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Sample records for ectosylvian sulcus siv

  1. Subcortical connections of an 'oculomotor' region in the ventral bank of the anterior ectosylvian sulcus in the cat.

    Science.gov (United States)

    Tamai, Y; Miyashita, E

    1989-12-01

    Subcortical connections of an 'oculomotor' region in the ventral bank of the anterior ectosylvian sulcus (AESo), where eye movements were evoked by intracortical microstimulation, were studied in cats using a wheatgerm agglutinin horseradish peroxidase (WGA-HRP) tracing method. Following injection of WGA-HRP into the AESo, both anterogradely-labeled terminals and retrogradely-labeled cells were found with the highest concentration in the suprageniculate nucleus and the medial zone of the lateroposterior nucleus of the thalamus. In the brainstem, anterogradely-labeled terminals were found in the superior colliculus, the pontine reticular formation, the pontine tegmental reticular formation and the pontine nuclei.

  2. SIV Infection of Lung Macrophages.

    Science.gov (United States)

    Li, Yue; Kang, Guobin; Duan, Lijie; Lu, Wuxun; Katze, Michael G; Lewis, Mark G; Haase, Ashley T; Li, Qingsheng

    2015-01-01

    HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  3. SIV Infection of Lung Macrophages.

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    Yue Li

    Full Text Available HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  4. Partial efficacy of a VSV-SIV/MVA-SIV vaccine regimen against oral SIV challenge in infant macaques.

    Science.gov (United States)

    Marthas, Marta L; Van Rompay, Koen K A; Abbott, Zachary; Earl, Patricia; Buonocore-Buzzelli, Linda; Moss, Bernard; Rose, Nina F; Rose, John K; Kozlowski, Pamela A; Abel, Kristina

    2011-04-12

    Despite antiretroviral medications, the rate of pediatric HIV-1 infections through breast-milk transmission has been staggering in developing countries. Therefore, the development of a vaccine to protect vulnerable infant populations should be actively pursued. We previously demonstrated that oral immunization of newborn macaques with vesicular stomatitis virus expressing simian immunodeficiency virus genes (VSV-SIV) followed 2 weeks later by an intramuscular boost with modified vaccinia ankara virus expressing SIV (MVA-SIV) successfully induced SIV-specific T and B cell responses in multiple lymphoid tissues, including the tonsil and intestine [13]. In the current study, we tested the oral VSV-SIV prime/systemic MVA-SIV boost vaccine for efficacy against multiple oral SIVmac251 challenges starting two weeks after the booster vaccination. The vaccine did not prevent SIV infection. However, in vaccinated infants, the level of SIV-specific plasma IgA (but not IgG) at the time of challenge was inversely correlated with peak viremia. In addition, the levels of SIV-specific IgA in saliva and plasma were inversely correlated with viral load at euthanasia. Animals with tonsils that contained higher frequencies of SIV-specific TNF-α- or IFN-γ-producing CD8(+) T cells and central memory T cells at euthanasia also had lower viremia. Interestingly, a marked depletion of CD25(+)FoxP3(+)CD4(+) T cells was observed in the tonsils as well as the intestine of these animals, implying that T regulatory cells may be a major target of SIV infection in infant macaques. Overall, the data suggest that, in infant macaques orally infected with SIV, the co-induction of local antiviral cytotoxic T cells and T regulatory cells that promote the development of IgA responses may result in better control of viral replication. Thus, future vaccination efforts should be directed towards induction of IgA and mucosal T cell responses to prevent or reduce virus replication in infants. Copyright

  5. Surgical management of superior sulcus tumors.

    Science.gov (United States)

    Dartevelle, P; Macchiarini, P

    1999-01-01

    Superior sulcus tumor refers to any primary lung cancer presenting with constant pain in the nerve distribution of the eighth cervical, first and second thoracic nerve roots and Horner's syndrome caused by invasion of the stellate ganglion. The pain is steady, severe, and unrelenting, involving the shoulder, the vertebral margin of the scapula and ulnar distribution of the arm to the elbow and finally to the ulnar surface of the forearm, and the small and ring fingers of the hand (Pancoast-Tobias syndrome). Weakness and atrophy of the hand muscles can also occur as the lesions spreads to involve the first and second ribs and vertebrae. Radiologically, there is a small shadow at the extreme apex of the lung with rib and possible vertebral body invasion. Pulmonary symptoms are less frequent because of the peripheral location of the lesions. Since Shaw and Paulson approached superior sulcus tumors in 1961 by using preoperative radiation-therapy (30 to 45 Gy in four weeks including the primary tumor, mediastinum and supraclavicular region) followed by surgical resection, this radiosurgical approach shortly became the standard treatment yielding better disease control and survival than that offered by other treatment modalities. It has now become evident that en bloc resection of the chest wall, involved adjacent structures as well as lobectomy must be considered the standard surgical approach for superior sulcus tumors combined with external radiation (preoperative, postoperative, or both). The goal of the operation is the complete and en bloc resection of the upper lobe in continuity with the invaded ribs, transverse processes, subclavian vessels, T1 nerve root, upper dorsal sympathetic chain and prevertebral muscles.

  6. Ab interno sulcus placement of glaucoma tube implants.

    Science.gov (United States)

    Camejo, Larissa; Noecker, Robert

    2008-01-01

    A modified technique for sulcus placement of glaucoma silicone tubes is described. Sulcus placement can be useful in patients with penetrating keratoplasty or in those who are at risk for corneal endothelial decompensation. However, correct placement can be difficult to confirm with a traditional ab externo approach. An ab interno technique for sulcus placement of glaucoma tube implants that both offers an easier approach and facilitates accurate positioning is described.

  7. Immunization with single-cycle SIV significantly reduces viral loads after an intravenous challenge with SIV(mac239.

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    Bin Jia

    2009-01-01

    Full Text Available Strains of simian immunodeficiency virus (SIV that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type SIV(mac239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (scSIV. Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of scSIV and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G trans-complemented scSIV. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented scSIV (VSV G scSIV. Broad T cell recognition of multiple viral antigens and Gag-specific CD4(+ T cell responses were also observed after boosting with VSV G scSIV. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with SIV(mac239. However, significantly lower viral loads and higher memory CD4(+ T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both scSIV immunization regimens resulted in containment of SIV(mac239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by scSIV was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV.

  8. Characterization of SIV in the Oral Cavity and in Vitro Inhibition of SIV by Rhesus Macaque Saliva

    Science.gov (United States)

    Thomas, Jessica S.; Lacour, Nedra; Kozlowski, Pamela A.; Nelson, Steve; Bagby, Gregory J.

    2010-01-01

    Abstract Human immunodeficiency virus (HIV) infections are rarely acquired via an oral route in adults. Previous studies have shown that human whole saliva inhibits HIV infection in vitro, and multiple factors present in human saliva have been shown to contribute to this antiviral activity. Despite the widespread use of simian immunodeficiency virus (SIV)-infected rhesus macaques as models for HIV pathogenesis and transmission, few studies have monitored SIV in the oral cavity of infected rhesus macaques and evaluated the viral inhibitory capacity of macaque saliva. Utilizing a cohort of rhesus macaques infected with SIVMac251, we monitored virus levels and genotypic diversity in the saliva throughout the course of the disease; findings were similar to previous observations in HIV-infected humans. An in vitro infectivity assay was utilized to measure inhibition of HIV/SIV infection by normal human and rhesus macaque whole saliva. Both human and macaque saliva were capable of inhibiting HIV and SIV infection. The inhibitory capacity of saliva samples collected from a cohort of animals postinfection with SIV increased over the course of disease, coincident with the development of SIV-specific antibodies in the saliva. These findings suggest that both innate and adaptive factors contribute to inhibition of SIV by whole macaque saliva. This work also demonstrates that SIV-infected rhesus macaques provide a relevant model to examine the innate and adaptive immune responses that inhibit HIV/SIV in the oral cavity. PMID:20672998

  9. Visualisation of Rouviere’s Sulcus during Laparoscopic Cholecystectomy

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    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.

  10. 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)

  11. CTL Escape and Viral Fitness in HIV/SIV Infection.

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    Seki, Sayuri; Matano, Tetsuro

    2011-01-01

    Cytotoxic T lymphocyte (CTL) responses exert a suppressive effect on HIV and simian immunodeficiency virus (SIV) replication. Under the CTL pressure, viral CTL escape mutations are frequently selected with viral fitness costs. Viruses with such CTL escape mutations often need additional viral genome mutations for recovery of viral fitness. Persistent HIV/SIV infection sometimes shows replacement of a CTL escape mutation with an alternative escape mutation toward higher viral fitness. Thus, multiple viral genome changes under CTL pressure are observed in the chronic phase of HIV/SIV infection. HIV/SIV transmission to HLA/MHC-mismatched hosts drives further viral genome changes including additional CTL escape mutations and reversions under different CTL pressure. Understanding of viral structure/function and host CTL responses would contribute to prediction of HIV evolution and control of HIV prevalence.

  12. 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.

  13. Evacuating Hypertensive Intracerebral Hematoma with a Cortical Sulcus Approach.

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    Gao, Zhibo; Qian, Lingtao; Niu, Chaoshi; Chen, Bin; Guo, Hongjun; Sun, Pengju; Wang, Yongzhi; Ning, Liang; Li, Qi; Fu, Xianming

    2016-11-01

    To study the curative effect and prognosis of patients with basal ganglia cerebral hemorrhages treated using a transcortical-sulcus approach and compare with results obtained using the traditional cerebral cortex approach. Clinical data were collected from 106 patients with hypertensive hemorrhage in the basal ganglia who were treated using either a transcortical-sulcus approach or traditional cerebral cortex approach. The rate of rehemorrhage, incidence of epilepsy, and 3-month efficacy (defined by an activities of daily living score) rate between the 2 groups were compared. The 3-month efficacy rates of patients treated using the transcortical-sulcus and traditional cerebral cortex surgical approaches were 78.4% and 60%, respectively (P seizures. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Mapping the small RNA content of simian immunodeficiency virions (SIV.

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    Markus Brameier

    Full Text Available Recent evidence indicates that regulatory small non-coding RNAs are not only components of eukaryotic cells and vesicles, but also reside within a number of different viruses including retroviral particles. Using ultra-deep sequencing we have comprehensively analyzed the content of simian immunodeficiency virions (SIV, which were compared to mock-control preparations. Our analysis revealed that more than 428,000 sequence reads matched the SIV mac239 genome sequence. Among these we could identify 12 virus-derived small RNAs (vsRNAs that were highly abundant. Beside known retrovirus-enriched small RNAs, like 7SL-RNA, tRNA(Lys3 and tRNA(Lys isoacceptors, we also identified defined fragments derived from small ILF3/NF90-associated RNA snaR-A14, that were enriched more than 50 fold in SIV. We also found evidence that small nucleolar RNAs U2 and U12 were underrepresented in the SIV preparation, indicating that the relative number or the content of co-isolated exosomes was changed upon infection. Our comprehensive atlas of SIV-incorporated small RNAs provides a refined picture of the composition of retrovirions, which gives novel insights into viral packaging.

  15. 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, ...Show Monocyte/macrophage traffic in HIV and SIV encephalitis. PubmedID 12960230 Title Monocyte/macrophage traffic

  16. Management of Lung Cancer Invading the Superior Sulcus.

    Science.gov (United States)

    Kratz, Johannes R; Woodard, Gavitt; Jablons, David M

    2017-05-01

    Superior sulcus tumors have posed a formidable therapeutic challenge since their original description by Pancoast and Tobias in the early twentieth century. Initial therapeutic efforts with radiotherapy were associated with high rates of relapse and mortality. Bimodality therapy with complete surgical resection in the 1960s paved the way for trimodality therapy as the current standard of care in the treatment of superior sulcus tumors. The evolution of treatment approaches over time has provided outcomes that come increasingly closer to rivaling those of similarly staged nonapical lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Rhesus macaque IFITM3 gene polymorphisms and SIV infection.

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    Michael Winkler

    Full Text Available Interferon-induced transmembrane proteins (IFITMs have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV and human immunodeficiency virus (HIV infection, respectively. Rhesus macaques (Macaca mulatta are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.

  18. Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation

    Science.gov (United States)

    Prétet, Jean-Luc; Michel-Salzat, Alice; Messent, Valérie; Bogdanova, Anna; Couëdel-Courteille, Anne; Souil, Evelyne; Cheynier, Rémi; Butor, Cécile

    2011-01-01

    Receptive ano-rectal intercourse is a major cause of HIV infection in men having sex with men and in heterosexuals. Current knowledge of the mechanisms of entry and dissemination during HIV rectal transmission is scarce and does not allow the development of preventive strategies. We investigated the early steps of rectal infection in rhesus macaques inoculated with the pathogenic isolate SIVmac251 and necropsied four hours to nine days later. All macaques were positive for SIV. Control macaques inoculated with heat-inactivated virus were consistently negative for SIV. SIV DNA was detected in the rectum as early as four hours post infection by nested PCR for gag in many laser-microdissected samples of lymphoid aggregates and lamina propria but never in follicle-associated epithelium. Scarce SIV antigen positive cells were observed by immunohistofluorescence in the rectum, among intraepithelial and lamina propria cells as well as in clusters in lymphoid aggregates, four hours post infection and onwards. These cells were T cells and non-T cells that were not epithelial cells, CD68+ macrophages, DC-SIGN+ cells or fascin+ dendritic cells. DC-SIGN+ cells carried infectious virus. Detection of Env singly spliced mRNA in the mucosa by nested RT-PCR indicated ongoing viral replication. Strikingly, four hours post infection colic lymph nodes were also infected in all macaques as either SIV DNA or infectious virus was recovered. Rapid SIV entry and dissemination is consistent with trans-epithelial transport. Virions appear to cross the follicle-associated epithelium, and also the digestive epithelium. Viral replication could however be more efficient in lymphoid aggregates. The initial sequence of events differs from both vaginal and oral infections, which implies that prevention strategies for rectal transmission will have to be specific. Microbicides will need to protect both digestive and follicle-associated epithelia. Vaccines will need to induce immunity in lymph nodes

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

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    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.

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

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    Roberts, Emily R; Carnathan, Diane G; Li, Hui; Shaw, George M; Silvestri, Guido; Betts, Michael R

    2016-12-01

    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.

  1. The integration hypothesis: An evolutionary pathway to benign SIV infection.

    NARCIS (Netherlands)

    Müller, V.; Boer, R.J. de

    Untreated human immunodeficiency virus (HIV) infection in humans is typically characterised by persistent high virus load, failure of the immune response to clear the virus, and fatal disease outcome. Natural hosts of closely related simian immunodeficiency viruses (SIVs)—e.g., sooty mangabeys

  2. Limited role for the thymus in SIV pathogenesis

    NARCIS (Netherlands)

    Borghans, José A. M.; Hazenberg, Mette D.; Miedema, Frank

    2005-01-01

    The role of the thymus in the pathogenesis of AIDS is a frequently discussed and controversial topic. Tuttleton Arron et al. studied the role of thymic output in SIV infection directly, by comparing the dynamics of TCR excision circles and CD4(+ )and CD8(+) T cell numbers in healthy and in

  3. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques

    Science.gov (United States)

    Guo, Ming; Xian, Qiao-Yang; Rao, Yan; Zhang, Jing; Wang, Yong; Huang, Zhi-Xiang; Wang, Xin; Bao, Rong; Zhou, Li; Liu, Jin-Biao; Tang, Zhi-Jiao; Guo, De-yin; Qin, Chuan; Li, Jie-Liang; Ho, Wen-Zhe

    2017-01-01

    Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-γ and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection. PMID:28133458

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

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    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

  5. Distal leucines are key functional determinants of Alix-binding simian immunodeficiency virus SIV(smE543) and SIV(mac239) type 3 L domains.

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    Bello, Nana F; Wu, Fan; Sette, Paola; Dussupt, Vincent; Hirsch, Vanessa M; Bouamr, Fadila

    2011-11-01

    In addition to PTAP L domains, primate lentiviruses carry Alix-binding motifs that include the recently described type 3 SREKPYKEVTEDLLHLNSLF sequence. We examined the requirements for the type 3 sequence motif in simian immunodeficiency virus SIV(smE543) and identified the (499)LNSLF(503) sequence as a key functional determinant. Mutation of distal leucines (499)L and (502)L (LL mutant) caused an inhibitory effect on Alix-dependent SIV(smE543) release that was quantitatively similar to that observed following disruption of the type 3 L domain or RNA interference (RNAi) depletion of Alix. Similar results were obtained with the SIV(mac239) LL mutant. Thus, distal leucines are key determinants of SIV(smE543) and SIV(mac239) type 3 L domains.

  6. Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV.

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    Van Rompay, Koen K A; Abel, Kristina; Earl, Patricia; Kozlowski, Pamela A; Easlick, Juliet; Moore, Joseph; Buonocore-Buzzelli, Linda; Schmidt, Kimberli A; Wilson, Robert L; Simon, Ian; Moss, Bernard; Rose, Nina; Rose, John; Marthas, Marta L

    2010-02-10

    In a previously developed infant macaque model mimicking HIV infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins provided partial protection against infection following oral inoculation with virulent SIV. In an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally administered, replicating vaccines. One group of newborn macaques received an oral prime immunization with a recombinant vesicular stomatitis virus expressing SIVmac239 gag, pol and env (VSV-SIVgpe), followed 2 weeks later by an intramuscular boost immunization with MVA-SIV. Another group received two immunizations with live-attenuated SIVmac1A11, administered each time both orally and intravenously. Control animals received mock immunizations or non-SIV VSV and MVA control vectors. Analysis of SIV-specific immune responses in blood and lymphoid tissues at 4 weeks of age demonstrated that both vaccine regimens induced systemic antibody responses and both systemic and local cell-mediated immune responses. The safety and immunogenicity of the VSV-SIVgpe+MVA-SIV immunization regimen described in this report provide the scientific incentive to explore the efficacy of this vaccine regimen against virulent SIV exposure in the infant macaque model. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Dating the age of the SIV lineages that gave rise to HIV-1 and HIV-2.

    Directory of Open Access Journals (Sweden)

    Joel O Wertheim

    2009-05-01

    Full Text Available Great strides have been made in understanding the evolutionary history of simian immunodeficiency virus (SIV and the zoonoses that gave rise to HIV-1 and HIV-2. What remains unknown is how long these SIVs had been circulating in non-human primates before the transmissions to humans. Here, we use relaxed molecular clock dating techniques to estimate the time of most recent common ancestor for the SIVs infecting chimpanzees and sooty mangabeys, the reservoirs of HIV-1 and HIV-2, respectively. The date of the most recent common ancestor of SIV in chimpanzees is estimated to be 1492 (1266-1685, and the date in sooty mangabeys is estimated to be 1809 (1729-1875. Notably, we demonstrate that SIV sequences sampled from sooty mangabeys possess sufficient clock-like signal to calibrate a molecular clock; despite the differences in host biology and viral dynamics, the rate of evolution of SIV in sooty mangabeys is indistinguishable from that of its human counterpart, HIV-2. We also estimate the ages of the HIV-2 human-to-human transmissible lineages and provide the first age estimate for HIV-1 group N at 1963 (1948-1977. Comparisons between the SIV most recent common ancestor dates and those of the HIV lineages suggest a difference on the order of only hundreds of years. Our results suggest either that SIV is a surprisingly young lentiviral lineage or that SIV and, perhaps, HIV dating estimates are seriously compromised by unaccounted-for biases.

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

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    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.

  10. [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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Coding of multisensory temporal patterns in human superior temporal sulcus

    Directory of Open Access Journals (Sweden)

    Toemme eNoesselt

    2012-08-01

    Full Text Available Philosophers, psychologists, and neuroscientists have long been interested in how the temporal aspects of perception are represented in the brain. In the present study, we investigated the neural basis of the temporal perception of synchrony/asynchrony for audiovisual speech stimuli using functional magnetic imaging (fMRI. Subjects judged the temporal relation of (asynchronous audiovisual speech streams, and indicated any changes in their perception of the stimuli over time. Differential hemodynamic responses for synchronous versus asynchronous stimuli were observed in the multisensory superior temporal sulcus complex (mSTS-c and prefrontal cortex. Within mSTS-c we found adjacent regions expressing an enhanced BOLD-response to the different physical (asynchrony conditions. These regions were further modulated by the subjects’ perceptual state. By calculating the distances between the modulated regions within mSTS-c in single-subjects we demonstrate that the ‘auditory’ and ‘visual leading areas’ lie closer to ‘synchrony areas’ than to each other. Moreover, analysis of interregional connectivity indicates a stronger functional connection between multisensory prefrontal cortex and mSTS-c during the perception of asynchrony. Taken together, these results therefore suggest the presence of distinct sub-regions within the human STS-c for the maintenance of temporal relations for audiovisual speech stimuli plus differential functional connectivity with prefrontal regions. The respective local activity in mSTS-c is dependent both upon the physical properties of the stimuli presented and upon the subjects’ perception of (asynchrony.

  16. Social cognition and the superior temporal sulcus: implications in autism.

    Science.gov (United States)

    Saitovitch, A; Bargiacchi, A; Chabane, N; Brunelle, F; Samson, Y; Boddaert, N; Zilbovicius, M

    2012-10-01

    The most common clinical sign of autism spectrum disorders (ASD) is social interaction impairment, which is associated with communication deficits and stereotyped behaviors. Based on brain-imaging results, our hypothesis is that abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD. These abnormalities are characterized by decreased grey matter concentration, rest hypoperfusion and abnormal activation during social tasks. STS anatomofunctional anomalies occurring early across brain development could constitute the first step in the cascade of neural dysfunctions underlying autism. It is known that STS is highly implicated on social perception processing, from perception of biological movements, such as body movements or eye gaze, to more complex social cognition processes. Among the impairments that can be described in social perception processing, eye gaze perception is particularly relevant in autism. Gaze abnormalities can now be objectively measured using eye-tracking methodology. In the present work, we will review recent data on STS contributions to normal social cognition and its implication in autism, with particular focus on eye gaze perception. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. Keyhole supracerebellar transtentorial transcollateral sulcus approach to the lateral ventricle.

    Science.gov (United States)

    Marcus, Hani J; Sarkar, Hrishikesh; Mindermann, Thomas; Reisch, Robert

    2013-12-01

    Meningiomas of the lateral ventricles are commonly located in the atria. Surgical access to such tumors is challenging because of their deep location and proximity to critical neurovascular structures, particularly if situated on the dominant side. Although a number of approaches have been described in the literature, most carry the risk of postoperative neuropsychological, visual, or speech deficits, especially when operating on the dominant hemisphere. The supracerebellar transtentorial transcollateral sulcus (STTCS) approach offers the potential to circumvent functionally important structures, reducing the risk of these approach-related neurological deficits. Two patients with dominant hemisphere trigonal meningiomas underwent surgical resection with the use of the STTCS approach. Neuronavigation was used to carefully plan the incision, craniotomy, and exposure, and also intraoperatively to orientate the operating surgeon at key steps, particularly when raising the tentorial flap in line with the tumor. Endoscopy was used to provide increased light intensity, an extended viewing angle, and higher magnification in comparison with a microscope. Specially designed tube-shaft instruments were also used to assist with manipulation through the narrow surgical corridor. In both cases, the tumors were fully resected without approach-related morbidity. The STTCS approach provides good access to tumors located in the trigonal region, reducing the risk of iatrogenic language or visual field deficits. In dominant hemisphere lesions, in the hands of an experienced neurosurgeon, the STTCS approach is an effective alternative to existing techniques.

  18. 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

    in dextrals than in sinistrals. Sinistrals forced to write with their non-preferred right hand display a pattern of central sulcus size asymmetry which is typical of dextrals, yet forced dextrality does not shift the handedness-specific location of the "hand knob". Hence, cortical morphology in adults holds...... sulcus is largely unexplored. In this paper, we propose first an original strategy based on manifold learning to quantify the shape of the central sulcus. Using this approach we show that the "hand knob", a major landmark of the hand motor representation, is sited more dorsally in the left hemisphere...

  19. Functional Organization of Social Perception and Cognition in the Superior Temporal Sulcus

    National Research Council Canada - National Science Library

    Deen, Ben; Koldewyn, Kami; Kanwisher, Nancy; Saxe, Rebecca

    2015-01-01

    The superior temporal sulcus (STS) is considered a hub for social perception and cognition, including the perception of faces and human motion, as well as understanding others' actions, mental states, and language...

  20. 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.

  1. Coding of multisensory temporal patterns in human superior temporal sulcus.

    Science.gov (United States)

    Noesselt, Tömme; Bergmann, Daniel; Heinze, Hans-Jochen; Münte, Thomas; Spence, Charles

    2012-01-01

    Philosophers, psychologists, and neuroscientists have long been interested in how the temporal aspects of perception are represented in the brain. In the present study, we investigated the neural basis of the temporal perception of synchrony/asynchrony for audiovisual speech stimuli using functional magnetic resonance imaging (fMRI). Subjects judged the temporal relation of (a)synchronous audiovisual speech streams, and indicated any changes in their perception of the stimuli over time. Differential hemodynamic responses for synchronous versus asynchronous stimuli were observed in the multisensory superior temporal sulcus complex (mSTS-c) and prefrontal cortex. Within mSTS-c we found adjacent regions expressing an enhanced BOLD-response to the different physical (a)synchrony conditions. These regions were further modulated by the subjects' perceptual state. By calculating the distances between the modulated regions within mSTS-c in single-subjects we demonstrate that the "auditory leading (A(L))" and "visual leading (V(L)) areas" lie closer to "synchrony areas" than to each other. Moreover, analysis of interregional connectivity indicates a stronger functional connection between multisensory prefrontal cortex and mSTS-c during the perception of asynchrony. Taken together, these results therefore suggest the presence of distinct sub-regions within the human STS-c for the maintenance of temporal relations for audiovisual speech stimuli plus differential functional connectivity with prefrontal regions. The respective local activity in mSTS-c is dependent both upon the physical properties of the stimuli presented and upon the subjects' perception of (a)synchrony.

  2. Isolated Central Sulcus Hemorrhage: A Rare Presentation Most Frequently Associated with Cerebral Amyloid Angiopathy

    Directory of Open Access Journals (Sweden)

    Murthy R. Chamarthy

    2012-01-01

    Full Text Available Central sulcus hemorrhage is a rare imaging finding that can be related to cerebral amyloidosis in a normotensive non-traumatic elderly patient and present as an isolated finding or in association with other areas of involvement. We report a case presenting with an isolated central sulcus hemorrhage on computed tomography. Further imaging work-up excluded other potential causes of peripheral hemorrhages and established a putative diagnosis of cerebral amyloidosis.

  3. 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.

  4. Defining HIV and SIV Reservoirs in Lymphoid Tissues

    Directory of Open Access Journals (Sweden)

    Claire Deleage

    2016-06-01

    Full Text Available A primary obstacle to an HIV-1 cure is long-lived viral reservoirs, which must be eliminated or greatly reduced. Cure strategies have largely focused on monitoring changes in T cell reservoirs in peripheral blood (PB, even though the lymphoid tissues (LT are primary sites for viral persistence. To track and discriminate viral reservoirs within tissue compartments we developed a specific and sensitive next-generation in situ hybridization approach to detect vRNA, including vRNA+ cells and viral particles (“RNAscope”, vDNA+ cells (“DNAscope” and combined vRNA and vDNA with immunohistochemistry to detect and phenotype active and latently infected cells in the same tissue section. RNAscope is highly sensitive with greater speed of analysis compared to traditional in situ hybridization. Highly sensitive and specific DNAscope detected SIV/HIV vDNA+ cells, including duplexed detection of vDNA and vRNA or immunophenotypic markers in the same section. Analysis of LT samples from macaques prior to and during combination antiretroviral therapy demonstrated that B cell follicles are an important anatomical compartment for both latent and active viral persistence during treatment. These new tools should allow new insights into viral reservoir biology and evaluation of cure strategies.

  5. Vaccination with Live Attenuated Simian Immunodeficiency Virus (SIV) Protects from Mucosal, but Not Necessarily Intravenous, Challenge with a Minimally Heterologous SIV.

    Science.gov (United States)

    Sutton, Matthew S; Burns, Charles M; Weiler, Andrea M; Balgeman, Alexis J; Braasch, Andrew; Lehrer-Brey, Gabrielle; Friedrich, Thomas C; O'Connor, Shelby L

    2016-06-15

    Few studies have evaluated the impact of the viral challenge route on protection against a heterologous simian immunodeficiency virus (SIV) challenge. We vaccinated seven macaques with a live attenuated SIV that differed from SIVmac239Δnef by 24 amino acids, called m3KOΔnef. All animals were protected from an intrarectal SIVmac239 challenge, whereas only four animals were protected from subsequent intravenous SIVmac239 challenge. These data suggest that immune responses elicited by vaccination with live attenuated SIV in an individual animal can confer protection from intrarectal challenge while remaining insufficient for protection from intravenous challenge. Our study is important because we show that vaccinated animals can be protected from a mucosal challenge with a heterologous SIV, but the same animals are not necessarily protected from intravenous challenge with the same virus. This is unique because in most studies, either vaccinated animals are challenged multiple times by the same route or only a single challenge is performed. An individually vaccinated animal is rarely challenged multiple times by different routes, so protection from different challenge routes cannot be measured in the same animal. Our data imply that vaccine-elicited responses in an individual animal may be insufficient for protection from intravenous challenge but may be suitable for protection from a mucosal challenge that better approximates human immunodeficiency virus (HIV) exposure. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. A comprehensive statistical investigation of schlieren image velocimetry (SIV) using high-velocity helium jet

    Science.gov (United States)

    Biswas, Sayan; Qiao, Li

    2017-03-01

    A detailed statistical assessment of seedless velocity measurement using Schlieren Image Velocimetry (SIV) was explored using open source Robust Phase Correlation (RPC) algorithm. A well-known flow field, an axisymmetric turbulent helium jet, was analyzed near and intermediate region (0≤ x/d≤ 20) for two different Reynolds numbers, Re d = 11,000 and Re d = 22,000 using schlieren with horizontal knife-edge, schlieren with vertical knife-edge and shadowgraph technique, and the resulted velocity fields from SIV techniques were compared to traditional Particle Image Velocimetry (PIV) measurements. A novel, inexpensive, easy to setup two-camera SIV technique had been demonstrated to measure high-velocity turbulent jet, with jet exit velocities 304 m/s (Mach = 0.3) and 611 m/s (Mach = 0.6), respectively. Several image restoration and enhancement techniques were tested to improve signal to noise ratio (SNR) in schlieren and shadowgraph images. Processing and post-processing parameters for SIV techniques were examined in detail. A quantitative comparison between self-seeded SIV techniques and traditional PIV had been made using correlation statistics. While the resulted flow field from schlieren with horizontal knife-edge and shadowgraph showed excellent agreement with PIV measurements, schlieren with vertical knife-edge performed poorly. The performance of spatial cross-correlations at different jet locations using SIV techniques and PIV was evaluated. Turbulence quantities like turbulence intensity, mean velocity fields, Reynolds shear stress influenced spatial correlations and correlation plane SNR heavily. Several performance metrics such as primary peak ratio (PPR), peak to correlation energy (PCE), the probability distribution of signal and noise were used to compare capability and potential of different SIV techniques.

  7. 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.

  8. Looking for the lunate sulcus: a magnetic resonance imaging study in modern humans.

    Science.gov (United States)

    Allen, John S; Bruss, Joel; Damasio, Hanna

    2006-08-01

    The position of the lunate sulcus in fossil endocasts (when it can be determined) may serve as a potential marker of cognitive development in extinct hominid species. While the lunate sulcus is reliably present in the brains of great apes and forms the anterolateral boundary of the primary visual cortex, in humans its presentation is much more variable, and even if present, it does not correspond to a functional region. Grafton Elliot Smith, who named the lunate sulcus, claimed that it was homologous in humans and the great apes. Using high-resolution MRI, we assessed the presence/absence and course of the lunate sulcus in 110 adult subjects. We found that in the vast majority of cases, lunate sulci identified on the surface of the occipital lobe are actually composed of smaller sulcal segments that converge into an apparently continuous composite lunate sulcus. We found only 3 examples in 220 hemispheres (1.4%) of continuous lunate sulci that resembled ape lunates in form (albeit in a more posterior position). Composite lunate sulci were found in 32.7% of left hemispheres and 26.4% of right hemispheres. These results, combined with those from histological and functional imaging studies, indicate that human and ape lunate sulci are not homologous structures. We suggest that the extent of functional reorganization of the occipital region during hominid evolution has been underestimated, and that changes in this region were not just passively shaped by expansion of parietal association cortex.

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S., E-mail: rveazey@tulane.edu

    2013-11-15

    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.

  11. Capabilities of optical SIV technique in measurements of flow velocity vector field dynamics

    Science.gov (United States)

    Mikheev, N. I.; Dushin, N. S.; Saushin, I. I.

    2017-11-01

    The main difference between Smoke Image Velocimetry (SIV) technique and the conventional PIV is that higher concentration of tracer particles typical of smoke visualization techniques is used in SIV. Not separate particles but smoke structures with continuous pixel intensity are visible in the recorded images. Owing to better smoke reflectivity, higher spatial and temporal resolution is obtained in the case when relatively simple equipment (camera and laser) is used. It is simple enough to perform SIV measurements of velocity vector field dynamics at the frequency exceeding 15000 Hz, which offers new opportunities in unsteady flow examination. The paper describes fundamentals of SIV technique and gives some new results obtained using this method for the measurements that require high spatial and temporal resolution. The latter include frequency spectra of turbulent velocity fluctuations, turbulence dissipation profiles in the boundary layer and higher-order moments of velocity fluctuations. It has been shown that SIV technique considerably extends the potential of experimental studies of turbulence and flow structure in high-speed processes.

  12. 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 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Simian immunodeficiency virus (SIV)-specific CD8+ cytotoxic T lymphocyte responses of naive and vaccinated cynomolgus macaques infected with (SIV)mac32H(J5): quantitative analysis by in vitro antigenic stimulation.

    NARCIS (Netherlands)

    A.M. Geretti (Anna Maria); E.G.J. Hulskotte (Ellen); M.E.M. Dings (Marlinda); C.A. van Baalen (Carel); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

    1997-01-01

    textabstractDetailed analyses of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocyte (CTL) responses in vaccinated and infected macaques may help to clarify the role of CTL immunity in protection against lentiviruses. Here, the optimal conditions for the measurement of SIV

  14. Identification of unique reciprocal and non reciprocal cross packaging relationships between HIV-1, HIV-2 and SIV reveals an efficient SIV/HIV-2 lentiviral vector system with highly favourable features for in vivo testing and clinical usage

    Directory of Open Access Journals (Sweden)

    Caldwell Maeve

    2005-09-01

    Full Text Available Abstract Background Lentiviral vectors have shown immense promise as vehicles for gene delivery to non-dividing cells particularly to cells of the central nervous system (CNS. Improvements in the biosafety of viral vectors are paramount as lentiviral vectors move into human clinical trials. This study investigates the packaging relationship between gene transfer (vector and Gag-Pol expression constructs of HIV-1, HIV-2 and SIV. Cross-packaged vectors expressing GFP were assessed for RNA packaging, viral vector titre and their ability to transduce rat primary glial cell cultures and human neural stem cells. Results HIV-1 Gag-Pol demonstrated the ability to cross package both HIV-2 and SIV gene transfer vectors. However both HIV-2 and SIV Gag-Pol showed a reduced ability to package HIV-1 vector RNA with no significant gene transfer to target cells. An unexpected packaging relationship was found to exist between HIV-2 and SIV with SIV Gag-Pol able to package HIV-2 vector RNA and transduce dividing SV2T cells and CNS cell cultures with an efficiency equivalent to the homologous HIV-1 vector however HIV-2 was unable to deliver SIV based vectors. Conclusion This new non-reciprocal cross packaging relationship between SIV and HIV-2 provides a novel way of significantly increasing bio-safety with a reduced sequence homology between the HIV-2 gene transfer vector and the SIV Gag-Pol construct thus ensuring that vector RNA packaging is unidirectional.

  15. The M. obturator internus sulcus on middle and late Pleistocene human ischia.

    Science.gov (United States)

    Trinkaus, E

    1996-12-01

    Recent human ischia and those of Middle and Late Pleistocene hominids exhibit variation in the cranio-caudal location of the sulcus for the internal obturator muscle as it rounds the ischium through the lesser sciatic notch, from being fully cranial of the ischial tuberosity, to bordering the tuberosity, to crossing the superior tuberosity. Among two recent human samples, all three forms exist, with the cranial position of the sulcus being more common in a 20th century Euroamerican sample whereas the intermediate one predominates in a horticultural late prehistoric Amerindian sample. The available Pleistocene Homo fossil remains exhibit the full range of variation with no one form being dominant in Middle Pleistocene archaic humans and Middle Paleolithic late archaic and early modern humans. It is only within the Upper Paleolithic that the cranial and intermediate locations for the sulcus become predominant. These patterns therefore indicate that it is inappropriate to use this feature for distinguishing later Pleistocene hominid groups.

  16. [Genetic diversity and phylogeographic distribution of SIV: how to understand the origin of HIV].

    Science.gov (United States)

    Peeters, Martine; Chaix, Marie-Laure; Delaporte, Eric

    2008-01-01

    Emergence of human immunodeficiency viruses HIV-1 and HIV-2 results from interspecies transmission from simian viruses SIV. SIVcpzPtt infecting chimpanzees, and from which the HIV-1 (subgroups M and N) is derived is still found in the Pan troglodytes troglodytes population of south Cameroon chimpanzees. The ancestor of HIV-1 group O, is found in the Gorilla residing in Western Africa, but chimpanzees are in fact the initial reservoir of the SIV viruses SIVgor, and it is still unclear whether the group O HIV-1 has been transmitted to humans by gorillas and/or chimpanzees. At least eight interspecies transmissions between and humans implicating SIVsmm (from sooty mangabey monkeys) have occurred, corresponding to the eight VIH-2 groups. Since habits of hunting and meat preparation in the bush still persistently expose humans in Africa to SIV infection, new interspecies transmission of these viruses remains a possibility.

  17. 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.

  18. Identification and Structural Characterization of the ALIX-Binding Late Domains of Simian Immunodeficiency Virus SIV mac239 and SIV agmTan-1

    Energy Technology Data Exchange (ETDEWEB)

    Q Zhai; M Landesman; H Robinson; W Sundquist; C Hill

    2011-12-31

    Retroviral Gag proteins contain short late-domain motifs that recruit cellular ESCRT pathway proteins to facilitate virus budding. ALIX-binding late domains often contain the core consensus sequence YPX{sub n}L (where X{sub n} can vary in sequence and length). However, some simian immunodeficiency virus (SIV) Gag proteins lack this consensus sequence, yet still bind ALIX. We mapped divergent, ALIX-binding late domains within the p6{sup Gag} proteins of SIV{sub MAC239} ({sub 40}SREK{und P}YKE{und VT}ED{und L}LHLNSLF{sub 59}) and SIV{sub agmTan-1} ({sub 24}AAG{und A}YDP{und AR}KL{und L}EQYAKK{sub 41}). Crystal structures revealed that anchoring tyrosines (in lightface) and nearby hydrophobic residues (underlined) contact the ALIX V domain, revealing how lentiviruses employ a diverse family of late-domain sequences to bind ALIX and promote virus budding.

  19. 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

    2013-01-01

    Volume conduction models can help in acquiring knowledge about the distribution of the electric field induced by transcranial magnetic stimulation (TMS). 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 the CSF and GM (Thielscher et al. 2011; Bijsterbosch et al. 2012), or by resizing the whole brain (Wagner et al. 2008). 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 (MRI), 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. PMID:23787706

  20. 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, U; Wolters, C H; Stegeman, D F; Oostendorp, T F

    2013-07-21

    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.

  1. 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…

  2. Effects of tongue movements on lingual sulcus depth while border molding in mandibular complete dentures.

    Science.gov (United States)

    Denizoglu, Saip; Yanikoglu, Nuran; Yilmaz, Burak; Kürklü, Duygu

    2014-01-01

    In general, people speak and swallow frequently in their daily lives rather than making exaggerated tongue movements. The aim was to compare the effect of tongue movements on lingual sulcus depth, during the border molding process of impression making of mandibular complete dentures. In total, 32 double master impressions were made. One of these pairs was obtained by allowing the patient to swallow and the other by enabling the tongue to make excessive movements. Measurements were taken from different regions of the lingual sulcus by determining the length of the parallel lines drawn from fixed points marked on the residual ridge crest to the deepest point of the alveolingual sulcus. These measurements were performed using a RMI three-dimensional measurement system. Data were compared using the paired t-test (alpha = 0.05). The high value found in casts with border molding, while swallowing was statistically significant in vertical and horizontal directions of the anterior lingual sulcus region (movement of the tongue.

  3. Analysis of olfactory function and the depth of olfactory sulcus in patients with Parkinson's disease.

    Science.gov (United States)

    Kim, Ji Youn; Lee, Won Yong; Chung, Eun Joo; Dhong, Hun-Jong

    2007-08-15

    Olfactory deficit is known to occur frequently in Parkinson's disease (PD). This study aimed to explore olfactory deficit in PD and to investigate its possible correlation with the disease severity or the depth of the olfactory sulcus. Fifty-nine PD patients and 25 normal controls were examined by the odor identification test with the crosscultural smell identification test (CC-SIT). Among these subjects, the depth of the olfactory sulcus of 42 PD patients and 8 controls was measured in the plane of the posterior tangent through the eyeballs using the coronal view brain MRI. The CC-SIT scores of the PD patients were significantly lower than those of the normal control (P0.05). Our study confirms that CC-SIT is a helpful test in detecting the olfactory deficit in Korean PD patients. The absence of correlation of olfactory deficit with the disease severity or the depth of olfactory sulcus may suggest that olfactory loss precede the development of motor signs and not be a primary consequence of damage to the olfactory sulcus. Copyright (c) 2007 Movement Disorder Society.

  4. Evaluation of efficacy of different gingival displacement materials on gingival sulcus width.

    Science.gov (United States)

    Prasanna, G S Renuka; Reddy, Kesava; Kumar, R K Naveen; Shivaprakash, S

    2013-03-01

    The purpose of the present in vivo study was to measure the efficacy of different gingival displacement materials in achieving gingival tissue displacement and to compare the efficacy of Expasyl displacement paste (Pierre Rolland, France) and gingival displacement cord for gingival displacement. Sixteen subjects were included in the study. Premolars were prepared to receive full veneer crown, gingival displacement was carried using gingival retraction cord and gingival displacement paste. Impression of the gingival sulcus was made. Sulcus width after displacement was measured under magnification. The mean displacement value of sulcus width was 0.21 ± 0.01 mm for the gingival retraction cord and 0.26 ± 0.02 mm for the gingival displacement paste. 'F' test was used for statistical analysis. Difference among the two test agents was statistically significant (p paste showed better response in achieving horizontal displacement of the gingival sulcus than gingival retraction cord. Gingival displacement helps in recording the unprepared tooth surface adjacent to the finish line in the impression being made, thereby helping a better marginal adaptation and emergence profile in the extracoronal restoration.

  5. 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.

  6. High Rate of Simian Immunodeficiency Virus (SIV Infections in Wild Chimpanzees in Northeastern Gabon

    Directory of Open Access Journals (Sweden)

    Vanina Boué

    2015-09-01

    Full Text Available The emergence of HIV-1 groups M, N, O, and P is the result of four independent cross-species transmissions between chimpanzees (cpz and gorillas (gor from central/south Cameroon and humans respectively. Although the first two SIVcpz were identified in wild-born captive chimpanzees in Gabon in 1989, no study has been conducted so far in wild chimpanzees in Gabon. To document the SIVcpz infection rate, genetic diversity, and routes of virus transmission, we analyzed 1458 faecal samples collected in 16 different locations across the country, and we conducted follow-up missions in two of them. We found 380 SIV antibody positive samples in 6 different locations in the north and northeast. We determined the number of individuals collected by microsatellite analysis and obtained an adjusted SIV prevalence of 39.45%. We performed parental analysis to investigate viral spread between and within communities and found that SIVs were epidemiologically linked and were transmitted by both horizontal and vertical routes. We amplified pol and gp41 fragments and obtained 57 new SIVcpzPtt strains from three sites. All strains, but one, clustered together within a specific phylogeographic clade. Given that these SIV positive samples have been collected nearby villages and that humans continue to encroach in ape’s territories, the emergence of a new HIV in this area needs to be considered.

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

    Directory of Open Access Journals (Sweden)

    W L William Chang

    Full Text Available 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.

  8. Stable multi-infection of splenocytes during SIV infection - the basis for continuous recombination

    Directory of Open Access Journals (Sweden)

    Schultz Anke

    2012-04-01

    Full Text Available Abstract Background Recombination is an important mechanism in the generation of genetic diversity of the human (HIV and simian (SIV immunodeficiency viruses. It requires the co-packaging of divergent RNA genomes into the same retroviral capsid and subsequent template switching during the reverse transcription reaction. By HIV-specific fluorescence in situ hybridization (FISH, we have previously shown that the splenocytes from 2 chronically infected patients with Castelman's disease were multi-infected and thus fulfill the in vivo requirements to generate genetic diversity by recombination. In order to analyze when multi-infection first occurs during a lentivirus infection and how the distribution of multi-infection evolves during the disease course, we now determined the SIV copy numbers from splenocytes of 11 SIVmac251-infected rhesus macaques cross-sectionally covering the time span of primary infection throughout to end-stage immunodeficiency. Results SIV multi-infection of single splenocytes was readily detected in all monkeys and all stages of the infection. Single-infected cells were more frequent than double- or triple- infected cells. There was no strong trend linking the copy number distribution to plasma viral load, disease stage, or CD4 cell counts. Conclusions SIV multi-infection of single cells is already established during the primary infection phase thus enabling recombination to affect viral evolution in vivo throughout the disease course.

  9. Tissue-specific interferon alpha subtype response to SIV infection in brain, spleen, and lung.

    Science.gov (United States)

    Zaritsky, Luna Alammar; Dery, Alicia; Leong, Wan Yee; Gama, Lucio; Clements, Janice E

    2013-01-01

    Interferon alpha (IFNalpha) is a type I interferon that plays a major role in host defense. There are 13 different IFNalpha genes in humans, but much of the work concerning their role in viral defense has been limited to studying either subtype 2 or pan IFNalpha due to the inability to distinguish between highly similar genetic and amino acid sequences. Because of recent advances in molecular and biochemical techniques, it is possible to study the regulation of individual subtypes. It has been reported that HIV/SIV infection results in impaired IFNalpha responses in certain tissues. Using a pigtailed macaque SIV model, we examined the subtype response during acute infection in 3 tissues that are known to be infected with HIV/SIV, but whose IFNalpha subtype response has not been extensively studied: the brain, spleen, and lung. We found that the expression and regulation of specific subtypes occur in a tissue-specific manner. There was more limited IFNalpha subtype expression in the lung and brain, where predominantly macrophages are infected compared to the spleen, which contains both infected CD4+ lymphocytes and macrophages. Understanding the IFNalpha subtype response in tissues known to be infected with HIV/SIV can help tailor adjunctive treatment regimens to highly active antiretroviral therapy.

  10. Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys

    NARCIS (Netherlands)

    Liu, J.; O'Brien, K.L.; Lynch, D.M.; Simmons, N.L.; Porte, A. La; Riggs, A.M.; Abbink, P.; Coffey, R.T.; Grandpre, L.E.; Seaman, M.S.; Landucci, G.; Forthal, D.N.; Montefiori, D.C.; Carville, A.; Mansfield, K.G.; Havenga, M.J.; Pau, M.G.; Goudsmit, J.; Barouch, D.H.

    2009-01-01

    A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or

  11. Catalytic oxidation of S(IV) in seawater slurries of activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    B.F. Vidal; P. Ollero; F.J. Gutierrez Ortiz; R. Arjona [University of Seville, Sevilla (Spain). Department of Chemical and Environmental Engineering

    2005-07-01

    Flue gas desulfurization (FGD) by means of SO{sub 2} absorption in seawater is a well-known process with a main drawback; due to the low S(IV) oxidation rate at the low pH values of the absorption tower effluent, a large oxidation basin is required. Laboratory reactor tests, in which a commercially available activated carbon was used, showed a significant catalytic effect. It is shown that the kinetic equation for the catalytic oxidation of S(IV), in seawater slurries of activated carbon, is first-order with respect to S(IV) and zero-order with respect to oxygen. The dependence of the kinetic constant with respect to pH, temperature, and catalyst size particles were also obtained. The study showed that using an appropriated size and concentration of catalyst, it is possible to reach, at pH = 4, S(IV), oxidation rates similar to those obtained at pH = 6 without catalyst. Operating at pH = 4 requires less seawater flow rate in the oxidation basin than at pH = 6. Thus, the volume of the water treatment plant can be reduced too. The space requirements and both the capital and the operating cost are lower, a critical issue concerning the retrofitting of existing power stations. 12 refs., 9 figs., 3 tabs.

  12. 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.

  13. 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.

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

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    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

  15. Influence of naturally occurring simian foamy viruses (SFVs) on SIV disease progression in the rhesus macaque (Macaca mulatta) model.

    Science.gov (United States)

    Choudhary, Anil; Galvin, Teresa A; Williams, Dhanya K; Beren, Joel; Bryant, Mark A; Khan, Arifa S

    2013-06-06

    We have investigated the influence of naturally occurring simian foamy viruses (SFVs) on simian immunodeficiency virus (SIV) infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were injected with SIV(mac239) virus obtained from a molecular clone and four were injected with medium. Blood was collected every two weeks for evaluation of SIV infection based upon T cell-subsets, plasma viral load, development and persistence of virus-specific antibodies, and clinical changes by physical examination and hematology. Comparative analysis of SFV+/SIV+ and SFV-/SIV+ monkey groups indicated statistically significant differences in the plasma viral load between 6-28 weeks, particularly after reaching plateau at 20-28 weeks, in the CD4+ and CD8+ T-cell numbers over the entire study period (2-43 weeks), and in the survival rates evaluated at 49 weeks. There was an increase in the plasma viral load, a decreasing trend in the CD4+ T cells, and a greater number of animal deaths in the SFV+/SIV+ group. The results, although based upon a small number of animals, indicated that pre-existing SFV infection can influence SIV infection and disease outcome in the rhesus macaque model. The study highlights consideration of the SFV status in evaluating results from SIV pathogenesis and vaccine challenge studies in monkeys and indicates the potential use of the SFV/SIV monkey model to study the dynamics of SFV and HIV-1 dual infections, recently reported in humans.

  16. Form follows function: astrocyte morphology and immune dysfunction in SIV neuroAIDS.

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    Lee, Kim M; Chiu, Kevin B; Renner, Nicole A; Sansing, Hope A; Didier, Peter J; MacLean, Andrew G

    2014-10-01

    Cortical function is disrupted in neuroinflammatory disorders, including HIV-associated neurocognitive disorders (HAND). Astrocyte dysfunction includes retraction of foot processes from the blood-brain barrier and decreased removal of neurotransmitters from synaptic clefts. Mechanisms of astrocyte activation, including innate immune function and the fine neuroanatomy of astrocytes, however, remain to be investigated. We quantified the number of glial fibrillary acidic protein (GFAP)-labeled astrocytes per square millimeter and the proportion of astrocytes immunopositive for Toll-like receptor 2 (TLR2) to examine innate immune activation in astrocytes. We also performed detailed morphometric analyses of gray and white matter astrocytes in the frontal and parietal lobes of rhesus macaques infected with simian immunodeficiency virus (SIV), both with and without encephalitis, an established model of AIDS neuropathogenesis. Protoplasmic astrocytes (gray matter) and fibrous astrocytes (deep white matter) were imaged, and morphometric features were analyzed using Neurolucida. Gray matter and white matter astrocytes showed no change in cell body size in animals infected with SIV regardless of encephalitic status. In SIV-infected macaques, both gray and white matter astrocytes had shorter, less ramified processes, resulting in decreased cell arbor compared with controls. SIV-infected macaques with encephalitis showed decreases in arbor length in white matter astrocytes and reduced complexity in gray matter astrocytes compared to controls. These results provide the first evidence that innate immune activation of astrocytes is linked to altered cortical astrocyte morphology in SIV/HIV infection. Here, we demonstrate that astrocyte remodeling is correlated with infection. Perturbed neuron-glia signaling may be a driving factor in the development of HAND.

  17. Revisiting a historic human brain with magnetic resonance imaging – the first description of a divided central sulcus

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    Renate eSchweizer

    2014-05-01

    Full Text Available In 1860 and 1862, the German physiologist Wagner published two studies, in which he compared the cortical surfaces of brain specimens. This provided the first account of a rare anatomical variation – bridges across the central sulci in both hemispheres connecting the forward and backward facing central convolutions in one of the brains. The serendipitous rediscovery of the preserved historic brain specimen in the collections at Göttingen University, being mistaken as the brain of the mathematician C.F. Gauss, allowed us to further investigate the morphology of the bridges Wagner had described with magnetic resonance imaging (MRI. On the historic lithograph, current photographs and MRI surface reconstructions of the brain, a connection across the central sulcus can only be seen in the left hemisphere. In the right hemisphere, contrary to the description of Wagner, a connecting structure is only present across the postcentral sulcus. MRI reveals that the left-hemispheric bridge extends into the depth of the sulcus, forming a transverse connection between the two opposing gyri. This rare anatomical variation, generally not associated with neurological symptoms, would nowadays be categorized as a divided central sulcus. The left-hemispheric connection seen across the postcentral sulcus, represents the very common case of a segmented postcentral sulcus. MRI further disclosed a connection across the right-hemispheric central sulcus, which terminates just below the surface of the brain and is therefore not depicted on the historical lithography. This explains the apparent inconsistency between the bilateral description of bridges across the central sulci and the unilateral appearance on the brain surface. The results are discussed based on the detailed knowledge of anatomists of the late 19th century, who already recognized the divided central sulcus as an extreme variation of a deep convolution within the central sulcus.

  18. Revisiting a historic human brain with magnetic resonance imaging - the first description of a divided central sulcus.

    Science.gov (United States)

    Schweizer, Renate; Helms, Gunther; Frahm, Jens

    2014-01-01

    In 1860 and 1862, the German physiologist Wagner published two studies, in which he compared the cortical surfaces of brain specimens. This provided the first account of a rare anatomical variation - bridges across the central sulci in both hemispheres connecting the forward and backward facing central convolutions in one of the brains. The serendipitous rediscovery of the preserved historic brain specimen in the collections at Göttingen University, being mistaken as the brain of the mathematician C.F. Gauss, allowed us to further investigate the morphology of the bridges Wagner had described with magnetic resonance imaging (MRI). On the historic lithograph, current photographs and MRI surface reconstructions of the brain, a connection across the central sulcus can only be seen in the left hemisphere. In the right hemisphere, contrary to the description of Wagner, a connecting structure is only present across the post-central sulcus. MRI reveals that the left-hemispheric bridge extends into the depth of the sulcus, forming a transverse connection between the two opposing gyri. This rare anatomical variation, generally not associated with neurological symptoms, would nowadays be categorized as a divided central sulcus. The left-hemispheric connection seen across the post-central sulcus, represents the very common case of a segmented post-central sulcus. MRI further disclosed a connection across the right-hemispheric central sulcus, which terminates just below the surface of the brain and is therefore not depicted on the historical lithography. This explains the apparent inconsistency between the bilateral description of bridges across the central sulci and the unilateral appearance on the brain surface. The results are discussed based on the detailed knowledge of anatomists of the late 19th century, who already recognized the divided central sulcus as an extreme variation of a deep convolution within the central sulcus.

  19. Acute SIV infection in sooty mangabey monkeys is characterized by rapid virus clearance from lymph nodes and absence of productive infection in germinal centers.

    Science.gov (United States)

    Martinot, Amanda J; Meythaler, Mareike; Pozzi, Lu-Ann; Dalecki Boisvert, Karen; Knight, Heather; Walsh, Dennis; Westmoreland, Susan; Anderson, Daniel C; Kaur, Amitinder; O'Neil, Shawn P

    2013-01-01

    Lymphoid tissue immunopathology is a characteristic feature of chronic HIV/SIV infection in AIDS-susceptible species, but is absent in SIV-infected natural hosts. To investigate factors contributing to this difference, we compared germinal center development and SIV RNA distribution in peripheral lymph nodes during primary SIV infection of the natural host sooty mangabey and the non-natural host pig-tailed macaque. Although SIV-infected cells were detected in the lymph node of both species at two weeks post infection, they were confined to the lymph node paracortex in immune-competent mangabeys but were seen in both the paracortex and the germinal center of SIV-infected macaques. By six weeks post infection, SIV-infected cells were no longer detected in the lymph node of sooty mangabeys. The difference in localization and rate of disappearance of SIV-infected cells between the two species was associated with trapping of cell-free virus on follicular dendritic cells and higher numbers of germinal center CD4(+) T lymphocytes in macaques post SIV infection. Our data suggests that fundamental differences in the germinal center microenvironment prevent productive SIV infection within the lymph node germinal centers of natural hosts contributing to sustained immune competency.

  20. Acute SIV infection in sooty mangabey monkeys is characterized by rapid virus clearance from lymph nodes and absence of productive infection in germinal centers.

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    Amanda J Martinot

    Full Text Available Lymphoid tissue immunopathology is a characteristic feature of chronic HIV/SIV infection in AIDS-susceptible species, but is absent in SIV-infected natural hosts. To investigate factors contributing to this difference, we compared germinal center development and SIV RNA distribution in peripheral lymph nodes during primary SIV infection of the natural host sooty mangabey and the non-natural host pig-tailed macaque. Although SIV-infected cells were detected in the lymph node of both species at two weeks post infection, they were confined to the lymph node paracortex in immune-competent mangabeys but were seen in both the paracortex and the germinal center of SIV-infected macaques. By six weeks post infection, SIV-infected cells were no longer detected in the lymph node of sooty mangabeys. The difference in localization and rate of disappearance of SIV-infected cells between the two species was associated with trapping of cell-free virus on follicular dendritic cells and higher numbers of germinal center CD4(+ T lymphocytes in macaques post SIV infection. Our data suggests that fundamental differences in the germinal center microenvironment prevent productive SIV infection within the lymph node germinal centers of natural hosts contributing to sustained immune competency.

  1. Multiplexed Component Analysis to Identify Genes Contributing to the Immune Response during Acute SIV Infection.

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    Iraj Hosseini

    Full Text Available Immune response genes play an important role during acute HIV and SIV infection. Using an SIV macaque model of AIDS and CNS disease, our overall goal was to assess how the expression of genes associated with immune and inflammatory responses are longitudinally changed in different organs or cells during SIV infection. To compare RNA expression of a panel of 88 immune-related genes across time points and among three tissues - spleen, mesenteric lymph nodes (MLN and peripheral blood mononuclear cells (PBMC - we designed a set of Nanostring probes. To identify significant genes during acute SIV infection and to investigate whether these genes are tissue-specific or have global roles, we introduce a novel multiplexed component analysis (MCA method. This combines multivariate analysis methods with multiple preprocessing methods to create a set of 12 "judges"; each judge emphasizes particular types of change in gene expression to which cells could respond, for example, the absolute or relative size of expression change from baseline. Compared to bivariate analysis methods, our MCA method improved classification rates. This analysis allows us to identify three categories of genes: (a consensus genes likely to contribute highly to the immune response; (b genes that would contribute highly to the immune response only if certain assumptions are met - e.g. that the cell responds to relative expression change rather than absolute expression change; and (c genes whose contribution to immune response appears to be modest. We then compared the results across the three tissues of interest; some genes are consistently highly-contributing in all tissues, while others are specific for certain tissues. Our analysis identified CCL8, CXCL10, CXCL11, MxA, OAS2, and OAS1 as top contributing genes, all of which are stimulated by type I interferon. This suggests that the cytokine storm during acute SIV infection is a systemic innate immune response against viral

  2. Post-exposure prophylaxis for SIV revisited: Animal model for HIV prevention

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    Bekele Girma

    2006-11-01

    Full Text Available Abstract Background A 4-week, uninterrupted treatment with 9-(2-phosphonyl-methoxypropylyadenine (PMPA, commonly called tenofovir completely prevents simian immunodeficiency virus (SIVmne infection in cynomolgus macaques if treatment begins within 24 hours after SIVmne inoculation, but is less effective if treatment is delayed or duration of treatment is shortened. Critical factors for efficacy include timing and duration of treatment, potency of antiretroviral drug and a contribution from antiviral immune responses. Therefore, we evaluated the impact of one or more treatment interruptions plus SIVmne re-exposures on efficacy of PMPA treatment to prevent SIVmne infection in cynomolgus macaques. We also evaluated whether macaques with pre-existing SIV immune responses show increased efficacy of treatment. Eight PMPA-treated, virus-negative and seronegative macaques, and five PMPA-treated, virus-negative but weakly or strongly seropositive macaques were re-inoculated with SIVmne and treated with PMPA starting 24 hr post inoculation. Thereafter, they received either a 5-week treatment involving one interruption plus one SIVmne challenge or a 10-week treatment involving six interruptions plus six SIVmne challenges early during treatment. Parameters measured were plasma SIV RNA, SIV-antibody response, CD4+ T lymphocyte subsets and in vivo CD8+ cell-suppression of virus infection. Results All seronegative macaques developed persistent antibody response beginning 4 to 8 weeks after stopping PMPA-treatment in absence of viremia in a majority of macaques and coinciding with onset of intermittent viremia in other macaques. In contrast, all weakly or strongly seropositive macaques showed immediate increase in titers (> 1600 of SIV antibodies, even before the end of PMPA-treatment, and in absence of detectable viremia. However, in vivo CD8+ -cell depletion revealed CD8 cell-suppression of viremia and persistence of virus in the macaques as long as 2 years

  3. 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

  4. 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

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

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    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.

  6. ?Walk the Rim, Feel the Bone? Technique in Superior Sulcus Filling

    OpenAIRE

    Looi, Audrey L.G.; Yong, Kai-Ling

    2016-01-01

    Summary: 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 a...

  7. Cryoclast distribution on the damascus sulcus region of enceladus moon (saturn) using vims images

    Science.gov (United States)

    Forero, L. M.; Sánchez, J.; Saavedra, F.

    2017-07-01

    At Damascus Sulcus area within SPT (South Polar Terrain) there were interpreted a series of images where it was analyzed the distribution of different size particles that are ejected by distinct criovolcanic sources based on the analysis of the morphology, tectonic, reflectance and spectral signature of the surface material. This work shows these observations by comparing high resolution images of VIMS and ISS in combination with a Digital Elevation Model.

  8. Influence of Naturally Occurring Simian Foamy Viruses (SFVs on SIV Disease Progression in the Rhesus Macaque (Macaca mulatta Model

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    Joel Beren

    2013-06-01

    Full Text Available We have investigated the influence of naturally occurring simian foamy viruses (SFVs on simian immunodeficiency virus (SIV infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were injected with SIVmac239 virus obtained from a molecular clone and four were injected with medium. Blood was collected every two weeks for evaluation of SIV infection based upon T cell-subsets, plasma viral load, development and persistence of virus-specific antibodies, and clinical changes by physical examination and hematology. Comparative analysis of SFV+/SIV+ and SFV−/SIV+ monkey groups indicated statistically significant differences in the plasma viral load between 6–28 weeks, particularly after reaching plateau at 20–28 weeks, in the CD4+ and CD8+ T-cell numbers over the entire study period (2–43 weeks, and in the survival rates evaluated at 49 weeks. There was an increase in the plasma viral load, a decreasing trend in the CD4+ T cells, and a greater number of animal deaths in the SFV+/SIV+ group. The results, although based upon a small number of animals, indicated that pre-existing SFV infection can influence SIV infection and disease outcome in the rhesus macaque model. The study highlights consideration of the SFV status in evaluating results from SIV pathogenesis and vaccine challenge studies in monkeys and indicates the potential use of the SFV/SIV monkey model to study the dynamics of SFV and HIV-1 dual infections, recently reported in humans.

  9. Improvement of small incision transscleral sulcus fixation of Akreos Adapt AO foldable intraocular lens

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    Tao He

    2015-12-01

    Full Text Available AIM:to observe the effect of modified surgery of small incision transscleral sulcus fixation of Akreos Adapt AO foldable intraocular lens.METHODS:The study included 37 patients(37 eyeswho could not be performed the regular implantation of posterior chamber intraocular lens for the rupture of posterior capsule or for the zonular dialysis caused by trauma, congenital or surgery. Bausch & lomb Akreos Adapt AO fordable intraocular lens, VE22000 implantation device were applied in this study. Regular 2.4mm transparent cornea incision and pocket-like sclera incision were made. The intraocular lens were transscleral sulcus fixed by 10/0 prolene suture and the suture was buried within the scleral incision.RESULTS:The intraocular lenses were all well posited and the postoperative visual acuity(VAwas improved in all patients. Three eyes(8%were≥0.8 while 18 eyes(49%>0.4~≤0.6 and the remaining 16(43%were ≤ 0.4 at 3mo after surgery.Cornea astigmatism was 1.73D±1.22D and 1.62±1.34D before and after surgery, no statistic significance was observed(PCONCLUSION:The modified surgery of 2.4mm small incision transscleral sulcus fixation of Akreos Adapt AO foldable intraocular lens has the following advantages such as:good visual results, less postoperative astigmatism, small surgery incision, steady intraocular lens, less manipulation, less complication and more effective.

  10. 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.

  11. Total ear reconstruction: The role of bilateral triangular post-auricular flaps for creation of the cephaloauricular sulcus

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    Saad Mohamed Saad Ibrahiem

    2017-03-01

    Results: The technique was simple and effective with no post-operative complication regarding flaps viability. Patients requiring glasses have worn frames soon after the tie-over was removed and no sulcus problems have resulted.

  12. Comparison of CIV, SIV and AIV using Decision Tree and SVM

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    Park Hyorin

    2016-01-01

    Full Text Available The H3N2, the canine influenza virus has numerous types of animal hosts that can live and reproduce on. They mostly settle on pigs and birds. However, some concerned voices are rising that there is high possibility that humans could be an additional victim for the canine flu. Consequently, our project group expect that the information about the H3N2’s DNA are valuable, since the information could attribute to development of vaccine and medicine. In the experiments of analysing the properties of CIV, Canine Influenza Virus with the comparison of SIV, Swine Influenza Virus and AIV, Avian Influenza Virus with the decision tree and SVM, Support Vector Machine. The result came out that CIV, SIV and AIV are alike but also different in some aspects.

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

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    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.

  14. Nef gene evolution from a single transmitted strain in acute SIV infection

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    Bimber Benjamin N

    2009-06-01

    Full Text Available Abstract Background The acute phase of immunodeficiency virus infection plays a crucial role in determining steady-state virus load and subsequent progression of disease in both humans and nonhuman primates. The acute period is also the time when vaccine-mediated effects on host immunity are likely to exert their major effects on virus infection. Recently we developed a Monte-Carlo (MC simulation with mathematical analysis of viral evolution during primary HIV-1 infection that enables classification of new HIV-1 infections originating from multiple versus single transmitted viral strains and the estimation of time elapsed following infection. Results A total of 322 SIV nef SIV sequences, collected during the first 3 weeks following experimental infection of two rhesus macaques with the SIVmac239 clone, were analyzed and found to display a comparable level of genetic diversity, 0.015% to 0.052%, with that of env sequences from acute HIV-1 infection, 0.005% to 0.127%. We confirmed that the acute HIV-1 infection model correctly identified the experimental SIV infections in rhesus macaques as "homogenous" infections, initiated by a single founder strain. The consensus sequence of the sampled strains corresponded to the transmitted sequence as the model predicted. However, measured sequential decrease in diversity at day 7, 11, and 18 post infection violated the model assumption, neutral evolution without any selection. Conclusion While nef gene evolution over the first 3 weeks of SIV infection originating from a single transmitted strain showed a comparable rate of sequence evolution to that observed during acute HIV-1 infection, a purifying selection for the founder nef gene was observed during the early phase of experimental infection of a nonhuman primate.

  15. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

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    Ivona Pandrea

    2016-01-01

    Full Text Available Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX and of gut inflammation (Sulfasalazine-SFZ. RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

  16. Assembly of SIV virus-like particles containing envelope proteins using a baculovirus expression system.

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    Yamshchikov, G V; Ritter, G D; Vey, M; Compans, R W

    1995-12-01

    The requirements for SIV particle assembly and envelope incorporation were investigated using a baculovirus expression system. The Pr56gag precursor protein expressed under control of the polyhedrin promoter (pPolh) produced high levels of immature retrovirus-like particles (VLP) upon expression in Sf9 insect cells. To determine the optimal conditions for envelope protein (Env) incorporation into VLP, two recombinant baculoviruses expressing the SIV envelope protein under control of a very late pPolh or a hybrid late/very late capsid/polyhedrin (Pcap/polh) promoter and a recombinant expressing a truncated form of the SIV envelope protein (Envt) under the hybrid Pcap/polh promoter were compared. We have observed that utilization of the earlier hybrid promoter resulted in higher levels of Env expression on the cell surface and its incorporation into budding virus particles. We have also found that the Envt protein is transported to the cell surface of insect cells and incorporated into VLP more efficiently than full-length Env. In addition, we examined the effect of coexpression of the protease furin, which has been implicated in the proteolytic cleavage of the Env precursor gp160 in mammalian cells. Coexpression of furin in insect cells resulted in more efficient proteolytic cleavage into gp120 and gp41, and the cleaved proteins were incorporated into VLP.

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

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    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.

  18. 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.

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

    Science.gov (United States)

    Policicchio, Benjamin B; Xu, Cuiling; Brocca-Cofano, Egidio; Raehtz, Kevin D; He, Tianyu; Ma, Dongzhu; Li, Hui; Sivanandham, Ranjit; Haret-Richter, George S; Dunsmore, Tammy; Trichel, Anita; Mellors, John W; Hahn, Beatrice H; Shaw, George M; Ribeiro, Ruy M; Pandrea, Ivona; Apetrei, Cristian

    2016-09-01

    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 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. Comparison of the

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

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    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.

  1. Single buccal sulcus approach with fluoroscan assistance for the management of simple zygomatic fractures.

    Science.gov (United States)

    Chen, Chih-Hao; Mao, Shih-Hsuan; Shyu, Victor Bong-Hang; Chen, Chien-Tzung

    2015-05-01

    Zygomatic fractures are associated with functional and aesthetic problems. The purpose of this study was to evaluate the adequacy of management and the surgical satisfaction of patients with simple zygomatic fractures treated through a single buccal sulcus approach and fluoroscan assistance. Between 2008 and 2012, 42 patients with simple zygomatic fractures were included in the study. The surgical procedure was performed through a single buccal sulcus incision. The fracture sites were aligned under direct vision and fluoroscan assistance and stabilized with rigid internal fixation. The adequacy of reduction was evaluated based on postoperative plain radiographic films and computed tomographic scans using mirror image analyses. The satisfaction of functional and aesthetic results was also evaluated subjectively using a visual analog scale during follow-up. Twenty-nine male and thirteen female patients with a mean age of 33.2 years were evaluated. Motorcycle crashes (78.6%) were the most common mechanism of trauma. Based on follow-up imaging studies, 2 patients had inadequate reduction of zygomatic body, and there was a slight depression of the zygomatic arch in one patient. Ninety-three percent (39/42) of patients had satisfactory results, although one patient complained of malar asymmetry and another felt a depression in the arch area. Two patients complained of persistent hypesthesia during follow-up at 6 months. Our results suggest that a single buccal sulcus approach without lower eyelid or lateral eyebrow incision in the repair of simple fractures of the zygoma can be achieved with high patient satisfaction if the reduction and fixation are adequate and stable.

  2. Recombinant rubella vectors elicit SIV Gag-specific T cell responses with cytotoxic potential in rhesus macaques.

    Science.gov (United States)

    Rosati, Margherita; Alicea, Candido; Kulkarni, Viraj; Virnik, Konstantin; Hockenbury, Max; Sardesai, Niranjan Y; Pavlakis, George N; Valentin, Antonio; Berkower, Ira; Felber, Barbara K

    2015-04-27

    Live-attenuated rubella vaccine strain RA27/3 has been demonstrated to be safe and immunogenic in millions of children. The vaccine strain was used to insert SIV gag sequences and the resulting rubella vectors were tested in rhesus macaques alone and together with SIV gag DNA in different vaccine prime-boost combinations. We previously reported that such rubella vectors induce robust and durable SIV-specific humoral immune responses in macaques. Here, we report that recombinant rubella vectors elicit robust de novo SIV-specific cellular immune responses detectable for >10 months even after a single vaccination. The antigen-specific responses induced by the rubella vector include central and effector memory CD4(+) and CD8(+) T cells with cytotoxic potential. Rubella vectors can be administered repeatedly even after vaccination with the rubella vaccine strain RA27/3. Vaccine regimens including rubella vector and SIV gag DNA in different prime-boost combinations resulted in robust long-lasting cellular responses with significant increase of cellular responses upon boost. Rubella vectors provide a potent platform for inducing HIV-specific immunity that can be combined with DNA in a prime-boost regimen to elicit durable cellular immunity. Published by Elsevier Ltd.

  3. SiV center photoluminescence induced by C=O termination in nanocrystalline diamond and graphite loops hybridized films

    Science.gov (United States)

    Mei, Yingshuang; Fan, Dong; Lu, Shaohua; Shen, Yaogen; Hu, Xiaojun

    2016-12-01

    We performed a series of thermal oxidation at different temperatures on nanocrystalline diamond (NCD) films to construct various surface termination states of NCD grains and investigated their effects on silicon-vacancy (SiV) photoluminescence (PL) at 738 nm. Experiments and first principles calculations show that the negative electron affinity surface induced by C-H bond termination quenches the SiV PL, while the positive electron affinity surface originating from C=O bond termination removes this quenching. Moreover, oxidation at 600 °C results in the transition from amorphous carbon to graphite loops with an interlayer space of 0.4 nm, so that NCD and graphite loops' hybridized structure is formed. This allows oxygen atoms to contact with inside NCD grains to form more C=O bonds on the surface, producing much larger positive electron affinity in the surface. It traps the excited state electrons, lets them scatter back to the ground state, and emits SiV PL. These results reveal that C=O bonds play a crucial role in SiV PL of NCD grains and well explain the experimentally observed quenching effect. A novel way by changing the surface termination states is proposed to control the PL of NCD grains with SiV centers for potential quantum information processing and biological sensing.

  4. Limited contribution of mucosal IgA to Simian immunodeficiency virus (SIV)-specific neutralizing antibody response and virus envelope evolution in breast milk of SIV-infected, lactating rhesus monkeys.

    Science.gov (United States)

    Permar, Sallie R; Wilks, Andrew B; Ehlinger, Elizabeth P; Kang, Helen H; Mahlokozera, Tatenda; Coffey, Rory T; Carville, Angela; Letvin, Norman L; Seaman, Michael S

    2010-08-01

    Breast milk transmission of human immunodeficiency virus (HIV) remains an important mode of infant HIV acquisition. Interestingly, the majority of infants remain uninfected during prolonged virus exposure via breastfeeding, raising the possibility that immune components in milk prevent mucosal virus transmission. HIV-specific antibody responses are detectable in the milk of HIV-infected women and simian immunodeficiency virus (SIV)-infected monkeys; however, the role of these humoral responses in virus neutralization and local virus quasispecies evolution has not been characterized. In this study, four lactating rhesus monkeys were inoculated with SIVmac251 and monitored for SIV envelope-specific humoral responses and virus evolution in milk and plasma throughout infection. While the kinetics and breadth of the SIV-specific IgG and IgA responses in milk were similar to those in plasma, the magnitude of the milk responses was considerably lower than that of the plasma responses. Furthermore, a neutralizing antibody response against the inoculation virus was not detected in milk samples at 1 year after infection, despite a measurable autologous neutralizing antibody response in plasma samples obtained from three of four monkeys. Interestingly, while IgA is the predominant immunoglobulin in milk, the milk SIV envelope-specific IgA response was lower in magnitude and demonstrated more limited neutralizing capacity against a T-cell line-adapted SIV compared to those of the milk IgG response. Finally, amino acid mutations in the envelope gene product of SIV variants in milk and plasma samples occurred in similar numbers and at similar positions, indicating that the humoral immune pressure in milk does not drive distinct virus evolution in the breast milk compartment.

  5. Spatial working memory and spatial attention rely on common neural processes in the intraparietal sulcus.

    Science.gov (United States)

    Silk, Timothy J; Bellgrove, Mark A; Wrafter, Pia; Mattingley, Jason B; Cunnington, Ross

    2010-11-01

    Our ability to remember locations in space (spatial working memory) and our ability to direct attention to those locations (spatial attention) are two fundamental and closely related cognitive processes. A growing body of behavioural evidence suggests that spatial working memory and spatial attention share common resources, while neuroimaging studies show some overlap in the neural regions that mediate these two cognitive functions. The current study used fMRI to directly examine the extent to which spatial working memory and spatial attention rely on common underlying neural mechanisms. Twenty healthy participants underwent functional MRI while performing a dual task of spatial working memory incorporating a visual search task during the working memory retention interval. Working memory and visual search task loads were parametrically modulated. A wide network of prefrontal, premotor, and parietal regions showed increasing activity with increased spatial working memory load. Of these areas, part of the right supramarginal gyrus, lying along the intraparietal sulcus, showed a significant interaction such that the neural activity associated with spatial working memory load was significantly attenuated as visual search load in the dual task was increased. This interaction suggests that this part of the supramarginal gyrus, along the intraparietal sulcus, is critical for mediating both spatial working memory and shifts in spatial attention. Copyright 2010 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Vos, C.G.; Paul, M.A. [VU University Medical Center, Departments of Surgery, Amsterdam (Netherlands); Dahele, M.; Soernsen de Koste, J.R. van; Senan, S. [VU University Medical Center, Departments of Radiation Oncology, Amsterdam (Netherlands); Bahce, I.; Smit, E.F. [VU University Medical Center, Departments of Pulmonary Diseases, Amsterdam (Netherlands); Thunnissen, E. [VU University Medical Center, Departments of Pathology, Amsterdam (Netherlands); Hartemink, K.J. [VU University Medical Center, Departments of Surgery, Amsterdam (Netherlands); Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AVL), Department of Surgery, Amsterdam (Netherlands)

    2014-02-15

    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{sup 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.)

  7. Vaccination and timing influence SIV immune escape viral dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Liyen Loh

    2008-01-01

    Full Text Available CD8+ cytotoxic T lymphocytes (CTL can be effective at controlling HIV-1 in humans and SIV in macaques, but their utility is partly offset by mutational escape. The kinetics of CTL escape and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help us understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. Traditional methods for following CTL escape and reversion are, however, insensitive to minor viral quasispecies. We developed sensitive quantitative real-time PCR assays to track the viral load of SIV Gag164-172 KP9 wild-type (WT and escape mutant (EM variants in pigtail macaques. Rapid outgrowth of EM virus occurs during the first few weeks of infection. However, the rate of escape plateaued soon after, revealing a prolonged persistence of WT viremia not detectable by standard cloning and sequencing methods. The rate of escape of KP9 correlated with levels of vaccine-primed KP9-specific CD8+ T cells present at that time. Similarly, when non-KP9 responder (lacking the restricting Mane-A*10 allele macaques were infected with SHIVmn229 stock containing a mixture of EM and WT virus, rapid reversion to WT was observed over the first 2 weeks following infection. However, the rate of reversion to WT slowed dramatically over the first month of infection. The serial quantitation of escape mutant viruses evolving during SIV infection shows that rapid dynamics of immune escape and reversion can be observed in early infection, particularly when CD8 T cells are primed by vaccination. However, these early rapid rates of escape and reversion are transient and followed by a significant slowing in these rates later during infection, highlighting that the rate of escape is significantly influenced by the timing of its occurrence.

  8. 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...... immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected...... animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia....

  9. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection.

    Directory of Open Access Journals (Sweden)

    David Favre

    2009-02-01

    Full Text Available Chronic immune activation and progression to AIDS are observed after SIV infection in macaques but not in natural host primate species. To better understand this dichotomy, we compared acute pathogenic SIV infection in pigtailed macaques (PTs to non-pathogenic infection in African green monkeys (AGMs. SIVagm-infected PTs, but not SIVagm-infected AGMs, rapidly developed systemic immune activation, marked and selective depletion of IL-17-secreting (Th17 cells, and loss of the balance between Th17 and T regulatory (Treg cells in blood, lymphoid organs, and mucosal tissue. The loss of Th17 cells was found to be predictive of systemic and sustained T cell activation. Collectively, these data indicate that loss of the Th17 to Treg balance is related to SIV disease progression.

  10. Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.

    Science.gov (United States)

    Roff, Shannon R; Sanou, Missa P; Rathore, Mobeen H; Levy, Jay A; Yamamoto, Janet K

    2015-01-01

    Cross-reactive peptides on HIV-1 and FIV p24 protein sequences were studied using peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected long-term survivors (LTS; >10 y of infection without antiretroviral therapy, ART), short-term HIV-1 infected subjects not on ART, and ART-treated HIV-1 infected subjects. IFNγ-ELISpot and CFSE-proliferation analyses were performed with PBMC using overlapping HIV-1 and FIV p24 peptides. Over half of the HIV-1 infected subjects tested (22/31 or 71%) responded to one or more FIV p24 peptide pools by either IFNγ or T-cell proliferation analysis. PBMC and T cells from infected subjects in all 3 HIV(+) groups predominantly recognized one FIV p24 peptide pool (Fp14) by IFNγ production and one additional FIV p24 peptide pool (Fp9) by T-cell proliferation analysis. Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9. The responses to these FIV peptide pools were highly reproducible and persisted throughout 2-4 y of monitoring. Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a. Selected FIV and corresponding SIV epitopes recognized by HIV-1 infected patients indicate that these protein sequences are evolutionarily conserved on both SIV and HIV-1 (e.g., Hp15:Fp14:Sp14). These studies demonstrate that comparative immunogenicity analysis of HIV-1, FIV, and SIV can identify evolutionarily-conserved T cell-associated lentiviral epitopes, which could be used as a vaccine for prophylaxis or immunotherapy.

  11. 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.

  12. Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques

    Science.gov (United States)

    2013-01-01

    Background Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens because its safety and immunogenicity have been demonstrated in millions of children. One dose protects for life against rubella infection. In previous studies, rubella vectors replicated to high titers in cell culture while stably expressing SIV and HIV antigens. Their viability in vivo, however, as well as immunogenicity and antibody persistence, were unknown. Results This paper reports the first successful trial of rubella vectors in rhesus macaques, in combination with DNA vaccines in a prime and boost strategy. The vectors grew robustly in vivo, and the protein inserts were highly immunogenic. Antibody titers elicited by the SIV Gag vector were greater than or equal to those elicited by natural SIV infection. The antibodies were long lasting, and they were boosted by a second dose of replication-competent rubella vectors given six months later, indicating the induction of memory B cells. Conclusions Rubella vectors can serve as a vaccine platform for safe delivery and expression of SIV and HIV antigens. By presenting these antigens in the context of an acute infection, at a high level and for a prolonged duration, these vectors can stimulate a strong and persistent immune response, including maturation of memory B cells. Rhesus macaques will provide an ideal animal model for demonstrating immunogenicity of novel vectors and protection against SIV or SHIV challenge. PMID:24041113

  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. 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.

  15. Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

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    Marx Preston

    2006-12-01

    Full Text Available Abstract Background Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1 is a major obstacle to successful antiretroviral therapy (ART in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV. Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. Results Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. Conclusion

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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

  18. 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

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

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    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

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

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    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.

  1. Ion therapy within the trimodal management of superior sulcus tumors: the INKA trial.

    Science.gov (United States)

    Hauswald, Henrik; Rieken, Stefan; Dienemann, Hendrik C; Thomas, Michael; Kieser, Meinhard; Debus, Jürgen; Herfarth, Klaus

    2015-03-28

    The standard trimodal treatment concept in locally advanced and non-metastasized non-small-cell superior sulcus tumors consists of a preoperative chemoradiation followed by surgical resection. High linear energy transfer (LET) radiation as, for example, C12 heavy-ion beam therapy theoretically offers biological advantages compared to high energy x-ray therapy as, for example, higher biological efficiency. In the present prospective, single-armed, open pilot study performed at the Heidelberg Ion-Beam Therapy Center (HIT) in Heidelberg, the radiation treatment within the standard trimodal concept will be exchanged against C12 heavy-ion beam treatment and apply 39GyE in 13 single fractions in combination with a chemotherapy consisting of cisplatin and vinorelbine (local standard). The primary endpoint is feasibility and safety measured by the incidence of NCI-CTCAE grade 3/4 toxicity and/or discontinuation due to any reason. Secondary endpoint is the degree of regression in the histological specimen. The main inclusion criteria are histologically confirmed non-small-cell superior sulcus tumor, nodal disease stage ≤ N2, Karnofsky performance score ≥70%, patient age between 18 and 75 years as well as written informed consent. The main exclusion criteria include medical contraindications against elements of the trimodal treatment concept, PET confirmed nodal disease stage N3, stage IV disease, prior thoracic irradiation and decompensated diseases of the lung, cardio-vascular system, metabolism, hematopoietic and coagulation system and renal function. Furthermore, patients with implanted active medical devices without certification for ion-beam therapy are not allowed to take part in the study. DRKS00006323 ( www.drks.de ).

  2. An effective and safe surgical approach for a superior sulcus tumor: A case report.

    Science.gov (United States)

    Oka, Soichi; Kobayashi, Kenichi; Matsumiya, Hiroki; Kanayama, Masatoshi; Shinohara, Shuichi; Shinohara, Shinji; Taira, Akihiro; Kuwata, Taiji; Takenaka, Masaru; Chikaishi, Yasuhiro; Hirai, Ayako; Tashima, Yuko; Imanishi, Naoko; Kuroda, Koji; Ichiki, Yoshinobu; Tanaka, Fumihiro

    2017-01-01

    Superior sulcus tumors, frequently referred to as Pancoast tumors, are a wide range of tumors invading a section of the apical chest wall called the thoracic inlet. For this reason, a surgical approach and complete resection may be difficult to accomplish. We experienced a locally advanced superior sulcus tumor (SST) located from the anterior to posterior apex thoracic inlet and performed complete resection after definitive chemoradiation. A 71-year-old Japanese male presented at our hospital due to left back pain and an abnormal chest computed tomography (CT) scan showing 80×70×60-mm tumor located in the left middle apex thoracic inlet. This tumor was located near the subclavian artery, and the subclavian lymph nodes were swollen. The tumor was found to be an adenocarcinoma (clinical-T3N3M0 stage IIIB). Therefore, we performed definitive chemoradiation therapy. Slight reduction in the tumor size was noted after the treatment, and the subclavian lymph nodes were not swollen. We next performed surgical resection for this SST. Regarding the surgical approaches, the anterior approach was a transmanubrial approach, and the posterior approach was a Paulson's thoracotomy. In this manner, we were able to perform complete en-bloc resection of this tumor. This surgical approach was effective and safe for treating a SST located from the anterior to posterior apex of the thoracic inlet. The patient remains healthy and recurrence-free at 2.5 years after the operation. Surgical approach for SST is difficult. Therefore, this approach is effective and safety. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. CD4 depletion in SIV-infected macaques results in macrophage and microglia infection with rapid turnover of infected cells.

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    Luca Micci

    2014-10-01

    Full Text Available In rhesus macaques (RMs, experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes. In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources of the increased viral burden and the lifespan of productively infected cells. CD4-depleted animals showed (i set-point viral load two-logs higher than controls; (ii macrophages constituting 80% of all SIV vRNA+ cells in lymph node and mucosal tissues; (iii substantial expansion of pro-inflammatory monocytes; (iv aberrant activation and infection of microglial cells; and (v lifespan of productively infected cells significantly longer in comparison to controls, but markedly shorter than previously estimated for macrophages. The net effect of CD4+ T-cell depletion is an inability to control SIV replication and a shift in the tropism of infected cells to macrophages, microglia, and, potentially, other CD4-low cells which all appear to have a shortened in vivo lifespan. We believe these findings have important implications for HIV eradication studies.

  4. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection.

    Science.gov (United States)

    Glavan, T W; Gaulke, C A; Santos Rocha, C; Sankaran-Walters, S; Hirao, L A; Raffatellu, M; Jiang, G; Bäumler, A J; Goulart, L R; Dandekar, S

    2016-05-01

    HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRRs) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRRs and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of Toll-like receptor 4 (TLR4) and TLR8 was downmodulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early antiretroviral therapy led to viral suppression but only partial maintenance of gut PRRs and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes, and ineffective viral clearance.

  5. 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

  6. Association of activating KIR copy number variation of NK cells with containment of SIV replication in rhesus monkeys.

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    Ina Hellmann

    2011-12-01

    Full Text Available While the contribution of CD8⁺ cytotoxic T lymphocytes to early containment of HIV-1 spread is well established, a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain. The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate these effector cells and might therefore modulate their activity against HIV-1-infected cells. In the present study, we investigated copy number variation in KIR3DH loci encoding the only activating KIR receptor family in rhesus monkeys and its effect on simian immunodeficiency virus (SIV replication during primary infection in rhesus monkeys. We observed an association between copy numbers of KIR3DH genes and control of SIV replication in Mamu-A*01⁻ rhesus monkeys that express restrictive TRIM5 alleles. These findings provide further evidence for an association between NK cells and the early containment of SIV replication, and underscore the potential importance of activating KIRs in stimulating NK cell responses to control SIV spread.

  7. 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.

  8. 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.

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

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    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.

  10. Non-symbolic and symbolic notations in simple arithmetic differentially involve intraparietal sulcus and angular gyrus activity

    NARCIS (Netherlands)

    Ven, F. van der; Takashima, A.; Segers, E.; Fernandez, G.S.E.; Verhoeven, L.

    2016-01-01

    Addition problems can be solved by mentally manipulating quantities for which the bilateral intraparietal sulcus (IPS) is likely recruited, or by retrieving the answer directly from fact memory in which the left angular gyrus (AG) and perisylvian areas may play a role. Mental addition is usually

  11. 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.

  12. The Balanced Two-String Technique for Sulcus Intraocular Lens Implantation in the Absence of Capsular Support

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    Hesham A. Ibrahim

    2015-01-01

    Full Text Available Purpose. To describe and explore an alternative approach for sulcus intraocular lens (IOL implantation in the absence of capsular support. Methods. The commonly available one-piece poly(methyl methacrylate (PMMA lens is stabilized in the sulcus by two intraocular horizontal strings of 10/0 polypropylene suture passed through the lens dialing holes in opposite directions to achieve a mechanical balance. The horizontal strings of 10/0 polypropylene work as a rail track for the IOL optics, allowing some side to side lens adjustment even following wound closure. The stability of the IOL was tested in vitro. Six aphakic patients underwent in-sulcus IOL secondary implantation using the balanced two-string technique. Patients were followed up for a minimum of six months. Best spectacle corrected vision was assessed. Lens centration and lens tilt were measured by anterior segment optical coherence tomography (AS-OCT. Results. All patients had successful lens insertion. Best spectacle corrected visual acuity (BSCVA improved in all patients. Lens decentration ranged between 0.21 mm and 0.9 mm (average 0.53 mm. Lens tilt ranged between 1.2° and 2.8° (average 2.17°. Conclusion. The mechanically balanced two-string technique is an alternative option for sulcus IOL implantation in absence of capsular support, allowing lens centration adjustment with no additional risks.

  13. SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination.

    Science.gov (United States)

    Klatt, Nichole R; Vinton, Carol L; Lynch, Rebecca M; Canary, Lauren A; Ho, Jason; Darrah, Patricia A; Estes, Jacob D; Seder, Robert A; Moir, Susan L; Brenchley, Jason M

    2011-11-24

    HIV infection is characterized by immune system dysregulation, including depletion of CD4+ T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4+ T cells. However, in SIV-infected animals, CD4+ T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections.

  14. Role of the long cytoplasmic domain of the SIV Env glycoprotein in early and late stages of infection

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    Khaoustov Vladimir

    2007-12-01

    Full Text Available Abstract Background The Env glycoproteins of retroviruses play an important role in the initial steps of infection involving the binding to cell surface receptors and entry by membrane fusion. The Env glycoprotein also plays an important role in viral assembly at a late step of infection. Although the Env glycoprotein interacts with viral matrix proteins and cellular proteins associated with lipid rafts, its possible role during the early replication events remains unclear. Truncation of the cytoplasmic tail (CT of the Env glycoprotein is acquired by SIV in the course of adaptation to human cells, and is known to be a determinant of SIV pathogenicity. Results We compared SIV viruses with full length or truncated (T Env glycoproteins to analyze possible differences in entry and post-entry events, and assembly of virions. We observed that early steps in replication of SIV with full length or T Env were similar in dividing and non-dividing cells. However, the proviral DNA of the pathogenic virus clone SIVmac239 with full length Env was imported to the nucleus about 20-fold more efficiently than proviral DNA of SIVmac239T with T Env, and 100-fold more efficiently than an SIVmac18T variant with a single mutation A239T in the SU subunit and with a truncated cytoplasmic tail (CT. In contrast, proviral DNA of SIVmac18 with a full length CT and with a single mutation A239T in the SU subunit was imported to the nucleus about 50-fold more efficiently than SIVmac18T. SIV particles with full length Env were released from rhesus monkey PBMC, whereas a restriction of release of virus particles was observed from human 293T, CEMx174, HUT78 or macrophages. In contrast, SIV with T Envs were able to overcome the inhibition of release in human HUT78, CEMx174, 293T or growth-arrested CEMx174 cells and macrophages resulting in production of infectious particles. We found that the long CT of the Env glycoprotein was required for association of Env with lipid rafts. An

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

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    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

  16. A Case Study on Uruk Sulcus, Ganymede: How Variations in Fault Strike and Stress Distribution can Affect Shear Failure

    Science.gov (United States)

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

    2016-12-01

    Ganymede's fractured surface reveals many morphologically distinct regions of inferred distributed shear and strike-slip faulting that may be important to the structural development of its surface. To better understand the role of strike-slip tectonism in shaping Ganymede's complex icy surface, we perform a detailed mapping of key examples of strike-slip morphologies from Galileo and Voyager imagery. We investigate the role of tidal stresses using the numerical code SatStress to calculate both diurnal and non-synchronous rotation (NSR) tidal stresses at Ganymede's surface. We then compute Coulomb failure conditions, which are a function of fault strike and regional stress magnitudes, for the mapped regions. Previous work at Dardanus Sulcus, Tiamat Sulcus, and Uruk Sulcus, regions with an inferred right-lateral sense of slip, suggests that global tidal stress models of both diurnal and NSR stress contributions readily generate shear and normal stress magnitudes ( 1.1 MPa) that could give rise to shear failure at depth ( 2 km). While models for both Dardanus and Tiamat Sulcus accurately predict right-lateral motion, stresses at Uruk Sulcus suggest a left-lateral sense of slip for the current fault strike orientation. This presents an opportunity to examine the role of temporal fault strike variations, as well as changes in the distribution of stresses, on shear failure and sense of slip. We find that models with a 10 - 40° clockwise rotation of Uruk's fault strike predict the expected right-lateral slip. Strain ellipses derived from morphological mapping efforts suggest as much as 50° of rotation may have occurred here. Such a rotation may be plausible if the feature formed in a different orientation than it presently possesses due to migration of the ice shell. Further investigation of changes in distribution of stress, perhaps due to a NSR bulge shift or true polar wander, help provide insight into how features on Ganymede may have evolved through time.

  17. A limited number of simian immunodeficiency virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251.

    Science.gov (United States)

    Stone, Mars; Keele, Brandon F; Ma, Zhong-Min; Bailes, Elizabeth; Dutra, Joseph; Hahn, Beatrice H; Shaw, George M; Miller, Christopher J

    2010-07-01

    Single-genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Use of this strategy as a means for identifying transmitted viruses suggested that intrarectal simian immunodeficiency virus (SIV) inoculation of macaques recapitulates key features of human rectal infection. However, no studies have used the SGA strategy to identify vaginally transmitted virus(es) in macaques or to determine how early SIV diversification in vaginally infected animals compares with HIV-1 in humans. We used SGA to amplify 227 partial env sequences from a SIVmac251 challenge stock and from seven rhesus macaques at the earliest plasma viral RNA-positive time point after low- and high-dose intravaginal inoculation. Sequences were analyzed phylogenetically to determine the relationship of transmitted/founder viruses within and between each animal and the challenge stock. In each animal, discrete low-diversity env sequence lineages were evident, and these coalesced phylogenetically to identical or near-identical env sequences in the challenge stock, thus confirming the validity of the SGA sequencing and modeling strategy for identifying vaginally transmitted SIV. Between 1 and 10 viruses were responsible for systemic infection, similar to humans infected by sexual contact, and the set of viruses transmitted to the seven animals studied represented the full genetic constellation of the challenge stock. These findings recapitulate many of the features of sexual HIV-1 transmission in women. Furthermore, the SIV rhesus macaque model can be used to understand the factors that influence the transmission of single versus multiple SIV variants.

  18. Global threshold dynamics of an SIVS model with waning vaccine-induced immunity and nonlinear incidence.

    Science.gov (United States)

    Yang, Junyuan; Martcheva, Maia; Wang, Lin

    2015-10-01

    Vaccination is the most effective method of preventing the spread of infectious diseases. For many diseases, vaccine-induced immunity is not life long and the duration of immunity is not always fixed. In this paper, we propose an SIVS model taking the waning of vaccine-induced immunity and general nonlinear incidence into consideration. Our analysis shows that the model exhibits global threshold dynamics in the sense that if the basic reproduction number is less than 1, then the disease-free equilibrium is globally asymptotically stable implying the disease dies out; while if the basic reproduction number is larger than 1, then the endemic equilibrium is globally asymptotically stable indicating that the disease persists. This global threshold result indicates that if the vaccination coverage rate is below a critical value, then the disease always persists and only if the vaccination coverage rate is above the critical value, the disease can be eradicated. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. 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

    preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-Age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26......Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors......,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric...

  20. Plasmacytoid dendritic cell dynamics tune interferon-alfa production in SIV-infected cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Timothée Bruel

    2014-01-01

    Full Text Available IFN-I production is a characteristic of HIV/SIV primary infections. However, acute IFN-I plasma concentrations rapidly decline thereafter. Plasmacytoid dendritic cells (pDC are key players in this production but primary infection is associated with decreased responsiveness of pDC to TLR 7 and 9 triggering. IFNα production during primary SIV infection contrasts with increased pDC death, renewal and dysfunction. We investigated the contribution of pDC dynamics to both acute IFNα production and the rapid return of IFNα concentrations to pre-infection levels during acute-to-chronic transition. Nine cynomolgus macaques were infected with SIVmac251 and IFNα-producing cells were quantified and characterized. The plasma IFN-I peak was temporally associated with the presence of IFNα(+ pDC in tissues but IFN-I production was not detectable during the acute-to-chronic transition despite persistent immune activation. No IFNα(+ cells other than pDC were detected by intracellular staining. Blood-pDC and peripheral lymph node-pDC both lost IFNα(- production ability in parallel. In blood, this phenomenon correlated with an increase in the counts of Ki67(+-pDC precursors with no IFNα production ability. In tissues, it was associated with increase of both activated pDC and KI67(+-pDC precursors, none of these being IFNα(+ in vivo. Our findings also indicate that activation/death-driven pDC renewal rapidly blunts acute IFNα production in vivo: pDC sub-populations with no IFNα-production ability rapidly increase and shrinkage of IFNα production thus involves both early pDC exhaustion, and increase of pDC precursors.

  1. 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.

  2. 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

  3. Reconstructive surgery of the sulcus of glans penis for balanopreputial adhesion due to lichen sclerosus. Our experience and medicolegal implications.

    Science.gov (United States)

    Alei, Giovanni; Letizia, Piero; Alei, Lavinia; Massoni, Francesco; Ricci, Serafino

    2014-01-01

    Our exeperience with the reconstructive surgery of the adhesion of the glans with the preputial skin due to lichen sclerosus. Twentyeight patients (mean age, 44 years; range, 28-69) underwent reshaping of the balanopreputial sulcus at our institution. All patients presented with trapped penis resulting from adhesion at the sulcus of glans due to Lichen Sclerosus. The procedure entailed separating the coronal adhesion along its entire length with the use of a blunttipped forceps, then reshaping the balanopreputial sulcus. Though simple, the maneuver is delicate and requires scrupulous attention to the ventral aspect to avoid damaging the urethra. The adhesion is removed circumferentially around the glans by means of electrobistoury. The duration of the follow-up period was 24 months. All patients stated they were satisfied with the cosmetic results and functional outcome. Recurrence of the condition occurred in 7% of the patients and was treated medically; recurrence of adhesion occurred in 2% of the patients and was treated with repeat surgery. The indication for medical therapy in early LS is a selective criterion restricted to less severe cases; otherwise, the physician may be held responsible for treatment failure, justified claims for reimbursement, disease progression and the decidedly greater damage that may ensue. Such consequences can be averted when assessment is based on recent scientific evidence and the approach to treatment is appropriate in terms of efficacy and effectiveness. Surgical management is definitive and restores normal penile anatomy and function, including sexual and urinary function, thus enabling the patient to regain sexual confidence Lichen sclerosus et atrophicus is a rare disease, however, its management is not devoid of medicolegal considerations. The etiopathogenesis of the disease is unknown but progression to carcinoma of the penis has been reported in untreated cases. Consequently, timely diagnosis holds medicolegal relevance

  4. Neural responses to expression and gaze in the posterior superior temporal sulcus interact with facial identity.

    Science.gov (United States)

    Baseler, Heidi A; Harris, Richard J; Young, Andrew W; Andrews, Timothy J

    2014-03-01

    Neural models of human face perception propose parallel pathways. One pathway (including posterior superior temporal sulcus, pSTS) is responsible for processing changeable aspects of faces such as gaze and expression, and the other pathway (including the fusiform face area, FFA) is responsible for relatively invariant aspects such as identity. However, to be socially meaningful, changes in expression and gaze must be tracked across an individual face. Our aim was to investigate how this is achieved. Using functional magnetic resonance imaging, we found a region in pSTS that responded more to sequences of faces varying in gaze and expression in which the identity was constant compared with sequences in which the identity varied. To determine whether this preferential response to same identity faces was due to the processing of identity in the pSTS or was a result of interactions between pSTS and other regions thought to code face identity, we measured the functional connectivity between face-selective regions. We found increased functional connectivity between the pSTS and FFA when participants viewed same identity faces compared with different identity faces. Together, these results suggest that distinct neural pathways involved in expression and identity interact to process the changeable features of the face in a socially meaningful way.

  5. Functional Organization of Social Perception and Cognition in the Superior Temporal Sulcus.

    Science.gov (United States)

    Deen, Ben; Koldewyn, Kami; Kanwisher, Nancy; Saxe, Rebecca

    2015-11-01

    The superior temporal sulcus (STS) is considered a hub for social perception and cognition, including the perception of faces and human motion, as well as understanding others' actions, mental states, and language. However, the functional organization of the STS remains debated: Is this broad region composed of multiple functionally distinct modules, each specialized for a different process, or are STS subregions multifunctional, contributing to multiple processes? Is the STS spatially organized, and if so, what are the dominant features of this organization? We address these questions by measuring STS responses to a range of social and linguistic stimuli in the same set of human participants, using fMRI. We find a number of STS subregions that respond selectively to certain types of social input, organized along a posterior-to-anterior axis. We also identify regions of overlapping response to multiple contrasts, including regions responsive to both language and theory of mind, faces and voices, and faces and biological motion. Thus, the human STS contains both relatively domain-specific areas, and regions that respond to multiple types of social information. © The Author 2015. Published by Oxford University Press.

  6. Dynamic changes in superior temporal sulcus connectivity during perception of noisy audiovisual speech.

    Science.gov (United States)

    Nath, Audrey R; Beauchamp, Michael S

    2011-02-02

    Humans are remarkably adept at understanding speech, even when it is contaminated by noise. Multisensory integration may explain some of this ability: combining independent information from the auditory modality (vocalizations) and the visual modality (mouth movements) reduces noise and increases accuracy. Converging evidence suggests that the superior temporal sulcus (STS) is a critical brain area for multisensory integration, but little is known about its role in the perception of noisy speech. Behavioral studies have shown that perceptual judgments are weighted by the reliability of the sensory modality: more reliable modalities are weighted more strongly, even if the reliability changes rapidly. We hypothesized that changes in the functional connectivity of STS with auditory and visual cortex could provide a neural mechanism for perceptual reliability weighting. To test this idea, we performed five blood oxygenation level-dependent functional magnetic resonance imaging and behavioral experiments in 34 healthy subjects. We found increased functional connectivity between the STS and auditory cortex when the auditory modality was more reliable (less noisy) and increased functional connectivity between the STS and visual cortex when the visual modality was more reliable, even when the reliability changed rapidly during presentation of successive words. This finding matched the results of a behavioral experiment in which the perception of incongruent audiovisual syllables was biased toward the more reliable modality, even with rapidly changing reliability. Changes in STS functional connectivity may be an important neural mechanism underlying the perception of noisy speech.

  7. Effect of head orientation on gaze processing in fusiform gyrus and superior temporal sulcus.

    Science.gov (United States)

    Pageler, Natalie M; Menon, Vinod; Merin, Noah M; Eliez, Stephan; Brown, Wendy E; Reiss, Allan L

    2003-09-01

    We used functional MRI with an event-related design to dissociate the brain activation in the fusiform gyrus (FG) and posterior superior temporal sulcus (STS) for multiple face and gaze orientations. The event-related design allowed for concurrent behavioral analysis, which revealed a significant effect of both head and gaze orientation on the speed of gaze processing, with the face and gaze forward condition showing the fastest reaction times. In conjunction with this behavioral finding, the FG responded with the greatest activation to face and gaze forward, perhaps reflecting the unambiguous social salience of congruent face and gaze directed toward the viewer. Random effects analysis showed greater activation in both the FG and posterior STS when the subjects viewed a direct face compared to an angled face, regardless of gaze direction. Additionally, the FG showed greater activation for forward gaze compared to angled gaze, but only when the face was forward. Together, these findings suggest that head orientation has a significant effect on gaze processing and these effects are manifest not only in the STS, but also the FG.

  8. Biological motion processing: the left cerebellum communicates with the right superior temporal sulcus.

    Science.gov (United States)

    Sokolov, Arseny A; Erb, Michael; Gharabaghi, Alireza; Grodd, Wolfgang; Tatagiba, Marcos S; Pavlova, Marina A

    2012-02-01

    The cerebellum is thought to be engaged not only in motor control, but also in the neural network dedicated to visual processing of body motion. However, the pattern of connectivity within this network, in particular, between the cortical circuitry for observation of others' actions and the cerebellum remains largely unknown. By combining functional magnetic resonance imaging (fMRI) with functional connectivity analysis and dynamic causal modelling (DCM), we assessed cerebro-cerebellar connectivity during a visual perceptual task with point-light displays depicting human locomotion. In the left lateral cerebellum, regions in the lobules Crus I and VIIB exhibited increased fMRI response to biological motion. The outcome of the connectivity analyses delivered the first evidence for reciprocal communication between the left lateral cerebellum and the right posterior superior temporal sulcus (STS). Through communication with the right posterior STS that is a key node not only for biological motion perception but also for social interaction and visual tasks on theory of mind, the left cerebellum might be involved in a wide range of social cognitive functions. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Metagenomic Analysis of Gingival Sulcus Microbiota and Pathogenesis of Periodontitis Associated with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Babaev, E A; Balmasova, I P; Mkrtumyan, A M; Kostryukova, S N; Vakhitova, E S; Il'ina, E N; Tsarev, V N; Gabibov, A G; Arutyunov, S D

    2017-10-01

    Biofilm of the gingival sulcus from 22 patients with type 2 diabetes mellitus and periodontitis, 30 patients with periodontitis not complicated by diabetes mellitus (reference group), and 22 healthy volunteers without signs of gingival disease (control group) was studied by quantitative PCR. Quantitative analysis for the content of P. gingivalis, T. forsythia, A. ctinomycetemcomitans, T. denticola, P. intermedia, F. nucleatum/periodonticum, and P. endodontalis in the dental plaque was performed with a Dentoscreen kit. The presence of other bacterial groups was verified by metagenomic sequencing of the 16S rRNA gene to evaluate some specific features of the etiological factor for periodontitis in type 2 diabetes mellitus. Specimens of the Porphiromonadaceae and Fusobacteriaceae families were characterized by an extremely high incidence in combined pathology. The amount of Sphingobacteriaceae bacteria in the biofilm was shown to decrease significantly during periodontitis. Metagenomic analysis confirmed the pathogenic role of microbiota in combined pathology, as well as the hypothesis on a possible influence of periodontitis on the course and development of type 2 diabetes mellitus.

  10. 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.

  11. The posterior superior temporal sulcus is involved in social communication not specific for the eyes.

    Science.gov (United States)

    Materna, Simone; Dicke, Peter W; Thier, Peter

    2008-09-01

    Neuroimaging and lesion studies suggest that the superior temporal sulcus (STS) region is involved in eye gaze processing. Hence, the STS region is suggested to be the location of the "eye-direction detector", a key element in the "mindreading model" proposed by Baron-Cohen [Baron-Cohen, S. (1995). Mindblindness: An essay on autism and theory of mind. Cambridge: The MIT Press]. Not only the eyes, but also a pointing finger of another person can inform us about the direction of attention of the other one. In an event-related functional magnetic resonance imaging experiment, healthy human subjects actively followed a directional cue provided either by the eyes or, alternatively, the pointing finger of another person to make an eye movement toward an object in space. Our results show clearly that the posterior STS region is equally involved in processing directional information from either source. The only difference between the two cues was found in the lingual gyrus, in which a stronger blood-oxygen-level-dependent (BOLD) response was observed during the finger pointing compared to the gaze following task. We suggest that different structures might be involved in the initial processing of directional information coming from the eyes or the pointing finger. These different streams of information may then converge in the posterior STS region, orchestrating the usage of a wider range of socially relevant directional cues able to inform us about the direction of attention and the intentions of another person.

  12. Visual motion responses in the posterior cingulate sulcus: a comparison to V5/MT and MST.

    Science.gov (United States)

    Fischer, Elvira; Bülthoff, Heinrich H; Logothetis, Nikos K; Bartels, Andreas

    2012-04-01

    Motion processing regions apart from V5+/MT+ are still relatively poorly understood. Here, we used functional magnetic resonance imaging to perform a detailed functional analysis of the recently described cingulate sulcus visual area (CSv) in the dorsal posterior cingulate cortex. We used distinct types of visual motion stimuli to compare CSv with V5/MT and MST, including a visual pursuit paradigm. Both V5/MT and MST preferred 3D flow over 2D planar motion, responded less yet substantially to random motion, had a strong preference for contralateral versus ipsilateral stimulation, and responded nearly equally to contralateral and to full-field stimuli. In contrast, CSv had a pronounced preference to 2D planar motion over 3D flow, did not respond to random motion, had a weak and nonsignificant lateralization that was significantly smaller than that of MST, and strongly preferred full-field over contralateral stimuli. In addition, CSv had a better capability to integrate eye movements with retinal motion compared with V5/MT and MST. CSv thus differs from V5+/MT+ by its unique preference to full-field, coherent, and planar motion cues. These results place CSv in a good position to process visual cues related to self-induced motion, in particular those associated to eye or lateral head movements.

  13. 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.

  14. Quantitative Plasma Proteomic Profiling Identifies the Vitamin E Binding Protein Afamin as a Potential Pathogenic Factor in SIV Induced CNS Disease

    OpenAIRE

    Pendyala, Gurudutt; Trauger, Sunia A; Siuzdak, Gary; Fox, Howard S.

    2010-01-01

    Investigating, predicting, diagnosing and treating HIV-1-associated neurocognitive disorder (HAND) has been hindered by the lack of disease-related molecular markers. In this study, plasma from rhesus monkeys (n=6), before and after infection with simian immunodeficiency virus (SIV), was profiled to obtain differential fingerprints in protein expression during SIV-induced central nervous system (CNS) disease. A quantitative proteomic analysis was performed by means of isobaric tag for relativ...

  15. Measuring turnover of SIV DNA in resting CD4+ T cells using pyrosequencing: implications for the timing of HIV eradication therapies.

    Directory of Open Access Journals (Sweden)

    Jeanette C Reece

    Full Text Available Resting CD4+ T cells are a reservoir of latent HIV-1. Understanding the turnover of HIV DNA in these cells has implications for the development of eradication strategies. Most studies of viral latency focus on viral persistence under antiretroviral therapy (ART. We studied the turnover of SIV DNA resting CD4+ T cells during active infection in a cohort of 20 SIV-infected pigtail macaques. We compared SIV sequences at two Mane-A1*084:01-restricted CTL epitopes using serial plasma RNA and resting CD4+ T cell DNA samples by pyrosequencing, and used a mathematical modeling approach to estimate SIV DNA turnover. We found SIV DNA turnover in resting CD4+ T cells was slow in animals with low chronic viral loads, consistent with the long persistence of latency seen under ART. However, in animals with high levels of chronic viral replication, turnover was high. SIV DNA half-life within resting CD4 cells correleated with viral load (p = 0.0052 at the Gag KP9 CTL epitope. At a second CTL epitope in Tat (KVA10 there was a trend towards an association of SIV DNA half-life in resting CD4 cells and viral load (p = 0.0971. Further, we found that the turnover of resting CD4+ T cell SIV DNA was higher for escape during early infection than for escape later in infection (p = 0.0084. Our results suggest viral DNA within resting CD4 T cells is more labile and may be more susceptible to reactivation/eradication treatments when there are higher levels of virus replication and during early/acute infection.

  16. Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys.

    Directory of Open Access Journals (Sweden)

    Jörn E Schmitz

    2009-12-01

    Full Text Available African green monkeys (AGM and other natural hosts for simian immunodeficiency virus (SIV do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIV(agmVer90 to infect vervet AGM and pigtailed macaques (PTM. This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4 and AGM (n = 4, and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms.

  17. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load.

    Directory of Open Access Journals (Sweden)

    Collin R Diedrich

    2010-03-01

    Full Text Available HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb infection are at significantly greater risk of reactivation tuberculosis (TB than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV. Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection.

  18. [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)

  19. The mid-fusiform sulcus: A landmark identifying both cytoarchitectonic and functional divisions of human ventral temporal cortex

    Science.gov (United States)

    Weiner, Kevin S.; Golarai, Golijeh; Caspers, Julian; Chuapoco, Miguel R.; Mohlberg, Hartmut; Zilles, Karl; Amunts, Katrin; Grill-Spector, Kalanit

    2014-01-01

    Human ventral temporal cortex (VTC) plays a pivotal role in high-level vision. An under-studied macroanatomical feature of VTC is the mid-fusiform sulcus (MFS), a shallow longitudinal sulcus separating the lateral and medial fusiform gyrus (FG). Here, we quantified the morphological features of the MFS in 69 subjects (ages 7–40), and investigated its relationship to both cytoarchitectonic and functional divisions of VTC with four main findings. First, despite being a minor sulcus, we found that the MFS is a stable macroanatomical structure present in all 138 hemispheres with morphological characteristics developed by age 7. Second, the MFS is the locus of a lateral-medial cytoarchitechtonic transition within the posterior FG serving as the boundary between cytoarchitectonic regions FG1 and FG2. Third, the MFS predicts a lateral-medial functional transition in eccentricity bias representations in children, adolescents, and adults. Fourth, the anterior tip of the MFS predicts the location of a face-selective region, mFus-faces/FFA-2. These findings are the first to illustrate that a macroanatomical landmark identifies both cytoarchitectonic and functional divisions of high-level sensory cortex in humans and have important implications for understanding functional and structural organization in the human brain. PMID:24021838

  20. IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Liu, David X.; Moroney-Rasmussen, Terri; Lackner, Andrew A.; Veazey, Ronald S.

    2013-01-01

    SUMMARY Innate lymphoid cells (ILCs) are an emerging subset of lymphocytes involved in surveillance against virally infected cells. Here we show CD3−CD8high lymphocytes in macaque blood include major subsets of ILCs including NK cells expressing CD16, NKp46 and NKG2A, but also populations of ILCs in mucosal tissues having different properties. One ILC subset secreted IL-17 (ILC17), but these were restricted to mucosal tissues. Some mucosal ILC17 cells expressed classical NK-cell markers, but little NKG2A or NKG2D. Some ILC17 cells secreted IL-22 and TNF-α, but few produced IFN-γ or contained granzyme B. IL-17 production by ILCs was induced by IL-6, TGF-β and IL-23. Further, SIV infection resulted in a significant loss of ILC17 cells, especially in the jejunum, which persisted throughout SIV infection. These findings ILC17 cells may be involved in innate mucosal immune responses, and their loss may contribute to loss of intestinal mucosal integrity and disease progression in HIV/SIV infection. PMID:22669579

  1. Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque.

    Science.gov (United States)

    Rotger, Margalida; Dalmau, Judith; Rauch, Andri; McLaren, Paul; Bosinger, Steven E; Martinez, Raquel; Sandler, Netanya G; Roque, Annelys; Liebner, Julia; Battegay, Manuel; Bernasconi, Enos; Descombes, Patrick; Erkizia, Itziar; Fellay, Jacques; Hirschel, Bernard; Miró, Jose M; Palou, Eduard; Hoffmann, Matthias; Massanella, Marta; Blanco, Julià; Woods, Matthew; Günthard, Huldrych F; de Bakker, Paul; Douek, Daniel C; Silvestri, Guido; Martinez-Picado, Javier; Telenti, Amalio

    2011-06-01

    High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

  2. Transcription Profiling Reveals Potential Mechanisms of Dysbiosis in the Oral Microbiome of Rhesus Macaques with Chronic Untreated SIV Infection

    Science.gov (United States)

    Ocon, Susan; Murphy, Christina; Dang, Angeline T.; Sankaran-Walters, Sumathi; Li, Chin-Shang; Tarara, Ross; Borujerdpur, Niku; Dandekar, Satya; Paster, Bruce J.; George, Michael D.

    2013-01-01

    A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and “macaque versions” of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides. PMID:24312248

  3. Characterization of antigens expressed in normal baboon trophoblast and cross-reactive with HIV/SIV antibodies.

    Science.gov (United States)

    Langat, D K; Johnson, P M; Rote, N S; Wango, E O; Owiti, G O; Isahakia, M A; Mwenda, J M

    1999-01-01

    Electron microscopic studies have revealed the presence of endogenous retroviral (ERV) particles in normal primate placental tissues. These particles have ultrastructural similarities to type C retroviral particles and are mainly associated with the trophoblast. In normal human placental tissues, they have antigenic similarity with exogenous retroviruses, such as the human immunodeficiency virus (HIV), and may have a role to play in the regulation of cellular gene expression, syncytiotrophoblast formation or pregnancy-related immunosuppression. In this study, a panel of antibodies (polyclonal and monoclonal antibodies) against viral proteins (anti-HIV and anti-SIV) and endogenous retroviral (ERV) proteins were assessed by immunohistochemistry and immunoblotting, for their cross-reactivity with ERV particles isolated from normal baboon placental tissues. The antibodies (anti-HERV-K RT, anti-ERV3 env, anti-HIV-1 p17, anti-HIV-2 gp120) reacted positively with the syncytiotrophoblast and each antibody recognized one or two proteins of molecular weights (MW) 38, 58 or 64 kDa present in the baboon placental villous tissues and SIV-infected molt-4 Cl8 cells, but not in uninfected cells. The results of this study confirm the specific expression of retroviral cross-reactive antigens in normal baboon placental tissues and suggest placental cellular proteins may have antigenic similarity with those recognized by anti-HIV/SIV antibodies. The role of these retroviral-related proteins expressed at the maternal-fetal interface remain unclear.

  4. Quantifying transmission by stage of infection in the field: the example of SIV-1 and STLV-1 infecting mandrills.

    Science.gov (United States)

    Roussel, Marion; Pontier, Dominique; Kazanji, Mirdad; Ngoubangoye, Barthélémy; Mahieux, Renaud; Verrier, Delphine; Fouchet, David

    2015-03-01

    The early stage of viral infection is often followed by an important increase of viral load and is generally considered to be the most at risk for pathogen transmission. Most methods quantifying the relative importance of the different stages of infection were developed for studies aimed at measuring HIV transmission in Humans. However, they cannot be transposed to animal populations in which less information is available. Here we propose a general method to quantify the importance of the early and late stages of the infection on micro-organism transmission from field studies. The method is based on a state space dynamical model parameterized using Bayesian inference. It is illustrated by a 28 years dataset in mandrills infected by Simian Immunodeficiency Virus type-1 (SIV-1) and the Simian T-Cell Lymphotropic Virus type-1 (STLV-1). For both viruses we show that transmission is predominant during the early stage of the infection (transmission ratio for SIV-1: 1.16 [0.0009; 18.15] and 9.92 [0.03; 83.8] for STLV-1). However, in terms of basic reproductive number (R0 ), which quantifies the weight of both stages in the spread of the virus, the results suggest that the epidemics of SIV-1 and STLV-1 are mainly driven by late transmissions in this population. © 2014 Wiley Periodicals, Inc.

  5. 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.

  6. [Olfactory bulb volume and depth of olfactory sulcus in patients with allergic rhinitis].

    Science.gov (United States)

    Zhang, Qiang; Liu, Gang; Hang, Wei

    2014-12-01

    To explore the olfactory abilities in patients with allergic rhinitis (AR), analyze the correlation between olfactory bulb (OB) volume with depth of olfactory sulcus (OS) and olfactory function in patients with AR. One hundred patients with AR were compared with one hundred controls in terms of olfactory function T&T testing, OB volume and depth of OS assessed with magnetic resonance imaging (MRI). T&T testing and MRI were done after a year in 100 AR patients,the results were compared with the initial results. The OB volume in AR patients was (29.53±3.95) mm3 on the left, (29.67±14.21)mm3 on the right, (29.61±4.05) mm3 on average; The OB volume in controls was (48.93±6.73)mm3 on the left side, (48.81±7.43)mm3 on the right side, (48.85±7.11)mm3 on average; The OB volume in AR patients was less then the control group(t= 6.321, 6.141, 6.221, P0.05). Olfactory discriminate threshold was negatively correlated with OB volume in AR patients (r=-0.46, P0.05). Among 100 followed-up AR patients, 43 showed increased in OB volume and olfactory function after a year, but there was no statistical difference (t= 0. 811,0. 843, 0.826, P>0.05; Z=1.911, P>0.05) ,and the other 57 showed no significant changes of OB volume and olfactory function. In AR patients, the OB volume and olfactory function decreased, but the depth of OS had no significant changes. The OB volume is correlated with olfactory function, while the depth of OS is no correlated with olfactory function. Conservative treatment had some clinical significance on the recovery of olfactory function in patients with AR.

  7. Peri-Implant Sulcus Fluid (PISF) Matrix Metalloproteinase (MMP) -8 Levels in Peri-Implantitis.

    Science.gov (United States)

    Thierbach, René; Maier, Kurt; Sorsa, Timo; Mäntylä, Päivi

    2016-05-01

    Matrix Metalloproteinase (MMP) -8 plays crucial role in pathogenesis of periodontitis and is also a possible biomarker candidate in peri-implantitis. The aim of the study was to analyse MMP-8 levels in peri-Implant Sulcus Fluid (PISF) from peri-implantitis affected implants in smoking and non-smoking patients with different periodontal health status of natural teeth before and after peri-implantitis treatment. Altogether 29 patients with peri-implantitis were recruited and divided into two study groups (11 with healthy periodontium or gingivitis, i.e. no marginal bone loss, and 18 with chronic periodontitis). PISF sample from one implant with peri-implantitis from each patient was collected at the baseline and six months after conservative and surgical peri-implantitis treatment, and clinical parameters were registered. Samples were analysed for MMP-8 with dento ELISA method applying a monoclonal antibody. Mucosal cell samples were also analysed for IL-1 gene polymorphism. PISF MMP-8 levels' differences between periodontal diagnosis groups and between smokers' and non-smokers' were analysed. Also, IL-1 polymorphism profiles were compared between study groups. PISF MMP-8 levels were higher at the baseline compared to and after the treatment when all sampled implant sites were analysed together (p = 0.001). MMP-8 levels' distribution was broader in periodontitis patients' PISF samples, and only in periodontitis patients' group levels decreased statistically significantly after the treatment (p = 0.005). Smokers'and non-smokers' PISF MMP-8 was at similar level both at the baseline and after the treatment. No difference between distributions of IL-1 genotypes was found between study groups. MMP-8 levels increase in peri-implantitis affected implants both in non-periodontitis and periodontitis patients, but levels still after treatment of the condition reflect intensified host response around implants and indicate challenges of controlling peri-Implantitis with any

  8. Perceived communicative intent in gesture and language modulates the superior temporal sulcus.

    Science.gov (United States)

    Redcay, Elizabeth; Velnoskey, Kayla R; Rowe, Meredith L

    2016-10-01

    Behavioral evidence and theory suggest gesture and language processing may be part of a shared cognitive system for communication. While much research demonstrates both gesture and language recruit regions along perisylvian cortex, relatively less work has tested functional segregation within these regions on an individual level. Additionally, while most work has focused on a shared semantic network, less has examined shared regions for processing communicative intent. To address these questions, functional and structural MRI data were collected from 24 adult participants while viewing videos of an experimenter producing communicative, Participant-Directed Gestures (PDG) (e.g., "Hello, come here"), noncommunicative Self-adaptor Gestures (SG) (e.g., smoothing hair), and three written text conditions: (1) Participant-Directed Sentences (PDS), matched in content to PDG, (2) Third-person Sentences (3PS), describing a character's actions from a third-person perspective, and (3) meaningless sentences, Jabberwocky (JW). Surface-based conjunction and individual functional region of interest analyses identified shared neural activation between gesture (PDGvsSG) and language processing using two different language contrasts. Conjunction analyses of gesture (PDGvsSG) and Third-person Sentences versus Jabberwocky revealed overlap within left anterior and posterior superior temporal sulcus (STS). Conjunction analyses of gesture and Participant-Directed Sentences to Third-person Sentences revealed regions sensitive to communicative intent, including the left middle and posterior STS and left inferior frontal gyrus. Further, parametric modulation using participants' ratings of stimuli revealed sensitivity of left posterior STS to individual perceptions of communicative intent in gesture. These data highlight an important role of the STS in processing participant-directed communicative intent through gesture and language. Hum Brain Mapp 37:3444-3461, 2016. © 2016 Wiley

  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. 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.

  11. 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.

  12. Underconnectivity of the superior temporal sulcus predicts emotion recognition deficits in autism

    Science.gov (United States)

    Woolley, Daniel G.; Steyaert, Jean; Di Martino, Adriana; Swinnen, Stephan P.; Wenderoth, Nicole

    2014-01-01

    Neurodevelopmental disconnections have been assumed to cause behavioral alterations in autism spectrum disorders (ASDs). Here, we combined measurements of intrinsic functional connectivity (iFC) from resting-state functional magnetic resonance imaging (fMRI) with task-based fMRI to explore whether altered activity and/or iFC of the right posterior superior temporal sulcus (pSTS) mediates deficits in emotion recognition in ASD. Fifteen adults with ASD and 15 matched-controls underwent resting-state and task-based fMRI, during which participants discriminated emotional states from point light displays (PLDs). Intrinsic FC of the right pSTS was further examined using 584 (278 ASD/306 controls) resting-state data of the Autism Brain Imaging Data Exchange (ABIDE). Participants with ASD were less accurate than controls in recognizing emotional states from PLDs. Analyses revealed pronounced ASD-related reductions both in task-based activity and resting-state iFC of the right pSTS with fronto-parietal areas typically encompassing the action observation network (AON). Notably, pSTS-hypo-activity was related to pSTS-hypo-connectivity, and both measures were predictive of emotion recognition performance with each measure explaining a unique part of the variance. Analyses with the large independent ABIDE dataset replicated reductions in pSTS-iFC to fronto-parietal regions. These findings provide novel evidence that pSTS hypo-activity and hypo-connectivity with the fronto-parietal AON are linked to the social deficits characteristic of ASD. PMID:24078018

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. Conserved molecular signatures in gp120 are associated with the genetic bottleneck during simian immunodeficiency virus (SIV), SIV-human immunodeficiency virus (SHIV), and HIV type 1 (HIV-1) transmission.

    Science.gov (United States)

    Gonzalez, Mileidy W; DeVico, Anthony L; Lewis, George K; Spouge, John L

    2015-04-01

    Human immunodeficiency virus (HIV) transmission typically results from infection by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly at random from the donor pool, or are they selected based on advantageous traits facilitating transmission? Finding evidence for selection during transmission is of particular interest, because it would indicate that phenotypic and/or genetic properties of the viruses might be harnessed as potential vaccine targets or immunotherapies. Here, we systematically evaluated the differences between the Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F variants in search of "signature" sites of transmission. We also surveyed residue preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed significant selection, and an additional two sites showed a similar trend. Therefore, the six sites clearly differentiate T/F viruses from the majority of circulating variants in the stocks. The selection of SIV/SHIV could be inferred reasonably across both vaccinated and unvaccinated subjects, with infections resulting from vaginal, rectal, and intravenous routes of transmission and regardless of viral dosage. The evidence for selection in SIV and SHIV T/F variants is strong and plentiful, and in HIV the evidence is suggestive though commensurate with the availability of suitable data for analysis. Two of the signature residues are completely conserved across the SIV, SHIV, and HIV variants we examined. Five of the signature residues map to the C1 region of gp120 and one to the signal peptide. Our data raise the possibility that C1, while governing the association between gp120 and gp41, modulates transmission efficiency, replicative fitness, and/or host cell tropism at the level of virus-cell attachment and entry. The present study finds significant evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data provide ancillary evidence suggesting the same sites

  16. Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL-21.

    Directory of Open Access Journals (Sweden)

    Suresh Pallikkuth

    Full Text Available In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs, preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIV(mac239 and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i higher expression of perforin and granzyme B in total and SIV-specific CD8⁺ T cells and (ii higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.

  17. Description of a Rare Case of Nodular Fasciitis of the Apical Aspect of the Upper Buccal Sulcus

    Directory of Open Access Journals (Sweden)

    Ana Amélia Souza

    2016-01-01

    Full Text Available This report describes a rare case of nodular fasciitis (NF of the oral cavity, discussing the clinical, histological, and immunohistochemical characteristics. Histopathologic diagnosis of this type of lesion can be challenging due to its differential diagnosis, which principally includes sarcoma. The patient presented with a painless, well-defined nodule, reported as increasing in size, located at the apical aspect of the upper left buccal sulcus. Histologically, the lesion revealed spindle cell proliferation arranged in fascicles, while immunohistochemistry demonstrated positivity for smooth muscle actin. Eight months after complete surgical excision, no signs of local recurrence have been observed.

  18. 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...... motor threshold. We pseudorandomly stimulated six targets located on a straight mediolateral line corresponding to the overall orientation of the central sulcus with a fixed coil orientation of 45° to the mid-sagittal line (STRAIGHT-450 FIX) or seven targets in the posterior part of the crown...

  19. Estimating the impact of vaccination in acute SHIV-SIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ruy [Los Alamos National Laboratory

    2008-01-01

    Human Immunodeficiency Virus (HIV) infects approxmately 0.5% of the world population, and is a major cause of morbidity and mortality worldwide. A vaccine for HIV is urgently required, and a variety of vaccine modalities have been tested in animal models of infection. A number of these studies have shown protection in monkey models of infection, although the ability of the vaccine to protect appears to vary with the viral strain and animal model used. The recent failure of a large vaccine study in humans suggests that further understanding of the basic dynamics of infection and impact of vaccination are required, in order to understand the variable efficacy of vaccination in different infections. The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio (R{sub 0}) of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, in the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in Simian Human Immunodeficiency Virus (SHIV) and Simian Immunodeficiency Virus (SIV) infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3 and 2 fold respectively. This method allows the comparison of vaccination efficacy amongst different viral strains and animal models in vivo.

  20. 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.

  1. 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.

  2. Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Hebblewaite Diane

    2011-01-01

    Full Text Available Abstract Background In many preclinical AIDS research studies, antiretroviral therapy (ART is administered to experimentally simian immunodeficiency (SIV-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r-(phosphonomethoxy propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology. In contrast, chronic administration of a low dose of PMPA (10 mg/kg subcutaneously once daily starting at birth does not seem to be associated with any adverse health effects within 3 years of treatment. In contrast to PMPA, limited information on systemic toxicity in rhesus monkeys is available for FTC (5-fluoro-1-(2R,5S-[2-(hydroxymethyl-1,3-oxathiolan-5-yl]cytosine; emtricitabine and stavudine (d4T. Results In this study, the clinical and biochemical correlates of tubular nephrosis in SIV-infected rhesus macaques associated with systemic administration of high-dose ART consisting of the three nucleoside analog inhibitors PMPA, FTC, and d4T were investigated. It was found that acute renal failure was uncommon (7.1% of treated animals and that morphologic evidence of nephropathy, which persisted for more than 300 days following discontinuation of the drug cocktail, was more frequent (52.4% of treated animals. While parameters from single time points lacked predictive value, biochemical alterations in Blood Urea Nitrogen (BUN and phosphorus were frequently identified longitudinally in the blood of ART-treated animals that developed evidence of nephropathy, and these longitudinal changes correlated with disease severity. Conclusions Recommendations are proposed to limit the impact of drug-induced renal disease in future SIV macaque studies.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Comparison of postoperative vault height predictability using white-to-white or sulcus diameter-based sizing for the visian implantable collamer lens.

    Science.gov (United States)

    Reinstein, Dan Z; Lovisolo, Carlo F; Archer, Timothy J; Gobbe, Marine

    2013-01-01

    To compare vault height predictability of Implantable Collamer Lens (ICL; Staar Surgical) sizing using a sulcus diameter-based formula or the manufacturer-recommended white-to-white-based method. In 50 myopic eyes, ICL size was calculated using both a formula including sulcus diameter and the traditional formula based on white-to-white diameter. Sulcus diameter was measured using Artemis 2 very high-frequency (VHF) digital ultrasound (ArcScan Inc). Implantation was based on the sulcus diameter derived size. Actual postoperative vault height achieved was measured by VHF digital ultrasound scanning. Circle segment trigonometry was used to calculate the vault height that would have resulted had lens sizing been based on the white-to-white formula. The same lens size would have been used in 60% of eyes, a smaller lens would have been used in 34% of eyes and a larger lens in 6% of eyes had lens sizing been based on the white-to-white formula. Mean vault for eyes with lenses sized using the sulcus diameter formula was 0.37±0.16 mm (range: 0.08 to 0.92 mm), with 2% trigonometry predicted that the vault height would have been 0.24±0.28 mm (range: -0.31 to 0.92 mm), with 26% <0.09 mm had lens sizing been based on the white-to-white formula. Significantly better predictability of postoperative vault height was achieved by including sulcus diameter into the ICL sizing formula compared with using the traditional white-to-white-based formula. Copyright 2013, SLACK Incorporated.

  5. Quantitative plasma proteomic profiling identifies the vitamin E binding protein afamin as a potential pathogenic factor in SIV induced CNS disease.

    Science.gov (United States)

    Pendyala, Gurudutt; Trauger, Sunia A; Siuzdak, Gary; Fox, Howard S

    2010-01-01

    Investigating, predicting, diagnosing, and treating HIV-1-associated neurocognitive disorder (HAND) has been hindered by the lack of disease-related molecular markers. In this study, plasma from rhesus monkeys (n = 6), before and after infection with simian immunodeficiency virus (SIV), was profiled to obtain differential fingerprints in protein expression during SIV-induced central nervous system (CNS) disease. A quantitative proteomic analysis was performed by means of isobaric tag for relative and absolute quantification (iTRAQ) labeling, using multidimensional liquid chromatography tandem mass spectrometry (LC-MS/MS) run on a linear ion trap mass spectrometer in an integrated mode comprising pulsed-Q-dissociation (PQD) and CID. Among a panel of proteins showing differential expression following SIV infection, we identified afamin, a member of the albumin superfamily, to be significantly down regulated after infection. Validation by Western blot confirmed this observation and, given its potential implication in neuroprotection by transport of alpha-tocopherol (alphaTocH), provides new avenues into further understanding HIV induced CNS disease. iTRAQ-based LC-MS/MS provides a valuable platform for plasma protein profiling and has important implications in identifying molecular markers relevant for the pathogenesis of neurodegenerative diseases. Using such an approach, we show its successful application in identifying differential fingerprints in SIV/HIV induced CNS disease.

  6. Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Deborah Heydenburg Fuller

    Full Text Available Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT, during antiretroviral therapy (ART induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans.

  7. 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.; Duijnhoven, G.C.F. van; Vliet, S.J. van; Schijndel, J.C.H.W. van; Engering, A.J.; Heeney, J.L.; Kooyk, Y. van

    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

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

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    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.

  9. 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

  10. Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus.

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    Meritxell Genescà

    Full Text Available BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-gamma production were similar, the SIV-specific CD8(+ T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+ T cells from untreated animals. CONCLUSIONS: Depo-Provera did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera(R on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results

  11. Changes in the Ratio of the Sulcus Acusticus Area to the Sagitta Area of Pomatoschistus-Minutus and P-Lozanoi (Pisces, Gobiidae)

    NARCIS (Netherlands)

    Arellano, R.V.; Hamerlynck, O.; Vincx, M.; Mees, J.; Hostens, K.; Gijselinck, W.

    1995-01-01

    The Pomatoschistus minutus (Pallas) and P. lozanoi (de Buen) stock of the ebb-tidal delta of the former Grevelingen estuary was sampled monthly from September 1992 to October 1993. Sagittae were extracted and the areas of the sagitta and sulcus acusticus were measured with a digitizer. The frequency

  12. Evaluation of the safety, immunogenicity, and protective efficacy of whole inactivated simian immunodeficiency virus (SIV) vaccines with conformationally and functionally intact envelope glycoproteins.

    Science.gov (United States)

    Lifson, Jeffrey D; Rossio, Jeffrey L; Piatak, Michael; Bess, Julian; Chertova, Elena; Schneider, Douglas K; Coalter, Vicky J; Poore, Barbara; Kiser, Rebecca F; Imming, Robert J; Scarzello, Anthony J; Henderson, Louis E; Alvord, W Gregory; Hirsch, Vanessa M; Benveniste, Raoul E; Arthur, Larry O

    2004-07-01

    A novel, general approach to chemical inactivation of retroviruses was used to produce inactivated simian immunodeficiency virus (SIV) particles with functional envelope glycoproteins. Inactivated virions of three different virus isolates (SIVmne E11S, SIVmac239, and SIVmac239 g4,5), prepared by treatment with 2,2'-dithiodipyridine (aldrithol-2, AT-2), were not detectably infectious, in vitro or in vivo. Immunization of pigtailed macaques with inactivated SIVmne E11S particles, without adjuvant, induced both humoral and cellular immune responses. Four of six animals immunized with the inactivated particles did not show measurable SIV RNA in plasma (virus (SIVmne E11S), compared to peak values of > or =10(6) copy Eq/ml in challenged SIV-naive control animals (p = 0.0001). Despite the absence of measurable viral RNA in plasma in these animals, culturable virus and viral DNA were initially detectable in blood and lymph node specimens; in contrast to control animals, SIV DNA could no longer be detected in PBMC by 10 weeks postchallenge in five of six SIV-immunized animals (p = 0.0001). However, vaccines did not resist a sequential rechallenge with the heterologous pathogenic virus SIVsm E660. AT-2-inactivated virus with functional envelope glycoproteins is a novel class of vaccine immunogen and was noninfectious, under conditions of rigorous in vivo challenge, and induced both binding and neutralizing antibody responses, along with cellular immune responses. Results suggest that immunization facilitated effective containment of pathogenic homologous challenge virus. With further optimization, AT-2-inactivated viral particles may be a useful class of immunogen in the development of a vaccine to prevent AIDS.

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

    Science.gov (United States)

    Damouche, Abderaouf; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-01-01

    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-grade chronic

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

    Directory of Open Access Journals (Sweden)

    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

  15. Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma.

    Directory of Open Access Journals (Sweden)

    Tricia H Burdo

    2010-04-01

    Full Text Available Cells of the myeloid lineage are significant targets for human immunodeficiency virus (HIV in humans and simian immunodeficiency virus (SIV in monkeys. Monocytes play critical roles in innate and adaptive immunity during inflammation. We hypothesize that specific subsets of monocytes expand with AIDS and drive central nervous system (CNS disease. Additionally, there may be expansion of cells from the bone marrow through blood with subsequent macrophage accumulation in tissues driving pathogenesis. To identify monocytes that recently emigrated from bone marrow, we used 5-bromo-2'-deoxyuridine (BrdU labeling in a longitudinal study of SIV-infected CD8+ T lymphocyte depleted macaques. Monocyte expansion and kinetics in blood was assessed and newly migrated monocyte/macrophages were identified within the CNS. Five animals developed rapid AIDS with differing severity of SIVE. The percentages of BrdU+ monocytes in these animals increased dramatically, early after infection, peaking at necropsy where the percentage of BrdU+ monocytes correlated with the severity of SIVE. Early analysis revealed changes in the percentages of BrdU+ monocytes between slow and rapid progressors as early as 8 days and consistently by 27 days post infection. Soluble CD163 (sCD163 in plasma correlated with the percentage of BrdU+ monocytes in blood, demonstrating a relationship between monocyte activation and expansion with disease. BrdU+ monocytes/macrophages were found within perivascular spaces and SIVE lesions. The majority (80-90% of the BrdU+ cells were Mac387+ that were not productively infected. There was a minor population of CD68+BrdU+ cells (<10%, very few of which were infected (<1% of total BrdU+ cells. Our results suggest that an increased rate of monocyte recruitment from bone marrow into the blood correlates with rapid progression to AIDS, and the magnitude of BrdU+ monocytes correlates with the severity of SIVE.

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

    Science.gov (United States)

    Damouche, Abderaouf; Lazure, Thierry; Avettand-Fènoël, Véronique; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-09-01

    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-grade chronic

  17. "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

  18. Genetic Factors and Orofacial Motor Learning Selectively Influence Variability in Central Sulcus Morphology in Chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Hopkins, William D; Coulon, Oliver; Meguerditchian, Adrien; Autrey, Michelle; Davidek, Kendall; Mahovetz, Lindsay; Pope, Sarah; Mareno, Mary Catherine; Schapiro, Steven J

    2017-05-31

    Captive chimpanzees (Pan troglodytes) have been shown to learn the use of novel attention-getting (AG) sounds to capture the attention of humans as a means of requesting or drawing their attention to a desired object or food. There are significant individual differences in the use of AG sounds by chimpanzees and, here, we examined whether changes in cortical organization of the central sulcus (CS) were associated with AG sound production. MRI scans were collected from 240 chimpanzees, including 122 that reliably produced AG sounds and 118 that did not. For each subject, the depth of CS was quantified along the superior-inferior plane with specific interest in the inferior portion corresponding to the region of the motor cortex where the mouth and orofacial movements are controlled. Results indicated that CS depth in the inferior, but not superior, portion was significantly greater in chimpanzees that reliably produced AG sounds compared with those who did not. Quantitative genetic analyses indicated that overall CS surface area and depth were significantly heritable, particularly in the superior regions, but less so in the inferior and central portions. Further, heritability in CS depth was altered as a function of acquisition of AG sounds. The collective results suggest that learning to produce AG sounds resulted in region-specific cortical reorganization within the inferior portion of the CS, a finding previously undocumented in chimpanzees or any nonhuman primate.SIGNIFICANCE STATEMENT Recent studies in chimpanzees (Pan troglodytes) have shown that some can learn to produce novel sounds by configuring different orofacial movement patterns and these sounds are used in communicatively relevant contexts. Here, we examined the neuromorphological correlates in the production of these sounds in chimpanzees. We show that chimpanzees that have learned to produce these sounds show significant differences in central sulcus (CS) morphology, particularly in the inferior

  19. The Superior Temporal Sulcus Is Causally Connected to the Amygdala: A Combined TBS-fMRI Study.

    Science.gov (United States)

    Pitcher, David; Japee, Shruti; Rauth, Lionel; Ungerleider, Leslie G

    2017-02-01

    Nonhuman primate neuroanatomical studies have identified a cortical pathway from the superior temporal sulcus (STS) projecting into dorsal subregions of the amygdala, but whether this same pathway exists in humans is unknown. Here, we addressed this question by combining theta burst transcranial magnetic stimulation (TBS) with fMRI to test the prediction that the STS and amygdala are functionally connected during face perception. Human participants (N = 17) were scanned, over two sessions, while viewing 3 s video clips of moving faces, bodies, and objects. During these sessions, TBS was delivered over the face-selective right posterior STS (rpSTS) or over the vertex control site. A region-of-interest analysis revealed results consistent with our hypothesis. Namely, TBS delivered over the rpSTS reduced the neural response to faces (but not to bodies or objects) in the rpSTS, right anterior STS (raSTS), and right amygdala, compared with TBS delivered over the vertex. By contrast, TBS delivered over the rpSTS did not significantly reduce the neural response to faces in the right fusiform face area or right occipital face area. This pattern of results is consistent with the existence of a cortico-amygdala pathway in humans for processing face information projecting from the rpSTS, via the raSTS, into the amygdala. This conclusion is consistent with nonhuman primate neuroanatomy and with existing face perception models. Neuroimaging studies have identified multiple face-selective regions in the brain, but the functional connections between these regions are unknown. In the present study, participants were scanned with fMRI while viewing movie clips of faces, bodies, and objects before and after transient disruption of the face-selective right posterior superior temporal sulcus (rpSTS). Results showed that TBS disruption reduced the neural response to faces, but not to bodies or objects, in the rpSTS, right anterior STS (raSTS), and right amygdala. These results are

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

    Science.gov (United States)

    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

  1. [Implantation of a sulcus-fixated toric additive intraocular lens in a case of high astigmatism after a triple procedure].

    Science.gov (United States)

    Linz, K; Auffarth, G U; Kretz, F T A

    2014-08-01

    Residual refractive errors, especially high-grade astigmatism after penetrating keratoplasty, often lead to a significant loss of vision. If high anismetropia could not be corrected with glasses or contact lenses, different kinds of surgical procedures are available for visual rehabilitation (intraocular lens exchange, astigmatic keratotomy, Excimer laser treatment, intrastromal corneal ring segment implantation and additive intraocular lens implantation). Toric add-on IOLs are especially designed for sulcus implantation and correcting high astigmatism in pseudophakic eyes. All toric IOLs are individually manufactured according to subjective refraction and biometry. Depending on the underlying manufacturer high-grade astigmatism can be corrected with a cylindrical power up to + 30.0 D. A 74-year-old patient presented with endothelial decompensation and an uncorrected distance visual acuity (UDVA) of 1.0 logMAR for penetrating keratoplasty on the right eye due to a Fuchs endothelial dystrophy. Postoperatively, the uncorrected distance visual acuity improved to 0.8 logMAR, with pinhole correction to 0.5 logMAR. After removing the sutures a high and irregular corneal astigmatism of 21.0 D was found. The corrected distance visual acuity (CDVA) with a refraction of + 5.5 D sph, - 21.0 D cyl 90° was 0.24 logMAR. Therefore an individually manufactured toric additive intraocular lens of + 25.0 D cylindrical and - 18.0 D spherical power for sulcus implantation was chosen and implanted uneventfully. Eight months after surgery refractive astigmatism was reduced significantly to - 0.75 D with an UDVA of 0.08 logMAR and a CDVA of 0.02 logMAR. During the 8-months follow-up period the additive IOL remained centered and no IOL rotation could be observed. Toric add-on IOLs are a safe and successful method for reducing high astigmatism and anisometropia after penetrating keratoplasty. One of the main advantages is the reversibility of the procedure by an explantation of

  2. Attentional orienting to mnemonic representations: reduction of load-sensitive maintenance-related activity in the intraparietal sulcus.

    Science.gov (United States)

    Trapp, Sabrina; Lepsien, Jöran

    2012-10-01

    The orienting of attention to internal or mnemonic representations held in visual working memory (VWM) has recently become a field of increasing interest. While a number of studies support the hypothesis that attention to selected representations in VWM reduces memory load, conclusive findings are still missing. In this event-related functional magnetic resonance imaging (fMRI) study, we directly investigated whether attentional orienting to mnemonic representations reduces activity in VWM storage-related areas of the brain. VWM load was manipulated by asking subjects to memorize two, four or six items. A retro-cue during the subsequent delay period asked subjects to attend to just one of these items for a subsequent test. This was compared to trials where subjects were required to continue attending to all items for the subsequent test. Data show reduction of load-sensitive maintenance-related activity along the right intraparietal sulcus (IPS), directly linked to attentional orienting. While activity in the anterior IPS reflected the number of representations in the focus of attention, the activation pattern in the posterior IPS suggested residual activation related to unattended items. This dissociation is in line with a functional subdivision of the right IPS according to attentional and mnemonic properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Time course of superior temporal sulcus activity in response to eye gaze: a combined fMRI and MEG study

    Science.gov (United States)

    Kochiyama, Takanori; Uono, Shota; Yoshikawa, Sakiko

    2008-01-01

    The human superior temporal sulcus (STS) has been suggested to be involved in gaze processing, but temporal data regarding this issue are lacking. We investigated this topic by combining fMRI and MEG in four normal subjects. Photographs of faces with either averted or straight eye gazes were presented and subjects passively viewed the stimuli. First, we analyzed the brain areas involved using fMRI. A group analysis revealed activation of the STS for averted compared to straight gazes, which was confirmed in all subjects. We then measured brain activity using MEG, and conducted a 3D spatial filter analysis. The STS showed higher activity in response to averted versus straight gazes during the 150–200 ms period, peaking at around 170 ms, after stimulus onset. In contrast, the fusiform gyrus, which was detected by the main effect of stimulus presentations in fMRI analysis, exhibited comparable activity across straight and averted gazes at about 170 ms. These results indicate involvement of the human STS in rapid processing of the eye gaze of another individual. PMID:19015114

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Femtosecond cataract laser capsulotomy enabling optic capture and secondary sulcus iol insertion in an eye with traumatic aniridia and aphakia.

    Science.gov (United States)

    Grewal, Dilraj S; Basti, Surendra

    2014-06-01

    To describe a surgical technique and intraoperative modifications to create a secondary capsulotomy using the femtosecond cataract laser in an eye with traumatic aphakia and aniridia. The expanded use of the femtosecond cataract laser (Catalys Precision Laser System; Optimedica, Sunnyvale, CA) for creation of a well-centered and circular secondary capsulotomy in the capsular remnants of an eye with traumatic aphakia and aniridia. Using software modifications based on intraoperative anterior segment spectral-domain optical coherence tomography imaging, and customizing the capsulotomy settings, the femtosecond cataract laser was able to penetrate through most of the fused anterior and posterior capsular leaflets and a circular capsulotomy was achieved. The latter permitted optic capture and excellent centration of a three-piece intraocular lens placed in the sulcus with good postoperative visual rehabilitation. The femtosecond cataract laser can be customized to create a well-centered and circular secondary capsulotomy in aniridic and aphakic eyes where optic capture is critical for long-term intraocular lens stability. Copyright 2014, SLACK Incorporated.

  6. Combined single-cell quantitation of host and SIV genes and proteins ex vivo reveals host-pathogen interactions in individual cells.

    Science.gov (United States)

    Bolton, Diane L; McGinnis, Kathleen; Finak, Greg; Chattopadhyay, Pratip; Gottardo, Raphael; Roederer, Mario

    2017-06-01

    CD4 T cells harboring HIV-1/SIV represent a formidable hurdle to eradicating infection, and yet their detailed phenotype remains unknown. Here we integrate two single-cell technologies, flow cytometry and highly multiplexed quantitative RT-PCR, to characterize SIV-infected CD4 T cells directly ex vivo. Within individual cells, we correlate the cellular phenotype, in terms of host protein and RNA expression, with stages of the viral life cycle defined by combinatorial expression of viral RNAs. Spliced RNA+ infected cells display multiple memory and activation phenotypes, indicating virus production by diverse CD4 T cell subsets. In most (but not all) cells, progressive infection accompanies post-transcriptional downregulation of CD4 protein, while surface MHC class I is largely retained. Interferon-stimulated genes were also commonly upregulated. Thus, we demonstrate that combined quantitation of transcriptional and post-transcriptional regulation at the single-cell level informs in vivo mechanisms of viral replication and immune evasion.

  7. 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.

  8. Attenuation of pathogenic immune responses during infection with human and simian immunodeficiency virus (HIV/SIV by the tetracycline derivative minocycline.

    Directory of Open Access Journals (Sweden)

    Julia L Drewes

    Full Text Available 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.

  9. 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.

  10. TCR Affinity Associated with Functional Differences between Dominant and Subdominant SIV Epitope-Specific CD8+ T Cells in Mamu-A*01+ Rhesus Monkeys

    OpenAIRE

    Osuna, Christa E; Ana Maria Gonzalez; Hsun-Hsien Chang; Amy Shi Hung; Elizabeth Ehlinger; Kara Anasti; S Munir Alam; Letvin, Norman L.

    2014-01-01

    Many of the factors that contribute to CD8+ T cell immunodominance hierarchies during viral infection are known. However, the functional differences that exist between dominant and subdominant epitope-specific CD8+ T cells remain poorly understood. In this study, we characterized the phenotypic and functional differences between dominant and subdominant simian immunodeficiency virus (SIV) epitope-specific CD8+ T cells restricted by the major histocompatibility complex (MHC) class I allele Mam...

  11. 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

  12. Reactions of SIV species with organic compounds: formation mechanisms of organo-sulfur derivatives in atmospheric aerosols

    Science.gov (United States)

    Passananti, Monica; Shang, Jing; Dupart, Yoan; Perrier, Sébastien; George, Christian

    2015-04-01

    Secondary organic aerosol (SOA) have an important impact on climate, air quality and human health. However the chemical reactions involved in their formation and growth are not fully understood or well-constrained in climate models. It is well known that inorganic sulfur (mainly in oxidation states (+IV) and (+VI)) plays a key role in aerosol formation, for instance sulfuric acid is known to be a good nucleating gas. In addition, acid-catalyzed heterogeneous reactions of organic compounds has shown to produce new particles, with a clear enhancement in the presence of ozone (Iinuma 2013). Organosulfates have been detected in tropospheric particles and aqueous phases, which suggests they are products of secondary organic aerosol formation process (Tolocka 2012). Originally, the production of organosulfates was explained by the esterification reaction of alcohols, but this reaction in atmosphere is kinetically negligible. Other formation pathways have been suggested such as hydrolysis of peroxides and reaction of organic matter with sulfite and sulfate radical anions (SO3-, SO4-) (Nozière 2010), but it remains unclear if these can completely explain atmospheric organo-sulfur aerosol loading. To better understand the formation of organo-sulfur compounds, we started to investigate the reactivity of SIV species (SO2 and SO32-) with respect to specific functional groups (organic acids and double bonds) on atmospherically relevant carboxylic acids and alkenes. The experiments were carried out in the homogeneous aqueous phase and at the solid-gas interface. A custom built coated-wall flow tube reactor was developed to control relativity humidity, SO2 concentration, temperature and gas flow rate. Homogeneous and heterogeneous reaction kinetics were measured and resulting products were identified using liquid chromatography coupled with an orbitrap mass spectrometer (LC-HR-MS). The experiments were performed with and without the presence of ozone in order to evaluate any

  13. 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.

  14. 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.

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

    Science.gov (United States)

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

    2016-04-23

    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. 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. 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.

  16. Naturalistic fMRI Mapping Reveals Superior Temporal Sulcus as the Hub for the Distributed Brain Network for Social Perception

    Science.gov (United States)

    Lahnakoski, Juha M.; Glerean, Enrico; Salmi, Juha; Jääskeläinen, Iiro P.; Sams, Mikko; Hari, Riitta; Nummenmaa, Lauri

    2012-01-01

    Despite the abundant data on brain networks processing static social signals, such as pictures of faces, the neural systems supporting social perception in naturalistic conditions are still poorly understood. Here we delineated brain networks subserving social perception under naturalistic conditions in 19 healthy humans who watched, during 3-T functional magnetic resonance imaging (fMRI), a set of 137 short (approximately 16 s each, total 27 min) audiovisual movie clips depicting pre-selected social signals. Two independent raters estimated how well each clip represented eight social features (faces, human bodies, biological motion, goal-oriented actions, emotion, social interaction, pain, and speech) and six filler features (places, objects, rigid motion, people not in social interaction, non-goal-oriented action, and non-human sounds) lacking social content. These ratings were used as predictors in the fMRI analysis. The posterior superior temporal sulcus (STS) responded to all social features but not to any non-social features, and the anterior STS responded to all social features except bodies and biological motion. We also found four partially segregated, extended networks for processing of specific social signals: (1) a fronto-temporal network responding to multiple social categories, (2) a fronto-parietal network preferentially activated to bodies, motion, and pain, (3) a temporo-amygdalar network responding to faces, social interaction, and speech, and (4) a fronto-insular network responding to pain, emotions, social interactions, and speech. Our results highlight the role of the pSTS in processing multiple aspects of social information, as well as the feasibility and efficiency of fMRI mapping under conditions that resemble the complexity of real life. PMID:22905026

  17. Naturalistic fMRI mapping reveals superior temporal sulcus as the hub for the distributed brain network for social perception

    Directory of Open Access Journals (Sweden)

    Juha Marko Lahnakoski

    2012-08-01

    Full Text Available Despite the abundant data on brain networks processing static social signals, such as pictures of faces, the neural systems supporting social perception in naturalistic conditions are still poorly understood. Here we delineated brain networks subserving social perception under naturalistic conditions in 19 healthy humans who watched, during 3-tesla functional magnetic imaging (fMRI, a set of 137 short (~16 s each, total 27 min audiovisual movie clips depicting pre-selected social signals. Two independent raters estimated how well each clip represented eight social features (faces, human bodies, biological motion, goal-oriented actions, emotion, social interaction, pain, and speech and six filler features (places, objects, rigid motion, people not in social interaction, non-goal-oriented action and non-human sounds lacking social content. These ratings were used as predictors in the fMRI analysis. The posterior superior temporal sulcus (STS responded to all social features but not to any non-social features, and the anterior STS responded to all social features except bodies and biological motion. We also found four partially segregated, extended networks for processing of specific social signals: 1 a fronto-temporal network responding to multiple social categories, 2 a fronto-parietal network preferentially activated to bodies, motion and pain, 3 a temporo-amygdalar network responding to faces, social interaction and speech, and 4 a fronto-insular network responding to pain, emotions, social interactions, and speech. Our results highlight the role of the posterior STS in processing multiple aspects of social information, as well as the feasibility and efficiency of fMRI mapping under conditions that resemble the complexity of real life.

  18. Mirror observation of finger action enhances activity in anterior intraparietal sulcus: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Numata, Kenji; Murayama, Takashi; Takasugi, Jun; Monma, Masahiko; Oga, Masaru

    2013-01-01

    Mirror therapy can be used to promote recovery from paralysis in patients with post-stroke hemiplegia, There are a lot of reports that mirror-image observation of the unilateral moving hand enhanced the excitability of the primary motor area (M1) ipsilateral to the moving hand in healthy subjects. but the neural mechanisms underlying its therapeutic effects are currently unclear. To investigate this issue, we used functional magnetic resonance imaging to measure activity in brain regions related to visual information processing during mirror image movement observation. Thirteen healthy subjects performed a finger-thumb opposition task with the left and right hands separately, with or without access to mirror observation. In the mirror condition, one hand was reflected in a mirror placed above the abdomen in the MRI scanner. In the masked mirror condition, subjects performed the same task but with the mirror obscured. In both conditions, the other hand was held at rest behind the mirror. A between-task comparison (mirror versus masked mirror) revealed significant activation in the ipsilateral hemisphere in the anterior intraparietal sulcus (aIP) while performing all tasks, regardless of which hand was used. The right aIP was significantly activated while moving the right hand. In contrast, in the left aIP, a small number of voxels showed a tendency toward activation during both left and right hand movement. The enhancement of ipsilateral aIP activity by the mirror image observation of finger action suggests that bimodal aIP neurons can be activated by visual information. We propose that activation in the M1 ipsilateral to the moving hand can be induced by information passing through the ventral premotor area from the aIP.

  19. Convergent BOLD and Beta-Band Activity in Superior Temporal Sulcus and Frontolimbic Circuitry Underpins Human Emotion Cognition

    Science.gov (United States)

    Jabbi, Mbemba; Kohn, Philip D.; Nash, Tiffany; Ianni, Angela; Coutlee, Christopher; Holroyd, Tom; Carver, Frederick W.; Chen, Qiang; Cropp, Brett; Kippenhan, J. Shane; Robinson, Stephen E.; Coppola, Richard; Berman, Karen F.

    2015-01-01

    The processing of social information in the human brain is widely distributed neuroanatomically and finely orchestrated over time. However, a detailed account of the spatiotemporal organization of these key neural underpinnings of human social cognition remains to be elucidated. Here, we applied functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in the same participants to investigate spatial and temporal neural patterns evoked by viewing videos of facial muscle configurations. We show that observing the emergence of expressions elicits sustained blood oxygenation level–dependent responses in the superior temporal sulcus (STS), a region implicated in processing meaningful biological motion. We also found corresponding event-related changes in sustained MEG beta-band (14–30 Hz) oscillatory activity in the STS, consistent with the possible role of beta-band activity in visual perception. Dynamically evolving fearful and happy expressions elicited early (0–400 ms) transient beta-band activity in sensorimotor cortex that persisted beyond 400 ms, at which time it became accompanied by a frontolimbic spread (400–1000 ms). In addition, individual differences in sustained STS beta-band activity correlated with speed of emotion recognition, substantiating the behavioral relevance of these signals. This STS beta-band activity showed valence-specific coupling with the time courses of facial movements as they emerged into full-blown fearful and happy expressions (negative and positive coupling, respectively). These data offer new insights into the perceptual relevance and orchestrated function of the STS and interconnected pathways in social–emotion cognition. PMID:24464944

  20. Convergent BOLD and Beta-Band Activity in Superior Temporal Sulcus and Frontolimbic Circuitry Underpins Human Emotion Cognition.

    Science.gov (United States)

    Jabbi, Mbemba; Kohn, Philip D; Nash, Tiffany; Ianni, Angela; Coutlee, Christopher; Holroyd, Tom; Carver, Frederick W; Chen, Qiang; Cropp, Brett; Kippenhan, J Shane; Robinson, Stephen E; Coppola, Richard; Berman, Karen F

    2015-07-01

    The processing of social information in the human brain is widely distributed neuroanatomically and finely orchestrated over time. However, a detailed account of the spatiotemporal organization of these key neural underpinnings of human social cognition remains to be elucidated. Here, we applied functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in the same participants to investigate spatial and temporal neural patterns evoked by viewing videos of facial muscle configurations. We show that observing the emergence of expressions elicits sustained blood oxygenation level-dependent responses in the superior temporal sulcus (STS), a region implicated in processing meaningful biological motion. We also found corresponding event-related changes in sustained MEG beta-band (14-30 Hz) oscillatory activity in the STS, consistent with the possible role of beta-band activity in visual perception. Dynamically evolving fearful and happy expressions elicited early (0-400 ms) transient beta-band activity in sensorimotor cortex that persisted beyond 400 ms, at which time it became accompanied by a frontolimbic spread (400-1000 ms). In addition, individual differences in sustained STS beta-band activity correlated with speed of emotion recognition, substantiating the behavioral relevance of these signals. This STS beta-band activity showed valence-specific coupling with the time courses of facial movements as they emerged into full-blown fearful and happy expressions (negative and positive coupling, respectively). These data offer new insights into the perceptual relevance and orchestrated function of the STS and interconnected pathways in social-emotion cognition. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Responses in the right posterior superior temporal sulcus show a feature-based response to facial expression.

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    Flack, Tessa R; Andrews, Timothy J; Hymers, Mark; Al-Mosaiwi, Mohammed; Marsden, Samuel P; Strachan, James W A; Trakulpipat, Chayanit; Wang, Liang; Wu, Tian; Young, Andrew W

    2015-08-01

    The face-selective region of the right posterior superior temporal sulcus (pSTS) plays an important role in analysing facial expressions. However, it is less clear how facial expressions are represented in this region. In this study, we used the face composite effect to explore whether the pSTS contains a holistic or feature-based representation of facial expression. Aligned and misaligned composite images were created from the top and bottom halves of faces posing different expressions. In Experiment 1, participants performed a behavioural matching task in which they judged whether the top half of two images was the same or different. The ability to discriminate the top half of the face was affected by changes in the bottom half of the face when the images were aligned, but not when they were misaligned. This shows a holistic behavioural response to expression. In Experiment 2, we used fMR-adaptation to ask whether the pSTS has a corresponding holistic neural representation of expression. Aligned or misaligned images were presented in blocks that involved repeating the same image or in which the top or bottom half of the images changed. Increased neural responses were found in the right pSTS regardless of whether the change occurred in the top or bottom of the image, showing that changes in expression were detected across all parts of the face. However, in contrast to the behavioural data, the pattern did not differ between aligned and misaligned stimuli. This suggests that the pSTS does not encode facial expressions holistically. In contrast to the pSTS, a holistic pattern of response to facial expression was found in the right inferior frontal gyrus (IFG). Together, these results suggest that pSTS reflects an early stage in the processing of facial expression in which facial features are represented independently. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Facial expression recognition takes longer in the posterior superior temporal sulcus than in the occipital face area.

    Science.gov (United States)

    Pitcher, David

    2014-07-02

    Neuroimaging studies have identified a face-selective region in the right posterior superior temporal sulcus (rpSTS) that responds more strongly during facial expression recognition tasks than during facial identity recognition tasks, but precisely when the rpSTS begins to causally contribute to expression recognition is unclear. The present study addressed this issue using transcranial magnetic stimulation (TMS). In Experiment 1, repetitive TMS delivered over the rpSTS of human participants, at a frequency of 10 Hz for 500 ms, selectively impaired a facial expression task but had no effect on a matched facial identity task. In Experiment 2, participants performed the expression task only while double-pulse TMS (dTMS) was delivered over the rpSTS or over the right occipital face area (rOFA), a face-selective region in lateral occipital cortex, at different latencies up to 210 ms after stimulus onset. Task performance was selectively impaired when dTMS was delivered over the rpSTS at 60-100 ms and 100-140 ms. dTMS delivered over the rOFA impaired task performance at 60-100 ms only. These results demonstrate that the rpSTS causally contributes to expression recognition and that it does so over a longer time-scale than the rOFA. This difference in the length of the TMS induced impairment between the rpSTS and the rOFA suggests that the neural computations that contribute to facial expression recognition in each region are functionally distinct. Copyright © 2014 the authors 0270-6474/14/349173-05$15.00/0.

  3. Incidence of deepening of upper eyelid sulcus after topical use of tafluprost ophthalmic solution in Japanese patients

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    Maruyama K

    2013-07-01

    Full Text Available Katsuhiko Maruyama,1 Asako Tsuchisaka,1 Jumpei Sakamoto,1 Shiroaki Shirato,2 Hiroshi Goto11Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan; 2Yotsuya Shirato Eye Clinic, Tokyo, JapanPurpose: To investigate the incidence of deepening of upper eyelid sulcus (DUES with topical use of tafluprost in Japanese glaucoma patients.Methods: This study was a prospective, open-label, non-controlled case series conducted at a single center. Thirty-six primary open-angle glaucoma Japanese patients who had no history of surgery were enrolled. The patients were prescribed 0.0015% topical tafluprost once daily to one eye that had the more severe visual field disorder, and observed during outpatient visits before and at 30, 60, and 90 days after starting treatment. At every visit, three examiners judged the presence of DUES unanimously by facial photographs including eyebrows and lower eyelids. The primary outcome variable was the incidence of DUES at the end of day 90 in the study as assessed by observer-masked facial photography. The patients were also asked if they noticed any subjective symptom of DUES. Gender, refraction, and intraocular pressure were evaluated as potential risk factors.Results: Thirty-two patients completed this clinical trial. DUES were identified objectively in 19% (6/32 of the patients after 90 days of treatment. The incidence was not related to gender, refraction, baseline or post-treatment intraocular pressure, or intraocular pressure reduction. Finally, 17% (1/6 of patients with objectively diagnosed DUES noticed the presence of DUES by themselves. No patient dropped out of the study because of DUES.Conclusion: Similar to other prostaglandin analogs, topical use of tafluprost ophthalmic solution is associated with DUES as a local adverse reaction.Keywords: prostaglandins, tafluprost, eyelid, deepening, side effect

  4. Mapping the macaque superior temporal sulcus: functional delineation of vergence and version eye-movement-related activity.

    Science.gov (United States)

    Ward, Matthew K; Bolding, Mark S; Schultz, Kevin P; Gamlin, Paul D

    2015-05-13

    It is currently thought that the primate oculomotor system has evolved distinct but interrelated subsystems to generate different types of visually guided eye movements (e.g., saccades/smooth pursuit/vergence). Although progress has been made in elucidating the neural basis of these movement types, no study to date has investigated all three movement types on a large scale and within the same animals. Here, we used fMRI in rhesus macaque monkeys to map the superior temporal sulcus (STS) for BOLD modulation associated with visually guided eye movements. Further, we ascertained whether modulation in a given area was movement type specific and, if not, the modulation each movement type elicited relative to the others (i.e., dominance). Our results show that multiple areas within STS modulate during all movement types studied, including the middle temporal, medial superior temporal, fundus of the superior temporal, lower superior temporal, and dorsal posterior inferotemporal areas. Our results also reveal an area in dorsomedial STS that is modulated almost exclusively by vergence movements. In contrast, we found that ventrolateral STS is driven preferentially during versional movements. These results illuminate an STS network involved in processes associated with multiple eye movement types, illustrate unique patterns of modulation within said network as a function of movement type, and provide evidence for a vergence-specific area within dorsomedial STS. We conclude that producing categorically different eye movement types requires access to a common STS network and that individual network nodes are recruited differentially based upon the type of movement generated. Copyright © 2015 the authors 0270-6474/15/357428-15$15.00/0.

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

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    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.

  6. Naturalistic FMRI mapping reveals superior temporal sulcus as the hub for the distributed brain network for social perception.

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    Lahnakoski, Juha M; Glerean, Enrico; Salmi, Juha; Jääskeläinen, Iiro P; Sams, Mikko; Hari, Riitta; Nummenmaa, Lauri

    2012-01-01

    Despite the abundant data on brain networks processing static social signals, such as pictures of faces, the neural systems supporting social perception in naturalistic conditions are still poorly understood. Here we delineated brain networks subserving social perception under naturalistic conditions in 19 healthy humans who watched, during 3-T functional magnetic resonance imaging (fMRI), a set of 137 short (approximately 16 s each, total 27 min) audiovisual movie clips depicting pre-selected social signals. Two independent raters estimated how well each clip represented eight social features (faces, human bodies, biological motion, goal-oriented actions, emotion, social interaction, pain, and speech) and six filler features (places, objects, rigid motion, people not in social interaction, non-goal-oriented action, and non-human sounds) lacking social content. These ratings were used as predictors in the fMRI analysis. The posterior superior temporal sulcus (STS) responded to all social features but not to any non-social features, and the anterior STS responded to all social features except bodies and biological motion. We also found four partially segregated, extended networks for processing of specific social signals: (1) a fronto-temporal network responding to multiple social categories, (2) a fronto-parietal network preferentially activated to bodies, motion, and pain, (3) a temporo-amygdalar network responding to faces, social interaction, and speech, and (4) a fronto-insular network responding to pain, emotions, social interactions, and speech. Our results highlight the role of the pSTS in processing multiple aspects of social information, as well as the feasibility and efficiency of fMRI mapping under conditions that resemble the complexity of real life.

  7. Mirror Observation of Finger Action Enhances Activity in Anterior Intraparietal Sulcus: A Functional Magnetic Resonance Imaging Study

    Science.gov (United States)

    Murayama, Takashi; Takasugi, Jun; Monma, Masahiko; Oga, Masaru

    2013-01-01

    Mirror therapy can be used to promote recovery from paralysis in patients with post-stroke hemiplegia, There are a lot of reports that mirror-image observation of the unilateral moving hand enhanced the excitability of the primary motor area (M1) ipsilateral to the moving hand in healthy subjects. but the neural mechanisms underlying its therapeutic effects are currently unclear. To investigate this issue, we used functional magnetic resonance imaging to measure activity in brain regions related to visual information processing during mirror image movement observation. Thirteen healthy subjects performed a finger-thumb opposition task with the left and right hands separately, with or without access to mirror observation. In the mirror condition, one hand was reflected in a mirror placed above the abdomen in the MRI scanner. In the masked mirror condition, subjects performed the same task but with the mirror obscured. In both conditions, the other hand was held at rest behind the mirror. A between-task comparison (mirror versus masked mirror) revealed significant activation in the ipsilateral hemisphere in the anterior intraparietal sulcus (aIP) while performing all tasks, regardless of which hand was used. The right aIP was significantly activated while moving the right hand. In contrast, in the left aIP, a small number of voxels showed a tendency toward activation during both left and right hand movement. The enhancement of ipsilateral aIP activity by the mirror image observation of finger action suggests that bimodal aIP neurons can be activated by visual information. We propose that activation in the M1 ipsilateral to the moving hand can be induced by information passing through the ventral premotor area from the aIP. PMID:25792898

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

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    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.

  9. An evaluation on the activity level of Aspartate aminotransferase and Alkaline phosphatase nzymes in peri-implant sulcus fluid

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    Paknegad M. Assistant Professor

    2003-07-01

    Full Text Available Statement of Problem: The correlation between the activity of aspartate aminotransferase (AST and alkaline phosphatase (ALP enzymes in gingival sulcular fluid (GCF with inflammation and periodontal attachment loss has been proved, however there are not adequate studies about dental implants. Purpose: The aim of present study was to investigate the presence and activity level of AST & ALP and their correlation with pocket depth (PD and bleeding of peri-implant slcular fluid (PISF, and to evaluate the possibility of using these assessments as a diagnostic index in oral implantology. Material and Methods: In this study, 41 implants as test group and 41 contralateral teeth as control group, in 21 patients were evaluated. At first visit, the general information about implants and the values of pocket probing depth (PPD, modified sulcus bleeding index (mSBl and modified plaque index (mPI were recorded. At the second visit, samples of GCF/PISF were collected. AST & ALP activity was determined spectrophotometrically and data were analyzed by "t", "Mann-Whitney" tests and Pearson Spearman correlation coefficient."nResults: The results showed that there was a significant difference in the activity of AST between two study groups (P<0.0001. The average activity of ALP in test group was more than control group but the difference was not significant. After elimination of the confounding variables, the average AST in test group was 54.6 (S£=2.3 and in control groups was 44.8 (SE=2.3 (P=0.004. The average ALP in test group (SE=2.2 and in control (SE=2.2 were 36.6 and 35.4, respectively. Values of AST and ALP were positively correlated with other clinical parameters such as PD and mSBI which was significant in test group."nConclusion: The present study suggests that PISF analysis could be considered as a proper diagnostic strategy in the evaluation of dental implant success.

  10. 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.

  11. Early biodistribution and persistence of a protective live attenuated SIV vaccine elicits localised innate responses in multiple lymphoid tissues.

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    Deborah Ferguson

    Full Text Available Vaccination of Mauritian cynomolgus macaques with the attenuated nef-truncated C8 variant of SIVmac251/32H (SIVmacC8 induces early, potent protection against pathogenic, heterologous challenge before the maturation of cognate immunity. To identify processes that contribute to early protection in this model the pathogenesis, anatomical distribution and viral vaccine kinetics were determined in relation to localised innate responses triggered by vaccination. The early biodistribution of SIVmacC8 was defined by rapid, widespread dissemination amongst multiple lymphoid tissues, detectable after 3 days. Cell-associated viral RNA dynamics identified mesenteric lymph nodes (MLN and spleen, as well as the gut mucosae, as early major contributors of systemic virus burden. Rapid, localised infection was populated by discrete foci of persisting virus-infected cells. Localised productive infection triggered a broad innate response, with type-1 interferon sensitive IRF-7, STAT-1, TRIM5α and ApoBEC3G genes all upregulated during the acute phase but induction did not prevent viral persistence. Profound changes in vaccine-induced cell-surface markers of immune activation were detected on macrophages, B-cells and dendritic cells (DC-SIGN, S-100, CD40, CD11c, CD123 and CD86. Notably, high DC-SIGN and S100 staining for follicular and interdigitating DCs respectively, in MLN and spleen were detected by 3 days, persisting 20 weeks post-vaccination. Although not formally evaluated, the early biodistribution of SIVmacC8 simultaneously targets multiple lymphoid tissues to induce strong innate immune responses coincident at the same sites critical for early protection from wild-type viruses. HIV vaccines which stimulate appropriate innate, as well as adaptive responses, akin to those generated by live attenuated SIV vaccines, may prove the most efficacious.

  12. Innate anti-viral immunity is associated with the protection elicited by the simian immunodeficiency virus (SIV) live attenuated virus vaccine in cynomolgus monkeys.

    Science.gov (United States)

    Goletti, Delia; Macchia, Iole; Leone, Pasqualina; Pace, Monica; Sernicola, Leonardo; Pavone-Cossut, Maria Rosaria; Maggiorella, Maria Teresa; Cafaro, Aurelio; Ensoli, Barbara; Titti, Fausto

    2006-10-01

    The Delta-nef live attenuated virus vaccine approach offered in the SIV-macaque model the opportunity to identify humoral and cell-mediated immune responses associated with protection against viral infections. In addition, soluble factors different from those related to specific immune responses appear to correlate with the establishment and maintenance of the protective status. Investigated were: 1) the ability of CD8+ T cells from cynomolgus monkeys vaccinated with SIV Delta-nef and long-term protected against sequential SIVs and SHIV challenges to inhibit in vitro SHIV replication in an acute infection cell system, 2) the ability of cell-free supernatants from CD8+ T cell cultures to inhibit replication of HIV in chronically infected cells, and 3) whether the antiviral activity of CD8+ T cells correlated with IFNgamma production. Soluble factor(s) secreted by CD8+ T cells from Delta-nef vaccinated monkeys significantly inhibited SHIV replication in an autologous cell system. This effect was not dependent on beta-chemokine secretion and correlated with an increased IFNgamma production. In addition, since supernatants from CD8+ T cells inhibited HIV production in chronically infected monocytic cells, the suppressive activity was not related to the viral strain. Vaccination with the live attenuated virus induces both a CD8+ T cell-dependent antiviral activity and IFNgamma responses potentially responsible for the protection from challenge with heterologous highly pathogenic SHIV89.6P. It is conceivable that boosting the "natural" along with the antigen-specific immunity is a desirable outcome to improve the protective efficacy of any vaccine approach.

  13. An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity.

    Science.gov (United States)

    Zapata, Juan C; Poonia, Bhawna; Bryant, Joseph; Davis, Harry; Ateh, Eugene; George, Lanea; Crasta, Oswald; Zhang, Yan; Slezak, Tom; Jaing, Crystal; Pauza, C David; Goicochea, Marco; Moshkoff, Dmitry; Lukashevich, Igor S; Salvato, Maria S

    2013-02-12

    Lassa hemorrhagic fever (LHF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs pathognomonic for arenavirus disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LHF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of HIV infection. SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for specific humoral and cellular immune responses, as well as for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, respiratory distress, malaise, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs, derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections, included increased expression of interferon-stimulated genes (ISG) and decreased expression of COX2, IL-1β, coagulation intermediates and nuclear receptors needed for stress signaling. All vaccinated monkeys showed ML29-specific antibody responses and ML29-specific cell-mediated immunity. SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and none developed chronic arenavirus infection. Importantly, none of the macaques developed signs, classical or non-classical, of arenavirus disease.

  14. The secretion of IL-22 from mucosal NKp44⁺ NK cells is associated with microbial translocation and virus infection in SIV/SHIV-infected Chinese macaques.

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    Wang, Wei; Wu, Fangxin; Cong, Zhe; Liu, Kejian; Qin, Chuan; Wei, Qiang

    2014-01-01

    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.

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

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    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.

  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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    Ploquin, Mickaël J.; Casrouge, Armanda; Huot, Nicolas; Passaes, Caroline; Lécuroux, Camille; Essat, Asma; Boufassa, Faroudy; Jacquelin, Béatrice; Jochems, Simon P.; Petitjean, Gaël; Angin, Mathieu; Gärtner, Kathleen; Garcia-Tellez, Thalía; Booiman, Thijs; Boeser-Nunnink, Brigitte D.; Roques, Pierre; Saez-Cirion, Asier; Vaslin, Bruno; Dereudre-Bosquet, Nathalie; Barré-Sinoussi, Françoise; Ghislain, Mathilde; Rouzioux, Christine; Lambotte, Olivier; Albert, Matthew L.; Goujard, Cécile; Kootstra, Neeltje; Meyer, Laurence; Müller-Trutwin, Michaela C.

    2016-01-01

    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. PMID:27509048

  17. 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.

  18. 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

  19. 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.

  20. 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

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

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    Takeshi Uno

    Full Text Available 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.

  2. 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

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    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.

  3. A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults

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    Ludwig, K U; Sämann, P; Alexander, M; Becker, J; Bruder, J; Moll, K; Spieler, D; Czisch, M; Warnke, A; Docherty, S J; Davis, O S P; Plomin, R; Nöthen, M M; Landerl, K; Müller-Myhsok, B; Hoffmann, P; Schumacher, J; Schulte-Körne, G; Czamara, D

    2013-01-01

    The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities (Pcomb=7.71 × 10−10, n=699), with an effect size of 4.87%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype. PMID:23423138

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

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    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

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

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    Pinkevych, Mykola; Reynaldi, Arnold; Reid, Carolyn; Newman, Laura; Lipkey, Leslie; Bosche, William J.; Ott, David E.; Estes, Jacob D.; Del Prete, Gregory Q.; Lifson, Jeffrey D.; Davenport, Miles P.; Keele, Brandon F.

    2017-01-01

    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 viremia. The

  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. Functional reorganization in the patient with progressing glioma of the pure primary motor cortex: a case report with special reference to the topographic central sulcus defined by somatosensory-evoked potential.

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    Hayashi, Yutaka; Nakada, Mitsutoshi; Kinoshita, Masashi; Hamada, Jun-ichiro

    2014-01-01

    The concept of human brain reorganization due to slow-growing lesions, including low-grade glioma, has been gradually and generally accepted. However, few cases have been reported in which the reorganization, especially in the topographic pure primary motor cortex, was observed during brain surgery. We report a case of slow-growing oligodendroglioma located in the pure primary motor cortex, as detected by magnetic resonance imaging that could be resected in part thanks to the brain plasticity. In addition, we describe a pitfall of topographic guidance using somatosensory-evoked potential (SEP) monitoring. A 36-year-old right-handed patient underwent resection of a gradually growing oligodendroglioma located in the right primary motor cortex, with no other adjacent lesions, 8 years after the initial biopsy. The central sulcus was defined with intraoperative SEP monitoring in both operations. Based on the findings of the intraoperative direct electrical stimulation under awake craniotomy, we suspect that motor function shifted posteriorly and reorganized beyond the central sulcus. Pure primary motor cortex could be reorganized by its own lesion. In reorganized brain, topographic central sulcus defined based on SEP findings may be an inappropriate guidance to estimate true functional area. In such a condition, intraoperative direct electrical stimulation under awake craniotomy makes it feasible to resect pure primary motor cortex invaded by tumors. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Behavioral, metabolic, and immune consequences of chronic alcohol or cannabinoids on HIV/AIDs: Studies in the Non-Human Primate SIV model

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    Molina, Patricia E.; Amedee, Angela M.; Winsauer, Peter; Nelson, Steve; Bagby, Gregory; Simon, Liz

    2015-01-01

    HIV-associated mortality has been significantly reduced with antiretroviral therapy (ART), and HIV infection has become a chronic disease that frequently coexists with many disorders, including substance abuse (Azar et al. 2010; Phillips et al. 2001). Alcohol and drugs of abuse may modify host-pathogen interactions at various levels including behavioral, metabolic, and immune consequences of HIV infection, as well as the ability of the virus to integrate into the genome and replicate in host cells. Identifying mechanisms responsible for these interactions is complicated by many factors, such as the tissue specific responses to viral infection, multiple cellular mechanisms involved in inflammatory responses, neuroendocrine and localized responses to infection, and kinetics of viral replication. An integrated physiological analysis of the biomedical consequences of chronic alcohol and drug use or abuse on disease progression is possible using rhesus macaques infected with simian immunodeficiency virus (SIV), a relevant model of HIV infection. This review will provide an overview of the data gathered using this model to show that chronic administration of two of the most commonly abused substances, alcohol and cannabinoids (Δ9-Tetrahydrocannabinol; THC), affect host-pathogen interactions. PMID:25795088

  9. Activation of the blood-brain barrier by SIV (simian immunodeficiency virus) requires cell-associated virus and is not restricted to endothelial cell activation.

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    MacLean, A G; Rasmussen, T A; Bieniemy, D; Lackner, A A

    2004-11-01

    The primary cell infected during acute HIV neuropathogenesis is the monocyte-derived macrophage. We have demonstrated that there is activation of the BBB (blood-brain barrier) during acute viral infection and at terminal AIDS. However, it has never been determined if there is a requirement for the virus to be carried through the BBB or how these Trojan horses would be induced to cross the BBB. We added SIVmac251-infected (SIV is simian immunodeficiency virus) mononuclear cells (and their supernatants) to the luminal or abluminal compartment of our BBB model. There was activation of both sides of the BBB model, only if viral-infected cells were added to the luminal compartment, as opposed to the addition of cell-free supernatants. This suggests that cell-associated virus is essential for the activation of the BBB. This, in turn, would be expected to lead to further infiltration of cells capable of viral infection. VCAM-1 (vascular cell adhesion molecule 1) staining revealed, for the first time, that there is an absolute requirement for virally infected cells, and not just the presence of virus for the activation of the BBB.

  10. A New Method for Rapid Screening of End-Point PCR Products: Application to Single Genome Amplified HIV and SIV Envelope Amplicons.

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    Laurent Houzet

    Full Text Available PCR is the most widely applied technique for large scale screening of bacterial clones, mouse genotypes, virus genomes etc. A drawback of large PCR screening is that amplicon analysis is usually performed using gel electrophoresis, a step that is very labor intensive, tedious and chemical waste generating. Single genome amplification (SGA is used to characterize the diversity and evolutionary dynamics of virus populations within infected hosts. SGA is based on the isolation of single template molecule using limiting dilution followed by nested PCR amplification and requires the analysis of hundreds of reactions per sample, making large scale SGA studies very challenging. Here we present a novel approach entitled Long Amplicon Melt Profiling (LAMP based on the analysis of the melting profile of the PCR reactions using SYBR Green and/or EvaGreen fluorescent dyes. The LAMP method represents an attractive alternative to gel electrophoresis and enables the quick discrimination of positive reactions. We validate LAMP for SIV and HIV env-SGA, in 96- and 384-well plate formats. Because the melt profiling allows the screening of several thousands of PCR reactions in a cost-effective, rapid and robust way, we believe it will greatly facilitate any large scale PCR screening.

  11. Detection of herpes simplex virus type 1 in gingival crevicular fluid of gingival sulcus/periodontal pocket using polymerase chain reaction

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    Matić-Petrović Sanja

    2014-01-01

    Full Text Available Introduction. Pathogenesis and some characteristics of periodontitis cannot be fully explained by bacterial etiology alone. Herpes viruses may bridge the gap between clinical characteristics and molecular understanding of periodontal destruction. Objective. The aim of this study was to investigate the prevalence of herpes simplex virus type 1 (HSV-1 in gingival crevicular fluid (GCF of healthy and damaged periodontium in Serbian population and to explore potential correlation between the presence of this virus and the level of periodontal destruction. Methods. Samples were collected from gingival sulcus/periodontal pockets by sterile paper points and the presence of viral DNA in gingival crevicular fluid was assessed by PCR. Results. There was no statistically significant difference in HSV-1 in presence between periodontitis patients (PG=38.9% and healthy controls (HC=32.3%, (Chi-square test, with Yates’ correction p=0.7574. However, HSV-1 positive patients showed significantly higher values of parameters of periodontal destruction (PPD=7.11±2.52, CAL=5.46±2.34 than periodontitis patients without HSV-1 in gingival crevicular fluid (PPD=4.70±1.79, CAL=3.39±2.65 (p values respectively, p=0.002 and p=0.023, Independent Samples T-Test. HSV-1 occurred more often in deeper (PPD≥6 mm (69.2% than in shallow pockets (3 mm

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

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    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.

  13. 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.

  14. The high stability of the triple helices formed between short purine oligonucleotides and SIV/HIV-2 vpx genes is determined by the targeted DNA structure.

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    Svinarchuk, F; Monnot, M; Merle, A; Malvy, C; Fermandjian, S

    1995-10-11

    In our previous works we have shown that the oligonucleotides 5'-GGGGAGGGGGAGG-3' and 5'-GGAGGGGGAGGGG-3' give very stable and specific triplexes with their target double stranded DNAs [Svinarchuk, F., Bertrand, J.-R. and Malvy, C. (1994) Nucleic Acids Res., 22, 3742-3747; Svinarchuk, F., Paoletti, J. and Malvy, C. (1995) J. Biol. Chem., 270, 14 068-14,071]. The target for the invariable part of these oligonucleotides, 5'-GGAGGGGGAGG-3', is found in a highly conserved 20 bp long purine/pyrimidine tract of the vpx gene of the SIV and HIV-2 viruses and could be a target for oligonucleotide directed antivirus therapy. Here were report on the ability of four purine oligonucleotides with different lengths (11-, 14-, 17- and 20-mer) to form triplexes with the purine/pyrimidine stretch of the vpx gene. Triplex formation was tested by joint dimethyl sulfate (DMS) footprint, gel-retardation assay, circular dichroism (CD) and UV-melting studies. Dimethyl sulfate footprint studies revealed the antiparallel orientation of the third strand to the purine strand of the Watson-Crick duplex. However, the protection of the guanines at the ends of the target sequence decreased as the length of the third strand oligonucleotide increased. Melting temperature studies provided profiles with only one transition for all of the triplexes. The melting temperatures of the triplexes were found to be the same as for the targeted duplex in the case of the 11- and 14-mer third strands while for the 17- and 20-mer third strands the melting temperature of the triplexes were correspondingly 4 and 8 degrees C higher than for the duplex. Heating and cooling melting curves were reversible for all of the tested triplexes except one with the 20-mer third strand oligonucleotide. Circular dichroism spectra showed the ability of the target DNA to adopt an A-like DNA conformation. Upon triplex formation the A-DNA form becomes even more pronounced. This effect depends on the length of the third strand

  15. 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.

  16. Activation of left intraparietal sulcus using a fMRI conceptual praxis paradigm Ativação do sulco intraparietal esquerdo utilizando RMf e um paradigma de praxis conceitual

    Directory of Open Access Journals (Sweden)

    JORGE MOLL

    1998-12-01

    Full Text Available The present paper reports the results of a fMRI subtraction study of the pattern of cortical activation induced by an ideational praxis paradigm in six normal right-handed subjects. The control task consisted of a sequence of complex meaningless hand movements. A complete study was done for each hand in each subject. The left intraparietal sulcus was the only structure activated in all subjects regardless of the hand used in the task. These findings, albeit preliminary, suggest that the organization of actions involving the mediation of tools and utensils are strongly lateralized to the left hemisphere and that damage to the dominant intraparietal sulcus may be critical for the development of the clinical syndrome of conceptual apraxia.No presente artigo, reportamos os resultados de RMf da ativação cortical induzida por um paradigma de praxis de uso de ferramentas em seis pessoas dextras normais. A tarefa-controle consistiu de uma sequência de movimentos unimanuais complexos, mas desprovidos de significado. Um estudo completo de pantomima e controle foi feito para cada mão. O sulco intraparietal esquerdo foi a única estrutura ativada em todos os indivíduos, independentemente da mão utilizada. Esses achados, embora preliminares, indicam que a organização de ações mediadas por ferramentas e utensílios são fortemente lateralizadas para o hemisfério esquerdo nas pessoas normais, e sugerem que lesões na região do sulco intraparietal do hemisfério dominante são críticas para o aparecimento de apraxia conceitual.

  17. DNA/Ad5 vaccination with SIV epitopes induced epitope-specific CD4⁺ T cells, but few subdominant epitope-specific CD8⁺ T cells.

    Science.gov (United States)

    Vojnov, Lara; Bean, Alexander T; Peterson, Eric J; Chiuchiolo, Maria J; Sacha, Jonah B; Denes, Ferencz S; Sandor, Matyas; Fuller, Deborah H; Fuller, James T; Parks, Christopher L; McDermott, Adrian B; Wilson, Nancy A; Watkins, David I

    2011-10-06

    The goals of a T cell-based vaccine for HIV are to reduce viral peak and setpoint and prevent transmission. While it has been relatively straightforward to induce CD8(+) T cell responses against immunodominant T cell epitopes, it has been more difficult to broaden the vaccine-induced CD8(+) T cell response against subdominant T cell epitopes. Additionally, vaccine regimens to induce CD4(+) T cell responses have been studied only in limited settings. In this study, we sought to elicit CD8(+) T cells against subdominant epitopes and CD4(+) T cells using various novel and well-established vaccine strategies. We vaccinated three Mamu-A*01(+) animals with five Mamu-A*01-restricted subdominant SIV-specific CD8(+) T cell epitopes. All three vaccinated animals made high frequency responses against the Mamu-A*01-restricted Env TL9 epitope with one animal making a low frequency CD8(+) T cell response against the Pol LV10 epitope. We also induced SIV-specific CD4(+) T cells against several MHC class II DRBw*606-restricted epitopes. Electroporated DNA with pIL-12 followed by a rAd5 boost was the most immunogenic vaccine strategy. We induced responses against all three Mamu-DRB*w606-restricted CD4 epitopes in the vaccine after the DNA prime. Ad5 vaccination further boosted these responses. Although we successfully elicited several robust epitope-specific CD4(+) T cell responses, vaccination with subdominant MHC class I epitopes elicited few detectable CD8(+) T cell responses. Broadening the CD8(+) T cell response against subdominant MHC class I epitopes was, therefore, more difficult than we initially anticipated. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Visual Field Map Clusters in High-Order Visual Processing: Organization of V3A/V3B and a New Cloverleaf Cluster in the Posterior Superior Temporal Sulcus.

    Science.gov (United States)

    Barton, Brian; Brewer, Alyssa A

    2017-01-01

    The cortical hierarchy of the human visual system has been shown to be organized around retinal spatial coordinates throughout much of low- and mid-level visual processing. These regions contain visual field maps (VFMs) that each follows the organization of the retina, with neighboring aspects of the visual field processed in neighboring cortical locations. On a larger, macrostructural scale, groups of such sensory cortical field maps (CFMs) in both the visual and auditory systems are organized into roughly circular cloverleaf clusters. CFMs within clusters tend to share properties such as receptive field distribution, cortical magnification, and processing specialization. Here we use fMRI and population receptive field (pRF) modeling to investigate the extent of VFM and cluster organization with an examination of higher-level visual processing in temporal cortex and compare these measurements to mid-level visual processing in dorsal occipital cortex. In human temporal cortex, the posterior superior temporal sulcus (pSTS) has been implicated in various neuroimaging studies as subserving higher-order vision, including face processing, biological motion perception, and multimodal audiovisual integration. In human dorsal occipital cortex, the transverse occipital sulcus (TOS) contains the V3A/B cluster, which comprises two VFMs subserving mid-level motion perception and visuospatial attention. For the first time, we present the organization of VFMs in pSTS in a cloverleaf cluster. This pSTS cluster contains four VFMs bilaterally: pSTS-1:4. We characterize these pSTS VFMs as relatively small at ∼125 mm2 with relatively large pRF sizes of ∼2-8° of visual angle across the central 10° of the visual field. V3A and V3B are ∼230 mm2 in surface area, with pRF sizes here similarly ∼1-8° of visual angle across the same region. In addition, cortical magnification measurements show that a larger extent of the pSTS VFM surface areas are devoted to the peripheral visual

  19. Full-Length Genome Analyses of Two New Simian Immunodeficiency Virus (SIV Strains from Mustached Monkeys (C. Cephus in Gabon Illustrate a Complex Evolutionary History among the SIVmus/mon/gsn Lineage

    Directory of Open Access Journals (Sweden)

    Florian Liégeois

    2014-07-01

    Full Text Available The Simian Immunodeficiency Virus (SIV mus/mon/gsn lineage is a descendant of one of the precursor viruses to the HIV-1/SIVcpz/gor viral lineage. SIVmus and SIVgsn were sequenced from mustached and greater spot nosed monkeys in Cameroon and SIVmon from mona monkeys in Cameroon and Nigeria. In order to further document the genetic diversity of SIVmus, we analyzed two full-length genomes of new strains identified in Gabon. The whole genomes obtained showed the expected reading frames for gag, pol, vif, vpr, tat, rev, env, nef, and also for a vpu gene. Analyses showed that the Gabonese SIVmus strains were closely related and formed a monophyletic clade within the SIVmus/mon/gsn lineage. Nonetheless, within this lineage, the position of both new SIVmus differed according to the gene analyzed. In pol and nef gene, phylogenetic topologies suggested different evolutions for each of the two new SIVmus strains whereas in the other nucleic fragments studied, their positions fluctuated between SIVmon, SIVmus-1, and SIVgsn. In addition, in C1 domain of env, we identified an insertion of seven amino acids characteristic for the SIVmus/mon/gsn and HIV‑1/SIVcpz/SIVgor lineages. Our results show a high genetic diversity of SIVmus in mustached monkeys and suggest cross-species transmission events and recombination within SIVmus/mon/gsn lineage. Additionally, in Central Africa, hunters continue to be exposed to these simian viruses, and this represents a potential threat to humans.

  20. S2-3: Double Dissociation between the Extrastriate Body Area and the Posterior Superior Temporal Sulcus during Biological Motion Perception: Converging Evidence from TMS and fMRI

    Directory of Open Access Journals (Sweden)

    Joris Vangeneugden

    2012-10-01

    Full Text Available Our brains engage numerous regions when exposed to biological motion, with the posterior superior temporal sulcus (pSTS being the primary locus. The exact roles of hMT+ and the extrastriate body area (EBA remain unclear. Here, we set out to determine the specific roles of pSTS and EBA during biological motion perception, focusing on walker orientation and walking direction. To obtain converging evidence, we conducted separate TMS and fMRI experiments within the same subjects (N = 12. Two separate tasks were used in the TMS study: walker orientation probing form processing and walking direction probing motion/sequence processing. Task performance was compared before and after applying repetitive offline TMS (1 Hz over EBA and pSTS (based on fMRI-guided stereotaxy. In the fMRI study, EBA and pSTS were mapped in separate scans using standard localizers. Subsequently, runs with point-light walkers were subjected to MVPA, determining the amount of static (orientation and dynamic (direction information present within EBA and pSTS. Both TMS and MVPA revealed a strong double dissociation between inferred functions of EBA and pSTS. Disrupting EBA impaired performance on the walker orientation task, while leaving walking direction performance intact. In contrast, disruption of pSTS processing resulted in the opposite effect (p < .001. Similarly, EBA BOLD response revealed significant walker orientation information and no walking direction information, while (again pSTS BOLD response displayed the opposite pattern (p < .005. We provide converging and causative evidence that dissociates EBA (static body processing from pSTS (dynamic body sequence processing during action perception.

  1. Grasping with the Press of a Button: Grasp-selective Responses in the Human Anterior Intraparietal Sulcus Depend on Nonarbitrary Causal Relationships between Hand Movements and End-effector Actions.

    Science.gov (United States)

    Frey, Scott H; Hansen, Marc; Marchal, Noah

    2015-06-01

    Evidence implicates ventral parieto-premotor cortices in representing the goal of grasping independent of the movements or effectors involved [Umilta, M. A., Escola, L., Intskirveli, I., Grammont, F., Rochat, M., Caruana, F., et al. When pliers become fingers in the monkey motor system. Proceedings of the National Academy of Sciences, U.S.A., 105, 2209-2213, 2008; Tunik, E., Frey, S. H., & Grafton, S. T. Virtual lesions of the anterior intraparietal area disrupt goal-dependent on-line adjustments of grasp. Nature Neuroscience, 8, 505-511, 2005]. Modern technologies that enable arbitrary causal relationships between hand movements and tool actions provide a strong test of this hypothesis. We capitalized on this unique opportunity by recording activity with fMRI during tasks in which healthy adults performed goal-directed reach and grasp actions manually or by depressing buttons to initiate these same behaviors in a remotely located robotic arm (arbitrary causal relationship). As shown previously [Binkofski, F., Dohle, C., Posse, S., Stephan, K. M., Hefter, H., Seitz, R. J., et al. Human anterior intraparietal area subserves prehension: A combined lesion and functional MRI activation study. Neurology, 50, 1253-1259, 1998], we detected greater activity in the vicinity of the anterior intraparietal sulcus (aIPS) during manual grasp versus reach. In contrast to prior studies involving tools controlled by nonarbitrarily related hand movements [Gallivan, J. P., McLean, D. A., Valyear, K. F., & Culham, J. C. Decoding the neural mechanisms of human tool use. Elife, 2, e00425, 2013; Jacobs, S., Danielmeier, C., & Frey, S. H. Human anterior intraparietal and ventral premotor cortices support representations of grasping with the hand or a novel tool. Journal of Cognitive Neuroscience, 22, 2594-2608, 2010], however, responses within the aIPS and premotor cortex exhibited no evidence of selectivity for grasp when participants employed the robot. Instead, these regions showed

  2. Estudos de lesão ao DNA promovida pela autoxidação de S(IV) na presença de complexos de Cu(III)/tetraglicina. Efeito sinérgico de Ni(II), Co(II) e Mn(II)

    OpenAIRE

    Ruben Gregorio Moreno Moreno

    2005-01-01

    O presente trabalho apresenta estudos de lesão em biomoléculas (DNA e 2\\'-deoxiguanosina) induzida por Cu(III)/tetraglicina (Cu(III)/G4), radicais de óxidos de enxofre (SO3·-, SO4·-, SO5·-), HO· e HSO5-, espécies estas geradas durante a autoxidação de S(IV) na presença de Cu(II)/G4 ou Cu(II) (ausência de tetraglicina) e traços de um segundo íon metálico (Ni(II), Co(II) ou Mn(II)). A formação dos radicais SO3·- e HO· foi detectada pela técnica de resso...

  3. 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

  4. 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

  5. Kohæsiv sedimenttransport i kystområder

    DEFF Research Database (Denmark)

    Larsen, Torben

    1995-01-01

    Denne tekst skal betragtes som en forklarende tekst til de 7 overheadslides med figurer, som benyttes ved indlægget og som ses som bilag hertil. Figurerne er taget fra de i referencelisten nævnte afhandlinger og papers.......Denne tekst skal betragtes som en forklarende tekst til de 7 overheadslides med figurer, som benyttes ved indlægget og som ses som bilag hertil. Figurerne er taget fra de i referencelisten nævnte afhandlinger og papers....

  6. 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

  7. White noise improves learning by modulating activity in dopaminergic midbrain regions and right superior temporal sulcus.

    Science.gov (United States)

    Rausch, Vanessa H; Bauch, Eva M; Bunzeck, Nico

    2014-07-01

    In neural systems, information processing can be facilitated by adding an optimal level of white noise. Although this phenomenon, the so-called stochastic resonance, has traditionally been linked with perception, recent evidence indicates that white noise may also exert positive effects on cognitive functions, such as learning and memory. The underlying neural mechanisms, however, remain unclear. Here, on the basis of recent theories, we tested the hypothesis that auditory white noise, when presented during the encoding of scene images, enhances subsequent recognition memory performance and modulates activity within the dopaminergic midbrain (i.e., substantia nigra/ventral tegmental area, SN/VTA). Indeed, in a behavioral experiment, we can show in healthy humans that auditory white noise-but not control sounds, such as a sinus tone-slightly improves recognition memory. In an fMRI experiment, white noise selectively enhances stimulus-driven phasic activity in the SN/VTA and auditory cortex. Moreover, it induces stronger connectivity between SN/VTA and right STS, which, in addition, exhibited a positive correlation with subsequent memory improvement by white noise. Our results suggest that the beneficial effects of auditory white noise on learning depend on dopaminergic neuromodulation and enhanced connectivity between midbrain regions and the STS-a key player in attention modulation. Moreover, they indicate that white noise could be particularly useful to facilitate learning in conditions where changes of the mesolimbic system are causally related to memory deficits including healthy and pathological aging.

  8. Superior sulcus (Pancoast) tumors: current evidence on diagnosis and radical treatment

    OpenAIRE

    Foroulis, Christophoros N.; Zarogoulidis, Paul; Darwiche, Kaid; Katsikogiannis, Nikolaos; Machairiotis, Nikolaos; Karapantzos, Ilias; Tsakiridis, Kosmas; Huang, Haidong; Zarogoulidis, Konstantinos

    2013-01-01

    Pancoast tumors account for less than 5% of all bronchogenic carcinomas. These tumors are located in the apex of the lung and involve through tissue contiguity the apical chest wall and/or the structures of the thoracic inlet. The tumors become clinically evident with the characteristic symptoms of the “Pancoast-Tobias syndrome” which includes Claude-Bernard-Horner syndrome, severe pain in the shoulder radiating toward the axilla and/or scapula and along the ulnar distribution of the upper ar...

  9. Superior sulcus (Pancoast) tumors: current evidence on diagnosis and radical treatment.

    Science.gov (United States)

    Foroulis, Christophoros N; Zarogoulidis, Paul; Darwiche, Kaid; Katsikogiannis, Nikolaos; Machairiotis, Nikolaos; Karapantzos, Ilias; Tsakiridis, Kosmas; Huang, Haidong; Zarogoulidis, Konstantinos

    2013-09-01

    Pancoast tumors account for less than 5% of all bronchogenic carcinomas. These tumors are located in the apex of the lung and involve through tissue contiguity the apical chest wall and/or the structures of the thoracic inlet. The tumors become clinically evident with the characteristic symptoms of the "Pancoast-Tobias syndrome" which includes Claude-Bernard-Horner syndrome, severe pain in the shoulder radiating toward the axilla and/or scapula and along the ulnar distribution of the upper arm, atrophy of hand and arm muscles and obstruction of the subclavian vein resulting in edema of the upper arm. The diagnosis will be made by the combination of the characteristic clinical symptoms with the radiographic findings of a mass or opacity in the apex of the lung infiltrating the 1(st) and/or 2(nd) ribs. A tissue diagnosis of the tumor via CT-guided FNA/B should always be available before the initiation of treatment. Bronchoscopy, thoracoscopy and biopsy of palpable supraclavicular nodes are alternative ways to obtain a tissue diagnosis. Adenocarcinomas account for 2/3 of all Pancoast tumors, while the rest of the tumors are squamous cell and large cell carcinomas. Magnetic resonance imaging of the thoracic inlet is always recommended to define the exact extent of tumor invasion within the thoracic inlet before surgical intervention. Pancoast tumors are by definition T3 or T4 tumors. Induction chemo-radiotherapy is the standard of care for any potentially resectable Pancoast tumor followed by an attempt to achieve a complete tumor resection. Resection can be made through a variety of anterior and posterior approaches to the thoracic inlet. The choice of the approach depends on the location of the tumor (posterior - middle - anterior compartment of the thoracic inlet) and the depth/extent of invasion. Prognosis depends mainly on T stage of tumor, response to preoperative chemo-radiotherapy and completeness of resection. Resection of the invaded strictures of the thoracic inlet should me made en bloc with pulmonary parenchyma resection, preferably an upper lobectomy. Invasion of the vertebral column is not a contraindication for surgery which, however, should be performed in oncologic centers with experience in spinal surgery. Surgery for Pancoast tumors is associated with 5% mortality rate and the complication rate varies from 7-38%. The overall 2-year survival rate after induction chemo-radiotherapy and resection varies from 55% to 70%, while the 5-year survival for R0 resections is quite good (54-77%). The main pattern of recurrence is that of distant metastases, especially in the brain.

  10. Bacterial colonization of the peri-implant sulcus in dentate patients : a prospective observational study

    NARCIS (Netherlands)

    Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L; Raghoebar, G M

    OBJECTIVES: The aim of the present study was to compare the composition of the periodontal microflora at baseline (T0) with the submucosal microflora at least 1 year after implant placement (T1) in periodontally healthy patients. MATERIAL AND METHODS: For all 169 consecutive patients that visited

  11. An anatomical and osteometric study of the femoral sulcus angle in ...

    African Journals Online (AJOL)

    The shape of the lower extremity of the femur is determined early in development, long before .... phasis in using one limb more than the other based on the nature of physical activities in which they are ... of the vastus medialis. Variations in the development of the origin of this muscle are evidenced on the spiral line.

  12. Statistical sulcal shape comparisons: application to the detection of genetic encoding of the central sulcus shape

    DEFF Research Database (Denmark)

    Le Goualher, G; Argenti, A.M.; Duyme, M

    2000-01-01

    of measurements in order to detect a statistically significant difference between two groups. We have applied this methodology to highlight evidence of genetic encoding of the shape of neuroanatomical structures. To investigate genetic constraint, we studied if shapes were more similar within 10 pairs......Principal Component Analysis allows a quantitative description of shape variability with a restricted number of parameters (or modes) which can be used to quantify the difference between two shapes through the computation of a modal distance. A statistical test can then be applied to this set...... of monozygotic twins than within interpairs and compared the results with those obtained from 10 pairs of dizygotic twins. The statistical analysis was performed using a Mantel permutation test. We show, using simulations, that this statistical test applied on modal distances can detect a possible genetic...

  13. Representation of Semantic Similarity in the Left Intraparietal Sulcus : Functional Magnetic Resonance Imaging Evidence

    NARCIS (Netherlands)

    Neyens, Veerle; Bruffaerts, Rose; Liuzzi, Antonietta Gabriella; Kalfas, Ioannis; Peeters, Ronald; Keuleers, Emmanuel; Vogels, Rufin; De Deyne, Simon; Storms, Gert; Dupont, Patrick; Vandenberghe, Rik

    2017-01-01

    According to a recent study, semantic similarity between concrete entities correlates with the similarity of activity patterns in left middle IPS during category naming. We examined the replicability of this effect under passive viewing conditions, the potential role of visuoperceptual similarity,

  14. Statistical sulcal shape comparisons: Application to the detection of genetic encoding of the central sulcus shape

    NARCIS (Netherlands)

    le Goualher, G.; Argenti, A.M.; Duyme, M.; Baare, W.F.C.; Hulshoff Poll, H.E.; Boomsma, D.I.; Zouaoui, A.; Barillot, C.; Evans, A.C.

    2000-01-01

    Principal Component Analysis allows a quantitative description of shape variability with a restricted number of parameters (or modes) which can be used to quantify the difference between two shapes through the computation of a modal distance. A statistical test can then be applied to this set of

  15. Periosteal fenestration vestibuloplasty procedure for sulcus deepening in a hemimandibulectomy patient following implant therapy

    Directory of Open Access Journals (Sweden)

    Bhavna Jha Kukreja

    2014-01-01

    Full Text Available Ablative surgery of the jaws may be necessary when malignant disease or destructive benign disease occurs. Surgical reconstruction needs to include the restoration of masticatory function so that the quality of life after the operation is optimal. When resection includes part of the upper or lower jaw, the aim of reconstruction should encompass not only the restoration of aesthetics, speech and swallowing, but also the recreation of an alveolar ridge suitable for prosthetic rehabilitation of the dental occlusion. In the present case, depth of vestibule was inadequate following implant placement thereby severely compromising prosthetic rehabilitation. Hence vestibuloplasty was done with periosteal fenestration operation, which provided retention and stability of mandibular prosthesis and hence greatly improved his overall quality of life.

  16. Superior sulcus (Pancoast) tumors: current evidence on diagnosis and radical treatment

    National Research Council Canada - National Science Library

    Foroulis, Christophoros N; Zarogoulidis, Paul; Darwiche, Kaid; Katsikogiannis, Nikolaos; Machairiotis, Nikolaos; Karapantzos, Ilias; Tsakiridis, Kosmas; Huang, Haidong; Zarogoulidis, Konstantinos

    2013-01-01

    .... The tumors become clinically evident with the characteristic symptoms of the "Pancoast-Tobias syndrome" which includes Claude-Bernard-Horner syndrome, severe pain in the shoulder radiating toward...

  17. Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy.

    Science.gov (United States)

    Holleran, Laurena; Kim, Joong Hee; Gangolli, Mihika; Stein, Thor; Alvarez, Victor; McKee, Ann; Brody, David L

    2017-03-01

    Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = -0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.

  18. Abordagem simplificada do nervo ciático por via posterior, no ponto médio do sulco glúteo-femoral, com uso de neuroestimulador Abordaje simplificado del nervio ciático por vía posterior, en el punto medio del sulco glúteo-femoral, con uso de neuroestimulador Simplified sciatic nerve approach by the posterior route at the median gluteus-femoral sulcus region, with a neurostimulator

    Directory of Open Access Journals (Sweden)

    Neuber Martins Fonseca

    2002-11-01

    adecuada en todos los casos con el volumen y concentración usados. En ningún paciente ocurrió anestesia del nervio cutáneo posterior del muslo. El tiempo de ejecución del bloqueo fue de 8,58 ± 5,71 min. la latencia fue de 5,88 ± 1,6 min. La duración sensitiva y motora del bloqueo fue de 4,05 ± 1,1 y 2,9 ± 0,8 horas, respectivamente. CONCLUSIONES: Ese nuevo abordaje es eficaz y de fácil ejecución. No está indicada si el bloqueo del nervio cutáneo posterior del muslo es necesario.BACKGROUND AND OBJECTIVES: The sciatic nerve may be blocked by several routes, all of them with advantages and disadvantages. It is the largest human nerve in diameter and length, being the prolongation of the upper sacral plexus fascicle (L4, L5, S2 and S3. It leaves the pelvis through the foramen ischiadicum majus, passing below the piriform muscle and going down between the greater trochanter and the ischial tuberosity, continuing along the femoral dorsum, anterior to biceps femoris and semitendinous muscles, to the lower femoral third, where it is divided in two major branches called tibial and common fibular nerves. It becomes superficial at the lower border of the gluteus maximus muscle. Based on this anatomic description, we developed a posterior approach with the following advantages: easy identification of the surface anatomy, superficial level of the nerve at this location; and less discomfort to patients since a 5 cm needle may be used. METHODS: Seventeen ASA I - III patients aged 21 to 79 years, weighing 55 to 90 kg, undergoing leg or foot surgery were studied. After monitoring, patients were placed in the prone position and blockade was performed at the middle point of the sulcus gluteus (skin fold between nates and posterior thigh, with the aid of a neurostimulator, using 1% plain lidocaine (300 mg. Onset time, blockade performing time, and tibial, common fibular and cutaneous femoris posterior nerves anesthesia were evaluated. Saphenous nerve was also blocked with 5 ml

  19. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys

    NARCIS (Netherlands)

    Barouch, Dan H.; Liu, Jinyan; Li, Hualin; Maxfield, Lori F.; Abbink, Peter; Lynch, Diana M.; Iampietro, M. Justin; Sanmiguel, Adam; Seaman, Michael S.; Ferrari, Guido; Forthal, Donald N.; Ourmanov, Ilnour; Hirsch, Vanessa M.; Carville, Angela; Mansfield, Keith G.; Stablein, Donald; Pau, Maria G.; Schuitemaker, Hanneke; Sadoff, Jerald C.; Billings, Erik A.; Rao, Mangala; Robb, Merlin L.; Kim, Jerome H.; Marovich, Mary A.; Goudsmit, Jaap; Michael, Nelson L.

    2012-01-01

    Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate

  20. Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

    Directory of Open Access Journals (Sweden)

    Maria S. Salvato

    2007-01-01

    Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

  1. Securing Australia – for SIVs, from SIEVs, via Edinburgh Gardens NYE

    Directory of Open Access Journals (Sweden)

    Pete Chambers

    2016-03-01

    Full Text Available Edinburgh Gardens is the crown jewel of Fitzroy North, one of inner northern Melbourne’s most gentrified suburbs. In 2009, Christian Lander, author of Stuff White People Like, dubbed Fitzroy North Melbourne’s whitest suburb. In January 2015, the median house price hit $1,050,000, a far cry from Chopper Reid’s stomping ground and the setting of precarious 70s student lives in Monkey Grip.

  2. Tissue-Specific Interferon Alpha Subtype Response to SIV Infection in Brain, Spleen, and Lung

    OpenAIRE

    Zaritsky, Luna Alammar; Dery, Alicia; Leong, Wan Yee; Gama, Lucio; Clements, Janice E.

    2013-01-01

    Interferon alpha (IFNalpha) is a type I interferon that plays a major role in host defense. There are 13 different IFNalpha genes in humans, but much of the work concerning their role in viral defense has been limited to studying either subtype 2 or pan IFNalpha due to the inability to distinguish between highly similar genetic and amino acid sequences. Because of recent advances in molecular and biochemical techniques, it is possible to study the regulation of individual subtypes. It has bee...

  3. Protective Efficacy of Adenovirus/Protein Vaccines Against SIV Challenges in Rhesus Monkeys

    Science.gov (United States)

    Barouch, Dan H.; Alter, Galit; Broge, Thomas; Linde, Caitlyn; Ackerman, Margaret E.; Brown, Eric P.; Borducchi, Erica N.; Smith, Kaitlin M.; Nkolola, Joseph P.; Liu, Jinyan; Shields, Jennifer; Parenteau, Lily; Whitney, James B.; Abbink, Peter; Ng’ang’a, David M.; Seaman, Michael S.; Lavine, Christy L.; Perry, James R.; Li, Wenjun; Colantonio, Arnaud D.; Lewis, Mark G.; Chen, Bing; Wenschuh, Holger; Reimer, Ulf; Piatak, Michael; Lifson, Jeffrey D.; Handley, Scott A.; Virgin, Herbert W.; Koutsoukos, Marguerite; Lorin, Clarisse; Voss, Gerald; Weijtens, Mo; Pau, Maria G.; Schuitemaker, Hanneke

    2015-01-01

    Preclinical studies of viral vector-based HIV-1 vaccine candidates have previously shown partial protection against stringent virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy of adenovirus serotype 26 (Ad26) vector priming followed by boosting with a purified envelope (Env) glycoprotein. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env/Gag/Pol antigens and boosted with AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete protection in 50% of vaccinated animals against a series of repetitive, heterologous, intrarectal SIVmac251 challenges that infected all controls. Protective efficacy correlated with the functionality of Env-specific antibody responses. Comparable protection was also observed with a similar Ad/Env vaccine against repetitive, heterologous, intrarectal SHIV-SF162P3 challenges. These data demonstrate robust protection by Ad/Env vaccines against acquisition of stringent virus challenges in rhesus monkeys. PMID:26138104

  4. An evaluation of traffic-awareness campaign videos: empathy induction is associated with brain function within superior temporal sulcus

    Czech Academy of Sciences Publication Activity Database

    Zelinková, J.; Shaw, D. J.; Mikl, M.; Mareček, R.; Urbánek, Tomáš; Havlíčková, D.; Zámečník, P.; Haitová, P.; Brázdil, M.

    2014-01-01

    Roč. 10, č. 27 (2014) ISSN 1744-9081 Institutional support: RVO:68081740 Keywords : fMRI * Traffic-awareness campaign * Socio-emotional processing Subject RIV: AN - Psychology Impact factor: 1.972, year: 2014 http://www.behavioralandbrainfunctions.com/content/10/1/27

  5. Out of sight but not out of mind : The neurophysiology of iconic memory in the superior temporal sulcus

    NARCIS (Netherlands)

    Keysers, C; Xiao, DK; Foldiak, P; Perrett, DI

    2005-01-01

    Iconic memory, the short-lasting visual memory of a briefly flashed stimulus, is an important component of most models of visual perception. Here we investigate what physiological mechanisms underlie this capacity by showing rapid serial visual presentation (RSVP) sequences with and without

  6. Functional connectivity indicates differential roles for the intraparietal sulcus and the superior parietal lobule in multiple object tracking.

    Science.gov (United States)

    Alnæs, Dag; Sneve, Markus H; Richard, Geneviève; Skåtun, Kristina C; Kaufmann, Tobias; Nordvik, Jan Egil; Andreassen, Ole A; Endestad, Tor; Laeng, Bruno; Westlye, Lars T

    2015-12-01

    Attentive tracking requires sustained object-based attention, rather than passive vigilance or rapid attentional shifts to brief events. Several theories of tracking suggest a mechanism of indexing objects that allows for attentional resources to be directed toward the moving targets. Imaging studies have shown that cortical areas belonging to the dorsal frontoparietal attention network increase BOLD-signal during multiple object tracking (MOT). Among these areas, some studies have assigned IPS a particular role in object indexing, but the neuroimaging evidence has been sparse. In the present study, we tested participants on a continuous version of the MOT task in order to investigate how cortical areas engage in functional networks during attentional tracking. Specifically, we analyzed the data using eigenvector centrality mapping (ECM) analysis, which provides estimates of individual voxels' connectedness with hub-like parts of the functional network. The results obtained using permutation based voxel-wise statistics support the proposed role for the IPS in object indexing as this region displayed increased centrality during tracking as well as increased functional connectivity with both prefrontal and visual perceptual cortices. In contrast, the opposite pattern was observed for the SPL, with decreasing centrality, as well as reduced functional connectivity with the visual and frontal cortices, in agreement with a hypothesized role for SPL in attentional shifts. These findings provide novel evidence that IPS and SPL serve different functional roles during MOT, while at the same time being highly engaged during tracking as measured by BOLD-signal changes. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 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

    . Of the 34 cases which had no radial nerve injury, 16 had fracture of SNR region. CONCLUSIONS: As a result; radial nerve injury rate was 37.5% for the fractures of SNR region and it was higher compared to other studies. We concluded that the fractures of SNR region do not increase the risk of radial nerve...

  8. Virtual lesion of right posterior superior temporal sulcus modulates conscious visual perception of fearful expressions in faces and bodies.

    Science.gov (United States)

    Candidi, Matteo; Stienen, Bernard M C; Aglioti, Salvatore M; de Gelder, Beatrice

    2015-04-01

    The posterior Superior Temporal Suclus (pSTS) represents a central hub in the complex cerebral network for person perception and emotion recognition as also suggested by its heavy connections with face- and body-specific cortical (e.g., the fusiform face area, FFA and the extrastriate body area, EBA) and subcortical structures (e.g., amygdala). Information on whether pSTS is causatively involved in sustaining conscious visual perception of emotions expressed by faces and bodies is lacking. We explored this issue by combining a binocular rivalry procedure (where emotional and neutral face and body postures rivaled with house images) with off-line, 1-Hz repetitive transcranial magnetic stimulation (rTMS). We found that temporary inhibition of the right pSTS reduced perceptual dominance of fearful faces and increased perceptual dominance of fearful bodies, while leaving unaffected the perception of neutral face and body images. Inhibition of the vertex had no effect on conscious visual perception of neutral or emotional face or body stimuli. Thus, the right pSTS plays a causal role in shortening conscious vision of fearful faces and in prolonging conscious vision of fearful bodies. These results suggest that pSTS selectively modulates the activity of segregated networks involved in the conscious visual perception of emotional faces or bodies. We speculate that the opposite role of the right pSTS for conscious perception of fearful face and body may be explained by the different connections that this region entertains with face- and body-selective visual areas as well as with amygdalae and premotor regions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Nociones actuales sobre la flora microbiana del surco gingival Current notions on the microbial flora of the gingival sulcus

    Directory of Open Access Journals (Sweden)

    Tatiana Peña Ruiz

    2007-09-01

    Full Text Available La enfermedad periodontal es un problema de salud bucal a escala mundial. Con el transcurso del tiempo, el conocimiento de la gingivitis ha sufrido grandes cambios, y es hoy en día una de las enfermedades de mayor frecuencia entre los pacientes que asisten a los servicios estomatológicos. Se realiza este estudio con el objetivo de profundizar en la relación entre los microorganismos de la placa dental y la etiología de la periodontitis. La placa dental es una comunidad microbiana compleja; como consecuencia de las interacciones entre las especies, se produce un nicho ecológico que favorece el crecimiento y la supervivencia de especies proteolíticas anaerobias estrictas, así como condiciones apropiadas para el desarrollo de periodontitis.Periodontal disease is an oral health problem worldwide. In the course of time, knowledge about gingivitis has greatly changed, and today, this is one of the most frequent diseases affecting the patients going to the dentistry service. This study was aimed at delving into the relationship between the dental plaque microorganisms and the periodontitis etiology. The dental plaque constitutes a complex microbial community; the interactions among the host species give rise to an ecological niche that favors growth and survival of strictly anaerobic proteolytic species as well as to adequate conditions for the onset of periodontitis.

  10. Ventral simultanagnosia and prosopagnosia for unfamiliar faces due to a right posterior superior temporal sulcus and angular gyrus lesion.

    Science.gov (United States)

    Sakurai, Yasuhisa; Hamada, Kensuke; Tsugawa, Naoya; Sugimoto, Izumi

    2016-01-01

    We report a patient with ventral simultanagnosia, prosopagnosia for "unfamiliar faces" (dorsal prosopagnosia), spatial agraphia, and constructional disorder, particularly on the left spatial side, due to a lesion in the right posterior superior and middle temporal gyri and angular gyrus. The patient showed impairment of fundamental visual and visuospatial recognition, such as in object size, configuration, and horizontal point location, which probably underlay the mechanism of simultanagnosia and prosopagnosia. This case also suggests that the coexistence of simultanagnosia and prosopagnosia results from a right hemispheric insult, and damage to the temporoparietal area interrupts the incorporation of spatial information into object recognition. This disconnection of information flow, together with impaired object recognition per se, may impair the parallel processing of multiple objects, leading to object-by-object or part-by-part recognition.

  11. Mirror Observation of Finger Action Enhances Activity in Anterior Intraparietal Sulcus: A Functional Magnetic Resonance Imaging Study

    National Research Council Canada - National Science Library

    NUMATA, Kenji; MURAYAMA, Takashi; TAKASUGI, Jun; MONMA, Masahiko; OGA, Masaru

    2013-01-01

    Mirror therapy can be used to promote recovery from paralysis in patients with post-stroke hemiplegia, There are a lot of reports that mirror-image observation of the unilateral moving hand enhanced...

  12. Mirror Observation of Finger Action Enhances Activity in Anterior Intraparietal Sulcus: A Functional Magnetic Resonance Imaging Study

    OpenAIRE

    Numata, Kenji; Murayama, Takashi; Takasugi, Jun; Monma, Masahiko; Oga, Masaru

    2013-01-01

    Mirror therapy can be used to promote recovery from paralysis in patients with post-stroke hemiplegia, There are a lot of reports that mirror-image observation of the unilateral moving hand enhanced the excitability of the primary motor area (M1) ipsilateral to the moving hand in healthy subjects. but the neural mechanisms underlying its therapeutic effects are currently unclear. To investigate this issue, we used functional magnetic resonance imaging to measure activity in brain regions rela...

  13. Next-generation in situ hybridization approaches to define and quantify HIV and SIV reservoirs in tissue microenvironments.

    Science.gov (United States)

    Deleage, Claire; Chan, Chi N; Busman-Sahay, Kathleen; Estes, Jacob D

    2018-01-09

    The development of increasingly safe and effective antiretroviral treatments for human immunodeficiency virus (HIV) over the past several decades has led to vastly improved patient survival when treatment is available and affordable, an outcome that relies on uninterrupted adherence to combination antiretroviral therapy for life. Looking to the future, the discovery of an elusive 'cure' for HIV will necessitate highly sensitive methods for detecting, understanding, and eliminating viral reservoirs. Next-generation, in situ hybridization (ISH) approaches offer unique and complementary insights into viral reservoirs within their native tissue environments with a high degree of specificity and sensitivity. In this review, we will discuss how modern ISH techniques can be used, either alone or in conjunction with phenotypic characterization, to probe viral reservoir establishment and maintenance. In addition to focusing on how these techniques have already furthered our understanding of HIV reservoirs, we discuss potential avenues for how high-throughput, next-generation ISH may be applied. Finally, we will review how ISH could allow deeper phenotypic and contextual insights into HIV reservoir biology that should prove instrumental in moving the field closer to viral reservoir elimination needed for an 'HIV cure' to be realized.

  14. Putative HIV and SIV G-Quadruplex Sequences in Coding and Noncoding Regions Can Form G-Quadruplexes

    Directory of Open Access Journals (Sweden)

    Petra Krafčíková

    2017-01-01

    Full Text Available The HIV virus is one of the most studied viruses in the world. This is especially true in terms of gene sequencing, and to date more than 9 thousand genomic sequences of HIV isolates have been sequenced and analyzed. In this study, a series of DNA sequences, which have the potential to form G-quadruplex structures, is analyzed. Several such sequences were found in various coding and noncoding virus domains, including the U3 LTR, tat, rev, env, and vpx regions. Interestingly, a homological sequence to the already well-known HIV integrase aptamer was identified in the minus-strand. The sequences derived from original isolates were analyzed using standard spectral and electrophoretic methods. In addition, a recently developed methodology is applied which uses induced circular dichroism spectral profiles of G-quadruplex-ligand (Thiazole Orange complexes to determine if G-rich sequences can adopt G-quadruplex structure. Targeting the G-quadruplexes or peptide domains corresponding to the G-rich coding sequence in HIV offers researchers attractive therapeutic targets which would be of particular use in the development of novel antiviral therapies. The analysis of G-rich regions can provide researchers with a path to find specific targets which could be of interest for specific types of virus.

  15. Transdominant Rev and Protease Mutant Proteins of HIV-SIV as Potential Antiviral Agents in Vitro and in Vivo (AIDS)

    Science.gov (United States)

    1993-10-30

    1577- 1580. 7. Sarver, N., E.M. Cantin , P.S. Chang, J.A. Zaia, P.A. Landne, D.A. Stephens, and J.J Rossi. 1990. Ribozymes as potential anti-HIV-1...activities. Nature (London) 334: 585-591. 16 Chang, P.S., E.M. Cantin , J.A. Zaia, P.A. Landne, D.A. Stephens, N. Sarver, and J.J. Rossi. 1990. Clinical

  16. Äriühingu püsiv maksejõuetus ja edasiste maksete tegemine. Kus on piir keelatu ja lubatu vahel? / Triin Toom

    Index Scriptorium Estoniae

    Toom, Triin, 1990-

    2014-01-01

    Äriühingu püsiva maksejõuetuse kindlakstegemisest ning maksete tegemise piirangu sisust ja ulatusest. Eesti ja Saksamaa õigusreeglite ja kohtupraktika võrdlev analüüs. Artikkel põhineb autori magistritööl

  17. RTE and CTE mRNA export elements synergistically increase expression of unstable, Rev-dependent HIV and SIV mRNAs

    Directory of Open Access Journals (Sweden)

    Michalowski Daniel

    2006-01-01

    Full Text Available Abstract Studies of retroviral mRNA export identified two distinct RNA export elements utilizing conserved eukaryotic mRNA export mechanism(s, namely the Constitutive Transport Element (CTE and the RNA Transport Element (RTE. Although RTE and CTE are potent in nucleocytoplasmic mRNA transport and expression, neither element is as powerful as the Rev-RRE posttranscriptional control. Here, we found that whereas CTE and the up-regulatory mutant RTEm26 alone increase expression from a subgenomic gag and env clones, the combination of these elements led to a several hundred-fold, synergistic increase. The use of the RTEm26-CTE combination is a simple way to increase expression of poorly expressed retroviral genes to levels otherwise only achieved via more cumbersome RNA optimization. The potent RTEm26-CTE element could be useful in lentiviral gene therapy vectors, DNA-based vaccine vectors, and gene transfer studies of other poorly expressed genes.

  18. Phenotypic changes in the brain of SIV-infected macaques exposed to methamphetamine parallel macrophage activation patterns induced by the common gamma-chain cytokine system

    Directory of Open Access Journals (Sweden)

    Nikki eBortell

    2015-09-01

    Full Text Available One factor in the development of neuroAIDS is the increase in the migration of pro-inflammatory CD8 T cells across the Blood Brain Barrier. Typically these cells are involved with keeping the viral load down. However, the persistence of above average numbers of CD8 T cells in the brain, not necessarily specific to viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma chain (γc cytokines. Here, using the non-human primate model of neuroAIDS, we have demonstrated that exposure to Methamphetamine, a powerful illicit drug that has been associated with HIV exposure and neuroAIDS severity, can cause an increase in molecules of the γc system. Among these molecules, IL15, which is upregulated in astrocytes by Methamphetamine, and that induces the proliferation of T cells, may also be involved in driving an inflammatory phenotype in innate immune cells of the brain. Therefore, Methamphetamine and IL15 may be critical in the development and aggravation of Central Nervous System immune-mediated inflammatory pathology in HIV-infected drug abusers.

  19. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ruy M [Los Alamos National Laboratory

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  20. A Novel Approach for Producing Lentiviruses That Are Limited to a Single Cycle of Infection

    OpenAIRE

    Evans, David T.; Bricker, Jennifer E.; Desrosiers, Ronald C.

    2004-01-01

    We have devised a novel approach for producing simian immunodeficiency virus (SIV) strains and, potentially, human immunodeficiency virus type 1 (HIV-1) strains that are limited to a single cycle of infection. Unlike previous lentiviral vectors, our single-cycle SIV is capable of expressing eight of the nine viral gene products and infected cells release immature virus particles that are unable to complete subsequent rounds of infection. Single-cycle SIV (scSIV) was produced by using a two-pl...

  1. Recombinant vaccinia DIs expressing simian immunodeficiency virus gag and pol in mammalian cells induces efficient cellular immunity as a safe immunodeficiency virus vaccine candidate.

    Science.gov (United States)

    Okamura, Tomotaka; Someya, Kenji; Matsuo, Kazuhiro; Hasegawa, Atsuhiko; Yamamoto, Naoki; Honda, Mitsuo

    2006-01-01

    A highly attenuated vaccinia virus substrain of Dairen-I (DIs) shows promise as a candidate vector for eliciting positive immunity against immune deficiency virus. DIs was randomly obtained by serial 1-day egg passages of a chorioarantoic membrane-adapted Dairen strain (DIE), resulting in substantial genomic deletion, including various genes regulating the virus-host-range. To investigate the impact of that deletion and of the subsequent insertion of a foreign gene into that region of DIs on the ability of the DIs recombinant to induce antigen-specific immunity, we generated a recombinant vaccinia DIs expressing fulllength gag and pol genes of simian immunodeficiency virus (SIV) (rDIsSIV gag/pol) and studied the biological and immunological characteristics of the recombinant natural mutant. The rDIsSIV gag/pol developed a tiny plaque on the chick embryo fibroblast (CEF). Viral particles of rDIsSIV gag/pol as well as SIV Gag-like particles were electromicroscopically detected in the cytoplasm. Interestingly, the recombinant DIs strain grows well in CEF cells but not in mammalian cells. While rDIsSIV gag/pol produces SIV proteins in mammalian HeLa and CV-1 cells, recombinant modified vaccinia Ankara strain (MVA) expressing SIV gag and pol genes (MVA/SIV239 gag/pol) clearly replicates in HeLa and CV-1 cell lines under synchronized growth conditions and produces the SIV protein in all cell lines. Moreover, intradermal administration of rDIsSIV gag/pol or of MVA/SIV239 gag/pol elicited similar levels of IFN-gamma spot-forming cells specific for SIV Gag. If the non-productive infection characteristically induced by recombinant DIs is sufficient to trigger immune induction, as we believe it is, then a human immunodeficiency virus vaccine employing the DIs recombinant would have the twin advantages of being both effective and safe.

  2. Orbitofrontal sulcal and gyrus pattern in human: an anatomical study

    Directory of Open Access Journals (Sweden)

    Thiago Pereira Rodrigues

    2015-05-01

    Full Text Available The anatomical characterization of the orbitofrontal cortex in human is limited in literature instead of many functional and clinical studies involving it. Objective Anatomically define the orbitofrontal region aiming to possible neurosurgical treatments and unify the scientific nomenclature as well. Method We analyze eighty four human hemispheres using a surgical microscope. Then we chose four hemispheres and dissect them according to Klinger’ technique. Results We found five main sulcus: olfatory sulcus, orbital medial sulcus, orbital lateral sulcus, orbital transverse sulcus and orbital intermediate sulcus. These sulcus, excluding the intermediate sulcus, delimit five gyrus: rectus gurys, orbital medial gyrus, orbital anterior gyrus, orbital lateral gyrus and orbital posterior gyrus. The main sulcal configuration can be divided on four more frequently patterns. Conclusion Orbitofrontal cortex is associated with many psychiatric disorders. Better anatomical and functional characterization of the orbitofrontal cortex and its connections will improve our knowledge about these diseases.

  3. Breaking Barriers to an AIDS Model with Macaque-Tropic HIV-1 Derivatives

    OpenAIRE

    Kimata, Jason T; Hongmei Ruan; Rajesh Thippeshappa

    2012-01-01

    The development of an animal model of human immunodeficiency virus type 1 (HIV-1)/AIDS that is suitable for preclinical testing of antiretroviral therapy, vaccines, curative strategies, and studies of pathogenesis has been hampered by the human-specific tropism of HIV-1. Although simian immunodeficiency virus (SIV) or HIV-1/SIV chimeric viruses (SHIVs)-rhesus macaque models are excellent surrogates for AIDS research, the genetic differences between SIV or SHIV and HIV-1 limit their utility as...

  4. Divergent CD4+ T memory stem cell dynamics in pathogenic and nonpathogenic simian immunodeficiency virus infections.

    Science.gov (United States)

    Cartwright, Emily K; McGary, Colleen S; Cervasi, Barbara; Micci, Luca; Lawson, Benton; Elliott, Sarah T C; Collman, Ronald G; Bosinger, Steven E; Paiardini, Mirko; Vanderford, Thomas H; Chahroudi, Ann; Silvestri, Guido

    2014-05-15

    Recent studies have identified a subset of memory T cells with stem cell-like properties (T(SCM)) that include increased longevity and proliferative potential. In this study, we examined the dynamics of CD4(+) T(SCM) during pathogenic SIV infection of rhesus macaques (RM) and nonpathogenic SIV infection of sooty mangabeys (SM). Whereas SIV-infected RM show selective numeric preservation of CD4(+) T(SCM), SIV infection induced a complex perturbation of these cells defined by depletion of CD4(+)CCR5(+) T(SCM), increased rates of CD4(+) T(SCM) proliferation, and high levels of direct virus infection. The increased rates of CD4(+) T(SCM) proliferation in SIV-infected RM correlated inversely with the levels of central memory CD4(+) T cells. In contrast, nonpathogenic SIV infection of SM evidenced preservation of both CD4(+) T(SCM) and CD4(+) central memory T cells, with normal levels of CD4(+) T(SCM) proliferation, and lack of selective depletion of CD4(+)CCR5(+) T(SCM). Importantly, SIV DNA was below the detectable limit in CD4(+) T(SCM) from 8 of 10 SIV-infected SM. We propose that increased proliferation and infection of CD4(+) T(SCM) may contribute to the pathogenesis of SIV infection in RM.

  5. Enhanced antibody responses elicited by a CpG adjuvant do not improve the protective effect of an aldrithiol-2-inactivated simian immunodeficiency virus therapeutic AIDS vaccine.

    Science.gov (United States)

    Wang, Yichuan; Blozis, Shelley A; Lederman, Michael; Krieg, Arthur; Landay, Alan; Miller, Christopher J

    2009-04-01

    The potential benefit of using unmethylated CpG oligoribodeoxynucleotides (ODN) as an adjuvant in a therapeutic simian immunodeficiency virus (SIV) vaccine consisting of AT2-inactivated SIVmac239 was evaluated in SIV-infected rhesus macaques receiving antiretroviral therapy (ART). We hypothesized that using CpG ODN as an adjuvant in therapeutic vaccination would enhance SIV-specific immune responses and suppress SIV replication after ART was stopped. To test our hypothesis, we immunized chronically SIV-infected rhesus macaques receiving ART with one of the following therapeutic vaccines: (i) AT2-inactivated SIVmac239, (ii) CpG10103 plus AT2-inactivated SIVmac239, (iii) CpG10103, and (iv) saline. While immunization with CpG plus AT2-SIVmac239 significantly increased SIV-specific immunoglobulin G (IgG) antibody titers, the mean plasma viral RNA (vRNA) level in these animals after ART did not differ from those of saline-treated animals. The AT2-inactivated SIVmac239-immunized animal group had a significantly higher mean SIV-specific gamma interferon T-cell response after three immunizations and lower plasma vRNA levels for 6 weeks after ART was withdrawn compared to the saline-treated animal group. Compared to the saline control group, the animal group treated with CpG alone had a significantly higher mean SIV-specific lymphocyte proliferation index and a higher rate of plasma vRNA rebound after ART. These results demonstrate that while the use of CpG as an adjuvant enhances SIV-specific antibody responses, this does not improve the control of SIV replication after ART is stopped. The lack of benefit may be related to the high levels of SIV-specific lymphocyte proliferation in the CpG adjuvant group.

  6. Large-Scale Nucleotide Optimization of Simian Immunodeficiency Virus Reduces Its Capacity To Stimulate Type I Interferon In Vitro

    Science.gov (United States)

    Vabret, Nicolas; Bailly-Bechet, Marc; Lepelley, Alice; Najburg, Valérie; Schwartz, Olivier; Verrier, Bernard

    2014-01-01

    ABSTRACT Lentiviral RNA genomes present a strong bias in their nucleotide composition with extremely high frequencies of A nucleotide in human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Based on the observation that human optimization of RNA virus gene fragments may abolish their ability to stimulate the type I interferon (IFN-I) response, we identified the most biased sequences along the SIV genome and showed that they are the most potent IFN-I stimulators. With the aim of designing an attenuated SIV genome based on a reduced capacity to activate the IFN-I response, we synthesized artificial SIV genomes whose biased sequences were optimized toward macaque average nucleotide composition without altering their regulatory elements or amino acid sequences. A synthetic SIV optimized with 169 synonymous mutations in gag and pol genes showed a 100-fold decrease in replicative capacity. Interestingly, a synthetic SIV optimized with 70 synonymous mutations in pol had a normal replicative capacity. Its ability to stimulate IFN-I was reduced when infected cells were cocultured with reporter cells. IFN regulatory factor 3 (IRF3) transcription factor was required for IFN-I stimulation, implicating cytosolic sensors in the detection of SIV-biased RNA in infected cells. No reversion of introduced mutations was observed for either of the optimized viruses after 10 serial passages. In conclusion, we have designed large-scale nucleotide-modified SIVs that may display attenuated pathogenic potential. IMPORTANCE In this study, we synthesized artificial SIV genomes in which the most hyperbiased sequences were optimized to bring them closer to the nucleotide composition of the macaque SIV host. Interestingly, we generated a stable synthetic SIV optimized with 70 synonymous mutations in pol gene, which had a normal replicative capacity but a reduced ability to stimulate type I IFN. This demonstrates the possibility to rationally change viral

  7. Generalized immune activation and innate immune responses in simian immunodeficiency virus infection.

    Science.gov (United States)

    Bosinger, Steven E; Sodora, Donald L; Silvestri, Guido

    2011-09-01

    Chronic immune activation is a key factor driving the immunopathogenesis of AIDS. During pathogenic HIV/simian immunodeficiency virus (SIV) infections, innate and adaptive antiviral immune responses contribute to chronic immune activation. In contrast, nonpathogenic SIV infections of natural hosts such as sooty mangabeys and African green monkeys (AGMs) are characterized by low immune activation despite similarly high viremia. This review focuses on the role of innate immune responses in SIV infection. Several studies have examined the role of innate immune responses to SIV as potential drivers of immune activation. The key result of these studies is that both pathogenic SIV infection of macaques and nonpathogenic SIV infections of natural hosts are associated with strong innate immune responses to the virus, high production of type I interferons by plasmacytoid dendritic cells, and upregulation of interferon-stimulated genes (ISGs). However, SIV-infected sooty mangabeys and AGMs (but not SIV-infected macaques) rapidly downmodulate the interferon response within 4-6 weeks of infection, thus resulting in a state of limited immune activation during chronic infection. Studies in nonhuman primates suggest that chronic innate/interferon responses may contribute to AIDS pathogenesis. Further, the ability of natural host species to resolve innate immune responses after infection provides a novel avenue for potential immunotherapy.

  8. 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

    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 by th...

  9. No evidence for transmission of SIVwrc from western red colobus monkeys (piliocolobus badius badius) to wild west african chimpanzees (pan troglodytes verus) despite high exposure through hunting

    Science.gov (United States)

    2011-01-01

    Background Simian Immunodeficiency Viruses (SIVs) are the precursors of Human Immunodeficiency Viruses (HIVs) which have lead to the worldwide HIV/AIDS pandemic. By studying SIVs in wild primates we can better understand the circulation of these viruses in their natural hosts and habitat, and perhaps identify factors that influence susceptibility and transmission within and between various host species. We investigated the SIV status of wild West African chimpanzees (Pan troglodytes verus) which frequently hunt and consume the western red colobus monkey (Piliocolobus badius badius), a species known to be infected to a high percentage with its specific SIV strain (SIVwrc). Results Blood and plasma samples from 32 wild chimpanzees were tested with INNO-LIA HIV I/II Score kit to detect cross-reactive antibodies to HIV antigens. Twenty-three of the samples were also tested for antibodies to 43 specific SIV and HIV lineages, including SIVwrc. Tissue samples from all but two chimpanzees were tested for SIV by PCRs using generic SIV primers that detect all known primate lentiviruses as well as primers designed to specifically detect SIVwrc. Seventeen of the chimpanzees showed varying degrees of cross-reactivity to the HIV specific antigens in the INNO-LIA test; however no sample had antibodies to SIV or HIV strain - and lineage specific antigens in the Luminex test. No SIV DNA was found in any of the samples. Conclusions We could not detect any conclusive trace of SIV infection from the red colobus monkeys in the chimpanzees, despite high exposure to this virus through frequent hunting. The results of our study raise interesting questions regarding the host-parasite relationship of SIVwrc and wild chimpanzees in their natural habitat. PMID:21284842

  10. Risk of immunodeficiency virus infection may increase with vaccine-induced immune response.

    Science.gov (United States)

    Tenbusch, Matthias; Ignatius, Ralf; Temchura, Vladimir; Nabi, Ghulam; Tippler, Bettina; Stewart-Jones, Guillaume; Salazar, Andres M; Sauermann, Ülrike; Stahl-Hennig, Christiane; Uberla, Klaus

    2012-10-01

    To explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for HIV infection, rhesus monkeys primed by different DNA vaccines were boosted with virus-like particles (VLP) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (SIV). Characteristic of the cellular immune response after the VLP booster immunization were high numbers of SIV-specific, gamma interferon-secreting cells after stimulation with inactivated SIV particles, but not SIV peptides, and the absence of detectable levels of CD8(+) T cell responses. Antibodies specific to SIV Gag and SIV Env could be induced in all animals, but, consistent with a poor neutralizing activity at the time of challenge, vaccinated monkeys were not protected from acquisition of infection and did not control viremia. Surprisingly, vaccinees with high numbers of SIV-specific, gamma interferon-secreting cells were infected fastest during the repeated low-dose exposures and the numbers of these immune cells in vaccinated macaques correlated with susceptibility to infection. Thus, in the absence of protective antibodies or cytotoxic T cell responses, vaccine-induced immune responses may increase the susceptibility to acquisition of immunodeficiency virus infection. The results are consistent with the hypothesis that virus-specific T helper cells mediate this detrimental effect and contribute to the inefficacy of past HIV vaccination attempts (e.g., STEP study).

  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. Loss of effector and anti-inflammatory natural killer T lymphocyte function in pathogenic simian immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    Namita Rout

    2012-09-01

    Full Text Available Chronic immune activation is a key determinant of AIDS progression in HIV-infected humans and simian immunodeficiency virus (SIV-infected macaques but is singularly absent in SIV-infected natural hosts. To investigate whether natural killer T (NKT lymphocytes contribute to the differential modulation of immune activation in AIDS-susceptible and AIDS-resistant hosts, we compared NKT function in macaques and sooty mangabeys in the absence and presence of SIV infection. Cynomolgus macaques had significantly higher frequencies of circulating invariant NKT lymphocytes compared to both rhesus macaques and AIDS-resistant sooty mangabeys. Despite this difference, mangabey NKT lymphocytes were functionally distinct from both macaque species in their ability to secrete significantly more IFN-γ, IL-13, and IL-17 in response to CD1d/α-galactosylceramide stimulation. While NKT number and function remained intact in SIV-infected mangabeys, there was a profound reduction in NKT activation-induced, but not mitogen-induced, secretion of IFN-γ, IL-2, IL-10, and TGF-β in SIV-infected macaques. SIV-infected macaques also showed a selective decline in CD4(+ NKT lymphocytes which correlated significantly with an increase in circulating activated memory CD4(+ T lymphocytes. Macaques with lower pre-infection NKT frequencies showed a significantly greater CD4(+ T lymphocyte decline post SIV infection. The disparate effect of SIV infection on NKT function in mangabeys and macaques could be a manifestation of their differential susceptibility to AIDS. Alternately, these data also raise the possibility that loss of anti-inflammatory NKT function promotes chronic immune activation in pathogenic SIV infection, while intact NKT function helps to protect natural hosts from developing immunodeficiency and aberrant immune activation.

  13. 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.

  14. Healthcare worker's attitude to seasonal influenza vaccination in the South Tyrolean province of Italy: barriers and facilitators.

    Science.gov (United States)

    Rabensteiner, Andrea; Buja, Alessandra; Regele, Dagmar; Fischer, Martin; Baldo, Vincenzo

    2018-01-25

    Seasonal influenza vaccination (SIV) is an effective and safe way to prevent influenza. Public health institutions around the world consequently recommend SIV to certain groups at risk, including healthcare worker's (HCWs). Even if SIV is free of charge, the vaccination coverage rate remains low, however. The aim of this study was to gain information on the sociodemographics, lifestyle and knowledge of HCWs associated with their attitude to SIV, also investigating the differences between different professional categories of HCW. A cross-sectional study was conducted over six consecutive weeks from October to December 2016. It was based on an anonymous online questionnaire administered to all employees (N = 9633) of the South Tyrolean Health Service. Coverage rates and attitudes to SIV were assessed by type of HCW. A logistic regression analysis was run to test the associations between SIV in the winter of 2015/2016 and potential predictors of the HCWs' attitude to vaccination. In all, 4091 employees (42.4% of the total) took part in the study. Statistically significant differences emerged between the different healthcare professions in terms of their reported vaccination rates and their attitudes to SIV. Among the different types of HCW, physicians had the highest rate of vaccination uptake. There were sociocultural and lifestyle factors associated with SIV in HCWs, as well as these worker's professional roles and the ward where they worked. All the professionals agreed that specific training was the best way to improve HCW vaccination rates. Low compliance with SIV among HCWs is attributable to numerous factors, some of which relate to their attitude to health issues. Commitment and accountability to patients and society should be further developed in HCWs. Specific training and information, also through informal scientific channels, should be provided to improve their knowledge of influenza and attitude to vaccination. Copyright © 2017 Elsevier Ltd. All

  15. Strike-Slip Faulting Processes on Ganymede: Global Morphological Mapping and Structural Interpretation of Grooved and Transitional Terrains

    Science.gov (United States)

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

    2015-12-01

    Ganymede's fractured surface reveals many large-scale, morphologically distinct regions of inferred distributed shear and strike-slip faulting that may be important to the structural development of its surface and in the transition from dark to light (grooved) materials. To better understand the role of strike-slip tectonism in shaping Ganymede's complex icy surface, we perform a detailed mapping of key examples of strike-slip morphologies (i.e., en echelon structures, strike-slip duplexes, laterally offset pre-existing features, and possible strained craters) from Galileo and Voyager images. We focus on complex structures associated with grooved terrain (e.g. Nun Sulcus, Dardanus Sulcus, Tiamat Sulcus, and Arbela Sulcus) and terrains transitional from dark to light terrain (e.g. the boundary between Nippur Sulcus and Marius Regio, including Byblus Sulcus and Philus Sulcus). Detailed structural interpretations suggest strong evidence of strike-slip faulting in some regions (i.e., Nun and Dardanus Sulcus); however, further investigation of additional strike-slip structures is required of less convincing regions (i.e., Byblus Sulcus). Where applicable, these results are synthesized into a global database representing an inferred sense of shear for many of Ganymede's fractures. Moreover, when combined with existing observations of extensional features, these results help to narrow down the range of possible principal stress directions that could have acted at the regional or global scale to produce grooved terrain on Ganymede.

  16. Genetic subspecies diversity of the chimpanzee CD4 virus-receptor gene

    DEFF Research Database (Denmark)

    Hvilsom, Christina; Carlsen, Frands; Siegismund, Hans R

    2008-01-01

    Chimpanzees are naturally and asymptomatically infected by simian immunodeficiency virus (SIV). Pathogenic properties of SIV/HIV vary and differences in susceptibility and pathogenicity of SIV/HIV depend in part on host-specific factors such as virus-receptor/co-receptor interactions. Since CD4...... plays a primary role in virus binding and since SIVcpz have been found only in two African chimpanzee subspecies, we characterized the genetic diversity of CD4 receptors in all four recognized subspecies of chimpanzees. We found noticeable variation in the first variable region V1 of CD4 and in intron...

  17. Estimating of higher order velocity moments and their derivatives in boundary layer by Smoke Image Velocimetry

    Science.gov (United States)

    Mikheev, N. I.; Goltsman, A. E.; Salekhova, I. G.; Saushin, I. I.

    2017-11-01

    The results of an experimental evaluation of the third-order moments profiles of velocity fluctuations and their partial derivatives in a zero pressure-gradient turbulent boundary layer are presented. Profiles of characteristics are estimated on the basis of the dynamics of two-component instantaneous velocity vector fields measured by the optical method Smoke Image Velocimetry (SIV). Comparison SIV-measurements with the results of measurements by a thermoanemometer and DNS data with similar Reθ and Reτ showed good agreement between the profiles of +, +, ∂+/∂y+ и ∂+/∂y+ obtained by SIV and DNS.

  18. Binaural-level functions in ferret auditory cortex: evidence for a continuous distribution of response properties.

    Science.gov (United States)

    Campbell, Robert A A; Schnupp, Jan W H; Shial, Akhil; King, Andrew J

    2006-06-01

    Many previous studies have subdivided auditory neurons into a number of physiological classes according to various criteria applied to their binaural response properties. However, it is often unclear whether such classifications represent discrete classes of neurons or whether they merely reflect a potentially convenient but ultimately arbitrary partitioning of a continuous underlying distribution of response properties. In this study we recorded the binaural response properties of 310 units in the auditory cortex of anesthetized ferrets, using an extensive range of interaural level differences (ILDs) and average binaural levels (ABLs). Most recordings were from primary auditory fields on the middle ectosylvian gyrus and from neurons with characteristic frequencies >5 kHz. We used simple multivariate statistics to quantify a fundamental coding feature: the shapes of the binaural response functions. The shapes of all 310 binaural response surfaces were represented as points in a five-dimensional principal component space. This space captured the underlying shape of all the binaural response surfaces. The distribution of binaural level functions was not homogeneous because some shapes were more common than others. Despite this, clustering validation techniques revealed no evidence for the existence of discrete, or partially overlapping, clusters that could serve as a basis for an objective classification of binaural-level functions. We also examined the gradients of the response functions for the population of units; these gradients were greatest near the midline, which is consistent with free-field data showing that cortical neurons are most sensitive to changes in stimulus location in this region of space.

  19. Determination of sulphite in wine by coulometric titration.

    Science.gov (United States)

    Lowinsohn, D; Bertotti, M

    2001-09-01

    A method for the determination of both free and bound S(IV) in white wine samples by coulometric titration with electrogenerated iodine is described, the S(IV) speciation being performed by extracting SO2 from samples acidified wiith hydrochloric acid. Titrations of samples treated with NaOH led to the total S(IV) concentration, the results being in agreement with the ones obtained by the distillation procedure as well as by using the classical Monier-Williams method. An average recovery of 97% was obtained for samples spiked with S(IV) in the range 0.4-1.2 mM, which demonstrated the validity of the proposed procedure. The repeatability was 1.3% and the limit of detection was estimated as 0.01 mM. Results from direct titrations of wine added to the electrochemical cell are reported, which give indications of the stability of adducts towards the reaction with iodine.

  20. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms

    National Research Council Canada - National Science Library

    Hansen, Scott G; Sacha, Jonah B; Hughes, Colette M; Ford, Julia C; Burwitz, Benjamin J; Scholz, Isabel; Gilbride, Roxanne M; Lewis, Matthew S; Gilliam, Awbrey N; Ventura, Abigail B; Malouli, Daniel; Xu, Guangwu; Richards, Rebecca; Whizin, Nathan; Reed, Jason S; Hammond, Katherine B; Fischer, Miranda; Turner, John M; Legasse, Alfred W; Axthelm, Michael K; Edlefsen, Paul T; Nelson, Jay A; Lifson, Jeffrey D; Früh, Klaus; Picker, Louis J

    2013-01-01

    ...) vectors elicit SIV-specific CD8(+) T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules...

  1. 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

    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....... 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...... 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...

  2. Swine Influenza Viruses – Evolution and Zoonotic Potential

    DEFF Research Database (Denmark)

    Fobian, Kristina

    virulent viruses with the capacity to cause severe pandemics. Therefore, it is important to gain a deeper understanding of the evolution of SIVs, their zoonotic potential as well as host-range characteristics and this PhD project aimed at elucidating parts of these important points. The PhD thesis begins...... that potentially indicated drift away from current H1 viruses. The time of most recent common ancestor for H1 was estimated to be markedly earlier than previously suggested. Phylogenetic analysis of the Danish N2 gene revealed that two different lineages are circulating in Denmark. Manuscript II describes...... the biological characterization of four different Danish SIVs and includes an experimental pathogenesis study performed in ferrets, which are regarded as the most appropriate small animal model for human IAV infections. The viruses chosen for this study were two enzootic SIVs (H3N2 and H1N2) and two new SIV...

  3. 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

  4. A novel aliasing-free subband information fusion approach for wideband sparse spectral estimation

    Science.gov (United States)

    Luo, Ji-An; Zhang, Xiao-Ping; Wang, Zhi

    2017-12-01

    Wideband sparse spectral estimation is generally formulated as a multi-dictionary/multi-measurement (MD/MM) problem which can be solved by using group sparsity techniques. In this paper, the MD/MM problem is reformulated as a single sparse indicative vector (SIV) recovery problem at the cost of introducing an additional system error. Thus, the number of unknowns is reduced greatly. We show that the system error can be neglected under certain conditions. We then present a new subband information fusion (SIF) method to estimate the SIV by jointly utilizing all the frequency bins. With orthogonal matching pursuit (OMP) leveraging the binary property of SIV's components, we develop a SIF-OMP algorithm to reconstruct the SIV. The numerical simulations demonstrate the performance of the proposed method.

  5. Can NK cells purge HIV sanctuaries?

    NARCIS (Netherlands)

    Bunders, Madeleine J.; Altfeld, Marcus

    2017-01-01

    A recent study identifies a population of CXCR5(+) natural killer (NK) cells patrolling B cell follicles in simian immunodeficiency virus (SIV)-infected African green monkeys that might contribute to the lack of disease progression in this nonpathogenic model

  6. New Diamond Color Center for Quantum Communication

    Science.gov (United States)

    Huang, Ding; Rose, Brendon; Tyryshkin, Alexei; Sangtawesin, Sorawis; Srinivasan, Srikanth; Twitchen, Daniel; Markham, Matthew; Edmonds, Andrew; Gali, Adam; Stacey, Alastair; Wang, Wuyi; D'Haenens-Johansson, Ulrika; Zaitsev, Alexandre; Lyon, Stephen; de Leon, Nathalie

    2017-04-01

    Color centers in diamond are attractive for quantum communication applications because of their long electron spin coherence times and efficient optical transitions. Previous demonstrations of color centers as solid-state spin qubits were primarily focused on centers that exhibit either long coherence times or highly efficient optical interfaces. Recently, we developed a method to stabilize the neutral charge state of silicon-vacancy center in diamond (SiV0) with high conversion efficiency. We observe spin relaxation times exceeding 1 minute and spin coherence times of 1 ms for SiV0 centers. Additionally, the SiV0 center also has > 90 % of its emission into its zero-phonon line and a narrow inhomogeneous optical linewidth. The combination of a long spin coherence time and efficient optical interface make the SiV0 center a promising candidate for applications in long distance quantum communication.

  7. 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.

  8. 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

    2011-11-01

    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. © 2011 Blackwell Publishing Ltd.

  9. Kumu täidavad rahvuslikud sümbolid, rasked valikud ja elav haridustöö / Marika Valk, Tiina Abel, Eha Komissarov...[jt.] ; interv. Ave Randviir

    Index Scriptorium Estoniae

    2006-01-01

    Eesti Kunstimuuseumi direktor Marika Valk, Kumu hariduskeskuse kunstnik-metoodik Anu Purre, Kumu kuraatorid Tiina Abel (püsiväljapanek Eesti kunsti klassikast ) ja Eha Komissarov (püsiväljapanek Eesti kunstist Teise Maailmasõja lõpust taasiseseisvumiseni) ning Kumu auditooriumi programmijuht-kuraator Maria-Kristiina Soomre uue muuseumi rollist, väljapanekutest, haridusprogrammidest. Lõpus "Pärle Kumu kuraatorite valikul"

  10. Risk of Immunodeficiency Virus Infection May Increase with Vaccine-Induced Immune Response

    OpenAIRE

    Tenbusch, Matthias; Ignatius, Ralf; Temchura, Vladimir; Nabi, Ghulam; Tippler, Bettina; Stewart-Jones, Guillaume; Salazar, Andres M.; Sauermann, Ulrike; Stahl-Hennig, Christiane; Überla, Klaus

    2012-01-01

    To explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for HIV infection, rhesus monkeys primed by different DNA vaccines were boosted with virus-like particles (VLP) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (SIV). Characteristic of the cellular immune response after the VLP booster immunization were high numbers of SIV-specific, gamma interferon-secreting cells after stimulation with inacti...

  11. Structure and Immunogenicity of Alternative Forms of the Simian Immunodeficiency Virus Gag Protein Expressed Using Venezuelan Equine Encephalitis Virus Replicon Particles

    OpenAIRE

    Cecil, Chad; West, Ande; Collier, Martha; Jurgens, Christy; Madden, Victoria; Whitmore, Alan; Johnston, Robert; Moore, Dominic T.; Swanstrom, Ronald; Davis, Nancy L.

    2007-01-01

    Venezuelan equine encephalitis virus replicon particles (VRP) were engineered to express different forms of SIV Gag to compare expression in vitro, formation of intra- and extracellular structures and induction of humoral and cellular immunity in mice. The three forms examined were full-length myristylated SIV Gag (Gagmyr+), full-length Gag lacking the myristylation signal (Gagmyr-), or a truncated form of Gagmyr- comprising only the matrix and capsid domains (MA/CA). Comparison of VRP-infect...

  12. Detection and Partial Characterization of Simian Immunodeficiency Virus SIVsm Strains from Bush Meat Samples from Rural Sierra Leone

    OpenAIRE

    Apetrei, Cristian; Metzger, Michael J.; Richardson, David; Ling, Binhua; Telfer, Paul T.; Reed, Patricia; Robertson, David L.; Marx, Preston A.

    2005-01-01

    Human immunodeficiency virus type 2 (HIV-2) originated from simian immunodeficiency viruses (SIVs) that naturally infect sooty mangabeys (SMs; Cercocebus atys). In order to further investigate the relationship between HIV-2 and SIVsm, the SIV specific to the SM, we characterized seven new SIVsm strains from SMs sold in Sierra Leone markets as bush meat. The gag, pol, and env sequences showed that, while the viruses of all seven SMs belonged to the SIVsm-HIV-2 lineage, they were highly diverge...

  13. Overcoming maternal antibody interference by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of swine influenza virus.

    Science.gov (United States)

    Wesley, Ronald D; Lager, Kelly M

    2006-11-26

    Sows and gilts lack immunity to human adenovirus 5 (Ad-5) vectored vaccines so immunogens of swine pathogens can be expressed with these vaccines in order to immunize suckling piglets that have interfering, maternally derived antibodies. In this study 7-day-old piglets, that had suckled H3N2 infected gilts, were sham-inoculated with a non-expressing Ad-5 vector or given a primary vaccination with replication-defective Ad-5 viruses expressed the H3 hemagglutinin and the nucleoprotein of swine influenza virus (SIV) subtype H3N2. The hemagglutination inhibition (HI) titer of the sham-inoculated group (n = 12) showed continued antibody decay whereas piglets vaccinated with Ad-5 SIV (n = 23) developed an active immune response by the second week post-vaccination. At 4 weeks-of-age when the HI titer of the sham-inoculated group had decayed to 45, the sham-inoculated group and half of the Ad-5 SIV vaccinated pigs were boosted with a commercial inactivated SIV vaccine. The boosted pigs that had been primed in the presence of maternal interfering antibodies had a strong anamnestic response while sham-inoculated pigs did not respond to the commercial vaccine. Two weeks after the booster vaccination the pigs were challenged with a non-homologous H3N2 virulent SIV. The efficacy of the vaccination protocol was demonstrated by abrogation of clinical signs, by clearance of challenge virus from pulmonary lavage fluids, by markedly reduced virus shedding in nasal secretions, and by the absence of moderate or severe SIV-induced lung lesions. These recombinant Ad-5 SIV vaccines are useful for priming the immune system to override the effects of maternally derived antibodies which interfere with conventional SIV vaccines.

  14. CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells.

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    Nichole R Klatt

    2010-01-01

    Full Text Available While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV and late (day 177 post-SIV chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.

  15. 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.

  16. Factors Influencing Seasonal Influenza Vaccination Uptake in Emergency Medical Services Workers: A Concept Mapping Approach.

    Science.gov (United States)

    Subramaniam, Dipti P; Baker, Elizabeth A; Zelicoff, Alan P; Elliott, Michael B

    2016-08-01

    Seasonal influenza has serious impacts on morbidity and mortality and has a significant economic toll through lost workforce time and strains on the health system. Health workers, particularly emergency medical services (EMS) workers have the potential to transmit influenza to those in their care, yet little is known of the factors that influence EMS workers' decisions regarding seasonal influenza vaccination (SIV) uptake, a key factor in reducing potential for transmitting disease. This study utilizes a modified Theory of Planned Behavior (TPB) model as a guiding framework to explore the factors that influence SIV uptake in EMS workers. Concept mapping, which consists of six-stages (preparation, generation, structuring, representation, interpretation, and utilization) that use quantitative and qualitative approaches, was used to identify participants' perspectives towards SIV. This study identified nine EMS-conceptualized factors that influence EMS workers' vaccination intent and behavior. The EMS-conceptualized factors align with the modified TPB model and suggest the need to consider community-wide approaches that were not initially conceptualized in the model. Additionally, the expansion of non-pharmaceutical measures went above and beyond original conceptualization. Overall, this study demonstrates the need to develop customized interventions such as messages highlighting the importance of EMS workers receiving SIV as the optimum solution. EMS workers who do not intend to receive the SIV should be provided with accurate information on the SIV to dispel misconceptions. Finally, EMS workers should also receive interventions which promote voluntary vaccination, encouraging them to be proactive in the health decisions they make for themselves.

  17. 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.

  18. 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.

  19. Abordagem simplificada do nervo ciático por via posterior, no ponto médio do sulco glúteo-femoral, com uso de neuroestimulador Abordaje simplificado del nervio ciático por vía posterior, en el punto medio del sulco glúteo-femoral, con uso de neuroestimulador Simplified sciatic nerve approach by the posterior route at the median gluteus-femoral sulcus region, with a neurostimulator

    OpenAIRE

    Neuber Martins Fonseca; Fernando Xavier Ferreira; Roberto Araújo Ruzi; Gulherme Carnaval Souza Pereira

    2002-01-01

    JUSTIFICATIVA E OBJETIVOS: O bloqueio do nervo ciático pode ser realizado por várias abordagens com vantagens e desvantagens. O nervo ciático é o maior nervo do corpo humano em diâmetro e comprimento. É a continuação do fascículo superior do plexo sacral (L4, L5, S1, S2 e S3). Sai da pelve através do forâmen isquiático maior, passando por baixo do músculo piriforme, desce entre o trocânter maior do fêmur e a tuberosidade isquiática, e ao longo do dorso da coxa, anterior aos músculos bíceps fe...

  20. 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.

  1. MORPHOMETRIC ANALYSES OF THE PARACENTRAL LOBE

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    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.

  2. Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

    Science.gov (United States)

    Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

    2017-09-01

    Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4(+) T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU(+)] CD163(+)), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants.IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model

  3. Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

    Science.gov (United States)

    Jensen, Kara; dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R.; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R.; Hudgens, Michael G.; Amedee, Angela; Kozlowski, Pamela A.; Estes, Jacob D.; Lifson, Jeffrey D.; Van Rompay, Koen K. A.; Larsen, Michelle

    2016-01-01

    ABSTRACT Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. PMID:27655885

  4. CD4+ levels control the odds of induction of humoral immune responses to tracer doses of therapeutic antibodies.

    Science.gov (United States)

    Srinivasula, Sharat; Gabriel, Erin; Kim, Insook; DeGrange, Paula; St Claire, Alexis; Mallow, Candace; Donahue, Robert E; Paik, Chang; Lane, H C; Di Mascio, Michele

    2017-01-01

    Rapidly increasing number of therapeutic antibodies are being repurposed to imaging probes for noninvasive diagnosis, as well as monitoring during treatment or disease recurrence. Though antibody-based imaging involves tracer doses (~3 log lower than therapeutic doses), and immune responses are severely reduced in patients with impaired immunity, formation of anti-tracer antibodies (ATA) has been observed hampering further diagnostic monitoring. Here, we explored the potential to develop humoral responses to intravenously administered tracer dose of a monoclonal antibody F(ab΄)2 fragment, and associated with host related immune measures in 49 rhesus macaques categorized into healthy (uninfected controls), SIV-progressors, SIV non-progressors, or total body irradiated (TBI). Antibody fragment administered in tracer amount (~100μg) induced immune responses with significantly lower odds in SIV-progressors or TBI macaques (P<0.005) as compared to healthy animals. Peripheral blood (PB) CD4+ cell counts, but not CD20+ cell levels, were associated with significantly higher risk of developing a humoral response (P<0.001). Doubling the PB CD4+ counts is associated with an odds ratio of developing an immune response of 1.73. Among SIV-infected animals, CD4+ cell count was a stronger predictor of immune response than plasma SIV-RNA levels. Both SIV-progressors and TBI macaques showed higher odds of responses with increasing CD4+ counts, however when compared to healthy or SIV non-progressors with similar CD4+ count, they were still functionally incompetent in generating a response (P<0.01). Moreover, presence of ATA in systemic circulation altered the in vivo biodistribution by increasing hepatic uptake and decreasing plasma radiotracer clearance, with minimal to no binding detected in targeted tissues.

  5. Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine.

    Science.gov (United States)

    Jensen, Kara; Dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R; Hudgens, Michael G; Amedee, Angela; Kozlowski, Pamela A; Estes, Jacob D; Lifson, Jeffrey D; Van Rompay, Koen K A; Larsen, Michelle; De Paris, Kristina

    2017-01-01

    Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. Copyright © 2017 American Society for Microbiology.

  6. 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

  7. Chronic Δ9-Tetrahydrocannabinol Administration May Not Attenuate Simian Immunodeficiency Virus Disease Progression in Female Rhesus Macaques

    Science.gov (United States)

    Amedee, Angela M.; Nichols, Whitney A.; LeCapitaine, Nicole J.; Stouwe, Curtis Vande; Birke, Leslie L.; Lacour, Nedra; Winsauer, Peter J.

    2014-01-01

    Abstract Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; Δ9-THC dronabinol). Previously, we demonstrated that chronic Δ9-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Δ9-THC (0.18–0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Δ9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ ratio, were not altered by Δ9-THC compared to control females; however, females that received chronic Δ9-THC did not gain as much weight as control animals. In addition, Δ9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+ and CD8+ T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Δ9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Δ9-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Δ9-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. PMID:25113915

  8. Real time reverse transcription (RRT)-polymerase chain reaction (PCR) methods for detection of pandemic (H1N1) 2009 influenza virus and European swine influenza A virus infections in pigs.

    Science.gov (United States)

    Slomka, Marek J; Densham, Anstice L E; Coward, Vivien J; Essen, Steve; Brookes, Sharon M; Irvine, Richard M; Spackman, Erica; Ridgeon, Jonathan; Gardner, Rebecca; Hanna, Amanda; Suarez, David L; Brown, Ian H

    2010-09-01

    There is a requirement to detect and differentiate pandemic (H1N1) 2009 (H1N1v) and established swine influenza A viruses (SIVs) by real time reverse transcription (RRT) PCR methods. First, modify an existing matrix (M) gene RRT PCR for sensitive generic detection of H1N1v and other European SIVs. Second, design an H1 RRT PCR to specifically detect H1N1v infections. RRT PCR assays were used to test laboratory isolates of SIV (n = 51; 37 European and 14 North American), H1N1v (n = 5) and avian influenza virus (AIV; n = 43). Diagnostic sensitivity and specificity were calculated for swabs (n = 133) and tissues (n = 116) collected from field cases and pigs infected experimentally with SIVs and H1N1v. The "perfect match" M gene RRT PCR was the most sensitive variant of this test for detection of established European SIVs and H1N1v. H1 RRT PCR specifically detected H1N1v but not European SIVs. Validation with clinical specimens included comparison with virus isolation (VI) as a "gold standard", while field infection with H1N1v in swine was independently confirmed by sequencing H1N1v amplified by conventional RT PCR. "Perfect match" M gene RRT PCR had 100% sensitivity and 95.2% specificity for swabs, 93.6% and 98.6% for tissues. H1 RRT PCR demonstrated sensitivity and specificity of 100% and 99.1%, respectively, for the swabs, and 100% and 100% for the tissues. Two RRT PCRs for the purposes of (i) generic detection of SIV and H1N1v infection in European pigs, and for (ii) specific detection of H1N1v (pandemic influenza) infection were validated.

  9. Ultrasound Biomicroscopy Comparison of Ab Interno and Ab Externo Intraocular Lens Scleral Fixation.

    Science.gov (United States)

    Horiguchi, Lie; Garcia, Patricia Novita; Malavazzi, Gustavo Ricci; Allemann, Norma; Gomes, Rachel L R

    2016-01-01

    Purpose. To compare ab interno and ab externo scleral fixation of posterior chamber intraocular lenses (PCIOL) using ultrasound biomicroscopy (UBM). Methods. Randomized patients underwent ab externo or ab interno scleral fixation of a PCIOL. Ultrasound biomicroscopy was performed 3 to 6 months postoperatively, to determine PCIOL centration, IOL distance to the iris at 12, 3, 6, and 9 hours, and haptics placement in relation to the ciliary sulcus. Results. Fifteen patients were enrolled in the study. The ab externo technique was used in 7 eyes (46.6%) and the ab interno in 8 eyes (53.3%). In the ab externo technique, 14 haptics were located: 4 (28.57%) in the ciliary sulcus; 2 (14.28%) anterior to the sulcus; and 8 (57.14%) posterior to the sulcus, 6 in the ciliary body and 2 posterior to the ciliary body. In the ab interno group, 4 haptics (25.0%) were in the ciliary sulcus, 2 (12.50%) anterior to the sulcus, and 10 (75.0%) posterior to the sulcus, 4 in the ciliary body and 6 posterior to the ciliary body. Conclusions. Ab externo and ab interno scleral fixation techniques presented similar results in haptic placement. Ab externo technique presented higher vertical tilt when compared to the ab interno.

  10. Ultrasound Biomicroscopy Comparison of Ab Interno and Ab Externo Intraocular Lens Scleral Fixation

    Directory of Open Access Journals (Sweden)

    Lie Horiguchi

    2016-01-01

    Full Text Available Purpose. To compare ab interno and ab externo scleral fixation of posterior chamber intraocular lenses (PCIOL using ultrasound biomicroscopy (UBM. Methods. Randomized patients underwent ab externo or ab interno scleral fixation of a PCIOL. Ultrasound biomicroscopy was performed 3 to 6 months postoperatively, to determine PCIOL centration, IOL distance to the iris at 12, 3, 6, and 9 hours, and haptics placement in relation to the ciliary sulcus. Results. Fifteen patients were enrolled in the study. The ab externo technique was used in 7 eyes (46.6% and the ab interno in 8 eyes (53.3%. In the ab externo technique, 14 haptics were located: 4 (28.57% in the ciliary sulcus; 2 (14.28% anterior to the sulcus; and 8 (57.14% posterior to the sulcus, 6 in the ciliary body and 2 posterior to the ciliary body. In the ab interno group, 4 haptics (25.0% were in the ciliary sulcus, 2 (12.50% anterior to the sulcus, and 10 (75.0% posterior to the sulcus, 4 in the ciliary body and 6 posterior to the ciliary body. Conclusions. Ab externo and ab interno scleral fixation techniques presented similar results in haptic placement. Ab externo technique presented higher vertical tilt when compared to the ab interno.

  11. 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

  12. 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

  13. Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin.

    Science.gov (United States)

    Wei, Qiang; Liu, Li; Cong, Zhe; Wu, Xiaoxian; Wang, Hui; Qin, Chuan; Molina, Patricia; Chen, Zhiwei

    2016-09-01

    Delta9-tetrahydrocannabinol (Δ(9)-THC) is the major psychoactive component of the cannabis plant. Δ(9)-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ(9)-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ(9)-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIVmac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ(9)-THC(+)SIV(+), Δ(9)-THC(+)SIV(-), PBO/SIV(+) and PBO/SIV(-) (n = 4/group). One-month after daily Δ(9)-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251/CNS, which was isolated from the brain of a Chinese macaque with end-staged neuroAIDS. No significant differences in peak and steady state plasma viral loads were seen between Δ(9)-THC(+)SIV(+) and PBO/SIV(+) macaques. Regardless of Δ(9)-THC, all infected macaques displayed significant drop of CD4/CD8 T cell ratio, loss of CD4(+) T cells and higher persistent levels of Ki67(+)CD8(+) T cells compared with uninfected animals. Moreover, long-term Δ(9)-THC treatment reduced significantly the frequency of circulating IgE(+)B cells. Only one Δ(9)-THC(+)SIV(+) macaque died of simian AIDS with paralyzed limbs compared with two deaths in the PBO/SIV(+) group during the study period. These findings indicate that chronic Δ(9)-THC administration resulted in reduction of IgE(+)B cells, yet it unlikely enhanced pathogenic SIVmac251/CNS infection in male Rhesus macaques of Chinese origin.

  14. 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.

  15. Sulfate production by reactive bromine: Implications for the global sulfur and reactive bromine budgets

    Science.gov (United States)

    Chen, Q.; Schmidt, J. A.; Shah, V.; Jaeglé, L.; Sherwen, T.; Alexander, B.

    2017-07-01

    Sulfur and reactive bromine (Bry) play important roles in tropospheric chemistry and the global radiation budget. The oxidation of dissolved SO2 (S(IV)) by HOBr increases sulfate aerosol abundance and may also impact the Bry budget, but is generally not included in global climate and chemistry models. In this study, we implement HOBr + S(IV) reactions into the GEOS-Chem global chemical transport model and evaluate the global impacts on both sulfur and Bry budgets. Modeled HOBr mixing ratios on the order of 0.1-1.0 parts per trillion (ppt) lead to HOBr + S(IV) contributing to 8% of global sulfate production and up to 45% over some tropical ocean regions with high HOBr mixing ratios (0.6-0.9 ppt). Inclusion of HOBr + S(IV) in the model leads to a global Bry decrease of 50%, initiated by the decrease in bromide recycling in cloud droplets. Observations of HOBr are necessary to better understand the role of HOBr + S(IV) in tropospheric sulfur and Bry cycles.

  16. The relationship of personality dimensions in adult male rhesus macaques to progression of simian immunodeficiency virus disease.

    Science.gov (United States)

    Capitanio, J P; Mendoza, S P; Baroncelli, S

    1999-06-01

    Studies of nonhuman primate personality have suggested that physiological correlates of relevant behavioral dimensions exist. The present study examined personality using techniques similar to those employed in human personality research. Adult male rhesus monkeys were each rated on 25 adjectives while living in their natal groups. Approximately 1.5 years later, 18 animals were inoculated with the simian immunodeficiency virus (SIV) and exposed to socially stable or socially unstable conditions. Behavior, viral load (SIV RNA), plasma cortisol concentrations, and the IgG response to SIV and to rhesus cytomegalovirus were measured at regular intervals. Multiple regression analyses revealed that the four personality dimensions (Sociability, Confidence, Equability, Excitability) were correlated with various measures. Following inoculation with SIV, animals higher in Sociability showed a more rapid decline in plasma cortisol concentrations, elevations in the anti-RhCMV IgG response, and a decline in SIV RNA. The results indicate that personality factors in rhesus monkeys do have physiological correlates that have significance for disease processes and that in the context of a social manipulation, Sociability, reflecting the tendency to engage in affiliative interactions, is an important factor in explaining outcome measures at early time points. Copyright 1999 Academic Press.

  17. Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

    Science.gov (United States)

    Klatt, Nichole R.; Canary, Lauren A.; Vanderford, Thomas H.; Vinton, Carol L.; Engram, Jessica C.; Dunham, Richard M.; Cronise, Heather E.; Swerczek, Joanna M.; Lafont, Bernard A. P.; Picker, Louis J.; Silvestri, Guido

    2012-01-01

    Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4+ T cell depletion, as CD4+ T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression. PMID:22090099

  18. Full molecular characterization of a simian immunodeficiency virus, SIVwrcpbt from Temminck's red colobus (Piliocolobus badius temminckii) from Abuko Nature Reserve, The Gambia.

    Science.gov (United States)

    Locatelli, Sabrina; Lafay, Bénédicte; Liegeois, Florian; Ting, Nelson; Delaporte, Eric; Peeters, Martine

    2008-06-20

    Simian immunodeficiency viruses (SIVs) are found in an extensive number of African primates, and humans continue to be exposed to these viruses by hunting and handling of primate bushmeat. The purpose of our study was to examine to what extent Piliocolobus badius subspecies are infected with SIV in order to better characterize SIVwrc in general and to gain further insight into the impact of geographic barriers and subspeciation on the evolution of SIVwrc. We analysed sixteen faecal samples and two tissue samples of the P. b. temminckii subspecies collected in the Abuko Nature Reserve (The Gambia, West Africa). SIV infection could only be identified in one tissue sample, and phylogenetic tree analyses of partial pol and env sequences showed that the new SIVwrcPbt virus is closely related to SIVwrcPbb strains from P. b. badius in the Taï forest (Côte d'Ivoire), thus suggesting that geographically separated subspecies are infected with a closely related virus. Molecular characterization and phylogenetic analysis of the full-length genome sequence confirmed that SIVwrcPbt is a species-specific SIV lineage, although it is distantly related to the SIVlho and SIVsun lineages across its entire genome. Characterization of additional SIVwrc viruses is needed to understand the ancestral phylogenetic relation to SIVs from l'Hoest and sun-tailed monkeys and whether recombination occurred between ancestors of the SIVwrc and SIVlho/sun lineages.

  19. Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA.

    Science.gov (United States)

    Gordon, Shari N; Kines, Rhonda C; Kutsyna, Galyna; Ma, Zhong-Min; Hryniewicz, Anna; Roberts, Jeffery N; Fenizia, Claudio; Hidajat, Rachmat; Brocca-Cofano, Egidio; Cuburu, Nicolas; Buck, Christopher B; Bernardo, Marcelino L; Robert-Guroff, Marjorie; Miller, Christopher J; Graham, Barney S; Lowy, Douglas R; Schiller, John T; Franchini, Genoveffa

    2012-01-15

    The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV. We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV(mac251.) HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.

  20. A challenge to the ancient origin of SIVagm based on African green monkey mitochondrial genomes.

    Directory of Open Access Journals (Sweden)

    Joel O Wertheim

    2007-07-01

    Full Text Available While the circumstances surrounding the origin and spread of HIV are becoming clearer, the particulars of the origin of simian immunodeficiency virus (SIV are still unknown. Specifically, the age of SIV, whether it is an ancient or recent infection, has not been resolved. Although many instances of cross-species transmission of SIV have been documented, the similarity between the African green monkey (AGM and SIVagm phylogenies has long been held as suggestive of ancient codivergence between SIVs and their primate hosts. Here, we present well-resolved phylogenies based on full-length AGM mitochondrial genomes and seven previously published SIVagm genomes; these allowed us to perform the first rigorous phylogenetic test to our knowledge of the hypothesis that SIVagm codiverged with the AGMs. Using the Shimodaira-Hasegawa test, we show that the AGM mitochondrial genomes and SIVagm did not evolve along the same topology. Furthermore, we demonstrate that the SIVagm topology can be explained by a pattern of west-to-east transmission of the virus across existing AGM geographic ranges. Using a relaxed molecular clock, we also provide a date for the most recent common ancestor of the AGMs at approximately 3 million years ago. This study substantially weakens the theory of ancient SIV infection followed by codivergence with its primate hosts.

  1. Mode of Effective Connectivity within a Putative Neural Network Differentiates Moral Cognitions Related to Care and Justice Ethics: e14730

    National Research Council Canada - National Science Library

    Ricardo Cáceda; G Andrew James; Timothy D Ely; John Snarey; Clinton D Kilts

    2011-01-01

    ...) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition...

  2. Mode of effective connectivity within a putative neural network differentiates moral cognitions related to care and justice ethics

    National Research Council Canada - National Science Library

    Cáceda, Ricardo; James, G Andrew; Ely, Timothy D; Snarey, John; Kilts, Clinton D

    2011-01-01

    ...) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition...

  3. Surgery of the eloquent area using neuronavigation system

    Energy Technology Data Exchange (ETDEWEB)

    Nakai, Hirofumi; Tanaka, Tatsuya; Hashizume, Kiyotaka; Hodozuka, Akira [Asahikawa Medical Coll., Hokkaido (Japan)

    2001-09-01

    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)

  4. 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

  5. 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.

  6. 9 CFR 11.21 - Inspection procedures for designated qualified persons (DQP's).

    Science.gov (United States)

    2010-01-01

    ... (flexor) surface. The DQP shall apply digital pressure to the pocket (sulcus), including the bulbs of the heel, and continue the palpation to the medial and lateral surfaces of the pastern, being careful to...

  7. Contorted and ordinary body postures in the human brain

    NARCIS (Netherlands)

    Cross, E.S.; Mackie, E.C.; Wolford, G.; Hamilton, A.F.D.C.

    2010-01-01

    Social interaction and comprehension of non-verbal behaviour requires a representation of people's bodies. Research into the neural underpinnings of body representation implicates several brain regions including extrastriate and fusiform body areas (EBA and FBA), superior temporal sulcus (STS),

  8. Molecular and Genetic Investigation of Tau in Chronic Traumatic Encephalopthy

    Science.gov (United States)

    2016-10-01

    Pure CTE Pure CTE Abundant macrophages, gliosis in white matter, several tangles Hemosiderin present in dilated vessels. No visible tau...Possible pretangles around sulcus. Hemosiderin common around vessels. No tangles or 9 Controls macrophages. 10 Controls Vacuolization in

  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. 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.

  11. Proceedings of the fourth National Congress of the Italian Society of Virology.

    Science.gov (United States)

    Salata, Cristiano; Parolin, Cristina; Palù, Giorgio

    2005-09-01

    The aim of the yearly National Congress of the Italian Society of Virology (SIV) is to promote the discussion between senior and younger researchers to improve the knowledge and scientific collaboration among the various areas of Virology. The invited and selected lecturers of the fourth National Congress of SIV covered the following topics: general Virology and viral Genetics; virus host interactions and pathogenesis; viral immunology and vaccines; emerging and re-emerging viral diseases; antiviral therapy; innovative diagnostics; viral biotechnologies and gene therapy. As in the previous edition (Salata and Palù, 2004 J Cell Physiol 199:171-173), a specific topic was thoroughly covered in a roundtable. In this edition the overviewed topic was HCV, from epidemiology and genetic variability to immunology and antiviral therapy. The final program can be found at the web site http://www.siv-virologia.it. A summary of the oral presentations of the 2004 meeting is reported. Copyright 2005 Wiley-Liss, Inc.

  12. Identification and structural characterization of the ALIX-binding late domains of simian immunodeficiency virus SIVmac239 and SIVagmTan-1.

    Science.gov (United States)

    Zhai, Qianting; Landesman, Michael B; Robinson, Howard; Sundquist, Wesley I; Hill, Christopher P

    2011-01-01

    Retroviral Gag proteins contain short late-domain motifs that recruit cellular ESCRT pathway proteins to facilitate virus budding. ALIX-binding late domains often contain the core consensus sequence YPX(n)L (where X(n) can vary in sequence and length). However, some simian immunodeficiency virus (SIV) Gag proteins lack this consensus sequence, yet still bind ALIX. We mapped divergent, ALIX-binding late domains within the p6(Gag) proteins of SIV(mac239) ((40)SREKPYKEVTEDLLHLNSLF(59)) and SIV(agmTan-1) ((24)AAGAYDPARKLLEQYAKK(41)). Crystal structures revealed that anchoring tyrosines (in lightface) and nearby hydrophobic residues (underlined) contact the ALIX V domain, revealing how lentiviruses employ a diverse family of late-domain sequences to bind ALIX and promote virus budding.

  13. Linking pig-tailed macaque major histocompatibility complex class I haplotypes and cytotoxic T lymphocyte escape mutations in simian immunodeficiency virus infection.

    Science.gov (United States)

    Gooneratne, Shayarana L; Alinejad-Rokny, Hamid; Ebrahimi, Diako; Bohn, Patrick S; Wiseman, Roger W; O'Connor, David H; Davenport, Miles P; Kent, Stephen J

    2014-12-01

    The influence of major histocompatibility complex class I (MHC-I) alleles on human immunodeficiency virus (HIV) diversity in humans has been well characterized at the population level. MHC-I alleles likely affect viral diversity in the simian immunodeficiency virus (SIV)-infected pig-tailed macaque (Macaca nemestrina) model, but this is poorly characterized. We studied the evolution of SIV in pig-tailed macaques with a range of MHC-I haplotypes. SIV(mac251) genomes were amplified from the plasma of 44 pig-tailed macaques infected with SIV(mac251) at 4 to 10 months after infection and characterized by Illumina deep sequencing. MHC-I typing was performed on cellular RNA using Roche/454 pyrosequencing. MHC-I haplotypes and viral sequence polymorphisms at both individual mutations and groups of mutations spanning 10-amino-acid segments were linked using in-house bioinformatics pipelines, since cytotoxic T lymphocyte (CTL) escape can occur at different amino acids within the same epitope in different animals. The approach successfully identified 6 known CTL escape mutations within 3 Mane-A1*084-restricted epitopes. The approach also identified over 70 new SIV polymorphisms linked to a variety of MHC-I haplotypes. Using functional CD8 T cell assays, we confirmed that one of these associations, a Mane-B028 haplotype-linked mutation in Nef, corresponded to a CTL epitope. We also identified mutations associated with the Mane-B017 haplotype that were previously described to be CTL epitopes restricted by Mamu-B*017:01 in rhesus macaques. This detailed study of pig-tailed macaque MHC-I genetics and SIV polymorphisms will enable a refined level of analysis for future vaccine design and strategies for treatment of HIV infection. Cytotoxic T lymphocytes select for virus escape mutants of HIV and SIV, and this limits the effectiveness of vaccines and immunotherapies against these viruses. Patterns of immune escape variants are similar in HIV type 1-infected human subjects that

  14. Trained Immunity and Susceptibility to HIV.

    Science.gov (United States)

    Derrick, Steven C

    2017-01-01

    In this issue of Clinical and Vaccine Immunology, K. Jensen et al. (Clin Vaccine Immunol 24:e00360-16, 2017, https://doi.org/10.1128/CVI.00360-16) describe a dual-purpose attenuated Mycobacterium tuberculosis-simian immunodeficiency virus vaccine (AMTB-SIV). Interestingly, immunized infant macaques required fewer oral exposures to SIV to become infected relative to nonimmunized animals. The authors hypothesized that augmented susceptibility to SIV was due to activation of CD4+ T cells through trained immunity. This commentary explores the possible relationship between trained immunity, enhanced CD4 T cell responses, and increased susceptibility to human immunodeficiency virus (HIV). Copyright © 2017 American Society for Microbiology.

  15. Technique for velocity vector field dynamics measurement on the basis of smoke visualization of flow

    Science.gov (United States)

    Mikheev, N. I.; Dushin, N. S.; Saushin, I. I.

    2017-09-01

    The main difference between Smoke Image Velocimetry (SIV) technique and traditional PIV is that the smoke with continuous intensity in the image is seeded into the flow instead of separate particles. Owing to better smoke reflectivity, relatively primitive equipment is enough to measure the dynamics of velocity vector fields with the frequency of 25 kHz and higher. The image processing algorithm is adapted to high tracer concentration and relatively large displacement of smoke patches between two consecutive frames. The results of SIV testing are presented, including the estimations of the most measurement noise sensitive characteristics of turbulence calculated from spatial derivatives of fluctuations of small-scale turbulence. The measurement results have been shown to agree well with the data obtained by other methods. Application of SIV technique opens new possibilities in the research of flow pattern and turbulence in unsteady and fast processes.

  16. Neural correlates of successful and unsuccessful syntactic processing in primary progressive aphasia

    Directory of Open Access Journals (Sweden)

    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.

  17. Soft-tissue cephalometric norms for the Lambada population in Telangana Region of Andhra Pradesh

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. Pregnancy outcome and clinical status of gilts following experimental infection by H1N2, H3N2 and H1N1pdm09 influenza A viruses during the last month of gestation.

    Science.gov (United States)

    Kwit, Krzysztof; Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona

    2015-10-01

    The present study was planned to study the effect of various subtypes of swine influenza virus (SIV) circulating among pigs (H1N2, H3N2 and emerging pandemic strain of H1N1 influenza A virus (H1N1pdm09) on the course of pregnancy in naïve gilts experimentally infected during the last month of pregnancy. In addition, the clinical course of infection, distribution of viruses in various tissues (blood, placenta, fetal lung), and selected immunological, reproductive and productive parameters were also investigated. All SIV-inoculated gilts became infected. No abortions, stillbirths, intrauterine deaths or mummified fetuses were observed. No clinical signs of influenza virus infection or other disorders were observed in piglets born from infected and control gilts. There was a significant decrease in the number and frequency of lymphocytes in gilts inoculated with all influenza viruses. In general, the concentrations of IL-6, IL-10 and TNF-α were significantly higher in SIV-inoculated gilts as than in control animals, while IL-4 and IFN-γ were not detected in plasma at any time post-inoculation in SIV- or mock-inoculated gilts. No evidence for transplacental transmission of SIV was found. Viremia was also not observed in any of the infected females. On the basis of recent results, we hypothesize that pregnancy failure observed during SIV infection under field conditions is probably related to high fever and pro-inflammatory cytokines rather than a direct effect of the virus on the placenta, embryo or fetus.

  1. 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.

  2. 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.

  3. Rhesus macaque model of chronic opiate dependence and neuro-AIDS: longitudinal assessment of auditory brainstem responses and visual evoked potentials.

    Science.gov (United States)

    Riazi, Mariam; Marcario, Joanne K; Samson, Frank K; Kenjale, Himanshu; Adany, Istvan; Staggs, Vincent; Ledford, Emily; Marquis, Janet; Narayan, Opendra; Cheney, Paul D

    2009-06-01

    Our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a rhesus macaque model of neuro-AIDS utilizing a chronic continuous drug delivery paradigm. The goal of this study was to clarify whether morphine is protective, or if it exacerbates simian immunodeficiency virus (SIV)-related systemic and neurological disease. Our model employs a macrophage tropic CD4/CCR5 coreceptor virus, SIV(mac)239 (R71/E17), which crosses the blood-brain barrier shortly after inoculation and closely mimics the natural disease course of human immunodeficiency virus infection. The cohort was divided into three groups: morphine only, SIV only, and SIV + morphine. Evoked potential (EP) abnormalities in subclinically infected macaques were evident as early as 8 weeks postinoculation. Prolongations in EP latencies were observed in SIV-infected macaques across all modalities. Animals with the highest cerebrospinal fluid viral loads and clinical disease showed more abnormalities than those with subclinical disease, confirming our previous work (Raymond et al., J Neurovirol 4:512-520, 1998; J Neurovirol 5:217-231, 1999; AIDS Res Hum Retroviruses 16:1163-1173, 2000). Although some differences were observed in auditory and visual evoked potentials in morphine-treated compared to morphine-untreated SIV-infected animals, the effects were relatively small and not consistent across evoked potential type. However, morphine-treated animals with subclinical disease had a clear tendency toward higher virus loads in peripheral and central nervous system tissues (Marcario et al., J Neuroimmune Pharmacol 3:12-25, 2008) suggesting that if had been possible to follow all animals to end-stage disease, a clearer pattern of evoked potential abnormality might have emerged.

  4. 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.

  5. 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.

  6. Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells

    OpenAIRE

    Kamada, Kazuya; IGARASHI, Tatsuhiko; Martin, Malcolm A.; KHAMSRI, BOONRUANG; Hatcho, Kazuki; Yamashita, Tomoki; Fujita, Mikako; Uchiyama, Tsuneo; Adachi, Akio

    2006-01-01

    The narrow host range of human immunodeficiency virus type 1 (HIV-1) is caused in part by innate cellular factors such as apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) and TRIM5α, which restrict virus replication in monkey cells. Variant HIV-1 molecular clones containing both a 21-nucleotide simian immunodeficiency virus (SIV) Gag CA element, corresponding to the HIV-1 cyclophilin A-binding site, and the entire SIV vif gene were constructed. Long-term passage i...

  7. A significant productive in vivo infection of resting cells with simian immunodeficiency virus in a macaque with AIDS.

    Science.gov (United States)

    Pahar, Bapi; Lala, Wendy; Kuebler, Dot; Liu, David

    2017-04-01

    Identifying the cells that can be infected with HIV in vivo and thus potentially persist as latent reservoirs is of high priority. Here, we report the major infected cells in a chronically simian immunodeficiency virus (SIV)-infected macaque that developed AIDS and encephalitis. A majority of the infected cells were detected as non-proliferating resting cells. SIV-infected non-proliferating resting cells were found to be playing an important role in viral pathogenesis, persistence, or reservoir formation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Pregnant Guppy in Flight

    Science.gov (United States)

    1960-01-01

    The Pregnant Guppy is a modified Boeing B-377 Stratocruiser used to transport the S-IV (second) stage for the Saturn I launch vehicle between manufacturing facilities on the West coast, and testing and launch facilities in the Southeast. The fuselage of the B-377 was lengthened to accommodate the S-IV stage and the plane's cabin section was enlarged to approximately double its normal volume. The idea was originated by John M. Conroy of Aero Spaceliners, Incorporated, in Van Nuys, California. The former Stratocruiser became a B-377 PG: the Pregnant Guppy. This photograph depicts the Pregnant Guppy in flight.

  9. Transmission of simian immunodeficiency virus carrying multiple cytotoxic T-lymphocyte escape mutations with diminished replicative ability can result in AIDS progression in rhesus macaques.

    Science.gov (United States)

    Seki, Sayuri; Kawada, Miki; Takeda, Akiko; Igarashi, Hiroko; Sata, Tetsutaro; Matano, Tetsuro

    2008-05-01

    Cytotoxic T-lymphocyte (CTL) responses frequently select for immunodeficiency virus mutations that result in escape from CTL recognition with viral fitness costs. The replication in vivo of such viruses carrying not single but multiple escape mutations in the absence of the CTL pressure has remained undetermined. Here, we have examined the replication of simian immunodeficiency virus (SIV) with five gag mutations selected in a macaque possessing the major histocompatibility complex haplotype 90-120-Ia after its transmission into 90-120-Ia-negative macaques. Our results showed that even such a "crippled" SIV infection can result in persistent viral replication, multiple reversions, and AIDS progression.

  10. Subdivisions and connectional networks of the lateral prefrontal cortex in the macaque monkey.

    Science.gov (United States)

    Saleem, Kadharbatcha S; Miller, Brad; Price, Joseph L

    2014-05-01

    Neuroanatomical studies have long indicated that corticocortical connections are organized in networks that relate distinct sets of areas. Such networks have been emphasized by development of functional imaging methods for correlating activity across the cortex. Previously, two networks were recognized in the orbitomedial prefrontal cortex, the "orbital" and "medial" networks (OPFC and MPFC, respectively). In this study, three additional networks are proposed for the lateral prefrontal cortex: 1) a ventrolateral network (VLPFC) in and ventral to the principal sulcus; 2) a dorsal network (DPFC) in and dorsal to the principal sulcus and in the frontal pole; 3) a caudolateral network (CLPFC) in and rostral to the arcuate sulcus and the caudal principal sulcus. The connections of the first two networks are described here. Areas in each network are connected primarily with other areas in the same network, with overlaps around the principal sulcus. The VLPFC and DPFC are also connected with the OPFC and MPFC, respectively. Outside the prefrontal cortex, the VLPFC connects with specific areas related to somatic/visceral sensation and vision, in the frontoparietal operculum, insula, ventral bank/fundus of the superior temporal sulcus, inferior temporal gyrus, and inferior parietal cortex. In contrast, the DPFC connects with the rostral superior temporal gyrus, dorsal bank of the superior temporal sulcus, parahippocampal cortex, and posterior cingulate and retrosplenial cortex. Area 45a, in caudal VLPFC, is unique, having connections with all the networks. Its extrinsic connections resemble those of the DPFC. In addition, it has connections with both auditory belt/parabelt areas, and visual related areas. Copyright © 2013 Wiley Periodicals, Inc.

  11. Conditional virus replication as an approach to a safe live attenuated human immunodeficiency virus vaccine

    NARCIS (Netherlands)

    Berkhout, Ben; Verhoef, Koen; Marzio, Giuseppe; Klaver, Bep; Vink, Monique; Zhou, Xue; Das, Atze T.

    2002-01-01

    Despite intensive efforts, no safe and effective vaccine has been developed for the prophylaxis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Studies with the simian immunodeficiency virus (SIV)/macaque model demonstrated that live attenuated viruses are the most

  12. Structural and catalytic properties of a novel vanadium containing ...

    Indian Academy of Sciences (India)

    Abstract. A novel vanadium containing solid core mesoporous silica shell catalyst was synthesized with different Si/V ratios by sol-gel method under neutral conditions. The synthesized materials were characterized by various techniques and gas phase diphenyl methane oxidation reaction. The mesoporosity combined with ...

  13. Contributions of Mamu-A*01 status and TRIM5 allele expression, but not CCL3L copy number variation, to the control of SIVmac251 replication in Indian-origin rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    So-Yon Lim

    2010-06-01

    Full Text Available CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L copy number variation (CNV is associated with resistance to HIV-1 acquisition and with both viral load and disease progression following infection with HIV-1. An association has also been reported between CCL3L CNV and clinical sequelae of the simian immunodeficiency virus (SIV infection in vivo in rhesus monkeys. The present study was initiated to explore the possibility of an association of CCL3L CNV with the control of virus replication and AIDS progression in a carefully defined cohort of SIVmac251-infected, Indian-origin rhesus monkeys. Although we demonstrated extensive variation in copy number of CCL3L in this cohort of monkeys, CCL3L CNV was not significantly associated with either peak or set-point plasma SIV RNA levels in these monkeys when MHC class I allele Mamu-A*01 was included in the models or progression to AIDS in these monkeys. With 66 monkeys in the study, there was adequate power for these tests if the correlation of CCL3L and either peak or set-point plasma SIV RNA levels was 0.34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis.

  14. Contributions of Mamu-A*01 status and TRIM5 allele expression, but not CCL3L copy number variation, to the control of SIVmac251 replication in Indian-origin rhesus monkeys.

    Science.gov (United States)

    Lim, So-Yon; Chan, Tiffany; Gelman, Rebecca S; Whitney, James B; O'Brien, Kara L; Barouch, Dan H; Goldstein, David B; Haynes, Barton F; Letvin, Norman L

    2010-06-24

    CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral load and disease progression following infection with HIV-1. An association has also been reported between CCL3L CNV and clinical sequelae of the simian immunodeficiency virus (SIV) infection in vivo in rhesus monkeys. The present study was initiated to explore the possibility of an association of CCL3L CNV with the control of virus replication and AIDS progression in a carefully defined cohort of SIVmac251-infected, Indian-origin rhesus monkeys. Although we demonstrated extensive variation in copy number of CCL3L in this cohort of monkeys, CCL3L CNV was not significantly associated with either peak or set-point plasma SIV RNA levels in these monkeys when MHC class I allele Mamu-A*01 was included in the models or progression to AIDS in these monkeys. With 66 monkeys in the study, there was adequate power for these tests if the correlation of CCL3L and either peak or set-point plasma SIV RNA levels was 0.34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis.

  15. 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

  16. Vaccine-induced virus-neutralizing antibodies and cytotoxic T cells do not protect macaques from experimental infection with simian immunodeficiency virus SIVmac32H (J5).

    NARCIS (Netherlands)

    E.G.J. Hulskotte (Ellen); A.M. Geretti (Anna Maria); C.H.J. Siebelink (Kees); G. van Amerongen (Geert); M.P. Cranage (Martin); E. Rud; S.G. Norley (Stephen); P. de Vries (Petra); A.D.M.E. Osterhaus (Albert)

    1995-01-01

    textabstractTo gain further insight into the ability of subunit vaccines to protect monkeys from experimental infection with simian immunodeficiency virus (SIV), two groups of cynomolgus macaques were immunized with either recombinant SIVmac32H-derived envelope glycoproteins (Env) incorporated into

  17. african journal of clinical and experimental microbkoidgy ajcem ...

    African Journals Online (AJOL)

    CHANGES INfiZV'SIV'IERIPHERAL LEUKOCYTE AND BODY FLUIDS OF. ONCHOCERCIASIS PATIENTS ... This study evaluated the peripheral leukocyte count and the presence of microfllariae in the body fluids of onchocerciasis patients treated with ... immunological balance of the host. The present study was designed ...

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

    Science.gov (United States)

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

    2014-01-01

    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. PMID:24781023

  19. Kinetics and mechanism of the reactions of hexaaqua rhodium (III ...

    Indian Academy of Sciences (India)

    Unknown

    RhOH2. 3+ + SIV for which fast formation of the O- bonded sulphito complex was observed.9 Several. (aqua)(amine)cobalt (III) ions have been shown to undergo fast and reversible formation of the O-bon- ded sulphito complexes in the presence of SO2 in mild acidic media.8. On immediate acidification of the reaction mix-.

  20. Polyoxometalate delignification of birch kraft pulp and effect on residual lignin

    Science.gov (United States)

    Biljana Bujanovic; Richard S. Reiner; Sally A. Ralph; Rajai H. Atalla

    2011-01-01

    To advance the understanding of delignification with polyoxometalates (POMs) that have been explored for use in bleaching of chemical pulps, the transformation of lignin during anaerobic treatment of birch kraft pulp with an equilibrated POM mixture composed of Na5(+2)[SiV1(-0.1)MoW10(+0.1)O

  1. 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

  2. Human immunodeficiency virus type 2: pathogenesis and antiretroviral therapy

    NARCIS (Netherlands)

    M.E. van der Ende (Marchina)

    2000-01-01

    textabstractHuman immunodeficiency virus type1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and simian immunodeficiency virus (SIV) have been identified as hither unknown primate members of the Lentivirinae subfamily of the family Retroviridae in 1983, 1986 and 1985 respectively, HIV-1

  3. Construction of a doxycycline-dependent simian immunodeficiency virus reveals a nontranscriptional function of tat in viral replication

    NARCIS (Netherlands)

    Das, Atze T.; Klaver, Bep; Harwig, Alex; Vink, Monique; Ooms, Marcel; Centlivre, Mireille; Berkhout, Ben

    2007-01-01

    In the quest for an effective vaccine against human immunodeficiency virus (HIV), live attenuated virus vaccines have proven to be very effective in the experimental model system of simian immunodeficiency virus (SIV) in macaques. However, live attenuated HIV vaccines are considered unsafe for use

  4. 75 FR 12761 - Government-Owned Inventions; Availability for Licensing

    Science.gov (United States)

    2010-03-17

    ... HTLV-II based vaccine for HIV an excellent unique candidate to target mucosal tissues and provide long... licensing is in the field of vaccines and vaccine vectors. More specifically the invention provides... the invention claims vaccines against HIV and SIV. Applications: The technology can be used for DNA...

  5. Antigenicity and immunogenicity of recombinant envelope glycoproteins of SIVmac32H with different in vivo passage histories.

    NARCIS (Netherlands)

    E.G.J. Hulskotte (Ellen); G.F. Rimmelzwaan (Guus); J. Boes (Jolande); M.L. Bosch (Marnix); J.L. Heeney (Jonathan); S.G. Norley (Stephen); P. de Vries (Petra); A.D.M.E. Osterhaus (Albert)

    1995-01-01

    textabstractShortly after infection of two rhesus monkeys (Macaca mulatta) either with a SIVmac32H challenge stock or with the same virus that had been passaged in another rhesus monkey for 11 months, SIV-envelope genes were cloned from their peripheral blood mononuclear cells and subsequently

  6. Chemical inactivation of recombinant vaccinia viruses and the effects on antigenicity and immunogenicity of recombinant simian immunodeficiency virus envelope glycoproteins.

    NARCIS (Netherlands)

    E.G.J. Hulskotte (Ellen); M.E.M. Dings (Marlinda); S.G. Norley (Stephen); A.D.M.E. Osterhaus (Albert)

    1997-01-01

    textabstractThe efficiency of paraformaldehyde (PFA) and binary ethylenimine (BEI) in inactivating recombinant vaccinia virus (rVV), present in baby hamster kidney cells expressing simian immunodeficiency virus envelope glycoproteins (SIV-Env), was measured in a series of inactivation studies. Both

  7. Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Shudo, Emi [Los Alamos National Laboratory; Ribeiro, Ruy M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2008-01-01

    While CD8+ T cell responses are clearly important in anti-viral immunity during HIV/SIV infection, the mechanisms by which CD8+ T cells induce this effect remain poorly understood, as emphasized by the failure of the Merck adenovirus-based, cytotoxic T lymphocyte (CTL)-inducing AIDS vaccine in a large phase IIb clinical trial. In this study, we measured the in vivo effect of CD8+ lymphocytes on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques by treating two groups of animals (i.e., CD8+ lymphocyte-depleted or controls) with antiretroviral therapy (PMPA and FTC). The lifespan of productively infected cells was calculated based on the slope of the decline of SIV plasma viremia using a well-accepted mathematical model. We found that, in both early (i.e., day 57 post-inoculation) and late (i.e., day 177 post-inoculation) chronic SIV infection, depletion of CD8+ lymphocytes did not result in an increased lifespan of productively infected cells in vivo. This result indicates that direct killing of cells producing virus is unlikely to be a major mechanism underlying the anti-viral effect of CD8+ T cells during SIV infection. These results have profound implications for the development of AIDS vaccines.

  8. Functional analysis of the complex trans-activating response element RNA structure in simian immunodeficiency virus

    NARCIS (Netherlands)

    Centlivre, Mireille; Klaver, Bep; Berkhout, Ben; Das, Atze T.

    2008-01-01

    Transcription of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is activated through binding of the viral Tat protein to the trans-activating response (TAR) element at the 5 ' end of the nascent transcript. Whereas HIV type 1 (HIV-1) TAR folds a simple hairpin structure,

  9. 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...

  10. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

    NARCIS (Netherlands)

    A.C. van der Kuyl (Antoinette); R. van den Burg (Remco); M.J. Hoyer (Mark); R.A. Gruters (Rob); A.D.M.E. Osterhaus (Albert); B. Berkhout (Ben)

    2004-01-01

    textabstractA 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

  11. 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

  12. 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

  13. Retrovirus Studies in Nonhuman Primates at Four Regional Primate Research Centers.

    Science.gov (United States)

    1989-12-31

    pneumonia and enterocolitis , while the other had hepatitis, peritonitis and pancreatitis. To determine the minimum dose of SIV needed to infect female rhesus...by Campylobacter coll and although Shigella was suspected in several animals, based on elevated WBC and the response to antibiotic therapy, no clear

  14. Characterization and comparison of recombinant simian immunodeficiency virus from drill (Mandrillus leucophaeus) and mandrill (Mandrillus sphinx) isolates.

    Science.gov (United States)

    Hu, Jinjie; Switzer, William M; Foley, Brian T; Robertson, David L; Goeken, Robert M; Korber, Bette T; Hirsch, Vanessa M; Beer, Brigitte E

    2003-04-01

    Since simian immunodeficiency virus (SIV) was found to be the source of the human AIDS pandemic, a major goal has been to characterize the diversity of SIV strains in the wild and to assess their potential for crossover into humans. In the present study, SIV was isolated from a seropositive drill (Mandrillus leucophaeus) and three seropositive mandrills (Mandrillus sphinx) by using macaque peripheral blood mononuclear cells (PBMC). Full-length sequences were obtained from a drill and mandrill and designated SIVdrl1FAO and SIVmnd5440, respectively. A 182-bp fragment of the pol genes of the two remaining mandrill SIV isolates was also analyzed. Phylogenetic analyses demonstrated that SIVdrl1FAO formed a monophyletic clade with SIVmnd5440 and SIVmndM14, recently designated SIVmnd type 2. Both the SIVdrl and SIVmnd type 2 genomes carried a vpx gene and appeared to share a common ancestor with SIVrcm in the 5' region of the genome and with SIVmndGB1 (type 1) in the 3' region of the genome. A statistically significant recombination breakpoint was detected at the beginning of envelope, suggesting that the viruses were descendents of the same recombinant. Phylogenetic analysis of vpx and vpr genes demonstrated that the vpx genes formed a monophyletic cluster that grouped with vpr from SIVagm. In addition, both SIVdrl1FAO and SIVmnd5440 replicated in human PBMC and therefore could pose a risk of transmission to the human population.

  15. Egiptuse valimisel presidendi trump / Sergei Stadnikov

    Index Scriptorium Estoniae

    Stadnikov, Sergei, 1956-

    2005-01-01

    Autori väitel on Egiptuse praeguse presidendi Hosni Mubaraki võidu teel eelseisvatel presidendivalimistel vaid kaks tõsist probleemi: püsiv terrorismioht ja juhtivate poliitiliste oponentide järjestikune keeldumine oma kandidatuuri ülesseadmisest

  16. 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

  17. Swine influenza virus co-infection with Bordetella bronchiseptica enhances bacterial colonization and host immune responses exacerbating pulmonary lesions

    Science.gov (United States)

    Swine influenza virus (SIV) is one of the most important disease causing agents for the U.S. swine industry, not only as a primary pathogen but as a predisposing agent to secondary bacterial infection. Bordetella bronchiseptica (Bb) is often isolated from swine and has been shown to contribute to th...

  18. 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).

  19. 75 FR 65021 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2010-10-21

    ... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis Panel; Mechanisms and Prevention of Sexual Transmission of HIV/SIV. Date: November 17-18, 2010. Time: 8... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases...

  20. 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

  1. 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

  2. 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.

  3. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1.

    Science.gov (United States)

    Keele, Brandon F; Li, Hui; Learn, Gerald H; Hraber, Peter; Giorgi, Elena E; Grayson, Truman; Sun, Chuanxi; Chen, Yalu; Yeh, Wendy W; Letvin, Norman L; Mascola, John R; Nabel, Gary J; Haynes, Barton F; Bhattacharya, Tanmoy; Perelson, Alan S; Korber, Bette T; Hahn, Beatrice H; Shaw, George M

    2009-05-11

    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.

  4. EFSA Panel Animal Health and Welfare (AHAW); Scientific Opinion on the pandemic (H1N1) 2009 influenza and its potential implications for animal health

    DEFF Research Database (Denmark)

    Bøtner, Anette; Brown, Ian; Capua, Ilaria

    . Such vaccines efficiently prevent disease by reducing virus replication in the lungs. However, voluntary vaccination of swine with these vaccines has not halted the circulation of SIV in swine. There is no urgency for vaccination of pigs against pH1N1 virus. Currently, no vaccines against H1 viruses for poultry...

  5. Natural simian immunodeficiency virus transmission in mandrills: a family affair?

    Science.gov (United States)

    Fouchet, David; Verrier, Delphine; Ngoubangoye, Barthélémy; Souquière, Sandrine; Makuwa, Maria; Kazanji, Mirdad; Gonzalez, Jean-Paul; Pontier, Dominique

    2012-09-07

    Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens.

  6. EJST V9N2

    African Journals Online (AJOL)

    breast height (1.5m) and by using the formula. Species Important Value (SIV) combines data from three parameters ... eminens, Dalbergia lactea, Pterolobium stellatum, and Ricinus communis. The ground cover species ... Euphorbia ampliphylla and Dalbergia lactea. Albizia gummifera, Allophylus abyssinicus,. Apodytes ...

  7. 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.

  8. African green monkey TRIM5α restriction in simian immunodeficiency virus-specific rhesus macaque effector CD4 T cells enhances their survival and antiviral function.

    Science.gov (United States)

    Jain, Sumiti; Trivett, Matthew T; Ayala, Victor I; Ohlen, Claes; Ott, David E

    2015-04-01

    The expression of xenogeneic TRIM5α proteins can restrict infection in various retrovirus/host cell pairings. Previously, we have shown that African green monkey TRIM5α (AgmTRIM5α) potently restricts both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus mac239 (SIV(mac239)) replication in a transformed human T-cell line (L. V. Coren, et al., Retrovirology 12:11, 2015, http://dx.doi.org/10.1186/s12977-015-0137-9). To assess AgmTRIM5α restriction in primary cells, we transduced AgmTRIM5α into primary rhesus macaque CD4 T cells and infected them with SIV(mac239). Experiments with T-cell clones revealed that AgmTRIM5α could reproducibly restrict SIV(mac239) replication, and that this restriction synergizes with an intrinsic resistance to infection present in some CD4 T-cell clones. AgmTRIM5α transduction of virus-specific CD4 T-cell clones increased and prolonged their ability to suppress SIV spread in CD4 target cells. This increased antiviral function was strongly linked to decreased viral replication in the AgmTRIM5α-expressing effectors, consistent with restriction preventing the virus-induced cytopathogenicity that disables effector function. Taken together, our data show that AgmTRIM5α restriction, although not absolute, reduces SIV replication in primary rhesus CD4 T cells which, in turn, increases their antiviral function. These results support prior in vivo data indicating that the contribution of virus-specific CD4 T-cell effectors to viral control is limited due to infection. The potential of effector CD4 T cells to immunologically modulate SIV/HIV infection likely is limited by their susceptibility to infection and subsequent inactivation or elimination. Here, we show that AgmTRIM5α expression inhibits SIV spread in primary effector CD4 T cells in vitro. Importantly, protection of effector CD4 T cells by AgmTRIM5α markedly enhanced their antiviral function by delaying SIV infection, thereby extending their viability

  9. 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

  10. Genetic correlation between current circulating H1N1 swine and human influenza viruses.

    Science.gov (United States)

    Lu, Lu; Yin, Yanbo; Sun, Zhongsheng; Gao, Lei; Gao, George F; Liu, Sidang; Sun, Lei; Liu, Wenjun

    2010-11-01

    H1N1 is the main subtype influenza A virus circulating in human and swine population, and has long been a threat to economy and public health. To explore the genetic correlation between current circulating H1N1 swine and human influenza viruses. Three new H1N1 swine influenza viruses (SIVs) were isolated and genomes sequencing were conducted followed by phylogenetic and molecular analysis of all swine and human H1N1 influenza viruses isolated in China in the past five years. Homology and phylogenetic analysis revealed that the three isolates possessed different characteristics: the genome of A/Swine/Shandong/1112/2008 was closely related to that of classical H1N1 SIV, while A/Swine/Shandong/1123/2008 was a reassortant with NS gene from the human-like H3N2 influenza virus and other genes from the classical H1N1 SIV, and A/Swine/Fujian/0325/2008 fell into a lineage of seasonal human H1N1 influenza viruses. Genetically, 2009 H1N1 influenza A viruses (2009 H1N1) in China were contiguous to the SIV lineages rather than the seasonal H1N1 human influenza virus's lineage. Furthermore, molecular analysis among human and swine influenza viruses provided more detail information for understanding their genetic correlation. These results suggested that in China in the past five years, the classical, avian-like and human-like H1N1 SIV existed in swine herds and the reassortment between H1N1 swine and H3N2 human influenza viruses was identified. In addition, the present data showed no evidence to support a strong correlation between the 2009 H1N1 and the swine influenza virus circulating in China. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections.

    Directory of Open Access Journals (Sweden)

    Jacob D Estes

    Full Text Available The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4(+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication.

  12. 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

  13. Simian Immunodeficiency Virus Infects Follicular Helper CD4 T Cells in Lymphoid Tissues during Pathogenic Infection of Pigtail Macaques

    Science.gov (United States)

    Xu, Yin; Weatherall, Chris; Bailey, Michelle; Alcantara, Sheilajen; De Rose, Robert; Estaquier, Jerome; Wilson, Kim; Suzuki, Kazuo; Corbeil, Jacques; Cooper, David A.; Kent, Stephen J.; Kelleher, Anthony D.

    2013-01-01

    T follicular helper (Tfh) cells are a specialized subset of memory CD4+ T cells that are found exclusively within the germinal centers of secondary lymphoid tissues and are important for adaptive antibody responses and B cell memory. Tfh cells do not express CCR5, the primary entry coreceptor for both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), and therefore, we hypothesized that these cells would avoid infection. We studied lymph nodes and spleens from pigtail macaques infected with pathogenic strain SIVmac239 or SIVmac251, to investigate the susceptibility of Tfh cells to SIV infection. Pigtail macaque PD-1high CD127low memory CD4+ T cells have a phenotype comparable to that of human Tfh cells, expressing high levels of CXCR5, interleukin-21 (IL-21), Bcl-6, and inducible T cell costimulator (ICOS). As judged by either proviral DNA or cell-associated viral RNA measurements, macaque Tfh cells were infected with SIV at levels comparable to those in other CD4+ memory T cells. Infection of macaque Tfh cells was evident within weeks of inoculation, yet we confirmed that Tfh cells do not express CCR5 or either of the well-known alternative SIV coreceptors, CXCR6 and GPR15. Mutations in the SIV envelope gp120 region occurred in chronically infected macaques but were uniform across each T cell subset investigated, indicating that the viruses used the same coreceptors to enter different cell subsets. Early infection of Tfh cells represents an unexpected focus of viral infection. Infection of Tfh cells does not interrupt antibody production but may be a factor that limits the quality of antibody responses and has implications for assessing the size of the viral reservoir. PMID:23325697

  14. Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.

    Science.gov (United States)

    Johnston, J M; Denning, G; Doering, C B; Spencer, H T

    2013-06-01

    We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fVIII. The bioengineered construct then was used effectively to treat knockout mice with hemophilia A. In the current study, we focused on optimizing self-inactivating (SIN) lentiviral vector systems by analyzing the efficacy of various lentiviral components in terms of virus production, transduction efficiency and transgene expression. Specifically, three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3) various internal promoters. The inclusion of a WPRE sequence had negligible effects on viral production and HP-fVIII expression. HIV and SIV vectors were compared and found to be similar with respect to transduction efficiency in both K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII by the SIV system, which was evident in both K562 and BHK-M cell lines. To further compare expression of HP-fVIII from an SIV-based lentiviral system, we constructed expression vectors containing the high expression transgene and a human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase promoter. Expression was significantly greater from the CMV promoter, which also yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these studies, an optimized vector contains the HP-fVIII transgene driven by a CMV internal promoter within a SIV-based lentiviral backbone lacking a WPRE.

  15. 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.

  16. Influence of Maturation, Pathology and Functional Lateralization on 3D Sulcal Morphology using MRI

    DEFF Research Database (Denmark)

    Jensen, Betina Vase

    condition, anosmia, in the olfactory sulcus. This thesis describes and uses methods for sulci segmentation, sulci registration, sulci representation, and statistics for modeling sulci shape and testing sulcal morphology. This thesis describes methods to analyze sulcal morphology and show how sulci...... unknown. The shape of cortical sulci and gyri are determined in part by forces exerted by white matter fiber connections between various cortical regions. Studying the shape of the cortical sulci hence contributes to the understanding of the variation in the folding. This thesis concerns sulcal...... morphometry using Magnetic Resonance Imaging (MRI) and spatial statistical methods. The sulcal morphology has been studied with respect to: the normal development of a central sulcus; in relation to functional lateralization of the motor hand area in central sulcus and, finally, in relation to a pathological...

  17. Assignment Confidence in Localization of the Hand Motor Cortex: Comparison of Structural Imaging With Functional MRI.

    Science.gov (United States)

    Sahin, Neslin; Mohan, Suyash; Maralani, Pejman J; Duddukuri, Srikalyan; O'Rourke, Donald M; Melhem, Elias R; Wolf, Ronald L

    2016-12-01

    The purpose of this study was to assign confidence levels to structural MRI and functional MRI (fMRI) for localization of the primary motor cortex. Ninety-one fMRI studies with at least one motor task (178 hemispheres) were identified. Three anatomic assessments were used to localize the primary motor cortex: relation between the superior frontal sulcus and precentral sulcus; cortical thickness; and configuration of the precentral knob. In 105 hemispheres, interreader agreement was assessed for two investigators with different experience levels. Confidence ratings from 0 to 5 (0, no confidence; 5, 100% confidence) were assigned for fMRI and each anatomic localization method. Cortical thickness had the highest confidence rating (mean, 4.90 ± 0.47 [SD]) with only one failure. The relation between the superior frontal sulcus and precentral sulcus had the lowest confidence rating (4.33 ± 0.91) with three failures. The greatest statistical significance was observed for the cortical thickness and superior frontal sulcus-precentral sulcus methods (post hoc Bonferroni test, p Confidence rating scores were significantly higher for the cortical thickness sign than for fMRI results (4.72 ± 0.54) for a single motor task (post hoc Bonferroni test, p = 0.006); however, the mean confidence rating for fMRI improved to 4.87 ± 0.36 when additional motor tasks were performed. Interreader differences were least for the cortical thickness sign (paired t test, t = 4.25, p confidence regarding localization of the primary motor cortex; however, localization of motor function is more specific when combined with fMRI findings. Multiple techniques can be used to increase confidence in identifying the hand motor cortex.

  18. Dentoskeletal and Soft Tissue Profile Changes Associated with Mandibular Setback Osteotomy: A Cephalometric Study

    Directory of Open Access Journals (Sweden)

    Manish Goyal

    2011-01-01

    The conclusions indicated that the facial concavity, in regard to the relationship of the hard and soft tissue chin to the upper face, was decreased by this surgical procedure; facial esthetics was improved. The mandible assumed a more normal relationship to the upper denture base. The least amount of change of the soft tissue profile was exhibited by the upper lip and maxillary sulcus of the upper lip. The greatest amount of change of the soft tissue profile was exhibited by the lower lip, the mandibular sulcus of the lower lip and the soft tissue chin.

  19. Intact type I Interferon production and IRF7 function in sooty mangabeys.

    Directory of Open Access Journals (Sweden)

    Steven E Bosinger

    Full Text Available In contrast to pathogenic HIV/SIV infections of humans and rhesus macaques (RMs, natural SIV infection of sooty mangabeys (SMs is typically non-pathogenic despite high viremia. Several studies suggested that low immune activation and relative resistance of CD4+ central memory T-cells from virus infection are mechanisms that protect SMs from AIDS. In 2008 it was reported that plasmacytoid dendritic cells (pDCs of SMs exhibit attenuated interferon-alpha (IFN-α responses to TLR7/9 ligands in vitro, and that species-specific amino acid substitutions in SM Interferon Regulatory Factor-7 (IRF7 are responsible for this observation. Based on these findings, these authors proposed that "muted" IFN-α responses are responsible for the benign nature of SIV infection in SMs. However, other studies indicated that acutely SIV-infected SMs show robust IFN-α responses and marked upregulation of Interferon Stimulated Genes (ISGs. To investigate this apparent disparity, we first examined the role of the reported IRF7 amino acid substitutions in SMs. To this end, we sequenced all IRF7 exons in 16 breeders, and exons displaying variability (exons 2,3,5,6,7,8 in the remainder of the colony (177 animals. We found that the reported Ser-Gly substitution at position 191 was a sequencing error, and that several of the remaining substitutions represent only minor alleles. In addition, functional assays using recombinant SM IRF7 showed no defect in its ability to translocate in the nucleus and drive transcription from an IFN-α promoter. Furthermore, in vitro stimulation of SM peripheral blood mononuclear cells with either the TLR7 agonist CL097 or SIV(mac239 induced an 500-800-fold induction of IFN-α and IFN-β mRNA, and levels of IFN-α production by pDCs similar to those of RMs or humans. These data establish that IFN-α and IRF7 signaling in SMs are largely intact, with differences with RMs that are minor and unlikely to play any role in the AIDS resistance of SIV

  20. 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

  1. Vpx is Critical for SIVmne infection of pigtail macaques

    Directory of Open Access Journals (Sweden)

    Belshan Michael

    2012-04-01

    Full Text Available Abstract Background Viral protein X (Vpx of SIV has been reported to be important for establishing infection in vivo. Vpx has several different activities in vitro, promoting preintegration complex import into the nucleus in quiescent lymphocytes and overcoming a block in reverse transcription in macrophages. Vpx interacts with the DDB1-CUL4-DCAF1 E3 ligase complex, which may or may not be required for the ascribed functions. The goal of the current study was to determine whether these activities of Vpx are important in vivo. Results An infectious, pathogenic clone of SIVmne was used to examine correlations between Vpx functions in vitro and in vivo. Three previously described HIV-2 Vpx mutants that were shown to be important for nuclear import of the preintegration complex in quiescent lymphocytes were constructed in SIVmne: A vpx-deleted virus, a truncation of Vpx at amino acid 102 that deletes the C-terminal proline-rich domain (X(102, and a mutant with tyrosines 66, 69, and 71 changed to alanine (X(y-a. All mutant viruses replicated similarly to wild type SIVmne027 in primary pigtail macaque PBMCs, and were only slightly retarded in CEMx174 cells. However, all the vpx mutant viruses were defective for replication in both human and pigtail monocyte-derived macrophages. PCR assays demonstrated that the efficiency of reverse transcription and the levels of viral integration in macrophages were substantially reduced for the vpx mutant viruses. In vitro, the X(y-a mutant, but not the X(102 mutant lost interaction with DCAF1. The wild type SIVmne027 and the three vpx mutant SIVs were inoculated by the intra-rectal route into pigtail macaques. Peak levels of plasma viremia of the vpx mutant SIVs were variable, but consistently lower than that observed in macaques infected with wild type SIVmne. In situ hybridization for SIV demonstrated that compared to wild type SIVmne infected macaques five of the six animals inoculated with the vpx mutant SIVs

  2. 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

    DEFF Research Database (Denmark)

    Simon, Gaelle; Larsen, Lars Erik; Duerrwald, Ralf

    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......, 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...

  3. Assessing the status of glaciers in part of the Chandra basin, Himachal Himalaya: A multiparametric approach

    Science.gov (United States)

    Garg, Purushottam Kumar; Shukla, Aparna; Tiwari, Reet Kamal; Jasrotia, Avtar Singh

    2017-05-01

    This study investigates the change in multiple glacier parameters of three valley-type glaciers (Sakchum (SC), Chhota Shigri (CS), and Bara Shigri (BS)) located in Chandra basin, Himachal Himalaya, sharing the same climatic regime, and assesses the control of nonclimatic factors on wholesome glacier response. Multitemporal satellite remote sensing data from Landsat-TM/ETM/OLI (1993-2014), and Terra-ASTER (2002-2014) along with an SRTM digital elevation model were used for extraction of the glacier parameters. Results show that while SC and BS retreated (SC: 10.65 ± 2.52 m/y; BS: 15.51 ± 2.52 m/y) and lost area (SC: 0.49 ± 0.0032 km2, BS: 1.18 ± 0.0032 km2), the CS remained relatively stable (retreat rate: 4.06 ± 2.52 m/y, area loss: 0.19 ± 0.0032 km2) during 1993-2014. However, results of surface ice velocities (SIV) change (SC: 24.41%, CS: 21.60%, and BS: 28.49%) and surface elevation change (SC: - 1.22 m/y, CS: - 0.91 m/y and BS: - 1.21 m/y) suggest a comparable slowing down and surface lowering from 2002 to 2014. Debris cover also varied substantially (SC: 30.25%, CS: 11.96%, BS: 19.61%) on these glaciers. Results reveal that higher retreat/deglaciation of glaciers was associated with higher altitudinal range, slow SIV in lower ablation zones (LAZ), and glacier hypsometry. Debris cover on glaciers was found to be controlled by slope, higher deglaciation rates, higher SIV in the upper ablation zone (UAZ) coupled with lower SIV in LAZ and surface lowering. Glacier SIV was primarily governed by slope gradient, differential surface lowering, and size of accumulation zone (ACZ). The SIV results confirm the presence of stagnant zones in the lower ablations of SC (Glacier surface lowering seemed to be influenced by ice-flux, changing spatial distribution of debris cover, presence of supraglacial lakes, and ice cliffs bordering them. Melting around supraglacial lakes and backwasting of ice cliffs may be the prime reasons behind intense mass loss observed in the

  4. 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.

  5. European surveillance network for influenza in pigs 3 (ESNIP 3)

    DEFF Research Database (Denmark)

    Reid, Scott M.; Simon, Gaëlle; Larsen, Lars Erik

    Objectives: The “European surveillance network for influenza in pigs (ESNIP) 3” continues a surveillance network previously established during concerted actions ESNIP 1 and ESNIP 2. Running from 2010-2013, ESNIP 3 represents the only organised surveillance network for influenza in pigs in Europe...... 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...

  6. Report of the 2011 annual meeting of the Italian Society for Virology.

    Science.gov (United States)

    Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Palù, Giorgio

    2012-07-01

    The 10th annual meeting of the Italian Society for Virology (SIV) comprised seven plenary sessions focused on: General virology and viral genetics; Virus-Host interaction and pathogenesis; Viral oncology; Emerging viruses and zoonotic, foodborne and environmental pathways of transmission; Viral immunology and vaccines; Medical virology and antiviral therapy; Viral biotechnologies and gene therapy. The meeting had an attendance of 143 virologists, about 60% were senior, and the other were young scientists. The submitted abstracts amounted to 88 and the abstracts selected for oral presentation were 41. Complete abstracts of oral and poster presentations are available at the web site www.siv-virologia.it. A summary of the plenary lectures and oral selected presentations is reported. Copyright © 2012 Wiley Periodicals, Inc.

  7. Highlights from the 5th Annual Meeting of the Italian Society of Virology.

    Science.gov (United States)

    Salata, Cristiano; Calistri, Arianna; Palù, Giorgio

    2006-07-01

    The 5th National Congress of the Italian Society of Virology (SIV) was attended by junior- and senior-level virologists to promote interactions and scientific collaborations among the different areas of Virology and allied sciences. The invited and selected lecturers covered the following topics: General Virology and Viral Genetics; Virus-host Interaction and Pathogenesis; Viral Oncogenesis; Viral Immunology and Vaccines; Anti-viral Therapy; Innovative Diagnostics; Viral Biotechnologies and Cell and Gene Therapy. As in the previous editions (Salata and Palù, 2004; Salata et al., 2005), a specific topic was thoroughly covered in a roundtable. This year the elected subject was "HIV: determinants of pathogenicity and clinical implications." The final program and the abstract book can be found at the web site http://www.siv-virologia.it. This report summarizes the lessons learned from the plenary lectures and the selected oral presentations of the 2005 meeting. Copyright 2006 Wiley-Liss, Inc.

  8. 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.

  9. Rapid microstill determination of free and total sulfite in wine with conductimetric detection.

    Science.gov (United States)

    McLeod, Stan; Davey, David E

    2007-09-26

    The development and optimization of on-line microdistillation for free and total sulfite (S(IV)) in grape juice and wine is reported. The microstill used both heat and an air stream to separate sulfur dioxide from the wine samples; the distillation product was captured in a peroxide solution, and converted to sulfuric acid, mirroring accepted industry practice. Measured from 1 to 300 mgL(-1) as SO(2) by conductance, sample throughputs of 60 h(-1) for free and 20 h(-1) for total sulfite were achieved. Data for bound S(IV) emphasises the slow kinetics of release reactions in some wines. The microstill method is more efficient for total sulfite than the accepted manual technique. Good correlation was found between the microstill and manual methods under specified control conditions.

  10. Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein

    DEFF Research Database (Denmark)

    Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma

    2014-01-01

    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....

  11. Terrestrial Biological Inventory, Hillview Drainage and Levee District, Greene and Scott Counties, Illinois.

    Science.gov (United States)

    1982-01-01

    1971, 1972, 1973, 1974, 1977) have compiled state- wide distributional data on several avian families (mimic thrushes, thrushes, swallows, shrikes...1980. (Nomenclature follows American Ornithologists’ Union 1967; 1973; 1976.) Order Family Species Podicipediformes Ardea herodias Great Blue Heron...Pogonla Dink SaamaderPlantain-leaved Sedge Snake-mouth SivSa amaumn Sedge (24 specdes) Yellow-lipped Ladles’Tresse Spte Tel Galingals Hooded Ladles

  12. Attitudes of Elementary Schools Pupils to the Physical and Sport Education

    Science.gov (United States)

    Kolofík, Tomáš

    2015-01-01

    The aim of the research was to find out the attitudes of the pupils of the seventh, eighth and ninth year-classes of the elementary schools in Banská Bystrica to the physical and sport education. The research sample comprised 1092 pupils, out of which 584 were boys and 508 were girls. A standardised questionnaire according to Sivák et al. (2000)…

  13. Expression of CD154 by a Simian Immunodeficiency Virus Vector Induces Only Transitory Changes in Rhesus Macaques

    OpenAIRE

    Vida L. Hodara; Velasquillo, M. Cristina; Parodi, Laura M.; Giavedoni, Luis D.

    2005-01-01

    Human immunodeficiency virus infection is characterized by dysregulation of antigen-presenting cell function and defects in cell-mediated immunity. Recent evidence suggests that impaired ability of CD4+ T cells to upregulate the costimulatory molecule CD154 is at the core of this dysregulation. To test the hypothesis that increased expression of CD154 on infected CD4+ T cells could modulate immune function, we constructed a replication-competent simian immunodeficiency virus (SIV) vector that...

  14. 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...

  15. Lymphocyte-Dominant Encephalitis and Meningitis in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    Science.gov (United States)

    Mangus, Lisa M; Beck, Sarah E; Queen, Suzanne E; Brill, Samuel A; Shirk, Erin N; Metcalf Pate, Kelly A; Muth, Dillon C; Adams, Robert J; Gama, Lucio; Clements, Janice E; Mankowski, Joseph L

    2018-01-01

    A retrospective neuropathologic review of 30 SIV-infected pigtailed macaques receiving combination antiretroviral therapy (cART) was conducted. Seventeen animals with lymphocyte-dominant inflammation in the brain and/or meninges that clearly was morphologically distinct from prototypic SIV encephalitis and human immunodeficiency virus encephalitis were identified. Central nervous system (CNS) infiltrates in cART-treated macaques primarily comprised CD20+ B cells and CD3+ T cells with fewer CD68+ macrophages. Inflammation was associated with low levels of SIV RNA in the brain as shown by in situ hybridization, and generally was observed in animals with episodes of cerebrospinal fluid (CSF) viral rebound or sustained plasma and CSF viremia during treatment. Although the lymphocytic CNS inflammation in these macaques shared morphologic characteristics with uncommon immune-mediated neurologic disorders reported in treated HIV patients, including CNS immune reconstitution inflammatory syndrome and neurosymptomatic CSF escape, the high prevalence of CNS lesions in macaques suggests that persistent adaptive immune responses in the CNS also may develop in neuroasymptomatic or mildly impaired HIV patients yet remain unrecognized given the lack of access to CNS tissue for histopathologic evaluation. Continued investigation into the mechanisms and outcomes of CNS inflammation in cART-treated, SIV-infected macaques will advance our understanding of the consequences of residual CNS HIV replication in patients on cART, including the possible contribution of adaptive immune responses to HIV-associated neurocognitive disorders. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. Lignin modification in the initial phase of softwood kraft pulp delignification with polyoxometalates (POMs)

    Science.gov (United States)

    Biljana Bujanovic; Sally A. Ralph; Richard S. Reiner; Rajai H. Atalla

    2007-01-01

    Commercial softwood kraft pulp with kappa number 30.5 (KP30.5) was delignified with polyoxometalates (POM, Na5(+2)[SiV1(-0.1)MoW10(+0.1)O40]), and POM-treated kraft pulp of kappa number 23.6 was obtained (KPPOM,23.6). Residual lignin from pulps was isolated by mild acid hydrolysis and characterized by analytical and spectral methods to gain insight into lignin...

  17. 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.

  18. Retrovirus Studies in Nonhuman Primates at Four Regional Primate Research Centers.

    Science.gov (United States)

    1990-09-30

    208, 1987. Anderson, D., Fultz, P., and McClure, H.: Necrotizing gingivitis (NOMA) in an SIV/SMM infected neonatal mangabey monkey. In: Proceedings of...disseminated cytomegalovirus infection, ulcerative gastritis and severe interstitial pneumonia with multinucleate giant cells. In addition to the above...genital tract and that this model can be further developed to test the role of chemical and pharmacologic contraceptives as well as surgical contraceptive

  19. Interpersonal values and their relation to attributional styles in fifth high school students

    OpenAIRE

    Tueros C., Rosa; Doctorado en Psicología, Facultad de Psicología, Universidad Nacional Mayor de San Marcos, Lima, Perú; Matalinares C., María; Facultad de Psicología, Universidad Nacional Mayor de San Marcos, Lima, Perú; Raymundo V., Ornella; Maestría en Psicología, Facultad de Psicología, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    This research aimed to establish the degree of relationship between interpersonal values and attributional styles of male and female students of the 5th year of secondary education. We used a descriptive correlational method, the sample consisted of 400 students, distributed in proportion to the population. The research was carried out, using the attributional style questionnaire and the Interpersonal Values Questionnaire SIV Leonard Gordon 1977. The results indicate according to the Spearman...

  20. The entry price threshold in EU F&V sector: deterrence or effective barrier?

    OpenAIRE

    Cioffi, Antonio; Santeramo, Fabio G.

    2011-01-01

    The paper investigates the effects of the entry price scheme for fresh fruit and vegetables. The analysis is conducted on the EU prices of tomatoes, lemons and apples for some of the main competing countries on the EU domestic markets: Morocco, Argentina, Turkey and China. The econometric analysis is based on testing and estimating a switching vector autoregressive model with endogenous threshold entry price level. The model shows the isolation effects and the accumulation of SIVs above the t...

  1. Minimally invasive monitoring of CD4 T cells at multiple mucosal tissues after intranasal vaccination in rhesus macaques.

    Science.gov (United States)

    Dorta-Estremera, Stephanie; Nehete, Pramod N; Yang, Guojun; He, Hong; Nehete, Bharti P; Shelton, Kathryn A; Barry, Michael A; Sastry, K Jagannadha

    2017-01-01

    Studies in nonhuman primates (NHP) for prospective immune cell monitoring subsequent to infection and/or vaccination usually rely on periodic sampling of the blood samples with only occasional collections of biopsies from mucosal tissues because of safety concerns and practical constraints. Here we present evidence in support of cytobrush sampling of oral, rectal, and genital mucosal tissues as a minimally invasive approach for the phenotypic analyses of different T cells subsets de novo as well as prospectively after intranasal immunization in rhesus macaques. Significant percentages of viable lymphocytes were obtained consistently from both naïve and chronically SIV-infected rhesus macaques. The percentages of CD3+ T cells in the blood were significantly higher compared to those in the mucosal tissues analyzed in the naïve animals, while in the SIV+ animals the CD3+ T cells were significantly elevated in the rectal tissues, relative to all other sites analyzed. In the naïve, but not SIV+ macaques, the rectal and vaginal mucosal tissues, compared to oral mucosa and blood, showed higher diversity and percentages of CD4+ T cells expressing the HIV entry co-receptor CCR5 and mucosal specific adhesion (CD103) as well as activation (HLA-DR) and proliferation (Ki67) markers. Sequential daily cytobrush sampling from the oral, rectal, and genital mucosal tissues was performed in SIV+ animals from an ongoing study where they were administered intranasal immunization with adenoviral vectored vaccines incorporating the green fluorescent protein (GFP) reporter gene. We detected a transient increase in GFP+ CD4 T cells in only oral mucosa suggesting limited mucosal trafficking. In general, CD4+ and CD8+ T cells expressing Ki67 transiently increased in all mucosal tissues, but those expressing the CCR5, HLA-DR, and CD103 markers exhibited minor changes. We propose the minimally invasive cytobrush sampling as a practical approach for effective and prospective immune

  2. A Novel DNA-Based Vaccine Methodology for Aids

    Science.gov (United States)

    1998-11-01

    to Malaria Elicited by Hybrid Hepatits B Virus Core Particles Carrying Circumsporozoite Protein Eptiopes. JExp Med 180:1037-1046 41. Hanke, T...marked as limited rights data shall not, without the written permission of the above contractor, be (a) released or disclosed outside the government, ( b ...EBV- transformed autologous B cell targets infected with a recombinant vaccinia expressing SIV gag, pol, or env. Preliminary data in Table 1 shows

  3. Uuendatud arhitektuurimuuseum nüüd publikusõbralikum / Ave Randviir

    Index Scriptorium Estoniae

    Randviir, Ave, 1981-

    2006-01-01

    Tänavu 15-aastaseks saanud Eesti Arhitektuurimuuseumi ruumide ümberehitusest Rotermanni soolalaos Tallinnas. Siseaarhitekt Priit Põldme, kohviku lampide autor Tarmo Luisk, laudade autor Martin Pärn, toolide autor Eero Aarnio. Muuseumi direktriss Karin Hallas-Murula uuest püsiväljapanekust "Eesti arhitektuur makettidel" ja näitusest "Arhitekt Raine Karp", mida täiendavad Kaido Haageni fotod

  4. DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant.

    Science.gov (United States)

    Menon, Veena; Ayala, Victor I; Rangaswamy, Sneha P; Kalisz, Irene; Whitney, Stephen; Galmin, Lindsey; Ashraf, Asma; LaBranche, Celia; Montefiori, David; Petrovsky, Nikolai; Kalyanaraman, Vaniambadi S; Pal, Ranajit

    2017-08-01

    The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high-affinity interaction with CD4 and were highly immunogenic in rabbits, inducing Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA prime and protein boost together with Advax was evaluated in Chinese rhesus macaques. DNA administration elicited antibodies to both envelopes, and titres were markedly enhanced following homologous protein boosts via intranasal and intramuscular routes. Strong antibody responses were detected against the V1 and V2 domains of gp120. During peak immune responses, a low to moderate level of neutralizing activity was detected against Tier 1A/1B SIV isolates, with a moderate level noted against a Tier 2 isolate. Increased serum antibody affinity to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in the immunized macaques. Animals were subjected to low-dose intravaginal challenge with SIVmac251 one week after the last protein boost. One out of three immunized animals was protected from infection. Although performed with a small number of macaques, this study demonstrates the utility of oligomeric envelopes formulated with Advax in eliciting broad antibody responses with the potential to provide protection against SIV transmission.

  5. Editoriale / Editorial

    Directory of Open Access Journals (Sweden)

    Balloni Augusto

    2011-12-01

    Full Text Available Nel 1991 si è costituita la nostra Società Italiana di Vittimologia (S.I.V. e in questi vent’anni molte attività hanno attirato interesse da parte di diversi settori: si sono sviluppati rapporti con istituzioni del territorio e con organizzazioni nazionali e internazionali; inoltre la Rivista di Criminologia, Vittimologia e Sicurezza è diventata un importante strumento per il giusto riconoscimento e la necessaria visibilità delle vittime.

  6. The levels of DNGR-1 and its ligand-bearing cells were altered after human and simian immunodeficiency virus infection.

    Science.gov (United States)

    Yao, Wen-Rong; Li, Dong; Yu, Lei; Wang, Feng-Jie; Xing, Hui; Yang, Gui-Bo

    2017-08-01

    Dendritic cell NK lectin Group Receptor-1 (DNGR-1), also known as C-type lectin domain family 9, member A (CLEC9A), is a member of C-type lectin receptor superfamily expressed primarily on dendritic cells (DC) that excel in cross-presentation of exogenous antigens. To find out whether and how it is affected in human immunodeficiency virus infections or acquired immunodeficiency syndromes (HIV/AIDS), DNGR-1 expression and DNGR-1-binding cells in simian/human immunodeficiency virus (SHIV) and simian immunodeficiency virus (SIV)-infected rhesus macaques and antiretroviral therapy (ART)-treated AIDS patients were examined by real-time RT-PCR, flow cytometry, and confocal microscopy. DNGR-1 expression was observed in both lymphoid and non-lymphoid tissues including gut-associated lymphoid tissues (GALT) of rhesus macaques. DNGR-1 mRNA levels were significantly reduced in the blood while significantly elevated in the GALT of SHIV/SIV-infected rhesus macaques. DNGR-1 transcription levels were also significantly reduced in the blood of ART-treated AIDS patients irrespective of viral status. White blood cells with exposed DNGR-1 ligands were significantly increased in ART-treated AIDS patients, while significantly decreased in SIV-infected rhesus macaques. These data indicate that DNGR-1 expression, and by extension, the function of cross-presentation of antigens associated with dead/damaged cells might be compromised in HIV/SIV infection, which might play a role in HIV/AIDS pathogenesis and should be taken into consideration in therapeutic AIDS vaccine development.

  7. 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.

  8. Competition advantages by efficient maintenance management. Integrated IT system offers saving potentials; Wettbewerbsvorteile durch effizientes Instandhaltungsmanagement. Integriertes IT-System eroeffnet Einsparpotenziale

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, W.; Daug, S. [SIV AG, Roggentin (Germany)

    2005-08-22

    Competition on the deregulated energy market has made internal processes of industrial organisations come to the fore as a matter of interest. Efficient planning of investments and maintenance is a key factor of success. The integrated system of SIV AG is presented as an exemplary solution for profit-oriented asset management, enabling the user to plan resources accurately and to make correct investment decisions. (orig.)

  9. Arteriviruses, Pegiviruses, and Lentiviruses Are Common among Wild African Monkeys.

    Science.gov (United States)

    Bailey, Adam L; Lauck, Michael; Ghai, Ria R; Nelson, Chase W; Heimbruch, Katelyn; Hughes, Austin L; Goldberg, Tony L; Kuhn, Jens H; Jasinska, Anna J; Freimer, Nelson B; Apetrei, Cristian; O'Connor, David H

    2016-08-01

    Nonhuman primates (NHPs) are a historically important source of zoonotic viruses and are a gold-standard model for research on many human pathogens. However, with the exception of simian immunodeficiency virus (SIV) (family Retroviridae), the blood-borne viruses harbored by these animals in the wild remain incompletely characterized. Here, we report the discovery and characterization of two novel simian pegiviruses (family Flaviviridae) and two novel simian arteriviruses (family Arteriviridae) in wild African green monkeys from Zambia (malbroucks [Chlorocebus cynosuros]) and South Africa (vervet monkeys [Chlorocebus pygerythrus]). We examine several aspects of infection, including viral load, genetic diversity, evolution, and geographic distribution, as well as host factors such as age, sex, and plasma cytokines. In combination with previous efforts to characterize blood-borne RNA viruses in wild primates across sub-Saharan Africa, these discoveries demonstrate that in addition to SIV, simian pegiviruses and simian arteriviruses are widespread and prevalent among many African cercopithecoid (i.e., Old World) monkeys. Primates are an important source of viruses that infect humans and serve as an important laboratory model of human virus infection. Here, we discover two new viruses in African green monkeys from Zambia and South Africa. In combination with previous virus discovery efforts, this finding suggests that these virus types are widespread among African monkeys. Our analysis suggests that one of these virus types, the simian arteriviruses, may have the potential to jump between different primate species and cause disease. In contrast, the other virus type, the pegiviruses, are thought to reduce the disease caused by human immunodeficiency virus (HIV) in humans. However, we did not observe a similar protective effect in SIV-infected African monkeys coinfected with pegiviruses, possibly because SIV causes little to no disease in these hosts. Copyright © 2016

  10. 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?

  11. Clinical research in HIV-1 infected children

    OpenAIRE

    Fraaij, Pieter

    2005-01-01

    textabstractAcquired immune deficiency syndrome (AIDS) was described for the first time in 1981. Two years later the previously unknown human immunodeficiency virus (HIV) was identified as the causative agent. HIV has been included in the genus Lent/viruses of the Retroviridae family. Two types are recognized: HIV-1 and HIV-2. Of these, HIV-1 is the primary etiologic agent of the current pandemic. HIV probably originates from simian immunodeficiency virus (SIV) which is endemic in African mon...

  12. Approximale Kastenelevationstechnik – Einfluss auf die marginale Adaptation von Kompositinlays

    OpenAIRE

    Dippold, Christoph

    2013-01-01

    Hintergrund und Fragestellung Zahnfarbene Restaurationen aus Komposit und Keramik setzen sich weiter durch und werden von immer mehr Patienten gewünscht. Doch der adhäsive Verbund zu den Zahnhartsubstanzen: Schmelz, Dentin und Zement ist oft mit Misserfolgen verbunden. Gerade bei ausgedehnten Defekten werden indirekt hergestellte Versorgungen wie Kompositinlays empfohlen, um die Restzahnsubstanz adhäsiv optimal zu stützen. Im Fall eines sehr tiefen, apikal der Schmelz-Zement-Grenze befi...

  13. The Development of Trust Similarities and Differences for Senior Leaders in Other Cultural Environments

    Science.gov (United States)

    2009-04-30

    34Hersey, Paul and Blanchard, Kenneth, 1982. Management of Organizational Behavior , Prentice Hall: Englewood Cliffs, NJ. p. 6. 35 Note: While not...Blanchard, Kenneth, 1982. Management of Organizational Behavior , Prentice Hall: Englewood Cliffs, NJ. 345 p. Huxham, Chris and Vangen, Siv...of this paradigm that include government politics, organizational behavior and the rational actor perspective.1It is where clear articulation of the

  14. Closed-mill delignification by design using polyoxometalates

    Science.gov (United States)

    C. J. Houtman; R. S. Reiner; S. E. Reichel; M. J. Birchmeier; C. E. Sullivan; L. A. Weinstock; R. H. Atalla

    1999-01-01

    Polyoxometalates (POMs) are a class of delignification agents that promise to provide the basis for a new closed-mill bleaching technology. The results presented here are based on the use of Na6SiV2W10O40, which is effective in reducing the Kappa number of softwood Kraft pulp from 30 to below 10 with minimal loss in viscosity. A critical part of a viable POM process is...

  15. Laser Capture Microdissection Assessment of Virus Compartmentalization in the Central Nervous Systems of Macaques Infected with Neurovirulent Simian Immunodeficiency Virus

    Science.gov (United States)

    Matsuda, Kenta; Brown, Charles R.; Foley, Brian; Goeken, Robert; Whitted, Sonya; Dang, Que; Wu, Fan; Plishka, Ronald; Buckler-White, Alicia

    2013-01-01

    Nonhuman primate-simian immunodeficiency virus (SIV) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (HIV-1) in the brain. Our laboratory recently isolated a neuropathogenic viral swarm, SIVsmH804E, a derivative of SIVsmE543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with SIV encephalitis. Animals infected with SIVsmH804E or its precursor (SIVsmH783Br) developed SIV meningitis and/or encephalitis at high frequencies. Since we observed macaques with a combination of meningitis and encephalitis, as well as animals in which meningitis or encephalitis was the dominant component, we hypothesized that distinct mechanisms could be driving the two pathological states. Therefore, we assessed viral populations in the meninges and the brain parenchyma by laser capture microdissection. Viral RNAs were isolated from representative areas of the meninges, brain parenchyma, terminal plasma, and cerebrospinal fluid (CSF) and from the inoculum, and the SIV envelope fragment was amplified by PCR. Phylogenetic analysis of envelope sequences from the conventional progressors revealed compartmentalization of viral populations between the meninges and the parenchyma. In one of these animals, viral populations in meninges were closely related to those from CSF and shared signature truncations in the cytoplasmic domain of gp41, consistent with a common origin. Apart from magnetic resonance imaging (MRI) and positron-emission tomography (PET) imaging, CSF is the most accessible assess to the central nervous system for HIV-1-infected patients. However, our results suggest that the virus in the CSF may not always be representative of viral populations in the brain and that caution should be applied in extrapolating between the properties of viruses in these two compartments. PMID:23720733

  16. Influence of substrate material on spectral properties and thermal quenching of photoluminescence of silicon vacancy colour centres in diamond thin films

    Czech Academy of Sciences Publication Activity Database

    Dragounová, Kateřina; Ižák, Tibor; Kromka, Alexander; Potůček, Z.; Bryknar, Z.; Potocký, Štěpán

    2017-01-01

    Roč. 68, č. 7 (2017), s. 3-9 ISSN 1335-3632 R&D Projects: GA MŠk(CZ) LD15003; GA ČR(CZ) GA14-04790S Institutional support: RVO:68378271 Keywords : diamond * Si-V centre * photoluminescence * microwave-plasma enhanced CVD * activation energy Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.483, year: 2016

  17. Pangaskandaal heidab varju Eesti ärieliidile / Aivar Reinap

    Index Scriptorium Estoniae

    Reinap, Aivar, 1968-

    2005-01-01

    Kuigi investeerimispanga Lõhmus, Haavel &Viisemann töötajad Oliver Peek ja Kristjan Lepik põhjendavad õnnestunud väärtpaberitehinguid USA aktsiaturgudel hea analüüsivõime ja turu tundmisega, on nad vihjamisi tunnistanud, et kasutasid Business Wire'is leiduvat siseinfot. Kui investeerimispank ei suuda New Yorgis 8. novembril algaval kohtuprotsessil oma mitteseotust tehingutega tõestada, ähvardavad panka suured tagasilöögid

  18. Studies in the Nature and Control of Sepsis in Thermal and Combined Thermal-Irradiation Injuries

    Science.gov (United States)

    1970-03-01

    relationship to synergism in poly- microbic in rections; III- Clinical evaluation of Pseudomonas Vaccine, SIV. . Gnotobiotic studies of the response...DA-49-193-MD-20( Altemeier et al March 31, 1970 Page seven tetracycline, and chloramphenicol . The cyclic variation in penicillin resistance of the...relation to their symbiosis and possible synergism . Of further interest has been the incidence of the non-sporulating anaerobes in body fluids other than

  19. CD8+ T Cell Escape Mutations in Simian Immunodeficiency Virus SIVmac239 Cause Fitness Defects In Vivo, and Many Revert after Transmission▿†

    OpenAIRE

    Mudd, Philip A.; Ericsen, Adam J.; Walsh, Andrew D.; León, Enrique J.; Wilson, Nancy A.; Maness, Nicholas J.; Friedrich, Thomas C.; Watkins, David I.

    2011-01-01

    Virus-specific CD8+ T lymphocytes select for escape mutations in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). To assess the effects of these mutations on viral fitness, we introduced escape mutations into 30 epitopes (bound by five major histocompatibility complex class I [MHC-I] molecules) in three different viruses. Two of these MHC-I alleles are associated with elite control. Two of the three viruses demonstrated reduced fitness in vivo, and 27% of the introd...

  20. Consequences of Non-Intervention for Infectious Disease in African Great Apes

    OpenAIRE

    Ryan, Sadie J.; Peter D Walsh

    2011-01-01

    Infectious disease has recently joined poaching and habitat loss as a major threat to African apes. Both "naturally" occurring pathogens, such as Ebola and Simian Immunodeficiency Virus (SIV), and respiratory pathogens transmitted from humans, have been confirmed as important sources of mortality in wild gorillas and chimpanzees. While awareness of the threat has increased, interventions such as vaccination and treatment remain controversial. Here we explore both the risk of disease to Africa...

  1. Chronic Δ9-Tetrahydrocannabinol Administration Reduces IgE+B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin

    OpenAIRE

    Qin, CHUN-CHUNG; Molina, P; Liu, L; Cong, Z; Wu, X; Wang, H; Chen, Z; Wei, Q

    2016-01-01

    Delta9-tetrahydrocannabinol (Δ9-THC) is the major psychoactive component of the cannabis plant. Δ9-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ9-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Her...

  2. An amelanotic malignant melanoma masquerading as hypergranulation tissue.

    Science.gov (United States)

    Cahill, S; Cryer, J R; Otter, S J; Ramesar, K

    2009-01-01

    We report a case of amelanotic malignant melanoma occurring in the nail sulcus of the hallux, which on initial presentation was mistaken for hypergranulation tissue due to an in-growing toenail. We highlight the importance of this differential diagnosis as such lesions can have serious sequelae.

  3. Morphometric Studies Of The Cerebellum And Forebrain Of The ...