in human pSTS for speech-related expressions compared to chewing and emotional expressions. To conclude, we found consistent laterality effects in human posterior STS but not

  9. Clinical outcomes of Ahmed glaucoma valve in anterior chamber versus ciliary sulcus.

    Science.gov (United States)

    Bayer, A; Önol, M

    2017-04-01

    PurposeTo evaluate the outcomes of Ahmed glaucoma valve (AGV) tube insertion through the anterior chamber angle (ACA) or through the ciliary sulcus (CS).Patients and methodsIn this case-control study, we retrospectively reviewed the charts of consecutive glaucoma patients who had undergone AGV implantation either through the ACA or the CS between March 2009 and December 2014. The main outcome measures were intraocular pressure (IOP), number of glaucoma medications prescribed, best corrected visual acuity (BCVA), glaucoma type, success rate, complications, and survival ratios. Statistical analysis was carried out using SPSS.ResultsThere were 68 eyes in the ACA group and 35 eyes in the CS group. There were no significant differences between the groups for age, sex, laterality, IOP, preoperative glaucoma medication number, BCVA or glaucoma type (P>0.05). The postoperative follow-up period was 27.2±16.5 months and 30.2±17.7 months for the ACA and the CS groups (P=0.28); IOP values were significantly reduced at the last visit to 16.4±7.2 mm Hg and 14.4±6.8 mm Hg. The difference in the last-visit IOP between the groups was not significant (P=0.06), but the IOP reduction ratio was higher in the CS group (P=0.03). There was no significant difference in the number of postoperative medications (P=0.18). Postoperative complications were similar, but the incidence of flat anterior chamber was higher in the ACA group (P=0.05).ConclusionsThe use of an AGV can control IOP in the majority of cases whether placed in the ACA or the CS. The IOP reduction ratio seemed to be higher in the CS group.

  10. Comparative study of the stridulatorium sulcus, buccula and rostrum of nymphs of Triatoma klugi Carcavallo et al, Triatoma vandae Carcavallo et al and Triatoma williami Galvao et al (Hemiptera: Redivide)

    International Nuclear Information System (INIS)

    Silva, Maria B.A.; Jurberg, Jose; Galvao, Cleber; Barbosa, Helene S.

    2010-01-01

    Ultrastructural analysis of the ventral region of the head - rostrum, buccula and stridulatorium sulcus - of 1st, 3rd and 5th instars of Triatoma klugi Carcavallo et al, Triatoma vandae Carcavallo et al, and Triatoma williami Galvao et al, are described in here. Morphological differences in the analyzed structures for all three Triatoma species studied were detected under scanning electron microscopy, allowing their grouping by their morphological similarities. Species-specific differences at each nymphal development stage were analyzed as well. (author)

  11. Comparative study of the stridulatorium sulcus, buccula and rostrum of nymphs of Triatoma klugi Carcavallo et al, Triatoma vandae Carcavallo et al and Triatoma williami Galvao et al (Hemiptera: Redivide)

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Maria B.A.; Jurberg, Jose; Galvao, Cleber; Barbosa, Helene S. [Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Lab. de Biologia Estrutural. Lab. Nacional e Internacional de Referencia em Taxonomia de Triatomineos

    2010-01-15

    Ultrastructural analysis of the ventral region of the head - rostrum, buccula and stridulatorium sulcus - of 1st, 3rd and 5th instars of Triatoma klugi Carcavallo et al, Triatoma vandae Carcavallo et al, and Triatoma williami Galvao et al, are described in here. Morphological differences in the analyzed structures for all three Triatoma species studied were detected under scanning electron microscopy, allowing their grouping by their morphological similarities. Species-specific differences at each nymphal development stage were analyzed as well. (author)

  12. Functional integration of the posterior superior temporal sulcus correlates with facial expression recognition.

    Science.gov (United States)

    Wang, Xu; Song, Yiying; Zhen, Zonglei; Liu, Jia

    2016-05-01

    Face perception is essential for daily and social activities. Neuroimaging studies have revealed a distributed face network (FN) consisting of multiple regions that exhibit preferential responses to invariant or changeable facial information. However, our understanding about how these regions work collaboratively to facilitate facial information processing is limited. Here, we focused on changeable facial information processing, and investigated how the functional integration of the FN is related to the performance of facial expression recognition. To do so, we first defined the FN as voxels that responded more strongly to faces than objects, and then used a voxel-based global brain connectivity method based on resting-state fMRI to characterize the within-network connectivity (WNC) of each voxel in the FN. By relating the WNC and performance in the "Reading the Mind in the Eyes" Test across participants, we found that individuals with stronger WNC in the right posterior superior temporal sulcus (rpSTS) were better at recognizing facial expressions. Further, the resting-state functional connectivity (FC) between the rpSTS and right occipital face area (rOFA), early visual cortex (EVC), and bilateral STS were positively correlated with the ability of facial expression recognition, and the FCs of EVC-pSTS and OFA-pSTS contributed independently to facial expression recognition. In short, our study highlights the behavioral significance of intrinsic functional integration of the FN in facial expression processing, and provides evidence for the hub-like role of the rpSTS for facial expression recognition. Hum Brain Mapp 37:1930-1940, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Fowlpoxvirus recombinants coding for the CIITA gene increase the expression of endogenous MHC-II and Fowlpox Gag/Pro and Env SIV transgenes.

    Science.gov (United States)

    Bissa, Massimiliano; Forlani, Greta; Zanotto, Carlo; Tosi, Giovanna; De Giuli Morghen, Carlo; Accolla, Roberto S; Radaelli, Antonia

    2018-01-01

    A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+ T helper cells. Here, we report on construction of novel FPgp and FPenv recombinants that express the highly immunogenic SIV Gag-pro and Env structural antigens. Several FP-based recombinants, with single or dual genes, were also developed that express CIITA, driven from H6 or SP promoters. These recombinants were used to infect CEF and Vero cells in vitro and determine transgene expression, which was evaluated by real-time PCR and Western blotting. Subcellular localisation of the different proteins was evaluated by confocal microscopy, whereas HLA-DR or MHC-II expression was measured by flow cytometry. Fowlpox recombinants were also used to infect syngeneic T/SA tumour cells, then injected into Balb/c mice to elicit MHC-II immune response and define the presentation of the SIV transgene products in the presence or absence of FPCIITA. Antibodies to Env were measured by ELISA. Our data show that the H6 promoter was more efficient than SP to drive CIITA expression and that CIITA can enhance the levels of the gag/pro and env gene products only when infection is performed by FP single recombinants. Also, CIITA expression is higher when carried by FP single recombinants than when combined with FPgp or FPenv constructs and can

  14. Pharmacological inactivation does not support a unique causal role for intraparietal sulcus in the discrimination of visual number.

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    Nicholas K DeWind

    Full Text Available The "number sense" describes the intuitive ability to quantify without counting. Single neuron recordings in non-human primates and functional imaging in humans suggest the intraparietal sulcus is an important neuroanatomical locus of numerical estimation. Other lines of inquiry implicate the IPS in numerous other functions, including attention and decision making. Here we provide a direct test of whether IPS has functional specificity for numerosity judgments. We used muscimol to reversibly and independently inactivate the ventral and lateral intraparietal areas in two monkeys performing a numerical discrimination task and a color discrimination task, roughly equilibrated for difficulty. Inactivation of either area caused parallel impairments in both tasks and no evidence of a selective deficit in numerical processing. These findings do not support a causal role for the IPS in numerical discrimination, except insofar as it also has a role in the discrimination of color. We discuss our findings in light of several alternative hypotheses of IPS function, including a role in orienting responses, a general cognitive role in attention and decision making processes and a more specific role in ordinal comparison that encompasses both number and color judgments.

  15. A computational model of fMRI activity in the intraparietal sulcus that supports visual working memory.

    Science.gov (United States)

    Domijan, Dražen

    2011-12-01

    A computational model was developed to explain a pattern of results of fMRI activation in the intraparietal sulcus (IPS) supporting visual working memory for multiobject scenes. The model is based on the hypothesis that dendrites of excitatory neurons are major computational elements in the cortical circuit. Dendrites enable formation of a competitive queue that exhibits a gradient of activity values for nodes encoding different objects, and this pattern is stored in working memory. In the model, brain imaging data are interpreted as a consequence of blood flow arising from dendritic processing. Computer simulations showed that the model successfully simulates data showing the involvement of inferior IPS in object individuation and spatial grouping through representation of objects' locations in space, along with the involvement of superior IPS in object identification through representation of a set of objects' features. The model exhibits a capacity limit due to the limited dynamic range for nodes and the operation of lateral inhibition among them. The capacity limit is fixed in the inferior IPS regardless of the objects' complexity, due to the normalization of lateral inhibition, and variable in the superior IPS, due to the different encoding demands for simple and complex shapes. Systematic variation in the strength of self-excitation enables an understanding of the individual differences in working memory capacity. The model offers several testable predictions regarding the neural basis of visual working memory.

  16. Increased likelihood of bacterial pathogens in the coronal sulcus and urethra of uncircumcised men in a diverse group of HIV infected and uninfected patients in India

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    John A Schneider

    2012-01-01

    Full Text Available Background: The biological mechanism of circumcision as potentiating HIV prevention is poorly understood. Foreskin microbiota has been postulated as having a potential role; however, little is known about the relationship between bacterial pathogens and circumcision in adults. Materials and Methods: We sampled the coronal sulcus of a diverse group of circumcised and uncircumcised men (n=315 from a government chest hospital and fertility clinic in Hyderabad, Andhra Pradesh, India. Genital examination was conducted on three groups of men: Group 1 - HIV infected; Group 2 - TB infected; Group 3 - control. Aerobic and anaerobic specimens were cultured according to standard clinical protocols, and results were analyzed following multivariate logistic regression models. Results: Three hundred fifteen study participants - 47.6% of Group 1, 36.5% of Group 2, and 15.9% of Group 3 - were enrolled in the study and included in all analyses. Overall 37.1% of the participants were circumcised without variation across groups (P=0.29. Smegma was observed in 18.7% of the participants with no cases observed in Group 3 (P<0.001. Gram-negative pathogens were more prevalent among study participants in Group 1 (22.7% and Group 2 (30.4% as compared with those in Group 3 (6.0% (P=0.003. In multivariate regression analysis, controlling for group, age, and presence of smegma, uncircumcised men were more likely to be colonized with gram positives [Adjusted Odds Ratio (AOR 1.9; P<0.05], gram negatives (AOR 2.4; P<0.05, or any pathogen (AOR 2.8; P<0.005. Conclusions: Uncircumcised men in this population in South India are more likely to harbor bacterial pathogens in the coronal sulcus than do their circumcised counterparts. Future studies should examine the relationship between foreskin microbiota and HIV transmission.

  17. Pure word deafness with auditory object agnosia after bilateral lesion of the superior temporal sulcus.

    Science.gov (United States)

    Gutschalk, Alexander; Uppenkamp, Stefan; Riedel, Bernhard; Bartsch, Andreas; Brandt, Tobias; Vogt-Schaden, Marlies

    2015-12-01

    Based on results from functional imaging, cortex along the superior temporal sulcus (STS) has been suggested to subserve phoneme and pre-lexical speech perception. For vowel classification, both superior temporal plane (STP) and STS areas have been suggested relevant. Lesion of bilateral STS may conversely be expected to cause pure word deafness and possibly also impaired vowel classification. Here we studied a patient with bilateral STS lesions caused by ischemic strokes and relatively intact medial STPs to characterize the behavioral consequences of STS loss. The patient showed severe deficits in auditory speech perception, whereas his speech production was fluent and communication by written speech was grossly intact. Auditory-evoked fields in the STP were within normal limits on both sides, suggesting that major parts of the auditory cortex were functionally intact. Further studies showed that the patient had normal hearing thresholds and only mild disability in tests for telencephalic hearing disorder. Prominent deficits were discovered in an auditory-object classification task, where the patient performed four standard deviations below the control group. In marked contrast, performance in a vowel-classification task was intact. Auditory evoked fields showed enhanced responses for vowels compared to matched non-vowels within normal limits. Our results are consistent with the notion that cortex along STS is important for auditory speech perception, although it does not appear to be entirely speech specific. Formant analysis and single vowel classification, however, appear to be already implemented in auditory cortex on the STP. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Involvement of the dorsolateral prefrontal cortex and superior temporal sulcus in impaired social perception in schizophrenia.

    Science.gov (United States)

    Shin, Jung Eun; Choi, Soo-Hee; Lee, Hyeongrae; Shin, Young Seok; Jang, Dong-Pyo; Kim, Jae-Jin

    2015-04-03

    Schizophrenia is a mental disorder characterized by impairments in diverse thinking and emotional responses, which are related to social perception dysfunction. This fMRI study was designed to investigate a neurobiological basis of social perception deficits of patients with schizophrenia in various social situations of daily life and their relationship with clinical symptoms and social dysfunction. Seventeen patients and 19 controls underwent functional magnetic resonance imaging, during which participants performed a virtual social perception task, containing an avatar's speech with positive, negative or neutral emotion in a virtual reality space. Participants were asked to determine whether or not the avatar's speech was appropriate to each situation. The significant group×appropriateness interaction was seen in the left dorsolateral prefrontal cortex (DLPFC), resulting from lower activity in patients in the inappropriate condition, and left DLPFC activity was negatively correlated with the severity of negative symptoms and positively correlated with the level of social functioning. The significant appropriateness×emotion interaction observed in the left superior temporal sulcus (STS) was present in controls, but absent in patients, resulting from the existence and absence of a difference between the inappropriate positive and negative conditions, respectively. These findings indicate that dysfunction of the DLPFC-STS network may underlie patients' abnormal social perception in various social situations of daily life. Abnormal functioning of this network may contribute to increases of negative symptoms and decreases of social functioning. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Christine M Fennessey

    2017-05-01

    Full Text Available HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART for 82 days starting on day 6 post-infection (study 1. Plasma viremia was reduced from >106 to <15 vRNA copies/mL by the time treatment was interrupted. Virus rapidly rebounded following treatment interruption and between 87 and 136 distinct clonotypes were detected in plasma at peak rebound viremia. This study confirmed that SIVmac239M viremia could be successfully curtailed with cART, and that upon cART discontinuation, rebounding viral variants could be identified and quantified. An additional 6 animals infected with SIVmac239M were treated with cART beginning on day 4 post-infection for 305, 374, or 482 days (study 2. Upon treatment interruption, between 4 and 8 distinct viral clonotypes were detected in each animal at peak rebound

  20. [Adverse effects of seasonal flu vaccine and new influenza A (H1N1) vaccine in health care workers].

    Science.gov (United States)

    Torruella, Joan Inglés; Soto, Rosa Gil; Valls, Rosa Carreras; Lozano, Judit Valverde; Carreras, Dolors Benito; Cunillera, Arnau Besora

    2013-01-01

    To assess and compare adverse effects of Seasonal Influenza Vaccine (SIV) and new Influenza A(H1N1) Vaccine (AIV) in health care workers. Multicenter cross-sectional study in health care workers from acute care hospitals, primary health care centers, social centers, mental health centers and a geriatric hospital participating in the 2009 vaccination campaign. Self-administered questionnaires were sent to all workers vaccinated with SIV and/or AIV. 527 valid questionnaires were collected out of 1123 sent to SIV vaccinated workers (46.9%), and 241 out of 461 sent to AIV vaccinated workers (52.%%). Participant workers include 527 vaccinated only with SIV, 117 first vaccinated with SIV and later with AIV (SIV+AIV), and 125 vaccinated only with AIV. Overall, 18.4% (95%CI 15.1-21.7) of workers vaccinated only with SIV reported adverse effects, as compared to 45.3% (95I 36.3-54.3) reporting adverse effects to AIV in the SIV+AIV group and 46.4% (95%CI 37.7-55.1) of workers vaccinated only with AIV. In all participants the most common adverseeffect was a local reaction. Women wre more reactive to both SIV and AIV than men. In all age groups SIV vaccination alone caused fewer reactions that either AIV only or the combination of SIV+AIV, with the exception of workers below 29 years of age. AIV was associated with more reactions than SIV, with no differences observed in relation to administration sequence. There were differences by sex and age, but reactions always occurred more commonly with AIV. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

  1. Associations of olfactory bulb and depth of olfactory sulcus with basal ganglia and hippocampus in patients with Parkinson's disease.

    Science.gov (United States)

    Tanik, Nermin; Serin, Halil Ibrahim; Celikbilek, Asuman; Inan, Levent Ertugrul; Gundogdu, Fatma

    2016-05-04

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by hyposmia in the preclinical stages. We investigated the relationships of olfactory bulb (OB) volume and olfactory sulcus (OS) depth with basal ganglia and hippocampal volumes. The study included 25 patients with PD and 40 age- and sex-matched control subjects. Idiopathic PD was diagnosed according to published diagnostic criteria. The Hoehn and Yahr (HY) scale, the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS III), and the Mini-Mental State Examination (MMSE) were administered to participants. Volumetric measurements of olfactory structures, the basal ganglia, and hippocampus were performed using magnetic resonance imaging (MRI). OB volume and OS depth were significantly reduced in PD patients compared to healthy control subjects (p<0.001 and p<0.001, respectively). The OB and left putamen volumes were significantly correlated (p=0.048), and the depth of the right OS was significantly correlated with right hippocampal volume (p=0.018). We found significant correlations between OB and putamen volumes and OS depth and hippocampal volume. Our study is the first to demonstrate associations of olfactory structures with the putamen and hippocampus using MRI volumetric measurements. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Olfactory bulb and olfactory sulcus depths are associated with disease duration and attack frequency in multiple sclerosis patients.

    Science.gov (United States)

    Tanik, Nermin; Serin, Halil Ibrahim; Celikbilek, Asuman; Inan, Levent Ertugrul; Gundogdu, Fatma

    2015-11-15

    Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease that progresses to axonal loss and demyelinization. Olfactory dysfunction in patients with MS has been reported frequently. We were interested in the associations of olfactory bulb (OB) and olfactory sulcus depth (OSD) with disease duration and attack frequency. We included 25 patients with MS and 30 age- and sex-matched controls in this study. The Expanded Disability Status Scale, Beck Depression Inventory, and Mini Mental State Examination were applied. OB, OSD, and magnetic resonance imaging plaque numbers were calculated. OB volume and OSD in patients with MS were significantly lower than those in the control group (right and left OB: p<0.001; right OSD: p=0.001; and left OSD: p=0.039). Disease duration was negatively correlated with right and left OB volume (right OB: r=-0.434, p=0.030 and left OB: r=-0.518, p=0.008). Attack frequency was negatively correlated with left OB volume and left OSD (left OB: r=-0.428, p=0.033 and left OSD: r=-0.431, p=0.032). The OB and OSD were atrophied significantly in patients with MS, and this was correlated with disease duration and attack frequency. The left side tended to be dominant. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Nueva variante de abordaje al surco ciliar en la fijación transescleral de lentes de cámara posterior New variant of approach to the ciliary sulcus in the transcleral fixation of posterior chamber lens

    Directory of Open Access Journals (Sweden)

    Ileana Vila Dópico

    2002-06-01

    Full Text Available Se expone una variante de abordaje al surco ciliar para la fijación del lente intraocular de cámara posterior, que está a nuestro alcance, en pacientes en que no existe soporte capsular o este es insuficiente. Se describe la técnica. Se realizó en 17 pacientes de los que se obtuvo mejoría visual en todos los casos (20/50-20/20 con un seguimiento promedio de 12 meses. Esta variante tiene la ventaja de evitar el paso de la aguja por el surco ciliar a ciegas, pues se utiliza el abordaje a través de la esclera y con ello evitamos dañar estructuras oculares aledañas evitando el riesgo de complicaciones por lo que se logra la recuperación anatómica y funcional en todos los casos.A variant to approach the ciliary sulcus for fixating the posterior chamber intraocular lens, which is within our reach, in patients with insufficient or no capsular support, is explained. The technique is described here and it was applied to 17 patients. Visual improvement was obtained in all cases (20/50-20/20 with an average follow-up of 12 months. This variant allows to prevent the blind passage of the needle through the ciliary sulcus, since it is approached via the sclera, avoiding to damage adjoining ocular structures and to have complications, and making possible the anatomic and functional recovery of all patients.

  4. GABA concentration in superior temporal sulcus predicts gamma power and perception in the sound-induced flash illusion.

    Science.gov (United States)

    Balz, Johanna; Keil, Julian; Roa Romero, Yadira; Mekle, Ralf; Schubert, Florian; Aydin, Semiha; Ittermann, Bernd; Gallinat, Jürgen; Senkowski, Daniel

    2016-01-15

    In everyday life we are confronted with inputs of multisensory stimuli that need to be integrated across our senses. Individuals vary considerably in how they integrate multisensory information, yet the neurochemical foundations underlying this variability are not well understood. Neural oscillations, especially in the gamma band (>30Hz) play an important role in multisensory processing. Furthermore, gamma-aminobutyric acid (GABA) neurotransmission contributes to the generation of gamma band oscillations (GBO), which can be sustained by activation of metabotropic glutamate receptors. Hence, differences in the GABA and glutamate systems might contribute to individual differences in multisensory processing. In this combined magnetic resonance spectroscopy and electroencephalography study, we examined the relationships between GABA and glutamate concentrations in the superior temporal sulcus (STS), source localized GBO, and illusion rate in the sound-induced flash illusion (SIFI). In 39 human volunteers we found robust relationships between GABA concentration, GBO power, and the SIFI perception rate (r-values=0.44 to 0.53). The correlation between GBO power and SIFI perception rate was about twofold higher when the modulating influence of the GABA level was included in the analysis as compared to when it was excluded. No significant effects were obtained for glutamate concentration. Our study suggests that the GABA level shapes individual differences in audiovisual perception through its modulating influence on GBO. GABA neurotransmission could be a promising target for treatment interventions of multisensory processing deficits in clinical populations, such as schizophrenia or autism. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Variation in functional connectivity along anterior-to-posterior intraparietal sulcus, and relationship with age across late childhood and adolescence

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    Sarah A. Vinette

    2015-06-01

    Full Text Available The intraparietal sulcus (IPS, a region in the dorsal attention network (DAN, has been implicated in multi-sensory attention and working memory. Working memory and attention develop across childhood; changes in functional connectivity within the DAN may relate to this maturation. Previous findings regarding fronto-parietal intrinsic functional connectivity age-effects were mixed. Our study aimed to circumvent limitations of previous work using a large cross-sectional sample, 183 typically developing participants 6.5–20 years, from the Autism Brain Imaging Data Exchange, and seed regions along the anterior-to-posterior axis of the IPS. These seeds, IPS0-4, were entered into functional connectivity models. Group-level models investigated differential connectivity along the IPS and relationships with age. Anterior IPS3/4 exhibited greater connectivity with sensorimotor/pre-motor regions. Posterior IPS0/1 demonstrated greater connectivity with dorsal and ventral visual regions. Positive age-effects were found between IPS3-4 and visual regions. Negative age-effects were found between IPS and superior parietal and medial orbitofrontal cortices. Follow-up region of interest analyses were used to estimate age-effects for DAN and anticorrelated default mode network regions. Results suggest age-effects on IPS functional connectivity are relatively modest, and may differ pre- and across-adolescence. Studying typical age-related connectivity variability within this network may help to understand neurodevelopmental disorders marked by impaired attention.

  6. Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

    Directory of Open Access Journals (Sweden)

    John K. Maxi

    2016-11-01

    Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

  7. Stability of the gorilla microbiome despite simian immunodeficiency virus infection

    OpenAIRE

    Moeller, A. H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, E. M.; Esteban, A.; Hahn, B. H.; Ochman, H.

    2015-01-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. H...

  8. Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV Nef

    International Nuclear Information System (INIS)

    Bouzar, Baya Amel; Rea, Angela; Hoc-Villet, Stephanie; Garnier, Celine; Guiguen, Francois; Jin Yuhuai; Narayan, Opendra; Chebloune, Yahia

    2007-01-01

    Caprine arthritis encephalitis virus (CAEV) is the natural lentivirus of goats, well known for its tropism for macrophages and its inability to cause infection in lymphocytes. The viral genome lacks nef, tat, vpu and vpx coding sequences. To test the hypothesis that when nef is expressed by the viral genome, the virus became toxic for lymphocytes during replication in macrophages, we inserted the SIVsmm PBj14 nef coding sequences into the genome of CAEV thereby generating CAEV-nef. This recombinant virus is not infectious for lymphocytes but is fully replication competent in goat macrophages in which it constitutively expresses the SIV Nef. We found that goat lymphocytes cocultured with CAEV-nef-infected macrophages became activated, showing increased expression of the interleukin-2 receptor (IL-2R). Activation correlated with increased proliferation of the cells. Interestingly, a dual effect in terms of apoptosis regulation was observed in exposed goat lymphocytes. Nef was found first to induce a protection of lymphocytes from apoptosis during the first few days following exposure to infected macrophages, but later it induced increased apoptosis in the activated lymphocytes. This new recombinant virus provides a model to study the functions of Nef in the context of infection of macrophages, but in absence of infection of T lymphocytes and brings new insights into the biological effects of Nef on lymphocytes

  9. Superior sulcus non-small cell lung carcinoma: A comparison of IMRT and 3D-RT dosimetry.

    Science.gov (United States)

    Truntzer, Pierre; Antoni, Delphine; Santelmo, Nicola; Schumacher, Catherine; Falcoz, Pierre-Emmanuel; Quoix, Elisabeth; Massard, Gilbert; Noël, Georges

    2016-01-01

    A dosimetric study comparing intensity modulated radiotherapy (IMRT) by TomoTherapy to conformational 3D radiotherapy (3D-RT) in patients with superior sulcus non-small cell lung cancer (NSCLC). IMRT became the main technique in modern radiotherapy. However it was not currently used for lung cancers. Because of the need to increase the dose to control lung cancers but because of the critical organs surrounding the tumors, the gains obtainable with IMRT is not still demonstrated. A dosimetric comparison of the planned target and organs at risk parameters between IMRT and 3D-RT in eight patients who received preoperative or curative intent irradiation. In the patients who received at least 66 Gy, the mean V95% was significantly better with IMRT than 3D-RT (p = 0.043). IMRT delivered a lower D2% compared to 3D-RT (p = 0.043). The IH was significantly better with IMRT (p = 0.043). The lung V 5 Gy and V 13 Gy were significantly higher in IMRT than 3D-RT (p = 0.043), while the maximal dose (D max) to the spinal cord was significantly lower in IMRT (p = 0.043). The brachial plexus D max was significantly lower in IMRT than 3D-RT (p = 0.048). For patients treated with 46 Gy, no significant differences were found. Our study showed that IMRT is relevant for SS-NSCLC. In patients treated with a curative dose, it led to a reduction of the exposure of critical organs, allowing a better dose distribution in the tumor. For the patients treated with a preoperative schedule, our results provide a basis for future controlled trials to improve the histological complete response by increasing the radiation dose.

  10. Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

    Science.gov (United States)

    Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John

    2009-08-01

    There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

  11. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    Science.gov (United States)

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  12. Development of a real-time method for the measurement of sulfur(IV) in cloud water with a counter-flow virtual impactor

    International Nuclear Information System (INIS)

    Dixon, R.W.

    1991-01-01

    A novel method, using a counter-flow virtual impactor (CVI) to measure S(IV) concentrations in cloud water, is described. The CVI collects and evaporates cloud droplets, converting aqueous S(IV) into gaseous SO 2 for analysis with a pulsed-fluorescence detector. Based on calculations and laboratory experiments with acidic droplets, S(IV), except that complexed as hydroxymethanesulfonate (HMS), is expected to be released to the gas phase during droplet evaporation. Evidence for the production of HMS in aerosol particles following droplet evaporation also was obtained from measurements of complexes S(IV) in ambient aerosol samples. Field measurements were performed with a CVI mounted on a research aircraft during the Frontal Boundary Study in Ohio to evaluate the CVI for measuring S(IV) in cloud water. From the signal of the SO 2 analyzer, the aqueous S(IV) concentration was determined. Measurements in clouds showed similar temporal variation of S(IV) (aq) with other cloud parameters following required data treatment. A detection limit of 0.1 nmol per m 3 of air was achieved over one minute intervals and was limited mainly by the noise of the SO 2 analyzer. Determination of molar S(IV) (aq) concentrations requires simultaneous measurements of the water vapor released by the evaporated droplets collected by the CVI which was not made

  13. Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.

    Science.gov (United States)

    Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko

    2013-04-01

    The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.

  14. Swine influenza virus vaccines: to change or not to change-that's the question.

    Science.gov (United States)

    Van Reeth, Kristien; Ma, Wenjun

    2013-01-01

    Commercial vaccines currently available against swine influenza virus (SIV) are inactivated, adjuvanted, whole virus vaccines, based on H1N1 and/or H3N2 and/or H1N2 SIVs. In keeping with the antigenic and genetic differences between SIVs circulating in Europe and the US, the vaccines for each region are produced locally and contain different strains. Even within a continent, there is no standardization of vaccine strains, and the antigen mass and adjuvants can also differ between different commercial products. Recombinant protein vaccines against SIV, vector, and DNA vaccines, and vaccines attenuated by reverse genetics have been tested in experimental studies, but they have not yet reached the market. In this review, we aim to present a critical analysis of the performance of commercial inactivated and novel generation SIV vaccines in experimental vaccination challenge studies in pigs. We pay special attention to the differences between commercial SIV vaccines and vaccination attitudes in Europe and in North America, to the issue of vaccine strain selection and changes, and to the potential advantages of novel generation vaccines over the traditional killed SIV vaccines.

  15. The anterior intraparietal sulcus mediates grasp execution, independent of requirement to update: new insights from transcranial magnetic stimulation.

    Science.gov (United States)

    Rice, Nichola J; Tunik, Eugene; Grafton, Scott T

    2006-08-02

    Although a role of the intraparietal sulcus (IPS) in grasping is becoming evident, the specific contribution of regions within the IPS remains undefined. In this vein, transcranial magnetic stimulation (TMS) was delivered to the anterior (aIPS), middle (mIPS), and caudal (cIPS) IPS in two tasks designed to dissociate the potential roles of the IPS in either grasp planning or execution (task 1) and its involvement in error detection or error correction (task 2). Determining the involvement of specific regions of the IPS in perceptual (planning and error detection) versus motor (execution and correction) components of grasping allowed us to assess the ecological validity of competing computational models attempting to simulate reach-to-grasp movements. In task 1, we demonstrate that, when no on-line adjustment is necessary, TMS to aIPS (but not mIPS or cIPS) disrupts grasping; this disruption is only elicited when TMS is applied during the execution (but not the planning) phase of the movement. Task 2 reveals that TMS to aIPS (but not mIPS or cIPS) disrupts grasping in the presence of a perturbation; this disruption is only elicited when TMS is applied during the error correction (but not error detection) phase of the movement. We propose that the specific contribution of the aIPS in grasping is in the on-line computation of a difference vector based on motor goal, efference copy, and sensory inputs. This computation is performed for both stable and perturbed motor goals.

  16. Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.

    Science.gov (United States)

    Stieh, Daniel J; Maric, Danijela; Kelley, Z L; Anderson, Meegan R; Hattaway, Holly Z; Beilfuss, Beth A; Rothwangl, Katharina B; Veazey, Ronald S; Hope, Thomas J

    2014-10-01

    The majority of new HIV infections occur in women as a result of heterosexual intercourse, overcoming multiple innate barriers to infection within the mucosa. However, the avenues through which infection is established, and the nature of bottlenecks to transmission, have been the source of considerable investigation and contention. Using a high dose of a single round non-replicating SIV-based vector containing a novel dual reporter system, we determined the sites of infection by the inoculum using the rhesus macaque vaginal transmission model. Here we show that the entire female reproductive tract (FRT), including the vagina, ecto- and endocervix, along with ovaries and local draining lymph nodes can contain transduced cells only 48 hours after inoculation. The distribution of infection shows that virions quickly disseminate after exposure and can access target cells throughout the FRT, with an apparent preference for infection in squamous vaginal and ectocervical mucosa. JRFL enveloped virions infect diverse CD4 expressing cell types, with T cells resident throughout the FRT representing the primary target. These findings establish a new perspective that the entire FRT is susceptible and virus can reach as far as the ovary and local draining lymph nodes. Based on these findings, it is essential that protective mechanisms for prevention of HIV acquisition must be present at protective levels throughout the entire FRT to provide complete protection.

  17. Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1.

    Science.gov (United States)

    Greenwood, Edward J D; Schmidt, Fabian; Liégeois, Florian; Kondova, Ivanela; Herbert, Anaïs; Ngoubangoye, Barthelemy; Rouet, François; Heeney, Jonathan L

    2014-01-01

    Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

  18. Excitation of nanowire surface plasmons by silicon vacancy centers in nanodiamonds

    DEFF Research Database (Denmark)

    Kumar, Shailesh; Davydov, Valery A.; Agafonov, Viatcheslav N.

    2017-01-01

    Silicon vacancy (SiV) centers in diamonds have emerged as a very promising candidate for quantum emitters due to their narrow emission line resulting in their indistinguishability. While many different quantum emitters have already been used for the excitation of various propagating plasmonic modes......, the corresponding exploitation of SiV centers has remained so far uncharted territory. Here, we report on the excitation of surface plasmon modes supported by silver nanowires using SiV centers in nanodiamonds. The coupling of SiV center fluorescence to surface plasmons is observed, when a nanodiamond situated...

  19. Three interesting cases of gyral infarction as detected by CT in the vicinity of the central sulcus

    International Nuclear Information System (INIS)

    Tokiguchi, Susumu; Kurashima, Akihiko; Tsuchiya, Toshiaki; Ito, Jusuke

    1986-01-01

    In most cases of senile brain, the arrangement of the cerebral sulci and gyri of the superior surface of the hemisphere is well demonstrated by thin-sectioned CT. In these cases, it is not very difficult to identify the cortical gyri anatomically. We experienced three interesting cases with a small gyral infarction in the vicinity of the central sulcus (Roland). The lesions were detected and their anatomical localizations were precisely identified by CT, and they correlated well with their clinical findings. In Case 1, who suddenly developed clumsiness of the left hand, neurological findings were confined to her left hand, where a marked impairment of the combined sensation and position sense was found. However, there was no weakness or impaired vibration sense or disturbed superficial sensation. Since vibratory appreciation is seldom disturbed by lesions above the level of the thalamus, and since the combined sensation and joint sense were selectively impaired in this case, a lesion in the right parietal lobe was suggested. CT scan revealed a small gyral infarction which was strictly confined to the right postcentral gyrus. Case 2, developed weakness of the left hand. He could not extend the wrist against gravity, but dorsiflexion of the wrist could be elicited by grasping. Weakness was confined to his left hand, and there was no sensory disturbance. Neurological findings suggested a small cortical infraction in the right precentral gyrus. CT showed a small lesion just under the right precentral gyrus, where the cortical representation of the hand was thought to be arranged. In Case 3, who developed an adversive seizure, CT clearly demonstrated a lesion in the contralateral premotor area. Our method of the anatomical identification of the sulci and the gyri of the superior surface of the cerebral hemisphere was described. (author)

  20. The first Swedish H1N2 swine influenza virus isolate represents an uncommon reassortant

    Directory of Open Access Journals (Sweden)

    Renström Lena HM

    2009-10-01

    Full Text Available Abstract The European swine influenza viruses (SIVs show considerable diversity comprising different types of H1N1, H3N2, and H1N2 strains. The intensifying full genome sequencing efforts reveal further reassortants within these subtypes. Here we report the identification of an uncommon reassortant variant of H1N2 subtype influenza virus isolated from a pig in a multisite herd where H1N2 swine influenza was diagnosed for the first time in Sweden during the winter of 2008-2009. The majority of the European H1N2 swine influenza viruses described so far possess haemagglutinin (HA of the human-like H1N2 SIV viruses and the neuraminidase (NA of either the European H1N2 or H3N2 SIV-like viruses. The Swedish isolate has an avian-like SIV HA and a H3N2 SIV-like NA, which is phylogenetically more closely related to H3N2 SIV NAs from isolates collected in the early '80s than to the NA of H3N2 origin of the H1N2 viruses isolated during the last decade, as depicted by some German strains, indicative of independent acquisition of the NA genes for these two types of reassortants. The internal genes proved to be entirely of avian-like SIV H1N1 origin. The prevalence of this SIV variant in pig populations needs to be determined, as well as the suitability of the routinely used laboratory reagents to analyze this strain. The description of this H1N2 SIV adds further information to influenza epidemiology and supports the necessity of surveillance for influenza viruses in pigs.

  1. The first Swedish H1N2 swine influenza virus isolate represents an uncommon reassortant.

    Science.gov (United States)

    Bálint, Adám; Metreveli, Giorgi; Widén, Frederik; Zohari, Siamak; Berg, Mikael; Isaksson, Mats; Renström, Lena Hm; Wallgren, Per; Belák, Sándor; Segall, Thomas; Kiss, István

    2009-10-28

    The European swine influenza viruses (SIVs) show considerable diversity comprising different types of H1N1, H3N2, and H1N2 strains. The intensifying full genome sequencing efforts reveal further reassortants within these subtypes. Here we report the identification of an uncommon reassortant variant of H1N2 subtype influenza virus isolated from a pig in a multisite herd where H1N2 swine influenza was diagnosed for the first time in Sweden during the winter of 2008-2009. The majority of the European H1N2 swine influenza viruses described so far possess haemagglutinin (HA) of the human-like H1N2 SIV viruses and the neuraminidase (NA) of either the European H1N2 or H3N2 SIV-like viruses. The Swedish isolate has an avian-like SIV HA and a H3N2 SIV-like NA, which is phylogenetically more closely related to H3N2 SIV NAs from isolates collected in the early '80s than to the NA of H3N2 origin of the H1N2 viruses isolated during the last decade, as depicted by some German strains, indicative of independent acquisition of the NA genes for these two types of reassortants. The internal genes proved to be entirely of avian-like SIV H1N1 origin. The prevalence of this SIV variant in pig populations needs to be determined, as well as the suitability of the routinely used laboratory reagents to analyze this strain.The description of this H1N2 SIV adds further information to influenza epidemiology and supports the necessity of surveillance for influenza viruses in pigs.

  2. Silicon-Vacancy Spin Qubit in Diamond: A Quantum Memory Exceeding 10 ms with Single-Shot State Readout

    Science.gov (United States)

    Sukachev, D. D.; Sipahigil, A.; Nguyen, C. T.; Bhaskar, M. K.; Evans, R. E.; Jelezko, F.; Lukin, M. D.

    2017-12-01

    The negatively charged silicon-vacancy (SiV- ) color center in diamond has recently emerged as a promising system for quantum photonics. Its symmetry-protected optical transitions enable the creation of indistinguishable emitter arrays and deterministic coupling to nanophotonic devices. Despite this, the longest coherence time associated with its electronic spin achieved to date (˜250 ns ) has been limited by coupling to acoustic phonons. We demonstrate coherent control and suppression of phonon-induced dephasing of the SiV- electronic spin coherence by 5 orders of magnitude by operating at temperatures below 500 mK. By aligning the magnetic field along the SiV- symmetry axis, we demonstrate spin-conserving optical transitions and single-shot readout of the SiV- spin with 89% fidelity. Coherent control of the SiV- spin with microwave fields is used to demonstrate a spin coherence time T2 of 13 ms and a spin relaxation time T1 exceeding 1 s at 100 mK. These results establish the SiV- as a promising solid-state candidate for the realization of quantum networks.

  3. Silicon-vacancy centre as an artificial atom in diamond

    International Nuclear Information System (INIS)

    Lachlan Rogers

    2014-01-01

    A transition at 738 nm in diamond has been attributed to the silicon vacancy (SiV) colour centre. Much less is known about this defect site than the famous nitrogen-vacancy centre, but it appears to have advantages for some applications It is particularly promising as a single-photon source, due to a bright optical transition which has most of its intensity in the zero-phonon-line and only a small phonon sideband. A number of results will be reported for single SiV sites in bulk diamond, complementing recent activity on SiV in nanodiamonds. Individual SiV sites in the low-strain environment of bulk diamond show almost no variation in photoluminescence spectra. By fabricating a solid-immersion lens in the diamond over a SiV site we have enhanced the photon collection rate by nearly a factor of ten. In order to identify whether the SiV centre could be useful for broader quantum information processing application, it is first necessary to establish its electronic structure. Recent experimental developments in this direction will be discussed. (author)

  4. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

    Science.gov (United States)

    Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

    2015-02-01

    Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

  5. Dissociated roles of the inferior frontal gyrus and superior temporal sulcus in audiovisual processing: top-down and bottom-up mismatch detection.

    Science.gov (United States)

    Uno, Takeshi; Kawai, Kensuke; Sakai, Katsuyuki; Wakebe, Toshihiro; Ibaraki, Takuya; Kunii, Naoto; Matsuo, Takeshi; Saito, Nobuhito

    2015-01-01

    Visual inputs can distort auditory perception, and accurate auditory processing requires the ability to detect and ignore visual input that is simultaneous and incongruent with auditory information. However, the neural basis of this auditory selection from audiovisual information is unknown, whereas integration process of audiovisual inputs is intensively researched. Here, we tested the hypothesis that the inferior frontal gyrus (IFG) and superior temporal sulcus (STS) are involved in top-down and bottom-up processing, respectively, of target auditory information from audiovisual inputs. We recorded high gamma activity (HGA), which is associated with neuronal firing in local brain regions, using electrocorticography while patients with epilepsy judged the syllable spoken by a voice while looking at a voice-congruent or -incongruent lip movement from the speaker. The STS exhibited stronger HGA if the patient was presented with information of large audiovisual incongruence than of small incongruence, especially if the auditory information was correctly identified. On the other hand, the IFG exhibited stronger HGA in trials with small audiovisual incongruence when patients correctly perceived the auditory information than when patients incorrectly perceived the auditory information due to the mismatched visual information. These results indicate that the IFG and STS have dissociated roles in selective auditory processing, and suggest that the neural basis of selective auditory processing changes dynamically in accordance with the degree of incongruity between auditory and visual information.

  6. PB1-F2 Protein Does Not Impact the Virulence of Triple-Reassortant H3N2 Swine Influenza Virus in Pigs but Alters Pathogenicity and Transmission in Turkeys.

    Science.gov (United States)

    Deventhiran, Jagadeeswaran; Kumar, Sandeep R P; Raghunath, Shobana; Leroith, Tanya; Elankumaran, Subbiah

    2016-01-01

    PB1-F2 protein, the 11th influenza A virus (IAV) protein, is considered to play an important role in primary influenza virus infection and postinfluenza secondary bacterial pneumonia in mice. The functional role of PB1-F2 has been reported to be a strain-specific and host-specific phenomenon. Its precise contribution to the pathogenicity and transmission of influenza virus in mammalian host, such as swine, and avian hosts, such as turkeys, remain largely unknown. In this study, we explored the role of PB1-F2 protein of triple-reassortant (TR) H3N2 swine influenza virus (SIV) in pigs and turkeys. Using the eight-plasmid reverse genetics system, we rescued wild-type SIV A/swine/Minnesota/1145/2007 (H3N2) (SIV 1145-WT), a PB1-F2 knockout mutant (SIV 1145-KO), and its N66S variant (SIV 1145-N66S). The ablation of PB1-F2 in SIV 1145 modulated early-stage apoptosis but did not affect the viral replication in swine alveolar macrophage cells. In pigs, PB1-F2 expression did not affect nasal shedding, lung viral load, immunophenotypes, and lung pathology. On the other hand, in turkeys, SIV 1145-KO infected poults, and its in-contacts developed clinical signs earlier than SIV 1145-WT groups and also displayed more extensive histopathological changes in intestine. Further, turkeys infected with SIV 1145-N66S displayed poor infectivity and transmissibility. The more extensive histopathologic changes in intestine and relative transmission advantage observed in turkeys infected with SIV 1145-KO need to be further explored. Taken together, these results emphasize the host-specific roles of PB1-F2 in the pathogenicity and transmission of IAV. Novel triple-reassortant H3N2 swine influenza virus emerged in 1998 and spread rapidly among the North American swine population. Subsequently, it showed an increased propensity to reassort, generating a range of reassortants. Unlike classical swine influenza virus, TR SIV produces a full-length PB1-F2 protein, which is considered an important

  7. Displacement of the central sulcus in cerebral arteriovenous malformations situated in the peri-motor cortex as assessed by magnetoencephalography

    International Nuclear Information System (INIS)

    Shimamura, Norihito; Ohkuma, Hiroki; Ogane, Kazumi; Manabe, Hiroshi; Yagihashi, Akinori; Kikkawa, Tomoshige; Suzuki, Shigeharu

    2003-01-01

    In order to determine the optimal treatment for a pen-motor cortex lesion, preoperative orientation of central sulcus (CS) is indispensable. The purpose of this study is to detect a discrepancy between ''functional'' CS and ''anatomical'' CS in cerebral lesions. Stereotactic mapping of functional'' CS was performed on 12 subjects using somatosensory evoked fields (SEFs) with MRI-linked whole head magnetoencephalography (MEG) system preoperatively. All subjects who underwent axial T1-weighted MRI scans had a left-sided lesion with diagnoses including: three arteriovenous malformations (AVM), six gliomas and three meningiomas. Two certified neurosurgeons identified the anatomical CS of the cerebral hemispheres in MRI. Right median nerves were stimulated at the wrists using the following parameters of stimulation: 1 Hz rectangular electrical wave, 0.2 msec duration, and 3 to 5 mA intensity. The sampling rate was 600 Hz and band pass filters were 0.1 to 200 Hz. One hundred epochs were averaged to determine SEFs during a 50 msec pre-stimulus to 300 msec following stimulus onset. Estimations of single dipole were corresponded with N20m of SEFs. Estimated current dipoles were superimposed on the MR images. Anatomical CS accorded with functional CS in the intracranial tumor cases. AVM cases in which the nidus was situated in the peri-motor cortex showed discrepancies between functional CS and anatomical CS marking one gyrus. AVMs situated in the peri-motor area have the ability to displace the CS. Preoperative consideration for AVM treatment should include functional brain mapping to decide the most suitable operative approach and avoid postoperative deficits. (author)

  8. Feasibility of Using Ultrasonography to Establish Relationships Among Sacral Base Position, Sacral Sulcus Depth, Body Mass Index, and Sex.

    Science.gov (United States)

    Lockwood, Michael D; Kondrashova, Tatyana; Johnson, Jane C

    2015-11-01

    Identifying relationships among anatomical structures is key in diagnosing somatic dysfunction. Ultrasonography can be used to visualize anatomical structures, identify sacroiliac landmarks, and validate anatomical findings and measurements in relation to somatic dysfunction. As part of the osteopathic manipulative medicine course at A.T. Still University-Kirksville College of Osteopathic Medicine, first-year students are trained to use ultrasonography to establish relationships among musculoskeletal structures. To determine the ability of first-year osteopathic medical students to establish sacral base position (SBP) and sacral sulcus depth (SSD) using ultrasonography and to identify the relationship of SBP and SSD to body mass index (BMI) and sex. Students used ultrasonography to obtain the distance between the skin and the sacral base (the SBP) and the distance between the skin and the tip of the posterior superior iliac spine bilaterally. Next, students calculated the SSD (the distance between the tip of the posterior superior iliac spine and the SBP). Data were analyzed with respect to side of the body, BMI, sex, and age. The BMI data were subdivided into normal (18-25 mg/kg) and overweight (25-30 mg/kg) groups. Ultrasound images of 211 students were included in the study. The SBP was not significantly different between the left and right sides (36.5 mm vs 36.5 mm; P=.95) but was significantly different between normal and overweight BMI categories (33.0 mm vs 40.0 mm; Psex may point to more soft tissue overlaying the sacrum in these groups. Further research is needed on the use of ultrasonography to establish criteria for somatic dysfunction.

  9. Feminist therapy with people who self-inflict violence.

    Science.gov (United States)

    Brown, Laura S; Bryan, Tracy C

    2007-11-01

    In this article, the authors describe how a feminist therapist approaches work with clients who practice self-inflicted violence (SIV). They begin by discussing feminist therapy, with its focus on empowerment of clients and the use of noncoercive strategies. The feminist perspective on understanding SIV behaviors is described, with SIV being defined as a coping strategy used by survivors of complex trauma as a means of self-care. Feminist therapy is illustrated with a case example of a woman who used SIV, and the challenges to a therapist wishing to promote client safety while empowering the client. Practice recommendations and cautions are advanced.

  10. Pathogenicity and transmission of triple reassortant H3N2 swine influenza A viruses is attenuated following Turkey embryo propagation.

    Science.gov (United States)

    Raghunath, Shobana; Pudupakam, Raghavendra Sumanth; Deventhiran, Jagadeeswaran; Tevatia, Rahul; Leroith, Tanya

    2017-03-01

    Genetic lineages of swine influenza A viruses (SIVs) have recently been established in Turkeys in the United States. To identify molecular determinants that are involved in virulence and transmission of SIVs to Turkeys, we sequentially passaged two triple reassortant H3N2 SIV isolates from Minnesota in ten day old specific-pathogen free (SPF) Turkey embryos and tested them in seven-day old Turkey poults. We found that SIV replication in Turkey embryos led to minimal mutations in and around the receptor binding and antigenic sites of the HA molecule, while other gene segments were unchanged. The predominant changes associated with Turkey embryo passage were A223V, V226A and T248I mutations in the receptor-binding and glycosylation sites of the HA molecule. Furthermore, Turkey embryo propagation altered receptor specificity in SIV strain 07-1145. Embryo passaged 07-1145 virus showed a decrease in α2, 6 sialic acid receptor binding compared to the wild type virus. Intranasal infection of wild type SIVs in one-week-old Turkey poults resulted in persistent diarrhea and all the infected birds seroconverted at ten days post infection. The 07-1145 wild type virus also transmitted to age matched in-contact birds introduced one-day post infection. Turkeys infected with embryo passaged viruses displayed no clinical signs and were not transmitted to in-contact poults. Our results suggest that Turkey embryo propagation attenuates recent TR SIVs for infectivity and transmission in one week old Turkeys. Our findings will have important implications in identifying molecular determinants that control the transmission and virulence of TR SIVs in Turkeys and other species. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Discovery and full genome characterization of two highly divergent simian immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus guereza) in Kibale National Park, Uganda.

    Science.gov (United States)

    Lauck, Michael; Switzer, William M; Sibley, Samuel D; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Taylor, Bill; Shankar, Anupama; Ting, Nelson; Chapman, Colin A; Friedrich, Thomas C; Goldberg, Tony L; O'Connor, David H

    2013-10-21

    African non-human primates (NHPs) are natural hosts for simian immunodeficiency viruses (SIV), the zoonotic transmission of which led to the emergence of HIV-1 and HIV-2. However, our understanding of SIV diversity and evolution is limited by incomplete taxonomic and geographic sampling of NHPs, particularly in East Africa. In this study, we screened blood specimens from nine black-and-white colobus monkeys (Colobus guereza occidentalis) from Kibale National Park, Uganda, for novel SIVs using a combination of serology and "unbiased" deep-sequencing, a method that does not rely on genetic similarity to previously characterized viruses. We identified two novel and divergent SIVs, tentatively named SIVkcol-1 and SIVkcol-2, and assembled genomes covering the entire coding region for each virus. SIVkcol-1 and SIVkcol-2 were detected in three and four animals, respectively, but with no animals co-infected. Phylogenetic analyses showed that SIVkcol-1 and SIVkcol-2 form a lineage with SIVcol, previously discovered in black-and-white colobus from Cameroon. Although SIVkcol-1 and SIVkcol-2 were isolated from the same host population in Uganda, SIVkcol-1 is more closely related to SIVcol than to SIVkcol-2. Analysis of functional motifs in the extracellular envelope glycoprotein (gp120) revealed that SIVkcol-2 is unique among primate lentiviruses in containing only 16 conserved cysteine residues instead of the usual 18 or more. Our results demonstrate that the genetic diversity of SIVs infecting black-and-white colobus across equatorial Africa is greater than previously appreciated and that divergent SIVs can co-circulate in the same colobine population. We also show that the use of "unbiased" deep sequencing for the detection of SIV has great advantages over traditional serological approaches, especially for studies of unknown or poorly characterized viruses. Finally, the detection of the first SIV containing only 16 conserved cysteines in the extracellular envelope protein

  12. Metal Oxide Supported Vanadium Substituted Keggin Type Polyoxometalates as Catalyst For Oxidation of Dibenzothiophene

    Science.gov (United States)

    Lesbani, Aldes; Novri Meilyana, Sarah; Karim, Nofi; Hidayati, Nurlisa; Said, Muhammad; Mohadi, Risfidian; Miksusanti

    2018-01-01

    Supported polyoxometalatate H4[γ-H2SiV2W10O40]·nH2O with metal oxide i.e. silica, titanium, and tantalum was successfully synthesized via wet impregnation method to form H4[γ-H2SiV2W10O40]·nH2O-Si, H4[γ-H2SiV2W10O40]·nH2O-Ti, and H4[γ-H2SiV2W10O40]·nH2O-Ta. Characterization was performed using FTIR spectroscopy, X-Ray analyses, and morphology analyses using SEM. All compounds were used as the catalyst for desulfurization of dibenzothiophene (DBT). Silica and titanium supported polyoxometalate H4[γ-H2SiV2W10O40]·nH2O better than tantalum due to retaining crystallinity after impregnation process. On the other hand, compound H H4[γ-H2SiV2W10O40]·nH2O-Ta showed high catalytic activity than other supported metal oxides for desulfurization of DBT. Optimization desulfurization process resulted in 99% conversion of DBT under a mild condition at 70 °C, 0.1 g catalyst, and reaction for 3 hours. Regeneration studies showed catalyst H4[γ-H2SiV2W10O40]·nH2O-Ti was remaining catalytic activity for desulfurization of DBT.

  13. Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatability complex class I-mediated control

    Science.gov (United States)

    Beck, Sarah E.; Queen, Suzanne E.; Viscidi, Raphael; Johnson, Darius; Kent, Stephen J.; Adams, Robert J.; Tarwater, Patrick M.; Mankowski, Joseph L.

    2016-01-01

    In the fourth decade of the HIV epidemic, the relationship between host immunity and HIV central nervous system (CNS) disease remains incompletely understood. Using a simian immunodeficiency virus (SIV)/macaque model, we examined CNS outcomes in pigtailed macaques expressing the MHC class I allele Mane-A1*084:01 which confers resistance to SIV-induced CNS disease and induces the prototypic viral escape mutation Gag K165R. Insertion of gag K165R into the neurovirulent clone SIV/17E-Fr reduced viral replication in vitro compared to SIV/17E-Fr. We also found lower CSF, but not plasma, viral loads in macaques inoculated with SIV/17E-Fr K165R versus those inoculated with wildtype. Although escape mutation K165R was genotypically stable in plasma, it rapidly reverted to wildtype Gag KP9 in both CSF and in microglia cultures. We induced robust Gag KP9-specific CTL tetramer responses by vaccinating Mane-A*084:01-positive pigtailed macaques with a Gag KP9 virus-like particle (VLP) vaccine. Upon SIV/17E-Fr challenge, vaccinated animals had lower SIV RNA in CSF compared to unvaccinated controls, but showed no difference in plasma viral loads. These data clearly demonstrate that viral fitness in the CNS is distinct from the periphery and underscores the necessity of understanding the consequences of viral escape in CNS disease with the advent of new therapeutic vaccination strategies. PMID:26727909

  14. Top-down modulation from inferior frontal junction to FEFs and intraparietal sulcus during short-term memory for visual features.

    Science.gov (United States)

    Sneve, Markus H; Magnussen, Svein; Alnæs, Dag; Endestad, Tor; D'Esposito, Mark

    2013-11-01

    Visual STM of simple features is achieved through interactions between retinotopic visual cortex and a set of frontal and parietal regions. In the present fMRI study, we investigated effective connectivity between central nodes in this network during the different task epochs of a modified delayed orientation discrimination task. Our univariate analyses demonstrate that the inferior frontal junction (IFJ) is preferentially involved in memory encoding, whereas activity in the putative FEFs and anterior intraparietal sulcus (aIPS) remains elevated throughout periods of memory maintenance. We have earlier reported, using the same task, that areas in visual cortex sustain information about task-relevant stimulus properties during delay intervals [Sneve, M. H., Alnæs, D., Endestad, T., Greenlee, M. W., & Magnussen, S. Visual short-term memory: Activity supporting encoding and maintenance in retinotopic visual cortex. Neuroimage, 63, 166-178, 2012]. To elucidate the temporal dynamics of the IFJ-FEF-aIPS-visual cortex network during memory operations, we estimated Granger causality effects between these regions with fMRI data representing memory encoding/maintenance as well as during memory retrieval. We also investigated a set of control conditions involving active processing of stimuli not associated with a memory task and passive viewing. In line with the developing understanding of IFJ as a region critical for control processes with a possible initiating role in visual STM operations, we observed influence from IFJ to FEF and aIPS during memory encoding. Furthermore, FEF predicted activity in a set of higher-order visual areas during memory retrieval, a finding consistent with its suggested role in top-down biasing of sensory cortex.

  15. Impurities of oxygen in silicon

    International Nuclear Information System (INIS)

    Gomes, V.M.S.

    1985-01-01

    The electronic structure of oxygen complex defects in silicon, using molecular cluster model with saturation by watson sphere into the formalism of Xα multiple scattering method is studied. A systematic study of the simulation of perfect silicon crystal and an analysis of the increasing of atom number in the clusters are done to choose the suitable cluster for the calculations. The divacancy in three charge states (Si:V 2 + , Si:V 2 0 , Si:V 2 - ), of the oxygen pair (Si:O 2 ) and the oxygen-vacancy pair (Si:O.V) neighbours in the silicon lattice, is studied. Distortions for the symmetry were included in the Si:V 2 + and Si:O 2 systems. The behavior of defect levels related to the cluster size of Si:V 2 0 and Si:O 2 systems, the insulated oxygen impurity of silicon in interstitial position (Si:O i ), and the complexes involving four oxygen atoms are analysed. (M.C.K.) [pt

  16. Replication of swine and human influenza viruses in juvenile and layer turkey hens.

    Science.gov (United States)

    Ali, Ahmed; Yassine, Hadi; Awe, Olusegun O; Ibrahim, Mahmoud; Saif, Yehia M; Lee, Chang-Won

    2013-04-12

    Since the first reported isolation of swine influenza viruses (SIVs) in turkeys in the 1980s, transmission of SIVs to turkeys was frequently documented. Recently, the 2009 pandemic H1N1 virus, that was thought to be of swine origin, was detected in turkeys with a severe drop in egg production. In this study, we assessed the infectivity of different mammalian influenza viruses including swine, pandemic H1N1 and seasonal human influenza viruses in both juvenile and layer turkeys. In addition, we investigated the potential influenza virus dissemination in the semen of experimentally infected turkey toms. Results showed that all mammalian origin influenza viruses tested can infect turkeys. SIVs were detected in respiratory and digestive tracts of both juvenile and layer turkeys. Variations in replication efficiencies among SIVs were observed especially in the reproductive tract of layer turkeys. Compared to SIVs, limited replication of seasonal human H1N1 and no detectable replication of recent human-like swine H1N2, pandemic H1N1 and seasonal human H3N2 viruses was noticed. All birds seroconverted to all tested viruses regardless of their replication level. In turkey toms, we were able to detect swine H3N2 virus in semen and reproductive tract of infected toms by real-time RT-PCR although virus isolation was not successful. These data suggest that turkey hens could be affected by diverse influenza strains especially SIVs. Moreover, the differences in the replication efficiency we demonstrated among SIVs and between SIV and human influenza viruses in layer turkeys suggest a possible use of turkeys as an animal model to study host tropism and pathogenesis of influenza viruses. Our results also indicate a potential risk of venereal transmission of influenza viruses in turkeys. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Pre-infection of pigs with Mycoplasma hyopneumoniae modifies outcomes of infection with European swine influenza virus of H1N1, but not H1N2, subtype.

    Science.gov (United States)

    Deblanc, C; Gorin, S; Quéguiner, S; Gautier-Bouchardon, A V; Ferré, S; Amenna, N; Cariolet, R; Simon, G

    2012-05-25

    Swine influenza virus (SIV) and Mycoplasma hyopneumoniae (Mhp) are widespread in farms and are major pathogens involved in the porcine respiratory disease complex (PRDC). The aim of this experiment was to compare the pathogenicity of European avian-like swine H1N1 and European human-like reassortant swine H1N2 viruses in naïve pigs and in pigs previously infected with Mhp. Six groups of SPF pigs were inoculated intra-tracheally with either Mhp, or H1N1, or H1N2 or Mhp+H1N1 or Mhp+H1N2, both pathogens being inoculated at 21 days intervals in these two last groups. A mock-infected group was included. Although both SIV strains induced clinical signs when singly inoculated, results indicated that the H1N2 SIV was more pathogenic than the H1N1 virus, with an earlier shedding and a greater spread in lungs. Initial infection with Mhp before SIV inoculation increased flu clinical signs and pathogenesis (hyperthermia, loss of appetite, pneumonia lesions) due to the H1N1 virus but did not modify significantly outcomes of H1N2 infection. Thus, Mhp and SIV H1N1 appeared to act synergistically, whereas Mhp and SIV H1N2 would compete, as H1N2 infection led to the elimination of Mhp in lung diaphragmatic lobes. In conclusion, SIV would be a risk factor for the severity of respiratory disorders when associated with Mhp, depending on the viral subtype involved. This experimental model of coinfection with Mhp and avian-like swine H1N1 is a relevant tool for studying the pathogenesis of SIV-associated PRDC and testing intervention strategies for the control of the disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States.

    Science.gov (United States)

    Vincent, Amy L; Ma, Wenjun; Lager, Kelly M; Gramer, Marie R; Richt, Juergen A; Janke, Bruce H

    2009-10-01

    H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 2003–2004; antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian pigs were human lineage in entirety or double (human–swine) reassortants. Here, we report the whole genome sequence analysis of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA) most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV. This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates with contemporary SIVs as a distinct genetic cluster of H1 SIV.

  19. A novel protective MHC-I haplotype not associated with dominant Gag-specific CD8+ T-cell responses in SIVmac239 infection of Burmese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Naofumi Takahashi

    Full Text Available Several major histocompatibility complex class I (MHC-I alleles are associated with lower viral loads and slower disease progression in human immunodeficiency virus (HIV and simian immunodeficiency virus (SIV infections. Immune-correlates analyses in these MHC-I-related HIV/SIV controllers would lead to elucidation of the mechanism for viral control. Viral control associated with some protective MHC-I alleles is attributed to CD8+ T-cell responses targeting Gag epitopes. We have been trying to know the mechanism of SIV control in multiple groups of Burmese rhesus macaques sharing MHC-I genotypes at the haplotype level. Here, we found a protective MHC-I haplotype, 90-010-Id (D, which is not associated with dominant Gag-specific CD8+ T-cell responses. Viral loads in five D+ animals became significantly lower than those in our previous cohorts after 6 months. Most D+ animals showed predominant Nef-specific but not Gag-specific CD8+ T-cell responses after SIV challenge. Further analyses suggested two Nef-epitope-specific CD8+ T-cell responses exerting strong suppressive pressure on SIV replication. Another set of five D+ animals that received a prophylactic vaccine using a Gag-expressing Sendai virus vector showed significantly reduced viral loads compared to unvaccinated D+ animals at 3 months, suggesting rapid SIV control by Gag-specific CD8+ T-cell responses in addition to Nef-specific ones. These results present a pattern of SIV control with involvement of non-Gag antigen-specific CD8+ T-cell responses.

  20. New STLV-3 strains and a divergent SIVmus strain identified in non-human primate bushmeat in Gabon

    Directory of Open Access Journals (Sweden)

    Liégeois Florian

    2012-03-01

    Full Text Available Abstract Background Human retroviral infections such as Human Immunodeficiency Virus (HIV or Human T-cell Lymphotropic Virus (HTLV are the result of simian zoonotic transmissions through handling and butchering of Non-Human Primates (NHP or by close contact with pet animals. Recent studies on retroviral infections in NHP bushmeat allowed for the identification of numerous Simian Immunodeficiency Viruses (SIV and Simian T-cell Lymphotropic Viruses (STLV to which humans are exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter interface remain scarce. We conducted a pilot study on 63 blood and/or tissues samples derived from NHP bushmeat seized by the competent authorities in different locations across the country. Results SIV and STLV were detected by antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an HIV or/and HTLV-like or indeterminate profile. Fourteen percent of the samples cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1 infections in five of the seven species tested. STLV-3 infections, including a new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3 infections were observed in red-capped mangabeys (C.torquatus. We confirmed SIV infections by PCR and sequence analyses in mandrills, red-capped mangabeys and showed that mustached monkeys in Gabon are infected with a new SIV strain basal to the SIVgsn/mus/mon lineage that did not fall into the previously described SIVmus lineages reported from the corresponding species in Cameroon. The same monkey (subspecies can thus be carrier of, at least, three distinct SIVs. Overall, the minimal prevalence observed for both STLV and SIV natural infections were 26.9% and 11.1% respectively. Conclusions Overall, these data, obtained from a restricted sampling, highlight the need for further studies on simian retroviruses in sub-Saharan Africa to better understand their evolutionary history and to

  1. Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution

    Directory of Open Access Journals (Sweden)

    Piatak Mike

    2008-06-01

    Full Text Available Abstract Background Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox. Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient dox administration. Since the effectiveness and safety of such a conditionally live virus vaccine should be tested in macaques, we constructed a similar dox-dependent SIV variant. The Tat-TAR transcription control mechanism in this virus was inactivated through mutation and functionally replaced by the dox-inducible Tet-On regulatory system. This SIV-rtTA variant replicated in a dox-dependent manner in T cell lines, but not as efficiently as the parental SIVmac239 strain. Since macaque studies will likely require an efficiently replicating variant, we set out to optimize SIV-rtTA through in vitro viral evolution. Results Upon long-term culturing of SIV-rtTA, additional nucleotide substitutions were observed in TAR that affect the structure of this RNA element but that do not restore Tat binding. We demonstrate that the bulge and loop mutations that we had introduced in the TAR element of SIV-rtTA to inactivate the Tat-TAR mechanism, shifted the equilibrium between two alternative conformations of TAR. The additional TAR mutations observed in the evolved variants partially or completely restored this equilibrium, which suggests that the balance between the two TAR conformations is important for efficient viral replication. Moreover, SIV-rtTA acquired mutations in the U3 promoter region. We demonstrate

  2. PA-X protein contributes to virulence of triple-reassortant H1N2 influenza virus by suppressing early immune responses in swine.

    Science.gov (United States)

    Xu, Guanlong; Zhang, Xuxiao; Liu, Qinfang; Bing, Guoxia; Hu, Zhe; Sun, Honglei; Xiong, Xin; Jiang, Ming; He, Qiming; Wang, Yu; Pu, Juan; Guo, Xin; Yang, Hanchun; Liu, Jinhua; Sun, Yipeng

    2017-08-01

    Previous studies have identified a functional role of PA-X for influenza viruses in mice and avian species; however, its role in swine remains unknown. Toward this, we constructed PA-X deficient virus (Sw-FS) in the background of a Triple-reassortment (TR) H1N2 swine influenza virus (SIV) to assess the impact of PA-X in viral virulence in pigs. Expression of PA-X in TR H1N2 SIV enhanced viral replication and host protein synthesis shutoff, and inhibited the mRNA levels of type I IFNs and proinflammatory cytokines in porcine cells. A delay of proinflammatory responses was observed in lungs of pigs infected by wild type SIV (Sw-WT) compared to Sw-FS. Furthermore, Sw-WT virus replicated and transmitted more efficiently than Sw-FS in pigs. These results highlight the importance of PA-X in the moderation of virulence and immune responses of TR SIV in swine, which indicated that PA-X is a pro-virulence factor in TR SIV in pigs. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Assessment of gastrointestinal parasites in wild chimpanzees (Pan troglodytes troglodytes) in southeast Cameroon.

    Science.gov (United States)

    Drakulovski, Pascal; Bertout, Sébastien; Locatelli, Sabrina; Butel, Christelle; Pion, Sébastien; Mpoudi-Ngole, Eitel; Delaporte, Eric; Peeters, Martine; Mallié, Michèle

    2014-07-01

    We tested 114 faecal samples from wild simian immunodeficiency virus (SIV)-positive (n = 43) and SIV-negative (n = 71) chimpanzees (Pan troglodytes troglodytes) in southeast Cameroon for the presence of gastrointestinal parasites by direct smear. We observed cysts from different protozoa (Entamoeba coli and Entamoeba histolytica / Entamoeba dispar, Endolimax nana, Iodamoeba butschlii, Chilomastix mesnili, Balantidium coli and Blastocystis cells) and trophozoites from Troglodytella abrassarti and Balantidium coli. Eggs from different helminths (strongylids, Ascaris lumbricoides, Abbreviata caucasica, Trichuris sp., Capillaria sp., Enterobius anthropopeci, Bertiella sp., Hymenolepis diminuta and an undetermined fluke) were also observed. Finally, we observed eggs that could not be properly identified and classified. We did not observe any differences between the SIV+ and SIV- samples except for the unidentified eggs. The studied chimpanzees were highly parasitised by strongylid (85.1% of prevalence), Troglodytella (43.8%) and Blastocystis (2.9%), and the frequency of the other parasites ranged from 0.9 to 8.8%. These high levels of parasite infections could represent an additional burden in a population where there is a high rate of the SIV virus in circulation.

  4. Rapid detection and subtyping of European swine influenza viruses in porcine clinical samples by haemagglutinin- and neuraminidase-specific tetra- and triplex real-time RT-PCRs

    DEFF Research Database (Denmark)

    Henritzi, Dinah; Zhao, Na; Starick, Elke

    2016-01-01

    diagnostic methods which allow for cost-effective large-scale analysis. Methods New SIV haemagglutinin (HA) and neuraminidase (NA) subtype- and lineage-specific multiplex real-time RT-PCRs (RT-qPCR) have been developed and validated with reference virus isolates and clinical samples. Results A diagnostic....... Swine influenza viruses (SIV) are widespread in European domestic pig populations and evolve dynamically. Knowledge regarding occurrence, spread and evolution of potentially zoonotic SIV in Europe is poorly understood. Objectives Efficient SIV surveillance programmes depend on sensitive and specific......Background A diversifying pool of mammalian-adapted influenza A viruses (IAV) with largely unknown zoonotic potential is maintained in domestic swine populations worldwide. The most recent human influenza pandemic in 2009 was caused by a virus with genes originating from IAV isolated from swine...

  5. The decreasing of NFκB level in gingival junctional epithelium of rat exposed to Porphyromonas gingivalis with application of 1% curcumin on gingival sulcus

    Directory of Open Access Journals (Sweden)

    Agung Krismariono

    2015-03-01

    Full Text Available Background: Periodontal disease is a chronic, multi-factorial disease. Chronic periodontitis is one of the main causes of tooth loss. Chronic periodontitis is usually caused by Porphyromonas gingivalis (P. gingivalis. P. gingivalis can induce NFκB activation resulting in the increasing of periodontal extracellular matrix degradation. Curcumin can inhibit NFκB activation and reduce the severity of periodontal degradation. Purpose: This research was aimed to observe level of NFκB in gingival junctional epithelium of rat exposed to Porphyromonas gingivalis with local administration of curcumin. Methods: Sixteen Wistar rat were divided into two groups. Group 1 (treatment consisted of eight rat given 2 x 106CFU/ml P. gingivalis and 1% curcumin. Meanwhile, group 2 (control consisted of eight rat given 2 x 106 CFU/ml P. gingivalis only. GCF samples were collected from gingival sulcus. The samples were biochemically analyzed with ELISA method. Data were then analyzed statistically by using independent t-test (α=0.05. Results: The examination of NFκB level showed that there was significant difference between treatment group and control group (p<0.05. The level of NFκB in the treatment group was significantly lower than the control group. Conclusion: It can be concluded that 1% curcumin application can reduce NFκB level in gingival junctional epithelium of rat exposed to P. gingivalis.

  6. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Matusali, G.; Dereuddre-Bosquet, N.; Le Tortorec, A.; Moreau, M.; Satie, A.-P.; Mahé, D.; Roumaud, P.; Bourry, O.; Sylla, N.; Bernard-Stoecklin, S.; Pruvost, A.; Le Grand, R.

    2015-01-01

    ABSTRACT A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV

  7. Virological surveillance and preliminary antigenic characterization of influenza viruses in pigs in five European countries from 2006 to 2008.

    Science.gov (United States)

    Kyriakis, C S; Brown, I H; Foni, E; Kuntz-Simon, G; Maldonado, J; Madec, F; Essen, S C; Chiapponi, C; Van Reeth, K

    2011-03-01

    This study presents the results of the virological surveillance for swine influenza viruses (SIVs) in Belgium, UK, Italy, France and Spain from 2006 to 2008. Our major aims were to clarify the occurrence of the three SIV subtypes - H1N1, H3N2 and H1N2 - at regional levels, to identify novel reassortant viruses and to antigenically compare SIVs with human H1N1 and H3N2 influenza viruses. Lung tissue and/or nasal swabs from outbreaks of acute respiratory disease in pigs were investigated by virus isolation. The hemagglutinin (HA) and neuraminidase (NA) subtypes were determined using standard methods. Of the total 169 viruses, 81 were classified as 'avian-like' H1N1, 36 as human-like H3N2 and 47 as human-like H1N2. Only five novel reassortant viruses were identified: two H1N1 viruses had a human-like HA and three H1N2 viruses an avian-like HA. All three SIV subtypes were detected in Belgium, Italy and Spain, while only H1N1 and H1N2 viruses were found in UK and Northwestern France. Cross-hemagglutination inhibition (HI) tests with hyperimmune sera against selected older and recent human influenza viruses showed a strong antigenic relationship between human H1N1 and H3N2 viruses from the 1980s and H1N2 and H3N2 human-like SIVs, confirming their common origin. However, antisera against human viruses isolated during the last decade did not react with currently circulating H1 or H3 SIVs, suggesting that especially young people may be, to some degree, susceptible to SIV infections. © 2009 Blackwell Verlag GmbH.

  8. Different evolutionary trends of swine H1N2 influenza viruses in Italy compared to European viruses.

    Science.gov (United States)

    Moreno, Ana; Gabanelli, Elena; Sozzi, Enrica; Lelli, Davide; Chiapponi, Chiara; Ciccozzi, Massimo; Zehender, Gianguglielmo; Cordioli, Paolo

    2013-12-01

    European H1N2 swine influenza viruses (EU H1N2SIVs) arose from multiple reassortment events among human H1N1, human H3N2, and avian influenza viruses. We investigated the evolutionary dynamics of 53 Italian H1N2 strains by comparing them with EU H1N2 SIVs. Hemagglutinin (HA) phylogeny revealed Italian strains fell into four groups: Group A and B (41 strains) had a human H1 similar to EU H1N2SIVs, which probably originated in 1986. However Group B (38 strains) formed a subgroup that had a two-amino acid deletion at positions 146/147 in HA. Group C (11 strains) contained an avian H1 that probably originated in 1996, and Group D (1 strain) had an H1 characteristic of the 2009 pandemic strain. Neuraminidase (NA) phylogeny suggested a series of genomic reassortments had occurred. Group A had an N2 that originated from human H3N2 in the late 1970s. Group B had different human N2 that most likely arose from a reassortment with the more recent human H3N2 virus, which probably occurred in 2000. Group C had an avian-like H1 combined with an N2 gene from one of EU H1N2SIVs, EU H3N2SIVs or Human H3N2. Group D was part of the EU H3N2SIVs clade. Although selection pressure for HA and NA was low, several positively selected sites were identified in both proteins, some of which were antigenic, suggesting selection influenced the evolution of SIV. The data highlight different evolutionary trends between European viruses and currently circulating Italian B strains and show the establishment of reassortant strains involving human viruses in Italian pigs.

  9. Tolerance to Chronic Delta-9-Tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus

    Science.gov (United States)

    Winsauer, Peter J.; Molina, Patricia E.; Amedee, Angela M.; Filipeanu, Catalin M.; McGoey, Robin R.; Troxclair, Dana A.; Walker, Edith M.; Birke, Leslie L.; Stouwe, Curtis Vande; Howard, Jessica M.; Leonard, Stuart T.; Moerschbaecher, Joseph M.; Lewis, Peter B.

    2011-01-01

    Although Δ9-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ9-THC before and after inoculation with simian immunodeficiency virus(SIVmac251, 100 TCID50/ml, i.v.). Prior to chronic Δ9-THC and SIV inoculation, 0.032– 0.32 mg/kg of Δ9-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ9-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/−SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ9-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ9-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. PMID:21463073

  10. Effectiveness of teaching automated external defibrillators use using a traditional classroom instruction versus self-instruction video in non-critical care nurses

    Directory of Open Access Journals (Sweden)

    Ismail M. Saiboon

    2016-04-01

    Full Text Available Objectives: To evaluate the effectiveness and retention of learning automated external defibrillator (AED usage taught through a traditional classroom instruction (TCI method versus a novel self instructed video (SIV technique in non-critical care nurses (NCCN. Methods: A prospective single-blind randomized study was conducted over 7 months (April-October 2014 at the Universiti Kebangsaan Malaysia Medical Center, Kuala Lampur, Malaysia. Eighty nurses were randomized into either TCI or SIV instructional techniques. We assessed knowledge, skill and confidence level at baseline, immediate and 6-months post-intervention. Knowledge and confidence were assessed via questionnaire; skill was assessed by a calibrated and blinded independent assessor using an objective structured clinical examination (OSCE method. Results: Pre-test mean scores for knowledge in the TCI group was 10.87 ± 2.34, and for the SIV group was 10.37 ± 1.85 (maximum achievable score 20.00; 4.05 ± 2.87 in the TCI and 3.71 ± 2.66 in the SIV (maximum score 11.00 in the OSCE evaluation and 9.54 ± 3.65 in the TCI and 8.56 ± 3.47 in the SIV (maximum score 25.00 in the individual’s personal confidence level. Both methods increased the mean scores significantly during immediate post-intervention (0-month. At 6-months, the TCI group scored lower than the SIV group in all aspects 11.13 ± 2.70 versus 12.95 ± 2.26 (p=0.03 in knowledge, 7.27 ± 1.62 versus 7.68 ± 1.73 (p=0.47 in the OSCE, and 16.40 ± 2.72 versus 18.82 ± 3.40 (p=0.03 in confidence level. Conclusion: In NCCN’s, SIV is as good as TCI in providing the knowledge, competency, and confidence in performing AED defibrillation.

  11. The roles of polycarboxylates in Cr(VI)/sulfite reaction system: Involvement of reactive oxygen species and intramolecular electron transfer

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Bo, E-mail: bjiang86upc@163.com [State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Qingdao 266580, Shandong (China); School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266033 (China); Wang, Xianli; Liu, Yukun [State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Qingdao 266580, Shandong (China); Wang, Zhaohui [College of Environmental Science and Engineering, Donghua University, Shanghai 201620 (China); Southern Cross GeoScience, Southern Cross University, Lismore, NSW 2480 (Australia); Zheng, Jingtang, E-mail: jtzheng03@163.com [State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Qingdao 266580, Shandong (China); Wu, Mingbo, E-mail: wumb@upc.edu.cn [State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Qingdao 266580, Shandong (China)

    2016-03-05

    Highlights: • The formations of SO{sub 4}·{sup −} and OH·, involve in Cr(VI) reduction induced by S(IV). • Affinity of polycarboxylate to Cr(VI) accelerates Cr(VI) reduction rate. • Polycarboxylates can act as electron donors for Cr(VI) reduction retrenching S(IV). • Only oxalate can enhance the formations of SO{sub 4}·{sup −} and OH· in Cr(VI)/S(IV) system. - Abstract: In this study, the effects of polycarboxylates on both Cr(VI) reduction and S(IV) consumption in Cr(VI)/S(IV) system was investigated in acidic solution. Under aerobic condition, the productions of reactive oxygen species (ROS), i.e., SO{sub 4}·{sup −} and OH·, have been confirmed in S(IV) reducing Cr(VI) process by using electron spin resonance and fluorescence spectrum techniques, leading to the excess consumption of S(IV). However, when polycarboxylates (oxalic, citric, malic and tartaric acid) were present in Cr(VI)/S(IV) system, the affinity of polycarboxylates to CrSO{sub 6}{sup 2−} can greatly promote the reduction of Cr(VI) via expanding the coordination of Cr(VI) species from tetrahedron to hexahedron. Besides, as alternatives to S(IV), these polycarboxylates can also act as electron donors for Cr(VI) reduction via intramolecular electron transfer reaction, which is dependent on the energies of the highest occupied molecular orbital of these polycarboxylates. Notably, the variant electron donating capacity of these polycarboxylates resulted in different yield of ROS and therefore the oxidation efficiencies of other pollutants, e.g., rhodamine B and As(III). Generally, this study does not only shed light on the mechanism of S(IV) reducing Cr(VI) process mediated by polycarboxylates, but also provides an escalated, cost-effective and green strategy for the remediation of Cr(VI) using sulfite as a reductant.

  12. Interaction between Mycoplasma hyopneumoniae and Swine Influenza Virus

    Science.gov (United States)

    Thacker, Eileen L.; Thacker, Brad J.; Janke, Bruce H.

    2001-01-01

    An experimental respiratory model was used to investigate the interaction between Mycoplasma hyopneumoniae and swine influenza virus (SIV) in the induction of pneumonia in susceptible swine. Previous studies demonstrated that M. hyopneumoniae, which produces a chronic bronchopneumonia in swine, potentiates a viral pneumonia induced by the porcine reproductive and respiratory syndrome virus (PRRSV). In this study, pigs were inoculated with M. hyopneumoniae 21 days prior to inoculation with SIV. Clinical disease as characterized by the severity of cough and fever was evaluated daily. Percentages of lung tissue with visual lesions and microscopic lesions were assessed upon necropsy at 3, 7, 14, and 21 days following SIV inoculation. Clinical observations revealed that pigs infected with both SIV and M. hyopneumoniae coughed significantly more than pigs inoculated with a single agent. Macroscopic pneumonia on necropsy at days 3 and 7 was greatest in both SIV-infected groups, with minimal levels of pneumonia in the M. hyopneumoniae-only-infected pigs. At 14 days post-SIV inoculation, pneumonia was significantly more severe in pigs infected with both pathogens. However, by 21 days postinoculation, the level of pneumonia in the dual-infected pigs was similar to that of the M. hyopneumoniae-only-infected group, and the pneumonia in the pigs inoculated with only SIV was nearly resolved. Microscopically, there was no apparent increase in the severity of pneumonia in pigs infected with both agents compared to that of single-agent-challenged pigs. The results of this study found that while pigs infected with both agents exhibited more severe clinical disease, the relationship between the two pathogens lacked the profound potentiation found with dual infection with M. hyopneumoniae and PRRSV. These findings demonstrate that the relationship between mycoplasmas and viruses varies with the individual agent. PMID:11427564

  13. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Directory of Open Access Journals (Sweden)

    Jennifer H Campbell

    2014-12-01

    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  14. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Science.gov (United States)

    Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

    2014-12-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  15. Complete Quantum Control of a Single Silicon-Vacancy Center in a Diamond Nanopillar

    Science.gov (United States)

    Zhang, Jingyuan Linda; Lagoudakis, Konstantinos G.; Tzeng, Yan-Kai; Dory, Constantin; Radulaski, Marina; Kelaita, Yousif; Shen, Zhi-Xun; Melosh, Nicholas A.; Chu, Steven; Vuckovic, Jelena

    Coherent quantum control of a quantum bit (qubit) is an important step towards its use in a quantum network. SiV- center in diamond offers excellent physical qualities such as low inhomogeneous broadening, fast photon emission, and a large Debye-Waller factor, while the fast spin manipulation and techniques to extend the spin coherence time are under active investigation. Here, we demonstrate full coherent control over the state of a single SiV- center in a diamond nanopillar using ultrafast optical pulses. The high quality of the chemical vapor deposition grown SiV- centers allows us to coherently manipulate and quasi-resonantly read out the state of the single SiV- center. Moreover, the SiV- centers being coherently controlled are integrated into diamond nanopillar arrays in a site-controlled, individually addressable manner with high yield, low strain, and high spectral stability, which paves the way for scalable on chip optically accessible quantum system in a quantum photonic network. Financial support is provided by the DOE Office of Basic Energy Sciences, Division of Materials Sciences through Stanford Institute for Materials and Energy Sciences (SIMES) under contract DE-AC02-76SF00515.

  16. Neutral Silicon-Vacancy Center in Diamond: Spin Polarization and Lifetimes

    Science.gov (United States)

    Green, B. L.; Mottishaw, S.; Breeze, B. G.; Edmonds, A. M.; D'Haenens-Johansson, U. F. S.; Doherty, M. W.; Williams, S. D.; Twitchen, D. J.; Newton, M. E.

    2017-09-01

    We demonstrate optical spin polarization of the neutrally charged silicon-vacancy defect in diamond (SiV0 ), an S =1 defect which emits with a zero-phonon line at 946 nm. The spin polarization is found to be most efficient under resonant excitation, but nonzero at below-resonant energies. We measure an ensemble spin coherence time T2>100 μ s at low-temperature, and a spin relaxation limit of T1>25 s . Optical spin-state initialization around 946 nm allows independent initialization of SiV0 and NV- within the same optically addressed volume, and SiV0 emits within the telecoms down-conversion band to 1550 nm: when combined with its high Debye-Waller factor, our initial results suggest that SiV0 is a promising candidate for a long-range quantum communication technology.

  17. The Impact of Single Session Intermittent Theta-Burst Stimulation over the Dorsolateral Prefrontal Cortex and Posterior Superior Temporal Sulcus on Adults with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Hsing-Chang Ni

    2017-05-01

    Full Text Available Intermittent theta burst stimulation (iTBS, a patterned repetitive transcranial magnetic stimulation, was applied over the posterior superior temporal sulcus (pSTS or dorsolateral prefrontal cortex (DLPFC to explore its impact in adults with autism spectrum disorder (ASD. Among 25 adults with ASD, 19 (mean age: 20.8 years completed the randomized, sham-controlled, crossover trial. Every participant received iTBS over the bilateral DLPFC, bilateral pSTS and inion (as a sham control stimulation in a randomized order with a 1-week interval. Neuropsychological functions were assessed using the Conners' Continuous Performance Test (CCPT and the Wisconsin Card Sorting Test (WCST. Behavioral outcomes were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS and the Social Responsiveness Scale (SRS. In comparison to that in the sham stimulation, the reaction time in the CCPT significantly decreased following single DLPFC session (p = 0.04, effect size = 0.71 while there were no significant differences in the CCPT and WCST following single pSTS session. Besides, the results in behavioral outcomes were inconsistent and had discrepancy between reports of parents and patients. In conclusion, a single session of iTBS over the bilateral DLPFC may alter the neuropsychological function in adults with ASD. The impacts of multiple-sessions iTBS over the DLPFC or pSTS deserve further investigations.

  18. Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test.

    Science.gov (United States)

    De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien

    2015-05-11

    The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test

  19. Stability of the gorilla microbiome despite simian immunodeficiency virus infection.

    Science.gov (United States)

    Moeller, Andrew H; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H; Ochman, Howard

    2015-02-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1-infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority. © 2014 John Wiley & Sons Ltd.

  20. Immunovirological analyses of chronically simian immunodeficiency virus SIVmnd-1- and SIVmnd-2-infected mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Apetrei, Cristian; Sumpter, Beth; Souquiere, Sandrine; Chahroudi, Ann; Makuwa, Maria; Reed, Patricia; Ribeiro, Ruy M; Pandrea, Ivona; Roques, Pierre; Silvestri, Guido

    2011-12-01

    Simian immunodeficiency virus (SIV) infection in African nonhuman primate (NHP) natural hosts is usually nonpathogenic, despite high levels of virus replication. We have previously shown that chronic SIV infection in sooty mangabeys (SMs) and African green monkeys (AGMs) is associated with low levels of immune activation and bystander T cell apoptosis. To compare these features with those observed in another natural host, the mandrill (MND), we conducted a cross-sectional survey of the 23 SIV-infected and 25 uninfected MNDs from the only semifree colony of mandrills available worldwide. Viral loads (VLs) were determined and phenotypic and functional analysis of peripheral blood- and lymph node-derived lymphocytes was performed. We found that mandrills chronically infected with SIVmnd-1 or SIVmnd-2 have similar levels of viral replication, and we observed a trend toward lower CD4+ T cell counts in chronically SIVmnd-2-infected MNDs than SIVmnd-1-infected MNDs. No correlation between CD4+ T cell counts and VLs in SIV-infected MNDs could be established. Of note, the levels of T cell activation, proliferation, and apoptosis were comparable between SIVmnd-1- and SIVmnd-2-infected MNDs and to those observed in uninfected animals, with the only exception being an increase in tumor necrosis factor alpha-producing CD8+ T cells in SIVmnd-2-infected MNDs. Overall, these findings recapitulate previous observations in SIV-infected SMs and AGMs and lend further evidence to the hypothesis that low levels of immune activation protect natural SIV hosts from disease progression.

  1. Varying temperature and silicon content in nanodiamond growth: effects on silicon-vacancy centres.

    Science.gov (United States)

    Choi, Sumin; Leong, Victor; Davydov, Valery A; Agafonov, Viatcheslav N; Cheong, Marcus W O; Kalashnikov, Dmitry A; Krivitsky, Leonid A

    2018-02-28

    Nanodidamonds containing colour centres open up many applications in quantum information processing, metrology, and quantum sensing. However, controlling the synthesis of nanodiamonds containing silicon vacancy (SiV) centres is still not well understood. Here we study nanodiamonds produced by a high-pressure high-temperature method without catalyst metals, focusing on two samples with clear SiV signatures. Different growth temperatures and relative content of silicon in the initial compound between the samples altered their nanodiamond size distributions and abundance of SiV centres. Our results show that nanodiamond growth can be controlled and optimised for different applications.

  2. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. © FASEB.

  3. MORPHOMETRIC ANALYSES OF THE PARACENTRAL LOBE

    Directory of Open Access Journals (Sweden)

    Moacyr Oliveira Neto

    2014-03-01

    Full Text Available ntroduction:There are no studies that evaluate measurements of the distances between the grooves that delimit the Paracentral Lobule (PCL in the literature. This study seeks to contribute to the knowledge regarding the anatomy of the PCL, conducting an analysis of morphometric measurements in this region and its correlation with the paracentral sulcus, marginal branch of the cingulate and central sulcus. Methods:42 hemispheres were evaluated, 20 were right and 22 left. Using digital caliper Dc - 6 Western ®, measurements of the size of PCL in the sagittal axis and coronal axis were made, in addition to measures of the Central Sulcus to the Paracentral Sulcus (motor area and Central Sulcus to Marginal Branch of the Cingulate Sulcus (somesthetic area, comparing the prevalence of each of these lengths between hemispheres. Results:The average length between the Paracentral Sulcus and the Central Sulcus was 24.49 cm(14.2 to 38.6 cm in the right hemisphere and 25.50 cm(11.7 to 37.0 cm in the left. As between the Central Sulcus and the Marginal Branch of the Cingulate Sulcus was in average 10.03 cm(2.6 to 22.7 cm in the right and in the left PCL 9.17cm(2.6 to 22.7 cm. In the right hemisphere, 19 samples(86,4% presented greater motor area than somesthetic and, in the left hemisphere, 19 samples(95% had greater motor area. Conclusion:The motor area showed prevalence in relation to the sensory area in the analysis of the two hemispheres, while the comparison of other measures between the two hemispheres showed no significance.

  4. Influences of Long-Term Memory-Guided Attention and Stimulus-Guided Attention on Visuospatial Representations within Human Intraparietal Sulcus.

    Science.gov (United States)

    Rosen, Maya L; Stern, Chantal E; Michalka, Samantha W; Devaney, Kathryn J; Somers, David C

    2015-08-12

    Human parietal cortex plays a central role in encoding visuospatial information and multiple visual maps exist within the intraparietal sulcus (IPS), with each hemisphere symmetrically representing contralateral visual space. Two forms of hemispheric asymmetries have been identified in parietal cortex ventrolateral to visuotopic IPS. Key attentional processes are localized to right lateral parietal cortex in the temporoparietal junction and long-term memory (LTM) retrieval processes are localized to the left lateral parietal cortex in the angular gyrus. Here, using fMRI, we investigate how spatial representations of visuotopic IPS are influenced by stimulus-guided visuospatial attention and by LTM-guided visuospatial attention. We replicate prior findings that a hemispheric asymmetry emerges under stimulus-guided attention: in the right hemisphere (RH), visual maps IPS0, IPS1, and IPS2 code attentional targets across the visual field; in the left hemisphere (LH), IPS0-2 codes primarily contralateral targets. We report the novel finding that, under LTM-guided attention, both RH and LH IPS0-2 exhibit bilateral responses and hemispheric symmetry re-emerges. Therefore, we demonstrate that both hemispheres of IPS0-2 are independently capable of dynamically changing spatial coding properties as attentional task demands change. These findings have important implications for understanding visuospatial and memory-retrieval deficits in patients with parietal lobe damage. The human parietal lobe contains multiple maps of the external world that spatially guide perception, action, and cognition. Maps in each cerebral hemisphere code information from the opposite side of space, not from the same side, and the two hemispheres are symmetric. Paradoxically, damage to specific parietal regions that lack spatial maps can cause patients to ignore half of space (hemispatial neglect syndrome), but only for right (not left) hemisphere damage. Conversely, the left parietal cortex has

  5. On-Demand Generation of Neutral and Negatively Charged Silicon-Vacancy Centers in Diamond

    Science.gov (United States)

    Dhomkar, Siddharth; Zangara, Pablo R.; Henshaw, Jacob; Meriles, Carlos A.

    2018-03-01

    Point defects in wide-band-gap semiconductors are emerging as versatile resources for nanoscale sensing and quantum information science, but our understanding of the photoionization dynamics is presently incomplete. Here, we use two-color confocal microscopy to investigate the dynamics of charge in type 1b diamond hosting nitrogen-vacancy (NV) and silicon-vacancy (SiV) centers. By examining the nonlocal fluorescence patterns emerging from local laser excitation, we show that, in the simultaneous presence of photogenerated electrons and holes, SiV (NV) centers selectively transform into the negative (neutral) charge state. Unlike NVs, 532 nm illumination ionizes SiV- via a single-photon process, thus hinting at a comparatively shallower ground state. In particular, slower ionization rates at longer wavelengths suggest the latter lies approximately ˜1.9 eV below the conduction band minimum. Building on the above observations, we demonstrate on-demand SiV and NV charge initialization over large areas via green laser illumination of variable intensity.

  6. Detection of microbial translocation in HIV and SIV infection using the Limulus amebocyte lysate assay is masked by serum and plasma.

    Directory of Open Access Journals (Sweden)

    Ashwin Balagopal

    Full Text Available Microbial translocation (MT is thought to be a major contributor to the pathogenesis of HIV-related immune activation, and circulating lipopolysaccharide (LPS from gram-negative bacteria is the principle measurement of this process. However, related research has been impeded by inconsistent LPS test results.Specimens were obtained from HIV-infected adults enrolled in the PEARLS study (ACTG A5175 and HIV-HCV co-infected participants enrolled in a study of liver disease staging using MRI elastography. Pig-tailed macaque specimens were obtained from SIV-infected and -uninfected animals. Samples were tested for LPS using the LAL assay with diazo-coupling modifications to improve sensitive detection.When exogenous LPS was added to macaque plasma, >25% inhibition of LPS detection was found in 10/10 (100% samples at 20% plasma concentration compared to control; in contrast 5/10 (50% samples at 2% plasma concentration (p = 0.07 and 0/10 (0% at 0.1% plasma concentration (p = 0.004 showed >25% inhibition of LPS detection. Similarly, when LPS was added to human serum, >25% inhibition of LPS detection was found in 5/12 (42% of samples at 2% serum concentration compared to control, while 0/12 (0% of samples in 0.1% serum showed >25% inhibition of LPS detection (p = 0.07. Likewise, LPS detection in human sera without exogenous LPS was improved by dilution: LPS was detected in 2/12 (17% human samples in 2% serum, ranging from 3,436-4,736 pg/mL, compared to 9/12 (75% samples in 0.1% serum, ranging from 123 pg/mL -60,131 pg/mL (p = 0.016. In a separate validation cohort of HIV-HCV co-infected participants sampled at two different times on the same day, LPS measured in 0.2% plasma and with diazo-coupling was closely correlated between the first and second samples (R = 0.66, p<0.05.Undiluted serum and plasma mask LPS detection. The extent of MT may be substantially underestimated.

  7. Personal decision-making criteria related to seasonal and pandemic A(H1N1 influenza-vaccination acceptance among French healthcare workers.

    Directory of Open Access Journals (Sweden)

    Lila Bouadma

    Full Text Available BACKGROUND: Influenza-vaccination rates among healthcare workers (HCW remain low worldwide, even during the 2009 A(H1N1 pandemic. In France, this vaccination is free but administered on a voluntary basis. We investigated the factors influencing HCW influenza vaccination. METHODS: In June-July 2010, HCW from wards of five French hospitals completed a cross-sectional survey. A multifaceted campaign aimed at improving vaccination coverage in this hospital group was conducted before and during the 2009 pandemic. Using an anonymous self-administered questionnaire, we assessed the relationships between seasonal (SIV and pandemic (PIV influenza vaccinations, and sociodemographic and professional characteristics, previous and current vaccination statuses, and 33 statements investigating 10 sociocognitive domains. The sociocognitive domains describing HCWs' SIV and PIV profiles were analyzed using the classification-and-regression-tree method. RESULTS: Of the HCWs responding to our survey, 1480 were paramedical and 401 were medical with 2009 vaccination rates of 30% and 58% for SIV and 21% and 71% for PIV, respectively (p<0.0001 for both SIV and PIV vaccinations. Older age, prior SIV, working in emergency departments or intensive care units, being a medical HCW and the hospital they worked in were associated with both vaccinations; while work shift was associated only with PIV. Sociocognitive domains associated with both vaccinations were self-perception of benefits and health motivation for all HCW. For medical HCW, being a role model was an additional domain associated with SIV and PIV. CONCLUSIONS: Both vaccination rates remained low. Vaccination mainly depended on self-determined factors and for medical HCW, being a role model.

  8. Three-dimensional reconstruction of brain surface anatomy: technique comparison between flash and diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Sun Jianzhong; Wang Zhikang; Gong Xiangyang

    2006-01-01

    Objective: To compare two methods 3D flash and diffusion-weighted images (DWI) in reconstructing the brain surface anatomy, and to evaluate their displaying ability, advantages, limitations and clinical application. Methods: Thrity normal cases were prospectively examined with 3D flash sequence and echo-planar DWI. Three-dimensional images were acquired with volume-rendering on workstation. Brain surface structures were evaluated and scored by a group of doctors. Results: Main structures of brain surface were clearly displayed on three-dimensional images based on 3D flash sequence. Average scores were all above 2.50. For images based on DWI, precentral gyrus, postcentral gyrus, superior parietal lobule, superior frontal gyrus, precentral sulcus, central sulcus, postcentral sulcus, intraparietal sulcus and superior frontal sulcus were best shown with average scores between 2.60-2.75, However, supramarginal gyrus, angular gyrus, middle frontal gyrus, inferior frontal gyrus, superior temporal gyrus, lateral sulcus, inferior frontal sulcus could not be well shown, with average scores between 1.67-2.48. Middle temporal gyrus, inferior temporal gyrus, superior temporal sulcus and inferior temporal sulcus can only get scores from 0.88 to 1.27. Scores of images based on 3D flash were much higher than that based on DWI with distinct differentiations, P values were all below 0.01. Conclusion: Three-dimensional images based on 3D flash can really display brain surface structures. It is very useful for anatomic researches. Three-dimensional reconstruction of brain surface based on DWI is a worthy technique to display brain surface anatomy, especially for frontal and parietal structures. (authors)

  9. Development of a primer–probe energy transfer based real-time PCR for the detection of Swine influenza virus

    DEFF Research Database (Denmark)

    Kowalczyk, Andrzej; Markowska-Daniel, Iwona; Rasmussen, Thomas Bruun

    2013-01-01

    Swine influenza virus (SIV) causes a contagious and requiring official notification disease of pigs and humans. In this study, a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay based on primer–probe energy transfer (PriProET) for the detection of SIV RNA was developed...... of the specific product amplification. The assay is specific for influenza virus with a sensitivity of detection limit of approximately 10 copies of RNA by PCR. Based on serial dilutions of SIV, the detection limit of the assay was approximately 0.003 TCID50/ml for H1N1 A/Swine/Poland/KPR9/2004 virus. The Pri...

  10. Silicon-Vacancy Color Centers in Nanodiamonds: Cathodoluminescence Imaging Marker in the Near Infrared

    OpenAIRE

    Zhang, Huiliang; Aharonovich, Igor; Glenn, David R.; Schalek, R.; Magyar, Andrew P.; Lichtman, Jeff W.; Hu, Evelyn L.; Walsworth, Ronald L.

    2013-01-01

    We demonstrate that nanodiamonds fabricated to incorporate silicon-vacancy (Si-V) color centers provide bright, spectrally narrow, and stable cathodoluminescence (CL) in the near-infrared. Si-V color centers containing nanodiamonds are promising as non-bleaching optical markers for correlated CL and secondary electron microscopy, including applications to nanoscale bioimaging.

  11. [Viral contamination of polio vaccines in context of antivaccination mythology].

    Science.gov (United States)

    Mats, A N; Kuz'mina, M N; Cheprasova, E V

    2010-01-01

    Analysis of publications about real and suggested contamination of polio vaccines produced in 1950s and 1960s with simian viruses--SV40 and SIV--is performed. Factual data are discussed and antivaccination fictions about calamitous consequences of really occurred contamination with SV40 and concocted contamination with SIV are refuted.

  12. Evaluation of the zoonotic potential of a novel reassortant H1N2 swine influenza virus with gene constellation derived from multiple viral sources.

    Science.gov (United States)

    Lee, Jee Hoon; Pascua, Philippe Noriel Q; Decano, Arun G; Kim, Se Mi; Park, Su-Jin; Kwon, Hyeok-Il; Kim, Eun-Ha; Kim, Young-Il; Kim, HyongKyu; Kim, Seok-Yong; Song, Min-Suk; Jang, Hyung-Kwan; Park, Bong Kyun; Choi, Young Ki

    2015-08-01

    In 2011-2012, contemporary North American-like H3N2 swine influenza viruses (SIVs) possessing the 2009 pandemic H1N1 matrix gene (H3N2pM-like virus) were detected in domestic pigs of South Korea where H1N2 SIV strains are endemic. More recently, we isolated novel reassortant H1N2 SIVs bearing the Eurasian avian-like swine H1-like hemagglutinin and Korean swine H1N2-like neuraminidase in the internal gene backbone of the H3N2pM-like virus. In the present study, we clearly provide evidence on the genetic origins of the novel H1N2 SIVs virus through genetic and phylogenetic analyses. In vitro studies demonstrated that, in comparison with a pre-existing 2012 Korean H1N2 SIV [A/swine/Korea/CY03-11/2012 (CY03-11/2012)], the 2013 novel reassortant H1N2 isolate [A/swine/Korea/CY0423/2013 (CY0423-12/2013)] replicated more efficiently in differentiated primary human bronchial epithelial cells. The CY0423-12/2013 virus induced higher viral titers than the CY03-11/2012 virus in the lungs and nasal turbinates of infected mice and nasal wash samples of ferrets. Moreover, the 2013 H1N2 reassortant, but not the intact 2012 H1N2 virus, was transmissible to naïve contact ferrets via respiratory-droplets. Noting that the viral precursors have the ability to infect humans, our findings highlight the potential threat of a novel reassortant H1N2 SIV to public health and underscore the need to further strengthen influenza surveillance strategies worldwide, including swine populations. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Dietary Enterococcus faecium NCIMB 10415 and Zinc Oxide Stimulate Immune Reactions to Trivalent Influenza Vaccination in Pigs but Do Not Affect Virological Response upon Challenge Infection

    Science.gov (United States)

    Wang, Zhenya; Burwinkel, Michael; Chai, Weidong; Lange, Elke; Blohm, Ulrike; Breithaupt, Angele; Hoffmann, Bernd; Twardziok, Sven; Rieger, Juliane; Janczyk, Pawel; Pieper, Robert; Osterrieder, Nikolaus

    2014-01-01

    Swine influenza viruses (SIV) regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E.) faecium NCIMB 10415 or zinc (Zn) oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Znhigh; 50 ppm, Znlow). Half of the piglets were vaccinated intramuscularly (VAC) twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Znhigh and E. faecium groups gained weight after infection while those in the control group (Znlow) lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI) titers were also observed in the Znhigh+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Znhigh and E. faecium groups at single time points after infection compared to the Znlow control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology. PMID:24489827

  14. Induction of Th1-Biased T Follicular Helper (Tfh) Cells in Lymphoid Tissues during Chronic Simian Immunodeficiency Virus Infection Defines Functionally Distinct Germinal Center Tfh Cells.

    Science.gov (United States)

    Velu, Vijayakumar; Mylvaganam, Geetha Hanna; Gangadhara, Sailaja; Hong, Jung Joo; Iyer, Smita S; Gumber, Sanjeev; Ibegbu, Chris C; Villinger, Francois; Amara, Rama Rao

    2016-09-01

    Chronic HIV infection is associated with accumulation of germinal center (GC) T follicular helper (Tfh) cells in the lymphoid tissue. The GC Tfh cells can be heterogeneous based on the expression of chemokine receptors associated with T helper lineages, such as CXCR3 (Th1), CCR4 (Th2), and CCR6 (Th17). However, the heterogeneous nature of GC Tfh cells in the lymphoid tissue and its association with viral persistence and Ab production during chronic SIV/HIV infection are not known. To address this, we characterized the expression of CXCR3, CCR4, and CCR6 on GC Tfh cells in lymph nodes following SIVmac251 infection in rhesus macaques. In SIV-naive rhesus macaques, only a small fraction of GC Tfh cells expressed CXCR3, CCR4, and CCR6. However, during chronic SIV infection, the majority of GC Tfh cells expressed CXCR3, whereas the proportion of CCR4(+) cells did not change, and CCR6(+) cells decreased. CXCR3(+), but not CXCR3(-), GC Tfh cells produced IFN-γ (Th1 cytokine) and IL-21 (Tfh cytokine), whereas both subsets expressed CD40L following stimulation. Immunohistochemistry analysis demonstrated an accumulation of CD4(+)IFN-γ(+) T cells within the hyperplastic follicles during chronic SIV infection. CXCR3(+) GC Tfh cells also expressed higher levels of ICOS, CCR5, and α4β7 and contained more copies of SIV DNA compared with CXCR3(-) GC Tfh cells. However, CXCR3(+) and CXCR3(-) GC Tfh cells delivered help to B cells in vitro for production of IgG. These data demonstrate that chronic SIV infection promotes expansion of Th1-biased GC Tfh cells, which are phenotypically and functionally distinct from conventional GC Tfh cells and contribute to hypergammaglobulinemia and viral reservoirs. Copyright © 2016 by The American Association of Immunologists, Inc.

  15. Rapid detection and subtyping of European swine influenza viruses in porcine clinical samples by haemagglutinin- and neuraminidase-specific tetra- and triplex real-time RT-PCRs.

    Science.gov (United States)

    Henritzi, Dinah; Zhao, Na; Starick, Elke; Simon, Gaelle; Krog, Jesper S; Larsen, Lars Erik; Reid, Scott M; Brown, Ian H; Chiapponi, Chiara; Foni, Emanuela; Wacheck, Silke; Schmid, Peter; Beer, Martin; Hoffmann, Bernd; Harder, Timm C

    2016-11-01

    A diversifying pool of mammalian-adapted influenza A viruses (IAV) with largely unknown zoonotic potential is maintained in domestic swine populations worldwide. The most recent human influenza pandemic in 2009 was caused by a virus with genes originating from IAV isolated from swine. Swine influenza viruses (SIV) are widespread in European domestic pig populations and evolve dynamically. Knowledge regarding occurrence, spread and evolution of potentially zoonotic SIV in Europe is poorly understood. Efficient SIV surveillance programmes depend on sensitive and specific diagnostic methods which allow for cost-effective large-scale analysis. New SIV haemagglutinin (HA) and neuraminidase (NA) subtype- and lineage-specific multiplex real-time RT-PCRs (RT-qPCR) have been developed and validated with reference virus isolates and clinical samples. A diagnostic algorithm is proposed for the combined detection in clinical samples and subtyping of SIV strains currently circulating in Europe that is based on a generic, M-gene-specific influenza A virus RT-qPCR. In a second step, positive samples are examined by tetraplex HA- and triplex NA-specific RT-qPCRs to differentiate the porcine subtypes H1, H3, N1 and N2. Within the HA subtype H1, lineages "av" (European avian-derived), "hu" (European human-derived) and "pdm" (human pandemic A/H1N1, 2009) are distinguished by RT-qPCRs, and within the NA subtype N1, lineage "pdm" is differentiated. An RT-PCR amplicon Sanger sequencing method of small fragments of the HA and NA genes is also proposed to safeguard against failure of multiplex RT-qPCR subtyping. These new multiplex RT-qPCR assays provide adequate tools for sustained SIV monitoring programmes in Europe. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  16. Swine Influenza Virus Antibodies in Humans, Western Europe, 2009

    Science.gov (United States)

    Gerloff, Nancy A.; Kremer, Jacques R.; Charpentier, Emilie; Sausy, Aurélie; Olinger, Christophe M.; Weicherding, Pierre; Schuh, John; Van Reeth, Kristien

    2011-01-01

    Serologic studies for swine influenza viruses (SIVs) in humans with occupational exposure to swine have been reported from the Americas but not from Europe. We compared levels of neutralizing antibodies against 3 influenza viruses—pandemic (H1N1) 2009, an avian-like enzootic subtype H1N1 SIV, and a 2007–08 seasonal subtype H1N1—in 211 persons with swine contact and 224 matched controls in Luxembourg. Persons whose profession involved contact with swine had more neutralizing antibodies against SIV and pandemic (H1N1) 2009 virus than did the controls. Controls also had antibodies against these viruses although exposure to them was unlikely. Antibodies against SIV and pandemic (H1N1) 2009 virus correlated with each other but not with seasonal subtype H1N1 virus. Sequential exposure to variants of seasonal influenza (H1N1) viruses may have increased chances for serologic cross-reactivity with antigenically distinct viruses. Further studies are needed to determine the extent to which serologic responses correlate with infection. PMID:21392430

  17. Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses

    Directory of Open Access Journals (Sweden)

    Ryan P. McNamara

    2018-02-01

    Full Text Available Extracellular vesicles (EVs or exosomes have been implicated in the pathophysiology of infections and cancer. The negative regulatory factor (Nef encoded by simian immunodeficiency virus (SIV and human immunodeficiency virus (HIV plays a critical role in the progression to AIDS and impairs endosomal trafficking. Whether HIV-1 Nef can be loaded into EVs has been the subject of controversy, and nothing is known about the connection between SIV Nef and EVs. We find that both SIV and HIV-1 Nef proteins are present in affinity-purified EVs derived from cultured cells, as well as in EVs from SIV-infected macaques. Nef-positive EVs were functional, i.e., capable of membrane fusion and depositing their content into recipient cells. The EVs were able to transfer Nef into recipient cells. This suggests that Nef readily enters the exosome biogenesis pathway, whereas HIV virions are assembled at the plasma membrane. It suggests a novel mechanism by which lentiviruses can influence uninfected and uninfectable, i.e., CD4-negative, cells.

  18. Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

    Science.gov (United States)

    Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

    1999-01-01

    The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

  19. Schlieren image velocimetry measurements in a rocket engine exhaust plume

    Science.gov (United States)

    Morales, Rudy; Peguero, Julio; Hargather, Michael

    2017-11-01

    Schlieren image velocimetry (SIV) measures velocity fields by tracking the motion of naturally-occurring turbulent flow features in a compressible flow. Here the technique is applied to measuring the exhaust velocity profile of a liquid rocket engine. The SIV measurements presented include discussion of visibility of structures, image pre-processing for structure visibility, and ability to process resulting images using commercial particle image velocimetry (PIV) codes. The small-scale liquid bipropellant rocket engine operates on nitrous oxide and ethanol as propellants. Predictions of the exhaust velocity are obtained through NASA CEA calculations and simple compressible flow relationships, which are compared against the measured SIV profiles. Analysis of shear layer turbulence along the exhaust plume edge is also presented.

  20. Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

    International Nuclear Information System (INIS)

    Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L.

    1991-01-01

    Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV mac ) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV mac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV mac activity in vitro. Plasma of these animals efficiently blocks SIV mac replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV mac -infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4 + but not CD8 + concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals

  1. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    International Nuclear Information System (INIS)

    Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-01-01

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

  2. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

    2015-01-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

  3. Function connectivity MRI to evaluate the changes of the motorial nerve net in patients with brain tumors adjacent to the central sulcus occurred with reorganization of motor function

    International Nuclear Information System (INIS)

    Han Tong; Liu Meili; Cui Shimin; Liu Li; Jin Song; Lei Jing; Liu Hui; Guo Jun; Hao Nina; Guo Ying; Xiang Huadong; Weng Xuchu

    2008-01-01

    Objective: We investigated the changes of the motorial network in patients suffered from brain tumors adjacent to the central sulcus occurred with reorganization of motor function using function connectivity MRI (fcMRI) technique in order to provide the new evidence for the compensational hypothesis of the reorganization caused by focal lesions. Methods: Using 1.5 T MRI unit, 14 patients with brain tumors in the vicinity of the central sulcus occurred with reorganization of motor function and 6 normal volunteers were examined with fcMRI technique while the subjects performed no task. By selecting seed voxels (region of interest) in the regions showing the most activation in Mi area on the activated map and cross correlating with every, voxel within the brain, the fcMRI maps based on unilateral primary motor (M1) area were calculated. The location, extent and volume of the region showing significant connectivity to the several seed voxel, such as left/right M1 area in the health group and affected/unaffected Mlarea in the patient group were evaluated on the fcMRI map. Results: In healthy group, the extent and volume of the region showing significant connectivity to the left Mlarea [(9514.17±186.92)mm 3 ] were almost similar to those to the right M1 area [(9364.67±382.75) mm 3 ]. There showed no significant difference in motor connectivity between the two groups (P>0.05). In the tumor group, the volume of regions showing significant connectivity to the M1 area located in the affected hemisphere [(11193.14 ± 811.29) mm 3 ] was obviously higher than that of regions based on the seed voxel in the unaffected side [(6549.86± 400.94) mm 3 ] (t=20.383, P<0.01). The volume was significantly different among the regions showing high connectivity to the M1 of the affected side in patient group, those showing significant connectivity to the left M1 and right M1 in health group (P<0.01), the former was the biggest (P<0.01). The extent of the regions showing connectivity to

  4. Evidence of reassortment of pandemic H1N1 influenza virus in swine in Argentina: are we facing the expansion of potential epicenters of influenza emergence?

    Science.gov (United States)

    Pereda, Ariel; Rimondi, Agustina; Cappuccio, Javier; Sanguinetti, Ramon; Angel, Matthew; Ye, Jianqiang; Sutton, Troy; Dibárbora, Marina; Olivera, Valeria; Craig, Maria I.; Quiroga, Maria; Machuca, Mariana; Ferrero, Andrea; Perfumo, Carlos; Perez, Daniel R.

    2011-01-01

    Please cite this paper as: Pereda et al. (2011) Evidence of reassortment of pandemic H1N1 influenza virus in swine in Argentina: are we facing the expansion of potential epicenters of influenza emergence? Influenza and Other Respiratory Viruses 5(6), 409–412. In this report, we describe the occurrence of two novel swine influenza viruses (SIVs) in pigs in Argentina. These viruses are the result of two independent reassortment events between the H1N1 pandemic influenza virus (H1N1pdm) and human‐like SIVs, showing the constant evolution of influenza viruses at the human–swine interface and the potential health risk of H1N1pdm as it appears to be maintained in the swine population. It must be noted that because of the lack of information regarding the circulation of SIVs in South America, we cannot discard the possibility that ancestors of the H1N1pdm or other SIVs have been present in this part of the world. More importantly, these findings suggest an ever‐expanding geographic range of potential epicenters of influenza emergence with public health risks. PMID:21668680

  5. Improved survival in rhesus macaques immunized with modified vaccinia virus Ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory CD4+ T-cell loss and higher titers of neutralizing antibody.

    Science.gov (United States)

    Ourmanov, Ilnour; Kuwata, Takeo; Goeken, Robert; Goldstein, Simoy; Iyengar, Ranjani; Buckler-White, Alicia; Lafont, Bernard; Hirsch, Vanessa M

    2009-06-01

    Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high viremia and AIDS following challenge with a pathogenic strain of SIV. Although all animals became infected, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines compared with animals that received nonrecombinant MVA. Most importantly, the reduction in viremia resulted in a significant increase in median and cumulative survival. Continued analysis of these animals over the subsequent 9 years has shown that they maintain a survival advantage, although all but two of the macaques have progressed to AIDS. Importantly, improved survival correlated with preservation of memory CD4(+) T cells in the peripheral blood. The greatest survival advantage was observed in macaques immunized with regimens containing SIV Env, and the titer of neutralizing antibodies to the challenge virus prior to or shortly following challenge correlated with preservation of CD4(+) T cells. These data are consistent with a role for neutralizing antibodies in nonsterilizing protection from high viremia and associated memory CD4(+) T-cell loss.

  6. Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

    Science.gov (United States)

    Vaccari, Monica; Gordon, Shari N; Fourati, Slim; Schifanella, Luca; Liyanage, Namal P M; Cameron, Mark; Keele, Brandon F; Shen, Xiaoying; Tomaras, Georgia D; Billings, Erik; Rao, Mangala; Chung, Amy W; Dowell, Karen G; Bailey-Kellogg, Chris; Brown, Eric P; Ackerman, Margaret E; Vargas-Inchaustegui, Diego A; Whitney, Stephen; Doster, Melvin N; Binello, Nicolo; Pegu, Poonam; Montefiori, David C; Foulds, Kathryn; Quinn, David S; Donaldson, Mitzi; Liang, Frank; Loré, Karin; Roederer, Mario; Koup, Richard A; McDermott, Adrian; Ma, Zhong-Min; Miller, Christopher J; Phan, Tran B; Forthal, Donald N; Blackburn, Matthew; Caccuri, Francesca; Bissa, Massimiliano; Ferrari, Guido; Kalyanaraman, Vaniambadi; Ferrari, Maria G; Thompson, DeVon; Robert-Guroff, Marjorie; Ratto-Kim, Silvia; Kim, Jerome H; Michael, Nelson L; Phogat, Sanjay; Barnett, Susan W; Tartaglia, Jim; Venzon, David; Stablein, Donald M; Alter, Galit; Sekaly, Rafick-Pierre; Franchini, Genoveffa

    2016-07-01

    A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

  7. The research of morphological variations and sexual dimorphism of primary grooves on the medial side of brain hemispheres in humans

    Directory of Open Access Journals (Sweden)

    Spasojević Goran

    2012-01-01

    Full Text Available Morphological studies of the various parts of the brain show certain morphological and morphometric differences in correlation with sex, so-called sexual dimorphism of the brain. Our research has been done on the cerebral hemispheres, taken from cadavers of both sexes and different age without pathological processes in the brain. The sample comprised 26 male brains and 16 female brains. We studied three primary grooves (sulcus cinguli, sulcus parietooccipitalis and sulcus calcarinus of the medial surface of the human cerebral hemispheres. We conducted morphological typology of grooves and morphometric measurements of primary brain grooves length in relation to sex and side of hemisphere. The results showed a statistically significant sex difference in the cingulate sulcus length (p0,05. Determined morphometric sexual dimorphism in cingulate sulcus length is significant because it implies the correlation between morphology and function of the explored areas of the cerebral cortex.

  8. Molecular evolution of H1N1 swine influenza in Guangdong, China, 2016-2017.

    Science.gov (United States)

    Cai, Mengkai; Huang, Junming; Bu, Dexin; Yu, Zhiqing; Fu, Xinliang; Ji, Chihai; Zhou, Pei; Zhang, Guihong

    2018-06-01

    Swine are the main host of the H1N1 swine influenza virus (SIV), however, H1N1 can also infect humans and occasionally cause serious respiratory disease. To trace the evolution of the SIV in Guangdong, China, we performed an epidemic investigation during the period of 2016-2017. Nine H1N1 influenza viruses were isolated from swine nasal swabs. Antigenic analysis revealed that these viruses belonged to two distinct antigenic groups, represented by A/Swine/Guangdong/101/2016 and A/Swine/Guangdong/52/2017. Additionally, three genotypes, known as GD52/17-like, GD493/17-like and GD101/16-like, were identified by phylogenetic analysis. Importantly, the genotypes including a minimum of 4 pdm/09-origin internal genes have become prevalent in China in recent years. A total of 2966 swine serum samples were used to perform hemagglutination inhibition (HI) tests, and the results showed that the seroprevalence values of SW/GD/101/16 (32.2% in 2016, 32.1% in 2017) were significantly higher than the seroprevalence values of SW/GD/52/17 (18.0% in 2016, 16.7% in 2017). Our study showed that the three reassortant genotypes of H1N1 SIV currently circulating in China are stable, but H1N1pdm09 poses challenges to human health by the introduction of internal genes into these reassortant genotypes. Strengthening SIV surveillance is therefore critical for SIV control and minimizing its potential threat to public health. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Sur la modélisation des supraconducteurs: le "modèle de l'état critique" de bean, en trois dimensions

    Science.gov (United States)

    Bossavit, A.

    1994-03-01

    La formule (22), p. 386, soit u_x(v) = si|v| < j_c(x); alors; 0; sinon; ρ(x)|v|^2/2, aurait dû être u_x(v) = si|v| < j_c(x); alors; 0; sinon; ρ(x)(|v|^2)/2. La même erreur apparaît dans l'introduction (page 376, une ligne après l'équation (10)) et page 390.

  10. Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003.

    Science.gov (United States)

    Van Reeth, Kristien; Brown, Ian H; Dürrwald, Ralf; Foni, Emanuela; Labarque, Geoffrey; Lenihan, Patrick; Maldonado, Jaime; Markowska-Daniel, Iwona; Pensaert, Maurice; Pospisil, Zdenek; Koch, Guus

    2008-05-01

    Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance Network for Influenza in Pigs 1', aimed to determine the seroprevalence of the H1N2 virus in different European regions and to compare the relative prevalences of each SIV between regions. Laboratories from Belgium, the Czech Republic, Germany, Italy, Ireland, Poland and Spain participated in an international serosurvey. A total of 4190 sow sera from 651 farms were collected in 2002-2003 and examined in haemagglutination inhibition tests against H1N1, H3N2 and H1N2. In Belgium, Germany, Italy and Spain seroprevalence rates to each of the three SIV subtypes were high (> or =30% of the sows seropositive) to very high (> or =50%), except for a lower H1N2 seroprevalence rate in Italy (13.8%). Most sows in these countries with high pig populations had antibodies to two or three subtypes. In Ireland, the Czech Republic and Poland, where swine farming is less intensive, H1N1 was the dominant subtype (8.0-11.7% seropositives) and H1N2 and H3N2 antibodies were rare (0-4.2% seropositives). Thus, SIV of H1N1, H3N2 and H1N2 subtype are enzootic in swine producing regions of Western Europe. In Central Europe, SIV activity is low and the circulation of H3N2 and H1N2 remains to be confirmed. The evolution and epidemiology of SIV throughout Europe is being further monitored through a second 'European Surveillance Network for Influenza in Pigs'.

  11. Dietary Enterococcus faecium NCIMB 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection.

    Science.gov (United States)

    Wang, Zhenya; Burwinkel, Michael; Chai, Weidong; Lange, Elke; Blohm, Ulrike; Breithaupt, Angele; Hoffmann, Bernd; Twardziok, Sven; Rieger, Juliane; Janczyk, Pawel; Pieper, Robert; Osterrieder, Nikolaus

    2014-01-01

    Swine influenza viruses (SIV) regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E.) faecium NCIMB 10415 or zinc (Zn) oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high); 50 ppm, Zn(low)). Half of the piglets were vaccinated intramuscularly (VAC) twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high) and E. faecium groups gained weight after infection while those in the control group (Zn(low)) lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI) titers were also observed in the Zn(high)+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high) and E. faecium groups at single time points after infection compared to the Zn(low) control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.

  12. Dietary Enterococcus faecium NCIMB 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection.

    Directory of Open Access Journals (Sweden)

    Zhenya Wang

    Full Text Available Swine influenza viruses (SIV regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E. faecium NCIMB 10415 or zinc (Zn oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high; 50 ppm, Zn(low. Half of the piglets were vaccinated intramuscularly (VAC twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high and E. faecium groups gained weight after infection while those in the control group (Zn(low lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI titers were also observed in the Zn(high+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high and E. faecium groups at single time points after infection compared to the Zn(low control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.

  13. [An overview on swine influenza viruses].

    Science.gov (United States)

    Yang, Shuai; Zhu, Wen-Fei; Shu, Yue-Long

    2013-05-01

    Swine influenza viruses (SIVs) are respiratory pathogens of pigs. They cause both economic bur den in livestock-dependent industries and serious global public health concerns in humans. Because of their dual susceptibility to human and avian influenza viruses, pigs are recognized as intermediate hosts for genetic reassortment and interspecies transmission. Subtypes H1N1, H1N2, and H3N2 circulate in swine populations around the world, with varied origin and genetic characteristics among different continents and regions. In this review, the role of pigs in evolution of influenza A viruses, the genetic evolution of SIVs and interspecies transmission of SIVs are described. Considering the possibility that pigs might produce novel influenza viruses causing more outbreaks and pandemics, routine epidemiological surveillance of influenza viruses in pig populations is highly recommended.

  14. Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

    Science.gov (United States)

    Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

    2017-08-15

    A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV/SIV

  15. Can Taichi reshape the brain? A brain morphometry study.

    Directory of Open Access Journals (Sweden)

    Gao-Xia Wei

    Full Text Available Although research has provided abundant evidence for Taichi-induced improvements in psychological and physiological well-being, little is known about possible links to brain structure of Taichi practice. Using high-resolution MRI of 22 Tai Chi Chuan (TCC practitioners and 18 controls matched for age, sex and education, we set out to examine the underlying anatomical correlates of long-term Taichi practice at two different levels of regional specificity. For this purpose, parcel-wise and vertex-wise analyses were employed to quantify the difference between TCC practitioners and the controls based on cortical surface reconstruction. We also adopted the Attention Network Test (ANT to explore the effect of TCC on executive control. TCC practitioners, compared with controls, showed significantly thicker cortex in precentral gyrus, insula sulcus and middle frontal sulcus in the right hemisphere and superior temporal gyrus and medial occipito-temporal sulcus and lingual sulcus in the left hemisphere. Moreover, we found that thicker cortex in left medial occipito-temporal sulcus and lingual sulcus was associated with greater intensity of TCC practice. These findings indicate that long-term TCC practice could induce regional structural change and also suggest TCC might share similar patterns of neural correlates with meditation and aerobic exercise.

  16. Lentiviral Gag assembly analyzed through the functional characterization of chimeric simian immunodeficiency viruses expressing different domains of the feline immunodeficiency virus capsid protein.

    Directory of Open Access Journals (Sweden)

    María J Esteva

    Full Text Available To gain insight into the functional relationship between the capsid (CA domains of the Gag polyproteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively, we constructed chimeric SIVs in which the CA-coding region was partially or totally replaced by the equivalent region of the FIV CA. The phenotypic characterization of the chimeras allowed us to group them into three categories: the chimeric viruses that, while being assembly-competent, exhibit a virion-associated unstable FIV CA; a second group represented only by the chimeric SIV carrying the N-terminal domain (NTD of the FIV CA which proved to be assembly-defective; and a third group constituted by the chimeric viruses that produce virions exhibiting a mature and stable FIV CA protein, and which incorporate the envelope glycoprotein and contain wild-type levels of viral genome RNA and reverse transcriptase. Further analysis of the latter group of chimeric SIVs demonstrated that they are non-infectious due to a post-entry impairment, such as uncoating of the viral core, reverse transcription or nuclear import of the preintegration complex. Furthermore, we show here that the carboxyl-terminus domain (CTD of the FIV CA has an intrinsic ability to dimerize in vitro and form high-molecular-weight oligomers, which, together with our finding that the FIV CA-CTD is sufficient to confer assembly competence to the resulting chimeric SIV Gag polyprotein, provides evidence that the CA-CTD exhibits more functional plasticity than the CA-NTD. Taken together, our results provide relevant information on the biological relationship between the CA proteins of primate and nonprimate lentiviruses.

  17. Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection

    International Nuclear Information System (INIS)

    Zhang Zhiqiang; Casimiro, Danilo R.; Schleif, William A.; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A.; Shiver, John W.

    2007-01-01

    Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4 + T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection

  18. Comparison of stress-induced voiding phenomena in copper line–via structures with different dielectric materials

    International Nuclear Information System (INIS)

    Hou, Yuejin; Tan, Cher Ming

    2009-01-01

    The package level stress-induced voiding (SIV) test of Cu dual-damascene line–via structures is performed. Two different dielectrics, undoped silica glass (USG) and carbon doped oxide (CDO), are used in this work. After 1344 h of high temperature storage test, the resistance drift of USG interconnects is found to be much smaller than that of CDO interconnects and voids are located at the bottom of the via for both USG and CDO interconnects. However, horizontal voids grown along the via bottom is observed for USG interconnects, whilst voids are found to grow vertically along the via sidewall for CDO interconnects. The phenomena are explained using finite element analysis in this work, and the observed poor SIV performance for CDO interconnects is also explained. With this finite element analysis, the implications of different low-k dielectrics on SIV reliability are discussed

  19. Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

    Science.gov (United States)

    Shan, Liang; Siliciano, Robert F.

    2014-01-01

    Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection. PMID:24837427

  20. Novel reassortant swine influenza viruses are circulating in Danish pigs

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    of the reassortant viruses comprised a HA gene similar to H1 of H1N1 avian-like swine influenza virus (SIV) and a NA gene most closely related to N2 gene of human H3N2 influenza virus that circulated in humans in the mid 1990s. The internal genes of this reassortant virus with the subtype H1avN2hu all belonged...... to the H1N1 avian-like SIV lineages. Until now this novel virus H1avN2hu has only been detected in Danish swine. The other novel reassortant virus contained the HA gene from H1N1pdm09 virus and a NA gene similar to the N2 gene of H3N2 SIV that have been circulating in European swine since the mid 1980s...

  1. Advantages of T2 reversed fast spin-echo image and enhanced three-dimensional surface MR angiography for the diagnosis of cerebral arteriovenous malformations

    International Nuclear Information System (INIS)

    Tanabe, Sumiyoshi; Honmou, Osamu; Minamida, Yoshihiro; Hashi, Kazuo

    2001-01-01

    Although the anatomical investigation of cerebral arteriovenous malformation (AVM) with conventional neuro-imagings considerably supports the preoperative evaluation, it is still hard to dissect the detailed anatomical conformations of AVMs such as location of nidus, identification of feeding arteries or draining veins, and the three-dimensional configuration of nidus in sulci or gyri. In this study, we investigated the efficacy of enhanced three-dimensional surface MR angiography (surface MRA) and T2 reversed image (T2R image) in the diagnosis and surgical planning for cerebral AVMs. The diagnostic accuracy was studied in twelve AVMs: four AVMs closed to motor area, one to Broca area, one to Wernicke area, four in temporal lobe, and two in occipital lobe. Images were obtained with a SIGNA HORIZON LX 1.5T VER 8.2. To construct T2R, the brain is scanned by fast SE method with long TR and was displayed with the reversed gray scale, which seemed similar to T1WI. Surface MRA is a fusion image of MRA and surface image in the workstation. The original data was obtained by enhanced 3D-SPGR method. MRA image was reconstructed with MIP method, and surface image was manipulated with a volume rendering method. T2R images demonstrated seven sulcal AVMs, three gyral AVMs, and two sulco-gyral AVMs; five AVMs located on cortex, four extended to subcortex, and three to paraventricular brain. The images clearly showed six AVMs had hypervascular network such as modja-modja vascular formation. Surface MRA represented nidus adjacent to eloquent area. They were present in central sulcus, precentral sulcus, intraparietal sulcus, inferior frontal sulcus, sylvian fissure, superior temporal sulcus, inferior temporal sulcus, superior temporal gyrus, inferior temporal gyrus, medial temporal gyrus, premotor area and superior frontal sulcus, precuneus and parieto-occipital sulcus. It was easy to identify the point of feeding arteries going down into the sulcus and the junction-point of nidus

  2. Advantages of T2 reversed fast spin-echo image and enhanced three-dimensional surface MR angiography for the diagnosis of cerebral arteriovenous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Sumiyoshi; Honmou, Osamu; Minamida, Yoshihiro; Hashi, Kazuo [Sapporo Medical Univ. (Japan). School of Medicine

    2001-09-01

    Although the anatomical investigation of cerebral arteriovenous malformation (AVM) with conventional neuro-imagings considerably supports the preoperative evaluation, it is still hard to dissect the detailed anatomical conformations of AVMs such as location of nidus, identification of feeding arteries or draining veins, and the three-dimensional configuration of nidus in sulci or gyri. In this study, we investigated the efficacy of enhanced three-dimensional surface MR angiography (surface MRA) and T2 reversed image (T2R image) in the diagnosis and surgical planning for cerebral AVMs. The diagnostic accuracy was studied in twelve AVMs: four AVMs closed to motor area, one to Broca area, one to Wernicke area, four in temporal lobe, and two in occipital lobe. Images were obtained with a SIGNA HORIZON LX 1.5T VER 8.2. To construct T2R, the brain is scanned by fast SE method with long TR and was displayed with the reversed gray scale, which seemed similar to T1WI. Surface MRA is a fusion image of MRA and surface image in the workstation. The original data was obtained by enhanced 3D-SPGR method. MRA image was reconstructed with MIP method, and surface image was manipulated with a volume rendering method. T2R images demonstrated seven sulcal AVMs, three gyral AVMs, and two sulco-gyral AVMs; five AVMs located on cortex, four extended to subcortex, and three to paraventricular brain. The images clearly showed six AVMs had hypervascular network such as modja-modja vascular formation. Surface MRA represented nidus adjacent to eloquent area. They were present in central sulcus, precentral sulcus, intraparietal sulcus, inferior frontal sulcus, sylvian fissure, superior temporal sulcus, inferior temporal sulcus, superior temporal gyrus, inferior temporal gyrus, medial temporal gyrus, premotor area and superior frontal sulcus, precuneus and parieto-occipital sulcus. It was easy to identify the point of feeding arteries going down into the sulcus and the junction-point of nidus

  3. CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes

    OpenAIRE

    Arthos, James; Rubbert, Andrea; Rabin, Ronald L.; Cicala, Claudia; Machado, Elizabeth; Wildt, Kathryne; Hanbach, Meredith; Steenbeke, Tavis D.; Swofford, Ruth; Farber, Joshua M.; Fauci, Anthony S.

    2000-01-01

    The capacity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelopes to transduce signals through chemokine coreceptors on macrophages was examined by measuring the ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to those observed when macrophages were treated with MIP-1β. Distinct differences in the capacity o...

  4. [Swine influenza virus: evolution mechanism and epidemic characterization--a review].

    Science.gov (United States)

    Qi, Xian; Lu, Chengping

    2009-09-01

    Pigs may play an important role in the evolution and ecology of influenza A virus. The tracheal epithelium of pigs contain both SA alpha 2,6 Gal and SA alpha 2,3 Gal receptors and can be infected with swine, human and avian viruses, therefore, pigs have been considered as an intermediate host for the adaptation of avian influenza viruses to humans or as mixing vessels for the generation of genetically reassortant viruses. Evolution patterns among swine influenza viruses including evolution of host adaptation, antigenic drift and genetic reassortment, and the latter is the main one. Unlike human influenza viruses, swine viruses have different epizootiological patterns in different areas of world, which is enzootic and geographic dependence. Currently, three predominant subtypes of influenza virus are prevalent in pig populations worldwide: H1N1, H3N2, and H1N2, and these include classical swine H1N1, avian-like H1N1, human-like H3N2, reassortant H3N2 and various genotype H1N2 viruses. In Europe, North America and China, influenza A viruses circulating in pigs are distinct in the genetic characteristics and genetic sources. Since 1979, three subtypes, avian-like H1N1, reassortant H1N2 and H3N2 viruses, have been co-circulating in European swine. Before 1998, classical H1N1 viruses were the exclusive cause of swine influenza in North America. However, after that, three triple-reassortant H1N2, H3N2 and H1N1 viruses with genes of human, swine and avian virus began to emerge in pigs. Genetically, the pandemic viruses emerging in human, so called influenza A (H1N1) viruses, contain genes from both Europe and North American SIV lineages. SIV is not the same as Europe and the United States in the prevalence and genetic background in China, mainly classical swine H1N1 and human-like H3N2 type virus. However, in recent years, SIV from Europe and North America have been introduced into Chinese pig herds, so more attention should be given on the evolutionary of SIV in China

  5. Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

    Science.gov (United States)

    Chowdhury, Ankita; Hayes, Timothy L; Bosinger, Steven E; Lawson, Benton O; Vanderford, Thomas; Schmitz, Joern E; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D; Silvestri, Guido

    2015-09-01

    Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8(+) T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8(+) T-bet(+) lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4(+) central memory T lymphocytes (TCM) and CD4(+) effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4(+) TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4(+) T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8(+) T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8(+) T lymphocytes. In this study, we further dissect the impact of CD8(+) T lymphocytes on HIV/SIV replication during SIV infection. CD8(+) T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8(+) T lymphocyte depletion

  6. Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus

    OpenAIRE

    Cromwell, Mandy A.; Veazey, Ronald S.; Altman, John D.; Mansfield, Keith G.; Glickman, Rhona; Allen, Todd M.; Watkins, David I.; Lackner, Andrew A.; Johnson, R. Paul

    2000-01-01

    Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8+ lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor α4β7 and traffic to the intestinal mucosa. SIV-...

  7. Utilizing a TLR5-Adjuvanted Cytomegalovirus as a Lentiviral Vaccine in the Nonhuman Primate Model for AIDS.

    Directory of Open Access Journals (Sweden)

    Jesse D Deere

    Full Text Available Despite tremendous progress in our understanding of human immunodeficiency virus (HIV natural history and advances in HIV treatment, there is neither an approved vaccine nor a cure for infection. Here, we describe the development and characterization of a novel replicating vaccine vector utilizing Cytomegalovirus (CMV and a TLR5 adjuvant. After partial truncation of the central, immunodominant hypervariable domain, flagellin (fliC from Salmonella was cloned downstream of a codon optimized gag gene from simian immunodeficiency virus (SIV and transiently expressed in telomerized rhesus fibroblast (TeloRF cells in culture. Lysates generated from these transfected cells induced the tumor necrosis factor alpha (TNF-α, in a mouse macrophage cell line, in a TLR5-dependent manner. The Gag/FliC expression construct was cloned into a bacterial artificial chromosome encoding the rhesus CMV (RhCMV genome, and infectious RhCMV was generated following transfection of TeloRF cells. This virus stably expressed an SIV Gag/FliC fusion protein through four serial passages. Lysates generated from infected cells induced TNF-α in a TLR5-dependent manner. Western blot analysis of infected cell lysates verified expression of a Gag/FliC fusion protein using a SIV p27 capsid monoclonal antibody. Lastly, rhesus macaques inoculated with this novel RhCMV virus demonstrated increased inflammatory responses at the site of inoculation seven days post-infection when compared to the parental RhCMV. These results demonstrate that an artificially constructed replicating RhCMV expressing an SIV Gag/FliC fusion protein is capable of activating TLR5 in a macrophage cell line in vitro and induction of an altered inflammatory response in vivo. Ongoing animals studies are aimed at determining vaccine efficacy, including subsequent challenge with pathogenic SIV.

  8. Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines

    Directory of Open Access Journals (Sweden)

    Rahmberg Andrew R

    2011-05-01

    Full Text Available Abstract Background Molecular adjuvants are a promising method to enhance virus-specific immune responses and protect against HIV-1 infection. Immune activation by ligands for receptors such as CD40 can induce dendritic cell activation and maturation. Here we explore the incorporation of two CD40 mimics, Epstein Barr Virus gene LMP1 or an LMP1-CD40 chimera, into a strain of SIV that was engineered to be limited to a single cycle of infection. Results Full length LMP1 or the chimeric protein LMP1-CD40 was cloned into the nef-locus of single-cycle SIV. Human and Macaque monocyte derived macrophages and DC were infected with these viruses. Infected cells were analyzed for activation surface markers by flow cytometry. Cells were also analyzed for secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12p70 and TNF by cytometric bead array. Conclusions Overall, single-cycle SIV expressing LMP1 and LMP1-CD40 produced a broad and potent TH1-biased immune response in human as well as rhesus macaque macrophages and DC when compared with control virus. Single-cycle SIV-LMP1 also enhanced antigen presentation by lentiviral vector vaccines, suggesting that LMP1-mediated immune activation may enhance lentiviral vector vaccines against HIV-1.

  9. Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection

    OpenAIRE

    Campbell, Jennifer H.; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J.; Tse, Samantha; Miller, Andrew D.; González, R. Gilberto; Salemi, Marco; Burdo, Tricia H.; Williams, Kenneth C.

    2014-01-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages a...

  10. Total ear reconstruction: The role of bilateral triangular post ...

    African Journals Online (AJOL)

    Saad Mohamed Saad Ibrahiem

    2016-03-16

    Mar 16, 2016 ... Patients requiring glasses have worn frames soon after the tie-over was removed .... skin grafts), which frequently end with shallow sulcus. Nagata4 used a ... forces of fibrosis along one direction and keep the sulcus deep.

  11. High-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection

    Energy Technology Data Exchange (ETDEWEB)

    George, Michael D; Sankaran, Sumathi; Reay, Elizabeth; Gelli, Angie C; Dandekar, Satya

    2003-07-20

    During primary simian immunodeficiency virus (SIV) infection, CD4+ T cells are severely depleted in gut-associated lymphoid tissue (GALT), while CD8+ T-cell numbers dramatically increase. To gain an understanding of the molecular basis of this disruption in T-cell homeostasis, host gene expression was monitored in longitudinal jejunum tissue biopsies from SIV-infected rhesus macaques by DNA microarray analysis. Transcription of cyclin E1, CDC2, retinoblastoma, transforming growth factor (TGF), fibroblast growth factor (FGF), and interleukin-2 was repressed while cyclins B1 and D2 and transcription factor E2F were upregulated, indicating a complex dysregulation of growth and proliferation within the intestinal mucosa. Innate, cell-mediated, and humoral immune responses were markedly upregulated in animals that significantly reduced their viral loads and retained more intestinal CD4+ T cells. We conclude that the alterations in intestinal gene expression during primary SIV infection were characteristic of a broad-range immune response, and reflective of the efficacy of viral suppression.

  12. High-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection

    International Nuclear Information System (INIS)

    George, Michael D.; Sankaran, Sumathi; Reay, Elizabeth; Gelli, Angie C.; Dandekar, Satya

    2003-01-01

    During primary simian immunodeficiency virus (SIV) infection, CD4+ T cells are severely depleted in gut-associated lymphoid tissue (GALT), while CD8+ T-cell numbers dramatically increase. To gain an understanding of the molecular basis of this disruption in T-cell homeostasis, host gene expression was monitored in longitudinal jejunum tissue biopsies from SIV-infected rhesus macaques by DNA microarray analysis. Transcription of cyclin E1, CDC2, retinoblastoma, transforming growth factor (TGF), fibroblast growth factor (FGF), and interleukin-2 was repressed while cyclins B1 and D2 and transcription factor E2F were upregulated, indicating a complex dysregulation of growth and proliferation within the intestinal mucosa. Innate, cell-mediated, and humoral immune responses were markedly upregulated in animals that significantly reduced their viral loads and retained more intestinal CD4+ T cells. We conclude that the alterations in intestinal gene expression during primary SIV infection were characteristic of a broad-range immune response, and reflective of the efficacy of viral suppression

  13. Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection

    Directory of Open Access Journals (Sweden)

    Barbara Tavano

    2017-03-01

    Full Text Available The human immunodeficiency virus (HIV accesses the central nervous system (CNS early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing. These immunologic alterations were not accompanied by differences in SIV transcriptional activity within the tissue. Altered expression of genes associated with neurotoxicity was observed in both midbrain and frontal lobe. The segregation of inflammatory responses to specific regions of the CNS may both account for HIV-associated neurological symptoms and constitute a critical hurdle for HIV eradication by shielding the CNS viral reservoir from antiviral immunity.

  14. HIV Infection of Macrophages: Implications for Pathogenesis and Cure

    Directory of Open Access Journals (Sweden)

    Kiera Leigh Clayton

    2017-05-01

    Full Text Available Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

  15. Statistical intensity variation analysis for rapid volumetric imaging of capillary network flux.

    Science.gov (United States)

    Lee, Jonghwan; Jiang, James Y; Wu, Weicheng; Lesage, Frederic; Boas, David A

    2014-04-01

    We present a novel optical coherence tomography (OCT)-based technique for rapid volumetric imaging of red blood cell (RBC) flux in capillary networks. Previously we reported that OCT can capture individual RBC passage within a capillary, where the OCT intensity signal at a voxel fluctuates when an RBC passes the voxel. Based on this finding, we defined a metric of statistical intensity variation (SIV) and validated that the mean SIV is proportional to the RBC flux [RBC/s] through simulations and measurements. From rapidly scanned volume data, we used Hessian matrix analysis to vectorize a segment path of each capillary and estimate its flux from the mean of the SIVs gathered along the path. Repeating this process led to a 3D flux map of the capillary network. The present technique enabled us to trace the RBC flux changes over hundreds of capillaries with a temporal resolution of ~1 s during functional activation.

  16. Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.

    Science.gov (United States)

    Verhoeven, D; Sankaran, S; Dandekar, S

    2007-08-01

    Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

  17. Surgery of the eloquent area using neuronavigation system

    International Nuclear Information System (INIS)

    Nakai, Hirofumi; Tanaka, Tatsuya; Hashizume, Kiyotaka; Hodozuka, Akira

    2001-01-01

    The efficacy of a neuronavigation system for surgery of lesions near Broca's area (6 patients), skull base (5 patients), or paracentral sulcus (10 patients) was evaluated in this study. Using the neuronavigation system, three-dimensional (3D) brain images were reconstructed by plotting cerebral sulcus obtained by MRI and CT. For paracentral sulcus lesions, patients underwent blood oxygen level-dependent fMRI while performing a finger-tapping motor paradigm. 3D reconstructed images were demonstrated to be useful for understanding the anatomical relationship between the lesions and the surrounding vital structures. The precentral gyri identified by 3D reconstructed brain images coincided well with that identified by fMRI. In lesions near Broca's area, skull base, and paracentral sulcus, 3D reconstructed brain images were very useful for both the preoperative surgical simulation and the intraoperative neuronavigation to preserve the postoperative neurological function and to perform less invasive surgery. (author)

  18. Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms

    Directory of Open Access Journals (Sweden)

    Aghokeng Avelin F

    2011-01-01

    Full Text Available Abstract Background Data on the evolution of natural SIV infection in chimpanzees (SIVcpz and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (Pan troglodytes schweinfurthii, and no data exist for Central chimpanzees (Pan troglodytes troglodytes, the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a P.t.troglodytes chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection. Results A male chimpanzee (Cam155, 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine. Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm3 in 2004 vs 287 in 2009, a severe thrombocytopenia (130,000 cells/mm3 in 2004 vs 5,000 cells/mm3 in 2009, a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg and frequent periods of infections with diverse pathogens. DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpzPtt-Cam155 genomes. SIVcpzPtt-Cam155 was phylogenetically related to other SIVcpzPtt from Cameroon (SIVcpzPtt-Cam13 and Gabon (SIVcpzPtt-Gab1. Ten molecular clones 5 years apart, spanning the V1V4 gp120 env region (1,100 bp, were obtained. Analyses of the env region showed positive selection (dN-dS >0, intra-host length variation and extensive amino acid diversity between clones, greater in 2009. Over 5 years, N-glycosylation site frequency significantly increased (p Conclusions Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected P.t.troglodytes chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that

  19. Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab)

    Science.gov (United States)

    Gill, Amanda L.; Green, Samantha A.; Abdullah, Shahed; Le Saout, Cecile; Pittaluga, Stefania; Chen, Hui; Turnier, Refika; Lifson, Jeffrey; Godin, Steven; Qin, Jing; Sneller, Michael C.; Cuillerot, Jean-Marie; Sabzevari, Helen; Lane, H. Clifford; Catalfamo, Marta

    2016-01-01

    Objective: The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. Methods: Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. Results: PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. Conclusion: Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans. PMID:27490642

  20. Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti-programed death-ligand 1 (Avelumab).

    Science.gov (United States)

    Gill, Amanda L; Green, Samantha A; Abdullah, Shahed; Le Saout, Cecile; Pittaluga, Stefania; Chen, Hui; Turnier, Refika; Lifson, Jeffrey; Godin, Steven; Qin, Jing; Sneller, Michael C; Cuillerot, Jean-Marie; Sabzevari, Helen; Lane, H Clifford; Catalfamo, Marta

    2016-10-23

    The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans.

  1. Functional rearrangement of the primary and secondary motor cortex in patients with primary tumors of the central nervous system located in the region of the central sulcus depending on the histopathological type and the size of tumor: Examination by means of functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bryszewski, Bartosz; Pfajfer, Lucjan; Antosik-Biernacka, Aneta; Tybor, Krzysztof; Śmigielski, Janusz; Zawirski, Marek; Majos, Agata

    2012-01-01

    The aim of this study was to analyze the reorganization of the centers of the motor cortex in patients with primary neuroepithelial tumors of the central nervous system (CNS) located in the region of the central sulcus in relation to the histopathological type and the size of tumor, as determined by means of functional magnetic resonance imaging (fMRI). The fMRI was performed prior to the surgical treatment of patients with tumors located in the region of the central sulcus (WHO stage I and II, n=15; WHO stage III and IV, n=25). The analysis included a record of the activity in the areas of the primary motor cortex (M1) and the secondary motor cortex: the premotor cortex (PMA) and the accessory motor area (SMA). The results were correlated with the histopathological type of the tumor and its size expressed in cm 3 . The frequency of activation of the motor center was higher in the group of patients who had less aggressive tumors, such as low-grade glioma (LGG), as well as in tumors of lower volume, and this was true both for the hemisphere where the tumor was located and in the contralateral one. Mean values of t-statistics of activation intensity, mean numbers of activated clusters, and their ranges were lower in all analyzed motor areas of LGG tumors. The values of t-statistics and activation areas were higher in the case of small tumors located in ipsilateral centers, and in large tumors located in contralateral centers, aside from the SMA area where the values of t-statistics were equal for both groups. The contralateral SMA area was characterized by the highest stability of all examined centers of secondary motor cortex. No significant association (p>0.05) was observed between the absolute value of the mean registered activity (t-statistics) and the size of examined areas (number of clusters) when the groups were stratified with regards to the analyzed parameters. The presence of a neoplastic lesion, its histopathological type and finally its size modulate the

  2. [Origin and evolution of human immunodeficiency viruses].

    Science.gov (United States)

    Marian, Constantin V

    2009-01-01

    After the diagnosis of the AIDS symptoms, in 1981, and after the discovery of the virus that causes AIDS, in 1983, the virologists have formulated different theories about its origin. Some of them involved natural causes, e.g., HIV origin from SIV strains. Other theories go further to the possibility of a deadly man-made virus escaped from laboratories or voluntary spread by some conspirative organisations. At this moment, the scientists limits themselves to search proofs to sustain the zoonotic origin of HIV from SIV and its accomodation to human body conditions.

  3. European surveillance network for influenza in pigs: surveillance programs, diagnostic tools and Swine influenza virus subtypes identified in 14 European countries from 2010 to 2013.

    Directory of Open Access Journals (Sweden)

    Gaëlle Simon

    Full Text Available Swine influenza causes concern for global veterinary and public health officials. In continuing two previous networks that initiated the surveillance of swine influenza viruses (SIVs circulating in European pigs between 2001 and 2008, a third European Surveillance Network for Influenza in Pigs (ESNIP3, 2010-2013 aimed to expand widely the knowledge of the epidemiology of European SIVs. ESNIP3 stimulated programs of harmonized SIV surveillance in European countries and supported the coordination of appropriate diagnostic tools and subtyping methods. Thus, an extensive virological monitoring, mainly conducted through passive surveillance programs, resulted in the examination of more than 9 000 herds in 17 countries. Influenza A viruses were detected in 31% of herds examined from which 1887 viruses were preliminary characterized. The dominating subtypes were the three European enzootic SIVs: avian-like swine H1N1 (53.6%, human-like reassortant swine H1N2 (13% and human-like reassortant swine H3N2 (9.1%, as well as pandemic A/H1N1 2009 (H1N1pdm virus (10.3%. Viruses from these four lineages co-circulated in several countries but with very different relative levels of incidence. For instance, the H3N2 subtype was not detected at all in some geographic areas whereas it was still prevalent in other parts of Europe. Interestingly, H3N2-free areas were those that exhibited highest frequencies of circulating H1N2 viruses. H1N1pdm viruses were isolated at an increasing incidence in some countries from 2010 to 2013, indicating that this subtype has become established in the European pig population. Finally, 13.9% of the viruses represented reassortants between these four lineages, especially between previous enzootic SIVs and H1N1pdm. These novel viruses were detected at the same time in several countries, with increasing prevalence. Some of them might become established in pig herds, causing implications for zoonotic infections.

  4. Surveillance programs in Denmark has revealed the circulation of novel reassortant influenza A viruses in swine

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    2014-01-01

    avH1N1 and H3N2 which is different from the dominating European H1N2 subtype (1). The prevalence of the H1N1pdm09 virus in swine has increased since 2009 in some countries including Denmark. Here we present the results of the national passive surveillance program on influenza in swine performed from...... by the combination of the gene segments hemagglutinin (HA) and neuraminidase (NA). In most European countries, the avian-like (av)H1N1, the 2009 pandemic variant (H1N1pdm09), H1N2 and H3N2 subtypes have constituted the dominating SIV subtypes during recent years. In Denmark, the H1N2 subtype is a reassortant between......Swine influenza is a respiratory disease caused by multiple subtypes of influenza A virus. Swine influenza virus (SIV) is enzootic in swine populations in Europe, Asia, North and South America. The influenza A virus genome consist of eight distinct gene segments and SIV subtypes are defined...

  5. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

    International Nuclear Information System (INIS)

    Kaur, Amitinder; Sanford, Hannah B.; Garry, Deirdre; Lang, Sabine; Klumpp, Sherry A.; Watanabe, Daisuke; Bronson, Roderick T.; Lifson, Jeffrey D.; Rosati, Margherita; Pavlakis, George N.; Felber, Barbara K.; Knipe, David M.; Desrosiers, Ronald C.

    2007-01-01

    The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS

  6. Intradermal immunization with inactivated swine influenza virus and adjuvant polydi(sodium carboxylatoethylphenoxy)phosphazene (PCEP) induced humoral and cell-mediated immunity and reduced lung viral titres in pigs.

    Science.gov (United States)

    Magiri, Royford; Lai, Ken; Chaffey, Alyssa; Zhou, Yan; Pyo, Hyun-Mi; Gerdts, Volker; Wilson, Heather L; Mutwiri, George

    2018-03-14

    Swine influenza virus is endemic worldwide and it is responsible for significant economic losses to the swine industry. A vaccine that stimulates a rapid and long-lasting protective immune response to prevent this infection is highly sought. Poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP) has demonstrated adjuvant activity when formulated as part of multiple vaccines in mice and pigs. In this study we examined the magnitude and type of immune response induced in pigs vaccinated via the intramuscular or intradermal routes with inactivated swine influenza virus (SIV) H1N1 vaccine formulated with PCEP. Intradermal administration of PCEP-adjuvanted inactivated SIV vaccine stimulated significant anti-SIV antibody titres, increased neutralizing antibodies, and significantly reduced lung virus load with limited reduction of gross lung lesions after challenge with virulent H1N1 relative to control animals. These results indicate that PCEP may be effective as a vaccine adjuvant against swine influenza viruses in pigs and should be considered a potential candidate adjuvant for future swine intradermal influenza vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Patellofemoral joint motion

    International Nuclear Information System (INIS)

    Stanford, W.; Phelan, J.; Albright, J.; Kathol, M.; Rooholamini, S.A.; El-Khoury, G.Y.; Palutsis, G.R.

    1988-01-01

    This paper describes the use of ultrafast computed tomography (CT) to obtain dynamic images of the patellofemoral joint during active motion. Thirty-eight patients underwent measurements of tangent offset, bisect offset, congruence angle, patellar tilt angle, lateral patellofemoral angle, sulcus angle, and sulcus depth made during leg movement. Selected parameters were compared with Merchant views. Significant correlations were obtained between Merchant views and comparable ultrafast CT views for all parameters except sulcus angle. Correlations between the other parameters were poor. Cine strips showed two patterns of movement; the patella remained centered either throughout excursion or until the last 20 0 of full extension, when it would sublux laterally

  8. Suppression of HIV replication by CD8+regulatory T-cells in elite controllers

    Directory of Open Access Journals (Sweden)

    Wei eLu

    2016-04-01

    Full Text Available We previously demonstrated in the Chinese macaque model that an oral vaccine made of inactivated SIV and lactobacillus plantarum induced CD8+regulatory T-cells which suppressed the activation of SIV+CD4+T-cells, prevented SIV replication and protected macaques from SIV challenges.Here ,we sought whether a similar population of CD8+T-regs would induce the suppression of HIV replication in elite controllers (ECs, a small population (3‰ of HIV-infected patients with undetectable HIV replication. For that purpose, we investigated the in vitro antiviral activity of fresh CD8+T-cells on HIV-infected CD4+T-cells taken from 10 ECs. The 10 ECs had a classical genomic profile: all of them carried the KIR3DL1 gene and nine carried at least one allele of HLA-B:Bw4-80Ile ( i.e. with an isoleucine residue at position 80. In the nine HLA-B:Bw4-80Ile positive patients, we demonstrated a strong viral suppression byKIR3DL1-expressing CD8+T-cells that required cell-to-cell contact to switch off the activation signals in infected CD4+T-cells. KIR3DL1-expressing CD8+T-cells withdrawal and KIR3DL1 neutralization by a specific anti-KIR antibody inhibited the suppression of viral replication. Our findings provide the first evidence for an instrumental role of KIR-expressing CD8+ regulatory T- cells in the natural control of HIV-1 infection.

  9. Enhanced degradation of organic contaminants in water by peroxydisulfate coupled with bisulfite

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Chengdu, E-mail: qichengdu@mail.tsinghua.edu.cn [State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875 (China); State Key Joint Laboratory of Environment Simulation and Pollution Control (SKLESPC), Beijing Key Laboratory for Emerging Organic Contaminants Control, School of Environment, Tsinghua University, Beijing 100084 (China); Liu, Xitao, E-mail: liuxt@bnu.edu.cn [State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875 (China); Li, Yang; Lin, Chunye; Ma, Jun; Li, Xiaowan; Zhang, Huijuan [State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875 (China)

    2017-04-15

    Highlights: • S(IV)/PDS system showed synergistic degradation of BPA than S(IV) and PDS. • BPA degradation involved hydroxyl and oxysulfur radicals in the S(IV)/PDS system. • Based on the identified intermediates, the BPA degradation pathway was proposed. - Abstract: In this study, the bisulfite-peroxydisulfate system (S(IV)/PDS) widely used in polymerization was innovatively applied for organic contaminants degradation in water. The addition of S(IV) into PDS system remarkably enhanced the degradation efficiency of bisphenol A (BPA, a frequently detected endocrine disrupting chemical in the environments) from 17.0% to 84.7% within 360 min. The degradation efficiency of BPA in the S(IV)/PDS system followed pseudo-first-order kinetics, with rate constant values ranging from 0.00005 min{sup −1} to 0.02717 min{sup −1} depending on the operating parameters, such as the initial S(IV) and PDS dosage, solution pH, reaction temperature, chloride and water type. Furthermore, nitrogen purging experiment, radical scavenging experiment and electron spin resonance (ESR) analysis were used to elucidate the possible mechanism. The results revealed that sulfate radical was the dominant reactive species in the S(IV)/PDS system. Finally, based on the results of liquid chromatography–mass spectrometry (LC–MS) and gas chromatography–mass spectrometry (GC–MS), the BPA degradation pathway was proposed to involve β-scission (C−C), hydroxylation, dehydration, oxidative skeletal rearrangement, and ring opening. This study helps to characterize the combination of PDS and inorganic S(IV), a common industrial contaminant, to generate reactive species to enhance organic contaminants degradation in water.

  10. Oxidation of sulfur (IV by oxygen in aqueous solution: role of some metal ions

    Directory of Open Access Journals (Sweden)

    Martins Claudia R.

    1999-01-01

    Full Text Available Catalytic effect of metal ions: Cr(VI, Cr(III, Cd(II, V(V and chloride anion, on the oxidation of S(IV in aqueous solution, at concentrations of metal ions and S(IV usually found in urban atmospheres, were studied under controlled experimental conditions (pH (2.1 - 4,5, T (25.0 - 35.0 °C, air flow rate, concentration of reactants, etc.... The kinetic constant determined at 25.0 °C and pH range (2.1 - 4.5, using ultra pure water was 8.0 ± 0.5 x 10-4 s-1. This value was considered as a reference for the oxidation reaction rate. The kinetic constants determined in the presence of Cr(VI revealed that the oxidation reaction of S(IV is quite influenced by the acidity. At pH = 2.1 (K = 2.3 x 10-2 mg-1 L s-1 the reaction is carried out with a rate five times greater when compared to pH = 2.6 (K = 4.3 x 10-3 mg-1 L s-1 and thirty times greater when compared to pH = 3.4 (K= 8.0 x 10 -4 mg-1 L s-1. The following rate expression was obtained at pH = 2.6: -r(S(IV =K [Cr(VI] [S(IV] and the activation energy found was: Ea =70.3KJ/mol. No catalytic effects were observed for Cd(II or chloride ion, while inhibitory effects were observed for Cr(III and V(V ions.

  11. Pathogenesis of swine influenza virus (Thai isolates in weanling pigs: an experimental trial

    Directory of Open Access Journals (Sweden)

    Kitikoon Pravina

    2009-03-01

    Full Text Available Abstract Background The objective of this study is to investigate the pathogenesis of swine influenza virus (SIV subtype H1N1 and H3N2 (Thai isolates in 22-day-old SPF pigs. Results The study found that all pigs in the infected groups developed typical signs of flu-like symptoms on 1–4 days post- infection (dpi. The H1N1-infected pigs had greater lung lesion scores than those of the H3N2-infected pigs. Histopathological lesions related to swine influenza-induced lesions consisting of epithelial cells damage, airway plugging and peribronchial and perivascular mononuclear cell infiltration were present in both infected groups. Immunofluorescence and immunohistochemistry using nucleoprotein specific monoclonal antibodies revealed positive staining cells in lung sections of both infected groups at 2 and 4 dpi. Virus shedding was detected at 2 dpi from both infected groups as demonstrated by RT-PCR and virus isolation. Conclusion The results demonstrated that both SIV subtypes were able to induce flu-like symptoms and lung lesions in weanling pigs. However the severity of the diseases with regards to lung lesions both gross and microscopic lesions was greater in the H1N1-infected pigs. Based on phylogenetic analysis, haemagglutinin gene of subtype H1N1 from Thailand clustered with the classical H1 SIV sequences and neuraminidase gene clustered with virus of avian origin, whereas, both genes of H3N2 subtype clustered with H3N2 human-like SIV from the 1970s.

  12. Cortico-cortical connections of areas 44 and 45B in the macaque monkey.

    Science.gov (United States)

    Frey, Stephen; Mackey, Scott; Petrides, Michael

    2014-04-01

    In the human brain, areas 44 and 45 constitute Broca's region, the ventrolateral frontal region critical for language production. The homologues of these areas in the macaque monkey brain have been established by direct cytoarchitectonic comparison with the human brain. The cortical areas that project monosynaptically to areas 44 and 45B in the macaque monkey brain require clarification. Fluorescent retrograde tracers were placed in cytoarchitectonic areas 44 and 45B of the macaque monkey, as well as in the anterior part of the inferior parietal lobule and the superior temporal gyrus. The results demonstrate that ipsilateral afferent connections of area 44 arise from local frontal areas, including rostral premotor cortical area 6, from secondary somatosensory cortex, the caudal insula, and the cingulate motor region. Area 44 is strongly linked with the anterior inferior parietal lobule (particularly area PFG and the adjacent anterior intraparietal sulcus). Input from the temporal lobe is limited to the fundus of the superior temporal sulcus extending caudal to the central sulcus. There is also input from the sulcal part of area Tpt in the upper bank of the superior temporal sulcus. Area 45B shares some of the connections of area 44, but can be distinguished from area 44 by input from the caudal inferior parietal lobule (area PG) and significant input from the part of the superior temporal sulcus that extends anterior to the central sulcus. Area 45B also receives input from visual association cortex that is not observed in area 44. The results have provided a clarification of the relative connections of areas 44 and 45B of the ventrolateral frontal region which, in the human brain, subserves certain aspects of language processing. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Short-Term Memory for Space and Time Flexibly Recruit Complementary Sensory-Biased Frontal Lobe Attention Networks.

    Science.gov (United States)

    Michalka, Samantha W; Kong, Lingqiang; Rosen, Maya L; Shinn-Cunningham, Barbara G; Somers, David C

    2015-08-19

    The frontal lobes control wide-ranging cognitive functions; however, functional subdivisions of human frontal cortex are only coarsely mapped. Here, functional magnetic resonance imaging reveals two distinct visual-biased attention regions in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis demonstrates that sPCS and iPCS fall within a broad visual-attention network, while tgPCS and cIFS fall within a broad auditory-attention network. Interestingly, we observe that spatial and temporal short-term memory (STM), respectively, recruit visual and auditory attention networks in the frontal lobe, independent of sensory modality. These findings not only demonstrate that both sensory modality and information domain influence frontal lobe functional organization, they also demonstrate that spatial processing co-localizes with visual processing and that temporal processing co-localizes with auditory processing in lateral frontal cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Short-term memory for space and time flexibly recruit complementary sensory-biased frontal lobe attention networks

    Science.gov (United States)

    Michalka, Samantha W.; Kong, Lingqiang; Rosen, Maya L.; Shinn-Cunningham, Barbara G.; Somers, David C.

    2015-01-01

    Summary The frontal lobes control wide-ranging cognitive functions; however, functional subdivisions of human frontal cortex are only coarsely mapped. Here, functional magnetic resonance imaging reveals two distinct visual-biased attention regions in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis demonstrates that sPCS and iPCS fall within a broad visual-attention network, while tgPCS and cIFS fall within a broad auditory-attention network. Interestingly, we observe that spatial and temporal short-term memory (STM), respectively, recruit visual and auditory attention networks in the frontal lobe, independent of sensory modality. These findings not only demonstrate that both sensory modality and information domain influence frontal lobe functional organization, they also demonstrate that spatial processing co-localizes with visual processing and that temporal processing co-localizes with auditory processing in lateral frontal cortex. PMID:26291168

  15. Multiplex RT-PCR assay for differentiating European swine influenza virus subtypes H1N1, H1N2 and H3N2.

    Science.gov (United States)

    Chiapponi, Chiara; Moreno, Ana; Barbieri, Ilaria; Merenda, Marianna; Foni, Emanuela

    2012-09-01

    In Europe, three major swine influenza viral (SIV) subtypes (H1N1, H1N2 and H3N2) have been isolated in pigs. Developing a test that is able to detect and identify the subtype of the circulating strain rapidly during an outbreak of respiratory disease in the pig population is of essential importance. This study describes two multiplex RT-PCRs which distinguish the haemagglutinin (HA) gene and the neuraminidase (NA) gene of the three major subtypes of SIV circulating in Europe. The HA PCR was able to identify the lineage (avian or human) of the HA of H1 subtypes. The analytical sensitivity of the test, considered to be unique, was assessed using three reference viruses. The detection limit corresponded to 1×10(-1) TCID(50)/200μl for avian-like H1N1, 1×10(0) TCID(50)/200μl for human-like H1N2 and 1×10(1) TCID(50)/200μl for H3N2 SIV. The multiplex RT-PCR was first carried out on a collection of 70 isolated viruses showing 100% specificity and then on clinical samples, from which viruses had previously been isolated, resulting in an 89% positive specificity of the viral subtype. Finally, the test was able to identify the viral subtype correctly in 56% of influenza A positive samples, from which SIV had not been isolated previously. It was also possible to identify mixed viral infections and the circulation of a reassortant strain before performing genomic studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses.

    Science.gov (United States)

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

    2014-09-24

    The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.

  17. Antiviral therapy during primary simian immunodeficiency virus infection fails to prevent acute loss of CD4+ T cells in gut mucosa but enhances their rapid restoration through central memory T cells.

    Science.gov (United States)

    Verhoeven, David; Sankaran, Sumathi; Silvey, Melanie; Dandekar, Satya

    2008-04-01

    Gut-associated lymphoid tissue (GALT) is an early target of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) and a site for severe CD4+ T-cell depletion. Although antiretroviral therapy (ART) is effective in suppressing HIV replication and restoring CD4+ T cells in peripheral blood, restoration in GALT is delayed. The role of restored CD4+ T-cell help in GALT during ART and its impact on antiviral CD8+ T-cell responses have not been investigated. Using the SIV model, we investigated gut CD4+ T-cell restoration in infected macaques, initiating ART during either the primary stage (1 week postinfection), prior to acute CD4+ cell loss (PSI), or during the chronic stage at 10 weeks postinfection (CSI). ART led to viral suppression in GALT and peripheral blood mononuclear cells of PSI and CSI animals at comparable levels. CSI animals had incomplete CD4+ T-cell restoration in GALT. In PSI animals, ART did not prevent acute CD4+ T-cell loss by 2 weeks postinfection in GALT but supported rapid and complete CD4+ T-cell restoration thereafter. This correlated with an accumulation of central memory CD4+ T cells and better suppression of inflammation. Restoration of CD4+ T cells in GALT correlated with qualitative changes in SIV gag-specific CD8+ T-cell responses, with a dominance of interleukin-2-producing responses in PSI animals, while both CSI macaques and untreated SIV-infected controls were dominated by gamma interferon responses. Thus, central memory CD4+ T-cell levels and qualitative antiviral CD8+ T-cell responses, independent of viral suppression, were the immune correlates of gut mucosal immune restoration during ART.

  18. Significant Depletion of CD4+ T Cells Occurs in the Oral Mucosa during Simian Immunodeficiency Virus Infection with the Infected CD4+ T Cell Reservoir Continuing to Persist in the Oral Mucosa during Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Jeffy George

    2015-01-01

    Full Text Available Human and simian immunodeficiency virus (HIV and SIV infections are characterized by manifestation of numerous opportunistic infections and inflammatory conditions in the oral mucosa. The loss of CD4+ T cells that play a critical role in maintaining mucosal immunity likely contributes to this process. Here we show that CD4+ T cells constitute a minor population of T cells in the oral mucosa and display a predominantly central memory phenotype mirroring other mucosal sites such as the rectal mucosa. Chronic SIV infection was associated with a near total depletion of CD4+ T cells in the oral mucosa that appear to repopulate during antiretroviral therapy (ART. Repopulating CD4+ T cells harbored a large fraction of Th17 cells suggesting that ART potentially reconstitutes oral mucosal immunity. However, a minor fraction of repopulating CD4+ T cells harbored SIV DNA suggesting that the viral reservoir continues to persist in the oral mucosa during ART. Therapeutic approaches aimed at obtaining sustainable CD4+ T cell repopulation in combination with strategies that can eradicate the latent viral reservoir in the oral mucosa are essential for better oral health and long-term outcome in HIV infected patients.

  19. Extractive Spectrophotometric Determination of Nortriptyline Hydrochloride Using Sudan II, IV and Black B

    Directory of Open Access Journals (Sweden)

    A. S. Amin

    2017-08-01

    formulations based on the formation of ion-pair complexes with sudun II (SII, sudan (IV (SIV and sudan black B (SBB. The selectivity of the method was improved through extraction with chloroform. The optimum conditions for complete extracted colour development were assessed. The absorbance measurements were made at 534, 596 and 649 nm for SII, SIV and SBB complexes, respectively. The calibration graph was linear in the ranges 0.5- 280. 0.5- 37.5 and 0.5 – 31.0 μg ml−1 of the drug usiny the same reagents, respectively. The precision of the procedure was checked by calculating the relative standard deviation of ten replicate determinations on 15 μg ml−1 of nortriptyline HCI and was found to be 1.7, 1.3 and 1.55% using SII, SIV, and SBB complexes, respectively. The molar absorptivity and Sandell sensitivity for each ion-pair were calculated. The proposed methods were successfully applied to the deterniination of pure nortriptyline HCI and in pharmaceutical formulations, and the results demonstrated that the method is equally accurate, precise and reproducible as the official method.

  20. Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses

    OpenAIRE

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

    2014-01-01

    Background The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. Findings The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decrease...

  1. All-Optical Nanoscale Thermometry using Silicon-Vacancy Centers in Diamond

    Science.gov (United States)

    Nguyen, Christian; Evans, Ruffin; Sipahigil, Alp; Bhaskar, Mihir; Sukachev, Denis; Lukin, Mikhail

    2017-04-01

    Accurate thermometry at the nanoscale is a difficult challenge, but building such a thermometer would be a powerful tool for discovering and understanding new processes in biology, chemistry and physics. Applications include cell-selective treatment of disease, engineering of more efficient integrated circuits, or even the development of new chemical and biological reactions. In this work, we study how the bulk properties of the Silicon Vacancy center (SiV) in diamond depend on temperature, and use them to measure temperature with 100mK accuracy. Using SiVs in 200 nm nanodiamonds, we measure the temperature with 100 nm spatial resolution over a 10 μm area.

  2. Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.

    Science.gov (United States)

    Byrareddy, Siddappa N; Kallam, Brianne; Arthos, James; Cicala, Claudia; Nawaz, Fatima; Hiatt, Joseph; Kersh, Ellen N; McNicholl, Janet M; Hanson, Debra; Reimann, Keith A; Brameier, Markus; Walter, Lutz; Rogers, Kenneth; Mayne, Ann E; Dunbar, Paul; Villinger, Tara; Little, Dawn; Parslow, Tristram G; Santangelo, Philip J; Villinger, Francois; Fauci, Anthony S; Ansari, Aftab A

    2014-12-01

    α4β7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.

  3. An aberrant vascular channel in the petrous bone: persistent lateral capital vein?

    International Nuclear Information System (INIS)

    Hermans, Robert; Rensburg, Leon J. van

    2009-01-01

    An aberrant channel was identified on CT in the petrous bone in four patients presenting with unrelated otological symptoms. These channels occurred unilaterally in each case. In two patients, the channel was seen to run between the sigmoid sinus sulcus and the superior petrosal sinus sulcus; in one of these patients, a vascular structure was identified within this channel on MRI, connecting the sigmoid sinus and the superior petrosal sinus. In the two other patients, an aberrant channel was seen between the superior petrosal sinus sulcus and the posterior genu of the facial nerve canal. There were no symptoms that could be attributed to the presence of these channels. We postulate that these aberrant vascular channels correspond to a persistent embryological vein, the lateral capital vein. (orig.)

  4. An aberrant vascular channel in the petrous bone: persistent lateral capital vein?

    Energy Technology Data Exchange (ETDEWEB)

    Hermans, Robert [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Rensburg, Leon J. van [University of the Western Cape, Department of Radiology and Diagnostics, Tygerberg (South Africa)

    2009-12-15

    An aberrant channel was identified on CT in the petrous bone in four patients presenting with unrelated otological symptoms. These channels occurred unilaterally in each case. In two patients, the channel was seen to run between the sigmoid sinus sulcus and the superior petrosal sinus sulcus; in one of these patients, a vascular structure was identified within this channel on MRI, connecting the sigmoid sinus and the superior petrosal sinus. In the two other patients, an aberrant channel was seen between the superior petrosal sinus sulcus and the posterior genu of the facial nerve canal. There were no symptoms that could be attributed to the presence of these channels. We postulate that these aberrant vascular channels correspond to a persistent embryological vein, the lateral capital vein. (orig.)

  5. Neural correlates of the numerical distance effect in children

    Directory of Open Access Journals (Sweden)

    Christophe eMussolin

    2013-10-01

    Full Text Available In number comparison tasks, the performance is better when the distance between the two numbers to compare increases. During development this so-called numerical distance effect decreases with age and the neuroanatomical correlates of these age-related changes are poorly known. Using functional magnetic resonance imaging, we recorded the brain activity changes in children aged from 8 to 14 years while they performed a number comparison task on pairs of Arabic digits and a control colour comparison task on non-numerical symbols. On the one hand, we observed developmental changes in the recruitment of frontal regions and the left intraparietal sulcus, with lower activation as the age increased. On the other hand, we found that a behavioural index of selective sensitivity to the numerical distance effect was positively correlated with higher brain activity in a right lateralized occipito-temporo-parietal network including the intraparietal sulcus. This leads us to propose that the left intraparietal sulcus would be engaged in the refinement of cognitive processes involved in number comparison during development, while the right intraparietal sulcus would underlie the semantic representation of numbers and its activation would be mainly affected by the numerical proximity between them.

  6. Maksulepingute rakendamise aktuaalprobleeme ettevõtete maksustamisel : [bakalaureusetöö] / Lada Smirnova ; Tartu Ülikool, õigusteaduskond ; juhendaja: Lasse Lehis

    Index Scriptorium Estoniae

    Smirnova, Lada

    2006-01-01

    Rahvusvahelise maksuõiguse alused, topeltmaksustamise avaldumisvormid, rahvusvahelised tulumaksu puudutavad lepingud, ettevõte kui maksustamise subjekt, püsiv tegevuskoht, ärikasum, assotsieerunud ettevõtted

  7. Surgery of the eloquent area using neuronavigation system

    International Nuclear Information System (INIS)

    Nakai, Hirofumi; Tanaka, Tatsuya; Hashizume, Kiyotaka; Hodozuka, Akira; Ono, Hidetoshi; Goto, Takumi; Aburano, Tamio

    2001-01-01

    The purpose of this minimally invasive study was to evaluate the efficacy of a neuronavigation system for surgery of lesions near Broca's area, skull base, or paracentral sulcus. With regards to paracentral sulcus lesions, precise localization of the precentral gyrus was evaluated not only with preoperative 3D images of the brain but also confirmed by the combination of fMRI and intraoperative SEP. Using the neuronavigation system, Viewing Wand (ISG Technologies), three-dimensional (3D) brain images were reconstructed by plotting cerebral sulcus and skull representations obtained by MRI and CT. Six patients with lesions near Broca's area, 5 patients with skull base lesions, and 9 patients with lesions near the central sulcus were analyzed. For paracentral sulcus lesions, patients underwent blood oxygen level-dependent fMRI while performing a finger-tapping motor paradigm, which was composed of repetition of rest-task every in 30 seconds for 150 seconds, in a 1.5-tesla echo-speed MR imager (Signa Horizon; General Electric Medical Systems, Milwaukee, WI). Statistical cross-correlation functional maps were generated and overlaid onto high-resolution anatomical MR images. Presurgical assessment of 3D reconstructed brain images were performed in all cases. They were analyzed in Broca's lesions, skull base lesions and paracentral sulcus lesions and were demonstrated to be useful for understanding the anatomical relationship between the lesions and the surrounding vital structures. In fMRI, motor activation sites were obtained on both ipsilateral and contralateral hemispheres in all patients except for one patient with a hemorrhagic cyst. Locations of precentral gyri were predicted preoperatively. In all patients except for one case, fMRI was obtained even in tumor patient in whom intraoperative SEP was technically not feasible due to severe cortical brain damage from the paracentral tumor. The precentral gyri identified by 3D reconstructed brain images coincided well

  8. Reassortant swine influenza viruses isolated in Japan contain genes from pandemic A(H1N1) 2009.

    Science.gov (United States)

    Kanehira, Katsushi; Takemae, Nobuhiro; Uchida, Yuko; Hikono, Hirokazu; Saito, Takehiko

    2014-06-01

    In 2013, three reassortant swine influenza viruses (SIVs)-two H1N2 and one H3N2-were isolated from symptomatic pigs in Japan; each contained genes from the pandemic A(H1N1) 2009 virus and endemic SIVs. Phylogenetic analysis revealed that the two H1N2 viruses, A/swine/Gunma/1/2013 and A/swine/Ibaraki/1/2013, were reassortants that contain genes from the following three distinct lineages: (i) H1 and nucleoprotein (NP) genes derived from a classical swine H1 HA lineage uniquely circulating among Japanese SIVs; (ii) neuraminidase (NA) genes from human-like H1N2 swine viruses; and (iii) other genes from pandemic A(H1N1) 2009 viruses. The H3N2 virus, A/swine/Miyazaki/2/2013, comprised genes from two sources: (i) hemagglutinin (HA) and NA genes derived from human and human-like H3N2 swine viruses and (ii) other genes from pandemic A(H1N1) 2009 viruses. Phylogenetic analysis also indicated that each of the reassortants may have arisen independently in Japanese pigs. A/swine/Miyazaki/2/2013 were found to have strong antigenic reactivities with antisera generated for some seasonal human-lineage viruses isolated during or before 2003, whereas A/swine/Miyazaki/2/2013 reactivities with antisera against viruses isolated after 2004 were clearly weaker. In addition, antisera against some strains of seasonal human-lineage H1 viruses did not react with either A/swine/Gunma/1/2013 or A/swine/Ibaraki/1/2013. These findings indicate that emergence and spread of these reassortant SIVs is a potential public health risk. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  9. Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

    Science.gov (United States)

    Venkataswamy, Manjunatha M; Ng, Tony W; Kharkwal, Shalu S; Carreño, Leandro J; Johnson, Alison J; Kunnath-Velayudhan, Shajo; Liu, Zheng; Bittman, Robert; Jervis, Peter J; Cox, Liam R; Besra, Gurdyal S; Wen, Xiangshu; Yuan, Weiming; Tsuji, Moriya; Li, Xiangming; Ho, David D; Chan, John; Lee, Sunhee; Frothingham, Richard; Haynes, Barton F; Panas, Michael W; Gillard, Geoffrey O; Sixsmith, Jaimie D; Korioth-Schmitz, Birgit; Schmitz, Joern E; Larsen, Michelle H; Jacobs, William R; Porcelli, Steven A

    2014-01-01

    Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC) into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

  10. Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

    Directory of Open Access Journals (Sweden)

    Manjunatha M Venkataswamy

    Full Text Available Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag. We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

  11. Self-induced vomiting and dental erosion--a clinical study.

    Science.gov (United States)

    Uhlen, Marte-Mari; Tveit, Anne Bjørg; Stenhagen, Kjersti Refsholt; Mulic, Aida

    2014-07-29

    In individuals suffering from eating disorders (ED) characterized by vomiting (e.g. bulimia nervosa), the gastric juice regularly reaches the oral cavity, causing a possible risk of dental erosion. This study aimed to assess the occurrence, distribution and severity of dental erosions in a group of Norwegian patients experiencing self-induced vomiting (SIV). The individuals included in the study were all undergoing treatment at clinics for eating disorders and were referred to a university dental clinic for examinations. One calibrated clinician registered erosions using the Visual Erosion Dental Examination (VEDE) system. Of 72 referred patients, 66 (63 females and three males, mean age 27.7 years) were or had been experiencing SIV (mean duration 10.6 years; range: 3 - 32 years), and were therefore included in the study. Dental erosions were found in 46 individuals (69.7%), 19 had enamel lesions only, while 27 had both enamel and dentine lesions. Ten or more teeth were affected in 26.1% of those with erosions, and 9% had ≥10 teeth with dentine lesions. Of the erosions, 41.6% were found on palatal/lingual surfaces, 36.6% on occlusal surfaces and 21.8% on buccal surfaces. Dentine lesions were most often found on lower first molars, while upper central incisors showed enamel lesions most frequently. The majority of the erosive lesions (48.6%) were found in those with the longest illness period, and 71.7% of the lesions extending into dentine were also found in this group. However, despite suffering from SIV for up to 32 years, 30.3% of the individuals showed no lesions. Dental erosion commonly affects individuals with ED experiencing SIV, and is more often found on the palatal/lingual surfaces than on the buccal in these individuals, confirming a common clinical assumption.

  12. School-Based Influenza Vaccination: Health and Economic Impact of Maine's 2009 Influenza Vaccination Program.

    Science.gov (United States)

    Basurto-Dávila, Ricardo; Meltzer, Martin I; Mills, Dora A; Beeler Asay, Garrett R; Cho, Bo-Hyun; Graitcer, Samuel B; Dube, Nancy L; Thompson, Mark G; Patel, Suchita A; Peasah, Samuel K; Ferdinands, Jill M; Gargiullo, Paul; Messonnier, Mark; Shay, David K

    2017-12-01

    To estimate the societal economic and health impacts of Maine's school-based influenza vaccination (SIV) program during the 2009 A(H1N1) influenza pandemic. Primary and secondary data covering the 2008-09 and 2009-10 influenza seasons. We estimated weekly monovalent influenza vaccine uptake in Maine and 15 other states, using difference-in-difference-in-differences analysis to assess the program's impact on immunization among six age groups. We also developed a health and economic Markov microsimulation model and conducted Monte Carlo sensitivity analysis. We used national survey data to estimate the impact of the SIV program on vaccine coverage. We used primary data and published studies to develop the microsimulation model. The program was associated with higher immunization among children and lower immunization among adults aged 18-49 years and 65 and older. The program prevented 4,600 influenza infections and generated $4.9 million in net economic benefits. Cost savings from lower adult vaccination accounted for 54 percent of the economic gain. Economic benefits were positive in 98 percent of Monte Carlo simulations. SIV may be a cost-beneficial approach to increase immunization during pandemics, but programs should be designed to prevent lower immunization among nontargeted groups. © Health Research and Educational Trust.

  13. Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine

    Science.gov (United States)

    Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R.; Robinson, Harriet L.

    2012-01-01

    Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection. PMID:23111169

  14. Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.

    Science.gov (United States)

    Hu, Guiqing; Liu, Jun; Roux, Kenneth H; Taylor, Kenneth A

    2017-08-15

    The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. IMPORTANCE Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were "decorated" with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the

  15. Sulcal pattern, extension, and morphology of the precuneus in adult humans.

    Science.gov (United States)

    Pereira-Pedro, Ana Sofia; Bruner, Emiliano

    2016-11-01

    The precuneus represents a relevant cortical component of the parietal lobes. It is involved in visuospatial integration, imagery and simulation, self-awareness, and it is a main node of the Default Mode Network. Its morphology is extremely variable among adult humans, and it has been hypothesized to have undergone major morphological changes in the evolution of Homo sapiens. Recent studies have evidenced a marked variation also associated with its sulcal patterns. The present survey contributes to add further information on this topic, investigating the extension of its main folds, their geometrical influence on the lateral parietal areas, and the relationships with the sulcal schemes. The subparietal sulcus, on average, extends 14mm in its anterior and middle regions and 11mm in its posterior area. The precuneal area extends 36mm above this sulcus. The subparietal sulcus is generally wider on the right hemisphere. Males have larger values than females, but differences are not significant. Sulcal pattern is not correlated with the size of the subparietal sulcus extension. There is a lack of consistent correspondence between hemispheres in the sulcal patterns, pointing further towards a notable individual variability and random asymmetries. The vertical extension of the precuneus influences the height and proportions of the upper parietal profile, but the lateral parietal outline is not sensitive to precuneal variation. There is no correlation between external cortical shape and the size of the subparietal sulcus. Morphological analyses of the precuneus must be integrated with studies on histological factors involved in its variability and, ultimately, with analyses on possible relationships with functional factors. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. Neural correlates of visually induced self-motion illusion in depth.

    Science.gov (United States)

    Kovács, Gyula; Raabe, Markus; Greenlee, Mark W

    2008-08-01

    Optic-flow fields can induce the conscious illusion of self-motion in a stationary observer. Here we used functional magnetic resonance imaging to reveal the differential processing of self- and object-motion in the human brain. Subjects were presented a constantly expanding optic-flow stimulus, composed of disparate red-blue dots, viewed through red-blue glasses to generate a vivid percept of three-dimensional motion. We compared the activity obtained during periods of illusory self-motion with periods of object-motion percept. We found that the right MT+, precuneus, as well as areas located bilaterally along the dorsal part of the intraparietal sulcus and along the left posterior intraparietal sulcus were more active during self-motion perception than during object-motion. Additional signal increases were located in the depth of the left superior frontal sulcus, over the ventral part of the left anterior cingulate, in the depth of the right central sulcus and in the caudate nucleus/putamen. We found no significant deactivations associated with self-motion perception. Our results suggest that the illusory percept of self-motion is correlated with the activation of a network of areas, ranging from motion-specific areas to regions involved in visuo-vestibular integration, visual imagery, decision making, and introspection.

  17. [Surgical treatment of gliomas involving the supplementary motor area in the superior frontal gyrus].

    Science.gov (United States)

    Liu, Wei; Lai, Jian-jun; Qu, Yuan-ming

    2004-07-07

    To explore surgical treatment of gliomas involving the supplementary motor area (SMA) in the superior frontal gyrus. Clinical data and follow-up outcome of 16 patients with low graded astrocytomas involving the supplementary motor area were analyzed. SMA syndrome was developed in 6 patients in whom the posterior tumor resection line was at a distance of more than 1 cm from the precentral sulcus and resolved after 12 months. Hemiplegia occurred however in 8 patients in whom the resection line was less than 1 cm to precentral sulcus and only resolved in 3 patients during follow period 12 months. When the resection is performed at a distance of less than 1 cm from the precentral sulcus, surgery for gliomas of involving the supplementary motor area in the superior frontal gyrus may be result in permanent morbidity.

  18. Soft-tissue cephalometric norms for the Lambada population in Telangana Region of Andhra Pradesh

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    Mayuri Thomas

    2012-01-01

    Conclusion: Although established Caucasian norms are applicable to the Lambada ethnic tribe, few parameters like basic upper lip thickness (ULT and upper lip strain (ULS, skeletal convexity, inferior sulcus to H line (LS-H were significantly different. The male group exhibited straighter profile, thicker lips, prominent nose, deep mentolabial sulcus, and a prominent chin than females. The differences could be considered in diagnosis and treatment planning for orthodontic practice and for orthognathic surgery.

  19. Surgery of the eloquent area using neuronavigation system

    Energy Technology Data Exchange (ETDEWEB)

    Nakai, Hirofumi; Tanaka, Tatsuya; Hashizume, Kiyotaka; Hodozuka, Akira; Ono, Hidetoshi; Goto, Takumi; Aburano, Tamio [Asahikawa Medical Coll., Hokkaido (Japan)

    2001-03-01

    The purpose of this minimally invasive study was to evaluate the efficacy of a neuronavigation system for surgery of lesions near Broca's area, skull base, or paracentral sulcus. With regards to paracentral sulcus lesions, precise localization of the precentral gyrus was evaluated not only with preoperative 3D images of the brain but also confirmed by the combination of fMRI and intraoperative SEP. Using the neuronavigation system, Viewing Wand (ISG Technologies), three-dimensional (3D) brain images were reconstructed by plotting cerebral sulcus and skull representations obtained by MRI and CT. Six patients with lesions near Broca's area, 5 patients with skull base lesions, and 9 patients with lesions near the central sulcus were analyzed. For paracentral sulcus lesions, patients underwent blood oxygen level-dependent fMRI while performing a finger-tapping motor paradigm, which was composed of repetition of rest-task every in 30 seconds for 150 seconds, in a 1.5-tesla echo-speed MR imager (Signa Horizon; General Electric Medical Systems, Milwaukee, WI). Statistical cross-correlation functional maps were generated and overlaid onto high-resolution anatomical MR images. Presurgical assessment of 3D reconstructed brain images were performed in all cases. They were analyzed in Broca's lesions, skull base lesions and paracentral sulcus lesions and were demonstrated to be useful for understanding the anatomical relationship between the lesions and the surrounding vital structures. In fMRI, motor activation sites were obtained on both ipsilateral and contralateral hemispheres in all patients except for one patient with a hemorrhagic cyst. Locations of precentral gyri were predicted preoperatively. In all patients except for one case, fMRI was obtained even in tumor patient in whom intraoperative SEP was technically not feasible due to severe cortical brain damage from the paracentral tumor. The precentral gyri identified by 3D reconstructed brain images

  20. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

    Directory of Open Access Journals (Sweden)

    Osterhaus Albert DME

    2004-11-01

    Full Text Available Abstract A pol-fragment of simian immunodeficiency virus (SIV that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus was detected in two mandrills (Mandrillus sphinx from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Their mitochondrial haplotype suggested that they descended from founder animals in Cameroon or northern Gabon, close to the habitat of the drill. SIVdrl has once before been found in a wild-caught mandrill from the same region, indicating that mandrills are naturally infected with a SIVdrl-like virus. This suggests that mandrills are the first primate species to be infected with three strains of SIV: SIVmnd1, SIVmnd2, and SIVdrl.

  1. Connections of the medial posterior parietal cortex (area 7m) in the monkey.

    Science.gov (United States)

    Leichnetz, G R

    2001-06-01

    The afferent and efferent cortical and subcortical connections of the medial posterior parietal cortex (area 7m) were studied in cebus (Cebus apella) and macaque (Macaca fascicularis) monkeys using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique. The principal intraparietal corticocortical connections of area 7m in both cebus and macaque cases were with the ipsilateral medial bank of the intraparietal sulcus (MIP) and adjacent superior parietal lobule (area 5), inferior parietal lobule (area 7a), lateral bank of the IPS (area 7ip), caudal parietal operculum (PGop), dorsal bank of the caudal superior temporal sulcus (visual area MST), and medial prestriate cortex (including visual area PO and caudal medial lobule). Its principal frontal corticocortical connections were with the prefrontal cortex in the shoulder above the principal sulcus and the cortex in the shoulder above the superior ramus of the arcuate sulcus (SAS), the area purported to contain the smooth eye movement-related frontal eye field (FEFsem) in the cebus monkey by other investigators. There were moderate connections with the cortex in the rostral bank of the arcuate sulcus (purported to contain the saccade-related frontal eye field; FEFsac), supplementary eye field (SEF), and rostral dorsal premotor area (PMDr). Area 7m also had major connections with the cingulate cortex (area 23), particularly the ventral bank of the cingulate sulcus. The principal subcortical connections of area 7m were with the dorsal portion of the ventrolateral thalamic (VLc) nucleus, lateral posterior thalamic nucleus, lateral pulvinar, caudal mediodorsal thalamic nucleus and medial pulvinar, central lateral, central superior lateral, and central inferior intralaminar thalamic nuclei, dorsolateral caudate nucleus and putamen, middle region of the claustrum, nucleus of the diagonal band, zona incerta, pregeniculate nucleus, anterior and posterior pretectal nuclei, intermediate layer of

  2. Radiologic study of patellofemoral congruence in normal adults

    International Nuclear Information System (INIS)

    Diedrichs, L.C.

    1986-01-01

    In order to establish the normal position of the patella, in relation to the intercondilar sulcus, we have evaluated 72 adults patients, making use of the FICAT view in axial radiographys at 30 0 : a simple and accurate technique adopted to measure the congrunce angle in the detection of sub-luxation of the patella. The value of +9 0 was used as the normal pattern for the maximal lateral position of the patella in the intercondilar sulcus. (Author) [pt

  3. Neural correlates of successful and unsuccessful syntactic processing in primary progressive aphasia

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    Stephen M Wilson

    2015-04-01

    Our findings suggest that some of the regions modulated by a syntactic processing task reflect task-related functions such as working memory, attention, and executive function, specifically the anterior insula bilaterally, the supplementary motor cortex bilaterally, and left dorsal premotor cortex. In contrast, other regions were modulated only in individuals with relatively intact syntactic processing, namely the left inferior frontal junction, left posterior superior temporal sulcus, and left intraparietal sulcus, suggesting that these regions are important for syntactic processing.

  4. Sulcal and gyral anatomy of the basal occipital-temporal lobe.

    Science.gov (United States)

    Chau, Anthony Minh Tien; Stewart, Fiona; Gragnaniello, Cristian

    2014-12-01

    The sulcal and gyral anatomy of the basal occipital-temporal lobe is highly variable and detailed descriptions of this region are limited and often inconsistent. The aim of this study was to describe the salient features of the sulcal and gyral anatomy of the basal occipital-temporal lobe. We studied the sulcal and gyral patterns of 30 formalin-fixed cerebral hemispheres. The major landmarks are the collateral sulcus (separated into the rhinal, proper, and caudal segments) and occipitotemporal sulcus (often interrupted), which were always present in this study. The bifurcation of the caudal collateral sulcus is a useful landmark. In relation to these sulci, we have described the surface anatomy and nominated landmarks of the medial (parahippocampal and lingual) and lateral (fusiform) occipitotemporal gyri. Understanding of the sulcal and gyral patterns of the basal occipital-temporal lobe may provide valuable information in its radiological and intraoperative interpretation.

  5. Detection of cortical activities on eye movement using functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Yoshida, Masaki; Kawai, Kazushige; Kitahara, Kenji; Soulie, D.; Cordoliani, Y.S.; Iba-Zizen, M.T.; Cabanis, E.A.

    1997-01-01

    Cortical activity during eye movement was examined with functional magnetic resonance imaging. Horizontal saccadic eye movements and smooth pursuit eye movements were elicited in normal subjects. Activity in the frontal eye field was found during both saccadic and smooth pursuit eye movements at the posterior margin of the middle frontal gyrus and in parts of the precentral sulcus and precentral gyrus bordering the middle frontal gyrus (Brodmann's areas 8, 6, and 9). In addition, activity in the parietal eye field was found in the deep, upper margin of the angular gyrus and of the supramarginal gyrus (Brodmann's areas 39 and 40) during saccadic eye movement. Activity of V5 was found at the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus during smooth pursuit eye movement. Our results suggest that functional magnetic resonance imaging is useful for detecting cortical activity during eye movement. (author)

  6. High risk human papillomavirus in the periodontium : A case control study

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    Anna Shipilova

    2017-01-01

    Full Text Available Background: Human papilloma viruses (HPVs are small DNA viruses that have been identified in periodontal pocket as well as gingival sulcus. High risk HPVs are also associated with a subset of head and neck carcinomas. It is thought that the periodontium could be a reservoir for HPV. Aims: 1. Detection of Human Papilloma virus (HPV in periodontal pocket as well as gingival of patients having localized chronic periodontitis and gingival sulcus of periodontally healthy subjects. 2. Quantitative estimation of E6 and E7 mRNA in subjects showing presence of HPV3. To assess whether periodontal pocket is a reservoir for HPV. Settings and Design: This case-control study included 30 subjects with localized chronic Periodontitis (cases and 30 periodontally healthy subjects (controls. Two samples were taken from cases, one from periodontal pocket and one from gingival sulcus and one sample was taken from controls. Methods and Materials: Samples were collected in the form of pocket scrapings and gingival sulcus scrapings from cases and controls respectively. These samples were sent in storage media for identification and estimation of E6/E7 mRNA of HPV using in situ hybridization and flow cytometry. Statistical analysis: Statistical analysis was done by using, mean, percentage and Chi Square test. A statistical package SPSS version 13.0 was used to analyze the data. P value < 0.05 was considered as statistically significant. Results: pocket samples as well as sulcus samples for both cases and controls were found to contain HPV E6/E7 mRNAInterpretation and Conclusion: Presence of HPV E6/E7 mRNA in periodontium supports the hypothesis that periodontal tissues serve as a reservoir for latent HPV and there may be a synergy between oral cancer, periodontitis and HPV. However prospective studies are required to further explore this link.

  7. High risk human papillomavirus in the periodontium : A case control study.

    Science.gov (United States)

    Shipilova, Anna; Dayakar, Manjunath Mundoor; Gupta, Dinesh

    2017-01-01

    Human papilloma viruses (HPVs) are small DNA viruses that have been identified in periodontal pocket as well as gingival sulcus. High risk HPVs are also associated with a subset of head and neck carcinomas. It is thought that the periodontium could be a reservoir for HPV. 1. Detection of Human Papilloma virus (HPV) in periodontal pocket as well as gingival of patients having localized chronic periodontitis and gingival sulcus of periodontally healthy subjects. 2. Quantitative estimation of E6 and E7 mRNA in subjects showing presence of HPV3. To assess whether periodontal pocket is a reservoir for HPV. This case-control study included 30 subjects with localized chronic Periodontitis (cases) and 30 periodontally healthy subjects (controls). Two samples were taken from cases, one from periodontal pocket and one from gingival sulcus and one sample was taken from controls. Samples were collected in the form of pocket scrapings and gingival sulcus scrapings from cases and controls respectively. These samples were sent in storage media for identification and estimation of E6/E7 mRNA of HPV using in situ hybridization and flow cytometry. Statistical analysis was done by using, mean, percentage and Chi Square test. A statistical package SPSS version 13.0 was used to analyze the data. P value oral cancer, periodontitis and HPV. However prospective studies are required to further explore this link.

  8. Pigment dispersion glaucoma induced by the chafing effect of intraocular lens haptics in Asian eyes.

    Science.gov (United States)

    Hong, Ying; Sun, Yan-Xiu; Qi, Hong; Zhou, Ji-Chao; Hao, Yan-Sheng

    2013-03-01

    To study the possible mechanism and treatment for pigment dispersion glaucoma (PDG) caused by single-piece acrylic (SPA) intraocular lens (IOL) ciliary sulcus fixation in Asian eyes. Patients referred for PDG caused by SPA IOL ciliary sulcus fixation to our hospital from April 2005 to June 2011 were included. The patients' general information, IOL type, interval between initial surgery and PDG occurrence, examination findings, antiglaucoma medicine regimen and surgical interventions were recorded. In total, six eyes from five Chinese patients were included in this study. The intraocular pressure (IOP) increased 19-30 days after cataract surgery and was not satisfactorily controlled with antiglaucoma medication. Dense pigmentation was deposited on the IOLs and on the anterior chamber angle. IOL haptic chafing was noted on the rear iris surface. IOL repositioning in the capsular bag was performed in three eyes and was combined with trabeculectomy in two eyes with progressive glaucoma. An IOL exchange with three-piece IOL ciliary sulcus fixation was performed in the other three eyes. Scanning electron microscopy of the explanted IOLs demonstrated a rough edge on the IOL haptics. SPA IOLs were not suitable for ciliary sulcus fixation. The chafing effect of the IOL haptics on the posterior iris pigment epithelium could induce PDG in Asian eyes. IOLs should be positioned in the capsular bag or a three-piece IOL should be used instead.

  9. Periodontal Wound Healing Responses to Varying Oxygen Concentrations and Atmospheric Pressures.

    Science.gov (United States)

    1986-05-01

    DEFECT TO CEMENTO -ENAMEL JUNCTION 4. BD-CCT, BASE OF DEFECT TO MOST CORONAL CONNECTIVE TISSUE 5. SB-GM, SULCUS BASE TO GINGIVAL MARGIN 6. CCT-SB, MOST...connective tissue to alveolar bone* BD-GM, base of defect to gingival margin* BD-SB, base of defect to sulcus base* BD-CEJ, base of defect to cemento ... Cemento ,-namel Junction CcT - Most Coronal Connective Tissue Units = 20 microns AB - Alveolar Bcne -- -b! ,* S - 59 GROUP B DALY 1 RIGHT SIDE LMF

  10. Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

    Directory of Open Access Journals (Sweden)

    Song Chen

    Full Text Available BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs infected with simian immunodeficiency virus (SIV have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group challenged with intrarectal (i.r. SIVmac239, intravenous (i.v. SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68. The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v. than in those infected with SIVmac251 (i.v., allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

  11. Phenotypic and Functional Characterization of Monoclonal Antibodies with Specificity for Rhesus Macaque CD200, CD200R and Mincle.

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    Siddappa N Byrareddy

    Full Text Available Lectin-like molecules and their receptors are cell surface molecules that have been shown to play a role in either facilitating infection or serving as transporters of HIV/SIV in vivo. The role of these lectin-like molecules in the pathogenesis of HIV/SIV infection continues to be defined. In efforts to gain further insight on the potential role of these lectin-like molecules, our laboratory generated monoclonal antibodies (mAb against the human analogs of rhesus macaque CD200, CD200R and Mincle, since the rhesus macaques are accepted as the most reliable animal model to study human HIV infection. The characterization of the cell lineages from the blood and various tissues of rhesus macaques that express these lectin-like molecules are described herein. Among the mononuclear cells, the cells of the myeloid lineage of rhesus macaques are the predominant cell lineages that express readily detectable levels of CD200, CD200R and Mincle that is similar to the expression of Siglec-1 and Siglec-3 reported by our laboratory earlier. Subset analysis revealed that a higher frequency of the CD14+/CD16- subset from normal rhesus macaques express CD200, CD200R and Mincle. Differences in the frequencies and density of expression of these molecules by the gated population of CD14+ cells from various tissues are noted with PBMC and bone marrow expressing the highest and the mononuclear cells isolated from the colon and ileum expressing the lowest levels. While a significant frequency of pDCs and mDCs express Siglec-1/Siglec-3, a much lower frequency expresses CD200, CD200R and Mincle in PBMCs from rhesus macaques. The mAb against CD200 and CD200R but not Mincle appear to inhibit the infection of macrophage tropic SIV/SHIV in vitro. We conclude that these mAbs may have potential to be used as adjunctive therapeutic agents to control/inhibit SIV/HIV infection.

  12. Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides.

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    Jamie L Schafer

    2015-09-01

    Full Text Available Natural killer (NK cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs on NK cells and their major histocompatibility complex (MHC class I ligands on target cells. We previously reported that the binding of a common MHC class I molecule in the rhesus macaque, Mamu-A1*002, to the inhibitory receptor Mamu-KIR3DL05 is stabilized by certain simian immunodeficiency virus (SIV peptides, but not by others. Here we investigated the functional implications of these interactions by testing SIV peptides bound by Mamu-A1*002 for the ability to modulate Mamu-KIR3DL05+ NK cell responses. Twenty-eight of 75 SIV peptides bound by Mamu-A1*002 suppressed the cytolytic activity of primary Mamu-KIR3DL05+ NK cells, including three immunodominant CD8+ T cell epitopes previously shown to stabilize Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. Substitutions at C-terminal positions changed inhibitory peptides into disinhibitory peptides, and vice versa, without altering binding to Mamu-A1*002. The functional effects of these peptide variants on NK cell responses also corresponded to their effects on Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. In assays with mixtures of inhibitory and disinhibitory peptides, low concentrations of inhibitory peptides dominated to suppress NK cell responses. Consistent with the inhibition of Mamu-KIR3DL05+ NK cells by viral epitopes presented by Mamu-A1*002, SIV replication was significantly higher in Mamu-A1*002+ CD4+ lymphocytes co-cultured with Mamu-KIR3DL05+ NK cells than with Mamu-KIR3DL05- NK cells. These results demonstrate that viral peptides can differentially affect NK cell responses by modulating MHC class I interactions with inhibitory KIRs, and provide a mechanism by which immunodeficiency viruses may evade NK cell responses.

  13. Detection of cortical activities on eye movement using functional magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Masaki; Kawai, Kazushige; Kitahara, Kenji [Jikei Univ., Tokyo (Japan). School of Medicine; Soulie, D.; Cordoliani, Y.S.; Iba-Zizen, M.T.; Cabanis, E.A.

    1997-11-01

    Cortical activity during eye movement was examined with functional magnetic resonance imaging. Horizontal saccadic eye movements and smooth pursuit eye movements were elicited in normal subjects. Activity in the frontal eye field was found during both saccadic and smooth pursuit eye movements at the posterior margin of the middle frontal gyrus and in parts of the precentral sulcus and precentral gyrus bordering the middle frontal gyrus (Brodmann`s areas 8, 6, and 9). In addition, activity in the parietal eye field was found in the deep, upper margin of the angular gyrus and of the supramarginal gyrus (Brodmann`s areas 39 and 40) during saccadic eye movement. Activity of V5 was found at the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus during smooth pursuit eye movement. Our results suggest that functional magnetic resonance imaging is useful for detecting cortical activity during eye movement. (author)

  14. Insights into the Impact of CD8+ Immune Modulation on Human Immunodeficiency Virus Evolutionary Dynamics in Distinct Anatomical Compartments by Using Simian Immunodeficiency Virus-Infected Macaque Models of AIDS Progression.

    Science.gov (United States)

    Rife Magalis, Brittany; Nolan, David J; Autissier, Patrick; Burdo, Tricia H; Williams, Kenneth C; Salemi, Marco

    2017-12-01

    A thorough understanding of the role of human immunodeficiency virus (HIV) intrahost evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8 + lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to clinical manifestations similar to those for HIV-1 infection and AIDS progression, as well as a characteristic rapid disease onset. Comparison of this model with SIV-infected non-CD8 + lymphocyte-depleted macaques also provides a unique opportunity to investigate the role of CD8 + cells in viral evolution and population dynamics throughout the duration of infection. Using several different phylogenetic methods, we analyzed viral gp120 sequences obtained from extensive longitudinal sampling of multiple tissues and enriched leukocyte populations from SIVmac251-infected macaques with or without CD8 + lymphocyte depletion. SIV evolutionary and selection patterns in non-CD8 + lymphocyte-depleted animals were characterized by sequential population turnover and continual viral adaptation, a scenario readily comparable to intrahost evolutionary patterns during human HIV infection in the absence of antiretroviral therapy. Alternatively, animals that were depleted of CD8 + lymphocytes exhibited greater variation in population dynamics among tissues and cell populations over the course of infection. Our findings highlight the major role for CD8 + lymphocytes in prolonging disease progression through continual control of SIV subpopulations from various anatomical compartments and the potential for greater independent viral evolutionary behavior among these compartments in response to immune modulation. IMPORTANCE Although developments in combined antiretroviral therapy (cART) strategies have successfully prolonged the time to AIDS onset in HIV-1

  15. The oxidation of SO2 by NO2(g) at the air-water interface of aquated aerosol: implications for the rapid onset of haze-aerosol events in China

    Science.gov (United States)

    Li, L.; Colussi, A. J.; Hoffmann, M. R.

    2017-12-01

    Aqueous phase chemistry plays a vital role in the global atmosphere. The importance of heterogeneous chemistry has been recently underscored by the severe haze-fog pollution episodes experienced in Chinese megacities. A key finding is that despite reduced photochemistry during the wintertime haze events, the oxidation of S(IV) into sulfate aerosol occurs rapidly in spite of the low levels of ozone and H2O2. Field observations suggest that NO2 could serve as a suitable oxidant of S(IV) during the events under neutral pH conditions. However, the haze aerosols are mostly acidic. Furthermore, the air-water interface is more acidic than bulk-phase aquated system according to our recent findings. This work investigates the chemistry taking place as NO2(g) collides with the surface of aqueous S(IV) microdroplets as a function of pH to closely simulate actual haze aerosol events under atmospheric conditions. The reaction between NO2(g) and HSO3- (aq) is studied in situ under ambient temperature and pressure via online electrospray ionization mass spectrometry. The aqueous aerosols containing HSO3- is generated using a microjet which is exposed to NO2(g) alternatively, while the composition of the 1 nm interfacial liquid layer of the aerosol is instantaneously measured. The ratio of HSO3- to HSO4- is observed to decrease with the concomitant appearance of a strong m/z 62 signal upon NO2(g) exposure. The appearance of m/z 62 indicates the formation of NO3- via the disproportionation of NO2 (2NO2(g) + H2O (l) ⇌ H++NO3-(aq) + HONO(aq)) and thus impacts the ion-ion interactions of NO3- on the ratio of HSO3- to HSO4- in the outermost interfacial layers. Parallel experiments with NO3-(aq) additions are conducted to quantify the impact of NO3- on the the ratio, in order to unravel the contribution of NO2 to the oxidation of S(IV). After accounting for the HNO3 effect, it is concluded: (1) most NO2(g) is converted into NO3- via anion-catalyzed hydrolytic disproportionation; (2

  16. Understanding the Process of Envelope Glycoprotein Incorporation into Virions in Simian and Feline Immunodeficiency Viruses

    Directory of Open Access Journals (Sweden)

    José L. Affranchino

    2014-01-01

    Full Text Available The lentiviral envelope glycoproteins (Env mediate virus entry by interacting with specific receptors present at the cell surface, thereby determining viral tropism and pathogenesis. Therefore, Env incorporation into the virions formed by assembly of the viral Gag polyprotein at the plasma membrane of the infected cells is a key step in the replication cycle of lentiviruses. Besides being useful models of human immunodeficiency virus (HIV infections in humans and valuable tools for developing AIDS therapies and vaccines, simian and feline immunodeficiency viruses (SIV and FIV, respectively are relevant animal retroviruses; the study of which provides important information on how lentiviral replication strategies have evolved. In this review, we discuss the molecular mechanisms underlying the incorporation of the SIV and FIV Env glycoproteins into viral particles.

  17. European surveillance network for influenza in pigs 3 (ESNIP 3)

    DEFF Research Database (Denmark)

    Simon, G.; Reid, S. M.; Larsen, Lars Erik

    and seeks to strengthen formal interactions with human and avian surveillance networks. Materials and Methods: The project consortium comprises 24 participants, contributing a variety of specialism’s and skills ensuring multi-disciplinary cutting-edge outputs. Most partners are actively working with swine...... influenza virus (SIV) experimentally and in the field. Three work packages aim to increase knowledge of the epidemiology and evolution of SIV in European pigs to inform changes in disease trends and variation in contemporary viruses through organised field surveillance programmes. Results: An inventory...... of the programmes that are currently active in fifteen of the partners showed that passive surveillance was primarily used. Detected virus strains will be characterised by antigenic cartography (informing better evidence-based approaches for selection of vaccine strains) and genetically through full genome...

  18. Isotopically varying spectral features of silicon-vacancy in diamond

    International Nuclear Information System (INIS)

    Dietrich, Andreas; Jahnke, Kay D; Binder, Jan M; Rogers, Lachlan J; Jelezko, Fedor; Teraji, Tokuyuki; Isoya, Junichi

    2014-01-01

    The silicon-vacancy centre (SiV − ) in diamond has exceptional spectral properties for single-emitter quantum information applications. Most of the fluorescence is concentrated in a strong zero phonon line (ZPL), with a weak phonon sideband extending for 100 nm that contains several clear features. We demonstrate that the ZPL position can be used to reliably identify the silicon isotope present in a single SiV − centre. This is of interest for quantum information applications since only the 29 Si isotope has nuclear spin. In addition, we show that the sharp 64 meV phonon peak is due to a local vibrational mode of the silicon atom. The presence of a local mode suggests a plausible origin of the measured isotopic shift of the ZPL. (paper)

  19. Posterior diaphragmatic defect detected on chest CT: the incidence according to age and the lateral chest radiographic appearances

    International Nuclear Information System (INIS)

    Lee, Son Youl; Choi, Yo Won; Jeon, Seok Chol; Heo, Jeong Nam; Park, Choong Ki

    2007-01-01

    We wanted to investigate the incidence of posterior diaphragmatic defect on chest CT in various age groups and its lateral chest radiographic appearances. The chest CT scans of 78 patients of various ages with posterior diaphragmatic defect were selected among 1,991 patients, and they were analyzed for the incidence of defect in various age groups, the defect location and the herniated contents. Their lateral chest radiographs were analyzed for the shape of the posterior diaphragm and the posterior costophrenic sulcus. The patients' ages ranged from 34 to 87 with the tendency of a higher incidence in the older patients. The defect most frequently involved the medial two thirds (n = 49, 50.4%) and middle one third (n = 36, 37%) of the posterior diaphragm. The retroperitoneal fat was herniated into the thorax through the defect in all patients, and sometimes with the kidney (n = 8). Lateral chest radiography showed a normal diaphragmatic contour (n = 51, 49.5%), blunting of the posterior costophrenic sulcus (n = 41, 39.8%), focal humping of the posterior diaphragm (n = 7, 6.8%), or upward convexity (n = 4, 3.9%) of the posterior costophrenic sulcus on the affected side. The posterior diaphragmatic defect discovered in asymptomatic patients who are without a history of peridiaphragmatic disease is most likely acquired, and this malady increases in incidence according to age. An abnormal contour of the posterior diaphragm or the costophrenic sulcus on a lateral chest radiograph may be a finding of posterior diaphragmatic defect

  20. The importance of the prejowl notch in face lifting: the prejowl implant.

    Science.gov (United States)

    Shire, James R

    2008-02-01

    This article reviews the anatomy of the lower face in light of approach and techniques for prejowl implant. Implant sizing, patient selection and analysis, technique, and complications are presented. The author cites the manner of aging in the lower face and discusses the concept of augmenting the mandible to re-establish a youthful contour by correcting the prejowl sulcus and chin for rejuvenation. Because the prejowl sulcus and jowling camouflage the jawline, recontouring the mandible with implants restores the smooth jawline to provide optimal result by restoring the oval face shape.

  1. A key region in the human parietal cortex for processing proprioceptive hand feedback during reaching movements

    DEFF Research Database (Denmark)

    Reichenbach, Alexandra; Thielscher, Axel; Peer, Angelika

    2014-01-01

    of proprioceptive-only and of multi-sensory information about hand position when reaching for a visual target. TMS over two distinct stimulation sites elicited differential effects: TMS applied over the posterior part of the medial intraparietal sulcus (mIPS) compromised reaching accuracy when proprioception...... was the only sensory information available for correcting the reaching error. When visual feedback of the hand was available, TMS over the anterior intraparietal sulcus (aIPS) prolonged reaching time. Our results show for the first time the causal involvement of the posterior mIPS in processing proprioceptive...

  2. The Role of the Antiviral APOBEC3 Gene Family in Protecting Chimpanzees against Lentiviruses from Monkeys.

    Directory of Open Access Journals (Sweden)

    Lucie Etienne

    2015-09-01

    Full Text Available Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee's main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4(+ T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses.

  3. Ab initio theory of spin-orbit coupling for quantum bits in diamond exhibiting dynamic Jahn-Teller effect

    Science.gov (United States)

    Gali, Adam; Thiering, Gergő

    Dopants in solids are promising candidates for implementations of quantum bits for quantum computing. In particular, the high-spin negatively charged nitrogen-vacancy defect (NV) in diamond has become a leading contender in solid-state quantum information processing. The initialization and readout of the spin is based on the spin-selective decay of the photo-excited electron to the ground state which is mediated by spin-orbit coupling between excited states states and phonons. Generally, the spin-orbit coupling plays a crucial role in the optical spinpolarization and readout of NV quantum bit (qubit) and alike. Strong electron-phonon coupling in dynamic Jahn-Teller (DJT) systems can substantially influence the effective strength of spin-orbit coupling. Here we show by ab initio supercell density functional theory (DFT) calculations that the intrinsic spin-orbit coupling is strongly damped by DJT effect in the triplet excited state that has a consequence on the rate of non-radiative decay. This theory is applied to the ground state of silicon-vacancy (SiV) and germanium-vacancy (GeV) centers in their negatively charged state that can also act like qubits. We show that the intrinsic spin-orbit coupling in SiV and GeV centers is in the 100 GHz region, in contrast to the NV center of 10 GHz region. Our results provide deep insight in the nature of SiV and GeV qubits in diamond. EU FP7 DIADEMS project (Contract No. 611143).

  4. Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS.

    Directory of Open Access Journals (Sweden)

    Eva-Maria Ratai

    2010-05-01

    Full Text Available Despite the advent of highly active anti-retroviral therapy (HAART, HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury.Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi. Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN, microtubule-associated protein 2 (MAP2, and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP and ionized calcium binding adaptor molecule 1 (IBA-1, respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr, which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals.In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus.

  5. Püsiva andmekandja olemus ja veebilehe kui püsiva andmekandja määratlemine : [magistritöö] / Merili Truup ; Tartu Ülikool, õigusteaduskond ; juhendaja: Kadri Siibak

    Index Scriptorium Estoniae

    Truup, Merili

    2010-01-01

    Püsiva andmekandja kasutusvaldkondadest ja kohaldamisalast, sidevahendi abil sõlmitud lepingu regulatsioonist ja eesmärkidest, lepingu eripärast. Püsiva andmekandja olemusest, veebilehe kui püsiva andmekandja olemusest, püsiv andmekandja kui vorminõue

  6. Refractive Results: Safety and Efficacy of Secondary Piggyback Sensar™ AR40 Intraocular Lens Implantation to Correct Pseudophakic Refractive Error

    Directory of Open Access Journals (Sweden)

    Alahmady Hamad Alsmman Hassan

    2016-01-01

    Full Text Available In this study we evaluate the visual outcomes, safety, efficacy, and stability of implanting of second sulcus intraocular lens (IOL to correct unsatisfied ametropic patients after phacoemulsification. Methods. Retrospective study of 15 eyes (15 patients underwent secondary intraocular lens implanted into the ciliary sulcus. The IOL used was a Sensar IOL three-piece foldable hydrophobic acrylic IOL. The first IOL in all patients was acrylic intrabagal IOL implanted in uncomplicated phacoemulsification surgery. Results. Fifteen eyes (15 patients were involved in this study. Preoperatively, mean log⁡MAR UDVA and CDVA were 0.88 ± 0.22 and 0.19 ± 0.13, respectively, with a mean follow-up of 28 months (range: 24 to 36 months. At the end of the follow-up, all eyes achieved log⁡MAR UDVA of 0.20 ± 0.12 with postoperative refraction ranging from 0.00 to −0.50 D of attempted emmetropia. Conclusions. Implantation of the second sulcus SensarAR40 IOL was found to be safe, easy, and simple technique for management of ametropia following uncomplicated phacoemulsification.

  7. Evaluation of various somatosensory stimulations for functional MRI

    International Nuclear Information System (INIS)

    Hara, Kazushi; Nakasato, Nobukazu; Mizoi, Kazuo; Yoshimoto, Takashi; Shimizu, Hiroaki.

    1997-01-01

    The aim of this functional magnetic resonance imaging (fMRI) study was to test detectability of activated area using various somatosensory stimulations. The following stimulations were performed in normal volunteers: regular or irregular electrical median nerve stimulation (n=5, each), tactile stimulation to the palm and fingers (n=8), pain stimulation to the index finger (n=5) or to the palm and fingers (n=5). fMRI was acquired with a spoiled gradient echo sequence at 1.5 T. Detectability of activated area was the highest when the pain stimulation was applied to the palm and fingers (80%). A successful rate for the tactile stimulation was 25%, and the other stimulations failed to demonstrate any activation. When successful, the highest signal activation on fMRI was seen on a sulcus, which presumably arose from a vein. The sulcus was defined as the central sulcus by somatosensory evoked field using a median nerve stimulation. Our study indicates that the pain stimulation to the palm and fingers may be a choice for the sensory fMRI. (author)

  8. Infectious risk factors for individual postweaning multisystemic wasting syndrome (PMWS) development in pigs from affected farms in Spain and Denmark

    DEFF Research Database (Denmark)

    Grau-Roma, Llorenç; Stockmarr, Anders; Kristensen, Charlotte S.

    2012-01-01

    collected serum samples to detect antibodies against, PCV2, porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), swine influenza virus (SIV) and Lawsonia intracellularis (law), Mycoplasma hyopneumoniae, Aujeszky’s disease virus (ADV) and Salmonella spp. A Cox proportional...

  9. ORBIT AND OCULOPLASTY

    African Journals Online (AJOL)

    event, eye drops and other agents used in the eye, and causes that may be entirely .... function and quality of life outcome measures after blepharoptosis surgery. .... virus (SIV) which got mutated into the HIV after coming in contact with some ...

  10. Effect of Carbon Dioxide Laser on Increasing Vestibular Depth in Cleft Lip and Palate Patients.

    Science.gov (United States)

    Yassaei, Sogra; Aghili, Hossein; Azam, Alireza Navab; Moghadam, Mahjobeh Gholdani; Safari, Isa

    2017-09-01

    Shallow upper buccal sulcus deformity in cleft lip and palate patients is one of the common secondary deformities after primary cleft lip and palate repair; this deformity may prevent or complicate orthodontic and prosthodontic procedures causing aesthetic and functional problems. A number of methods are described to increase the anterior maxillary sulcus in these patients. This study assessed the use of a carbon dioxide laser (CO 2 ) to increase the sulcus depth. Fifteen patients with cleft lip and palate (eight unilateral and seven bilateral) were studied. The surgical procedure was performed using CO 2 laser. The vestibular depth and lip length were measured at three time points namely before surgery (T0), 1 week following surgery (T1), and 4 months following surgery (T2). After data collection, statistical analyses were done using PASW ® version 18 SPSS. The mean values of vestibular depth were 9.46 ± 1.92, 13.83 ± 1.88, and 13.23 ± 1.76 mm for T0, T1, and T2, respectively. The vestibular depth significantly increased after 4 months of follow-up (p = 0.001). The mean amount of vestibular depth gain was not significantly different in unilateral and bilateral cleft groups (p = 0.908). The mean value of upper lip length increased by a mean of 1.23 mm and was statistically significant (p = 0.001). Upper buccal sulcus reconstruction with CO 2 laser provides successful and stable results. CO 2 laser application is suggested as an alternative to conventional vestibuloplasty.

  11. Fully automated quantification of regional cerebral blood flow with three-dimensional stereotaxic region of interest template. Validation using magnetic resonance imaging. Technical note

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Ryo; Katayama, Shigenori; Takeda, Naoya; Fujita, Katsuzo [Nishi-Kobe Medical Center (Japan); Yonekura, Yoshiharu [Fukui Medical Univ., Matsuoka (Japan); Konishi, Junji [Kyoto Univ. (Japan). Graduate School of Medicine

    2003-03-01

    The previously reported three-dimensional stereotaxic region of interest (ROI) template (3DSRT-t) for the analysis of anatomically standardized technetium-99m-L,L-ethyl cysteinate dimer ({sup 99m}Tc-ECD) single photon emission computed tomography (SPECT) images was modified for use in a fully automated regional cerebral blood flow (rCBF) quantification software, 3DSRT, incorporating an anatomical standardization engine transplanted from statistical parametric mapping 99 and ROIs for quantification based on 3DSRT-t. Three-dimensional T{sub 2}-weighted magnetic resonance images of 10 patients with localized infarcted areas were compared with the ROI contour of 3DSRT, and the positions of the central sulcus in the primary sensorimotor area were also estimated. All positions of the 20 lesions were in strict accordance with the ROI delineation of 3DSRT. The central sulcus was identified on at least one side of 210 paired ROIs and in the middle of 192 (91.4%) of these 210 paired ROIs among the 273 paired ROIs of the primary sensorimotor area. The central sulcus was recognized in the middle of more than 71.4% of the ROIs in which the central sulcus was identifiable in the respective 28 slices of the primary sensorimotor area. Fully automated accurate ROI delineation on anatomically standardized images is possible with 3DSRT, which enables objective quantification of rCBF and vascular reserve in only a few minutes using {sup 99m}Tc-ECD SPECT images obtained by the resting and vascular reserve (RVR) method. (author)

  12. Fully automated quantification of regional cerebral blood flow with three-dimensional stereotaxic region of interest template. Validation using magnetic resonance imaging. Technical note

    International Nuclear Information System (INIS)

    Takeuchi, Ryo; Katayama, Shigenori; Takeda, Naoya; Fujita, Katsuzo; Yonekura, Yoshiharu; Konishi, Junji

    2003-01-01

    The previously reported three-dimensional stereotaxic region of interest (ROI) template (3DSRT-t) for the analysis of anatomically standardized technetium-99m-L,L-ethyl cysteinate dimer ( 99m Tc-ECD) single photon emission computed tomography (SPECT) images was modified for use in a fully automated regional cerebral blood flow (rCBF) quantification software, 3DSRT, incorporating an anatomical standardization engine transplanted from statistical parametric mapping 99 and ROIs for quantification based on 3DSRT-t. Three-dimensional T 2 -weighted magnetic resonance images of 10 patients with localized infarcted areas were compared with the ROI contour of 3DSRT, and the positions of the central sulcus in the primary sensorimotor area were also estimated. All positions of the 20 lesions were in strict accordance with the ROI delineation of 3DSRT. The central sulcus was identified on at least one side of 210 paired ROIs and in the middle of 192 (91.4%) of these 210 paired ROIs among the 273 paired ROIs of the primary sensorimotor area. The central sulcus was recognized in the middle of more than 71.4% of the ROIs in which the central sulcus was identifiable in the respective 28 slices of the primary sensorimotor area. Fully automated accurate ROI delineation on anatomically standardized images is possible with 3DSRT, which enables objective quantification of rCBF and vascular reserve in only a few minutes using 99m Tc-ECD SPECT images obtained by the resting and vascular reserve (RVR) method. (author)

  13. Immunogenicity of seven new recombinant yellow fever viruses 17D expressing fragments of SIVmac239 Gag, Nef, and Vif in Indian rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Mauricio A Martins

    Full Text Available An effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (HIV. Cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. Recombinant viral vectors can induce potent T-cell responses. Although several viral vectors have been developed to deliver HIV genes, only a few have been advanced for clinical trials. The live-attenuated yellow fever vaccine virus 17D (YF17D has many properties that make it an attractive vector for AIDS vaccine regimens. YF17D is well tolerated in humans and vaccination induces robust T-cell responses that persist for years. Additionally, methods to manipulate the YF17D genome have been established, enabling the generation of recombinant (rYF17D vectors carrying genes from unrelated pathogens. Here, we report the generation of seven new rYF17D viruses expressing fragments of simian immunodeficiency virus (SIVmac239 Gag, Nef, and Vif. Studies in Indian rhesus macaques demonstrated that these live-attenuated vectors replicated in vivo, but only elicited low levels of SIV-specific cellular responses. Boosting with recombinant Adenovirus type-5 (rAd5 vectors resulted in robust expansion of SIV-specific CD8(+ T-cell responses, particularly those targeting Vif. Priming with rYF17D also increased the frequency of CD4(+ cellular responses in rYF17D/rAd5-immunized macaques compared to animals that received rAd5 only. The effect of the rYF17D prime on the breadth of SIV-specific T-cell responses was limited and we also found evidence that some rYF17D vectors were more effective than others at priming SIV-specific T-cell responses. Together, our data suggest that YF17D - a clinically relevant vaccine vector - can be used to prime AIDS virus-specific T-cell responses in heterologous prime boost regimens. However, it will be important to optimize rYF17D

  14. Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance observed in peripheral blood during simian immunodeficiency virus infection.

    Science.gov (United States)

    Kader, M; Bixler, S; Piatak, M; Lifson, J; Mattapallil, J J

    2009-10-01

    Human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of Th-17 cells (IL-17(+)CD4(+) T cells) that has been associated with disease progression and systemic dissemination of bacterial infections. Anti-retroviral therapy (ART) has led to repopulation of CD4(+) T cells in peripheral tissues with little sustainable repopulation in mucosal tissues. Given the central importance of Th-17 cells in mucosal homeostasis, it is not known if the failure of ART to permanently repopulate mucosal tissues is associated with a failure to restore Th-17 cells that are lost during infection. Dynamics of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood of SIV infected rhesus macaques were evaluated and compared to animals that were treated with ART. The frequency of Th-17 and Tc-17 cells was determined following infection and after therapy. Relative expression of IL-21, IL-23, and TGFbeta was determined using Taqman PCR. Treatment of SIV infected rhesus macaques with anti-retroviral therapy was associated with a substantial repopulation of mucosal homing alpha4(+)beta7(hi)CD4(+) T cells in peripheral blood. This repopulation, however, was not accompanied by a restoration of Th-17 responses. Interestingly, SIV infection was associated with an increase in Tc-17 responses (IL-17(+)CD8(+) T cells) suggesting to a skewing in the ratio of Th-17: Tc-17 cells from a predominantly Th-17 phenotype to a predominantly Tc-17 phenotype. Surprisingly, Tc-17 responses remained high during the course of therapy suggesting that ART failed to correct the imbalance in Th-17 : Tc-17 responses induced following SIV infection. ART was associated with substantial repopulation of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood with little or no rebound of Th-17 cells. On the other hand, repopulation of alpha4(+)beta7(hi) CD4(+) T cells was accompanied by persistence of high levels of Tc-17 cells in peripheral blood. The dysregulation of Th-17

  15. HIV Persistence in Adipose Tissue Reservoirs.

    Science.gov (United States)

    Couturier, Jacob; Lewis, Dorothy E

    2018-02-01

    The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and

  16. A Small Molecule, Which Competes with MAdCAM-1, Activates Integrin α4β7 and Fails to Prevent Mucosal Transmission of SHIV-SF162P3.

    Directory of Open Access Journals (Sweden)

    Géraldine Arrode-Brusés

    2016-06-01

    Full Text Available Mucosal HIV-1 transmission is inefficient. However, certain viral and host characteristics may play a role in facilitating HIV acquisition and systemic expansion. Cells expressing high levels of integrin α4β7 have been implicated in favoring the transmission process and the infusion of an anti-α4β7 mAb (RM-Act-1 prior to, and during a repeated low-dose vaginal challenge (RLDC regimen with SIVmac251 reduced SIV acquisition and protected the gut-associated lymphoid tissues (GALT in the macaques that acquired SIV. α4β7 expression is required for lymphocyte trafficking to the gut lamina propria and gut inductive sites. Several therapeutic strategies that target α4β7 have been shown to be effective in treating inflammatory conditions of the intestine, such as inflammatory bowel disease (IBD. To determine if blocking α4β7 with ELN, an orally available anti-α4 small molecule, would inhibit SHIV-SF162P3 acquisition, we tested its ability to block MAdCAM-1 (α4β7 natural ligand and HIV-gp120 binding in vitro. We studied the pharmacokinetic profile of ELN after oral and vaginal delivery in macaques. Twenty-six macaques were divided into 3 groups: 9 animals were treated with ELN orally, 9 orally and vaginally and 8 were used as controls. All animals were challenged intra-vaginally with SHIV-SF162P3 using the RLDC regimen. We found that ELN did not protect macaques from SHIV acquisition although it reduced the SHIV-induced inflammatory status during the acute phase of infection. Notably, integrins can exist in different activation states and, comparing the effect of ELN and the anti-α4β7 mAb RM-Act-1 that reduced susceptibility to SIV infection, we determined that ELN induces the active conformation of α4β7, while RM-Act-1 inhibits its activation through an allosteric mechanism. These results suggest that inhibition of α4β7 activation may be necessary to reduce susceptibility to SIV/SHIV infection and highlight the complexity of anti

  17. European surveillance network for influenza in pigs

    NARCIS (Netherlands)

    Simon, Gaëlle; Larsen, Lars E.; Dürrwald, Ralf; Foni, Emanuela; Harder, Timm; Reeth, Van Kristien; Markowska-Daniel, Iwona; Reid, Scott M.; Dan, Adam; Maldonado, Jaime; Huovilainen, Anita; Billinis, Charalambos; Davidson, Irit; Agüero, Montserrat; Vila, Thaïs; Hervé, Séverine; Breum, Solvej Østergaard; Chiapponi, Chiara; Urbaniak, Kinga; Kyriakis, Constantinos S.; Brown, Ian H.; Loeffen, Willie; Meulen, Van der Karen; Schlegel, Michael; Bublot, Michel; Kellam, Paul; Watson, Simon; Lewis, Nicola S.; Pybus, Oliver G.; Webby, Richard; Chen, Hualan; Vincent, Amy L.

    2014-01-01

    Swine influenza causes concern for global veterinary and public health officials. In continuing two previous networks that initiated the surveillance of swine influenza viruses (SIVs) circulating in European pigs between 2001 and 2008, a third European Surveillance Network for Influenza in Pigs

  18. Induction of Mucosal and Systemic Immunity to a Recombinant Simian Immunodeficiency Viral Protein

    Science.gov (United States)

    Lehner, T.; Bergmeier, L. A.; Panagiotidi, C.; Tao, L.; Brookes, R.; Klavinskis, L. S.; Walker, P.; Walker, J.; Ward, R. G.; Hussain, L.; Gearing, A. J. H.; Adams, S. E.

    1992-11-01

    Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant, particulate SIV antigen. Vaginal, followed by oral, administration of the vaccine elicited three types of immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4^+ T cell proliferation and helper function in B cell p27-specific IgA synthesis in the genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4^+ T cell proliferative and helper functions in the circulating blood.

  19. Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus.

    Science.gov (United States)

    Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A

    2011-03-24

    Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.

  20. Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus: studies in the pig model of influenza.

    Science.gov (United States)

    Qiu, Yu; De Hert, Karl; Van Reeth, Kristien

    2015-09-24

    Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs.

  1. Prior DNA immunization enhances immune response to dominant and subdominant viral epitopes induced by a fowlpox-based SIVmac vaccine in long-term slow-progressor macaques infected with SIVmac251

    International Nuclear Information System (INIS)

    Radaelli, Antonia; Nacsa, Janos; Tsai, W.-P.; Edghill-Smith, Yvette; Zanotto, Carlo; Elli, Veronica; Venzon, David; Tryniszewska, Elzbieta; Markham, Phil; Mazzara, Gail P.; Panicali, Dennis; Morghen, Carlo De Giuli; Franchini, Genoveffa

    2003-01-01

    A therapeutic vaccine for individuals infected with HIV-1 and treated with antiretroviral therapy (ART) should be able to replenish virus-specific CD4+ T-cells and broaden the virus-specific CD8+ T-cell response in order to maintain CD8+ T-cell function and minimize viral immune escape after ART cessation. Because a combination of DNA and recombinant poxvirus vaccine modalities induces high levels of virus-specific CD4+ T-cell response and broadens the cytolytic activity in naive macaques, we investigated whether the same results could be obtained in SIVmac251-infected macaques. The macaques studied here were long-term nonprogressors that naturally contained viremia but were nevertheless treated with a combination of antiviral drugs to assess more carefully the effect of vaccination in the context of ART. The combination of a DNA expressing the gag and pol genes (DNA-SIV-gp) of SIVmac239 followed by a recombinant fowlpox expressing the same SIVmac genes (FP-SIV-gp) was significantly more immunogenic than two immunizations of FP-SIV-gp in SIVmac251-infected macaques treated with ART. The DNA/FP combination significantly expanded and broadened Gag-specific T-cell responses measured by tetramer staining, ELISPOT, and intracellular cytokine staining and measurement of ex vivo cytolytic function. Importantly, the combination of these vaccine modalities also induced a sizeable expansion in most macaques of Gag-specific CD8-(CD4+) T-cells able to produce TNF-α. Hopefully, this modality of vaccine combination may be useful in the clinical management of HIV-1-infected individuals

  2. Global and Regional Impacts of HONO on the Chemical Composition of Clouds and Aerosols

    Science.gov (United States)

    Elshorbany, Y. F.; Crutzen, P. J.; Steil, B.; Pozzer, A.; Tost, H.; Lelieveld, J.

    2014-01-01

    Recently, realistic simulation of nitrous acid (HONO) based on the HONO / NOx ratio of 0.02 was found to have a significant impact on the global budgets of HOx (OH + HO2) and gas phase oxidation products in polluted regions, especially in winter when other photolytic sources are of minor importance. It has been reported that chemistry-transport models underestimate sulphate concentrations, mostly during winter. Here we show that simulating realistic HONO levels can significantly enhance aerosol sulphate (S(VI)) due to the increased formation of H2SO4. Even though in-cloud aqueous phase oxidation of dissolved SO2 (S(IV)) is the main source of S(VI), it appears that HONO related enhancement of H2O2 does not significantly affect sulphate because of the predominantly S(IV) limited conditions, except over eastern Asia. Nitrate is also increased via enhanced gaseous HNO3 formation and N2O5 hydrolysis on aerosol particles. Ammonium nitrate is enhanced in ammonia-rich regions but not under ammonia-limited conditions. Furthermore, particle number concentrations are also higher, accompanied by the transfer from hydrophobic to hydrophilic aerosol modes. This implies a significant impact on the particle lifetime and cloud nucleating properties. The HONO induced enhancements of all species studied are relatively strong in winter though negligible in summer. Simulating realistic HONO levels is found to improve the model measurement agreement of sulphate aerosols, most apparent over the US. Our results underscore the importance of HONO for the atmospheric oxidizing capacity and corroborate the central role of cloud chemical processing in S(IV) formation

  3. The chemical composition of fogs and clouds in Southern California

    Energy Technology Data Exchange (ETDEWEB)

    Munger, J.W.

    1989-01-01

    The major inorganic species in cloud and fog water samples were NH{sub 4}{sup +}, H{sup +}, NO{sub 3}{sup {minus}}, and SO{sub 4}{sup 2{minus}}. Concentrations in fog water samples were 1 - 10 {times} 10{sup {minus}3} M; pH values ranged from {approx equal} 2 to 6. Nitrate usually exceeded sulfate. Acidity depended on the availability of NH{sub 3} from agricultural operations. Stratus cloudwater had somewhat lower concentrations; pH values were in the range 3-4. The major factors accounting for variation in fog- or cloudwater composition were the preexisting aerosol and gas concentrations and variations in liquid water content. Deposition and entrainment or advection of different air masses were also important during extended cloud or fog episodes. The droplet size dependence of cloudwater composition was investigated on one occasion in an intercepted coastal stratus clouds. Concentrations of S(IV) and CH{sub 2}O in the range 100-1000 {mu}M were observed in fogwater from urban sites in Southern California. Lower concentrations were observed in stratus clouds. The high levels of S(IV) and CH{sub 2}O were attributed to the formation of hydroxymethanesulfonate (HMSA), the S(IV) adduct of CH{sub 2}O. Direct measurements of HMSA in fogwater samples from Bakersfield, CA were made by ion-pairing chromatography. Glyoxal and methyglyoxal were observed at concentrations comparable to CH{sub 2}O in fogwater samples from Riverside, CA and in stratus cloudwater samples from sites along the Santa Barbara Channel.

  4. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

    NARCIS (Netherlands)

    van der Kuyl, Antoinette C.; van den Burg, Remco; Hoyer, Mark J.; Gruters, Rob A.; Osterhaus, Albert D. M. E.; Berkhout, Ben

    2004-01-01

    A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely

  5. Vöökirjatud veetorn Võrumaal / Tanel Veenre

    Index Scriptorium Estoniae

    Veenre, Tanel, 1977-

    2009-01-01

    Lasva renoveeritud veetornist (renoveerimisprojekt: arhitekt Veronika Valk), kus asub Veetorni galerii, mille dominant on mitmel häälel helisev klavertrepp (teostus: skulptor Kalle Pruuden, Kalle Tikas). Seintel on fotograaf Peeter Lauritsa ja ajaloolase Uuno Ojala koostatud piirkonda tutvustav püsiväljapanek

  6. 75 FR 65021 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2010-10-21

    ... Infectious Diseases Special Emphasis Panel; Mechanisms and Prevention of Sexual Transmission of HIV/SIV. Date... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal...

  7. Potential Impacts of two SO2 oxidation pathways on regional sulfate concentrations: acqueous-hase oxidation by NO2 and gas-phase oxidation by Stabilized Criegee Intermediates

    Science.gov (United States)

    We examine the potential impacts of two additional sulfate production pathways using the Community Multiscale Air Quality modeling system. First we evaluate the impact of the aqueous-phase oxidation of S(IV) by nitrogen dioxide using two published rate constants, differing by 1-2...

  8. Processing of vocalizations in humans and monkeys: A comparative fMRI study

    International Nuclear Information System (INIS)

    Joly, Olivier; Orban, Guy A.; Pallier, Christophe; Ramus, Franck; Pressnitzer, Daniel; Vanduffel, Wim

    2012-01-01

    Humans and many other animals use acoustical signals to mediate social interactions with con-specifics. The evolution of sound-based communication is still poorly understood and its neural correlates have only recently begun to be investigated. In the present study, we applied functional MRI to humans and macaque monkeys listening to identical stimuli in order to compare the cortical networks involved in the processing of vocalizations. At the first stages of auditory processing, both species showed similar fMRI activity maps within and around the lateral sulcus (the Sylvian fissure in humans). Monkeys showed remarkably similar responses to monkey calls and to human vocal sounds (speech or otherwise), mainly in the lateral sulcus and the adjacent superior temporal gyrus (STG). In contrast, a preference for human vocalizations and especially for speech was observed in the human STG and superior temporal sulcus (STS). The STS and Broca's region were especially responsive to intelligible utterances. The evolution of the language faculty in humans appears to have recruited most of the STS. It may be that in monkeys, a much simpler repertoire of vocalizations requires less involvement of this temporal territory. (authors)

  9. Identification of reassortant pandemic H1N1 influenza virus in Korean pigs.

    Science.gov (United States)

    Han, Jae Yeon; Park, Sung Jun; Kim, Hye Kwon; Rho, Semi; Nguyen, Giap Van; Song, Daesub; Kang, Bo Kyu; Moon, Hyung Jun; Yeom, Min Joo; Park, Bong Kyun

    2012-05-01

    Since the 2009 pandemic human H1N1 influenza A virus emerged in April 2009, novel reassortant strains have been identified throughout the world. This paper describes the detection and isolation of reassortant strains associated with human pandemic influenza H1N1 and swine influenza H1N2 (SIV) viruses in swine populations in South Korea. Two influenza H1N2 reassortants were detected, and subtyped by PCR. The strains were isolated using Madin- Darby canine kidney (MDCK) cells, and genetically characterized by phylogenetic analysis for genetic diversity. They consisted of human, avian, and swine virus genes that were originated from the 2009 pandemic H1N1 virus and a neuraminidase (NA) gene from H1N2 SIV previously isolated in North America. This identification of reassortment events in swine farms raises concern that reassortant strains may continuously circulate within swine populations, calling for the further study and surveillance of pandemic H1N1 among swine.

  10. A chimeric measles virus with a lentiviral envelope replicates exclusively in CD4+/CCR5+ cells

    International Nuclear Information System (INIS)

    Mourez, Thomas; Mesel-Lemoine, Mariana; Combredet, Chantal; Najburg, Valerie; Cayet, Nadege; Tangy, Frederic

    2011-01-01

    We generated a replicating chimeric measles virus in which the hemagglutinin and fusion surface glycoproteins were replaced with the gp160 envelope glycoprotein of simian immunodeficiency virus (SIVmac239). Based on a previously cloned live-attenuated Schwarz vaccine strain of measles virus (MV), this chimera was rescued at high titers using reverse genetics in CD4+ target cells. Cytopathic effect consisted in the presence of large cell aggregates evolving to form syncytia, as observed during SIV infection. The morphology of the chimeric virus was identical to that of the parent MV particles. The presence of SIV gp160 as the only envelope protein on chimeric particles surface altered the cell tropism of the new virus from CD46+ to CD4+ cells. Used as an HIV candidate vaccine, this MV/SIVenv chimeric virus would mimic transient HIV-like infection, benefiting both from HIV-like tropism and the capacity of MV to replicate in dendritic cells, macrophages and lymphocytes.

  11. Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

    International Nuclear Information System (INIS)

    Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-01

    Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

  12. A New Adjuvant Combined with Inactivated Influenza Enhances Specific CD8 T Cell Response in Mice and Decreases Symptoms in Swine Upon Challenge.

    Science.gov (United States)

    Bouguyon, Edwige; Goncalves, Elodie; Shevtsov, Alexander; Maisonnasse, Pauline; Remyga, Stepan; Goryushev, Oleg; Deville, Sebastien; Bertho, Nicolas; Ben Arous, Juliette

    2015-11-01

    Vaccination is the most effective way to control swine influenza virus (SIV) in the field. Classical vaccines are based on inactivated antigens formulated with an oil emulsion or a polymeric adjuvant. Standard adjuvants enhance the humoral response and orient the immune response toward a Th2 response. An important issue is that current vaccines do not protect against new strains. One approach to improve cross-protection is to enhance Th1 and cytotoxic responses. The development of adjuvants orienting the immune response of inactivated vaccines toward Th1/Cytotoxic responses would be highly beneficial. This study shows that the water in oil in water emulsion adjuvant Montanide™ ISA 201 VG allows the induction of anti-influenza CD8 T cell in mice and induces homologous protection against an H1N1 challenge in swine. Such adjuvants that induce both humoral and cell-mediated immunity could improve the protection conferred by SIV vaccines in the field.

  13. Seroprevalence of Antibodies to Main Porcine Infectious Pathogens in Wild Boars in Some Regions of Russia

    Directory of Open Access Journals (Sweden)

    BABORENKO, Elena

    2009-01-01

    Full Text Available Results of testing 107 serum samples from wild boars (Sus scrofa L., 1758 for thepresence of antibodies to six economically significant porcine infectious disease agents (porcinereproductive and respiratory syndrome (PRRS virus, porcine parvovirus (PPV, swine influenza virus(SIV of H1N1 and H3N2 subtypes, Aujeszky’s disease virus (ADV, porcine transmissiblegastroenteritis virus (TGEV and Mycoplasma hyopneumoniae are presented in the paper. Wild boarwere sampled in seven regions of Russia for diagnostic purposes. The obtained results showed thepresence of antibodies to ADV in 32.5% of samples (83/27, to PPV – in 62% of samples (92/57, toMycoplasma hyopneumoniae – in 52% of samples (98/51. All samples were seronegative to PRRSvirus (107/0, TGEV (91/0 and SIV of H1N1 (89/0 and H3N2 (58/0 subtypes. The researchesdemonstrated the extensive circulation of porcine parvovirus, Aujeszky’s disease virus andMycoplasma hyopneumoniae among Wild boar in some regions of Russia.

  14. Isotopic constraints on heterogeneous sulfate production in Beijing haze

    Science.gov (United States)

    He, Pengzhen; Alexander, Becky; Geng, Lei; Chi, Xiyuan; Fan, Shidong; Zhan, Haicong; Kang, Hui; Zheng, Guangjie; Cheng, Yafang; Su, Hang; Liu, Cheng; Xie, Zhouqing

    2018-04-01

    Discerning mechanisms of sulfate formation during fine-particle pollution (referred to as haze hereafter) in Beijing is important for understanding the rapid evolution of haze and for developing cost-effective air pollution mitigation strategies. Here we present observations of the oxygen-17 excess of PM2.5 sulfate (Δ17O(SO42-)) collected in Beijing haze from October 2014 to January 2015 to constrain possible sulfate formation pathways. Throughout the sampling campaign, the 12-hourly averaged PM2.5 concentrations ranged from 16 to 323 µg m-3 with a mean of (141 ± 88 (1σ)) µg m-3, with SO42- representing 8-25 % of PM2.5 mass. The observed Δ17O(SO42-) varied from 0.1 to 1.6 ‰ with a mean of (0.9 ± 0.3) ‰. Δ17O(SO42-) increased with PM2.5 levels in October 2014 while the opposite trend was observed from November 2014 to January 2015. Our estimate suggested that in-cloud reactions dominated sulfate production on polluted days (PDs, PM2.5 ≥ 75 µg m-3) of Case II in October 2014 due to the relatively high cloud liquid water content, with a fractional contribution of up to 68 %. During PDs of Cases I and III-V, heterogeneous sulfate production (Phet) was estimated to contribute 41-54 % to total sulfate formation with a mean of (48 ± 5) %. For the specific mechanisms of heterogeneous oxidation of SO2, chemical reaction kinetics calculations suggested S(IV) ( = SO2 ⚫ H2O + HSO3- + SO32-) oxidation by H2O2 in aerosol water accounted for 5-13 % of Phet. The relative importance of heterogeneous sulfate production by other mechanisms was constrained by our observed Δ17O(SO42-). Heterogeneous sulfate production via S(IV) oxidation by O3 was estimated to contribute 21-22 % of Phet on average. Heterogeneous sulfate production pathways that result in zero-Δ17O(SO42-), such as S(IV) oxidation by NO2 in aerosol water and/or by O2 via a radical chain mechanism, contributed the remaining 66-73 % of Phet. The assumption about the thermodynamic state of aerosols

  15. Biomicroscopia ultra-sônica na avaliação da posição das lentes intra-oculares em uma técnica de fixação escleral Ultrasound biomicroscopy in the assessment of the intraocular lenses positioning in a transscleral fixation technique

    Directory of Open Access Journals (Sweden)

    Raul de Camargo Vianna Filho

    2000-10-01

    Full Text Available Objetivo: Avaliar pela biomicrospia ultra-sônica (UBM o posicionamento, em relação ao sulco ciliar, das alças de lentes intra-oculares (LIO, em uma técnica de fixação escleral, avaliando-se também se dois pontos de fixação são suficientes para que não haja inclinação da parte óptica. Métodos: Dezesseis olhos afácicos foram submetidos a implante LIO por uma mesma técnica de fixação escleral, realizados por um mesmo cirurgião. Um mês após a cirurgia, o posicionamento das alças das LIO foram avaliados pelo UBM, assim como distâncias entre as LIO e córnea. Os resultados foram submetidos a testes estatísticos. Resultados: Das 32 alças fixadas à esclera, oito estavam localizadas no sulco ciliar e 24 fora deste. Não houve diferença estatística nas distâncias entre LIO e córnea para alças posicionadas no sulco ciliar quando comparadas àquelas localizadas fora do sulco. Isto sugere que, além da distância ao limbo que se transfixa a esclera, outros fatores devem estar associados ao posicionamento da alça no sulco ciliar. As medidas LIO -- córnea realizadas na periferia das LIO às 3, 6, 9, e 12 horas foram semelhantes, mostrando que dois pontos de fixação são suficientes para que a LIO não fique inclinada. Conclusões: Outros fatores (por exemplo o ângulo de abertura do corpo ciliar, além da distância ao limbo na qual se transfixa a esclera, são importantes para o posicionamento das alças no sulco ciliar. Dois pontos de fixação são suficientes para que a LIO não apresente inclinação dentro do olho.Purpose: To assess, through ultrasound biomicroscopy (UBM, the positioning of the intraocular lenses (IOL haptics as related to the ciliary sulcus by using a scleral fixation technique; and to evaluate, as well, if two fixation points are sufficient to avoid tilting of the lenses. Methods: Sixteen aphakic eyes underwent an IOL implan-tation by means of the same scleral fixation technique, performed by the

  16. Интерсемиотическое пространство : Адрианополь в Петербурге "Преступление и наказание" Ф. М. Достоевского / Пеэтер Тороп

    Index Scriptorium Estoniae

    Тороп, Пеэтер, 1950-

    2000-01-01

    The intersemiotic space: Adrianopol in F. Dostoevsky's "Crime and punishment" St. Petersburg. Lk. 116 ; Intersemiootiline ruum: Adrianopol F. Dostojevski "Kuritöö ja karistuse" Peterburis. Lk. 133. Intertekstuaalse kultuuriruumi eripärast ja analüüsivõimaluste otsimisest. Kõrvutatakse tasandi-, kompositsiooni- ja kronotoobilist analüüsi

  17. Design and performance of the CDC real-time reverse transcriptase PCR swine flu panel for detection of 2009 A (H1N1) pandemic influenza virus.

    Science.gov (United States)

    Shu, Bo; Wu, Kai-Hui; Emery, Shannon; Villanueva, Julie; Johnson, Roy; Guthrie, Erica; Berman, LaShondra; Warnes, Christine; Barnes, Nathelia; Klimov, Alexander; Lindstrom, Stephen

    2011-07-01

    Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10(-1.3 - -0.7) 50% infectious doses (ID(50)) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation.

  18. Design and Performance of the CDC Real-Time Reverse Transcriptase PCR Swine Flu Panel for Detection of 2009 A (H1N1) Pandemic Influenza Virus▿†‡

    Science.gov (United States)

    Shu, Bo; Wu, Kai-Hui; Emery, Shannon; Villanueva, Julie; Johnson, Roy; Guthrie, Erica; Berman, LaShondra; Warnes, Christine; Barnes, Nathelia; Klimov, Alexander; Lindstrom, Stephen

    2011-01-01

    Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10−1.3∼−0.7 50% infectious doses (ID50) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation. PMID:21593260

  19. Cryoelectron Tomography of HIV-1 Envelope Spikes: Further Evidence for Tripod-Like Legs

    Science.gov (United States)

    Zhu, Ping; Winkler, Hanspeter; Chertova, Elena; Taylor, Kenneth A.; Roux, Kenneth H.

    2008-01-01

    A detailed understanding of the morphology of the HIV-1 envelope (Env) spike is key to understanding viral pathogenesis and for informed vaccine design. We have previously presented a cryoelectron microscopic tomogram (cryoET) of the Env spikes on SIV virions. Several structural features were noted in the gp120 head and gp41 stalk regions. Perhaps most notable was the presence of three splayed legs projecting obliquely from the base of the spike head toward the viral membrane. Subsequently, a second 3D image of SIV spikes, also obtained by cryoET, was published by another group which featured a compact vertical stalk. We now report the cryoET analysis of HIV-1 virion-associated Env spikes using enhanced analytical cryoET procedures. More than 2,000 Env spike volumes were initially selected, aligned, and sorted into structural classes using algorithms that compensate for the “missing wedge” and do not impose any symmetry. The results show varying morphologies between structural classes: some classes showed trimers in the head domains; nearly all showed two or three legs, though unambiguous three-fold symmetry was not observed either in the heads or the legs. Subsequently, clearer evidence of trimeric head domains and three splayed legs emerged when head and leg volumes were independently aligned and classified. These data show that HIV-1, like SIV, also displays the tripod-like leg configuration, and, unexpectedly, shows considerable gp41 leg flexibility/heteromorphology. The tripod-like model for gp41 is consistent with, and helps explain, many of the unique biophysical and immunological features of this region. PMID:19008954

  20. Evolutionary and Functional Analysis of Old World Primate TRIM5 Reveals the Ancient Emergence of Primate Lentiviruses and Convergent Evolution Targeting a Conserved Capsid Interface.

    Directory of Open Access Journals (Sweden)

    Kevin R McCarthy

    2015-08-01

    Full Text Available The widespread distribution of lentiviruses among African primates, and the lack of severe pathogenesis in many of these natural reservoirs, are taken as evidence for long-term co-evolution between the simian immunodeficiency viruses (SIVs and their primate hosts. Evidence for positive selection acting on antiviral restriction factors is consistent with virus-host interactions spanning millions of years of primate evolution. However, many restriction mechanisms are not virus-specific, and selection cannot be unambiguously attributed to any one type of virus. We hypothesized that the restriction factor TRIM5, because of its unique specificity for retrovirus capsids, should accumulate adaptive changes in a virus-specific fashion, and therefore, that phylogenetic reconstruction of TRIM5 evolution in African primates should reveal selection by lentiviruses closely related to modern SIVs. We analyzed complete TRIM5 coding sequences of 22 Old World primates and identified a tightly-spaced cluster of branch-specific adaptions appearing in the Cercopithecinae lineage after divergence from the Colobinae around 16 million years ago. Functional assays of both extant TRIM5 orthologs and reconstructed ancestral TRIM5 proteins revealed that this cluster of adaptations in TRIM5 specifically resulted in the ability to restrict Cercopithecine lentiviruses, but had no effect (positive or negative on restriction of other retroviruses, including lentiviruses of non-Cercopithecine primates. The correlation between lineage-specific adaptations and ability to restrict viruses endemic to the same hosts supports the hypothesis that lentiviruses closely related to modern SIVs were present in Africa and infecting the ancestors of Cercopithecine primates as far back as 16 million years ago, and provides insight into the evolution of TRIM5 specificity.

  1. Evaluation of European Cranberrybush (Viburnum opulus L. genotypes for agro-morphological, biochemical and bioactive characteristics in Turkey

    Directory of Open Access Journals (Sweden)

    Ersoy Nilda

    2017-12-01

    Full Text Available The study evaluated some agro-morphological (fruit weight, fruit flesh ratio, fruit skin colour, number of fruits per raceme, number of racemes per bush, biochemical (vitamin C, soluble solids content, organic acids, and bioactive (total phenolics, total anthocyanins, total flavonoids, and antioxidant capacity characteristics of the fruit of a number of selected European Cranberrybush (Viburnum opulus L. genotypes grown in the Sivas province of Turkey. To evaluate the antioxidant capacity, ferric reducing antioxidant power (FRAP assays were performed. The results showed genotype-specific differences in most of the agro-morphological, biochemical and bioactive characteristics. The range of fruit weight, number of fruits per raceme, and number of racemes per bush was between 0.67 and 0.82 g, 40.7 and 57.1, and 470 and 581, respectively. The highest vitamin C and soluble solids contents were found in the fruits of genotypes SIV-9 and SIV-6 as 39 mg per 100 g and 12.6%, respectively. Tartaric acid was the main organic acid in all the genotypes; it ranged from 120 to 144 mg per 100 g of fruit FW. Total phenolic, total anthocyanin and total flavonoid contents ranged from 621 to 987 mg gallic acid equivalents per 100 g, 15 to 51 mg cyanidin-3-rutinoside equivalents per 100 g, and 202 to 318 mg rutin equivalents per 100 g, respectively. Genotype SIV-10 had the highest antioxidant capacity (34.90 μmol Trolox per g, based on FRAP assays. The present study shows the potential of the evaluated European Cranberrybush genotypes for improving the nutritional value through germplasm enhancement programmes.

  2. Cloud chemistry in eastern China: Observations from Mt. Tai

    Science.gov (United States)

    Collett, J. L.; Shen, X.; Lee, T.; Wang, X.; Li, Y.; Wang, W.; Wang, T.

    2010-07-01

    Until recently, studies of fog and cloud chemistry in China have been rare - even though the fate of China’s large sulfur dioxide emissions depends, in part, on the ability of regional clouds to support rapid aqueous oxidation to sulfate. Sulfur dioxide oxidized in regional clouds is more likely to be removed by wet deposition while sulfur dioxide that undergoes slower gas phase oxidation is expected to survive longer in the atmosphere and be transported over a much broader spatial scale. Two 2008 field campaigns conducted at Mt. Tai, an isolated peak on the NE China plain, provide insight into the chemical composition of regional clouds and the importance of various aqueous phase sulfur oxidation pathways. Single and two-stage Caltech Active Strand Cloudwater Collectors were used to collect bulk and drop size-resolved samples of cloudwater. Collected cloudwater was analyzed for key species that influence in-cloud sulfate production, including pH, S(IV), H2O2, Fe and Mn. Other major cloud solutes, including inorganic ions, total organic carbon (TOC), formaldehyde, and organic acids were also analyzed, as were gas phase concentrations of SO2, O3, and H2O2. A wide range of cloud pH was observed, from below 3 to above 6. High concentrations of cloudwater sulfate were consistent with abundant sulfur dioxide emissions in the region. Sampled clouds were also found to contain high concentrations of ammonium, nitrate, and organic carbon. Peak TOC concentrations reached approximately 200 ppmC, among the highest concentrations ever measured in cloudwater. Hydrogen peroxide was found to be the dominant aqueous phase S(IV) oxidant when cloud pH was less than approximately 5.4. Despite its fast reaction with sulfur dioxide in cloud droplets, high concentrations of residual hydrogen peroxide were measured in some clouds implying a substantial additional capacity for sulfate production. Ozone was found to be an important S(IV) oxidant when cloud pH was high. Oxidation of S(IV

  3. Developmental dyslexia in Chinese and English populations: dissociating the effect of dyslexia from language differences

    Science.gov (United States)

    Hu, Wei; Lee, Hwee Ling; Zhang, Qiang; Liu, Tao; Geng, Li Bo; Seghier, Mohamed L.; Shakeshaft, Clare; Twomey, Tae; Green, David W.; Yang, Yi Ming

    2010-01-01

    Previous neuroimaging studies have suggested that developmental dyslexia has a different neural basis in Chinese and English populations because of known differences in the processing demands of the Chinese and English writing systems. Here, using functional magnetic resonance imaging, we provide the first direct statistically based investigation into how the effect of dyslexia on brain activation is influenced by the Chinese and English writing systems. Brain activation for semantic decisions on written words was compared in English dyslexics, Chinese dyslexics, English normal readers and Chinese normal readers, while controlling for all other experimental parameters. By investigating the effects of dyslexia and language in one study, we show common activation in Chinese and English dyslexics despite different activation in Chinese versus English normal readers. The effect of dyslexia in both languages was observed as less than normal activation in the left angular gyrus and in left middle frontal, posterior temporal and occipitotemporal regions. Differences in Chinese and English normal reading were observed as increased activation for Chinese relative to English in the left inferior frontal sulcus; and increased activation for English relative to Chinese in the left posterior superior temporal sulcus. These cultural differences were not observed in dyslexics who activated both left inferior frontal sulcus and left posterior superior temporal sulcus, consistent with the use of culturally independent strategies when reading is less efficient. By dissociating the effect of dyslexia from differences in Chinese and English normal reading, our results reconcile brain activation results with a substantial body of behavioural studies showing commonalities in the cognitive manifestation of dyslexia in Chinese and English populations. They also demonstrate the influence of cognitive ability and learning environment on a common neural system for reading. PMID:20488886

  4. Atypical sulcal anatomy in young children with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    G. Auzias

    2014-01-01

    Full Text Available Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory

  5. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

    NARCIS (Netherlands)

    Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

    2003-01-01

    We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

  6. Prosthetic

    Directory of Open Access Journals (Sweden)

    Pokpong Amornvit

    2014-01-01

    Full Text Available Ocular trauma can be caused by road traffic accidents, falls, assaults, or work-related accidents. Enucleation is often indicated after ocular injury or for the treatment of intraocular tumors, severe ocular infections, and painful blind eyes. Rehabilitation of an enucleated socket without an intraocular implant or with an inappropriately sized implant can result in superior sulcus deepening, enophthalmos, ptosis, ectropion, and lower lid laxity, which are collectively known as post-enucleation socket syndrome. This clinical report describes the rehabilitation of post-enucleation socket syndrome with a modified ocular prosthesis. Modifications to the ocular prosthesis were performed to correct the ptosis, superior sulcus deepening, and enophthalmos. The rehabilitation procedure produced satisfactory results.

  7. Listening to polyphonic music recruits domain-general attention and working memory circuits.

    Science.gov (United States)

    Janata, Petr; Tillmann, Barbara; Bharucha, Jamshed J

    2002-06-01

    Polyphonic music combines multiple auditory streams to create complex auditory scenes, thus providing a tool for investigating the neural mechanisms that orient attention in natural auditory contexts. Across two fMRI experiments, we varied stimuli and task demands in order to identify the cortical areas that are activated during attentive listening to real music. In individual experiments and in a conjunction analysis of the two experiments, we found bilateral blood oxygen level dependent (BOLD) signal increases in temporal (the superior temporal gyrus), parietal (the intraparietal sulcus), and frontal (the precentral sulcus, the inferior frontal sulcus and gyrus, and the frontal operculum) areas during selective and global listening, as compared with passive rest without musical stimulation. Direct comparisons of the listening conditions showed significant differences between attending to single timbres (instruments) and attending across multiple instruments, although the patterns that were observed depended on the relative demands of the tasks being compared. The overall pattern of BOLD signal increases indicated that attentive listening to music recruits neural circuits underlying multiple forms of working memory, attention, semantic processing, target detection, and motor imagery. Thus, attentive listening to music appears to be enabled by areas that serve general functions, rather than by music-specific cortical modules.

  8. HIV Structural Database

    Science.gov (United States)

    SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

  9. Keiserlik kullassepp Carl Fabergé : maailmast / Mirjam Peil

    Index Scriptorium Estoniae

    Peil, Mirjam, 1939-

    1998-01-01

    Peterburi meistri Carl Fabergé (1846-1920) tänapäeva rikkamatest kogudest USAs ja Venemaal. Huvi kasvust Fabergé loomingu vastu. Keiserliku kullassepa 1990. aastatel maailmas ringelnud suurnäitusest (koostajaiks Ermitaazh ja Washingtoni Fabergé Art Foundation). Lisaks Ermitaazhis püsiväljapanek Tsarskoe Selo ja Peterhofi kogudest

  10. Sotsioloogid räägivad TLÜ suvekoolis hirmust / Kaarel Kressa

    Index Scriptorium Estoniae

    Kressa, Kaarel, 1983-

    2011-01-01

    11. juulil alustab esimesi kursusi Tallinna ülikooli rahvusvaheline suveülikool Tallinn Summer School. Suvekooli peakursus on "Fear: Poetics and Practices", toimub ka sotsiaalturunduse, kommunikatsiooni ning ksenofoobia seoseid analüüsiv kursus. 22.-29 juulil õpetab suveülikoolis loovkirjutamist Kanada krimikirjanik Peter Robinson, kelle teoste aines kattub hirmukultuuri teemaga

  11. Software Independent Verification and Validation (SIV&V) Simplified

    Science.gov (United States)

    2006-12-01

    Midcourse Defense GOTS Government-Off-The-Shelf GSAM General Service Administration Acquisition Manual GTE General Telephone and Electronics GUI...Graphical User Interfaces HSI Hardware and Software Integration HSI Human Systems Integration HTP Hardware Test Plan HWCI Hardware...requirements are extracted and traced to the developer’s Software and Hardware Test Plans (STP and HTP ). This ensures adequacy of the test plans and also

  12. Superior temporal sulcus and social cognition in dangerous drivers

    Czech Academy of Sciences Publication Activity Database

    Zelinková, J.; Shaw, D. J.; Mareček, R.; Mikl, M.; Urbánek, Tomáš; Peterková, L.; Zámečník, P.; Brázdil, M.

    2013-01-01

    Roč. 83, December (2013), s. 1024-1030 ISSN 1053-8119 Institutional support: RVO:68081740 Keywords : fMRI * antisocial behavior * social cognition * STS Subject RIV: FH - Neurology Impact factor: 6.132, year: 2013

  13. In captive rhesus macaques, cervicovaginal inflammation is common but not associated with the stable polymicrobial microbiome.

    Directory of Open Access Journals (Sweden)

    Gregory Spear

    Full Text Available Vaginal inoculation of rhesus macaques (RM with simian immunodeficiency virus (SIV has been used to study the biology of HIV transmission. Although the results of vaginal SIV transmission experiments could be affected by vaginal inflammation, studies to date have been conducted without regard to levels of pre-existing genital inflammation present in RM. We collected cevicovaginal secretions (CVS from 33-36 RM during the mid menstrual cycle (day 10-20 at 2 time points approximately 8 months apart and characterized the mRNA and protein levels of inflammatory cytokines, chemokines and interferon-stimulated genes. There was extreme variability in the levels of inflammatory mediators (IFN-α, IFN-γ, IL-6, TNF, IL-1b, IP-10, MIG, IL-12 and IL-17. In most animals, the mRNA levels of the inflammatory mediators were similar in the 2 CVS samples collected 8 months apart, suggesting that genital inflammation is stable in a subset of captive female RM. At both time points the cervicovaginal microbiota had low levels of Lactobacillus and was relatively diverse with an average of 13 genera in the samples from the first time point (median 13, range 7-21 and an average of 11.5 genera in the samples from the second time point (median 11, range 5-20. Many of the macaques had similar microbiota in the samples collected 8 months apart. However, we found no correlation between specific bacterial genera and the mRNA or protein levels of the inflammatory mediators in the genital tract of RM in this study. It seems likely that results of published vaginal SIV transmission experiments in RM have been influenced by pre-existing inflammation in the animals used for the experiments.

  14. INCLUDING RISK IN ECONOMIC FEASIBILITY ANALYSIS:A STOCHASTIC SIMULATION MODEL FOR BLUEBERRY INVESTMENT DECISIONS IN CHILE

    Directory of Open Access Journals (Sweden)

    GERMÁN LOBOS

    2015-12-01

    Full Text Available ABSTRACT The traditional method of net present value (NPV to analyze the economic profitability of an investment (based on a deterministic approach does not adequately represent the implicit risk associated with different but correlated input variables. Using a stochastic simulation approach for evaluating the profitability of blueberry (Vaccinium corymbosum L. production in Chile, the objective of this study is to illustrate the complexity of including risk in economic feasibility analysis when the project is subject to several but correlated risks. The results of the simulation analysis suggest that the non-inclusion of the intratemporal correlation between input variables underestimate the risk associated with investment decisions. The methodological contribution of this study illustrates the complexity of the interrelationships between uncertain variables and their impact on the convenience of carrying out this type of business in Chile. The steps for the analysis of economic viability were: First, adjusted probability distributions for stochastic input variables (SIV were simulated and validated. Second, the random values of SIV were used to calculate random values of variables such as production, revenues, costs, depreciation, taxes and net cash flows. Third, the complete stochastic model was simulated with 10,000 iterations using random values for SIV. This result gave information to estimate the probability distributions of the stochastic output variables (SOV such as the net present value, internal rate of return, value at risk, average cost of production, contribution margin and return on capital. Fourth, the complete stochastic model simulation results were used to analyze alternative scenarios and provide the results to decision makers in the form of probabilities, probability distributions, and for the SOV probabilistic forecasts. The main conclusion shown that this project is a profitable alternative investment in fruit trees in

  15. Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences.

    Science.gov (United States)

    Love, Tanzy M T; Thurston, Sally W; Keefer, Michael C; Dewhurst, Stephen; Lee, Ha Youn

    2010-06-01

    The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef(103-111)RM9 (RM9), Tat(28-35)SL8 (SL8), and Gag(181-189)CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day(-1) within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day(-1) within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

  16. Is an HIV vaccine possible?

    Directory of Open Access Journals (Sweden)

    Nancy A. Wilson

    Full Text Available The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5 expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.

  17. Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Roman A Siddiqui

    Full Text Available In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV-infected male rhesus macaques, including an 'MHC adjusted' subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T, located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype.

  18. Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

    African Journals Online (AJOL)

    out to analyze the effects of various restriction enzymes on the HIV genome. A computer simulated model using Web cutter Version 2.0, and cytogenetic analysis. 339 restriction enzymes from Promega database, 10 HIV-1/SIVcpz genes, 10 HIV-2/SIVsmm genes and 10 other SIV genes. Gene sequences were fed into Web ...

  19. Evaluation of a hydrophilic gingival dental sealant in beagle dogs.

    Science.gov (United States)

    Sitzman, Clarence

    2013-01-01

    A liquid solution, gingival sealant containing polymers that form a barrier film upon application was evaluated in dogs. It is a non-toxic, low viscosity, hydrophilic barrier sealant that dries in approximately 10 to 15-seconds after subgingival application. It was designed as a preventative to be applied immediately following a professional oral hygiene procedure in order to block plaque and calculus formation in the sulcus and aid in the prevention of periodontal disease in companion animals. Additionally, the polymer was designed to promote an aerobic environment in the sulcus by oxygen and water transport through engineered pores within the polymer. A 30-day split-mouth, blinded study in two groups of 15 beagle dogs was used. Plaque was significantly (p periodontal disease in dogs.

  20. Young British Art / Hanno Soans

    Index Scriptorium Estoniae

    Soans, Hanno, 1974-

    2001-01-01

    1990ndate kunsti muutumisest. Inglise kunstniku Peter Daviese maalist "Kuum esimene sada" (1996), Gavin Turki vahakujuna valminud autoportreest "Pop". "Young British Art'i" uuskunstist ja Jasper Zoova installatsioonist "F1". Eri analüüsivõimalusi pakkuvatest töödest (Marko Laimre & Ene-Liis Semperi 2000. a. novembri ühisnäituse osa töid).

  1. Swine Influenza Viruses – Evolution and Zoonotic Potential

    DEFF Research Database (Denmark)

    Fobian, Kristina

    reassortants (H1avN2hu and H1pdmN2sw). The two reassortants were detected for the first time in 2011 and have since then become established and are now circulating in Danish pigs. Viral replication in nasal wash samples and viral load in respiratory organs were determined. Growth kinetics of the four SIVs were...

  2. DNH 109: A fragmentary hominin near-proximal ulna from Drimolen, South Africa

    Directory of Open Access Journals (Sweden)

    Andrew Gallagher

    2011-05-01

    Full Text Available We describe a fragmentary, yet significant, diminutive proximal ulna (DNH 109 from the Lower Pleistocene deposits of Drimolen, Republic of South Africa. On the basis of observable morphology and available comparative metrics, DNH 109 is definitively hominin and is the smallest African Plio-Pleistocene australopith ulna yet recovered. Mediolateral and anteroposterior dimensions of the proximal diaphysis immediately distal to the m. brachialis sulcus in DNH 109 yield an elliptical area (π/4 *m-l*a-p that is smaller than the A.L. 333-38 Australopithecus afarensis subadult from Hadar. Given the unusually broad mediolateral/anteroposterior diaphyseal proportions distal to the brachialis sulcus, the osseous development of the medial and lateral borders of the sulcus, and the overall size of the specimen relative to comparative infant, juvenile, subadult and adult comparative hominid ulnae (Gorilla, Pan and Homo, it is probable that DNH 109 samples an australopith of probable juvenile age at death. As a result of the fragmentary state of preservation and absence of association with taxonomically diagnostic craniodental remains, DNH 109 cannot be provisionally assigned to any particular hominin genus (Paranthropus or Homo at present. Nonetheless, DNH 109 increases our known sample of available Plio-Pleistocene subadult early hominin postcrania.

  3. Glial tumors in brodmann area 6: spread pattern and relationships to motor areas.

    Science.gov (United States)

    Shah, Komal B; Hayman, L Anne; Chavali, Lakshmi S; Hamilton, Jackson D; Prabhu, Sujit S; Wangaryattawanich, Pattana; Kumar, Vinodh A; Kumar, Ashok J

    2015-01-01

    The posterior frontal lobe of the brain houses Brodmann area 4, which is the primary motor cortex, and Brodmann area 6, which consists of the supplementary motor area on the medial portion of the hemisphere and the premotor cortex on the lateral portion. In this area, safe resection is dependent on accurate localization of the motor cortex and the central sulcus, which can usually be achieved by using thin-section imaging and confirmed by using other techniques. The most reliable anatomic landmarks are the "hand knob" area and the marginal ramus of the cingulate sulcus. Postoperatively, motor deficits can occur not only because of injury to primary motor cortex but also because of injury to the supplementary motor area. Unlike motor cortex injury, the supplementary motor area syndrome is transient, if it occurs at all. On the lateral hemisphere, motor and language deficits can also occur because of premotor cortex injury, but a dense motor deficit would indicate subcortical injury to the corticospinal tract. The close relationship of the subcortical motor fibers and premotor cortex is illustrated. In contrast to the more constant landmarks of the central sulcus and marginal ramus, which aid in preoperative localization, the variable interruptions in the precentral and cingulate sulci of the posterior frontal lobe seem to provide "cortical bridges" for spread of infiltrating gliomas. (©)RSNA, 2015.

  4. Association between patellar cartilage defects and patellofemoral geometry: a matched-pair MRI comparison of patients with and without isolated patellar cartilage defects.

    Science.gov (United States)

    Mehl, Julian; Feucht, Matthias J; Bode, Gerrit; Dovi-Akue, David; Südkamp, Norbert P; Niemeyer, Philipp

    2016-03-01

    To compare the geometry of the patellofemoral joint on magnetic resonance images (MRI) between patients with isolated cartilage defects of the patella and a gender- and age-matched control group of patients without patellar cartilage defects. A total of 43 patients (17 female, 26 male) with arthroscopically verified grade III and IV patellar cartilage defects (defect group) were compared with a matched-pair control group of patients with isolated traumatic rupture of the anterior cruciate ligament without cartilage defects of the patellofemoral joint. Preoperative MRI images were analysed retrospectively with regard to patellar geometry (width, thickness, facet angle), trochlear geometry (dysplasia according to Dejour, sulcus angle, sulcus depth, lateral condyle index, trochlea facet asymmetry, lateral trochlea inclination) and patellofemoral alignment (tibial tuberosity-trochlear groove distance, patella height, lateral patella displacement, lateral patellofemoral angle, patella tilt, congruence angle). In addition to the comparison of group values, the measured values were compared to normal values reported in the literature, and the frequency of patients with pathologic findings was compared between both groups. The defect group demonstrated a significantly higher proximal chondral sulcus angle (p patellofemoral joint. In particular, a flat and shallow trochlea, trochlea dysplasia and patella alta seem to contribute to the development of patellar cartilage defects, which must be taken into consideration when planning to do surgical cartilage repair at the patella. III.

  5. Clinical studies of brain functional images by motor activation using single photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Masahiro [Gifu Univ. (Japan). School of Medicine

    1998-09-01

    Thirty participants (10 normal controls; group A, 5 patients with brain tumors located near central sulcus without hemiparesis; group B, 10 patients with brain tumors located near central sulcus with hemiparesis; group C, and 5 patients with brain tumors besides the central regions with hemiparesis; group D) were enrolled. The images were performed by means of split-dose method with {sup 99m}Tc-ECD at rest condition (SPECT 1) and during hand grasping (SPECT 2). The activation SPECT were obtained by subtracting SPECT 1 from SPECT 2, and the functional mapping was made by the strict registration of the activation SPECT with 3D MRI. To evaluate the changes of CBF (%{Delta}CBF) of the sensorimotor and supplementary motor areas on the functional mapping, ratio of the average counts of SPECT 1 and SPECT 2 was calculated and statistically compared. The functional activation paradigms caused a significant increase of CBF in the sensorimotor area contra-lateral to the stimulated hand, although the sensorimotor area and the central sulcus in groups B and C were dislocated, compared with hemisphere of non-tumor side. The sensorimotor area ipsi-lateral to the stimulated hand could be detected in almost of all subjects. The supplementary motor area could be detected in all subjects. In group A, the average %{Delta}CBF were up 24.1{+-}4.3% in the contra-lateral sensorimotor area, and 22.3{+-}3.6% in the supplementary motor area, respectively. The average %{Delta}CBF in the contra-lateral sensorimotor area of group D was significantly higher than that of group A. The brain functional mapping by motor activation using SPECT could localize the area of cortical motor function in normal volunteers and patients with brain tumors. The changes of regional CBF by activation SPECT precisely assess the cortical motor function even in patients with brain tumors located near central sulcus. (K.H.)

  6. Real time fMRI: a tool for the routine presurgical localisation of the motor cortex

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, M.; Freund, M.; Schwindt, W.; Gaus, C.; Heindel, W. [University of Muenster, Department of Clinical Radiology, Munster (Germany); Greiner, C. [University of Muenster, Department of Neurosurgery, Munster (Germany)

    2005-02-01

    In patients with brain lesions adjacent to the central area, exact preoperative knowledge of the spatial relation of the tumour to the motor cortex is of major importance. Many studies have shown that functional magnetic resonance imaging (fMRI) is a reliable tool to identify the motor cortex. However, fMRI data acquisition and data processing are time-consuming procedures, and this prevents general routine clinical application. We report a new application of real time fMRI that allows immediate access to fMRI results by automatic on-line data processing. Prior to surgery we examined ten patients with a brain tumour adjacent to the central area. Three measurements were performed at a 1.5-T Magnetom Vision Scanner (Siemens, Forchheim, Germany) on seven patients and at a 1.5-T Intera Scanner (Philips, Best, The Netherlands) on three patients using a sequential finger-tapping paradigm for motor cortex activation versus at rest condition. Blood oxygen level-dependant (BOLD) images were acquired using a multislice EPI sequence (16 slices, TE 60, TR 6000, FOV 210 x 210, matrix 64 x 64). The central sulcus of the left hemisphere could be clearly identified by a maximum of cortical activity after finger tapping of the right hand in all investigated patients. In eight of ten patients the right central sulcus was localised by a signal maximum, whereas in two patients the central sulcus could not be identified due to a hemiparesis in one and strong motion artefacts in the second patient. Finger tapping with one side versus rest condition seems to result in more motion artefacts, while finger tapping of the right versus the left hand yielded the strongest signal in the central area. Real time fMRI is a quick and reliable method to identify the central sulcus and has the potential to become a clinical tool to assess patients non-invasively before neurosurgical treatment. (orig.)

  7. Clinical studies of brain functional images by motor activation using single photon emission computed tomography

    International Nuclear Information System (INIS)

    Kawaguchi, Masahiro

    1998-01-01

    Thirty participants (10 normal controls; group A, 5 patients with brain tumors located near central sulcus without hemiparesis; group B, 10 patients with brain tumors located near central sulcus with hemiparesis; group C, and 5 patients with brain tumors besides the central regions with hemiparesis; group D) were enrolled. The images were performed by means of split-dose method with 99m Tc-ECD at rest condition (SPECT 1) and during hand grasping (SPECT 2). The activation SPECT were obtained by subtracting SPECT 1 from SPECT 2, and the functional mapping was made by the strict registration of the activation SPECT with 3D MRI. To evaluate the changes of CBF (%ΔCBF) of the sensorimotor and supplementary motor areas on the functional mapping, ratio of the average counts of SPECT 1 and SPECT 2 was calculated and statistically compared. The functional activation paradigms caused a significant increase of CBF in the sensorimotor area contra-lateral to the stimulated hand, although the sensorimotor area and the central sulcus in groups B and C were dislocated, compared with hemisphere of non-tumor side. The sensorimotor area ipsi-lateral to the stimulated hand could be detected in almost of all subjects. The supplementary motor area could be detected in all subjects. In group A, the average %ΔCBF were up 24.1±4.3% in the contra-lateral sensorimotor area, and 22.3±3.6% in the supplementary motor area, respectively. The average %ΔCBF in the contra-lateral sensorimotor area of group D was significantly higher than that of group A. The brain functional mapping by motor activation using SPECT could localize the area of cortical motor function in normal volunteers and patients with brain tumors. The changes of regional CBF by activation SPECT precisely assess the cortical motor function even in patients with brain tumors located near central sulcus. (K.H.)

  8. An attempt to identify the functional areas of the cerebral cortex on CT slices parallel to the orbito-meatal line

    International Nuclear Information System (INIS)

    Tanabe, Hirotaka; Okuda, Junichiro; Nishikawa, Takashi; Nishimura, Tsuyoshi; Shiraishi, Junzo.

    1982-01-01

    In order to identify the functional brain areas, such as Broca's area, on computed tomography slices parallel to the orbito-meatal line, the numbers of Brodmann's cortical mapping were shown on a diagram of representative brain sections parallel to the orbito-meatal line. Also, we described a method, using cerebral sulci as anatomical landmarks, for projecting lesions shown by CT scan onto the lateral brain diagram. The procedures were as follows. The distribution of lesions on CT slices was determined by the identification of major cerebral sulci and fissures, such as the Sylvian fissure, the central sulcus, and the superior frontal sulcus. Those lesions were then projected onto the lateral diagram by comparing each CT slice with the horizontal diagrams of brain sections. The method was demonstrated in three cases developing neuropsychological symptoms. (author)

  9. Isotopic constraints on heterogeneous sulfate production in Beijing haze

    Directory of Open Access Journals (Sweden)

    P. He

    2018-04-01

    Full Text Available Discerning mechanisms of sulfate formation during fine-particle pollution (referred to as haze hereafter in Beijing is important for understanding the rapid evolution of haze and for developing cost-effective air pollution mitigation strategies. Here we present observations of the oxygen-17 excess of PM2.5 sulfate (Δ17O(SO42− collected in Beijing haze from October 2014 to January 2015 to constrain possible sulfate formation pathways. Throughout the sampling campaign, the 12-hourly averaged PM2.5 concentrations ranged from 16 to 323 µg m−3 with a mean of (141  ±  88 (1σ µg m−3, with SO42− representing 8–25 % of PM2.5 mass. The observed Δ17O(SO42− varied from 0.1 to 1.6 ‰ with a mean of (0.9  ±  0.3 ‰. Δ17O(SO42− increased with PM2.5 levels in October 2014 while the opposite trend was observed from November 2014 to January 2015. Our estimate suggested that in-cloud reactions dominated sulfate production on polluted days (PDs, PM2.5  ≥  75 µg m−3 of Case II in October 2014 due to the relatively high cloud liquid water content, with a fractional contribution of up to 68 %. During PDs of Cases I and III–V, heterogeneous sulfate production (Phet was estimated to contribute 41–54 % to total sulfate formation with a mean of (48  ±  5 %. For the specific mechanisms of heterogeneous oxidation of SO2, chemical reaction kinetics calculations suggested S(IV ( =  SO2 ⚫ H2O + HSO3−  +  SO32− oxidation by H2O2 in aerosol water accounted for 5–13 % of Phet. The relative importance of heterogeneous sulfate production by other mechanisms was constrained by our observed Δ17O(SO42−. Heterogeneous sulfate production via S(IV oxidation by O3 was estimated to contribute 21–22 % of Phet on average. Heterogeneous sulfate production pathways that result in zero-Δ17O(SO42−, such as S(IV oxidation by NO2 in aerosol water and/or by O2 via a

  10. Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003

    NARCIS (Netherlands)

    Reeth, K.; Brown, I.H.; Durrwald, R.; Foni, E.; Labarque, G.; Lenihan, P.; Maldonado, J.; Markowska-Daniel, I.; Pensaert, M.; Pospisil, Z.; Koch, G.

    2008-01-01

    Objectives Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance

  11. Influenza A virus infection dynamics in swine farms in Belgium, France, Italy and Spain 2006-2008

    NARCIS (Netherlands)

    Kyriakis, C.S.; Rose, N.; Foni, E.; Maldonado, J.; Loeffen, W.L.A.; Madec, F.; Simon, G.; Reeth, K.

    2013-01-01

    Avian-like H1N1 and reassortant H3N2 and H1N2 influenza A viruses with a human-like haemagglutinin have been co-circulating in swine in Europe for more than a decade. We aimed to examine the infection dynamics of the three swine influenza virus (SIV) lineages at the farm level, and to identify

  12. Crystallization and preliminary X-ray crystallographic analysis of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an immunodominant SIVmac239 Env epitope

    International Nuclear Information System (INIS)

    Gao, Feng; Bao, Jinku

    2013-01-01

    A primitive monoclinic crystal of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an SIVmac239 Env peptide was obtained and belonged to space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. The crystal diffracted to 2.55 Å resolution. Long-term nonprogression during simian immunodeficiency virus (SIV) infection has been strongly associated with the major histocompatibility complex (MHC) class I allele Mamu-B*17. Here, a complex of rhesus macaque Mamu-B*17 with rhesus macaque β 2 -microglobulin (β 2 m) and an immunodominant peptide (SIVmac239 Env241–251; LRCNDTNYSGF; Env LF11) derived from the SIV Env protein was crystallized by the hanging-drop method using PEG 3350 as a precipitating agent. The crystals belonged to the primitive monoclinic space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. Assuming the presence of one molecule in the asymmetric unit, the Matthews coefficient and solvent content were calculated to be 2.96 Å 3 Da −1 and 58.5%, respectively

  13. Viral/Host interaction in viral infections

    International Nuclear Information System (INIS)

    Le Grand, R.

    2006-01-01

    The major objectives of the Neuro-virology Department (SNV for 'Service de Neurovirologie') are related to the study of host/pathogen interactions, particularly during primate lentiviral infections. Various experimental models have been developed such as non-human primates infected with the HIV-related simian immunodeficiency viruses (SIV), as an animal model of human AIDS. The current research programs of the SNV following four main directions: 1) Study of the pathogenesis of primate lentiviral infection, including mucosal transmission of HIV/SIV, primary infection, dissemination to various reservoirs, neuro-pathogenesis and hematopoietic disorders; 2) Prevention of HIV transmission, particularly through vaccination but also by means of microbicides applied to genital mucosa and post-exposure treatment with antiviral drugs; 3) Cellular and molecular pharmacology of new antiviral compounds; 4) Development of new primate models of human hematological disorders like chronic myeloid leukemia cells and development on new gene transfer in hematopoietic cells based on the use of lentiviral vectors Main programs of the SNV will be presented as well as the perspective focused on the use of non invasive in vivo imaging approaches for the exploration of immune and hematopoietic cells

  14. Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein.

    Science.gov (United States)

    Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma; Heyndrickx, Leo; LaBranche, Celia; Applequist, Steven E; Jansson, Marianne; De Silva, Thushan; Back, Jaap Willem; Achour, Adnane; Scarlatti, Gabriella; Fomsgaard, Anders; Montefiori, David; Stewart-Jones, Guillaume; Spetz, Anna-Lena

    2014-06-15

    Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1. Copyright © 2014 by The American Association of Immunologists, Inc.

  15. An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy.

    Science.gov (United States)

    Lakritz, Jessica R; Yalamanchili, Samshita; Polydefkis, Michael J; Miller, Andrew D; McGrath, Michael S; Williams, Kenneth C; Burdo, Tricia H

    2017-08-01

    Peripheral neuropathy (PN) is a major comorbidity of HIV infection that is caused in part by chronic immune activation. HIV-PN is associated with infiltration of monocytes/macrophages to the dorsal root ganglia (DRG) causing neuronal loss and formation of Nageotte nodules. Here, we used an oral form of methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor, to specifically reduce activation of myeloid cells. MGBG is selectively taken up by monocyte/macrophages in vitro and inhibits HIV p24 expression and DNA viral integration in macrophages. Here, MGBG was administered to nine SIV-infected, CD8-depleted rhesus macaques at 21 days post-infection (dpi). An additional nine SIV-infected, CD8-depleted rhesus macaques were used as untreated controls. Cell traffic to tissues was measured by in vivo BrdU pulse labeling. MGBG treatment significantly diminished DRG histopathology and reduced the number of CD68+ and CD163+ macrophages in DRG tissue. The number of recently trafficked BrdU+ cells in the DRG was significantly reduced with MGBG treatment. Despite diminished DRG pathology, intraepidermal nerve fiber density (IENFD) did not recover after treatment with MGBG. These data suggest that MGBG alleviated DRG pathology and inflammation.

  16. Mamu-A*01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development

    International Nuclear Information System (INIS)

    Li Jinliang; Srivastava, Tumul; Rawal, Ravindra; Manuel, Edwin; Isbell, Donna; Tsark, Walter; La Rosa, Corinna; Wang Zhongde; Li Zhongqi; Barry, Peter A.; Hagen, Katharine D.; Longmate, Jeffrey; Diamond, Don J.

    2009-01-01

    We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2K b domains) MHC Class I molecules were derived by transgenesis of the H-2K b D b double MHC Class I knockout strain. After immunization of Mamu-A*01/K b Tg mice with rVV-SIVGag-Pol, the mice generated CD8 + T-cell IFN-γ responses to several known Mamu-A*01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A*01/K b Tg mice provide a model system to study the Mamu-A*01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.

  17. The Design and Risk Management of Structured Finance Vehicles

    Directory of Open Access Journals (Sweden)

    Sanjiv Das

    2016-10-01

    Full Text Available Special investment vehicles (SIVs, extremely popular financial structures for the creation of highly-rated tranched securities, experienced spectacular demise in the 2007-2008 financial crisis. These financial vehicles epitomize the shadow banking sector, characterized by high leverage, undiversified asset pools, and long-dated assets supported by short-term debt, thus bearing material rollover risk on their liabilities which led to defeasance. This paper models these vehicles, and shows that imposing leverage risk control triggers can be optimal for all capital providers, though they may not always be appropriate. The efficacy of these risk controls varies depending on anticipated asset volatility and fire-sale discounts on defeasance. Despite risk management controls, we show that a high failure rate is inherent in the design of these vehicles, and may be mitigated to some extent by including contingent capital provisions in the ex-ante covenants. Post the recent subprime financial crisis, we inform the creation of safer SIVs in structured finance, and propose avenues of mitigating risks faced by senior debt through deleveraging policies in the form of leverage risk controls and contingent capital.

  18. Kinetics, mechanism and thermodynamics of bisulfite-aldehyde adduct formation

    Energy Technology Data Exchange (ETDEWEB)

    Olson, T.M.; Boyce, S.D.; Hoffmann, M.R.

    1986-04-01

    The kinetics and mechanism of bisulfite addition to benzaldehyde were studied at low pH in order to assess the importance of this reaction in stabilizing S(IV) in fog-, cloud-, and rainwater. Previously, the authors established that appreciable concentrations of the formaldehyde-bisulfite adduct (HMSA) are often present in fogwater. Measured HMSA concentrations in fogwater often do not fully account for observed excess S(IV) concentrations, however, so that other S(IV)-aldehyde adducts may be present. Reaction rates were determined by monitoring the disappearance of benzaldehyde by U.V. spectrophotometry under pseudo-first order conditions, (S(IV))/sub T/ >>(phi-CHO)/sub T/, in the pH range 0 - 4.4 at 25/sup 0/C. The equilibrium constant was determined by dissolving the sodium salt of the addition compound in a solution adjusted to pH 3.9, and measuring the absorbance of the equilibrated solution at 250 nm. A literature value of the extinction coefficient for benzaldehyde was used to calculate the concentration of free benzaldehyde. All solutions were prepared under an N/sub 2/ atmosphere using deoxygenated, deionized water and ionic strength was maintained at 1.0 M with sodium chloride.

  19. Characterization of reactants, reaction mechanisms, and reaction products in atmospheric water droplets: fog, cloud, dew, and rain water chemistry. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, M.R.; Jacob, D.J.; Waldman, J.M.; Munger, J.W.; Flagan, R.C.

    1985-04-01

    Analyses of ground-based fogwater collected by inertial impaction in the Los Angeles basin, the San Gabriel Mountains, and the San Joaquin Valley revealed very high concentrations of NO3 SO4 S, NH4 , and other ions, often coupled with very high acidities. Fogs and strata in the Los Angeles basin typically had pH values ranging from 2 to 4. Acidities were not as high in the San Joaquin Valley, mostly because of scavenging by the fogs of ammonia from agricultural sources. Deposition of fogwater was observed to be an important pollutant sink during stagnation episodes in the San Joaquin Valley, and may also be an important source of acid input to surfaces in some areas. Kinetic experiments showed that H2O2 is important in the oxidation of S(IV) to S(VI) at low pH. Metal-catalyzed autoxidation could also be an important source of sulfate. However, the extreme acidities observed in fogs (below pH 3) require condensation on preexistent acidic nuclei and scavenging of gaseous nitric acid. Stabilization of S(IV) in the fog was observed, and this was attributed to the formation of S(IV)-aldehyde adducts.

  20. Viral/Host interaction in viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Le Grand, R. [CEA Fontenay-aux-Roses, Service de Neurovirologie, 92 (France)

    2006-07-01

    The major objectives of the Neuro-virology Department (SNV for 'Service de Neurovirologie') are related to the study of host/pathogen interactions, particularly during primate lentiviral infections. Various experimental models have been developed such as non-human primates infected with the HIV-related simian immunodeficiency viruses (SIV), as an animal model of human AIDS. The current research programs of the SNV following four main directions: 1) Study of the pathogenesis of primate lentiviral infection, including mucosal transmission of HIV/SIV, primary infection, dissemination to various reservoirs, neuro-pathogenesis and hematopoietic disorders; 2) Prevention of HIV transmission, particularly through vaccination but also by means of microbicides applied to genital mucosa and post-exposure treatment with antiviral drugs; 3) Cellular and molecular pharmacology of new antiviral compounds; 4) Development of new primate models of human hematological disorders like chronic myeloid leukemia cells and development on new gene transfer in hematopoietic cells based on the use of lentiviral vectors Main programs of the SNV will be presented as well as the perspective focused on the use of non invasive in vivo imaging approaches for the exploration of immune and hematopoietic cells.

  1. Ainuke püsiv asi on muutumine / Anneliis Aunapuu

    Index Scriptorium Estoniae

    Aunapuu, Anneliis

    2008-01-01

    Taani audiovideotehnikat disainivast firmast Jacob Jensen Design. Jacob Jenseni (sünd. 1926) asutatud büroo loomingut tutvustab tema poeg Timothy Jacob Jensen (sünd. 1962). Eesti disaini tasemest, Jaapani disainitoodangust. Esikaanel ja lk. B3 fotod Timothy Jacob Jensenist

  2. A selective sweep in chimpanzees : is SIV the culprit?

    NARCIS (Netherlands)

    Groot, N.G. de

    2010-01-01

    The human immunodeficiency virus type 1 (HIV-1) is a major threat to mankind, as most infected individuals develop a lethal disease called acquired immunodeficiency syndrome (AIDS). However, a minority group of individuals are long-term non-progressors (LTNP), and resistance to AIDS is strongly

  3. Bone single photon emission computed tomography (SPECT in a patient with Pancoast tumor: a case report

    Directory of Open Access Journals (Sweden)

    Hamid Javadi

    Full Text Available CONTEXT: Non-small cell lung carcinomas (NSCLCs of the superior sulcus are considered to be the most challenging type of malignant thoracic disease. In this disease, neoplasms originating mostly from the extreme apex of the lung expand to the chest wall and thoracic inlet structures. Multiple imaging procedures have been applied to identify tumors and to stage and predict tumor resectability in surgical operations. Clinical examinations to localize pain complaints in shoulders and down the arms, and to screen for Horner's syndrome and abnormalities seen in paraclinical assessments, have been applied extensively for differential diagnosis of superior sulcus tumors. Although several types of imaging have been utilized for diagnosing and staging Pancoast tumors, there have been almost no reports on the efficiency of whole-body bone scans (WBBS for detecting the level of abnormality in cases of superior sulcus tumors. CASE REPORT: We describe a case of Pancoast tumor in which technetium-99m methylene diphosphonate (Tc-99m MDP bone single-photon emission-computed tomography (SPECT was able to accurately detect multiple areas of abnormality in the vertebrae and ribs. In describing this case, we stress the clinical and diagnostic points, in the hope of stimulating a higher degree of suspicion and thereby facilitating appropriate diagnosis and treatment. From the results of this study, further clinical trials to evaluate the potential of SPECT as an efficient imaging tool for the work-up on cases of Pancoast tumor are recommended.

  4. Does increased femoral antetorsion predispose to cartilage lesions of the patellofemoral joint?

    Science.gov (United States)

    Oppermann, Johannes; Bredow, Jan; Wissusek, Boris; Spies, Christian Karl; Boese, Christoph Kolja; Chang, Shi-Min; Eysel, Peer; Dargel, Jens

    2017-09-01

    The purpose of this study was to investigate whether there was a relationship between femoral neck antetorsion and the presence and pattern of osteoarthritis of the patellofemoral joint. It was hypothesized that an increased femoral neck antetorsion (1) correlates with osteoarthritic changes of the lateral facet of the patellofemoral joint and (2) correlates with an increased lateral trochlear height and a decreased sulcus angle. Seventy-eight formalin-embedded cadaveric lower extremities from thirty-nine subjects with a median age of 74 years (range 60-88) were used. Surrounding soft tissues of the lower limb were removed. The femoral neck antetorsion was measured and referenced to the transepicondylar axis and the posterior condylar line. The height of the medial and lateral facet of the trochlea and the sulcus angle was measured. The location and the degree of patellofemoral cartilage degeneration were recorded. A Pearson's correlation analysis was performed to correlate the femoral neck antetorsion with the measured knee parameters. No significant correlation could be found between the femoral antetorsion and cartilage degeneration of the lateral patellofemoral joint (n.s.), the height of the lateral trochlea (n.s.) and the sulcus angle (n.s.). This study could not document that the femoral neck antetorsion and subsequent internal rotation of the distal femur correlated with the degree of degeneration of the lateral facet of the patellofemoral joint. Clinically, femoral internal rotation may play a minor role in the development of lateral patellofemoral joint degeneration.

  5. Anatomical study of minor alterations in neonate vocal folds.

    Science.gov (United States)

    Silva, Adriano Rezende; Machado, Almiro José; Crespo, Agrício Nubiato

    2014-01-01

    Minor structural alterations of the vocal fold cover are frequent causes of voice abnormalities. They may be difficult to diagnose, and are expressed in different manners. Cases of intracordal cysts, sulcus vocalis, mucosal bridge, and laryngeal micro-diaphragm form the group of minor structural alterations of the vocal fold cover investigated in the present study. The etiopathogenesis and epidemiology of these alterations are poorly known. To evaluate the existence and anatomical characterization of minor structural alterations in the vocal folds of newborns. 56 larynxes excised from neonates of both genders were studied. They were examined fresh, or defrosted after conservation via freezing, under a microscope at magnifications of 25× and 40×. The vocal folds were inspected and palpated by two examiners, with the aim of finding minor structural alterations similar to those described classically, and other undetermined minor structural alterations. Larynges presenting abnormalities were submitted to histological examination. Six cases of abnormalities were found in different larynges: one (1.79%) compatible with a sulcus vocalis and five (8.93%) compatible with a laryngeal micro-diaphragm. No cases of cysts or mucosal bridges were found. The observed abnormalities had characteristics similar to those described in other age groups. Abnormalities similar to sulcus vocalis or micro-diaphragm may be present at birth. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  6. Influence of bacterial colonization of the healing screws on peri-implant tissue

    Directory of Open Access Journals (Sweden)

    Simonetta D'Ercole

    2013-06-01

    Conclusion: The healing screws left in situ for a period of 90 days caused a peri-implant inflammation and the presence of periodontal pathogenic bacteria in the peri-implant sulcus, due to the plaque accumulation on screw surfaces.

  7. Clinical and radiological follow-ups on onlays and overlays from student courses

    International Nuclear Information System (INIS)

    Amann, W.

    1982-01-01

    45 patients, whose teeth had been given onlays/overlays in student courses, were followed-up. The following values were measured: plaque index, sulcus bleeding index, clinical depth of the sulcus and the clinical findings for D (decayed) according to the DMF index for the maintained surfaces as well as for the control surfaces; beyond this eye tooth contact in lateral protrusion, lack of contact, approximal contact and approximal spatial orientation were evaluated. Bite wing pictures were taken and evaluated for the comprehension of iatrogenic marginal imperfections, for the control of the dentine in the area of the cervical edge of the filling and for the evaluation of the control surfaces. The maintained approximal surfaces were divided according to the degree of marginal imperfection into four imperfection groups. The data which were collected into a study list were evaluated statistically. (TRV) [de

  8. Attempt to identify the functional areas of the cerebral cortex on CT slices parallel to the orbito-meatal line

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Hirotaka; Okuda, Junichiro; Nishikawa, Takashi; Nishimura, Tsuyoshi (Osaka Univ. (Japan). Faculty of Medicine); Shiraishi, Junzo

    1982-06-01

    In order to identify the functional brain areas, such as Broca's area, on computed tomography slices parallel to the orbito-meatal line, the numbers of Brodmann's cortical mapping were shown on a diagram of representative brain sections parallel to the orbito-meatal line. Also, we described a method, using cerebral sulci as anatomical landmarks, for projecting lesions shown by CT scan onto the lateral brain diagram. The procedures were as follows. The distribution of lesions on CT slices was determined by the identification of major cerebral sulci and fissures, such as the Sylvian fissure, the central sulcus, and the superior frontal sulcus. Those lesions were then projected onto the lateral diagram by comparing each CT slice with the horizontal diagrams of brain sections. The method was demonstrated in three cases developing neuropsychological symptoms.

  9. Koeajossa EBSCO Discovery Service versus Primo Central Index

    OpenAIRE

    Jokiranta, Hannu; Kivikoski, Kaija

    2015-01-01

    Laurean ja Metropolian kirjastot aloittivat lokakuussa 2015 EBSCO Discovery Servicen (EDS) koekäyttöjakson. Kirjastot tutkivat omalle organisaatiolle lisensioitujen artikkelitietokantojen sisältöjen löytyvyyttä EDS:ssä ja vertailivat tuloksia omien Finna-näkymiensä Primo Central Index (PCI) -haun kautta saatuihin tuloksiin. Löytyikö eroja ja kuinka finnat pärjäsivät EDS:lle?

  10. Kinetic analysis of polyoxometalate (POM) oxidation of non-phenolic lignin model compound

    Science.gov (United States)

    Tomoya Yokoyama; Hou-min Chang; Ira A. Weinstock; Richard S. Reiner; John F. Kadla

    2003-01-01

    Kinetic and reaction mechanism of non-phenolic lignin model compounds under anaerobic polyoxometalate (POM), Na5(+1.9)[SiV1(-0.1)MoW10(+0.1) 40], bleaching conditions were examined. Analyses using a syringyl type model, 1-(3,4,5-trimethoxyphenyl)ethanol (1), a guaiacyl type, 1-(3,4- imethoxyphenyl)ethanol (2), and 1- (4-ethoxy-3,5-dimethoxyphenyl)ethanol (3) suggest...

  11. Internal acid buffering in San Joaquin Valley fog drops and its influence on aerosol processing

    Science.gov (United States)

    Collett, Jeffrey L.; Hoag, Katherine J.; Rao, Xin; Pandis, Spyros N.

    Although several chemical pathways exist for S(IV) oxidation in fogs and clouds, many are self-limiting: as sulfuric acid is produced and the drop pH declines, the rates of these pathways also decline. Some of the acid that is produced can be buffered by uptake of gaseous ammonia. Additional internal buffering can result from protonation of weak and strong bases present in solution. Acid titrations of high pH fog samples (median pH=6.49) collected in California's San Joaquin Valley reveal the presence of considerable internal acid buffering. In samples collected at a rural location, the observed internal buffering could be nearly accounted for based on concentrations of ammonia and bicarbonate present in solution. In samples collected in the cities of Fresno and Bakersfield, however, significant additional, unexplained buffering was present over a pH range extending from approximately four to seven. The additional buffering was found to be associated with dissolved compounds in the fogwater. It could not be accounted for by measured concentrations of low molecular weight ( C1- C3) carboxylic acids, S(IV), phosphate, or nitrophenols. The amount of unexplained buffering in individual fog samples was found to correlate strongly with the sum of sample acetate and formate concentrations, suggesting that unmeasured organic species may be important contributors. Simulation of a Bakersfield fog episode with and without the additional, unexplained buffering revealed a significant impact on the fog chemistry. When the additional buffering was included, the simulated fog pH remained 0.3-0.7 pH units higher and the amount of sulfate present after the fog evaporated was increased by 50%. Including the additional buffering in the model simulation did not affect fogwater nitrate concentrations and was found to slightly decrease ammonium concentrations. The magnitude of the buffering effect on aqueous sulfate production is sensitive to the amount of ozone present to oxidize S(IV

  12. A simple Cr(VI)–S(IV)–O{sub 2} system for rapid and simultaneous reduction of Cr(VI) and oxidative degradation of organic pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Yanan; Yang, Shaojie [Department of Environmental Science, Hubei Key Lab of Biomass Resource Chemistry and Environmental Biotechnology, School of Resources and Environmental Science, Wuhan University, 430079 (China); Zhou, Danna, E-mail: zdncug@163.com [Faculty of Material Science and Chemistry, China University of Geosciences, Wuhan 430074 (China); Wu, Feng [Department of Environmental Science, Hubei Key Lab of Biomass Resource Chemistry and Environmental Biotechnology, School of Resources and Environmental Science, Wuhan University, 430079 (China)

    2016-04-15

    Highlights: • Rapid and simultaneous reduction of Cr(VI) and degradation of organic pollutants occur. • Oxysulfur radicals generated in Cr(VI)–S(IV)–O{sub 2} system oxidize the organic pollutants. • Acidic pH facilitates the reactions from both directions of reduction and oxidation. • Degradation potential of aromatic amines depends on the substituted groups. • Cr(VI)–S(IV)–O{sub 2} system is promising for “waste control by waste”. - Abstract: Hexavalent chromium (Cr(VI)), a heavy-metal contaminant, can be easily reduced to less toxic trivalent chromium (Cr(III)) by sulfite ions (S(IV)). However, S(IV) has not drawn as much attention as the ferrous ion has. We report herein a novel Cr(VI)–S(IV)–O{sub 2} system containing sulfite ions that rapidly and simultaneously reduces Cr(VI) and oxidize organic pollutants in the presence of oxygen in aqueous solutions. This Cr(VI)–S(IV)-O{sub 2} system contains the initiator Cr(VI), the reductant S(IV), and the oxidant O{sub 2}, which produce oxysulfur radicals (mainly SO{sub 4}·{sup −} and SO{sub 5}·{sup −}) and hydroxyl radicals (OH·). The Cr(VI)/S(IV) molar ratio, pH, and oxygen content play important roles in the entire reaction system. Acidic conditions (pH 3.0) facilitated degradation of organic compounds and reduction of Cr(VI) as well. In addition, experiments of rapid degradation of several kinds of organic pollutants such as azo dye (acid orange 7, AO7), aniline, phenol, bisphenol A etc were also conducted. Preliminary results show that the removal rates of the analogs of phenols or aromatic amines in this Cr(VI)–S(IV)–O{sub 2} system have a relationship with the electronic parameters (Hammett constant, σ) of the substituted groups. Thus, the Cr(VI)–S(IV)–O{sub 2} system, provides an excellent strategy of “waste control by waste” for removing multiple industrial contaminants.

  13. Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection

    Directory of Open Access Journals (Sweden)

    Pedersen Niels C

    2007-04-01

    Full Text Available Abstract Background We reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251 mutants with a K65R mutation in reverse transcriptase (RT, and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later. Results The early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia. Conclusion This is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be

  14. Oral lipomas: A report of two cases

    African Journals Online (AJOL)

    McRoy

    2014-03-30

    Mar 30, 2014 ... surfaced, yellowish pink mass covered by a readily vascular network ... ABSTRACT. Background: Lipomas of oral origin are rare unlike other parts of the body. ... a mass in the right buccal sulcus measuring 7.5 x 3 cm adjacent.

  15. The use of implant retained mandibular prostheses in the oral rehabilitation of head and neck cancer patients. A review and rationale for treatment planning

    NARCIS (Netherlands)

    Schoen, PJ; Reintsema, H; Raghoebar, GM; Vissink, A; Roodenburg, JLN

    2004-01-01

    Surgical treatment of malignancies in the oral cavity (tongue, floor of the mouth, alveolus, buccal sulcus, oropharynx) often results in an unfavourable anatomic situation for prosthodontic rehabilitation. The outcome is a severe disturbance of oral functioning despite the improved surgical

  16. Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets.

    Science.gov (United States)

    Fujino, Masayuki; Sato, Hirotaka; Okamura, Tomotaka; Uda, Akihiko; Takeda, Satoshi; Ahmed, Nursarat; Shichino, Shigeyuki; Shiino, Teiichiro; Saito, Yohei; Watanabe, Satoru; Sugimoto, Chie; Kuroda, Marcelo J; Ato, Manabu; Nagai, Yoshiyuki; Izumo, Shuji; Matsushima, Kouji; Miyazawa, Masaaki; Ansari, Aftab A; Villinger, Francois; Mori, Kazuyasu

    2017-07-01

    Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4 + T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4 + T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3 + CCR5 + CD4 + T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3 + T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14 + CD16 + monocytes and MAC387 + macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387 + macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages. IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4 + T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3

  17. Mesial temporal lobe morphology in intractable pediatric epilepsy: so-called hippocampal malrotation, associated findings, and relevance to presurgical assessment.

    Science.gov (United States)

    Leach, James L; Awwad, Reem; Greiner, Hansel M; Vannest, Jennifer J; Miles, Lili; Mangano, Francesco T

    2016-06-01

    OBJECTIVE Diagnostic criteria for hippocampal malrotation (HIMAL) on brain MRI typically include a rounded hippocampus, vertical collateral sulcus, and architectural blurring. Relationship to epileptogenesis remains speculative, and usefulness for surgical guidance is unknown. The study was performed to determine the prevalence of hippocampal rotational anomalies in a cohort of pediatric patients with intractable epilepsy undergoing evaluation for surgery and to determine the significance of this finding in the context of surgical planning. METHODS Forty-eight surgically treated children with intractable epilepsy were compared with matched healthy subjects; reviewers were blinded to surgical side. Each temporal lobe was evaluated for rounded hippocampus, blurring, vertical collateral sulcus, wide choroidal fissure, enlarged temporal horn, low fornix, hippocampal signal, and findings of hippocampal sclerosis. A mesial temporal lobe (MTL) score was calculated by summing the number of features, and the collateral sulcus angle (CSA) was measured in each temporal lobe. Surgical side, pathological diagnosis, and imaging findings elsewhere in the brain were tabulated. Presence of HIMAL, associated imaging features, and MTL score were compared between sides, between epilepsy and control groups, in relationship to side of surgery, and in relationship to postoperative outcome. RESULTS Only 3 epilepsy patients (6.2%) and no controls exhibited all 3 features of HIMAL (p = 0.12). Eight of 48 (16.7%) epilepsy versus 2 of 48 (4.6%) control subjects had both a rounded hippocampus and vertical collateral sulcus (suggesting HIMAL) (p = 0.045). In control and epilepsy subjects, most findings were more prevalent on the left, and the left CSA was more vertical (p Epilepsy subjects had higher MTL scores (z = -2.95, p = 0.002) and more acute CSAs (p = 0.04) than controls. Only lateralizing raw MTL score had a significant association with surgical side (p = 0.03, OR 7.33); however, this

  18. Multisensory Interactions between Auditory and Haptic Object Recognition

    DEFF Research Database (Denmark)

    Kassuba, Tanja; Menz, Mareike M; R�der, Brigitte

    2013-01-01

    and haptic object features activate cortical regions that host unified conceptual object representations. The left fusiform gyrus (FG) and posterior superior temporal sulcus (pSTS) showed increased activation during crossmodal matching of semantically congruent but not incongruent object stimuli. In the FG...

  19. Learning of spatial relationships between observed and imitated actions allows invariant inverse computation in the frontal mirror neuron system.

    Science.gov (United States)

    Oh, Hyuk; Gentili, Rodolphe J; Reggia, James A; Contreras-Vidal, José L

    2011-01-01

    It has been suggested that the human mirror neuron system can facilitate learning by imitation through coupling of observation and action execution. During imitation of observed actions, the functional relationship between and within the inferior frontal cortex, the posterior parietal cortex, and the superior temporal sulcus can be modeled within the internal model framework. The proposed biologically plausible mirror neuron system model extends currently available models by explicitly modeling the intraparietal sulcus and the superior parietal lobule in implementing the function of a frame of reference transformation during imitation. Moreover, the model posits the ventral premotor cortex as performing an inverse computation. The simulations reveal that: i) the transformation system can learn and represent the changes in extrinsic to intrinsic coordinates when an imitator observes a demonstrator; ii) the inverse model of the imitator's frontal mirror neuron system can be trained to provide the motor plans for the imitated actions.

  20. Vitrectorhexis and lens aspiration with posterior chamber intraocular lens implantation in spherophakia.

    Science.gov (United States)

    Al-Haddad, Christiane; Khatib, Lama

    2012-07-01

    We describe a technique that uses the vitrector to perform successful lens aspiration and posterior chamber intraocular lens (IOL) implantation in children with spherophakia and anterior lens subluxation. After an anterior chamber maintainer is placed, the ocutome is introduced through a limbal incision to perform a circular vitrectorhexis to avoid excessive manipulation of the unstable lens followed by gentle cortex aspiration. A foldable IOL is injected into the sulcus (3-piece IOL) or bag (1-piece IOL) if the capsule is sufficiently stable. Through a pars plana incision, the ocutome is then used to perform a posterior capsulotomy to prevent late posterior capsule opacification. In our patient, sulcus IOL placement was more stable than in-the-bag placement. Neither author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.