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Sample records for hsv-1 latent rabbit

  1. Rabbit and Mouse Models of HSV-1 Latency, Reactivation, and Recurrent Eye Diseases

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    Webre, Jody M.; Hill, James M.; Nolan, Nicole M.; Clement, Christian; McFerrin, Harris E.; Bhattacharjee, Partha S.; Hsia, Victor; Neumann, Donna M.; Foster, Timothy P.; Lukiw, Walter J.; Thompson, Hilary W.

    2012-01-01

    The exact mechanisms of HSV-1 establishment, maintenance, latency, reactivation, and also the courses of recurrent ocular infections remain a mystery. Comprehensive understanding of the HSV-1 disease process could lead to prevention of HSV-1 acute infection, reactivation, and more effective treatments of recurrent ocular disease. Animal models have been used for over sixty years to investigate our concepts and hypotheses of HSV-1 diseases. In this paper we present descriptions and examples of rabbit and mouse eye models of HSV-1 latency, reactivation, and recurrent diseases. We summarize studies in animal models of spontaneous and induced HSV-1 reactivation and recurrent disease. Numerous stimuli that induce reactivation in mice and rabbits are described, as well as factors that inhibit viral reactivation from latency. The key features, advantages, and disadvantages of the mouse and rabbit models in relation to the study of ocular HSV-1 are discussed. This paper is pertinent but not intended to be all inclusive. We will give examples of key papers that have reported novel discoveries related to the review topics. PMID:23091352

  2. Local CD4 and CD8 T-cell reactivity to HSV-1 antigens documents broad viral protein expression and immune competence in latently infected human trigeminal ganglia.

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    Monique van Velzen

    2013-08-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection results in lifelong chronic infection of trigeminal ganglion (TG neurons, also referred to as neuronal HSV-1 latency, with periodic reactivation leading to recrudescent herpetic disease in some persons. HSV-1 proteins are expressed in a temporally coordinated fashion during lytic infection, but their expression pattern during latent infection is largely unknown. Selective retention of HSV-1 reactive T-cells in human TG suggests their role in controlling reactivation by recognizing locally expressed HSV-1 proteins. We characterized the HSV-1 proteins recognized by virus-specific CD4 and CD8 T-cells recovered from human HSV-1-infected TG. T-cell clusters, consisting of both CD4 and CD8 T-cells, surrounded neurons and expressed mRNAs and proteins consistent with in situ antigen recognition and antiviral function. HSV-1 proteome-wide scans revealed that intra-TG T-cell responses included both CD4 and CD8 T-cells directed to one to three HSV-1 proteins per person. HSV-1 protein ICP6 was targeted by CD8 T-cells in 4 of 8 HLA-discordant donors. In situ tetramer staining demonstrated HSV-1-specific CD8 T-cells juxtaposed to TG neurons. Intra-TG retention of virus-specific CD4 T-cells, validated to the HSV-1 peptide level, implies trafficking of viral proteins from neurons to HLA class II-expressing non-neuronal cells for antigen presentation. The diversity of viral proteins targeted by TG T-cells across all kinetic and functional classes of viral proteins suggests broad HSV-1 protein expression, and viral antigen processing and presentation, in latently infected human TG. Collectively, the human TG represents an immunocompetent environment for both CD4 and CD8 T-cell recognition of HSV-1 proteins expressed during latent infection. HSV-1 proteins recognized by TG-resident T-cells, particularly ICP6 and VP16, are potential HSV-1 vaccine candidates.

  3. Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

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    Jones, Clinton

    2013-01-01

    α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts. PMID:25278776

  4. Lytic HSV-1 infection induces the multifunctional transcription factor Early Growth Response-1 (EGR-1 in rabbit corneal cells

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    McFerrin Harris E

    2011-05-01

    Full Text Available Abstract Background Herpes simplex virus type-1 (HSV-1 infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction between virus and host cells, critical for viral replication, is being extensively investigated by many laboratories. In this study, we tested the hypothesis that HSV-1 lytic infection triggers the expression of important multi-functional transcription factor Egr1. The mechanisms of induction are mediated, at least in part, by signaling pathways such as NFκB and CREB. Methods SIRC, VERO, and 293HEK cell lines were infected with HSV-1, and the Egr-1 transcript and protein were detected by RT-PCR and Western blot, respectively. The localization and expression profile of Egr-1 were investigated further by immunofluorescence microscopy analyses. The recruitment of transcription factors to the Egr-1 promoter during infection was studied by chromatin immunoprecipitation (ChIP. Various inhibitors and dominant-negative mutant were used to assess the mechanisms of Egr-1 induction and their effects were addressed by immunofluorescence microscopy. Results Western blot analyses showed that Egr-1 was absent in uninfected cells; however, the protein was detected 24-72 hours post treatment, and the response was directly proportional to the titer of the virus used for infection. Using recombinant HSV-1 expressing EGFP, Egr-1 was detected only in the infected cells. ChIP assays demonstrated that NFкB and cAMP response element binding protein (CREB were recruited to the Egr-1 promoter upon infection. Additional studies showed that inhibitors of NFкB and dominant-negative CREB repressed the Egr-1 induction by HSV-1 infection. Conclusion Collectively, these results demonstrate that Egr-1 is expressed rapidly upon HSV-1 infection and that this novel induction could be due to the NFкB/CREB-mediated transactivation. Egr-1 induction might play a key role in the viral gene

  5. The Herpes Simplex Virus Latency-Associated Transcript Gene Is Associated with a Broader Repertoire of Virus-Specific Exhausted CD8+ T Cells Retained within the Trigeminal Ganglia of Latently Infected HLA Transgenic Rabbits

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    Srivastava, Ruchi; Dervillez, Xavier; Khan, Arif A.; Chentoufi, Aziz A.; Chilukuri, Sravya; Shukr, Nora; Fazli, Yasmin; Ong, Nicolas N.; Afifi, Rasha E.; Osorio, Nelson; Geertsema, Roger; Nesburn, Anthony B.

    2016-01-01

    ABSTRACT Persistent pathogens, such as herpes simplex virus 1 (HSV-1), have evolved a variety of immune evasion strategies to avoid being detected and destroyed by the host's immune system. A dynamic cross talk appears to occur between the HSV-1 latency-associated transcript (LAT), the only viral gene that is abundantly transcribed during latency, and the CD8+ T cells that reside in HSV-1 latently infected human and rabbit trigeminal ganglia (TG). The reactivation phenotype of TG that are latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT+ TG) is significantly higher than TG latently infected with LAT-null mutant (i.e., LAT− TG). Whether LAT promotes virus reactivation by selectively shaping a unique repertoire of HSV-specific CD8+ T cells in LAT+ TG is unknown. In the present study, we assessed the frequency, function, and exhaustion status of TG-resident CD8+ T cells specific to 40 epitopes derived from HSV-1 gB, gD, VP11/12, and VP13/14 proteins, in human leukocyte antigen (HLA-A*0201) transgenic rabbits infected ocularly with LAT+ versus LAT– virus. Compared to CD8+ T cells from LAT– TG, CD8+ T cells from LAT+ TG (i) recognized a broader selection of nonoverlapping HSV-1 epitopes, (ii) expressed higher levels of PD-1, TIM-3, and CTLA-4 markers of exhaustion, and (iii) produced less tumor necrosis factor alpha, gamma interferon, and granzyme B. These results suggest a novel immune evasion mechanism by which the HSV-1 LAT may contribute to the shaping of a broader repertoire of exhausted HSV-specific CD8+ T cells in latently infected TG, thus allowing for increased viral reactivation. IMPORTANCE A significantly larger repertoire of dysfunctional (exhausted) HSV-specific CD8+ T cells were found in the TG of HLA transgenic rabbits latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT+ TG) than in a more restricted repertoire of functional HSV-specific CD8+ T cells in the TG of HLA transgenic rabbits latently

  6. Ocular HSV-1: Is the Cornea a Reservoir for Viral Latency or a Fast Pit Stop?

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    Kennedy, David P.; Clement, Christian; Arceneaux, Richard L.; Bhattacharjee, Partha S.; Huq, Tashfin S.; Hill, James M.

    2010-01-01

    Purpose To present a review supporting and refuting evidence from mouse, rabbit, non-human primate, and human studies of herpes simplex virus type 1 (HSV-1) concerning corneal latency. Methods More than 50 research papers on HSV-1 published in peer-reviewed journals were examined. Results Infectious HSV-1 has been found in mouse denervated tissues and in tissues with negative cultures from the corresponding ganglion. However, the different mouse strains have shown varied responses to different strains of HSV, making it difficult to relate such findings to humans. Rabbit studies provide excellent evidence for HSV-1 corneal latency including data on HSV-1 migration from the cornea into the corneoscleral rim and on the distribution of HSV-1 DNA in the cornea. However, the available methods for the detection of infectious HSV-1 may not be sensitive enough to detect low-level infection. Infectious HSV-1 has been successfully isolated from the tears of non-human primates in the absence of detectable corneal lesions. The recurrence of corneal ulcers in non-human primates before the appearance of infectious HSV-1 in tears suggests that the origin of the HSV-1 is the cornea, rather than the TG. Human studies presented evidence of both ganglion and corneal latency. Conclusion Understanding HSV-1 disease progression and the possibility of corneal latency could lead to more effective treatments for herpetic keratitis. However, it is unlikely that operational latency in the cornea will be definitively proven unless a new method with higher sensitivity for the detection of infectious virus is developed. PMID:21304287

  7. Therapeutic Immunization with a Mixture of Herpes Simplex Virus 1 Glycoprotein D-Derived “Asymptomatic” Human CD8+ T-Cell Epitopes Decreases Spontaneous Ocular Shedding in Latently Infected HLA Transgenic Rabbits: Association with Low Frequency of Local PD-1+ TIM-3+ CD8+ Exhausted T Cells

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    Khan, Arif A.; Srivastava, Ruchi; Chentoufi, Aziz A.; Geertsema, Roger; Thai, Nhi Thi Uyen; Dasgupta, Gargi; Osorio, Nelson; Kalantari, Mina; Nesburn, Anthony B.; Wechsler, Steven L.

    2015-01-01

    ABSTRACT Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus 1 (HSV-1) from latency rather than to primary acute infection. No herpes simplex vaccine is currently available for use in humans. In this study, we used the HLA-A*02:01 transgenic (HLA Tg) rabbit model of ocular herpes to assess the efficacy of a therapeutic vaccine based on HSV-1 gD epitopes that are recognized mainly by CD8+ T cells from “naturally” protected HLA-A*02:01-positive, HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease). Three ASYMP CD8+ T-cell epitopes (gD53–61, gD70–78, and gD278–286) were linked with a promiscuous CD4+ T-cell epitope (gD287–317) to create 3 separate pairs of CD4-CD8 peptides, which were then each covalently coupled to an Nε-palmitoyl-lysine moiety, a Toll-like receptor 2 (TLR-2) ligand. This resulted in the construction of 3 CD4-CD8 lipopeptide vaccines. Latently infected HLA Tg rabbits were immunized with a mixture of these 3 ASYMP lipopeptide vaccines, delivered as eye drops in sterile phosphate-buffered saline (PBS). The ASYMP therapeutic vaccination (i) induced HSV-specific CD8+ T cells that prevent HSV-1 reactivation ex vivo from latently infected explanted trigeminal ganglia (TG), (ii) significantly reduced HSV-1 shedding detected in tears, (iii) boosted the number and function of HSV-1 gD epitope-specific CD8+ T cells in draining lymph nodes (DLN), conjunctiva, and TG, and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1+ TIM-3+ CD8+ T cells. The results underscore the potential of an ASYMP CD8+ T-cell epitope-based therapeutic vaccine strategy against recurrent ocular herpes. IMPORTANCE Seventy percent to 90% of adults harbor herpes simplex virus 1 (HSV-1), which establishes lifelong latency in sensory neurons of the trigeminal ganglia. This latent state sporadically switches to spontaneous reactivation, resulting in viral shedding in tears. Most

  8. Therapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived “asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of local PD-1+ TIM-3+ CD8+ exhausted T cells.

    Science.gov (United States)

    Khan, Arif A; Srivastava, Ruchi; Chentoufi, Aziz A; Geertsema, Roger; Thai, Nhi Thi Uyen; Dasgupta, Gargi; Osorio, Nelson; Kalantari, Mina; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2015-07-01

    Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus 1 (HSV-1) from latency rather than to primary acute infection. No herpes simplex vaccine is currently available for use in humans. In this study, we used the HLA-A*02:01 transgenic (HLA Tg) rabbit model of ocular herpes to assess the efficacy of a therapeutic vaccine based on HSV-1 gD epitopes that are recognized mainly by CD8(+) T cells from "naturally" protected HLA-A*02:01-positive, HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease). Three ASYMP CD8(+) T-cell epitopes (gD(53-61), gD(70-78), and gD(278-286)) were linked with a promiscuous CD4(+) T-cell epitope (gD(287-317)) to create 3 separate pairs of CD4-CD8 peptides, which were then each covalently coupled to an Nε-palmitoyl-lysine moiety, a Toll-like receptor 2 (TLR-2) ligand. This resulted in the construction of 3 CD4-CD8 lipopeptide vaccines. Latently infected HLA Tg rabbits were immunized with a mixture of these 3 ASYMP lipopeptide vaccines, delivered as eye drops in sterile phosphate-buffered saline (PBS). The ASYMP therapeutic vaccination (i) induced HSV-specific CD8(+) T cells that prevent HSV-1 reactivation ex vivo from latently infected explanted trigeminal ganglia (TG), (ii) significantly reduced HSV-1 shedding detected in tears, (iii) boosted the number and function of HSV-1 gD epitope-specific CD8(+) T cells in draining lymph nodes (DLN), conjunctiva, and TG, and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1(+) TIM-3+ CD8(+) T cells. The results underscore the potential of an ASYMP CD8(+) T-cell epitope-based therapeutic vaccine strategy against recurrent ocular herpes. Seventy percent to 90% of adults harbor herpes simplex virus 1 (HSV-1), which establishes lifelong latency in sensory neurons of the trigeminal ganglia. This latent state sporadically switches to spontaneous reactivation, resulting in viral shedding in tears. Most blinding

  9. Natural infection with herpes simplex virus type 1 (HSV-1) induces humoral and T cell responses to the HSV-1 glycoprotein H : L complex

    NARCIS (Netherlands)

    Westra, DF; Verjans, GMGM; Osterhaus, ADME; van Kooij, A; Welling, GW; Scheffer, AJ; The, TH; Welling-Wester, S

    The glycoproteins of herpes simplex virus type 1 (HSV-1) are important targets for the immune system in the control of HSV-1 infections. The humoral and T cell responses to the glycoprotein (g)H-t(His):gL complex of HSV-1 were studied in seven HSV-1-seropositive and three HSV-1-seronegative healthy

  10. A truncation mutation of the neurovirulence ICP22 protein produced by a recombinant HSV-1 generated by bacterial artificial chromosome technology targets infected cell nuclei.

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    Bowles, Robert N; Blaho, John A

    2011-12-01

    The major regulatory protein ICP22 is unique among the immediate early proteins of herpes simplex virus. Viruses deleted for ICP22 replicate well in actively dividing cells, but not in quiescent cells or certain rodent lines. Accordingly, ICP22 represents an understudied herpes simplex virus (HSV) neurovirulence marker which is absolutely essential for viral neurogrowth. We utilized the bacterial artificial chromosome methodology to create a novel ICP22 truncation mutant, termed HSV-1(BACX). The integrity of HSV-1(BACX) was confirmed by detailed polymerase chain reaction analyses and immunoblotting using anti-ICP22 antibody. HSV-1(BACX) showed a reduced replication capacity in rabbit skin cells, consistent with previous studies using ICP22-null viruses. Importantly, HSV-1(BACX) localized to nuclei of infected primate Vero cells in a manner similar to wild-type ICP22. Thus, HSV-1(BACX) will serve as a useful tool to decipher the unusual biological properties and functions of the ICP22 protein.

  11. Engineering HSV-1 vectors for gene therapy.

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    Goins, William F; Huang, Shaohua; Cohen, Justus B; Glorioso, Joseph C

    2014-01-01

    Virus vectors have been employed as gene transfer vehicles for various preclinical and clinical gene therapy applications, and with the approval of Glybera (alipogene tiparvovec) as the first gene therapy product as a standard medical treatment (Yla-Herttuala, Mol Ther 20: 1831-1832, 2013), gene therapy has reached the status of being a part of standard patient care. Replication-competent herpes simplex virus (HSV) vectors that replicate specifically in actively dividing tumor cells have been used in Phase I-III human trials in patients with glioblastoma multiforme, a fatal form of brain cancer, and in malignant melanoma. In fact, T-VEC (talimogene laherparepvec, formerly known as OncoVex GM-CSF) displayed efficacy in a recent Phase III trial when compared to standard GM-CSF treatment alone (Andtbacka et al. J Clin Oncol 31: sLBA9008, 2013) and may soon become the second FDA-approved gene therapy product used in standard patient care. In addition to the replication-competent oncolytic HSV vectors like T-VEC, replication-defective HSV vectors have been employed in Phase I-II human trials and have been explored as delivery vehicles for disorders such as pain, neuropathy, and other neurodegenerative conditions. Research during the last decade on the development of HSV vectors has resulted in the engineering of recombinant vectors that are totally replication defective, nontoxic, and capable of long-term transgene expression in neurons. This chapter describes methods for the construction of recombinant genomic HSV vectors based on the HSV-1 replication-defective vector backbones, steps in their purification, and their small-scale production for use in cell culture experiments as well as preclinical animal studies.

  12. Nested PCR for detection of HSV-1 in oral mucosa.

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    Jalouli, Miranda-Masoumeh; Jalouli, Jamshid; Hasséus, Bengt; Öhman, Jenny; Hirsch, Jan-Michaél; Sand, Lars

    2015-11-01

    It has been estimated that 15%-20% of human tumours are driven by infection and inflammation, and viral infections play an important role in malignant transformation. The evidence that herpes simplex virus type 1 (HSV-1) could be involved in the aetiology of oral cancer varies from weak to persuasive. This study aimed to investigate by nested PCR (NPCR) the prevalence of HSV-1 in samples from normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma (OSCC). We investigated the prevalence of HSV-1 in biopsies obtained from 26 fresh, normal oral mucosa from healthy volunteers as well as 53 oral leukoplakia and 27 OSCC paraffin-embedded samples. DNA was extracted from the specimens and investigated for the presence of HSV-1 by nested polymerase chain reaction (NPCR) and DNA sequencing. HSV-1 was detected in 14 (54%) of the healthy samples, in 19 (36%) of the oral leukoplakia samples, and in 14 (52%) of the OSCC samples. The differences were not statistically significant. We observed a high incidence of HSV-1 in healthy oral mucosa, oral leukoplakia, and OSCC tissues. Thus, no connection between OSCC development and presence of HSV-1 was detected.

  13. IFI16 restricts HSV-1 replication by accumulating on the hsv-1 genome, repressing HSV-1 gene expression, and directly or indirectly modulating histone modifications.

    Directory of Open Access Journals (Sweden)

    Karen E Johnson

    2014-11-01

    Full Text Available Interferon-γ inducible factor 16 (IFI16 is a multifunctional nuclear protein involved in transcriptional regulation, induction of interferon-β (IFN-β, and activation of the inflammasome response. It interacts with the sugar-phosphate backbone of dsDNA and modulates viral and cellular transcription through largely undetermined mechanisms. IFI16 is a restriction factor for human cytomegalovirus (HCMV and herpes simplex virus (HSV-1, though the mechanisms of HSV-1 restriction are not yet understood. Here, we show that IFI16 has a profound effect on HSV-1 replication in human foreskin fibroblasts, osteosarcoma cells, and breast epithelial cancer cells. IFI16 knockdown increased HSV-1 yield 6-fold and IFI16 overexpression reduced viral yield by over 5-fold. Importantly, HSV-1 gene expression, including the immediate early proteins, ICP0 and ICP4, the early proteins, ICP8 and TK, and the late proteins gB and Us11, was reduced in the presence of IFI16. Depletion of the inflammasome adaptor protein, ASC, or the IFN-inducing transcription factor, IRF-3, did not affect viral yield. ChIP studies demonstrated the presence of IFI16 bound to HSV-1 promoters in osteosarcoma (U2OS cells and fibroblasts. Using CRISPR gene editing technology, we generated U2OS cells with permanent deletion of IFI16 protein expression. ChIP analysis of these cells and wild-type (wt U2OS demonstrated increased association of RNA polymerase II, TATA binding protein (TBP and Oct1 transcription factors with viral promoters in the absence of IFI16 at different times post infection. Although IFI16 did not alter the total histone occupancy at viral or cellular promoters, its absence promoted markers of active chromatin and decreased those of repressive chromatin with viral and cellular gene promoters. Collectively, these studies for the first time demonstrate that IFI16 prevents association of important transcriptional activators with wt HSV-1 promoters and suggest potential

  14. Nested PCR for detection of HSV-1 in oral mucosa

    OpenAIRE

    Jalouli, Miranda-Masoumeh; Jalouli, Jamshid; Hasséus, Bengt; Öhman, Jenny; Hirsch, Jan-Michaél; Sand, Lars

    2015-01-01

    Background: It has been estimated that 15%-20% of human tumours are driven by infection and inflammation, and viral infections play an important role in malignant transformation. The evidence that herpes simplex virus type 1 (HSV-1) could be involved in the aetiology of oral cancer varies from weak to persuasive. This study aimed to investigate by nested PCR (NPCR) the prevalence of HSV-1 in samples from normal oral mucosa, oral leukoplakia, and oral squamous ...

  15. In Vitro Synergism of Trifluorothymidine and Ganciclovir against HSV-1

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    Hobden, Jeffery A.; Kumar, Manish; Kaufman, Herbert E.; Clement, Christian; Varnell, Emily D.; Bhattacharjee, Partha S.

    2011-01-01

    Purpose. To determine whether trifluorothymidine (TFT) and ganciclovir (GCV) are synergistic against herpes simplex virus type 1 (HSV-1). Methods. TFT and GCV activity against 12 strains of HSV-1 (including an acyclovir-resistant strain) was measured by plaque-forming unit (PFU) inhibition. Cellular toxicity was assessed with an MTT dye reduction assay. Synergism was determined by calculating fractional inhibitory concentration (FIC indices) based on PFU reduction. Results. Concentrations of TFT resulting in 50% inhibition of PFUs (IC50) of acyclovir-susceptible HSV-1 strains ranged from 3.07 ± 0.36 to 12.52 ± 0.61 μM. GCV IC50 values ranged from 0.40 ± 0.02 to 1.59 ± 0.14 μM. IC50 values of TFT and GCV against the acyclovir-resistant strain were 15.40 ± 3.17 and 93.00 ± 9.64 μM, respectively. Concentrations of TFT or GCV resulting in 50% cell cytotoxicity (CC50) were 0.99 ± 0.01 and 92.91 ± 8.92 μM, respectively. TFT and GCV combined (10:1) were 10 times more potent against all acyclovir-susceptible HSV-1 strains. For 8 of 12 HSV-1 strains, the IC50 of TFT and GCV combined was lower than the CC50 of either drug. For acyclovir-susceptible HSV-1 strains, TFT and GCV combined generated a FIC index of <0.5, suggesting strong synergism between the two drugs. The FIC value for TFT and GCV combined against the acyclovir-resistant HSV-1 strain was 0.84, indicating nonantagonism. Conclusions. TFT and GCV are synergistic against acyclovir-susceptible HSV-1 at concentrations significantly less toxic than if each antiviral were used as a sole agent. PMID:20861476

  16. PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection.

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    He, Jiucheng; Neumann, Donna; Kakazu, Azucena; Pham, Thang Luong; Musarrat, Farhana; Cortina, M Soledad; Bazan, Haydee E P

    2017-08-01

    Herpes simplex virus type-1 (HSV-1) infection leads to impaired corneal sensation and, in severe cases, to corneal ulceration, melting and perforation. Here, we explore the potential therapeutic action of pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA) on corneal inflammation and nerve regeneration following HSV-1 infection. Rabbits inoculated with 100,000 PFU/eye of HSV-1 strain 17Syn+ were treated with PEDF + DHA or vehicle. PEDF + DHA treatment resulted in a biphasic immune response with stronger infiltration of CD4+T cells, neutrophils and macrophages at 7-days post-treatment (p.t.) that was significantly decreased by 14 days, compared to the vehicle-treated group. Screening of 14 immune-related genes by q-PCR showed that treatment induced higher expression of IFN-γ and CCL20 and inhibition of IL-18 by 7 days in the cornea. PEDF + DHA-treated animals developed less dendritic corneal lesions, opacity and neovascularization. Corneal nerve density increased at 12-weeks p.t. with functional recovery of corneal sensation. Treatment with PEDF + DHA that was postponed by 3 weeks also showed increased nerve density when compared to vehicle. Our data demonstrate that PEDF + DHA promotes resolution of the inflammatory response to the virus and, most importantly, induces regeneration of damaged corneal nerves vital for maintaining ocular surface homeostasis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Widespread disruption of host transcription termination in HSV-1 infection

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    Rutkowski, Andrzej J.; Erhard, Florian; L'Hernault, Anne; Bonfert, Thomas; Schilhabel, Markus; Crump, Colin; Rosenstiel, Philip; Efstathiou, Stacey; Zimmer, Ralf; Friedel, Caroline C.; Dölken, Lars

    2015-01-01

    Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription and RNA processing and their impact on translation can be analysed in a single experimental setting by applying 4sU-tagging of newly transcribed RNA and ribosome profiling to lytic HSV-1 infection. Unexpectedly, we find that HSV-1 triggers the disruption of transcription termination of cellular, but not viral, genes. This results in extensive transcription for tens of thousands of nucleotides beyond poly(A) sites and into downstream genes, leading to novel intergenic splicing between exons of neighbouring cellular genes. As a consequence, hundreds of cellular genes seem to be transcriptionally induced but are not translated. In contrast to previous reports, we show that HSV-1 does not inhibit co-transcriptional splicing. Our approach thus substantially advances our understanding of HSV-1 biology and establishes HSV-1 as a model system for studying transcription termination. PMID:25989971

  18. Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons.

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    Yanez, Andy A; Harrell, Telvin; Sriranganathan, Heather J; Ives, Angela M; Bertke, Andrea S

    2017-02-07

    Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG) and sympathetic superior cervical ganglia (SCG) after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF) deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN) and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons.

  19. Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons

    Directory of Open Access Journals (Sweden)

    Andy A. Yanez

    2017-02-01

    Full Text Available Herpes simplex viruses (HSV1 and HSV2 establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs. Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG and sympathetic superior cervical ganglia (SCG after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons.

  20. Effects of Electroacupuncture on Facial Nerve Function and HSV-1 DNA Quantity in HSV-1 Induced Facial Nerve Palsy Mice

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    Hongzhi Tang

    2014-01-01

    Full Text Available Acupuncture is a common and effective therapeutic method to treat facial nerve palsy (FNP. However, its underlying mechanism remains unclear. This study was aimed to investigate the effects of electroacupuncture on symptoms and content of HSV-1 DNA in FNP mice. Mice were randomized into four groups, an electroacupuncture treatment group, saline group, model animal group, and blank control group. Electroacupuncture was applied at Jiache (ST6 and Hegu (LI4 in electroacupuncture group once daily for 14 days, while electroacupuncture was not applied in model animal group. In electroacupuncture group, mice recovered more rapidly and HSV-1 DNA content also decreased more rapidly, compared with model animal group. We conclude that electroacupuncture is effective to alleviate symptoms and promote the reduction of HSV-1 in FNP.

  1. Effects of Electroacupuncture on Facial Nerve Function and HSV-1 DNA Quantity in HSV-1 Induced Facial Nerve Palsy Mice

    Science.gov (United States)

    Tang, Hongzhi; Feng, Shuwei; Chen, Jiao; Yang, Mingxiao; Zhong, Zhendong; Li, Ying; Liang, Fanrong

    2014-01-01

    Acupuncture is a common and effective therapeutic method to treat facial nerve palsy (FNP). However, its underlying mechanism remains unclear. This study was aimed to investigate the effects of electroacupuncture on symptoms and content of HSV-1 DNA in FNP mice. Mice were randomized into four groups, an electroacupuncture treatment group, saline group, model animal group, and blank control group. Electroacupuncture was applied at Jiache (ST6) and Hegu (LI4) in electroacupuncture group once daily for 14 days, while electroacupuncture was not applied in model animal group. In electroacupuncture group, mice recovered more rapidly and HSV-1 DNA content also decreased more rapidly, compared with model animal group. We conclude that electroacupuncture is effective to alleviate symptoms and promote the reduction of HSV-1 in FNP. PMID:24991226

  2. HSV-1-Based Vectors for Gene Therapy of Neurological Diseases and Brain Tumors: Part II. Vector Systems and Applications

    Directory of Open Access Journals (Sweden)

    Andreas Jacobs

    1999-11-01

    Full Text Available Many properties of HSV-1 are especially suitable for using this virus as a vector to treat diseases affecting the central nervous system (CNS, such as Parkinson's disease or malignant gliomas. These advantageous properties include natural neurotropism, high transduction efficiency, large transgene capacity, and the ability of entering a latent state in neurons. Selective oncolysis in combination with modulation of the immune response mediated by replication-conditional HSV-1 vectors appears to be a highly promising approach in the battle against malignant glioma. Helper virus-free HSV/AAV hybrid amplicon vectors have great promise in mediating long-term gene expression in the PNS and CNS for the treatment of various neurodegenerative disorders or chronic pain. Current research focuses on the design of HSV-1-derived vectors which are targeted to certain cell types and support transcriptionally regulatable transgene expression. Here, we review the recent developments on HSV-1-based vector systems and their applications in experimental and clinical gene therapy protocols.

  3. First HSV-1 non primary genital herpes in two patients.

    Science.gov (United States)

    Fouéré, Sébastien; Chaine, Bénédicte; Maylin, Sarah; Minier, Marine; Vallée, Pascale; Scieux, Catherine; Lassau, François; Legoff, Jérôme; Janier, Michel

    2016-05-01

    First HSV-1 genital episodes in HSV-2 infected patients however, had never been demonstrated until the 2 cases we observed. This scarcity could reflect the lower impact of HSV-2 on western populations but questions the existence of cross-protection between viral types. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Short hairpin RNA-mediated inhibition of HSV-1 gene expression and function during HSV-1 infection in Vero cells.

    Science.gov (United States)

    Liu, Yuan-yuan; Deng, Hai-ying; Yang, Guang; Jiang, Wen-lin; Grossin, Laurent; Yang, Zhan-qiu

    2008-08-01

    To evaluate the efficiency of 3 short hairpin RNA (shRNA) interfering with the herpes simplex virus type 1 (HSV-1) gene coding glycoprotein D (gD) for inhibiting the gD expression and virus replication in vitro. Vero cells were selected for an in vitro model of infection. Three shRNA sequences (shRNAgD1, -gD2, and -gD3) targeting specifically the gD gene of HSV-1 were selected for evaluating the antiviral effects. The antiviral effects of shRNA in the cells infected with HSV-1 were evaluated by cytopathic effect (CPE) observations and plaque assays. The transcription level of viral RNA and the gD expression were studied by RT-PCR, Western blotting, and flow cytometry. With the 3 shRNA at a final concentration of 120 nmol/L, a significant inhibition of CPE in the HSV-1-infected cells was observed. The ED50 of shRNA-gD1, gD2, and gD3 were 48.74+/-2.57, 57.13+/-3.24, and 114.64+/-5.12 nmol/L, respectively. The gD gene decreased significantly after viral infection in the Vero cells pretreated with shRNA compared to the virus group. The expressions of the gD protein, determined by Western blotting and flow cytometry, were also drastically decreased in shRNA-transfected cells. Exogenous shRNA molecules can suppress the HSV-1 gD expression. They are inhibitors of HSV replication during infection in Vero cells.

  5. Short hairpin-loop-structured oligodeoxynucleotides reduce HSV-1 replication

    Directory of Open Access Journals (Sweden)

    Heinrich Jochen

    2009-04-01

    Full Text Available Abstract The Herpes simplex virus (HSV is known as an infectious agent and widespread in the human population. The symptoms of HSV infections can range from mild to life threatening, especially in immune-compromised individuals. HSV infections are commonly treated with the guanosine analogue Aciclovir, but reports of resistance are increasing. Efforts are made to establish single-stranded antisense oligodeoxynucleotides (as and small interfering ribonucleic acids (siRNAs for antiviral treatment. Recently, another class of short interfering nucleic acids, partially double-stranded hairpin loop-structured 54 mer oligodeoxynucleotides (ODNs, was shown to allow hydrolysis of HIV RNA by binding to the viral RNA. This leads to a substrate for the viral RNase H. To assess the potential of such ODNs for inhibition of HSV-1 replication, five partially double-stranded ODNs were designed based on the sequences of known siRNAs against HSV-1 with antiviral activity. Three of them are directed against early and two against leaky late genes. Primary human lung fibroblasts, MRC-5, and African green monkey kidney cells, Vero, were transfected with ODNs and subsequently infected. The effect on HSV-1 replication was determined by analyzing the virus titer in cell culture supernatants by quantitative PCR and plaque assays. An inhibitory effect was observed with all five selected ODNs, with two cases showing statistical significance in both cell types. The observed effect was sequence-specific and dose dependent. In one case the ODN was more efficient than a previously described siRNA directed against the same target site in the mRNA of UL5, a component of the helicase/primase complex. HSV-1 virions and ODNs can be applied simultaneously without transfection reagent, but at a 50-fold higher concentration to Vero cells with similar efficiencies. The results underline the potential of partially double-stranded hairpin loop-structured ODNs as antiviral agents.

  6. Adeno-associated Virus Vectors Efficiently Transduce Mouse and Rabbit Sensory Neurons Coinfected with Herpes Simplex Virus 1 following Peripheral Inoculation.

    Science.gov (United States)

    Watson, Zachary L; Ertel, Monica K; Lewin, Alfred S; Tuli, Sonal S; Schultz, Gregory S; Neumann, Donna M; Bloom, David C

    2016-09-01

    Following infection of epithelial tissues, herpes simplex virus 1 (HSV-1) virions travel via axonal transport to sensory ganglia and establish a lifelong latent infection within neurons. Recent studies have revealed that, following intraganglionic or intrathecal injection, recombinant adeno-associated virus (rAAV) vectors can also infect sensory neurons and are capable of stable, long-term transgene expression. We sought to determine if application of rAAV to peripheral nerve termini at the epithelial surface would allow rAAV to traffic to sensory ganglia in a manner similar to that seen with HSV. We hypothesized that footpad or ocular inoculation with rAAV8 would result in transduction of dorsal root ganglia (DRG) or trigeminal ganglia (TG), respectively. To test this, we inoculated the footpads of mice with various amounts of rAAV as well as rAAV capsid mutants. We demonstrated that this method of inoculation can achieve a transduction rate of >90% of the sensory neurons in the DRG that innervate the footpad. Similarly, we showed that corneal inoculation with rAAV vectors in the rabbit efficiently transduced >70% of the TG neurons in the optic tract. Finally, we demonstrated that coinfection of mouse footpads or rabbit eyes with rAAV vectors and HSV-1 resulted in colocalization in nearly all of the HSV-1-positive neurons. These results suggest that rAAV is a useful tool for the study of HSV-1 infection and may provide a means to deliver therapeutic cargos for the treatment of HSV infections or of dysfunctions of sensory ganglia. Adeno-associated virus (AAV) has been shown to transduce dorsal root ganglion sensory neurons following direct intraganglionic sciatic nerve injection and intraperitoneal and intravenous injection as well as intrathecal injection. We sought to determine if rAAV vectors would be delivered to the same sensory neurons that herpes simplex virus (HSV-1) infects when applied peripherally at an epithelial surface that had been treated to expose

  7. Analysis of the SUMO2 Proteome during HSV-1 Infection.

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    Elizabeth Sloan

    2015-07-01

    Full Text Available Covalent linkage to members of the small ubiquitin-like (SUMO family of proteins is an important mechanism by which the functions of many cellular proteins are regulated. Sumoylation has roles in the control of protein stability, activity and localization, and is involved in the regulation of transcription, gene expression, chromatin structure, nuclear transport and RNA metabolism. Sumoylation is also linked, both positively and negatively, with the replication of many different viruses both in terms of modification of viral proteins and modulation of sumoylated cellular proteins that influence the efficiency of infection. One prominent example of the latter is the widespread reduction in the levels of cellular sumoylated species induced by herpes simplex virus type 1 (HSV-1 ubiquitin ligase ICP0. This activity correlates with relief from intrinsic immunity antiviral defence mechanisms. Previous work has shown that ICP0 is selective in substrate choice, with some sumoylated proteins such the promyelocytic leukemia protein PML being extremely sensitive, while RanGAP is completely resistant. Here we present a comprehensive proteomic analysis of changes in the cellular SUMO2 proteome during HSV-1 infection. Amongst the 877 potentially sumoylated species detected, we identified 124 whose abundance was decreased by a factor of 3 or more by the virus, several of which were validated by western blot and expression analysis. We found many previously undescribed substrates of ICP0 whose degradation occurs by a range of mechanisms, influenced or not by sumoylation and/or the SUMO2 interaction motif within ICP0. Many of these proteins are known or are predicted to be involved in the regulation of transcription, chromatin assembly or modification. These results present novel insights into mechanisms and host cell proteins that might influence the efficiency of HSV-1 infection.

  8. Visualization of mouse neuronal ganglia infected by Herpes Simplex Virus 1 (HSV-1) using multimodal non-linear optical microscopy.

    Science.gov (United States)

    Rochette, Pierre-Alexandre; Laliberté, Mathieu; Bertrand-Grenier, Antony; Houle, Marie-Andrée; Blache, Marie-Claire; Légaré, François; Pearson, Angela

    2014-01-01

    Herpes simplex virus 1 (HSV-1) is a neurotropic virus that causes skin lesions and goes on to enter a latent state in neurons of the trigeminal ganglia. Following stress, the virus may reactivate from latency leading to recurrent lesions. The in situ study of neuronal infections by HSV-1 is critical to understanding the mechanisms involved in the biology of this virus and how it causes disease; however, this normally requires fixation and sectioning of the target tissues followed by treatment with contrast agents to visualize key structures, which can lead to artifacts. To further our ability to study HSV-1 neuropathogenesis, we have generated a recombinant virus expressing a second generation red fluorescent protein (mCherry), which behaves like the parental virus in vivo. By optimizing the application of a multimodal non-linear optical microscopy platform, we have successfully visualized in unsectioned trigeminal ganglia of mice both infected cells by two-photon fluorescence microscopy, and myelinated axons of uninfected surrounding cells by coherent anti-Stokes Raman scattering (CARS) microscopy. These results represent the first report of CARS microscopy being combined with 2-photon fluorescence microscopy to visualize virus-infected cells deep within unsectioned explanted tissue, and demonstrate the application of multimodal non-linear optical microscopy for high spatial resolution biological imaging of tissues without the use of stains or fixatives.

  9. Autoradiography study and SPECT imaging of reporter gene HSV1-tk expression in heart

    Energy Technology Data Exchange (ETDEWEB)

    Lan Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, 430022 (China)], E-mail: LXL730724@hotmail.com; Liu Ying; He Yong; Wu Tao; Zhang Binqing; Gao Zairong; An Rui [Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, 430022 (China); Zhang Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, 430022 (China)], E-mail: zhyx1229@163.com

    2010-04-15

    Aim: To demonstrate the feasibility and optimal conditions of imaging herpes simplex virus 1-thymidine kinase (HSV1-tk) gene transferred into hearts with {sup 131}I-2'-fluoro-2'-deoxy-1-{beta}-D-arabinofuranosyl-5-iodouracil ({sup 131}I-FIAU) using autoradiography (ARG) and single photon emission computed tomography (SPECT) in animal models. Methods: HSV1-tk inserted into adenovirus vector (Ad5-tk) and adenovirus (Ad5-null) was prepared. Rats or rabbits were divided into a study group receiving intramyocardial injection of Ad5-tk, and a control group receiving Ad-null injection. In the study group of rats, two sets of experiments, time-course study and dose-dependence study, were performed. In time-course experiments, rats were injected with {sup 131}I-FIAU on Days 1, 2, 3, 5 and 7, after transfection of 1x10{sup 8} pfu Ad5-tk, to study the feasibility and suitable time course for reporter gene imaging. In dose-dependence study, various titers of Ad5-tk (5x10{sup 8}, 1x10{sup 8}, 5x10{sup 7} and 1x10{sup 7} pfu) were used to determine the threshold and optimal viral titer needed for detection of gene expression. The gamma counts of hearts were measured. The rat myocardium was analyzed by ARG and reverse transcriptase-polymerase chain reaction (RT-PCR). SPECT whole-body planar imaging and cardiac tomographic imaging were performed in the rabbit models. Results: From the ARG images, rats injected with Ad5-tk showed significant {sup 131}I-FIAU activity in the anterolateral wall compared with background signals seen in the control Ad5-null rats. In time-course study, the highest radioactivity in the focal myocardium could be seen on Day 1, and then progressively declined with time. In dose-dependence study, the level of {sup 131}I-FIAU accumulation in the transfected myocardium declined with the decrease of Ad viral titers. From the ARG analysis and gamma counting, the threshold viral titer was 5x10{sup 7} pfu, and the optimal Ad titer was 1x10{sup 8} pfu

  10. An attenuated herpes simplex virus type 1 (HSV1 encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

    Directory of Open Access Journals (Sweden)

    Mariaconcetta Sicurella

    Full Text Available Herpes simplex virus types 1 and 2 (HSV1 and HSV2 are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat. In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ, induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1

  11. Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection.

    Science.gov (United States)

    Zhang, Jie; Liu, Huan; Wei, Bin

    Herpes simplex virus type 1 (HSV-1), a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine candidates for HSV-1.

  12. HSV-1-Based Vectors for Gene Therapy of Neurological Diseases and Brain Tumors: Part I. HSV-1 Structure, Replication and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Andreas Jacobs

    1999-11-01

    Full Text Available The design of effective gene therapy strategies for brain tumors and other neurological disorders relies on the understanding of genetic and pathophysiological alterations associated with the disease, on the biological characteristics of the target tissue, and on the development of safe vectors and expression systems to achieve efficient, targeted and regulated, therapeutic gene expression. The herpes simplex virus type 1 (HSV-1 virion is one of the most efficient of all current gene transfer vehicles with regard to nuclear gene delivery in central nervous system-derived cells including brain tumors. HSV-1-related research over the past decades has provided excellent insight into the structure and function of this virus, which, in turn, facilitated the design of innovative vector systems. Here, we review aspects of HSV-1 structure, replication and pathogenesis, which are relevant for the engineering of HSV-1-based vectors.

  13. Seroprevalence of serum IgG of HSV-1 coinfected with HIV infected ...

    African Journals Online (AJOL)

    Purpose: To determine the seroprevalence of IgG of HSV-1 coinfected HIV patients who attended Offa General Hospital, Highly Active Antiretroviral Therapy Clinic (HAART). Methods: A cross sectional study used to study the seroprevalence of IgG of HSV-1 coinfected HIV infected patients that attended Offa Highly Active ...

  14. Herpes Simplex Virus (HSV-1 Encephalitis Mimicking Glioblastoma: Case Report and Review of the Literature

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    Burke A. Cunha

    2014-12-01

    Full Text Available Glioblastoma multiforme (GBM often presents as a brain mass with encephalitis. In a patient with GBM, subsequent presentation with new onset encephalitis may be due to another GBM or Herpes simplex virus 1 (HSV-1 encephalitis. We present a case of HSV-1 encephalitis mimicking GBM in a patient with previous GBM.

  15. Autologous antibody is protective against HSV-1 infection of the immunocompromised mouse.

    Science.gov (United States)

    Alexander, T S; Rosenthal, K S

    1990-09-01

    The protective capability of autologous anti-herpes simplex virus type 1 (anti-HSV-1) antibody was analyzed in immunosuppressed mice. Immunologically naive, immunosuppressed mice infected with a low-passage clinical HSV-1 isolate developed local site lesions, monoplegia, paraplegia, and died within 8 days. Mice that had recovered from a previous HSV-1 infection and were immunosuppressed with cyclophosphamide and then rechallenged with live virus showed no symptoms and survived. Untreated mice that had recovered from infection (primed mice) had high titers of anti-HSV-1 antibody and a delayed type hypersensitivity (DTH) response to virus challenge. Cyclophosphamide treatment, but not lethal irradiation, could ablate the DTH response, resulting in a lack of antivirus cell-mediated immunity. Antibody was the only demonstrable protective immune function in the cyclophosphamide-treated animals. This indicates that cell-mediated immunity is not required for protection against HSV-1 challenge in individuals with virus-specific antibody.

  16. Experimental infections of rabbits with proliferative and latent stages of Besnoitia besnoiti.

    Science.gov (United States)

    Liénard, Emmanuel; Pop, Loredana; Prevot, Françoise; Grisez, Christelle; Mallet, Virginie; Raymond-Letron, Isabelle; Bouhsira, Émilie; Franc, Michel; Jacquiet, Philippe

    2015-10-01

    Cattle besnoitiosis due to Besnoitia besnoiti is spreading across Europe and is responsible for severe economic losses in newly infected herds. Experimentally speaking, rabbits have been found to be susceptible to this parasite. The adaptation of B. besnoiti to rabbits may offer a new, easier and cheaper model of investigation for this disease. This study compared the virulence between tachyzoites and bradyzoites of B. besnoiti in rabbits. Eighteen New Zealand rabbits were allocated into three groups of six animals each. The rabbits from the control (group C), "tachyzoite" (group T) and "bradyzoite" (group B) groups were subcutaneously injected in the right flank with 66 μg of ovalbumin, 6.10(6) tachyzoites (125th passage on Vero cells) and 6.10(6) bradyzoites (collected from a natural infected cow) of B. besnoiti, respectively. Clinical follow-up and blood sampling for serological survey and qPCR were performed during 10 weeks until euthanasia. Molecular and immunohistochemistry examination was achieved on 25 samples of tissue per rabbit. Seroconversion occurred in group T without any clinical signs. Rabbits of group B exhibited a febrile condition (temperature above 40 °C from day 8 to day 11 following injection) with positive qPCR in blood. Cysts of B. besnoiti were found on skin samples and organs of rabbits from group B in tissue explored with threshold cycle (Ct) values below 30. These results suggest a higher virulence of bradyzoites in rabbits than Vero cell-cultivated tachyzoites. The proposed model could be used to assess the in vivo effectiveness of vaccine or drugs against cattle besnoitiosis.

  17. The effect of cellular differentiation on HSV-1 infection of oligodendrocytic cells.

    Directory of Open Access Journals (Sweden)

    Raquel Bello-Morales

    Full Text Available Herpes simplex type 1 (HSV-1 is a neurotropic virus that infects many types of cells. Previous studies have demonstrated that oligodendrocytic cells are highly susceptible to HSV-1 infection. Here we analysed HSV-1 infection of a human oligodendrocytic cell line, HOG, and oligodendrocyte precursor cells (OPCs cultured under growth or differentiation conditions. In addition to cell susceptibility, the role of the major cell receptors for viral entry was assessed. Our results revealed that OPCs and HOG cells cultured under differentiation conditions became more susceptible to HSV-1. On the other hand, viral infection induced morphological changes corresponding to differentiated cells, suggesting that HSV-1 might be inducing cell differentiation. We also observed colocalization of HVEM and nectin-1 with viral particles, suggesting that these two major HSV-1 receptors are functional in HOG cells. Finally, electron microscopy assays indicated that HSV-1 may be also entering OLs by macropinocytosis depending on their differentiation stage. In addition, vesicles containing intracellular enveloped virions observed in differentiated cells point to an endocytic mechanism of virus entry. All these data are indicative of diverse entry pathways dependent on the maturation stage of OLs.

  18. Mechanism of inhibition of HSV-1 replication by tumor necrosis factor and interferon gamma.

    Science.gov (United States)

    Feduchi, E; Carrasco, L

    1991-02-01

    Tumor necrosis factor (TNF) synergizes with interferon (IFN gamma) in the blockade of HSV-1 replication. Antibodies against IFN beta block this synergism, implying a role of IFN beta in the antiviral activity of TNF plus IFN gamma. IFN beta 1 added exogenously to Hep-2 cells shows antiviral activity against HSV-1 only at high concentrations, whereas IFN beta 2 (also known as IL-6) alone has no effect on the replication of VSV or HSV-1 even when 1,000 U/ml are present. Our results are in accordance with the idea that TNF induces IFN beta 1 and that both cytokines must be present in the culture medium to synergize with IFN gamma in order to inhibit HSV-1 replication.

  19. Inhibitory effect of aqueous extract of Echinacea purpurea and Nerium oleander on HSV-1 multiplication

    OpenAIRE

    Maliheh Farahani

    2014-01-01

    Background: Treatment of HSV-1 infections with the available chemical drugs may have some problems such as drug resistance and virus latency. Therefore, there is a requirement for new antiherpes drugs in today's world. The present study was carried out to analyze the inhibitory effect of Echinacea purpurea and Nerium oleander plants with ethnomedical background on HSV-1 replication. Methods: Plants were extracted by decoction method to obtain aqueous extract. These extracts were screened f...

  20. Combination of MPPa-PDT and HSV1-TK/GCV gene therapy on prostate cancer.

    Science.gov (United States)

    Liang, Liming; Bi, Wenxiang; Chen, Weiwen; Lin, Yani; Tian, Yuanyuan

    2018-02-01

    We combined pyropheophorbide-a methyl ester, photodynamic therapy (MPPa-PDT), 670 ± 10 nm, 4 mW/cm 2 , with herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV1-TK/GCV) to improve the therapeutic effect. We built HSV1-TK expression vector GV230-TK and we observed a bright green fluorescence under fluorescence microscope. It indicated the recombinant plasmid was transfected into PC-3M prostate cancer cells successfully. As the abundant glucose-regulated protein 78 (GRP78) promoter in PC-3M cells can cause active expression of HSV1-TK, cell protein was collected for western blot to determine the expression of HSV1-TK. In CCK-8 assay (n = 6), the cell survival rate of combined treatment group was about 10%, less than that of pure MPPa-PDT group (23%) and pure HSV1-TK/GCV group (35%) (t test, P PDT group (about 22%) and pure HSV1-TK/GCV group (about 19%). The results showed that the combination of the two treatments can effectively improve the cytocidal effect in PC-3M cells.

  1. Almond Skin Extracts Abrogate HSV-1 Replication by Blocking Virus Binding to the Cell

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    Carlo Bisignano

    2017-07-01

    Full Text Available The aim of the present research was to determine the effect of almond skin extracts on herpes simplex virus 1 (HSV-1 replication. Drug-resistant strains of HSV frequently develop following therapeutic treatment. Therefore, the discovery of novel anti-HSV drugs deserves great effort. Here, we tested both natural (NS and blanched (BS polyphenols-rich almond skin extracts against HSV-1. HPLC analysis showed that the prevalent compounds in NS and BS extracts contributing to their antioxidant activity were quercetin, epicatechin and catechin. Results of cell viability indicated that NS and BS extracts were not toxic to cultured Vero cells. Furthermore, NS extracts were more potent inhibitors of HSV-1 than BS extracts, and this trend was in agreement with different concentrations of flavonoids. The plaque forming assay, Western blot and real-time PCR were used to demonstrate that NS extracts were able to block the production of infectious HSV-1 particles. In addition, the viral binding assay demonstrated that NS extracts inhibited HSV-1 adsorption to Vero cells. Our conclusion is that natural products from almond skin extracts are an extraordinary source of antiviral agents and provide a novel treatment against HSV-1 infections.

  2. Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells

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    Lei-qing Li

    2013-01-01

    Full Text Available Although the combination of herpes simplex virus type 1 (HSV-1 thymidine kinase (TK with ganciclovir (GCV has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then the in vivo sensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5-dimethylthiahiazo-(-z-y1-3,5-di-phenytetrazoliumromide (MTT colorimetric assay and Hoechst-propidium iodide (PI staining. Finally, a subcutaneously C6 xenograft tumor model was established in the nude mice to test the in vitro efficacy of TK/GCV gene therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and in vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical setting.

  3. Assessment of Anti HSV-1 Activity of Aloe Vera Gel Extract: an In Vitro Study.

    Science.gov (United States)

    Rezazadeh, Fahimeh; Moshaverinia, Maryam; Motamedifar, Mohammad; Alyaseri, Montazer

    2016-03-01

    Herpes simplex virus (HSV) infection is one of the most common and debilitating oral diseases; yet, there is no standard topical treatment to control it. The extract of Aloe vera leaves has been previously reported to have anti-inflammatory, antibacterial, and also antiviral effects. There is no data on anti-Herpes simplex virus type 1 (HSV-1) activity of Aloe vera gel. This study aimed to evaluate the anti-HSV-1 activity of Aloe vera gel in Vero cell line. In this study, gel extraction and cytotoxicity of various increasing concentrations of Aloe vera gel (0.2, 0.5, 1, 2, and 5%) was evaluated in Dulbecco's Modified Eagle Medium (DMEM) containing 2% fetal bovine serum (FBS). Having been washed with phosphate buffered saline, 50 plaque-forming units (PFU) of HSV-1 was added to each well. After 1 hour of incubation at 37°C, cell monolayers in 24 well plates were exposed to different increasing concentrations of Aloe vera gel. The anti-HSV-1 activity of Aloe vera gel in different concentrations was assessed by plaque reduction assays. Data were analyzed by using One-way ANOVA. The cytotoxicity assay showed that Aloe vera in prearranged concentrations was cell-compatible. The inhibitory effect of various concentrations of Aloe vera was observed one hour after the Vero cell was infected with HSV-1. However, there was no significant difference between two serial concentrations (p> 0.05). One-way ANOVA also revealed no significant difference between the groups. The findings indicated a dose-dependent antiviral effect of Aloe vera. The findings showed significant inhibitory effect of 0.2-5% Aloe vera gel on HSV-1 growth in Vero cell line. Therefore, this gel could be a useful topical treatment for oral HSV-1 infections without any significant toxicity.

  4. DNA vaccine-encoded glycoprotein B of HSV-1 fails to protect chronic morphine-treated mice against HSV-1 challenge.

    Science.gov (United States)

    Jamali, Abbas; Roostaee, Mohammad H; Soleimanjahi, Hoorieh; Ghaderi Pakdel, Firouz; Bamdad, Taravat

    2007-03-01

    The use of morphine has been demonstrated to increase susceptibility to infections. Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen among immunocompromised individuals. In the present study, due to the importance of HSV vaccination in morphine abusers, the effects of chronic morphine exposure on the host response to a HSV-1 gB DNA-based vaccine have been investigated. The study is addressing an important aspect of vaccine development among the susceptible (immunocompromised) hosts. BALB/c mice were exposed to morphine over 11 days. They were then vaccinated with DNA vaccine or KOS strain as a live vaccine. The findings showed that the morphine-treated animals failed to respond to DNA vaccination evaluated by the anti-HSV gB antibody titer, delayed type hypersensitivity (DTH) and lethal HSV-1 challenge. Under the same conditions, the KOS vaccine showed a reduced Ab titer and DTH response in morphine-treated mice, but could protect mice against the lethal challenge and was safe for vaccination of morphine-treated animals.

  5. 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.

  6. HSV-1-induced chemokine expression via IFI16-dependent and IFI16-independent pathways in human monocyte-derived macrophages

    DEFF Research Database (Denmark)

    Søby, Stine; Laursen, Rune R; Østergaard, Lars Jørgen

    2012-01-01

    and monocytes were differentiated to macrophages. Macrophages infected with HSV-1 were analyzed using siRNA-mediated knock-down of IFI16 by real-time PCR, ELISA, and Western blotting. RESULTS: We determined that both CXCL10 and CCL3 are induced independent of HSV-1 replication. IFI16 mediates CCL3 m......RNA accumulation during early HSV-1 infection. In contrast, CXCL10 was induced independently of IFI16. CONCLUSIONS: Our data provide the first evidence of HSV-1-induced innate immune responses via IFI16 in human primary macrophages. In addition, the data suggest that at least one additional unidentified receptor...

  7. The antiviral effect of three plant species of Iran on HSV-1

    Directory of Open Access Journals (Sweden)

    malihe Farahani

    2016-05-01

    Full Text Available Background : plants have had special position in human life and their medicinal application have been observed in manuscripts of many world scientists. Nowadays the treatment of HSV-1 infections with the available  chemical drugs often leads to the problems due to viral resistance and virus latency duration, therefore there is a requirement for new anti-herpes drugs.In this research the antiviral effects of  Camellia sinesis, Echium amoenumL and Nerium oleander, with ethnomedical background on HSV-1 were studied. Materials and Methods:The plants were extracted with decoction method to obtain aqueous extracts and after evaluating their cytotoxicity on Hep-2 cell lines by evaluating CPE, antiherpes effect of the plants extracts were determined by cytopathic effect inhibition assay. Results: Nerium oleander extract had the  most toxicity (> 50 μg/ml on cell line and Camellia sinesis showed the most inhibitory property on HSV-1 multiplication. Echium amoenumL had the lowest antiherpes effect. Camellia sinesis was inhibitor of virus multiplication completely at 50-1000 μg/ml and Echium amoenumL at concentrations >300 μg/ml. Conclusion: Camellia sinesis and Echium amoenumL could inhibit well HSV-1 multiplication completely at concentrations nontoxic. Further researches are needed to find the effect mechanism of these drugs which may be used in the manufacture of new antiherpes drugs.

  8. Inhibitory effect of aqueous extract of Echinacea purpurea and Nerium oleander on HSV-1 multiplication

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    Maliheh Farahani

    2014-02-01

    Full Text Available Background: Treatment of HSV-1 infections with the available chemical drugs may have some problems such as drug resistance and virus latency. Therefore, there is a requirement for new antiherpes drugs in today's world. The present study was carried out to analyze the inhibitory effect of Echinacea purpurea and Nerium oleander plants with ethnomedical background on HSV-1 replication. Methods: Plants were extracted by decoction method to obtain aqueous extract. These extracts were screened for their cytotoxicity against Hep-2 cell line by CPE (cytopathic effect assay. Antiviral effect of the plant extracts were determined by the virus cytopathic effect inhibition assay. Results: Nerium oleander extract had the highest toxicity (>0.1 μg/ml on Hep-2 cells and Echinacea purpurea extract exhibited significant antiherpes effect at nontoxic concentrations used on the cell lines. Findings indicated that Echinacea purpurea extract inhibited HSV-1 multiplication at concentrations >400 μg/ml. Conclusion: Echinacea purpurea plant had no any effect on cells at nontoxic concentrations and inhibited HSV-1 multiplication at concentrations >400 μg/ml. Further research is needed to find out the anti herpetic mechanism of this plant.

  9. PD-L1-Expressing Dendritic Cells Contribute to Viral Resistance during Acute HSV-1 Infection

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    Katie M. Bryant-Hudson

    2012-01-01

    Full Text Available The inhibitory receptor, Programmed Death 1 (PD-1, and its ligands (PD-L1/PD-L2 are thought to play a role in immune surveillance during chronic viral infection. The contribution of the receptor/ligand pair during an acute infection is less understood. To determine the role of PD-L1 and PD-L2 during acute ocular herpes simplex virus type 1 (HSV-1 infection, HSV-1-infected mice administered neutralizing antibody to PD-L1 or PD-L2 were assessed for viral burden and host cellular immune responses. Virus titers were elevated in cornea and trigeminal ganglia (TG of anti-PD-L1-treated mice which corresponded with a reduced number of CD80-expressing dendritic cells, PD-L1+ dendritic cells, and HSV-1-specific CD8+ T cells within the draining (mandibular lymph node (MLN. In contrast, anti-PD-L2 treatment had no effect on viral replication or changes in the MLN population. Notably, analysis of CD11c-enriched MLN cells from anti-PD-L1-treated mice revealed impaired functional capabilities. These studies indicate PD-L1-expressing dendritic cells are important for antiviral defense during acute HSV-1 infection.

  10. Hsc70 focus formation at the periphery of HSV-1 transcription sites requires ICP27.

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    Ling Li

    Full Text Available BACKGROUND: The cellular chaperone protein Hsc70, along with components of the 26S proteasome and ubiquitin-conjugated proteins have been shown to be sequestered in discrete foci in the nuclei of herpes simplex virus 1 (HSV-1 infected cells. We recently reported that cellular RNA polymerase II (RNAP II undergoes proteasomal degradation during robust HSV-1 transcription, and that the immediate early protein ICP27 interacts with the C-terminal domain and is involved in the recruitment of RNAP II to viral transcription/replication compartments. METHODOLOGY/PRINCIPLE FINDINGS: Here we show that ICP27 also interacts with Hsc70, and is required for the formation of Hsc70 nuclear foci. During infection with ICP27 mutants that are unable to recruit RNAP II to viral replication sites, viral transcript levels were greatly reduced, viral replication compartments were poorly formed and Hsc70 focus formation was curtailed. Further, a dominant negative Hsc70 mutant that cannot hydrolyze ATP, interfered with RNAP II degradation during HSV-1 infection, and an increase in ubiquitinated forms of RNAP II was observed. There was also a decrease in virus yields, indicating that proteasomal degradation of stalled RNAP II complexes during robust HSV-1 transcription and replication benefits viral gene expression. CONCLUSIONS/SIGNIFICANCE: We propose that one function of the Hsc70 nuclear foci may be to serve to facilitate the process of clearing stalled RNAP II complexes from viral genomes during times of highly active transcription.

  11. Isolation, identification and function of a novel anti-HSV-1 protein from Grifola frondosa.

    Science.gov (United States)

    Gu, Chang-Qing; Li, Jun-Wen; Chao, Fuhuan; Jin, Min; Wang, Xin-Wei; Shen, Zhi-Qiang

    2007-09-01

    A novel antiviral protein was purified from an extract of Grifola frondosa fruiting bodies using a procedure that included 40% ammonium sulfate precipitation and DEAE-cellulose ion exchange chromatography, and designated GFAHP. This protein inhibited herpes simplex virus type 1 (HSV-1) replication in vitro with an IC(50) value of 4.1 microg/ml and a therapeutic index >29.3. Higher concentrations of GFAHP (125 and 500 microg/ml) also significantly reduced the severity of HSV-1 induced blepharitis, neovascularization, and stromal keratitis in a murine model. Topical administration of GFAHP to the mouse cornea resulted in a significant decrease in virus production (mean virus yields: 3.4log10PFU in the treated group and 4.19log10PFU in the control group). We proved that GFAHP directly inactivates HSV-1 while simultaneously inhibiting HSV-1 penetration into Vero cells. Gel electrophoresis showed that GFAHP had a molecular weight of 29.5 kDa. GFAHP was tryptic digested and analyzed from the PMF of matrix assisted desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and nanoelectrospray ionization tandem mass spectrometry. The N-terminal sequence of GFAHP consisted of an 11 amino acid peptide, NH(2)-REQDNAPCGLN-COOH that did not match any known amino acid sequences, indicating that GFAHP is likely to be a novel antivirus protein. To our knowledge, this is the first report that characterizes an anti-HSV protein from G. frondosa.

  12. A Cell Culture Model of Latent and Lytic Herpes Simplex Virus Type 1 Infection in Spiral Ganglion.

    Science.gov (United States)

    Liu, Yuehong; Li, Shufeng

    2015-01-01

    Reactivation of latent herpes simplex virus type 1 (HSV-1) in spiral ganglion neurons (SGNs) is supposed to be one of the causes of idiopathic sudden sensorineural hearing loss. This study aims to establish a cell culture model of latent and lytic HSV-1 infection in spiral ganglia. In the presence of acyclovir, primary cultures of SGNs were latently infected with HSV-1 expressing green fluorescent protein. Four days later, these cells were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1. TCID50 was used to measure the titers of virus in cultures on Vero cells. RNA from cultures was detected for the presence of transcripts of ICP27 and latency-associated transcript (LAT) using reverse transcription polymerase chain reaction. There is no detectable infectious HSV-1 in latently infected cultures, whereas they could be observed in both lytically infected and latently infected/TSA-treated cultures. LAT was the only detectable transcript during latent infection, whereas lytic ICP27 transcript was detected in lytically infected and latently infected/TSA-treated cultures. Cultured SGNs can be both latently and lytically infected with HSV-1. Furthermore, latently infected SGNs can be reactivated using TSA, yielding infectious virus.

  13. A cell culture model of facial palsy resulting from reactivation of latent herpes simplex type 1.

    Science.gov (United States)

    Kuhn, Maggie A; Nayak, Shruti; Camarena, Vladimir; Gardner, Jimmy; Wilson, Angus; Mohr, Ian; Chao, Moses V; Roehm, Pamela C

    2012-01-01

    Reactivation of herpes simplex virus type 1 (HSV-1) in geniculate ganglion neurons (GGNs) is an etiologic mechanism of Bell's palsy (BP) and delayed facial palsy (DFP) after otologic surgery. Several clinical studies, including temporal bone studies, antibody, titers, and intraoperative studies, suggest that reactivation of HSV-1 from latently infected GGNs may lead to both BP and DFP. However, it is difficult to study these processes in humans or live animals. Primary cultures of GGNs were latently infected with Patton strain HSV-1 expressing a green fluorescent protein-late lytic gene chimera. Four days later, these cultures were treated with trichostatin A (TSA), a known chemical reactivator of HSV-1 in other neurons. Cultures were monitored daily by fluorescent microscopy. Titers of media from lytic, latent, and latent/TSA treated GGN cultures were obtained using plaque assays on Vero cells. RNA was harvested from latently infected GGN cultures and examined for the presence of viral transcripts using reverse transcription-polymerase chain reaction. Latently infected GGN cultures displayed latency-associated transcripts only, whereas lytically infected and reactivated latent cultures produced other viral transcripts, as well. The GGN cultures displayed a reactivation rate of 65% after treatment with TSA. Media from latently infected cultures contained no detectable infectious HSV-1, whereas infectious virus was observed in both lytically and latently infected/TSA-treated culture media. We have shown that cultured GGNs can be latently infected with HSV-1, and HSV-1 in these latently infected neurons can be reactivated using TSA, yielding infectious virus. These results have implications for the cause of both BP and DFP.

  14. HSV-1 nucleocapsid egress mediated by UL31 in association with UL34 is impeded by cellular transmembrane protein 140

    Energy Technology Data Exchange (ETDEWEB)

    Guan, Ying [Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118 (China); Yunnan Academy of Tobacco Science, Kunming, Yunnan 650106 (China); Guo, Lei; Yang, Erxia; Liao, Yun; Liu, Longding; Che, Yanchun; Zhang, Ying; Wang, Lichun; Wang, Jingjing [Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118 (China); Li, Qihan, E-mail: imbcams.lq@gmail.com [Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118 (China)

    2014-09-15

    During HSV-1 infection, the viral UL31 protein forms a complex with the UL34 protein at the cellular nuclear membrane, where both proteins play important roles in the envelopment of viral nucleocapsids and their egress into the cytoplasm. To characterize the mechanism of HSV-1 nucleocapsid egress, we screened host proteins to identify proteins that interacted with UL31 via yeast two-hybrid analysis. Transmembrane protein 140 (TMEM140), was identified and confirmed to bind to and co-localize with UL31 during viral infection. Further studies indicated that TMEM140 inhibits HSV-1 proliferation through selectively blocking viral nucleocapsid egress during the viral assembly process. The blockage function of TMEM140 is mediated by impeding the formation of the UL31–UL34 complex due to competitive binding to UL31. Collectively, these data suggest the essentiality of the UL31–UL34 interaction in the viral nucleocapsid egress process and provide a new anti-HSV-1 strategy in viral assembly process of nucleocapsid egress. - Highlights: • Cellular TMEM140 protein interacts with HSV-1 UL31 protein during viral infection. • Increasing expression of TMEM140 leads to inhibition of HSV-1 proliferation. • Increasing expression of TMEM140 blocks HSV-1 nucleocapsid egress process. • Binding to UL31 of TMEM140 impedes formation of HSV-1 UL31–UL34 complex.

  15. Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice from Ocular Challenge with HSV-1.

    Science.gov (United States)

    Wang, Kening; Tomaras, Georgia D; Jegaskanda, Sinthujan; Moody, M Anthony; Liao, Hua-Xin; Goodman, Kyle N; Berman, Phillip W; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Nitayapan, Sorachai; Kaewkungwal, Jaranit; Haynes, Barton F; Cohen, Jeffrey I

    2017-10-01

    The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120) construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein D (gD) so that the first 40 amino acids of gp120 were replaced by the signal sequence and the first 27 amino acids of the mature form of gD. This region of gD contains most of the binding site for HVEM, an HSV receptor important for virus infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV that were partially protective against infection, as well as antibodies to HSV. We derived monoclonal antibodies (MAbs) from peripheral blood B cells of recipients of the RV144 HIV vaccine and showed that these antibodies neutralized HSV-1 infection in cells expressing HVEM, but not the other major virus receptor, nectin-1. The MAbs mediated antibody-dependent cellular cytotoxicity (ADCC), and mice that received the MAbs and were then challenged by corneal inoculation with HSV-1 had reduced eye disease, shedding, and latent infection. To our knowledge, this is the first description of MAbs derived from human recipients of a vaccine that specifically target the HVEM binding site of gD. In summary, we found that monoclonal antibodies derived from humans vaccinated with the HVEM binding domain of HSV-1 gD (i) neutralized HSV-1 infection in a cell receptor-specific manner, (ii) mediated ADCC, and (iii) reduced ocular disease in virus-infected mice. IMPORTANCE Herpes simplex virus 1 (HSV-1) causes cold sores and neonatal herpes and is a leading cause of blindness. Despite many trials, no HSV vaccine has been approved. Nectin-1 and HVEM are the two major cellular receptors for HSV. These receptors are expressed at different levels in various tissues, and the role of each receptor in HSV pathogenesis is not well understood. We derived human monoclonal antibodies from persons who received the HIV RV144 vaccine that contained the HVEM binding domain of HSV-1 gD fused to HIV gp120. These antibodies were

  16. PET imaging of HSV1-tk mutants with acquired specificity toward pyrimidine- and acycloguanosine-based radiotracers

    Energy Technology Data Exchange (ETDEWEB)

    Likar, Yury; Dobrenkov, Konstantin; Olszewska, Malgorzata; Shenker, Larissa; Hricak, Hedvig; Ponomarev, Vladimir [Memorial Sloan-Kettering Cancer Center, Molecular Imaging Laboratory, Department of Radiology, New York, NY (United States); Cai, Shangde [Memorial Sloan-Kettering Cancer Center, Radiochemistry/Cyclotron Core Facility, New York, NY (United States)

    2009-08-15

    The aim of this study was to create an alternative mutant of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene with reduced phosphorylation capacity for acycloguanosine derivatives, but not pyrimidine-based compounds that will allow for successful PET imaging. A new mutant of HSV1-tk reporter gene, suitable for PET imaging using pyrimidine-based radiotracers, was developed. The HSV1-tk mutant contains an arginine-to-glutamine substitution at position 176 (HSV1-R176Qtk) of the nucleoside binding region of the enzyme. The mutant-gene product showed favorable enzymatic characteristics toward pyrimidine-based nucleosides, while exhibiting reduced activity with acycloguanosine derivatives. In order to enhance HSV1-R176Qtk reporter activity with pyrimidine-based radiotracers, we introduced the R176Q substitution into the more active HSV1-sr39tk mutant. U87 human glioma cells transduced with the HSV1-R176Qsr39tk double mutant reporter gene showed high {sup 3}H-FEAU pyrimidine nucleoside and low {sup 3}H-penciclovir acycloguanosine analog uptake in vitro. PET imaging also demonstrated high {sup 18}F-FEAU and low {sup 18}F-FHBG accumulation in HSV1-R176Qsr39tk+ xenografts. The feasibility of imaging two independent nucleoside-specific HSV1-tk mutants in the same animal with PET was demonstrated. Two opposite xenografts expressing the HSV1-R176Qsr39tk reporter gene and the previously described acycloguanosine-specific mutant of HSV1-tk, HSV1-A167Ysr39tk reporter gene, were imaged using a short-lived pyrimidine-based {sup 18}F-FEAU and an acycloguanosine-based {sup 18}F-FHBG radiotracer, respectively, administered on 2 consecutive days. We conclude that in combination with acycloguanosine-specific HSV1-A167Ysr39tk reporter gene, a HSV1-tk mutant containing the R176Q substitution could be used for PET imaging of two different cell populations or concurrent molecular biological processes in the same living subject. (orig.)

  17. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU

    Energy Technology Data Exchange (ETDEWEB)

    Nanda, Dharmin [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands); Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Jong, Marion de; Bakker, Willem; Bijster, Magda; Cox, Peter [Department of Nuclear Medicine, University Hospital Rotterdam (Netherlands); Vogels, Ronald; Havenga, Menzo [Crucell Holland BV, Leiden (Netherlands); Driesse, Maarten; Avezaat, Cees [Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Morin, Kevin; Naimi, Ebrahim; Knaus, Edward; Wiebe, Leonard [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton (Canada); Smitt, Peter Sillevis [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands)

    2002-07-01

    Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives.The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy-{beta}-D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of {sup 123}I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with {sup 123}I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). {sup 123}I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with {sup 123}I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after {sup 123}I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with

  18. Improved long-term expression from helper virus-free HSV-1 vectors packaged using combinations of mutated HSV-1 proteins that include the UL13 protein kinase and specific components of the VP16 transcriptional complex

    Directory of Open Access Journals (Sweden)

    Geller Alfred I

    2009-06-01

    Full Text Available Abstract Background Herpes Simplex Virus (HSV-1 gene expression is thought to shut off recombinant gene expression from HSV-1 vectors; however, in a helper virus-free HSV-1 vector system, a number of promoters support only short-term expression. These results raise the paradox that recombinant gene expression remains short-term even in the absence of almost all (~99% of the HSV-1 genome, HSV-1 genes, and HSV-1 gene expression. To resolve this paradox, we hypothesized that specific proteins in the HSV-1 virus particle shut off recombinant gene expression. In two earlier studies, we examined the effects on recombinant gene expression of packaging vectors using specific mutated HSV-1 proteins. We found that vectors packaged using mutated UL13 (a protein kinase, or VP16, or UL46 and/or UL47 (components of the VP16 transcriptional complex supported improved long-term expression, and vectors packaged using mutated UL46 and/or UL47 also supported improved gene transfer (numbers of cells at 4 days. These results suggested the hypothesis that specific proteins in the HSV-1 particle act by multiple pathways to reduce recombinant gene expression. To test this hypothesis, we examined combinations of mutated proteins that included both UL13 and specific components of the VP16 transcriptional complex. Results A HSV-1 vector containing a neuronal-specific promoter was packaged using specific combinations of mutated proteins, and the resulting vector stocks were tested in the rat striatum. For supporting long-term expression, the preferred combination of mutated HSV-1 proteins was mutated UL13, UL46, and UL47. Vectors packaged using this combination of mutated proteins supported a higher efficiency of gene transfer and high levels expression for 3 months, the longest time examined. Conclusion Vector particles containing this combination of mutated HSV-1 proteins improve recombinant gene expression. Implications of these results for strategies to further improve

  19. Improved long-term expression from helper virus-free HSV-1 vectors packaged using combinations of mutated HSV-1 proteins that include the UL13 protein kinase and specific components of the VP16 transcriptional complex.

    Science.gov (United States)

    Liu, Meng; Wang, Xiaodan; Geller, Alfred I

    2009-06-16

    Herpes Simplex Virus (HSV-1) gene expression is thought to shut off recombinant gene expression from HSV-1 vectors; however, in a helper virus-free HSV-1 vector system, a number of promoters support only short-term expression. These results raise the paradox that recombinant gene expression remains short-term even in the absence of almost all (approximately 99%) of the HSV-1 genome, HSV-1 genes, and HSV-1 gene expression. To resolve this paradox, we hypothesized that specific proteins in the HSV-1 virus particle shut off recombinant gene expression. In two earlier studies, we examined the effects on recombinant gene expression of packaging vectors using specific mutated HSV-1 proteins. We found that vectors packaged using mutated UL13 (a protein kinase), or VP16, or UL46 and/or UL47 (components of the VP16 transcriptional complex) supported improved long-term expression, and vectors packaged using mutated UL46 and/or UL47 also supported improved gene transfer (numbers of cells at 4 days). These results suggested the hypothesis that specific proteins in the HSV-1 particle act by multiple pathways to reduce recombinant gene expression. To test this hypothesis, we examined combinations of mutated proteins that included both UL13 and specific components of the VP16 transcriptional complex. A HSV-1 vector containing a neuronal-specific promoter was packaged using specific combinations of mutated proteins, and the resulting vector stocks were tested in the rat striatum. For supporting long-term expression, the preferred combination of mutated HSV-1 proteins was mutated UL13, UL46, and UL47. Vectors packaged using this combination of mutated proteins supported a higher efficiency of gene transfer and high levels expression for 3 months, the longest time examined. Vector particles containing this combination of mutated HSV-1 proteins improve recombinant gene expression. Implications of these results for strategies to further improve long-term expression are discussed

  20. The antiviral effect of three plant species of Iran on HSV-1

    OpenAIRE

    malihe Farahani

    2016-01-01

    Background : plants have had special position in human life and their medicinal application have been observed in manuscripts of many world scientists. Nowadays the treatment of HSV-1 infections with the available  chemical drugs often leads to the problems due to viral resistance and virus latency duration, therefore there is a requirement for new anti-herpes drugs.In this research the antiviral effects of  Camellia sinesis, Echium amoenumL and Nerium oleander, with ethnomedica...

  1. Platelet Activating Factor (PAF) Receptor Deletion or Antagonism Attenuates Severe HSV-1 Meningoencephalitis.

    Science.gov (United States)

    Vilela, Márcia Carvalho; Lima, Graciela Kunrath; Rodrigues, David Henrique; Lacerda-Queiroz, Norinne; Pedroso, Vinicius Sousa Pietra; de Miranda, Aline Silva; Rachid, Milene Alvarenga; Kroon, Erna Geessien; Campos, Marco Antônio; Teixeira, Mauro Martins; Teixeira, Antonio Lucio

    2016-12-01

    Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The exacerbated immune response against the virus contributes to the disease severity and death. Platelet activating factor (PAF) is a mediator capable of inducing increase in vascular permeability, production of cytokines on endothelial cells and leukocytes. We aimed to investigate the activation of PAF receptor (PAFR) and its contribution to the severity of the inflammatory response in the brain following HSV-1 infection. C57BL/6 wild-type (WT) and PAFR deficient (PAFR-/-) mice were inoculated intracranially with 104 plaque-forming units (PFU) of HSV-1. Visualization of leukocyte recruitment was performed using intravital microscopy. Cells infiltration in the brain tissue were analyzed by flow cytometry. Brain was removed for chemokine assessment by ELISA and for histopathological analysis. The pharmacological inhibition by the PAFR antagonist UK-74,505 was also analyzed. In PAFR-/- mice, there was delayed lethality but no difference in viral load. Histopathological analysis of infected PAFR-/- mice showed that brain lesions were less severe when compared to their WT counterparts. Moreover, PAFR-/- mice showed less TCD4+, TCD8+ and macrophages in brain tissue. This reduction of the presence of leukocytes in parenchyma may be mechanistically explained by a decrease in leukocytes rolling and adhesion. PAFR-/- mice also presented a reduction of the chemokine CXCL9 in the brain. In addition, by antagonizing PAFR, survival of C57BL/6 infected mice increased. Altogether, our data suggest that PAFR plays a role in the pathogenesis of experimental HSV-1 meningoencephalitis, and its blockade prevents severe disease manifestation.

  2. Methimazole-Induced Hypothyroidism Enhances HSV-1 Infectivity without Altering Circulating Leukocytes in the Rat

    Directory of Open Access Journals (Sweden)

    Hadi Feizi

    2015-04-01

    Full Text Available Backgrounds & objectives: In addition to their genomic actions, thyroid hormones (THs can modulate the immune responses through cell surface receptors. One of these is the antiviral effect of THs. Methimazole, as an anti-thyroid compound, is widely used to treat hyperthyroid patients. It also reduces blood leukocytes, granulocytes in particular, and thereby may affect the immune response. Recently, we reported that methimazole-induced hypothyroidism intensifies herpes simplex virus-1(HSV-1 infectivity. To determine whether the effect is mediated through alterations in circulating leukocytes, we assessed the HSV-1 infectivity and circulating leukocytes in methimazole-induced hypothyroid rat.   Methods: Male Sprague Dawley rats received methimazole (200 μg/ml in their drinking water for 2 weeks. Rats were then inoculated with a non-lethal single dose of HSV-1, and sacrificed 3 days later to harvest their spleen. Spleen extract was prepared, and virus yield was determined by evaluation of cytopathic effects (CPE induced by the extract in a Vero cell culture system. For quantitative analysis, standard method of Reed-Muench was employed. The routine Wright’s staining protocol was used for blood leukocytes differential count.   Results: The CPE development was significantly increased in the cell cultures exposed to the spleen extract of methimazole-treated animals (P < 0.05, indicating a higher virus yield and intensified virus infectivity. However, the effect of methimazole on blood leukocytes was minimal.   Conclusion: Our data suggest that methimazole increases the susceptibility to HSV-1 infection, at least in part, by blocking THs synthesis but not alterations in circulating leukocytes.

  3. Characterization of Wild-type and Temperature Sensitive Mutants of HSV-1 DNA Polymerase

    Science.gov (United States)

    1988-08-15

    two genomic isomeric arrangements [Ben-Porat , 1979; Plummer, 1973] o Virus: Pseudorabies Virus (Suid herpesvirus 1) Equine Herpesvirus (Equid...Huang, 1975], equine herpesvirus [Cohen et al., 1975; Kemp et al., 1975) and HSV [Keir & Gold, 1963]. Since then, several herpesvirus DNA polymerases... hypersensitive to the inhibitor PAA, based on an in vivo plaque reduction assay, when compared to the levels of PAA needed to inhibit HSV-1 KOS plaque

  4. Newly Characterized Murine Undifferentiated Sarcoma Models Sensitive to Virotherapy with Oncolytic HSV-1 M002

    Directory of Open Access Journals (Sweden)

    Eric K. Ring

    2017-12-01

    Full Text Available Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45 and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1. Both models expressed high levels of the primary HSV entry molecule nectin-1 (CD111 and were susceptible to killing by interleukin-12 (IL-12 producing HSV-1 M002 in vitro and in vivo. M002 resulted in a significant intratumoral increase in effector CD4+ and CD8+ T cells and activated monocytes, and a decrease in myeloid-derived suppressor cells (MDSCs in immunocompetent mice. Compared to parent virus R3659 (no IL-12 production, M002 resulted in higher CD8:MDSC and CD8:T regulatory cell (Treg ratios, suggesting that M002 creates a more favorable immune tumor microenvironment. These data provide support for clinical trials targeting sarcomas with oncolytic HSV-1. These models provide an exciting opportunity to explore combination therapies for soft tissue sarcomas that rely on an intact immune system to reach full therapeutic potential.

  5. Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues.

    Science.gov (United States)

    Lucero, Bianca d'A; Gomes, Claudia Regina B; Frugulhetti, Izabel Christina de P P; Faro, Letícia V; Alvarenga, Lise; de Souza, Maria Cecília B V; de Souza, Thiago M L; Ferreira, Vitor F

    2006-02-15

    Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-l) and l-[(2-hydroxy-ethoxy)methyl]-4(1H)quinolone-3-carboxylic acids (3a-j and 3l) were synthesized and 2a-j, 2l and 3a-j, 3l were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: silylation of the desired quinolone (BSTFA 1% TMCS) followed by equimolar amount addition of 1,3-dioxolane, chlorotrimethylsilane and KI, at room temperature. The acyclonucleosides 2a-l were obtained in 40-77% yields. The esters 2a-j and 2l were subsequently converted into the corresponding hydroxyacids 3 in 40-70% yields. Attempts of hydrolysis of 2k produced only a mixture of degradation products. Antiviral activity of 2 and 3 on HSV-1 virus infection was assessed by the virus yield assay. Except for compounds 2i and 3e, the acyclonucleosides were found to reduce the virus yield by 70-99% at the concentration of 50 microM, being the acids, in general, more effective inhibitors than their corresponding esters. Compounds 3j and 2d exhibited antiviral activity against HSV-1 virus with EC50 of 0.7+/-0.04 and 0.8+/-0.09 microM, respectively. Both compounds were not toxic towards the Vero cell line.

  6. HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Through Dynamin-Dependent Endocytosis.

    Science.gov (United States)

    Albecka, Anna; Laine, Romain F; Janssen, Anne F J; Kaminski, Clemens F; Crump, Colin M

    2016-01-01

    Herpes simplex virus-1 (HSV-1) is a large enveloped DNA virus that belongs to the family of Herpesviridae. It has been recently shown that the cytoplasmic membranes that wrap the newly assembled capsids are endocytic compartments derived from the plasma membrane. Here, we show that dynamin-dependent endocytosis plays a major role in this process. Dominant-negative dynamin and clathrin adaptor AP180 significantly decrease virus production. Moreover, inhibitors targeting dynamin and clathrin lead to a decreased transport of glycoproteins to cytoplasmic capsids, confirming that glycoproteins are delivered to assembly sites via endocytosis. We also show that certain combinations of glycoproteins colocalize with each other and with the components of clathrin-dependent and -independent endocytosis pathways. Importantly, we demonstrate that the uptake of neutralizing antibodies that bind to glycoproteins when they become exposed on the cell surface during virus particle assembly leads to the production of non-infectious HSV-1. Our results demonstrate that transport of viral glycoproteins to the plasma membrane prior to endocytosis is the major route by which these proteins are localized to the cytoplasmic virus assembly compartments. This highlights the importance of endocytosis as a major protein-sorting event during HSV-1 envelopment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The Synthesis of the Stable IVDU Derivative for Imaging HSV-1 TK Expression

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Jung; Choi, Tae Hyun; Ahn, Soon Hyuk; Kim, Byoung Soo; Park, Hyun; Cheon, Gi Jeong; An, Gwang Il [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of); Rhee, Hak June [Hanyang University, Ansan (Korea, Republic of)

    2009-10-15

    5-iododeoxyuridine analogues have been exclusively developed for the potential antiviral and antitumor therapeutic agents. In this study, we synthesized carbocyclic radioiododeoxyuridineanalogue (ddIVDU) and carbocyclic intermediate as efficient carbocyclic radiopharmaceuticals. The synthesis is LAH reduction, hetero Diels-Alder reaction as key reactions including Pd(0)-catalyzed coupling reaction together with organotin. MCA-RH7777 (MCA) and MCA-tk (HSV1-tk positive) cells were treated with various concentration of carbocyclic ddIVDU, and GCV. Cytotoxicity was measured by the MTS methods. For in vitro uptake study, MCA and MCA-tk cells were incubated with 1uCi of [{sup 125}I]carbocyclic ddIVDU. Accumulated radioactivity was measured after various incubation times. The synthesis of ddIVDU and precursor for radioiodination were achieved from cyclopentadiene in good overall yield, respectively. The radioiododemetallation for radiolabeling gave more than 80% yield with > 95% radiochemical purity. GCV was more toxic than carbocyclic ddIVDU in MCA-tk cells. Accumulation of [{sup 125}I]carbocyclic ddIVDU was higher in MCA-tk cells than MCA cells. Biological data reveal that ddIVDU is stable in vitro, less toxic than ganciclovir (GCV), and selective in HSV1-tk expressed cells. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5- iodovinyluridine (carbocyclic ddIVDU), is a potential imaging probe for HSV1-tk.

  8. Inhibition of HSV-1 replication by laser diode-irradiation: possible mechanism of action.

    Science.gov (United States)

    Donnarumma, G; De Gregorio, V; Fusco, A; Farina, E; Baroni, A; Esposito, V; Contaldo, M; Petruzzi, M; Pannone, G; Serpico, R

    2010-01-01

    Herpes labialis are the most frequent clinical manifestations of HSV-1 infection. Epithelial cells are able to respond to HSV-1 presence inducing the expression of IL-6, IL-1, TNF-α and IL-8. These proinflammatory cytokines have a function in the acute-phase response mediation, chemotaxis, inflammatory cell activation and antigen-presenting cells. In the human epithelial cell models, it has been demonstrated that, after an early induction of proinflammatory host response, HSV-1 down-modulates the proinflammatory cytokine production through the accumulation of two viral proteins, ICP4 and ICP27, whose transcription is induced by tegument protein VP16. These viral proteins, through the decreasing of stabilizing the mRNAs of proinflammatory genes, delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins, ICP-0 and VP-16 induce IL-10 expression. The conventional treatment of herpes labialis involves the topical and systemic use of antiviral drugs but it is necessary to find new therapies that can act in a selective and non-cytotoxic manner in viral infection. Laser diode therapy has been considered as a non-invasive alternative treatment to the conventional treatment of herpes labialis in pain therapy, in modulation of inflammation and in wound healing. This study aims to report a possible mechanism of action of laser diode irradiation in prevention and reduction of severity of labial manifestations of herpes labialis virus. We investigated, in an in vitro model of epithelial cells HaCat, the laser-effect on HSV-1 replication and we evaluated the modulation of expression of certain proinflammatory cytokines (TNF-α, IL-1β and IL-6), antimicrobial peptide HBD2, chemokine IL-8 and the immunosuppressive cytokine, IL-10. Our results lead us to hypothesize that LD-irradiation acts in the final stage of HSV-1 replication by limiting viral spread from cell to cell and that laser therapy acts also on the host immune

  9. Helper virus-free HSV-1 vectors packaged both in the presence of VSV G protein and in the absence of HSV-1 glycoprotein B support gene transfer into neurons in the rat striatum.

    Science.gov (United States)

    Tang, J; Yang, T; Ghosh, H P; Geller, A I

    2001-12-01

    Herpes simplex virus (HSV-1) vectors have potential for gene transfer into quiescent cells, but the gene transfer process could be more efficient. In other vector systems, both the titers and the efficiency of gene transfer have been enhanced by pseudotyping the vector particles with vesicular stomatitis virus (VSV) G protein. In this report, we pseudotyped helper virus-free HSV-1 plasmid vectors with VSV G protein. Packaging was performed in the presence of both VSV G protein and a deletion in an essential HSV-1 glycoprotein, gB. The resulting vector stocks supported gene transfer into both fibroblast and neuronal cell lines. VSV G protein was required for gene transfer because preincubation of these vector stocks with antibodies directed against either VSV G protein or VSV reduced the titer to undetectable levels. Although the titers were lower than those obtained using the unmodified vector system, the titers were not increased by use of chimeric proteins that contain the extracellular domain of VSV G protein and the transmembrane and/or cytoplasmic domains of specific HSV-1 glycoproteins. Also, the titers were not increased by performing the packaging in the presence of deletions in multiple HSV-1 glycoproteins. Nonetheless, pHSVlac pseudotyped with VSV G protein supported gene transfer into striatal neurons in the rat brain. Thus, HSV-1 vectors pseudotyped with VSV G protein may be useful for specific gene transfer studies.

  10. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    Science.gov (United States)

    Sufiawati, Irna; Tugizov, Sharof M

    2014-01-01

    Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  11. Synthesis and Cellular Uptake of Radioiodine labeled 2{sup '}-deoxyuridine derivatives with HSV1-TK

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ah; Lee, Kyo Chul; Hong, Su Hee; Kim, Eun Jung; Lee, Jong Chan; An, Gwang Il; Choi, Tae Hyun; Cheon, Gi Jeong; Chun, Kwon Soo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2006-07-01

    Several different radiolabeled probes have been developed to image Herpes Simplex Virus Type-1 thyrimidine kinase gene (HSV1-TK) expression. The nucleoside prodrugs under investigation for HSV1-TK imaging generally fall into two main chemical and radioisotope categories: the pyrimidine nucleosides, primarily radioiodinated, and the purin nucleosides, primarily radiofluorinated, and their respective analogues. In non-invasive imaging of the HSV1-TK system, many nucleoside derivatives have been recommended as HSV1-TK substrates. Most of these nucleoside derivatives have been developed as prodrugs for tumor proliferation imaging or as anti-viral drugs. For example, 5-fluorouracil (5-FU) and IUdR have been used as tumor agents and acyclovir (ACV), ganciclovir (GCV) and (E)-5-(2-bromovinyl)-2{sup '}- deoxyuridine (BVDU) as an anti-viral agents for virus infection several 5-substituted uracil nucleoside derivatives have been identified to have high sensitivity and selective accumulation in HSV1-TK expressing cells. Of those, IVDU was shown to be rapidly accumulated in HSV1- TK expressing cells in vitro. Imaging of the HSV1-TK reporter gene along with various reporter probes is of current interest. In contrast to the mammalian kinase, which phosphorylates thymidine preferentially, HSV1-TK is less discriminative and phosphorylates a wide range of nucleoside analogues such as acycloguanosines and 2{sup '}-fluoro-2{sup '}-deoxyuridine derivatives that are not phosphorylated efficiently by the native enzyme. More specifically, 5-substituted 2{sup '}-fluoro-2{sup '}-deoxyarabinofuranosyluracil nucleosides are efficiently phosphorylated by HSV- TK. This property, together with the presence of fluorine in the 2{sup '}-arabino-position, endows the 2{sup '}-fluoro-2{sup '}-deoxyuridines with antiviral activity against HSV.

  12. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    Directory of Open Access Journals (Sweden)

    Irna Sufiawati

    Full Text Available Herpes simplex virus (HSV types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD. Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  13. Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160.

    Science.gov (United States)

    Polpitiya Arachchige, Sachith; Henke, Wyatt; Pramanik, Ankita; Kalamvoki, Maria; Stephens, Edward B

    2018-01-15

    Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways.IMPORTANCE HIV-1 infection of humans results in AIDS, characterized by the loss of CD4+ T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell. Copyright © 2018 American Society for Microbiology.

  14. Nonsulfated, cinnamic acid-based lignins are potent antagonists of HSV-1 entry into cells.

    Science.gov (United States)

    Thakkar, Jay N; Tiwari, Vaibhav; Desai, Umesh R

    2010-05-10

    In an effort to discover macromolecular mimetics of heparan sulfate (HS), we previously designed sulfated lignins (Raghuraman et al. Biomacromolecules 2007, 8, 1759-1763). To probe the relevance of sulfate groups of HS in viral entry, lignins completely devoid of sulfate moieties, and yet possessing an electrostatic surface equivalent to that of HS, were designed. Two carboxylated lignins based on a 4-hydroxy cinnamic acid scaffold were synthesized using enzymatic oxidative coupling in high yields, fractionated according to their sizes, and tested in cellular assays of herpes simplex virus-1 (HSV-1) infection. The two carboxylated lignins were found to not only inhibit HSV-1 entry into mammalian cells (IC(50) = 8-56 nM), but were more potent than sulfated lignins. In addition, shorter carboxylated lignins were found to be as active as the longer chains, suggesting that structural features, in addition to carboxylate groups, may be important. It can be expected that carboxylated lignins also antagonize the entry of other enveloped viruses, for example, HIV-1, Kaposi's sarcoma-associated herpes virus, and hepatitis C virus, that utilize HS to gain entry into cells. The results present major opportunities for developing lignin-based antiviral formulations for topical use.

  15. Cell Cycle-Dependent Expression of Adeno-Associated Virus 2 (AAV2) Rep in Coinfections with Herpes Simplex Virus 1 (HSV-1) Gives Rise to a Mosaic of Cells Replicating either AAV2 or HSV-1

    Science.gov (United States)

    Franzoso, Francesca D.; Seyffert, Michael; Vogel, Rebecca; Yakimovich, Artur; de Andrade Pereira, Bruna; Meier, Anita F.; Sutter, Sereina O.; Tobler, Kurt; Vogt, Bernd; Greber, Urs F.; Büning, Hildegard; Ackermann, Mathias

    2017-01-01

    ABSTRACT Adeno-associated virus 2 (AAV2) depends on the simultaneous presence of a helper virus such as herpes simplex virus 1 (HSV-1) for productive replication. At the same time, AAV2 efficiently blocks the replication of HSV-1, which would eventually limit its own replication by diminishing the helper virus reservoir. This discrepancy begs the question of how AAV2 and HSV-1 can coexist in a cell population. Here we show that in coinfected cultures, AAV2 DNA replication takes place almost exclusively in S/G2-phase cells, while HSV-1 DNA replication is restricted to G1 phase. Live microscopy revealed that not only wild-type AAV2 (wtAAV2) replication but also reporter gene expression from both single-stranded and double-stranded (self-complementary) recombinant AAV2 vectors preferentially occurs in S/G2-phase cells, suggesting that the preference for S/G2 phase is independent of the nature of the viral genome. Interestingly, however, a substantial proportion of S/G2-phase cells transduced by the double-stranded but not the single-stranded recombinant AAV2 vectors progressed through mitosis in the absence of the helper virus. We conclude that cell cycle-dependent AAV2 rep expression facilitates cell cycle-dependent AAV2 DNA replication and inhibits HSV-1 DNA replication. This may limit competition for cellular and viral helper factors and, hence, creates a biological niche for either virus to replicate. IMPORTANCE Adeno-associated virus 2 (AAV2) differs from most other viruses, as it requires not only a host cell for replication but also a helper virus such as an adenovirus or a herpesvirus. This situation inevitably leads to competition for cellular resources. AAV2 has been shown to efficiently inhibit the replication of helper viruses. Here we present a new facet of the interaction between AAV2 and one of its helper viruses, herpes simplex virus 1 (HSV-1). We observed that AAV2 rep gene expression is cell cycle dependent and gives rise to distinct time

  16. Small Neutral Amino Acid Ester Prodrugs of Acyclovir Targeting Amino Acid Transporters on the Cornea: Possible Antiviral Agents against Ocular HSV-1 Infections

    Directory of Open Access Journals (Sweden)

    Katragadda Suresh

    2010-01-01

    Full Text Available The aim of this study was to characterize the affinity and permeability patterns of the amino acid ester prodrugs of acyclovir (ACV, L-alanine-ACV (AACV, L-serine-ACV (SACV, L-serine-succinate-ACV (SSACV and L-cysteine-ACV (CACV on rabbit primary corneal epithelial cell culture (rPCEC and on rabbit cornea. Amino acid prodrugs of acyclovir, AACV, SACV, SSACV and CACV were synthesized in our laboratory. Chemical hydrolysis in aqueous buffer, enzymatic hydrolysis in corneal homogenates and transport across freshly excised rabbit cornea of these prodrugs were studied. SSACV inhibited the uptake of [ 3 H] L-alanine on rPCEC and across the intact rabbit cornea. Lineweaver-Burk plot transformation revealed competitive inhibition between L-alanine and SSACV. In corneal tissue homogenate, the half lives of SSACV, SACV and CACV (t 1/2 were observed to be 3.5 ± 0.4, 9.2 ± 0.6 and 1.8 ± 0.1 hr respectively, whereas AACV was readily converted to the active parent drug acyclovir exhibiting complete degradation before 5 min. Interestingly translocation of SACV across cornea was inhibited in the presence of 5 mM arginine (~51%, a specific substrate for cationic transport system and in presence of BCH (~38%, a substrate specific for large neutral amino acid transport system (LAT or cationic and neutral amino acid transport system (B 0,+ . SACV exhibited higher permeability across cornea along with excellent antiviral activity against herpes simplex virus (HSV-1 and varicella-zoster virus (VZV in comparison to ACV. Recognition by multiple transporters, stability in corneal homogenate and changes in physico-chemical properties contributed to the increased permeability of SACV across cornea.

  17. Identification of replication-competent HSV-1 Cgal+ strain targets in a mouse model of human hepatocarcinoma xenograft.

    Science.gov (United States)

    Santamaría, Enrique; Mora, María I; Carro-Roldán, Elvira; Molina, Manuela; Fernández-Irigoyen, Joaquín; Marconi, Peggy; Manservigi, Roberto; Greco, Anna; Epstein, Alberto L; Prieto, Jesús; Hernández-Alcoceba, Rubén; Corrales, Fernando J

    2009-11-02

    Recent studies based on animal models have shown the advantages and potential of oncolytic viral therapy using HSV-1 -based replication-competent vectors in the treatment of liver tumors, but little is known about the cellular targets that are modulated during viral infection. In the present work, we have studied the effects of intratumoral injections of HSV-1 Cgal(+) strain in a murine model of human hepatoma xenografts. Viral replication was assessed for more than 1month, leading to a significant reduction of tumor growth rate mediated, in part, by a cyclin B dependent cell proliferation arrest. Early events resulting in this effect were analyzed using a proteomic approach. Protein extracts from xenografted human hepatomas treated with saline or HSV-1 Cgal(+) strain during 24h were compared by 2-D DIGE and differential spots were identified by nanoLC-ESI-MS/MS. Alterations on glutathione S transferase 1 Omega, and ERp29 suggest novel HSV-1 Cgal(+) targets in solid liver tumors. Additionally, ERp29 showed a complex differential isoform pattern upon HSV-1 Cgal(+) infection, suggesting regulatory mechanisms based on post-translational modification events.

  18. In vitro Inactivation of Latent HSV by Targeted Mutagenesis Using an HSV-specific Homing Endonuclease

    Directory of Open Access Journals (Sweden)

    Martine Aubert

    2014-01-01

    Full Text Available Following acute infection, herpes simplex virus (HSV establishes latency in sensory neurons, from which it can reactivate and cause recurrent disease. Available antiviral therapies do not affect latent viral genomes; therefore, they do not prevent reactivation following therapy cessation. One possible curative approach involves the introduction of DNA double strand breaks in latent HSV genomes by rare-cutting endonucleases, leading to mutagenesis of essential viral genes. We tested this approach in an in vitro HSV latency model using the engineered homing endonuclease (HE HSV1m5, which recognizes a sequence in the HSV-1 gene UL19, encoding the virion protein VP5. Coexpression of the 3′-exonuclease Trex2 with HEs increased HE-mediated mutagenesis frequencies up to sixfold. Following HSV1m5/Trex2 delivery with adeno-associated viral (AAV vectors, the target site was mutated in latent HSV genomes with no detectable cell toxicity. Importantly, HSV production by latently infected cells after reactivation was decreased after HSV1m5/Trex2 exposure. Exposure to histone deacetylase inhibitors prior to HSV1m5/Trex2 treatment increased mutagenesis frequencies of latent HSV genomes another two- to fivefold, suggesting that chromatin modification may be a useful adjunct to gene-targeting approaches. These results support the continuing development of HEs and other nucleases (ZFNs, TALENs, CRISPRs for cure of chronic viral infections.

  19. In vitro Inactivation of Latent HSV by Targeted Mutagenesis Using an HSV-specific Homing Endonuclease.

    Science.gov (United States)

    Aubert, Martine; Boyle, Nicole M; Stone, Daniel; Stensland, Laurence; Huang, Meei-Li; Magaret, Amalia S; Galetto, Roman; Rawlings, David J; Scharenberg, Andrew M; Jerome, Keith R

    2014-02-04

    Following acute infection, herpes simplex virus (HSV) establishes latency in sensory neurons, from which it can reactivate and cause recurrent disease. Available antiviral therapies do not affect latent viral genomes; therefore, they do not prevent reactivation following therapy cessation. One possible curative approach involves the introduction of DNA double strand breaks in latent HSV genomes by rare-cutting endonucleases, leading to mutagenesis of essential viral genes. We tested this approach in an in vitro HSV latency model using the engineered homing endonuclease (HE) HSV1m5, which recognizes a sequence in the HSV-1 gene UL19, encoding the virion protein VP5. Coexpression of the 3'-exonuclease Trex2 with HEs increased HE-mediated mutagenesis frequencies up to sixfold. Following HSV1m5/Trex2 delivery with adeno-associated viral (AAV) vectors, the target site was mutated in latent HSV genomes with no detectable cell toxicity. Importantly, HSV production by latently infected cells after reactivation was decreased after HSV1m5/Trex2 exposure. Exposure to histone deacetylase inhibitors prior to HSV1m5/Trex2 treatment increased mutagenesis frequencies of latent HSV genomes another two- to fivefold, suggesting that chromatin modification may be a useful adjunct to gene-targeting approaches. These results support the continuing development of HEs and other nucleases (ZFNs, TALENs, CRISPRs) for cure of chronic viral infections.Molecular Therapy-Nucleic Acids (2014) 3, e1; doi:10.1038/mtna.2013.75; published online 4 February 2014.

  20. Developing de novo human artificial chromosomes in embryonic stem cells using HSV-1 amplicon technology.

    Science.gov (United States)

    Moralli, Daniela; Monaco, Zoia L

    2015-02-01

    De novo artificial chromosomes expressing genes have been generated in human embryonic stem cells (hESc) and are maintained following differentiation into other cell types. Human artificial chromosomes (HAC) are small, functional, extrachromosomal elements, which behave as normal chromosomes in human cells. De novo HAC are generated following delivery of alpha satellite DNA into target cells. HAC are characterized by high levels of mitotic stability and are used as models to study centromere formation and chromosome organisation. They are successful and effective as gene expression vectors since they remain autonomous and can accommodate larger genes and regulatory regions for long-term expression studies in cells unlike other viral gene delivery vectors currently used. Transferring the essential DNA sequences for HAC formation intact across the cell membrane has been challenging for a number of years. A highly efficient delivery system based on HSV-1 amplicons has been used to target DNA directly to the ES cell nucleus and HAC stably generated in human embryonic stem cells (hESc) at high frequency. HAC were detected using an improved protocol for hESc chromosome harvesting, which consistently produced high-quality metaphase spreads that could routinely detect HAC in hESc. In tumour cells, the input DNA often integrated in the host chromosomes, but in the host ES genome, it remained intact. The hESc containing the HAC formed embryoid bodies, generated teratoma in mice, and differentiated into neuronal cells where the HAC were maintained. The HAC structure and chromatin composition was similar to the endogenous hESc chromosomes. This review will discuss the technological advances in HAC vector delivery using HSV-1 amplicons and the improvements in the identification of de novo HAC in hESc.

  1. Docking of anti-HIV-1 oxoquinoline-acylhydrazone derivatives as potential HSV-1 DNA polymerase inhibitors

    Science.gov (United States)

    Yoneda, Julliane Diniz; Albuquerque, Magaly Girão; Leal, Kátia Zaccur; Santos, Fernanda da Costa; Batalha, Pedro Netto; Brozeguini, Leonardo; Seidl, Peter R.; de Alencastro, Ricardo Bicca; Cunha, Anna Cláudia; de Souza, Maria Cecília B. V.; Ferreira, Vitor F.; Giongo, Viveca A.; Cirne-Santos, Cláudio; Paixão, Izabel C. P.

    2014-09-01

    Although there are many antiviral drugs available for the treatment of herpes simplex virus (HSV) infections, still the synthesis of new anti-HSV candidates is an important strategy to be pursued, due to the emergency of resistant HSV strains mainly in human immunodeficiency virus (HIV) co-infected patients. Some 1,4-dihydro-4-oxoquinolines, such as PNU-183792 (1), show a broad spectrum antiviral activity against human herpes viruses, inhibiting the viral DNA polymerase (POL) without affecting the human POLs. Thus, on an ongoing antiviral research project, our group has synthesized ribonucleosides containing the 1,4-dihydro-4-oxoquinoline (quinolone) heterocyclic moiety, such as the 6-Cl derivative (2), which is a dual antiviral agent (HSV-1 and HIV-1). Molecular dynamics simulations of the complexes of 1 and 2 with the HSV-1 POL suggest that structural modifications of 2 should increase its experimental anti-HSV-1 activity, since its ribosyl and carboxyl groups are highly hydrophilic to interact with a hydrophobic pocket of this enzyme. Therefore, in this work, comparative molecular docking simulations of 1 and three new synthesized oxoquinoline-acylhydrazone HIV-1 inhibitors (3-5), which do not contain those hydrophilic groups, were carried out, in order to access these modifications in the proposition of new potential anti-HSV-1 agents, but maintaining the anti-HIV-1 activity. Among the docked compounds, the oxoquinoline-acylhydrazone 3 is the best candidate for an anti-HSV-1 agent, and, in addition, it showed anti-HIV-1 activity (EC50 = 3.4 ± 0.3 μM). Compounds 2 and 3 were used as templates in the design of four new oxoquinoline-acylhydrazones (6-9) as potential anti-HSV-1 agents to increase the antiviral activity of 2. Among the docked compounds, oxoquinoline-acylhydrazone 7 was selected as the best candidate for further development of dual anti-HIV/HSV activity.

  2. The use of human cornea organotypic cultures to study herpes simplex virus type 1 (HSV-1)-induced inflammation.

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    Drevets, Peter; Chucair-Elliott, Ana; Shrestha, Priyadarsini; Jinkins, Jeremy; Karamichos, Dimitrios; Carr, Daniel J J

    2015-10-01

    To determine the utility of human organotypic cornea cultures as a model to study herpes simplex virus type 1 (HSV-1)-induced inflammation and neovascularization. Human organotypic cornea cultures were established from corneas with an intact limbus that were retrieved from donated whole globes. One cornea culture was infected with HSV-1 (10(4) plaque-forming units), while the other cornea from the same donor was mock-infected. Supernatants were collected at intervals post-culture with and without infection to determine viral titer (by plaque assay) and pro-angiogenic and proinflammatory cytokine concentration by suspension array analysis. In some experiments, the cultured corneas were collected and evaluated for HSV-1 antigens by immunohistochemical means. Another set of experiments measured susceptibility of human three-dimensional cornea fibroblast constructs, in the presence and absence of TGF-β1, to HSV-1 infection in terms of viral replication and the inflammatory response to infection as a comparison to the organotypic cornea cultures. Organotypic cornea cultures and three-dimensional fibroblast constructs exhibited varying degrees of susceptibility to HSV-1. Fibroblast constructs were more susceptible to infection in terms of infectious virus recovered in a shorter period of time. There were changes in the levels of select pro-angiogenic or proinflammatory cytokines that were dictated as much by the cultures producing them as by whether they were infected with HSV-1 or treated with TGF-β1. Organotypic cornea and three-dimensional fibroblast cultures are likely useful for the identification and short-term study of novel antiviral compounds and virus replication, but are limited in the study of the local immune response to infection.

  3. Association between HSV1 seropositivity and obesity: data from the National Health and Nutritional Examination Survey, 2007-2008.

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    Zuzana Karjala

    Full Text Available BACKGROUND: Herpes simplex virus (HSV is among the most common sexually transmitted pathogens in the United States and worldwide. HSV has a high incidence of undetected cases. In addition, there is no treatment, and there is a lack of knowledge why disparities among populations exist. Research studies suggest that fat tissue may participate in body's immune responses, and the impact of obesity on susceptibility to HSV1 infection is not clear. The purpose of this study was to examine whether obesity is a risk factor for HSV1 infection using a large sample from the general population. METHODS/PRINCIPAL FINDINGS: This cross-sectional study used data from the National Health and Examination and Nutritional Examination Survey (NHANES from 2007-2008. Variables, gender, age, race/ethnicity, marital status, education, poverty level, and diabetes represented potential confounders and were included in analyses. The two-tailed Pearson's chi square, student's t test, and a multiple logistic regression analysis were applied to evaluate associations using a significance value of p≤0.05. Adjusted odds ratios with 95% confidence interval represented the degree of these associations. The prevalence of HSV1 infection in US population between 20 and 49 years old was 60.3% (n = 1,536. In this study, having a BMI classified as the obese group (BMI 30-39.9 was significantly associated with HSV1 infection before [unadjusted OR = 1.74 (95% CI 1.20-2.51, p = 0.006] and after controlling for socio-demographic factors [adjusted OR = 1.50 (95%CI 1.06-2.13], p = 0.026]. This association was stronger than three already established risk factors of age, female gender, and poverty level. CONCLUSIONS/SIGNIFICANCE: This study provides evidence that obesity may play a role in the susceptibility to HSV1 infection. Findings from this study suggest that obesity should be considered when designing preventive measures for HSV1 infection. These results may also

  4. PET imaging of oncolytic VSV expressing the mutant HSV-1 thymidine kinase transgene in a preclinical HCC rat model.

    Science.gov (United States)

    Muñoz-Álvarez, Kim A; Altomonte, Jennifer; Laitinen, Iina; Ziegler, Sibylle; Steiger, Katja; Esposito, Irene; Schmid, Roland M; Ebert, Oliver

    2015-04-01

    Hepatocellular carcinoma (HCC) is the most predominant form of liver cancer and the third leading cause of cancer-related death worldwide. Due to the relative ineffectiveness of conventional HCC therapies, oncolytic viruses have emerged as novel alternative treatment agents. Our previous studies have demonstrated significant prolongation of survival in advanced HCC in rats after oncolytic vesicular stomatitis virus (VSV) treatment. In this study, we aimed to establish a reporter system to reliably and sensitively image VSV in a clinically relevant model of HCC for clinical translation. To this end, an orthotopic, unifocal HCC model in immune-competent Buffalo rats was employed to test a recombinant VSV vector encoding for an enhanced version of the herpes simplex virus 1 (HSV-1) thymidine kinase (sr39tk) reporter, which would allow the indirect detection of VSV via positron emission tomography (PET). The resulting data revealed specific tracer uptake in VSV-HSV1-sr39tk-treated tumors. Further characterization of the VSV-HSV1-sr39tk vector demonstrated its optimal detection time-point after application and its detection limit via PET. In conclusion, oncolytic VSV expressing the HSV1-sr39tk reporter gene allows for highly sensitive in vivo imaging via PET. Therefore, this imaging system may be directly translatable and beneficial in further clinical applications.

  5. Characterization of Neuronal Populations in the Human Trigeminal Ganglion and Their Association with Latent Herpes Simplex Virus-1 Infection

    OpenAIRE

    Flowerdew, Sarah E.; Desiree Wick; Susanne Himmelein; Anja K E Horn; Inga Sinicina; Michael Strupp; Thomas Brandt; Diethilde Theil; Katharina Hüfner

    2013-01-01

    Following primary infection Herpes simplex virus-1 (HSV-1) establishes lifelong latency in the neurons of human sensory ganglia. Upon reactivation HSV-1 can cause neurological diseases such as facial palsy, vestibular neuritis or encephalitis. Certain populations of sensory neurons have been shown to be more susceptible to latent infection in the animal model, but this has not been addressed in human tissue. In the present study, trigeminal ganglion (TG) neurons expressing six neuronal marker...

  6. Detection of circulating tumor cells using oHSV1-hTERT-GFP in lung cancer.

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    Gao, Hongjun; Liu, Wenjing; Yang, Shaoxing; Zhang, Wen; Li, Xiaoyan; Qin, Haifeng; Wang, Weixia; Zhao, Changyun

    2017-10-25

    This study was conducted to evaluate the clinical utility of the oHSV1-hTERT-GFP circulating tumor cell (CTC) detection method in the peripheral blood of patients with lung cancer by comparing its sensitivity to the CellSearch CTC detection method. The oHSV1-hTERT-GFP and CellSearch CTC detection methods were compared using peripheral blood samples of patients pathologically diagnosed with lung cancer. A total of 240 patients with lung cancer were recruited, including 89 patients who were newly diagnosed and 151 patients who had previously received treatment. Sixty-six newly diagnosed patients were evaluated using both methods. The CTC detection rates were 71.2% and 33.3% using the oHSV1-hTERT-GFP and CellSearch methods, respectively; this difference was statistically significant (P = 0.000). Among the entire cohort (n = 240), the CTC detection rate using the oHSV1-hTERT-GFP method was 76.3%, with a CTC count of 0-81. The CTC detection rates were 76.7%, 68.9%, and 76.3% in patients with squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, respectively. There was no statistically significant difference in the CTC detection rates between these different pathological subtypes (P = 0.738). The CTC detection rates of 79.8% and 74.4% in patients with stage I-III and IV lung cancer, respectively, were not significantly different (P = 0.427). The oHSV1-hTERT-GFP method is highly effective for detecting CTCs in patients with lung cancer, independent of pathological type and disease stage, and is ideal for large-scale clinical applications. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  7. Integrating retroviral cassette extends gene delivery of HSV-1 expression vectors to dividing cells.

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    de Felipe, P; Izquierdo, M; Wandosell, F; Lim, F

    2001-08-01

    Retroviral vectors have long been used in a wide variety of gene transfer applications but have certain drawbacks, such as small cargo size, limited tropism, and low titers. HSV expression vectors overcome these disadvantages, but, because they persist in target cells as nonreplicative episomes, they are not retained in all the progeny of dividing cells. Chimeric HSV/AAV products that can mediate transgene integration in human mitotic cells have been constructed, but, to date, genetic modification of dividing cells in animal models using HSV products has not been possible. Here, we report the construction of hybrid HSV/retroviral vectors that exhibit up to 50-fold higher transgene integration efficiency compared to vectors containing only HSV-1 components. Efficient integration of a retroviral transgene cassette encoding pac in human cells required expression of the Moloney murine leukemia virus gag-pol genes, but in murine cells, could also be mediated by endogenous activities, albeit at a lower level. Gene delivery was equally efficient in BHK21, a cell line resistant to retroviral infection, and transgene retention and expression were observed to be stable for least one month in Hs683 human glioma cells. These vectors have wide applications for the genetic modification of many cell types.

  8. Ethosomes for the delivery of anti-HSV-1 molecules: preparation, characterization and in vitro activity.

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    Cortesi, R; Ravani, L; Zaid, A N; Menegatti, E; Romagnoli, R; Drechsler, M; Esposito, E

    2010-10-01

    This paper describes the production, characterization and in vitro activity of ethosomes containing two molecules with antiviral activity, such as acyclovir (ACY) and N1-beta-D-ribofuranosyl-pyrazole [3,4d]pyridazin-7(6p-chlorine-phenyl)-one nucleoside (N1CP). Ethosomes were prepared and morphologically characterized by Cryo-TEM. The encapsulation efficiency was 92.3 +/- 2.5% for ACY and 94.2 +/- 2.8% for N1CP. The release of the drug from vesicles, determined by a Franz cell method, indicated that both drugs were released in a controlled manner. In order to possibly guarantee the stability during long-term storage ethosome suspensions was freeze-dried. It was found that the freeze-dried ethosomes' cakes were compact, glassy characterized by low density and quick re-hydration. However, the storage time slightly influences the percentage of drug encapsulation within ethosomes showing a drug leakage after re-hydration around 10%. The antiviral activity against HSV-1 of both drugs was tested by plaque reduction assay in monolayer cultures of Vero cells. Data showed that ethosomes allowed a reduction of the ED50 of N1CP evidencing an increase of its antiviral activity. However, ACY remains more active than N1CP. No differences are appreciable between drug-containing ethosomes before and after freeze-drying. Taken together these results, ethosomal formulation could be possibly proposed as mean for topical administration of anti-herpetic molecules.

  9. Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection

    Energy Technology Data Exchange (ETDEWEB)

    Sae-Ueng, Udom; Li, Dong; Zuo, Xiaobing; Huffman, Jamie B.; Homa, Fred L.; Rau, Donald; Evilevitch, Alex

    2014-10-01

    DNA in the human Herpes simplex virus type 1 (HSV-1) capsid is packaged to a tight density. This leads to tens of atmospheres of internal pressure responsible for the delivery of the herpes genome into the cell nucleus. In this study we show that, despite its liquid crystalline state inside the capsid, the DNA is fluid-like, which facilitates its ejection into the cell nucleus during infection. We found that the sliding friction between closely packaged DNA strands, caused by interstrand repulsive interactions, is reduced by the ionic environment of epithelial cells and neurons susceptible to herpes infection. However, variations in the ionic conditions corresponding to neuronal activity can restrict DNA mobility in the capsid, making it more solid-like. This can inhibit intranuclear DNA release and interfere with viral replication. In addition, the temperature of the human host (37 °C) induces a disordering transition of the encapsidated herpes genome, which reduces interstrand interactions and provides genome mobility required for infection.

  10. Subcellular Trafficking and Functional Relationship of the HSV-1 Glycoproteins N and M

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    Striebinger, Hannah; Funk, Christina; Raschbichler, Verena; Bailer, Susanne M.

    2016-01-01

    The herpes simplex virus type 1 (HSV-1) glycoprotein N (gN/UL49.5) is a type I transmembrane protein conserved throughout the herpesvirus family. gN is a resident of the endoplasmic reticulum that in the presence of gM is translocated to the trans Golgi network. gM and gN are covalently linked by a single disulphide bond formed between cysteine 46 of gN and cysteine 59 of gM. Exit of gN from the endoplasmic reticulum requires the N-terminal core of gM composed of eight transmembrane domains but is independent of the C-terminal extension of gM. Co-transport of gN and gM to the trans Golgi network also occurs upon replacement of conserved cysteines in gM and gN, suggesting that their physical interaction is mediated by covalent and non-covalent forces. Deletion of gN/UL49.5 using bacterial artificial chromosome (BAC) mutagenesis generated mutant viruses with wild-type growth behaviour, while full deletion of gM/UL10 resulted in an attenuated phenotype. Deletion of gN/UL49.5 in conjunction with various gM/UL10 mutants reduced average plaque sizes to the same extent as either single gM/UL10 mutant, indicating that gN is nonessential for the function performed by gM. We propose that gN functions in gM-dependent as well as gM-independent processes during which it is complemented by other viral factors. PMID:26999189

  11. Subcellular Trafficking and Functional Relationship of the HSV-1 Glycoproteins N and M

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    Hannah Striebinger

    2016-03-01

    Full Text Available The herpes simplex virus type 1 (HSV-1 glycoprotein N (gN/UL49.5 is a type I transmembrane protein conserved throughout the herpesvirus family. gN is a resident of the endoplasmic reticulum that in the presence of gM is translocated to the trans Golgi network. gM and gN are covalently linked by a single disulphide bond formed between cysteine 46 of gN and cysteine 59 of gM. Exit of gN from the endoplasmic reticulum requires the N-terminal core of gM composed of eight transmembrane domains but is independent of the C-terminal extension of gM. Co-transport of gN and gM to the trans Golgi network also occurs upon replacement of conserved cysteines in gM and gN, suggesting that their physical interaction is mediated by covalent and non-covalent forces. Deletion of gN/UL49.5 using bacterial artificial chromosome (BAC mutagenesis generated mutant viruses with wild-type growth behaviour, while full deletion of gM/UL10 resulted in an attenuated phenotype. Deletion of gN/UL49.5 in conjunction with various gM/UL10 mutants reduced average plaque sizes to the same extent as either single gM/UL10 mutant, indicating that gN is nonessential for the function performed by gM. We propose that gN functions in gM-dependent as well as gM-independent processes during which it is complemented by other viral factors.

  12. Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS

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    Reinert, Line S; Lopušná, Katarína; Winther, Henriette

    2016-01-01

    Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced t......Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV......-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication...

  13. Colony Stimulating Factor-1 Receptor Expressing Cells Infiltrating the Cornea Control Corneal Nerve Degeneration in Response to HSV-1 Infection.

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    Chucair-Elliott, Ana J; Gurung, Hem R; Carr, Meghan M; Carr, Daniel J J

    2017-09-01

    Herpes simplex virus type-1 (HSV-1) is a leading cause of neurotrophic keratitis, characterized by decreased or absent corneal sensation due to damage to the sensory corneal innervation. We previously reported the elicited immune response to infection contributes to the mechanism of corneal nerve regression/damage during acute HSV-1 infection. Our aim is to further establish the involvement of infiltrated macrophages in the mechanism of nerve loss upon infection. Macrophage Fas-Induced Apoptosis (MAFIA) transgenic C57BL/6 mice were systemically treated with AP20187 dimerizer or vehicle (VEH), and their corneas, lymph nodes, and blood were assessed for CD45+CD11b+GFP+ cell depletion by flow cytometry (FC). Mice were ocularly infected with HSV-1 or left uninfected. At 2, 4, and/or 6 days post infection (PI), corneas were assessed for sensitivity and harvested for FC, nerve structure by immunohistochemistry, viral content by plaque assay, soluble factor content by suspension array, and activation of signaling pathways by Western blot analysis. C57BL6 mice were used to compare to the MAFIA mouse model. MAFIA mice treated with AP20187 had efficient depletion of CD45+CD11b+GFP+ cells in the tissues analyzed. The reduction of CD45+CD11b+GFP+ cells recruited to the infected corneas of AP20187-treated mice correlated with preservation of corneal nerve structure and function, decreased protein concentration of inflammatory cytokines, and decreased STAT3 activation despite no changes in viral content in the cornea compared to VEH-treated animals. Our results suggest infiltrated macrophages are early effectors in the nerve regression following HSV-1 infection. We propose the neurodegeneration mechanism involves macrophages, local up-regulation of IL-6, and activation of STAT3.

  14. Virus-Induced Chaperone-Enriched (VICE domains function as nuclear protein quality control centers during HSV-1 infection.

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    Christine M Livingston

    2009-10-01

    Full Text Available Virus-Induced Chaperone-Enriched (VICE domains form adjacent to nuclear viral replication compartments (RC during the early stages of HSV-1 infection. Between 2 and 3 hours post infection at a MOI of 10, host protein quality control machinery such as molecular chaperones (e.g. Hsc70, the 20S proteasome and ubiquitin are reorganized from a diffuse nuclear distribution pattern to sequestration in VICE domains. The observation that VICE domains contain putative misfolded proteins suggests that they may be similar to nuclear inclusion bodies that form under conditions in which the protein quality control machinery is overwhelmed by the presence of misfolded proteins. The detection of Hsc70 in VICE domains, but not in nuclear inclusion bodies, indicates that Hsc70 is specifically reorganized by HSV-1 infection. We hypothesize that HSV-1 infection induces the formation of nuclear protein quality control centers to remodel or degrade aberrant nuclear proteins that would otherwise interfere with productive infection. Detection of proteolytic activity in VICE domains suggests that substrates may be degraded by the 20S proteasome in VICE domains. FRAP analysis reveals that GFP-Hsc70 is dynamically associated with VICE domains, suggesting a role for Hsc70 in scanning the infected nucleus for misfolded proteins. During 42 degrees C heat shock, Hsc70 is redistributed from VICE domains into RC perhaps to remodel viral replication and regulatory proteins that have become insoluble in these compartments. The experiments presented in this paper suggest that VICE domains are nuclear protein quality control centers that are modified by HSV-1 to promote productive infection.

  15. Association between exposure to HSV1 and cognitive functioning in a general population of adolescents. The TRAILS study.

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    Iris Jonker

    Full Text Available Infections with different herpes viruses have been associated with cognitive functioning in psychiatric patients and healthy adults. The aim of this study was to find out whether antibodies to different herpes viruses are prospectively associated with cognitive functioning in a general adolescent population.This study was performed in TRAILS, a large prospective general population cohort (N = 1084, 54% female, mean age 16.2 years (SD 0.6. At age 16, immunoglobulin G antibodies against HSV1, HSV2, CMV and EBV were measured next to high sensitive C-Reactive Protein (hsCRP. Two years later, immediate memory and executive functioning were assessed using the 15 words task and the self ordered pointing task. Multiple linear regression analysis with bootstrapping was performed to study the association between viral infections and cognitive function, adjusting for gender, socioeconomic status, ethnicity, and cannabis use.Presence of HSV1 antibodies was associated with memory function ((B = -0.272, 95% CI = -0.556 to -0.016, p = 0.047, while the association with executive functioning did not reach statistical significance (B = 0.560, 95% CI is -0.053 to 1.184, p = 0.075. The level of HSV1 antibodies was associated with both memory function (B = -0.160, 95% CI = -0.280 to -0.039, p = 0.014 and executive functioning (B = 0.296, 95% CI = 0.011 to 0.578, p = 0.046. Other herpes viruses and hsCRP were not associated with cognitive functioning.Both presence and level of HSV1 antibodies are prospectively associated with reduced cognitive performance in a large cohort of adolescents.

  16. Efficacy of the ND:YAG laser therapy on EBV and HSV1 contamination in periodontal pockets.

    Science.gov (United States)

    Martelli, Francesco Saverio; Bacci, Giovanni; Martelli, Maria Laura; Nobili, Piero; Boddi, Anna; Rosati, Claudio; Fanti, Elena

    2015-01-01

    The aim of this retrospective multicenter study was to verify the efficacy of Nd:YAG laser in the treatment of periodontal pockets infected by Epstein-Barr Virus (EBV) and Herpes Simplex Virus 1 (HSV1). Subgingival plaque samples of 291 Italian periodontal patients were analyzed by Real Time PCR to evaluate the frequency of both viruses before and after Nd:YAG laser-assisted periodontal treatment. Before treatment, EBV and HSV1 were observed in 29.9% and in 3.8% of periodontal patients respectively, while co-infection with both viruses was detected in 1.7% of cases. Periodontal Nd:YAG laser treatment ("Periodontal Biological Laser-Assisted Therapy", PERIOBLAST) produced statistical significant benefits, especially in EBV periodontal infection: 78.2% of EBV positive patients became EBV-negative following treatment. Results of this preliminary study highlight that EBV is found in periodontal pockets more frequently than HSV1, supporting the theory of the potential role of EBV in the onset and progression of periodontal disease. Moreover, our data showed that Nd:YAG laser-assisted periodontal treatment (Perioblast) is also effective in case of viral infection, validating evidences that it represents a successful alternative approach to traditional periodontal protocols.

  17. Serum HSV-1 and 2 IgM in sexually transmitted diseases - more for screening less for diagnosis: An evaluation of clinical manifestation

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    Dharmishtha G Tada

    2012-01-01

    Full Text Available Background: Herpes simplex virus type 2 (HSV-2 is the cause of most genital herpes. Now, HSV-1 has become an important cause and represents even about 30% of genital herpes in some countries. So, study related to genital herpes should consider both HSV-1 and HSV-2. Aim: To examine trends in HSV-1 and 2 seroprevalence by Serum HSV-1 and 2 IgM in all type of sexually transmitted disease (STD patients and also to evaluate correlation of serum HSV-1 and 2 IgM in STD. Materials and Methods: 150 patients attending the STD clinic attached to a tertiary care hospital of Ahmedabad were included in the study. Serum HSV-1 and 2 IgM correlations with clinical manifestations of recurrent and non-recurrent type of genital herpes patients and other non-herpetic STD patients were studied. Results: The overall serum HSV-1 and 2 IgM in STD seroprevalence were 15.66%. Female has significant higher prevalence (P < 0.05. STD cases and HSV seroprevalence were specially concentrated in persons aged 21 to 30 years. Among those positive with HSV, the distribution of STD are wide spread and found in non-herpetic group at high frequency. Out of total 23 serum HSV-1 and 2 IgM positive, 12 and 11 are distributed in herpetic and non-herpetic STDs, respectively. Discussion and Conclusion: Though serum HSV-1 and 2 IgM in STDs are less diagnostic, they help to see the iceberg part of the infection among the population concerned in recent scenario or in another words, it provides recent infective burden.

  18. Seroprevalence of HSV-1 and HSV-2 antibodies in Canadian women screened for enrolment in a herpes simplex virus vaccine trial.

    Science.gov (United States)

    Gorfinkel, I S; Aoki, F; McNeil, S; Dionne, M; Shafran, S D; Zickler, P; Halperin, S; Langley, J; Bellamy, A; Schulte, J; Heineman, T; Belshe, R

    2013-05-01

    Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) infections continue to be among the most common and unrecognized sexually transmitted infections in the world. Although treatable, HSV-1 and HSV-2 infections remain incurable. Hence, there is interest in the development of a vaccine to prevent genital herpes. As part of a multicentre, randomized, placebo-controlled trial to test such a vaccine, healthy women 18-30 years were enrolled as volunteers in several Canadian centres between 2005 and 2007. This study reports the seroprevalence of HSV-1 and HSV-2 antibodies in this group. A total of 2694 adult female volunteers in Canada with no known history of herpes simplex were screened for HSV antibodies using Western blot assay (the gold standard for diagnosis of HSV) for potential participation in a randomized, double-blind efficacy field trial of a herpes simplex vaccine. This trial provides a unique opportunity to examine the prevalence of antibodies to HSV-1 and of antibodies to HSV-2 in women with no known history of herpes simplex infection. The prevalence of antibodies to HSV-1 and to HSV-2 is compared with that found in previous Canadian studies that focused on a more general population. The overall seroprevalence of antibody to HSV-1 was 43%; that of HSV-2 was 2.5% and seropositivity to both was 2%. The prevalence of antibody to both HSV-1 and to HSV-2 increased with age. Seronegativity to both HSV-1 and HSV-2 was 56% in participating centres with populations under 250,000 and 46% in participating centres with populations over 250,000. Significant racial differences in seropositivity to HSV-1 and to HSV-2 were noted. The likelihood of participants being seropositive to HSV-1 and to HSV-2 was found to increase with age and to positively correlate with the population of the city in which they resided. Hypotheses are proposed to account for differences in racial seropositivity to HSV-1 and to HSV-2.

  19. Performance evaluation of the Aptima HSV-1 and 2 assay for the detection of HSV in cutaneous and mucocutaneous lesion specimens.

    Science.gov (United States)

    Sam, Soya S; Caliendo, Angela M; Ingersoll, Jessica; Abdul-Ali, Deborah; Kraft, Colleen S

    2017-12-13

    Timely and precise laboratory diagnosis of Herpes simplex viruses (HSV) is required to guide clinical management. The study evaluated limit of detection (LOD) and performance characteristics of the Aptima HSV 1 & 2 assay in comparison to four assays. The multi-center study compared qualitative detection of HSV-1 and 2 by the Aptima HSV-1 and 2 assay (Hologic) to ELVIS culture, Lyra Direct (Quidel), AmpliVue (Quidel) and a laboratory developed test (LDT). LOD was performed using VTM and STM diluted viral concentrations and clinical performance was evaluated using 505 swab specimens. The Aptima LOD studies performed showed a lower detection limit for STM specimens as 1450 copies/mL and 430 copies/mL for HSV1 and HSV-2 respectively; the LOD for VTM specimens was 9370 copies/mL and 8045 copies/mL for HSV-1 and HSV-2 respectively. When the assays were analyzed based on the positive consensus result established the Aptima had 95% of percent positive agreement (PPA) and 100% negative percent agreement (NPA) for the HSV-1. For the HSV-2, the PPA and NPA for Aptima were 96% and 100% respectively. AmpliVue had 1.8% invalid rate, while Lyra had no invalid results but an inhibition rate of 0.8%. Aptima and LDT did not have any invalid or inhibited results. The results indicate that the Aptima HSV-1 & 2 assay is sensitive and the performance characteristics of the Aptima assay is comparable to the assays analyzed for the detection and differentiation of HSV-1 and 2 from cutaneous and mucocutaneous lesions. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. HSV-1 targets lymphatic vessels in the eye and draining lymph node of mice leading to edema in the absence of a functional type I interferon response.

    Science.gov (United States)

    Bryant-Hudson, Katie M; Chucair-Elliott, Ana J; Conrady, Christopher D; Cohen, Alex; Zheng, Min; Carr, Daniel J J

    2013-10-01

    Herpes simplex virus type-1 (HSV-1) induces new lymphatic vessel growth (lymphangiogenesis) in the cornea via expression of vascular endothelial growth factor by virally infected epithelial cells. Here, we extend this observation to demonstrate the selective targeting of corneal lymphatics by HSV-1 in the absence of functional type I interferon (IFN) pathway. Specifically, we examined the impact of HSV-1 replication on angiogenesis using type I IFN receptor deficient (CD118(-/-)) mice. HSV-1-induced lymphatic and blood vessel growth into the cornea proper was time-dependent in immunocompetent animals. In contrast, there was an initial robust growth of lymphatic vessels into the cornea of HSV-1-infected CD118(-/-)mice, but such vessels disappeared by day 5 postinfection. The loss was selective as blood vessel integrity remained intact. Magnetic resonance imaging and confocal microscopy analysis of the draining lymph nodes of CD118(-/-) mice revealed extensive edema and loss of lymphatics compared with wild-type mice. In addition to a loss of lymphatic vessels in CD118(-/-) mice, HSV-1 infection resulted in epithelial thinning associated with geographic lesions and edema within the cornea, which is consistent with a loss of lymphatic vasculature. These results underscore the key role functional type I IFN pathway plays in the maintenance of structural integrity within the cornea in addition to the anti-viral characteristics often ascribed to the type I IFN cytokine family. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Evaluation of antibodies against glycoprotein D (gD) and glycoprotein G (gG) in HSV-1 infected individuals' serum samples.

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    Meshkat, Z; Roostaee, M H; Soleimanjahi, M; Zandi, K

    2012-04-01

    Glycoproteins D (gD) and G (gG) of herpes simplex virus type 1 (HSV-1) are virus envelope glycoproteins that are able to induce HSV-1 antibody production in infected persons. Therefore, those proteins could be in interest to develop the serodiagnostic test(s) for HSV antibody detection. The aim of present study was the comparison of anti-gD and anti-gG antibodies in HSV-1 infected individuals' serum samples. In this study, recombinant gD and gG were prepared and used for western blot test to detect the antibodies against HSV-1. Our data showed the total gD antibody titer was higher than gG antibody titer in the HSV-1 infected patient's sera but the gG antibody titer was high significantly. According to our results, gD and gG can be used for designing the diagnostic laboratory tests to evaluate total antibody against HSV-1 and HSV-2.

  2. Functional Coexpression of HSV-1 Thymidine Kinase and Green Fluorescent Protein: Implications for Noninvasive Imaging of Transgene Expression

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    Andreas Jacobs

    1999-06-01

    Full Text Available Current gene therapy technology is limited by the paucity of methodology for determining the location and magnitude of therapeutic transgene expression in vivo. We describe and validate a paradigm for monitoring therapeutic transgene expression by noninvasive imaging of the herpes simplex virus type 1 thymidine kinase (HSV-1-tk marker gene expression. To test proportional coexpression of therapeutic and marker genes, a model fusion gene comprising green fluorescent protein (gfp and HSV-1-tk genes was generated (tkgfp gene and assessed for the functional coexpression of the gene product, TKGFP fusion protein, in rat 9L gliosarcoma, RG2 glioma, and W256 carcinoma cells. Analysis of the TKGFP protein demonstrated that it can serve as a therapeutic gene by rendering tkgfp transduced cells sensitive to ganciclovir or as a screening marker useful for identifying transduced cells by fluorescence microscopy or fluorescence-activated cell sorting (FACS. TK and GFP activities in the TKGFP fusion protein were similar to corresponding wild-type proteins and accumulation of the HSV-1-tk-specific radiolabeled substrate, 2′-fluoro-2′-deoxy-1β-D-arabino-furanosyl-5-iodo-uracil (FIAU, in stability transduced clones correlated with gfp-fluorescence intensity over a wide range of expression levels. The tkgfp fusion gene itself may be useful in developing novel cancer gene therapy approaches. Valuable information about the efficiency of gene transfer and expression could be obtained by non-invasive imaging of tkgfp expression with FIAU and clinical imaging devices (gamma camera, positron-emission tomography [PET], single photon emission computed tomography [SPECT], and/or direct visualization of gfp expression in situ by fluorescence microscopy or endoscopy.

  3. Detection of EBV, CMV and HSV-1 in subgingival samples of HIV positive and negative patients with chronic periodontitis.

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    Laura Escalona

    2016-06-01

    Full Text Available Objective: To detect the presence of infection by EBV (Epstein-Barr Virus, CMV (Cytomegalovirus and HSV-1 (Herpes Simplex Virus type 1 in subgingival samples from HIV- positive patients under HAART (High Activity Antiretroviral Therapy, HIV- positive patients without HAART, HIV-negative patients with chronic periodontitis and healthy controls. Methodology: Crevicular fluid samples of 11 HIV+ patients on therapy were evaluated, 6 without antiretroviral therapy, 7 HIV- negative subjects with chronic periodontitis and 7 periodontally-healthy controls. PI (Plaque index, GI (Gingival Index, PD (probing depth and CAL (Clinical Attachment Loss were registered at six sites per each tooth in all teeth and subgingival plaque samples of a tooth were collected per quadrant. Nested PCR was used to detect EBV and endpoint PCR to detect infection by CMV and HSV-1. Results: Clinical parameters showed statistically significant differences between HIV-positive patients and subjects with chronic periodontitis compared with the control group (p<0.05. DNA of EBV was detected mainly in HIV-positive patients under HAART, 91% (10/11. DNA of CMV was detected mainly in patients without HAART, 67% (4/6, while HSV-1 was observed in 27% (3/11 of patients under HAART. In the control group no virus was detected. Coinfection was observed in 50% of HIV patients without HAART, 36% of HIV patients with HAART and 14% of HIV-negative with chronic periodontitis. Conclusion: Viral infection was prevalent in HIV patients under HAART and EBV was the primary viral infection detected in HIV-positive patients with chronic periodontitis.

  4. Different strategies for reducing intestinal background radioactivity associated with imaging HSV1-tk expression using established radionucleoside probes

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    Ruggiero, Alessandro; Brader, Peter; Serganova, Inna; Zanzonico, Pat; Cai, Shangde; Lipman, Neil S.; Hricak, Hedvig; Blasberg, Ronald G.

    2011-01-01

    One limitation of HSV1-tk reporter PET imaging with nucleoside analogues is the high background radioactivity in the intestine. We hypothesized that endogenous expression of thymidine kinase in bacterial flora could phosphorylate and trap such radiotracers, contributing to the high radioactivity levels in the bowel and therefore explored different strategies to increase fecal elimination of radiotracer. Methods Intestinal radioactivity was assessed by in vivo microPET imaging and ex vivo tissue sampling following intravenous injection of 18F-FEAU, 124I-FIAU or 18F-FHBG in a germ-free mouse strain. We also explored the use of an osmotic laxative agent and/or a 100% enzymatically hydrolyzed liquid diet. Results No significant differences in intestinal radioactivity were observed between germ-free and normal mice. 18F-FHBG-derived intestinal radioactivity levels were higher than those of 18F-FEAU and 124I-FIAU; the intestine-to-blood ratio was more than 20-fold higher for 18F-FHBG than for 18F-FEAU and 124I-FIAU. The combination of Peptamen and Nulytely lowered intestinal radioactivity levels and increased (2.2-fold) the HSV1-tk transduced xenograft-to-intestine ratio for 18F-FEAU. Conclusions Intestinal bacteria in germ-free mice do not contribute to the high intestinal levels of radioactivity following injection of radionucleoside analogs. The combination of Peptamen and Nulytely increased radiotracer elimination by increasing bowel motility without inducing dehydration. PMID:20128998

  5. Barrier to auto integration factor becomes dephosphorylated during HSV-1 Infection and Can Act as a host defense by impairing viral DNA replication and gene expression.

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    Jamin, Augusta; Thunuguntla, Prasanth; Wicklund, April; Jones, Clinton; Wiebe, Matthew S

    2014-01-01

    BAF (Barrier to Autointegration Factor) is a highly conserved DNA binding protein that senses poxviral DNA in the cytoplasm and tightly binds to the viral genome to interfere with DNA replication and transcription. To counteract BAF, a poxviral-encoded protein kinase phosphorylates BAF, which renders BAF unable to bind DNA and allows efficient viral replication to occur. Herein, we examined how BAF phosphorylation is affected by herpes simplex virus type 1 (HSV-1) infection and tested the ability of BAF to interfere with HSV-1 productive infection. Interestingly, we found that BAF phosphorylation decreases markedly following HSV-1 infection. To determine whether dephosphorylated BAF impacts HSV-1 productive infection, we employed cell lines stably expressing a constitutively unphosphorylated form of BAF (BAF-MAAAQ) and cells overexpressing wild type (wt) BAF for comparison. Although HSV-1 production in cells overexpressing wtBAF was similar to that in cells expressing no additional BAF, viral growth was reduced approximately 80% in the presence of BAF-MAAAQ. Experiments were also performed to determine the mechanism of the antiviral activity of BAF with the following results. BAF-MAAAQ was localized to the nucleus, whereas wtBAF was dispersed throughout cells prior to infection. Following infection, wtBAF becomes dephosphorylated and relocalized to the nucleus. Additionally, BAF was associated with the HSV-1 genome during infection, with BAF-MAAAQ associated to a greater extent than wtBAF. Importantly, unphosphorylated BAF inhibited both viral DNA replication and gene expression. For example, expression of two regulatory proteins, ICP0 and VP16, were substantially reduced in cells expressing BAF-MAAAQ. However, other viral genes were not dramatically affected suggesting that expression of certain viral genes can be differentially regulated by unphosphorylated BAF. Collectively, these results suggest that BAF can act in a phosphorylation-regulated manner to impair

  6. Joint capsule treatment with enkephalin-encoding HSV-1 recombinant vector reduces inflammatory damage and behavioural sequelae in rat CFA monoarthritis.

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    Lu, Ying; McNearney, Terry A; Wilson, Steven P; Yeomans, David C; Westlund, Karin N

    2008-03-01

    This study assessed enkephalin expression induced by intra-articular application of recombinant, enkephalin-encoding herpes virus (HSV-1) and the impact of expression on nociceptive behaviours and synovial lining inflammation in arthritic rats. Replication-conditional HSV-1 recombinant vectors with cDNA encoding preproenkephalin (HSV-ENK), or control transgene beta-galactosidase cDNA (HSV-beta-gal; control) were injected into knee joints with complete Freund's adjuvant (CFA). Joint temperatures, circumferences and nociceptive behaviours were monitored on days 0, 7, 14 and 21 post CFA and vector treatments. Lumbar (L4-6) dorsal root ganglia (DRG) and spinal cords were immunostained for met-enkephalin (met-ENK), beta-gal, HSV-1 proteins and Fos. Joint tissues were immunostained for met-ENK, HSV-1 proteins, and inflammatory mediators Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and cyclo-oxygenase-2, or stained with haematoxylin and eosin for histopathology. Compared to exuberant synovial hypertrophy and inflammatory cell infiltration seen in arthritic rats treated with CFA only or CFA and HSV-beta-gal, the CFA- and HSV-ENK-treated arthritic rats had: (i) striking preservation of synovial membrane cytoarchitecture with minimal inflammatory cell infiltrates; (ii) significantly improved nociceptive behavioural responses to mechanical and thermal stimuli; (iii) normalized Fos staining in lumbar dorsal horn; and (iv) significantly increased met-ENK staining in ipsilateral synovial tissue, lumbar DRG and spinal cord. The HSV-1 and transgene product expression were confined to ipsilateral lumbar DRG (HSV-1, met-ENK, beta-gal). Only transgene product (met-ENK and beta-gal) was seen in lumbar spinal cord sections. Targeted delivery of enkephalin-encoding HSV-1 vector generated safe, sustained opioid-induced analgesia with protective anti-inflammatory blunting in rat inflammatory arthritis.

  7. Cytotoxicity and cellular uptake of pyrimidine nucleosides for imaging herpes simplex type-1 thymidine kinase (HSV-1 TK) expression in mammalian cells

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    Morin, Kevin W.; Duan Weili; Xu Lihua; Zhou Aihua; Moharram, Sameh; Knaus, Edward E.; McEwan, Alexander J.B.; Wiebe, Leonard I. E-mail: leonard.wiebe@ualberta.ca

    2004-07-01

    In vivo transfer of the herpes simplex virus type-1 thymidine kinase (HSV-1 TK) gene, with subsequent administration of antiviral drugs such as ganciclovir, has emerged as a promising gene therapy protocol for treating proliferative disorders. The in vitro cytotoxicities (IC{sub 50}) for two series of 5-iodo- and (E)-5-(2-iodovinyl)-substituted 2'-deoxy- and 2'-deoxy-2'-fluoro-pyrimidine nucleosides ranged from millimolar to low nanomolar concentrations in mammalian tumor cell lines (KBALB; R-970-5; 143B; EMT-6) and their counterparts engineered to express HSV-1 TK (KBALB-STK; 143B-LTK). Their HSV-1 TK selectivity indices ranged from one (nonselective) to one million (highly selective) based on cytotoxicity, with FIRU being the least toxic to all cell lines, and FIAU being most toxic. HSV-1 TK selectivity, based on uptake, ranged from 10 to 140, with IVDU being most selective for HSV-1 TK expressing cells, followed by IVFRU, FIRU, FIAU, IVFAU and finally IUDR. Phosphorylation of [{sup 125}I]FIAU led to incorporation of the radiolabel into nucleic acids, whereas IVFRU and FIRU radioactivity was trapped primarily in the nucleotide pool. These data indicate that cytotoxicity does not depend on initial metabolic trapping (e.g., phosphorylation), but on elaboration of the mononucleotides to more cytotoxic anabolites. Lipophilicities and nucleoside transport rates of the six nucleosides tested were within narrow ranges. This supports the premise that cellular biochemistry, and not cellular bioavailability, is responsible for the observed broad range of cytotoxicity and trapping. In vivo biodistribution studies with 5-[{sup 125}I]iodo-2'-fluoro-2'-deoxyribouridine (FIRU), 5-[{sup 125}I]iodo-2'-fluoro-2'-deoxyarabinouridine (FIAU) and (E)-5-(2-[{sup 125}I]iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) demonstrate selective accumulation of all three radiotracers in HSV-1 TK-expressing KBABK-STK tumors, compared to their very low

  8. Application of shRNA-containing herpes simplex virus type 1 (HSV-1)-based gene therapy for HSV-2-induced genital herpes.

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    Liu, Zhihong; Xiang, Yang; Wei, Zhun; Yu, Bo; Shao, Yong; Zhang, Jie; Yang, Hong; Li, Manmei; Guan, Ming; Wan, Jun; Zhang, Wei

    2013-11-01

    HSV-1-based vectors have been widely used to achieve targeted delivery of genes into the nervous system. In the current study, we aim to use shRNA-containing HSV-1-based gene delivery system for the therapy of HSV-2 infection. Guinea pigs were infected intravaginally with HSV-2 and scored daily for 100 days for the severity of vaginal disease. HSV-2 shRNA-containing HSV-1 was applied intravaginally daily between 8 and 14 days after HSV-2 challenge. Delivery of HSV-2 shRNA-containing HSV-1 had no effect on the onset of disease and acute virus shedding in animals, but resulted in a significant reduction in both the cumulative recurrent lesion days and the number of days with recurrent disease. Around half of the animals in the HSV-2 shRNA group did not develop recurrent disease 100 days post HSV-2 infection. In conclusion, HSV-2 shRNA-containing HSV-1 particles are effective in reducing the recurrence of genital herpes caused by HSV-2. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. A 17-year old patient with DOCK8 deficiency, severe oral HSV-1 and aggressive periodontitis - a case of virally induced periodontitis?

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    Betts, K; Abusleme, L; Freeman, A F; Sarmadi, M; Fahle, G; Pittaluga, S; Cuellar-Rodriguez, J; Hickstein, D; Holland, S M; Su, H; Moutsopoulos, N M

    2015-02-01

    We present a 17-year old girl with DOCK-8 deficiency, severe untreated oral HSV-1 infection and associated aggressive periodontitis. DOCK-8 deficiency is a primary immunodeficiency, caused by biallelicloss-of-function mutations in the DOCK8 gene, often leading to severe viral and fungal mucocutaneous infections. Nevertheless, to date DOCK8 has not been associated with severe periodontitis and inflammatory bone loss around teeth. Understanding whether DOCK8 deficiency or severe HSV-1 infection underlies susceptibility to periodontitis is central to this case and may provide insights into susceptibility factors for periodontitis in the general population. Our clinical and microbiological data suggest that severe HSV-1 infection is the driver of periodontal inflammation in this case. Published by Elsevier B.V.

  10. Inhibitory effects of lupene-derived pentacyclic triterpenoids from Bursera simaruba on HSV-1 and HSV-2 in vitro replication.

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    Álvarez, Ángel L; Habtemariam, Solomon; Parra, Francisco

    2015-01-01

    The cytotoxicity and antiviral properties of Bursera simaruba against herpes simplex viruses (HSV-1 and HSV-2) were investigated through a bioactivity-guided isolation protocol. The plant material was fractionated using solvent-solvent partitioning, size-exclusion and thin-layer chromatography. The antiviral compounds present in the most active fractions were identified by means of LC-MS and NMR. Three different methods were compared during the evaluation of antiviral activity of samples. Four lupene-related pentacyclic triterpenes were found to be responsible for the anti-herpesvirus effects of B. simaruba and were isolated from this species for the first time. The selective indexes (SI) of B. simaruba-derived samples ranged from 7.7 to 201.9.

  11. Repressor element-1 silencing transcription factor/neuronal restrictive silencer factor (REST/NRSF can regulate HSV-1 immediate-early transcription via histone modification

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    Hill James M

    2007-06-01

    Full Text Available Abstract Background During primary infection of its human host, Herpes Simplex Virus Type-1 (HSV-1 establishes latency in neurons where the viral genome is maintained in a circular form associated with nucleosomes in a chromatin configration. During latency, most viral genes are silenced, although the molecular mechanisms responsible for this are unclear. We hypothesized that neuronal factors repress HSV-1 gene expression during latency. A search of the HSV-1 DNA sequence for potential regulatory elements identified a Repressor Element-1/Neuronal Restrictive Silencer Element (RE-1/NRSE located between HSV-1 genes ICP22 and ICP4. We predicted that the Repressor Element Silencing Transcription Factor/Neuronal Restrictive Silencer Factor (REST/NRSF regulates expression of ICP22 and ICP4. Results Transient cotransfection indicated that REST/NRSF inhibited the activity of both promoters. In contrast, cotransfection of a mutant form of REST/NRSF encoding only the DNA-binding domain of the protein resulted in less inhibition. Stably transformed cell lines containing episomal reporter plasmids with a chromatin structure showed that REST/NRSF specifically inhibited the ICP4 promoter, but not the ICP22 promoter. REST/NRSF inhibition of the ICP4 promoter was reversed by histone deacetylase (HDAC inhibitor Trichostatin A (TSA. Additionally, chromatin immuno-precipitation (ChIP assays indicated that the corepressor CoREST was recruited to the proximity of ICP4 promoter and that acetylation of histone H4 was reduced in the presence of REST/NRSF. Conclusion Since the ICP4 protein is a key transactivator of HSV-1 lytic cycle genes, these results suggest that REST/NRSF may have an important role in the establishment and/or maintenance of HSV-1 gene silencing during latency by targeting ICP4 expression.

  12. Does porphyrin suppres the apoptotic and necrotic effects of bovine herpes virus type-1(BoHV-1) and herpes simplex virus type-1(HSV-1)?

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    Yavuz, Beyza; Yazici, Zafer

    2016-09-01

    In this study, antiviral effect of porphyrin was investigated. Cooper strain of Bovine Herpes Virus type 1(BoHV-1) and Kos strain of Herpes Simplex Virus type-1 (HSV-1) were used to determine the potential of porphyrins to inhibit infection in vitro (with morphological and cytopathological criteria). Apoptotic and necrotic changes were determined by using DAPI and propidium staining. The non-cytotoxic dose of porphyrin (NCD-p) was initially calculated as 312.50µg/mL on MDBK and Vero cells. The apoptotic cell (APC) count was found 10% with BoHV-1 while it was 5.3% with BoHV-1 treated with porphyrin on MDBK cells between 6th to 24th hours post infection (hpi). Necrotic cell (NEC) count was 51% with BoHV-1 and 37.8% BoHV-1 treated with porphyrin on MDBK cells at 24th hpi. On the other hand, the APC count was found 23% with HSV-1, while 22% with the HSV-1 treated with porphyrin on Vero cells between 6th to 24th hpi. NEC count was 49% with HSV-1 and 34% HSV-1 treated with porphyrin on MDBK cells at 24th hpi. The results show that BoHV-1 was inhibited by porphyrin resulting in decreased apoptotic and necrotic changes in MDBK cells. On the contrary, porphyrine was not effective in the inhibition of HSV-1 in terms of apoptosis but it caused necrotic changes in Vero cells.

  13. Stress Hormones Epinephrine and Corticosterone Selectively Modulate Herpes Simplex Virus 1 (HSV-1) and HSV-2 Productive Infections in Adult Sympathetic, but Not Sensory, Neurons.

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    Ives, Angela M; Bertke, Andrea S

    2017-07-01

    Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect and establish latency in peripheral neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is associated with the exacerbation of clinical symptoms and the induction of recurrences in humans and animal models. The viruses preferentially replicate and establish latency in different subtypes of sensory neurons, as well as in neurons of the autonomic nervous system that are highly responsive to stress hormones. To determine if stress-related hormones modulate productive HSV-1 and HSV-2 infections within sensory and autonomic neurons, we analyzed viral DNA and the production of viral progeny after treatment of primary adult murine neuronal cultures with the stress hormones epinephrine and corticosterone. Both sensory trigeminal ganglion (TG) and sympathetic superior cervical ganglion (SCG) neurons expressed adrenergic receptors (activated by epinephrine) and the glucocorticoid receptor (activated by corticosterone). Productive HSV infection colocalized with these receptors in SCG but not in TG neurons. In productively infected neuronal cultures, epinephrine treatment significantly increased the levels of HSV-1 DNA replication and production of viral progeny in SCG neurons, but no significant differences were found in TG neurons. In contrast, corticosterone significantly decreased the levels of HSV-2 DNA replication and production of viral progeny in SCG neurons but not in TG neurons. Thus, the stress-related hormones epinephrine and corticosterone selectively modulate acute HSV-1 and HSV-2 infections in autonomic, but not sensory, neurons. IMPORTANCE Stress exacerbates acute disease symptoms resulting from HSV-1 and HSV-2 infections and is associated with the appearance of recurrent skin lesions in millions of people. Although stress hormones are thought to impact HSV-1 and HSV-2 through immune system suppression, sensory and autonomic neurons that become

  14. False-negative type-specific glycoprotein G antibody responses in STI clinic patients with recurrent HSV-1 or HSV-2 DNA positive genital herpes, The Netherlands.

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    van Rooijen, Martijn S; Roest, Wim; Hansen, Gino; Kwa, David; de Vries, Henry J C

    2016-06-01

    Herpes simplex virus (HSV) type-discriminating antibody tests (glycoprotein G (gG) directed) are used to identify naïve persons and differentiate acute infections from recurrences. We studied test characteristics of three commercially available antibody tests in patients with recurrent (established by viral PCR tests) herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) genital herpes episodes. Serum samples (at minimum 3 months after t=0) were examined for the presence of gG-1-specific or gG-2-specific antibodies using the HerpeSelect 1 and 2 Immunoblot IgG, the HerpeSelect 1 and 2 enzyme linked immunoassays IgG and the LIAISON HSV-1 and HSV-2 IgG indirect chemiluminescence immunoassays. The immunoblot was HSV-1 positive in 70.6% (95% CI 44.0% to 89.7%), the LIAISON in 88.2% (95% CI 63.5% to 98.5%) and the ELISA in 82.4% (95% CI 56.6% to 96.2%) of the 17 patients with a recurrent HSV-1 episode. From 33 patients with a recurrent HSV-2 episode, the immunoblot was HSV-2 positive in 84.8% (95% CI 68.1% to 94.9%), the LIAISON in 69.7% (95% CI 51.3% to 84.4%) and the ELISA in 84.8% (95% CI 68.1% to 94.9%). Among 15/17 (88.2%; 95% CI 63.5% to 98.5%) patients with HSV-1 and 30/33 (90.1%; 95% CI 75.7% to 98.1%) patients with HSV-2, HSV-1 or HSV-2 antibodies, respectively, were detected in at least one of the three antibody tests. Commercial type-specific gG HSV-1 or HSV-2 antibody assays were false negative in 12-30% of patients with recurrent HSV-1 or HSV-2 DNA positive genital lesions. The clinical and epidemiological use of type-specific HSV serology can be hampered by false-negative results, especially if based on a single test. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Expresión en cultivo celular de la proteína VP6 de rotavirus mediante el uso de vectores virales basados en HSV-1

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    Carlos A. Palacios; Claus, Juan; Mattion, Nora

    2016-01-01

    HSV-1 vectors were developed for the expression of several rotavirus genes. Genes from other pathogens were also expressed, thus generating a set of tools to be tested as new vaccine candidates against In this section, we show two different HSV-1 vectors that express the VP6 protein from different rotavirus strains. Figure 1 shows a defective recombinant virus expressing simultaneously EGFP and VP6 from murine rotavirus strain EC, In Figure 2, an amplicon vector overexpressing VP6 from a Wa s...

  16. A high resolution melting (HRM) technology-based assay for cost-efficient clinical detection and genotyping of herpes simplex virus (HSV)-1 and HSV-2.

    Science.gov (United States)

    Lieveld, M; Carregosa, A; Benoy, I; Redzic, N; Berth, M; Vanden Broeck, D

    2017-10-01

    Genital herpes can be caused by two very similar viruses, herpes simplex virus (HSV)-1 or HSV-2. These two HSV types cannot be distinguished clinically, but genotyping is recommended in the first-episodes of genital herpes to guide counselling and management. Quantitative polymerase chain reaction (qPCR) is the preferred diagnostic method for HSV typing. However, commercial qPCR methods use expensive fluorescent labeled probes for detection. Furthermore, most low-cost methods are not able to differentiate between HSV-1 and -2. The aim of this study was to develop a high resolution melting (HRM) technology-based assay for sensitive HSV-1 and HSV-2 detection and genotyping. Using a panel of 46 clinical specimens, the performance of the HRM assay was compared to two commercial HSV tests: the HRM assay detected HSV in all 23 positive samples, with no false positive results (100% concordance with HSV I/II Real-TM assay). Additionally, the HRM assay correctly genotyped both HSV types in a subset of these clinical samples, as determined by the Realstar HSV PCR Kit. The HSV HRM assay provides a cost-effective alternative method to conventional more expensive assays and can be used in routine clinical specimens, in cases where it is particularly necessary to detect and distinguish HSV-1 from -2. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Performance of Focus ELISA Tests for HSV-1 and HSV-2 Antibodies Among University Students With No History of Genital Herpes

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    NANDA, JOY P.; ROBERTS, JESSICA; ROMPALO, ANNE; MELENDEZ, JOHAN H.; ZENILMAN, JONATHAN

    2009-01-01

    Objectives To define the performance characteristics of the Focus ELISA HSV-1 and HSV-2 assay among 100 university students. Study Design HSV-1 and HSV-2 Focus ELISA and Western Blot assays were performed on sera from university students who reported no history of genital herpes. Results HSV-2 and HSV-1 seroprevalence by Western Blot were 3.4% and 48%, respectively. In this population, the positive predictive value of the Focus HSV-2 ELISA was 37.5%, the sensitivity was 100%, and specificity was 94.1%. The PPV of the Focus HSV-1 ELISA was 96.7%, the sensitivity was 69.0%, and the specificity was 97.8%. Conclusions In this low-prevalence population, the positive predictive value of the Focus HSV-2 ELISA test was low. This finding, together with those reported elsewhere, indicates that caution is warranted when recommending HSV screening in low-prevalence or heterogeneous populations. Consideration should be given to raising the cutoff index value for defining a positive test result. PMID:17457239

  18. Prevalence of Conjunctivitis Infection by HSV-1 in Patients Referring to Hospitals Affiliated to Iran University of Medical Sciences (IUMS in 2009

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    L Noor Mohamadian

    2012-05-01

    Full Text Available

    Background and Objectives: The viruses are the most common cause of eye infection. The most common viruses in conjunctivitis infection include Herpes simplex virus, Adeno virus and Entrovirus. It has been estimated that HSV1 causes 60-90% conjunctival infectionsin adults. Recurrent infection by HSV1 results in Herpes keratitis that is the most common cause for blindness in developing countries. Therefore, a prompt laboratory diagnosis is often very useful. Theaim of this study was to evaluate the prevalence of conjunctivitis infection by HSV-1 Hospital affiliated to Iran University of Medical Sciences (IUMS in 2009.

     

    Methods: This descriptive cross-sectional study was doneon 100 tear film and eye swabs specimens from patient with symptoms of viral conjunctivitis. All samples werecollected in viral transport media (VTM and inoculated in Vero cell line. Viral cytopatic effect was compared with control sample. HSV1 DNA wasdetected by polymerase chain reaction (PCR. Chi-square test was used to for data analysis (p<0.05.

     

    Results: Out of 100 samples under study, 2% were positive samples by cell culture, whereas in PCR9% were positive. Patients with 6-29 years old had the highest rate of HSV1 infection (13.5% than other age groups. There was not any significant relationship between age, sex and infection.

     

    Conclusion: Herpes simplex virus infection is the major cause of conjunctivitis. Taking the recurrent infection and similarity in clinical manifestation to other infections into account, it seems necessary to have a quick and specific diagnosis of HSV for bettertreatment.

     

  19. Prevalence of Conjunctivitis Infection by HSV-1 in Patients Referring to Hospitals Affiliated to Iran University of Medical Sciences (IUMS in 2009

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    Ataei Pirkooh A

    2011-08-01

    Full Text Available Background and Objectives: The viruses are the most common cause of eye infection. The most common viruses in conjunctivitis infection include Herpes simplex virus, Adeno virus and Entrovirus. It has been estimated that HSV1 causes 60-90% conjunctival infectionsin adults. Recurrent infection by HSV1 results in Herpes keratitis that is the most common cause for blindness in developing countries. Therefore, a prompt laboratory diagnosis is often very useful. Theaim of this study was to evaluate the prevalence of conjunctivitis infection by HSV-1 Hospital affiliated to Iran University of Medical Sciences (IUMS in 2009.Methods: This descriptive cross-sectional study was doneon 100 tear film and eye swabs specimens from patient with symptoms of viral conjunctivitis. All samples werecollected in viral transport media (VTM and inoculated in Vero cell line. Viral cytopatic effect was compared with control sample. HSV1 DNA wasdetected by polymerase chain reaction (PCR. Chi-square test was used to for data analysis (p<0.05.Results: Out of 100 samples under study, 2% were positive samples by cell culture, whereas in PCR9% were positive. Patients with 6-29 years old had the highest rate of HSV1 infection (13.5% than other age groups. There was not any significant relationship between age, sex and infection.Conclusion: Herpes simplex virus infection is the major cause of conjunctivitis. Taking the recurrent infection and similarity in clinical manifestation to other infections into account, it seems necessary to have a quick and specific diagnosis of HSV for bettertreatment.

  20. Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense

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    Wang, Xing; Li, Yun; Liu, Shan; Yu, Xiaoliang; Li, Lin; Shi, Cuilin; He, Wenhui; Li, Jun; Xu, Lei; Hu, Zhilin; Yu, Lu; Yang, Zhongxu; Chen, Qin; Ge, Lin; Zhang, Zili; Zhou, Biqi; Jiang, Xuejun; Chen, She; He, Sudan

    2014-01-01

    The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6–RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1–infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism. PMID:25316792

  1. Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1.

    Science.gov (United States)

    Yu, Xiaoliang; Li, Yun; Chen, Qin; Su, Chenhe; Zhang, Zili; Yang, Chengkui; Hu, Zhilin; Hou, Jue; Zhou, Jinying; Gong, Ling; Jiang, Xuejun; Zheng, Chunfu; He, Sudan

    2015-11-11

    Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Repeated social stress enhances the innate immune response to a primary HSV-1 infection in the cornea and trigeminal ganglia of Balb/c mice.

    Science.gov (United States)

    Dong-Newsom, P; Powell, N D; Bailey, M T; Padgett, D A; Sheridan, J F

    2010-02-01

    Three to 5 days after a primary HSV-1 infection, macrophages infiltrate into the trigeminal ganglia (TG) and produce anti-viral cytokines to reduce viral replication. Previous research demonstrated that social disruption stress (SDR) enhances the trafficking of monocytes/macrophages from the bone marrow to the spleen and increases pro-inflammatory cytokine production in vitro and in vivo. The impact of SDR on the trafficking of these cells to loci of herpes simplex virus type 1 (HSV-1) infection and subsequent function has not been examined. The following studies were designed to determine whether SDR would enhance the innate immune response during a primary HSV-1 infection by increasing the number of macrophages in the cornea and TG, thus increasing anti-viral cytokine production and reducing viral replication. BALB/c mice were exposed to six cycles of SDR prior to ocular infection with HSV-1 McKrae virus. Flow cytometric analysis of cells from the TG revealed an increase in the percentage of CD11b+ macrophages in SDR mice compared to controls. Immune cell infiltration into the cornea, however, could not be determined due to low cell numbers. Although gene expression of IFN-beta was decreased, SDR increased gene expression of IFN-alpha, and TNF-alpha, in the cornea and TG. Examination of viral proteins showed decreased expression of infected cell protein 0 (ICP0), glycoprotein B (gB), glycoprotein H (gH) and latency-associated transcript (LAT) in the TG, however, expression of ICP0 and gB were elevated in the cornea of SDR mice. These results indicate that the innate immune response to HSV-1 was altered and enhanced by the experience of repeated social defeat. Copyright 2009 Elsevier Inc. All rights reserved.

  3. Interferon Regulator Factor 8 (IRF8 Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells.

    Directory of Open Access Journals (Sweden)

    Lin Sun

    Full Text Available Interferon Regulatory Factor-8 (IRF8 is constitutively expressed in monocytes and B cell lineages and plays important roles in immunity to pathogens and cancer. Although IRF8 expression is induced in activated T cells, the functional relevance of IRF8 in T cell-mediated immunity is not well understood. In this study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO to investigate the role of IRF8 in T cell-mediated responses during herpes simplex virus 1 (HSV-1 infection of the eye. In contrast to wild type mice, HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, which included marked expansion of HSV-1-specific CD8+ T cells, increased infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG and enhanced elimination of virus within the trigeminal ganglion. However, the consequence of the enhanced immunological response was the development of ocular inflammation, limbitis, and neutrophilic infiltration into the cornea of HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in virus-specific memory precursor effector cells (MPEC in IRF8KO mice, suggesting that IRF8 might play a role in regulating the differentiation of effector CD8+ T cells to the memory phenotype. Together, our data suggest that IRF8 might play a role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels in T cells can be exploited therapeutically to prevent immune-mediated ocular pathology during autoimmune and infectious diseases of the eye.

  4. Determination of HSV-1 UL5 and UL29 gene copy numbers in an HSV complementing Vero cell line.

    Science.gov (United States)

    Azizi, Ali; Aidoo, Francisca; Gisonni-Lex, Lucy; McNeil, Bryan

    2013-12-01

    The genetic stability of transgenes is a critical characteristic used to assess constructed cell lines used for vaccine production. The evaluation of gene copy numbers by a qPCR method, is one of the most common approaches used to assess the consistency of transgenes in a constructed cell line. The cell line AV529-19 is a Vero-based cell line specifically engineered to express the HSV-1 UL5 and UL29 open reading frames. AV529-19 is used to support the replication of a defective HSV-2 viral candidate vaccine called HSV529. To assess the genetic stability of the UL5 and UL29 transgenes in AV529-19 cells, a digital PCR-based approach was developed. During characterization of the test method, the specificity, accuracy, and intermediate precision of the assay was investigated based on regulatory guidelines. The developed assay was used to monitor the stability of the transgenes in the manufactured AV529-19 cell lines by comparison of transgene copy numbers in the master cell bank (MCB) with their copy numbers in the extended cell bank (ECB). Results showed that the UL29 and UL5 transgenes are stable in that there are one and three copies of the UL29 and UL5 genes, respectively, per cell in both the AV529-19 MCB and ECB. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Synthesis of a probe for monitoring HSV1-tk reporter gene expression using chemical exchange saturation transfer MRI.

    Science.gov (United States)

    Bar-Shir, Amnon; Liu, Guanshu; Greenberg, Marc M; Bulte, Jeff W M; Gilad, Assaf A

    2013-12-01

    In experiments involving transgenic animals or animals treated with transgenic cells, it is important to have a method to monitor the expression of the relevant genes longitudinally and noninvasively. An MRI-based reporter gene enables monitoring of gene expression in the deep tissues of living subjects. This information can be co-registered with detailed high-resolution anatomical and functional information. We describe here the synthesis of the reporter probe, 5-methyl-5,6-dihydrothymidine (5-MDHT), which can be used for imaging of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression in rodents by MRI. The protocol also includes data acquisition and data processing routines customized for chemical exchange saturation transfer (CEST) contrast mechanisms. The dihydropyrimidine 5-MDHT is synthesized through a catalytic hydrogenation of the 5,6-double bond of thymidine to yield 5,6-dihydrothymidine, which is methylated on the C-5 position of the resulting saturated pyrimidine ring. The synthesis of 5-MDHT can be completed within 5 d, and the compound is stable for more than 1 year.

  6. Anti-HSV-1, antioxidant and antifouling phenolic compounds from the deep-sea-derived fungus Aspergillus versicolor SCSIO 41502.

    Science.gov (United States)

    Huang, Zhonghui; Nong, Xuhua; Ren, Zhe; Wang, Jie; Zhang, Xiaoyong; Qi, Shuhua

    2017-02-15

    Chemical investigation of the deep-sea-derived fungus Aspergillus versicolor SCSIO 41502 resulted in the isolation of three new anthraquinones, aspergilols G-I (1-3), one new diphenyl ether, 4-carbglyceryl-3,3'-dihydroxy-5,5'-dimethyldiphenyl ether (4), and one new benzaldehyde derivative, 2,4-dihydroxy-6-(4-methoxy-2-oxopentyl)-3-methylbenzaldehyde (5), along with 23 known phenolic compounds (6-28). The structures of new compounds were elucidated by extensive spectroscopic analysis. The absolute configuration of 3 was established by CD spectrum and the modified Mosher method. Compounds 2, 3 and 9 had evident antiviral activity towards HSV-1 with EC50 values of 4.68, 6.25, and 3.12μM, respectively. Compounds 15, 18, 20 and 22-24 showed more potent antioxidant activity than l-ascorbic acid with IC50 values of 18.92-52.27μM towards DPPH radicals. Comparison of the structures and antioxidant activities of 1-28 suggests that the number of phenolic hydroxyl group that can freely rotate can significantly affect the antioxidant activity of phenolic compounds. In addition, 4, 22-24 and 27 had significant antifouling activity against Bugula neritina larval settlement with EC50 values of 1.28, 2.61, 5.48, 1.59, and 3.40μg/ml, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Multicenter Evaluation of Meridian Bioscience HSV 1&2 Molecular Assay for Detection of Herpes Simplex Virus 1 and 2 from Clinical Cutaneous and Mucocutaneous Specimens.

    Science.gov (United States)

    Faron, Matthew L; Ledeboer, Nathan A; Patel, Anami; Beqa, Safedin H; Yen-Lieberman, Belinda; Kohn, Debra; Leber, Amy L; Mayne, Donna; Northern, William I; Buchan, Blake W

    2016-08-01

    Herpes simplex virus (HSV) causes acute and relapsing symptoms characterized by ulcerative lesions. Laboratory diagnosis of HSV in cutaneous or mucocutaneous lesions has historically been performed with the use of viral cell culture systems; however, these tests are laborious and suffer decreased sensitivity for advanced-stage lesions. The recent availability of FDA-cleared moderately complex assays has resulted in the increased use of molecular diagnostics for the routine detection of HSV in superficial swab specimens. We performed a clinical evaluation of the recently FDA-cleared illumigene HSV 1&2 loop-mediated isothermal amplification (LAMP) assay (Meridian Bioscience, Cincinnati OH) for the detection and differentiation of HSV-1 and HSV-2 in cutaneous and mucocutaneous swab specimens. A total of 1,153 clinical swab specimens were collected and tested at 7 different clinical centers. Each specimen was tested for the presence of HSV-1 and HSV-2 using the illumigene assay, and results were compared to those of the enzyme-linked virus-inducible system (ELVIS) as the reference method. Overall, the illumigene assay demonstrated a sensitivity and specificity of 94.8% and 95.5%, respectively, for the detection of HSV-1. Detection of HSV-2 was similar, with a sensitivity of 98.9% and a specificity of 95.5%. Discrepant analysis was performed using an alternative molecular test (AmpliVue HSV1+2 assay; Quidel Molecular, San Diego, CA) on 91/99 specimens that were recorded as false positive (FP) or false negative (FN) compared to the reference method. In total, 57/78 (73%) FP and 9/13 (69%) FN illumigene results were supported by the AmpliVue result. The illumigene HSV 1&2 assay demonstrated high sensitivity and specificity to detect and differentiate HSV in clinical specimens and identified 57 additional specimens that were positive for HSV compared to culture. The use of LAMP eliminates the need for the cycling of temperatures and provides results in less than 60 min

  8. Cold Sores (HSV-1)

    Science.gov (United States)

    ... can be transmitted during oral sex and cause herpes in the genital area. Herpes simplex virus-1 also can spread ... For Kids For Parents MORE ON THIS TOPIC Genital Herpes Tips for Taking Care of Your Skin Mononucleosis ...

  9. Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy.

    Science.gov (United States)

    Castela, N; Vermerie, N; Chast, F; Sauvageon-Martre, H; Denis, J; Godard, V; Goldschmidt, P; Pouliquen, Y

    1994-01-01

    A chronic administration of three ganciclovir gels (0.2%, 0.05%, 0.0125%) was compared with a placebo gel and a 3% acyclovir ophthalmic ointment in the treatment of HSV-1 rabbit keratitis. All the ganciclovir gels showed a clinical efficacy: a significant reduction of the corneal ulcer area, clouding and vascularization (p efficacy was slower than using acyclovir ointment. No significant difference could be shown between the 0.2% and 0.05% ganciclovir gels or the 0.05% ganciclovir gel and the acyclovir treatment on viral isolation, when it was performed on pooled samples. The distribution of ganciclovir and acyclovir into the rabbit eyes (HPLC methods), were similar but markedly higher in solid tissues than ocular fluids. It might explain the recovery from tissue damages. The mean corneal ganciclovir concentrations were largely higher than ED 50 of ganciclovir for HSV-1. No toxicity was expected, due to very limited systemic availability. This study suggests a comparable activity on HSV-1 superficial keratitis between 0.05%, 0.2% ganciclovir gels and 3% acyclovir ointment. Higher concentration of ganciclovir gels are probably necessary in order to treat the HSV-1 kerato-uveitis.

  10. Dual monitoring using {sup 124}I-FIAU and bioluminescence for HSV1-tk suicide gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T. S.; Kim, J. H.; Kwon, H. C. [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2007-07-01

    Herpes simplex virus type I thymidine kinase (HSV-tk) is the most common reporter gene and is used in cancer gene therapy with a prodrug nucleoside analog, ganciclovir (GCV). The aim of this study is to evaluate therapeutic efficacy of suicide gene therapy with 2'-fluoro-2'-deoxy-1-D-arabinofuranosyl-5-[{sup 124}I] iodouracil ({sup 124}I - FIAU) and bioluminescence in retrovirally HSV -tk and firefly luciferase transduced hepatoma model. The HSV -tk and firefly luciferase (Luc) was retrovirally transduced and expressed in MCA rat Morris hepatoma cells. Nude mice with subcutaneous tumors, MCA and MCA-TK-Luc, were subjected to GCV treatment (50mg/Kg/d intraperitoneally) for 5 day. PET imaging and biodistribution with ({sup 124}I-FIAU) were performed at before and after initiation of therapy with GCV. Bioluminescent signal was also measured during GCV treatment. Before GCV treatment, no significant difference in tumor volume was found in tumors between MCA and MCA-TK-Luc. After GCV treatment, tumor volume of MCA-TK-Luc markedly reduced compared to that of MCA. In biodistribution study, {sup 124}I-FIAU uptake after GCV therapy significantly decreased compared with pretreatment levels (34.8 13.67 %ID/g vs 7.6 2.59 %ID/g) and bioluminescent signal was also significantly decreased compared with pretreatment levels. In small animal PET imaging, {sup 124}I-FIAU selectively localized in HSV -tk expressing tumor and the therapeutic efficacy of GCV treatment was evaluated by {sup 124}I-FIAU PET imaging. {sup 124}I-FIAU PET and bioluminescence imaging in HSV-tk suicide gene therapy were effective to evaluate the therapeutic response. {sup 124}I-FIAU may serve as an efficient and selective agent for monitoring of transduced HSV1-tk gene expression in vivo in clinical trials.

  11. The Role of LAT in Increased CD8+ T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1▿

    Science.gov (United States)

    Allen, Sariah J.; Hamrah, Pedram; Gate, David; Mott, Kevin R.; Mantopoulos, Dimosthenis; Zheng, Lixin; Town, Terrence; Jones, Clinton; von Andrian, Ulrich H.; Freeman, Gordon J.; Sharpe, Arlene H.; BenMohamed, Lbachir; Ahmed, Rafi; Wechsler, Steven L.; Ghiasi, Homayon

    2011-01-01

    Herpes simplex virus (HSV) infection is a classic example of latent viral infection in humans and experimental animal models. The HSV-1 latency-associated transcript (LAT) plays a major role in the HSV-1 latency reactivation cycle and thus in recurrent disease. Whether the presence of LAT leads to generation of dysfunctional T cell responses in the trigeminal ganglia (TG) of latently infected mice is not known. To address this issue, we used LAT-positive [LAT(+)] and LAT-deficient [LAT(−)] viruses to evaluate the effect of LAT on CD8 T cell exhaustion in TG of latently infected mice. The amount of latency as determined by quantitative reverse transcription-PCR (qRT-PCR) of viral DNA in total TG extracts was 3-fold higher with LAT(+) than with LAT(−) virus. LAT expression and increased latency correlated with increased mRNA levels of CD8, PD-1, and Tim-3. PD-1 is both a marker for exhaustion and a primary factor leading to exhaustion, and Tim-3 can also contribute to exhaustion. These results suggested that LAT(+) TG contain both more CD8+ T cells and more CD8+ T cells expressing the exhaustion markers PD-1 and Tim-3. This was confirmed by flow cytometry analyses of expression of CD3/CD8/PD-1/Tim-3, HSV-1, CD8+ T cell pentamer (specific for a peptide derived from residues 498 to 505 of glycoprotein B [gB498–505]), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α). The functional significance of PD-1 and its ligands in HSV-1 latency was demonstrated by the significantly reduced amount of HSV-1 latency in PD-1- and PD-L1-deficient mice. Together, these results may suggest that both PD-1 and Tim-3 are mediators of CD8+ T cell exhaustion and latency in HSV-1 infection. PMID:21307196

  12. UV-C irradiation of HSV-1 infected fibroblasts (HSV-FS) enhances human natural killer (NK) cell activity against these targets

    Energy Technology Data Exchange (ETDEWEB)

    Pettera, L.; Fitzgerald-Bocarsly, P. (New Jersey Medical School, Newark (United States))

    1991-03-11

    Expression of Herpes Simplex Virus Type 1 (HSV-1) immediate early gene products has been bound to be sufficient for NK cell mediated lysis of HSV-1 infected FS. To block the targets at various stages in the infectious cycle, HSV-FS were irradiated with UV light for 1 min at 2, 6, and 20 hr post-infection. NK mediated lysis of 2 hr and 5 hr UV treated HSV-FS was 2-fold higher than non-UV treated HSV-FS despite a {gt}99% inhibition in virus yield. In contrast, 20 hr infected targets were lysed less well than 2 and 6 hr targets despite strong glycoprotein expression and induction of high levels of interferon-alpha (IFN-{alpha}) production by effector PBMC's; this lysis was not enhanced by UV treatment. Since NK lysis of HSV-FS has been found to be dependent on an HLA-DR{sup +} accessory cell (AC), lysis of irradiated HSV-FS by PBMC's depleted of AC was measured. Such depletion eradicated NK lysis of the UV treated HSV-FS indicating that irradiation does not overcome the AC requirement for NK lysis. UV irradiation of another HLA-DR{sup +} dependent target, Vesicular Stomatitis Virus (VSV) infected FS led to a dramatic reduction in both NK lysis and IFN-{alpha} induction. HSV-1 is a DNA virus whose genes are expressed in a cascade fashion whereas VSV is an RNA virus. The authors hypothesize that the enhancement in AC dependent NK activity observed for UV irradiated HSV-FS, but not VSV-FS, targets is due to overproduction of either a cellular or viral gene product which specifically occurs early in the HSV-1 infectious cycle and is downregulated by 20 hr post-infection.

  13. Inhibition of human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1) infectivity with a broad range of lectins

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Vestergaard, B F

    1991-01-01

    Five lectins with specificity for N- and O-linked oligosaccharides were examined for inhibition of HIV-1 and HSV-1 infectivity in vitro. HIV-1 isolate HTLVIIIB was preincubated with lectin and subsequently inoculated onto MT-4 cells. Lectins specific for N-linked oligosaccharides blocked HIV infe......-1 infection, the most potent inhibition was found with the lectin HPA. These results indicate that lectins may have a broad antiviral effect on enveloped viruses only limited by types of oligosaccharides present on individual viruses.......Five lectins with specificity for N- and O-linked oligosaccharides were examined for inhibition of HIV-1 and HSV-1 infectivity in vitro. HIV-1 isolate HTLVIIIB was preincubated with lectin and subsequently inoculated onto MT-4 cells. Lectins specific for N-linked oligosaccharides blocked HIV...... infection in nanomolar-micromolar concentrations, but no anti-HIV effect was found with the lectin HPA, mainly reacting with O-linked oligosaccharides. HSV-1 infectivity was measured in a plaque reduction assay using Vero cells, and while both N- and O-linked oligosaccharide -specific lectins inhibited HSV...

  14. Efficacy of the anti-VZV (anti-HSV3 vaccine in HSV1 and HSV2 recurrent herpes simplex disease: a prospective study

    Directory of Open Access Journals (Sweden)

    Le Goaster J

    2012-07-01

    Full Text Available Jacqueline Le Goaster,1 Sylvie Gonzalo,2 Patrice Bourée,1 Frederic Tangy,3 Anne-Lise Haenni41Department of Tropical Diseases, Centre Hospitalo-Universitaire (CHU, University of Paris XI, Le Kremlin Bicêtre, 2Biomnis Laboratory, Ivry-sur-Seine, 3Retro-Virology, Centre National de Recherche Scientifique (CNRS, Pasteur Institute, Paris; 4Jacques Monod Institute, Centre National de Recherche Scientifique (CNRS, University of Paris VII, Paris, FranceBackground: The aim of this study was to evaluate the possibility of using the anti-varicella zoster virus (anti-VZV, also known as anti-HSV3 vaccine against orobuccal herpes simplex virus type 1 (HSV1 and genital herpes simplex virus type 2 (HSV2. This was suggested by study of the phylogenetic tree of members of the herpes virus family, which showed a close relationship between VZV (HSV3 and the HSV1 and HSV2 herpes viruses.Methods: The present prospective study was conducted from January 2005 through January 2011. Twenty-four patients afflicted with HSV1 and HSV2 herpes recurrences over a period of years, numbering 6–8 and more recurrences per year, agreed to receive the anti-VZV vaccine. They were compared with 26 nonvaccinated patients presenting with herpes simplex diseases 2–5 times a year. All 50 patients were documented with anti-HSV1, anti-HSV2, and anti-VZV antibody serological testing.Results: From 2005 through 2011, for the 24 anti-VZV vaccinated patients, the average number of herpes relapses decreased to 0, correlated with an increased anti-VZV antibody level and clinical recovery of all patients, whereas no improvement was observed for the 26 nonvaccinated herpes patients.Conclusion: Data for the anti-VZV serological antibody levels tested before and after anti-VZV vaccination showed a significant (P < 0.001 increase among vaccinated patients. This suggests defective anti-VZV immune power in these patients. After 6 years of positive results for anti-VZV vaccine, this is a logical and

  15. Inhibition of human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1) infectivity with a broad range of lectins

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Vestergaard, B F

    1991-01-01

    Five lectins with specificity for N- and O-linked oligosaccharides were examined for inhibition of HIV-1 and HSV-1 infectivity in vitro. HIV-1 isolate HTLVIIIB was preincubated with lectin and subsequently inoculated onto MT-4 cells. Lectins specific for N-linked oligosaccharides blocked HIV infe......-1 infection, the most potent inhibition was found with the lectin HPA. These results indicate that lectins may have a broad antiviral effect on enveloped viruses only limited by types of oligosaccharides present on individual viruses....

  16. Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model.

    Science.gov (United States)

    Boukhvalova, Marina; McKay, Jamall; Mbaye, Aissatou; Sanford-Crane, Hannah; Blanco, Jorge C G; Huber, Ashley; Herold, Betsy C

    2015-10-01

    Subunit vaccines based on the herpes simplex virus 2 (HSV-2) glycoprotein D (gD-2) have been the major focus of HSV-2 vaccine development for the past 2 decades. Based on the promising data generated in the guinea pig model, a formulation containing truncated gD-2, aluminum salt, and MPL (gD/AS04) advanced to clinical trials. The results of these trials, however, were unexpected, as the vaccine protected against HSV-1 infection but not against HSV-2. To address this discrepancy, we developed a Depot medroxyprogesterone acetate (DMPA)-treated cotton rat Sigmodon hispidus model of HSV-2 and HSV-1 genital infection. The severity of HSV-1 genital herpes was less than that of HSV-2 genital herpes in cotton rats, and yet the model allowed for comparative evaluation of gD/AS04 immunogenicity and efficacy. Cotton rats were intramuscularly vaccinated using a prime boost strategy with gD/AS04 (Simplirix vaccine) or control vaccine formulation (hepatitis B vaccine FENDrix) and subsequently challenged intravaginally with HSV-2 or HSV-1. The gD/AS04 vaccine was immunogenic in cotton rats and induced serum IgG directed against gD-2 and serum HSV-2 neutralizing antibodies but failed to efficiently protect against HSV-2 disease or to decrease the HSV-2 viral load. However, gD/AS04 significantly reduced vaginal titers of HSV-1 and better protected animals against HSV-1 compared to HSV-2 genital disease. The latter finding is generally consistent with the clinical outcome of the Herpevac trial of Simplirix. Passive transfer of serum from gD/AS04-immunized cotton rats conferred stronger protection against HSV-1 genital disease. These findings suggest the need for alternative vaccine strategies and the identification of new correlates of protection. In spite of the high health burden of genital herpes, there is still no effective intervention against the disease. The significant gap in knowledge on genital herpes pathogenesis has been further highlighted by the recent failure of GSK

  17. An Epigenetic Compound Library Screen Identifies BET Inhibitors That Promote HSV-1 and -2 Replication by Bridging P-TEFb to Viral Gene Promoters through BRD4.

    Directory of Open Access Journals (Sweden)

    Ke Ren

    2016-10-01

    Full Text Available The human HSV-1 and -2 are common pathogens of human diseases. Both host and viral factors are involved in HSV lytic infection, although detailed mechanisms remain elusive. By screening a chemical library of epigenetic regulation, we identified bromodomain-containing protein 4 (BRD4 as a critical player in HSV infection. We show that treatment with pan BD domain inhibitor enhanced both HSV infection. Using JQ1 as a probe, we found that JQ1, a defined BD1 inhibitor, acts through BRD4 protein since knockdown of BRD4 expression ablated JQ1 effect on HSV infection. BRD4 regulates HSV replication through complex formation involving CDK9 and RNAP II; whereas, JQ1 promotes HSV-1 infection by allocating the complex to HSV gene promoters. Therefore, suppression of BRD4 expression or inhibition of CDK9 activity impeded HSV infection. Our data support a model that JQ1 enhances HSV infection by switching BRD4 to transcription regulation of viral gene expression from chromatin targeting since transient expression of BRD4 BD1 or BD1/2 domain had similar effect to that by JQ1 treatment. In addition to the identification that BRD4 is a modulator for JQ1 action on HSV infection, this study demonstrates BRD4 has an essential role in HSV infection.

  18. RIG-I is required for VSV-induced cytokine production by murine glia and acts in combination with DAI to initiate responses to HSV-1.

    Science.gov (United States)

    Crill, Emma K; Furr-Rogers, Samantha R; Marriott, Ian

    2015-12-01

    A defining feature of viral central nervous system (CNS) infection is the rapid onset of severe neuroinflammation. However, the mechanisms underlying glial responses to replicative neurotropic viruses are only now becoming apparent with the discovery of a number of cytosolic sensors for viral nucleic acids. We have described the expression by murine and human glial cells of two disparate pattern recognition receptors, retinoic acid inducible gene-I (RIG-I) and DNA-dependent activator of interferon regulatory factors (DAI), receptors for viral RNA and DNA moieties, respectively. In the present study, we demonstrate the functional significance of RIG-I expression in primary murine microglia and astrocytes. Our data indicate that murine glial immune responses to a model neurotropic RNA virus, vesicular stomatitis virus, are RIG-I dependent and independent of levels of DAI expression or RNA polymerase III activity. In contrast, maximal glial inflammatory and antiviral responses to the DNA virus herpes simplex virus-1 (HSV-1) are dependent on the expression of both RIG-I and DAI, and require RNA polymerase III activity. These findings indicate that the RNA sensor, RIG-I, acts in parallel with DAI in an RNA polymerase III-dependent manner to initiate glial responses to HSV-1. We therefore suggest that RIG-I plays a significant role in the detection of both RNA and DNA pathogens by microglia and astrocytes. © 2015 Wiley Periodicals, Inc.

  19. Evaluation of reactivation of HSV1, HHV6, CMV and EBV in a population of patients undergoing allogeneic bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Caterina Matinato

    2011-06-01

    Full Text Available Herpes viruses are recognized as important pathogens as a result of viral reactivation in immunocompromised hosts, especially in patients undergoing bone marrow transplantation. Objectives of this study were the assessment of the reactivation of herpes virus HSV1, HHV6, CMV and EBV and the correlation between viral reactivation and progression of transplantation in a population of patients undergoing allogeneic bone marrow transplantation at Fondazione IRCCS Ospedale Maggiore Ca’ Granda Policlinico, Milan. Viral DNA was detected and quantified by Real Time PCR in a population of 35 patients undergoing allogeneic bone marrow transplantation. The viral reactivation was observed in 7 patients for HSV1 (20%, 6 patients for HHV6 (17.1%, 11 patients for CMV (31.4% and 4 patients for EBV (11.4%. Difference in the incidence of aGVDH between patients with viral reactivation versus those for which there was no reactivation was statistically significant. These data confirm the importance of monitoring viral load for the management of antiviral therapy in order to prevent CMV disease and complications related to herpes viruses reactivation.

  20. HSV-1 amplicon vectors launch the production of heterologous rotavirus-like particles and induce rotavirus-specific immune responses in mice.

    Science.gov (United States)

    Laimbacher, Andrea S; Esteban, Laura E; Castello, Alejandro A; Abdusetir Cerfoglio, Juan C; Argüelles, Marcelo H; Glikmann, Graciela; D'Antuono, Alejandra; Mattion, Nora; Berois, Mabel; Arbiza, Juan; Hilbe, Monika; Schraner, Elisabeth M; Seyffert, Michael; Dresch, Christiane; Epstein, Alberto L; Ackermann, Mathias; Fraefel, Cornel

    2012-09-01

    Virus-like particles (VLPs) are promising vaccine candidates because they represent viral antigens in the authentic conformation of the virion and are therefore readily recognized by the immune system. As VLPs do not contain genetic material they are safer than attenuated virus vaccines. In this study, herpes simplex virus type 1 (HSV-1) amplicon vectors were constructed to coexpress the rotavirus (RV) structural genes VP2, VP6, and VP7 and were used as platforms to launch the production of RV-like particles (RVLPs) in vector-infected mammalian cells. Despite the observed splicing of VP6 RNA, full-length VP6 protein and RVLPs were efficiently produced. Intramuscular injection of mice with the amplicon vectors as a two-dose regimen without adjuvants resulted in RV-specific humoral immune responses and, most importantly, immunized mice were partially protected at the mucosal level from challenge with live wild-type (wt) RV. This work provides proof of principle for the application of HSV-1 amplicon vectors that mediate the efficient production of heterologous VLPs as genetic vaccines.

  1. Comparative study of cellular kinetics of reporter probe [{sup 131}I]FIAU in neonatal cardiac myocytes after transfer of HSV1-tk reporter gene with two vectors

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    Lan Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022 (China)], E-mail: lxl730724@hotmail.com; Yin Xiaohua; Wang Ruihua; Liu Ying [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022 (China); Zhang Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China) and Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022 (China)], E-mail: zhyx1229@163.com

    2009-02-15

    Aim: Reporter gene imaging is a promising approach for noninvasive monitoring of cardiac gene therapy. In this study, HSV1-tk (herpes simplex virus type 1 thymidine kinase) and FIAU (2'-fluoro-2'-deoxy-1-{beta}-D-arabinofuranosyl-5-iodouracil) were used as the reporter gene and probe, respectively. Cellular uptakes of radiolabeled FIAU of neonatal rat cardiac myocytes transferred with HSV1-tk were compared between two vectors, adenovirus and liposome. The aims of this study were to choose the better vector and to provide a theoretical basis for good nuclide images. Methods: Neonatal cardiac myocytes were obtained from rat heart by single collagenase digestion. HSV1-tk inserted into adenovirus vector (recombinant adenovirus type 5, Ad5-tk) and plasmid (pDC316-tk) coated with Lipofectamine 2000 (pDC316-tk/lipoplex) were developed; thus, HSV1-tk could be transferred into neonatal cardiac myocytes. FAU (2'-fluoro-2'-deoxy-1-{beta}-D-arabinofuranosyluracil) was labeled with {sup 131}I, and the product was assessed after purification with reversed-phase Sep-Pak C-18 column. The uptake rates of [{sup 131}I]FIAU in the transferred cardiac myocytes at different times (0.5, 1, 2, 3, 4 and 5 h) were detected. Furthermore, mRNA expression and protein expression of HSV1-tk were detected by semiquantitative reverse-transcriptase polymerase chain reaction and immunocytochemistry. Results: FAU could be labeled with {sup 131}I, and the labeling efficiency and radiochemical purity rates were 53.82{+-}2.05% and 94.85{+-}1.76%, respectively. Time-dependent increase of the accumulation of [{sup 131}I]FIAU was observed in both the Ad5-tk group and the pDC316/lipoplex group, and the highest uptake rate occurred at 5 h, with peak values of 12.55{+-}0.37% and 2.09{+-}0.34%, respectively. Greater uptakes of [{sup 131}I]FIAU in Ad5-tk-infected cells compared with pDC316/lipoplex-transfected ones occurred at all the time points (t=12.978-38.253, P<.01). The exogenous gene

  2. A Herpes Simplex Virus Type 1 Human Asymptomatic CD8+ T-Cell Epitopes-Based Vaccine Protects Against Ocular Herpes in a “Humanized” HLA Transgenic Rabbit Model

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    Srivastava, Ruchi; Khan, Arif A.; Huang, Jiawei; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

    2015-01-01

    Purpose. A clinical vaccine that protects from ocular herpes simplex virus type 1 (HSV-1) infection and disease still is lacking. In the present study, preclinical vaccine trials of nine asymptomatic (ASYMP) peptides, selected from HSV-1 glycoproteins B (gB), and tegument proteins VP11/12 and VP13/14, were performed in the “humanized” HLA–transgenic rabbit (HLA-Tg rabbit) model of ocular herpes. We recently reported that these peptides are highly recognized by CD8+ T cells from “naturally” protected HSV-1–seropositive healthy ASYMP individuals (who have never had clinical herpes disease). Methods. Mixtures of three ASYMP CD8+ T-cell peptides derived from either HSV-1 gB, VP11/12, or VP13/14 were delivered subcutaneously to different groups of HLA-Tg rabbits (n = 10) in incomplete Freund's adjuvant, twice at 15-day intervals. The frequency and function of HSV-1 epitope-specific CD8+ T cells induced by these peptides and their protective efficacy, in terms of survival, virus replication in the eye, and ocular herpetic disease were assessed after an ocular challenge with HSV-1 (strain McKrae). Results. All mixtures elicited strong and polyfunctional IFN-γ– and TNF-α–producing CD107+CD8+ cytotoxic T cells, associated with a significant reduction in death, ocular herpes infection, and disease (P herpes, and provide a prototype vaccine formulation that may be highly efficacious for preventing ocular herpes in humans. PMID:26098469

  3. A spiroketal-enol ether derivative from Tanacetum vulgare selectively inhibits HSV-1 and HSV-2 glycoprotein accumulation in Vero cells.

    Science.gov (United States)

    Álvarez, Ángel L; Habtemariam, Solomon; Abdel Moneim, Ahmed E; Melón, Santiago; Dalton, Kevin P; Parra, Francisco

    2015-07-01

    The inhibitory effects of Tanacetum vulgare rhizome extracts on HSV-1 and HSV-2 in vitro replication were assessed. Unlike extracts obtained from the aerial parts, adsorption inhibition and virucidal activities seemed not to be relevant for the observed antiviral action of tansy rhizome extracts. Instead, the most significant effects were the inhibition of virus penetration and a novel mechanism consisting of the specific arrest of viral gene expression and consequently the decrease of viral protein accumulation within infected cells. Through a bioactivity-guided fractionation protocol we isolated and identified the spiroketal-enol ether derivative (E)-2-(2,4-hexadiynyliden)-1,6-dioxaspiro[4.5]dec-3-ene as the active compound responsible for this inhibitory effect. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Imaging grafted cells with [18F]FHBG using an optimized HSV1-TK mammalian expression vector in a brain injury rodent model.

    Science.gov (United States)

    Salabert, Anne-Sophie; Vaysse, Laurence; Beaurain, Marie; Alonso, Mathieu; Arribarat, Germain; Lotterie, Jean-Albert; Loubinoux, Isabelle; Tafani, Mathieu; Payoux, Pierre

    2017-01-01

    Cell transplantation is an innovative therapeutic approach after brain injury to compensate for tissue damage. To have real-time longitudinal monitoring of intracerebrally grafted cells, we explored the feasibility of a molecular imaging approach using thymidine kinase HSV1-TK gene encoding and [18F]FHBG as a reporter probe to image enzyme expression. A stable neuronal cell line expressing HSV1-TK was developed with an optimised mammalian expression vector to ensure long-term transgene expression. After [18F]FHBG incubation under defined parameters, calibration ranges from 1 X 104 to 3 X 106 Neuro2A-TK cells were analysed by gamma counter or by PET-camera. In parallel, grafting with different quantities of [18F]FHBG prelabelled Neuro2A-TK cells was carried out in a rat brain injury model induced by stereotaxic injection of malonate toxin. Image acquisition of the rats was then performed with PET/CT camera to study the [18F]FHBG signal of transplanted cells in vivo. Under the optimised incubation conditions, [18F]FHBG cell uptake rate was around 2.52%. In-vitro calibration range analysis shows a clear linear correlation between the number of cells and the signal intensity. The PET signal emitted into rat brain correlated well with the number of cells injected and the number of surviving grafted cells was recorded via the in-vitro calibration range. PET/CT acquisitions also allowed validation of the stereotaxic injection procedure. Technique sensitivity was evaluated under 5 X 104 grafted cells in vivo. No [18F]FHBG or [18F]metabolite release was observed showing a stable cell uptake even 2 h post-graft. The development of this kind of approach will allow grafting to be controlled and ensure longitudinal follow-up of cell viability and biodistribution after intracerebral injection.

  5. Imaging grafted cells with [18F]FHBG using an optimized HSV1-TK mammalian expression vector in a brain injury rodent model.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Salabert

    Full Text Available Cell transplantation is an innovative therapeutic approach after brain injury to compensate for tissue damage. To have real-time longitudinal monitoring of intracerebrally grafted cells, we explored the feasibility of a molecular imaging approach using thymidine kinase HSV1-TK gene encoding and [18F]FHBG as a reporter probe to image enzyme expression.A stable neuronal cell line expressing HSV1-TK was developed with an optimised mammalian expression vector to ensure long-term transgene expression. After [18F]FHBG incubation under defined parameters, calibration ranges from 1 X 104 to 3 X 106 Neuro2A-TK cells were analysed by gamma counter or by PET-camera. In parallel, grafting with different quantities of [18F]FHBG prelabelled Neuro2A-TK cells was carried out in a rat brain injury model induced by stereotaxic injection of malonate toxin. Image acquisition of the rats was then performed with PET/CT camera to study the [18F]FHBG signal of transplanted cells in vivo.Under the optimised incubation conditions, [18F]FHBG cell uptake rate was around 2.52%. In-vitro calibration range analysis shows a clear linear correlation between the number of cells and the signal intensity. The PET signal emitted into rat brain correlated well with the number of cells injected and the number of surviving grafted cells was recorded via the in-vitro calibration range. PET/CT acquisitions also allowed validation of the stereotaxic injection procedure. Technique sensitivity was evaluated under 5 X 104 grafted cells in vivo. No [18F]FHBG or [18F]metabolite release was observed showing a stable cell uptake even 2 h post-graft.The development of this kind of approach will allow grafting to be controlled and ensure longitudinal follow-up of cell viability and biodistribution after intracerebral injection.

  6. Imaging grafted cells with [18F]FHBG using an optimized HSV1-TK mammalian expression vector in a brain injury rodent model

    Science.gov (United States)

    Beaurain, Marie; Alonso, Mathieu; Arribarat, Germain; Lotterie, Jean-Albert; Loubinoux, Isabelle; Tafani, Mathieu; Payoux, Pierre

    2017-01-01

    Introduction Cell transplantation is an innovative therapeutic approach after brain injury to compensate for tissue damage. To have real-time longitudinal monitoring of intracerebrally grafted cells, we explored the feasibility of a molecular imaging approach using thymidine kinase HSV1-TK gene encoding and [18F]FHBG as a reporter probe to image enzyme expression. Methods A stable neuronal cell line expressing HSV1-TK was developed with an optimised mammalian expression vector to ensure long-term transgene expression. After [18F]FHBG incubation under defined parameters, calibration ranges from 1 X 104 to 3 X 106 Neuro2A-TK cells were analysed by gamma counter or by PET-camera. In parallel, grafting with different quantities of [18F]FHBG prelabelled Neuro2A-TK cells was carried out in a rat brain injury model induced by stereotaxic injection of malonate toxin. Image acquisition of the rats was then performed with PET/CT camera to study the [18F]FHBG signal of transplanted cells in vivo. Results Under the optimised incubation conditions, [18F]FHBG cell uptake rate was around 2.52%. In-vitro calibration range analysis shows a clear linear correlation between the number of cells and the signal intensity. The PET signal emitted into rat brain correlated well with the number of cells injected and the number of surviving grafted cells was recorded via the in-vitro calibration range. PET/CT acquisitions also allowed validation of the stereotaxic injection procedure. Technique sensitivity was evaluated under 5 X 104 grafted cells in vivo. No [18F]FHBG or [18F]metabolite release was observed showing a stable cell uptake even 2 h post-graft. Conclusion The development of this kind of approach will allow grafting to be controlled and ensure longitudinal follow-up of cell viability and biodistribution after intracerebral injection. PMID:28926581

  7. FasL and FADD delivery by a glioma-specific and cell cycle-dependent HSV-1 amplicon virus enhanced apoptosis in primary human brain tumors

    Directory of Open Access Journals (Sweden)

    Lam Paula Y

    2010-10-01

    Full Text Available Abstract Background Glioblastoma multiforme is the most malignant cancer of the brain and is notoriously difficult to treat due to the highly proliferative and infiltrative nature of the cells. Herein, we explored the combination treatment of pre-established human glioma xenograft using multiple therapeutic genes whereby the gene expression is regulated by both cell-type and cell cycle-dependent transcriptional regulatory mechanism conferred by recombinant HSV-1 amplicon vectors. Results We demonstrated for the first time that Ki67-positive proliferating primary human glioma cells cultured from biopsy samples were effectively induced into cell death by the dual-specific function of the pG8-FasL amplicon vectors. These vectors were relatively stable and exhibited minimal cytotoxicity in vivo. Intracranial implantation of pre-transduced glioma cells resulted in better survival outcome when compared with viral vectors inoculated one week post-implantation of tumor cells, indicating that therapeutic efficacy is dependent on the viral spread and mode of viral vectors administration. We further showed that pG8-FasL amplicon vectors are functional in the presence of commonly used treatment regimens for human brain cancer. In fact, the combined therapies of pG8-FasL and pG8-FADD in the presence of temozolomide significantly improved the survival of mice bearing intracranial high-grade gliomas. Conclusion Taken together, our results showed that the glioma-specific and cell cycle-dependent HSV-1 amplicon vector is potentially useful as an adjuvant therapy to complement the current gene therapy strategy for gliomas.

  8. Nucleotide sequences of Herpes Simplex Virus type 1 (HSV-1) affecting virus entry, cell fusion, and production of glycoprotein gB (VP7)

    Energy Technology Data Exchange (ETDEWEB)

    DeLuca, N.; Bzik, D.J.; Bond, V.C.; Person, S.; Snipes, W.

    1982-10-30

    The tsB5 strain of Herpes Simplex Virus type 1 (HSV-1) contains at least two mutations; one mutation specifies the syncytial phenotype and the other confers temperature sensitivity for virus growth. These functions are known to be located between the prototypic map coordinates 0.30 and 0.42. In this study it was demonstrated that tsB5 enters human embryonic lung (HEL) cells more rapidly than KOS, another strain of HSV-1. The EcoRI restriction fragment F from the KOS strain (map coordinates 0.315 to 0.421) was mapped with eight restriction endonucleases, and 16 recombinant plasmids were constructed which contained varying portions of the KOS genome. Recombinant viruses were generated by marker-rescue and marker-transfer cotransfection procedures, using intact DNA from one strain and a recombinant plasmid containing DNA from the other strain. The region of the crossover between the two nonisogenic strains was inferred by the identification of restriction sites in the recombinants that were characteristic of the parental strains. The recombinants were subjected to phenotypic analysis. Syncytium formation, rate of virus entry, and the production of gB were all separable by the crossovers that produced the recombinants. The KOS sequences which rescue the syncytial phenotype of tsB5 were localized to 1.5 kb (map coordinates 0.345 to 0.355), and the temperature-sensitive mutation was localized to 1.2 kb (0.360 to 0.368), giving an average separation between the mutations of 2.5 kb on the 150-kb genome. DNA sequences that specify a functional domain for virus entry were localized to the nucleotide sequences between the two mutations. All three functions could be encoded by the virus gene specifying the gB glycoprotein.

  9. Enzyme-Assisted Extraction of Bioactive Material from Chondrus crispus and Codium fragile and Its Effect on Herpes simplex Virus (HSV-1)

    Science.gov (United States)

    Kulshreshtha, Garima; Burlot, Anne-Sophie; Marty, Christel; Critchley, Alan; Hafting, Jeff; Bedoux, Gilles; Bourgougnon, Nathalie; Prithiviraj, Balakrishnan

    2015-01-01

    Codium fragile and Chondrus crispus are, respectively, green and red seaweeds which are abundant along the North Atlantic coasts. We investigated the chemical composition and antiviral activity of enzymatic extracts of C. fragile (CF) and C. crispus (CC). On a dry weight basis, CF consisted of 11% protein, 31% neutral sugars, 0.8% sulfate, 0.6% uronic acids, and 49% ash, while CC contained 27% protein, 28% neutral sugars, 17% sulfate, 1.8% uronic acids, and 25% ash. Enzyme-assisted hydrolysis improved the extraction efficiency of bioactive materials. Commercial proteases and carbohydrases significantly improved (p ≤ 0.001) biomass yield (40%–70% dry matter) as compared to aqueous extraction (20%–25% dry matter). Moreover, enzymatic hydrolysis enhanced the recovery of protein, neutral sugars, uronic acids, and sulfates. The enzymatic hydrolysates exhibited significant activity against Herpes simplex virus (HSV-1) with EC50 of 77.6–126.8 μg/mL for CC and 36.5–41.3 μg/mL for CF, at a multiplicity of infection (MOI) of 0.001 ID50/cells without cytotoxity (1–200 μg/mL). The extracts obtained from proteases (P1) and carbohydrases (C3) were also effective at higher virus MOI of 0.01 ID50/cells without cytotoxity. Taken together, these results indicate the potential application of enzymatic hydrolysates of C. fragile and C. crispus in functional food and antiviral drug discovery. PMID:25603348

  10. Phytochemical analysis and in vitro evaluation of the biological activity against herpes simplex virus type 1 (HSV-1) of Cedrus libani A. Rich.

    Science.gov (United States)

    Loizzo, Monica Rosa; Saab, Antoine; Tundis, Rosa; Statti, Giancarlo A; Lampronti, Ilaria; Menichini, Francesco; Gambari, Roberto; Cinatl, Jindrich; Doerr, Hans Wilhelm

    2008-01-01

    Cedrus libani are widely used as traditional medicine in Lebanon for treatment of different infection diseases. In the present study we reported the phytochemical composition analyzed by GC-MS of wood essential oil and cones and leaves ethanol extracts. The main components of wood essential oil were himachalol (22.50%), beta-himachalene (21.90%), and alpha-himachalene (10.50%). Leaves ethanol extract was characterized by a high content of germacrene d (29.40%). The same extract obtained from cones essentially contained alpha-pinene (51.0%) and beta-myrcene (13.0%). Moreover, we investigated extracts, essential oil, and identified compounds for their in vitro antiviral activities against herpes simplex virus type 1 (HSV-1). Cytotoxicity was evaluated by MTT assay in Vero cells. Cones and leaves ethanol extracts exhibited an interesting activity with IC50 of 0.50 and 0.66 mg/ml, respectively, at non-cytotoxic concentration. A comparable activity was found when essential oil was tested (IC50 of 0.44 mg/ml).

  11. Enzyme-Assisted Extraction of Bioactive Material from Chondrus crispus and Codium fragile and Its Effect on Herpes simplex Virus (HSV-1

    Directory of Open Access Journals (Sweden)

    Garima Kulshreshtha

    2015-01-01

    Full Text Available Codium fragile and Chondrus crispus are, respectively, green and red seaweeds which are abundant along the North Atlantic coasts. We investigated the chemical composition and antiviral activity of enzymatic extracts of C. fragile (CF and C. crispus (CC. On a dry weight basis, CF consisted of 11% protein, 31% neutral sugars, 0.8% sulfate, 0.6% uronic acids, and 49% ash, while CC contained 27% protein, 28% neutral sugars, 17% sulfate, 1.8% uronic acids, and 25% ash. Enzyme-assisted hydrolysis improved the extraction efficiency of bioactive materials. Commercial proteases and carbohydrases significantly improved (p ≤ 0.001 biomass yield (40%–70% dry matter as compared to aqueous extraction (20%–25% dry matter. Moreover, enzymatic hydrolysis enhanced the recovery of protein, neutral sugars, uronic acids, and sulfates. The enzymatic hydrolysates exhibited significant activity against Herpes simplex virus (HSV-1 with EC50 of 77.6–126.8 μg/mL for CC and 36.5–41.3 μg/mL for CF, at a multiplicity of infection (MOI of 0.001 ID50/cells without cytotoxity (1–200 μg/mL. The extracts obtained from proteases (P1 and carbohydrases (C3 were also effective at higher virus MOI of 0.01 ID50/cells without cytotoxity. Taken together, these results indicate the potential application of enzymatic hydrolysates of C. fragile and C. crispus in functional food and antiviral drug discovery.

  12. Differential Involvement during Latent Herpes Simplex Virus 1 Infection of the Superior and Inferior Divisions of the Vestibular Ganglia: Implications for Vestibular Neuritis

    Science.gov (United States)

    Lindemann, Anja; Sinicina, Inga; Horn, Anja K. E.; Brandt, Thomas; Strupp, Michael; Hüfner, Katharina

    2017-01-01

    ABSTRACT Controversy still surrounds both the etiology and pathophysiology of vestibular neuritis (VN). Especially uncertain is why the superior vestibular nerve (SVN) is more frequently affected than the inferior vestibular nerve (IVN), which is partially or totally spared. To address this question, we developed an improved method for preparing human vestibular ganglia (VG) and nerve. Subsequently, macro- and microanatomical as well as PCR studies were performed on 38 human ganglia from 38 individuals. The SVN was 2.4 mm longer than the IVN, and in 65% of the cases, the IVN ran in two separate bony canals, which was not the case for the SVN. Anastomoses between the facial and cochlear nerves were more common for the SVN (14/38 and 9/38, respectively) than for the IVN (7/38 and 2/38, respectively). Using reverse transcription-quantitative PCR (RT-qPCR), we found only a few latently herpes simplex virus 1 (HSV-1)-infected VG (18.4%). In cases of two separate neuronal fields, infected neurons were located in the superior part only. In summary, these PCR and micro- and macroanatomical studies provide possible explanations for the high frequency of SVN infection in vestibular neuritis. IMPORTANCE Vestibular neuritis is known to affect the superior part of the vestibular nerve more frequently than the inferior part. The reason for this clinical phenomenon remains unclear. Anatomical differences may play a role, or if latent HSV-1 infection is assumed, the etiology may be due to the different distribution of the infection. To shed further light on this subject, we conducted different macro- and microanatomical studies. We also assessed the presence of HSV-1 in VG and in different sections of the VG. Our findings add new information on the macro- and microanatomy of the VG as well as the pathophysiology of vestibular neuritis. We also show that latent HSV-1 infection of VG neurons is less frequent than previously reported. PMID:28446678

  13. Synthesis and preliminary evaluation of 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl) guanine ([{sup 18}F]FHBG) in HSV1-tk gene transduced hepatoma cell

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    Moon, Byung Seok; Lee, Tae Sup [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Myoung Keun [Yonsei University, Wonju (Korea, Republic of)] (and others)

    2006-08-15

    The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl) guanine ([{sup 18}F]FHBG) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with K[{sup 18}F]/K2.2.2. in acetonitrile using N2-monomethoxytrityl-9-[4-(tosly)-3-monomethoxytritylmethylbutl] guanine as a precursor, followed by deprotection with 1 N HCI. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of [{sup 18}F]FHBG were performed, and was analyzed correlation between [{sup 18}F]FHBG uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor beating Balb/c-nude mouse model. [{sup 18}F]FHBG was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiochemical yield was about 20-25% (corrected for decay), radiochemical purity was > 95% and specific activity was around > 55.5 GBq/ {mu} mol. Specific accumulation of [{sup 18}F]FHBG was observed in HSV1-tk gene transduced MCA-tk cells but not MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked [{sup 18}F]FHBG was retained inside of cells. The uptake of [{sup 18}F]FHBG was showed a highly significant linear correlation (R{sup 2} = 0.995) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. [{sup 18}F]FHBG appears

  14. Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes simplex virus elicit immune mediated antigliomal effect and antitumor memory

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    Mohammed G. Ghonime

    2018-02-01

    Full Text Available Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells. We sought to identify how C134 performed in an immunocompetent tumor model that restricts its replication advantage over first generation viruses. To achieve this we identified tumors that have intact IFN signaling responses that restrict C134 and first generation virus replication similarly. Our results show that both viruses elicit a T cell mediated anti-tumor effect and improved animal survival but that subtle difference exist between the viruses effect on median survival despite equivalent in vivo viral replication. To further investigate this we examined the anti-tumor activity in immunodeficient mice and in syngeneic models with re-challenge. These studies show that the T cell response is integral to C134 replication independent anti-tumor response and that OV therapy elicits a durable and circulating anti-tumor memory. The studies also show that repeated intratumoral administration can extend both OV anti-tumor effects and induce durable anti-tumor memory that is superior to tumor antigen exposure alone.

  15. HSV-1/HSV-2 Infection-Related Cancers in Bantu Populations Driving HIV-1 Prevalence in Africa: Tracking the Origin of AIDS at the Onset of the 20th Century

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    Jacqueline Le Goaster

    2016-11-01

    Full Text Available Introduction: At the onset of the 20th century, ancient clinical observations of cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They were reported from 1914 to 1960, but remained unexplained. In 1983, in San Francisco, Calif., USA, cancer epidemics were related to infections by the human immunodeficiency virus type 1 (HIV-1 known as AIDS disease. Yet since 1996, it is known that HIV-1 strains are not the only ones involved. In Sub-Saharan Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1 and genital recurrent herpes simplex virus type 2 (HSV-2 appeared many times prior to infection by HIV-1. Case Reports: Data on these ancient medical observations regarding African cancer epidemics can today be referred to as the relationship between the unfortunate immune deficiency of herpes in Bantu populations and HIV-1 viral strains. For centuries, the Bantu populations dispersed in forests were living in close proximity to chimpanzees infected by simian immunodeficiency virus (SIV and were exposed to SIV contamination which became HIV-1 in human beings. Presently, these unexplained Bantu cancer epidemics can be linked to the viral partnership of HSV-1/HSV-2 to HIV-1 strains. Conclusion: The key issue is now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment administered early during childhood to Bantu populations will offer a mean of preventing herpes diseases related to HIV-1 infection and hence avoid cancer epidemics.

  16. Vaccination of rhesus macaques with the live-attenuated HSV-1 vaccine VC2 stimulates the proliferation of mucosal T cells and germinal center responses resulting in sustained production of highly neutralizing antibodies.

    Science.gov (United States)

    Stanfield, Brent A; Pahar, Bapi; Chouljenko, Vladimir N; Veazey, Ronald; Kousoulas, Konstantin G

    2017-01-23

    We have shown that the live-attenuated HSV-1 VC2 vaccine strain with mutations in glycoprotein K (gK) and the membrane protein UL20 is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. To better understand the immune response generated by vaccination with VC2, we tested its ability to elicit immune responses in rhesus macaques. Vaccinated animals showed no signs of disease and developed increasing HSV-1 and HSV-2 reactive IgG 1 after two booster vaccinations, while IgG subtypes IgG 2 and IgG 3 remained at low to undetectable levels. All vaccinated animals produced high levels of cross protective neutralizing antibodies. Flow cytometry analysis of cells isolated from draining lymph nodes showed that VC2 vaccination stimulated significant increases in plasmablast (CD27 high CD38 high ) and mature memory (CD21 - IgM - ) B cells. T cell analysis on cells isolated from draining lymph node biopsies demonstrated a statistically significant increase in proliferating (Ki67 + ) follicular T helper cells and regulatory CXCR5 + CD8 + cytotoxic T cells. Analysis of plasma isolated two weeks post vaccination showed significant increases in circulating CXCL13 indicating increased germinal center activity. Cells isolated from vaginal biopsy samples collected over the course of the study exhibited vaccination-dependent increases in proliferating (Ki67 + ) CD4 + and CD8 + T cell populations. These results suggest that intramuscular vaccination with the live-attenuated HSV-1 VC2 vaccine strain can stimulate robust IgG 1 antibody responses that persist for >250days post vaccination. In addition, vaccination lead to the maturation of B cells into plasmablast and mature memory B cells, the expansion of follicular T helper cells, and affects in the mucosal immune responses. These data suggest that the HSV VC2 vaccine induces potent immune responses that could help

  17. Characterization of neuronal populations in the human trigeminal ganglion and their association with latent herpes simplex virus-1 infection.

    Directory of Open Access Journals (Sweden)

    Sarah E Flowerdew

    Full Text Available Following primary infection Herpes simplex virus-1 (HSV-1 establishes lifelong latency in the neurons of human sensory ganglia. Upon reactivation HSV-1 can cause neurological diseases such as facial palsy, vestibular neuritis or encephalitis. Certain populations of sensory neurons have been shown to be more susceptible to latent infection in the animal model, but this has not been addressed in human tissue. In the present study, trigeminal ganglion (TG neurons expressing six neuronal marker proteins were characterized, based on staining with antibodies against the GDNF family ligand receptor Ret, the high-affinity nerve growth factor receptor TrkA, neuronal nitric oxide synthase (nNOS, the antibody RT97 against 200 kDa neurofilament, calcitonin gene-related peptide and peripherin. The frequencies of marker-positive neurons and their average neuronal sizes were assessed, with TrkA-positive (61.82% neurons being the most abundant, and Ret-positive (26.93% the least prevalent. Neurons positive with the antibody RT97 (1253 µm(2 were the largest, and those stained against peripherin (884 µm(2 were the smallest. Dual immunofluorescence revealed at least a 4.5% overlap for every tested marker combination, with overlap for the combinations TrkA/Ret, TrkA/RT97 and Ret/nNOS lower, and the overlap between Ret/CGRP being higher than would be expected by chance. With respect to latent HSV-1 infection, latency associated transcripts (LAT were detected using in situ hybridization (ISH in neurons expressing each of the marker proteins. In contrast to the mouse model, co-localization with neuronal markers Ret or CGRP mirrored the magnitude of these neuron populations, whereas for the other four neuronal markers fewer marker-positive cells were also LAT-ISH+. Ret and CGRP are both known to label neurons related to pain signaling.

  18. Noninvasive theranostic imaging of HSV1-sr39TK-NTR/GCV-CB1954 dual-prodrug therapy in metastatic lung lesions of MDA-MB-231 triple negative breast cancer in mice.

    Science.gov (United States)

    Sekar, Thillai V; Foygel, Kira; Ilovich, Ohad; Paulmurugan, Ramasamy

    2014-01-01

    Metastatic breast cancer is an obdurate cancer type that is not amenable to chemotherapy regimens currently used in clinic. There is a desperate need for alternative therapies to treat this resistant cancer type. Gene-Directed Enzyme Prodrug Therapy (GDEPT) is a superior gene therapy method when compared to chemotherapy and radiotherapy procedures, proven to be effective against many types of cancer in pre-clinical evaluations and clinical trials. Gene therapy that utilizes a single enzyme/prodrug combination targeting a single cellular mechanism needs significant overexpression of delivered therapeutic gene in order to achieve therapy response. Hence, to overcome this obstacle we recently developed a dual therapeutic reporter gene fusion that uses two different prodrugs, targeting two distinct cellular mechanisms in order to achieve effective therapy with a limited expression of delivered transgenes. In addition, imaging therapeutic reporter genes offers additional information that indirectly correlates gene delivery, expression, and functional effectiveness as a theranostic approach. In the present study, we evaluate the therapeutic potential of HSV1-sr39TK-NTR fusion dual suicide gene therapy system that we recently developed, in MDA-MB-231 triple negative breast cancer lung-metastatic lesions in a mouse model. We compared the therapeutic potential of HSV1-sr39TK-NTR fusion with respective dual prodrugs GCV-CB1954 with HSV1-sr39TK/GCV and NTR/CB1954 single enzyme prodrug system in this highly resistant metastatic lesion of the lungs. In vitro optimization of dose and duration of exposure to GCV and CB1954 was performed in MDA-MB-231 cells. Drug combinations of 1 μg/ml GCV and 10 μM CB1954 for 3 days was found to be optimal regimen for induction of significant cell death, as assessed by FACS analysis. In vivo therapeutic evaluation in animal models showed a complete ablation of lung metastatic nodules of MDA-MB-231 triple negative breast cancer cells following

  19. Enhanced nigrostriatal neuron-specific, long-term expression by using neural-specific promoters in combination with targeted gene transfer by modified helper virus-free HSV-1 vector particles

    Directory of Open Access Journals (Sweden)

    Kong Lingxin

    2008-04-01

    Full Text Available Abstract Background Direct gene transfer into neurons has potential for developing gene therapy treatments for specific neurological conditions, and for elucidating neuronal physiology. Due to the complex cellular composition of specific brain areas, neuronal type-specific recombinant gene expression is required for many potential applications of neuronal gene transfer. One approach is to target gene transfer to a specific type of neuron. We developed modified Herpes Simplex Virus (HSV-1 particles that contain chimeric glycoprotein C (gC – glial cell line-derived neurotrophic factor (GDNF or brain-derived neurotrophic factor (BDNF proteins. HSV-1 vector particles containing either gC – GDNF or gC – BDNF target gene transfer to nigrostriatal neurons, which contain specific receptors for GDNF or BDNF. A second approach to achieve neuronal type-specific expression is to use a cell type-specific promoter, and we have used the tyrosine hydroxylase (TH promoter to restrict expression to catecholaminergic neurons or a modified neurofilament heavy gene promoter to restrict expression to neurons, and both of these promoters support long-term expression from HSV-1 vectors. To both improve nigrostriatal-neuron specific expression, and to establish that targeted gene transfer can be followed by long-term expression, we performed targeted gene transfer with vectors that support long-term, neuronal-specific expression. Results Helper virus-free HSV-1 vector packaging was performed using either gC – GDNF or gC – BDNF and vectors that contain either the TH promoter or the modified neurofilament heavy gene promoter. Vector stocks were injected into the midbrain proximal to the substantia nigra, and the rats were sacrificed at either 4 days or 1 month after gene transfer. Immunofluorescent costaining was performed to detect both recombinant gene products and nigrostriatal neurons. The combination of targeted gene transfer with neuronal

  20. Latent tree models

    OpenAIRE

    Zwiernik, Piotr

    2017-01-01

    Latent tree models are graphical models defined on trees, in which only a subset of variables is observed. They were first discussed by Judea Pearl as tree-decomposable distributions to generalise star-decomposable distributions such as the latent class model. Latent tree models, or their submodels, are widely used in: phylogenetic analysis, network tomography, computer vision, causal modeling, and data clustering. They also contain other well-known classes of models like hidden Markov models...

  1. Latent variable theory

    NARCIS (Netherlands)

    Borsboom, D.

    2008-01-01

    This paper formulates a metatheoretical framework for latent variable modeling. It does so by spelling out the difference between observed and latent variables. This difference is argued to be purely epistemic in nature: We treat a variable as observed when the inference from data structure to

  2. Latent myofascial trigger points.

    Science.gov (United States)

    Ge, Hong-You; Arendt-Nielsen, Lars

    2011-10-01

    A latent myofascial trigger point (MTP) is defined as a focus of hyperirritability in a muscle taut band that is clinically associated with local twitch response and tenderness and/or referred pain upon manual examination. Current evidence suggests that the temporal profile of the spontaneous electrical activity at an MTP is similar to focal muscle fiber contraction and/or muscle cramp potentials, which contribute significantly to the induction of local tenderness and pain and motor dysfunctions. This review highlights the potential mechanisms underlying the sensory-motor dysfunctions associated with latent MTPs and discusses the contribution of central sensitization associated with latent MTPs and the MTP network to the spatial propagation of pain and motor dysfunctions. Treating latent MTPs in patients with musculoskeletal pain may not only decrease pain sensitivity and improve motor functions, but also prevent latent MTPs from transforming into active MTPs, and hence, prevent the development of myofascial pain syndrome.

  3. STAT3 Regulates Proliferation and Survival of CD8+ T Cells: Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10+ Regulatory CD8+ T Cells in Autoimmune Uveitis

    Directory of Open Access Journals (Sweden)

    Cheng-Rong Yu

    2013-01-01

    Full Text Available STAT3 regulates CD4+ T cell survival and differentiation. However, its effects on CD8+ T cells are not well understood. Here, we show that in comparison to WT CD8+ T cells, STAT3-deficient CD8+ T cells exhibit a preactivated memory-like phenotype, produce more IL-2, proliferate faster, and are more sensitive to activation-induced cell death (AICD. The enhanced proliferation and sensitivity to AICD correlated with downregulation of class-O forkhead transcription factors (FoxO1, FoxO3A, , , Bcl-2, OX-40, and upregulation of FasL, Bax, and Bad. We examined whether STAT3-deficient CD8+ T cells can mount effective response during herpes simplex virus (HSV-1 infection and experimental autoimmune uveitis (EAU. Compared to WT mice, HSV-1-infected STAT3-deficient mice (STAT3KO produced less IFN- and virus-specific KLRG-1+ CD8+ T cells. STAT3KO mice are also resistant to EAU and produced less IL-17-producing Tc17 cells. Resistance of STAT3KO to EAU correlated with marked expansion of IL-10-producing regulatory CD8+ T cells (CD8-Treg implicated in recovery from autoimmune encephalomyelitis. Thus, increases of IL-6-induced STAT3 activation observed during inflammation may inhibit expansion of CD8-Tregs, thereby impeding recovery from uveitis. These results suggest that STAT3 is a potential therapeutic target for upregulating CD8+ T cell-mediated responses to viruses and suggest the successful therapeutic targeting of STAT3 as treatment for uveitis, derived, in part, from promoting CD8-Treg expansion.

  4. Latent classification models

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre

    2005-01-01

    parametric family ofdistributions.  In this paper we propose a new set of models forclassification in continuous domains, termed latent classificationmodels. The latent classification model can roughly be seen ascombining the \\NB model with a mixture of factor analyzers,thereby relaxing the assumptions...... classification model, and wedemonstrate empirically that the accuracy of the proposed model issignificantly higher than the accuracy of other probabilisticclassifiers....

  5. Latent olefin metathesis catalysts

    OpenAIRE

    Monsaert, Stijn; Lozano Vila, Ana; Drozdzak, Renata; Van Der Voort, Pascal; Verpoort, Francis

    2009-01-01

    Olefin metathesis is a versatile synthetic tool for the redistribution of alkylidene fragments at carbon-carbon double bonds. This field, and more specifically the development of task-specific, latent catalysts, attracts emerging industrial and academic interest. This tutorial review aims to provide the reader with a concise overview of early breakthroughs and recent key developments in the endeavor to develop latent olefin metathesis catalysts, and to illustrate their use by prominent exampl...

  6. Latent Structure Agreement Analysis

    Science.gov (United States)

    1989-11-01

    general approach of Lazarsfeld and Henry [2]. More recently, we have used an EM algorithm 130] related to that described by Goodman [3] and Dawid and...inverting the information matrix [2]. Identifiability Lazarsfeld and Henry [2], Goodman [3], and others discuss identifiability of latent class models...and Irwig [43]. The fixed panel agreement model corresponds closely to traditional latent class analysis applications as described by Lazarsfeld and

  7. Latent Virus Reactivation: From Space to Earth

    Science.gov (United States)

    Mehta, Satish K.; Cohrs, Randall J.; Gilden, Donald H.; Tyring, Stephen K.; Castro, Victoria A.; Ott, C. Mark; Pierson, Duane L.

    2010-01-01

    Reactivation of latent viruses is a recognized consequence of decreased immunity. More recently viral reactivation has been identified as an important in vivo indicator of clinically relevant immune changes. Viral reactivation can be determined quickly and easily by the presence of virus in saliva and other body fluids. Real-time polymerase chain reaction (PCR) is a highly sensitive and specific molecular method to detect the presence of specific viral DNA. Studies in astronauts demonstrated that herpes simplex virus type 1(HSV-1), Epstein-Barr Virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate at rates above normal during and after spaceflight in response to moderately decreased T-cell immunity. This technology was expanded to patients on Earth beginning with human immune deficiency virus (HIV) immuno-compromised patients. The HIV patients shed EBV in saliva at rates 9-fold higher than observed in astronauts demonstrating that the level of EBV shedding reflects the severity of impaired immunity. Whereas EBV reactivation is not expected to produce serious effects in astronauts on missions of 6 months or less, VZV reactivation in astronauts could produce shingles. Reactivation of live, infectious VZV in astronauts with no symptoms was demonstrated in astronauts during and after spaceflight. We applied our technology to study VZV-induced shingles in patients. In a study of 54 shingles patients, we showed salivary VZV was present in every patient on the day antiviral (acyclovir) treatment was initiated. Pain and skin lesions decreased with antiviral treatment. Corresponding decreases in levels of VZV were also observed and accompanied recovery. Although the level of VZV in shingles patients before the treatment was generally higher than those found in astronauts, lower range of VZV numbers in shingles patients overlapped with astronaut s levels. This suggests a potential risk of shingles to astronauts resulting from reactivation of VZV. In

  8. The Rabbit Stream Cipher

    DEFF Research Database (Denmark)

    Boesgaard, Martin; Vesterager, Mette; Zenner, Erik

    2008-01-01

    The stream cipher Rabbit was first presented at FSE 2003, and no attacks against it have been published until now. With a measured encryption/decryption speed of 3.7 clock cycles per byte on a Pentium III processor, Rabbit does also provide very high performance. This paper gives a concise...... description of the Rabbit design and some of the cryptanalytic results available....

  9. Incisor adjustment in rabbits.

    Science.gov (United States)

    Brown, Cyndi

    2009-06-01

    Rabbit incisor teeth are open-rooted and, in healthy animals, grow continuously. Incisor adjustments are often necessary to maintain the health and well-being of rabbits with incisor malocclusion. This column will describe some techniques used to manage incisor malocclusion in the rabbit.

  10. HSV-1 Encephalitis: High Index of Clinical Suspicion, Prompt Diagnosis, and Early Therapeutic Intervention Are the Triptych of Success—Report of Two Cases and Comprehensive Review of the Literature

    Directory of Open Access Journals (Sweden)

    Dimitrios Patoulias

    2017-01-01

    Full Text Available Herpes Simplex Virus (HSV encephalitis is an acute infectious disease of the Central Nervous System (CNS, usually affecting the limbic structures, the median temporal cortex, and the orbitofrontal regions. Its annual incidence has significantly increased over the last 20 years and the mortality rate is 7%, if early diagnosed and treated, and 70%, if left untreated, while it is associated with high rates of morbidity. It should be noted that even when Cerebrospinal fluid (CSF analysis seems normal, imaging studies are not specific and HSV Polymerase Chain Reaction (PCR test is negative; the clinician should be more aggressive, if clinical presentation is indicative for HSV encephalitis, by administrating acyclovir early after patient’s admission. The latter may be a vital intervention for the patient, modifying the patient’s clinical course. Through the presentation of two cases of HSV-1 encephalitis that we managed in our department over the last 1 year and after systematic and comprehensive research of the relevant literature, we aim at showing the crucial role of medical history and physical examination, along with the high index of clinical suspicion, in order to make promptly the diagnosis and administer timely intravenous acyclovir, limiting the possibility of complications during the disease’s course.

  11. Latent Semantic Analysis.

    Science.gov (United States)

    Dumais, Susan T.

    2004-01-01

    Presents a literature review that covers the following topics related to Latent Semantic Analysis (LSA): (1) LSA overview; (2) applications of LSA, including information retrieval (IR), information filtering, cross-language retrieval, and other IR-related LSA applications; (3) modeling human memory, including the relationship of LSA to other…

  12. Dynamic Latent Classification Model

    DEFF Research Database (Denmark)

    Zhong, Shengtong; Martínez, Ana M.; Nielsen, Thomas Dyhre

    as possible. Motivated by this problem setting, we propose a generative model for dynamic classification in continuous domains. At each time point the model can be seen as combining a naive Bayes model with a mixture of factor analyzers (FA). The latent variables of the FA are used to capture the dynamics...

  13. Models of latent tuberculosis: Their salient features, limitations, and development

    Directory of Open Access Journals (Sweden)

    Kamlesh Patel

    2011-01-01

    Full Text Available Latent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations.

  14. Models of Latent Tuberculosis: Their Salient Features, Limitations, and Development

    Science.gov (United States)

    Patel, Kamlesh; Jhamb, Sarbjit Singh; Singh, Prati Pal

    2011-01-01

    Latent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations. PMID:22219558

  15. Mycobacterial Infections in Rabbits: From the Wild to the Laboratory.

    Science.gov (United States)

    Arrazuria, R; Juste, R A; Elguezabal, N

    2017-08-01

    Tuberculous mycobacterial diseases such as leprosy and tuberculosis are ancient diseases that currently continue threatening human health in some countries. Non-tuberculous mycobacterial (NTM) infections cause a series of well-defined pathological entities, as well as some opportunistic diseases that have also increased worldwide, being more common among immunocompromised patients but rising also in immunocompetent individuals. Reports on natural infections by mycobacteria in rabbits are scarce and mainly involve NTM such as Mycobacterium avium subsp. avium in pigmy rabbits in the United States and Mycobacterium avium subsp. paratuberculosis in wild rabbits in Europe. Rabbits have been used as laboratory animals through the years, both to generate immunological reagents and as infection models. Mycobacterial infection models have been developed in this animal species showing different susceptibility patterns to mycobacteria in laboratory conditions. The latent tuberculosis model and the cavitary tuberculosis model have been widely used to elucidate pathogenic mechanisms and to evaluate chemotherapy and vaccination strategies. Rabbits have also been used as bovine paratuberculosis infection models. This review aimed to gather both wildlife and experimental infection data on mycobacteriosis in rabbits to assess their role in the spread of these infections as well as their potential use in the experimental study of mycobacterial pathogenesis and treatment. © 2016 Blackwell Verlag GmbH.

  16. Effect of a lytic bacteriophage on rabbits experimentally infected with pathogenic Escherichia coli

    OpenAIRE

    Zhao, J.; He, L; Pan, L.; Y. Liu; Yao, H; Bao, G.

    2017-01-01

    [EN] Pathogenic Escherichia coli (E. coli) is severely threatening the rabbit industry in China, and the concern over antibiotic-resistant bacteria has given rise to an urgent need for antibiotic alternatives. In this study, a member (ZRP1) of the Myoviridae family was isolated from rabbit faeces using a strain of rabbit atypical enteropathogenic E. coli (ZR1) as host. The one-step growth curve indicated that the latent period was around 25 to 30 min and the burst size was 144±31 plaque-formi...

  17. Utilization of tropical rabbits

    African Journals Online (AJOL)

    The productive performance of rabbits was evaluated on diets of alfalfa meal and tropical forages. The results showed that rabbits can utilize high forage diets wlth little or no cereal grain. Several tropical legumes (Desmodium distortum, Macrop tilium lathyroides, Clitoria ternata and Cassra tora) have the same feeding ...

  18. Pharmacokinetics of chloroquine in diabetic rabbits | Adelusi ...

    African Journals Online (AJOL)

    The pharmacokinetic parameters derived from diabetic rabbits have been compared to those of normal rabbits. Two sets of rabbits were used, normal rabbits and diabetic rabbits. The diabetic rabbits were obtained by inducing diabetes in rabbits using streptozotocin. Chloroquine at a dose of 10 mg/kg was administered to ...

  19. Learning multimodal latent attributes.

    Science.gov (United States)

    Fu, Yanwei; Hospedales, Timothy M; Xiang, Tao; Gong, Shaogang

    2014-02-01

    The rapid development of social media sharing has created a huge demand for automatic media classification and annotation techniques. Attribute learning has emerged as a promising paradigm for bridging the semantic gap and addressing data sparsity via transferring attribute knowledge in object recognition and relatively simple action classification. In this paper, we address the task of attribute learning for understanding multimedia data with sparse and incomplete labels. In particular, we focus on videos of social group activities, which are particularly challenging and topical examples of this task because of their multimodal content and complex and unstructured nature relative to the density of annotations. To solve this problem, we 1) introduce a concept of semilatent attribute space, expressing user-defined and latent attributes in a unified framework, and 2) propose a novel scalable probabilistic topic model for learning multimodal semilatent attributes, which dramatically reduces requirements for an exhaustive accurate attribute ontology and expensive annotation effort. We show that our framework is able to exploit latent attributes to outperform contemporary approaches for addressing a variety of realistic multimedia sparse data learning tasks including: multitask learning, learning with label noise, N-shot transfer learning, and importantly zero-shot learning.

  20. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands.

    Science.gov (United States)

    Burt, Sara A; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; van der Poel, Wim H M

    2016-09-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (0, 60, and 23 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates. Dutch rabbits are unlikely to be a zoonotic source.

  1. RabbitMQ essentials

    CERN Document Server

    Dossot, David

    2014-01-01

    This book is a quick and concise introduction to RabbitMQ. Follow the unique case study of Clever Coney Media as they progressively discover how to fully utilize RabbitMQ, containing clever examples and detailed explanations.Whether you are someone who develops enterprise messaging products professionally or a hobbyist who is already familiar with open source Message Queuing software and you are looking for a new challenge, then this is the book for you. Although you should be familiar with Java, Ruby, and Python to get the most out of the examples, RabbitMQ Essentials will give you the push y

  2. Prescription diets for rabbits.

    Science.gov (United States)

    Proença, Laila Maftoum; Mayer, Jörg

    2014-09-01

    Dietary management can be used with drug therapy for the successful treatment of many diseases. Therapeutic nutrition is well-recognized in dogs and cats and is beginning to increase among other pet species, including rabbits. The nutritional component of some rabbit diseases (eg, urolithiasis) is not completely understood, and the clinician should evaluate the use of prescription diets based on the scientific literature and individual needs. Long-term feeding trials are needed to further evaluate the efficacy of prescription diets in rabbits. Prescription diets are available for selected diseases in rabbits, including diets for immediate-term, short-term, and long-term management. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Nutrition of the domestic rabbit.

    Science.gov (United States)

    Cheeke, P R

    1976-08-01

    Recent studies on the nutritional needs of the rabbit were reviewed. Emphasis was placed on fiber utilization by rabbits, digestibility of forage protein, and unique aspects of mineral and vitamin requirements. In spite of the herbivorous nature of rabbits, their ability to digest fiber is low. Indigestible fiber may have a role in preventing enteritis. While lacking the ability to efficiently digest fiber, rabbits do make efficient use of forage protein, in contrast to most other monogastric animals. Differences in serum calcium homeostasis and calcium excretion as compared with other animals were discussed. The interrelationship between vitamin E and selenium appears different in the rabbit compared with other species. The limited information available on rabbit nutrition suggests that rabbits are unusual in their metabolism of several nutrients; because of their wide use in biological research, more extensive information on nutritional and metabolic characteristics of rabbits is needed.

  4. Seroprevalence of Toxoplasma gondii and Encephalitozoon cuniculi in rabbits from different farming systems.

    Science.gov (United States)

    Neumayerová, Helena; Juránková, Jana; Jeklová, Edita; Kudláčková, Hana; Faldyna, Martin; Kovařčík, Kamil; Jánová, Eva; Koudela, Břetislav

    2014-08-29

    The breeding of domestic rabbit (Oryctolagus cuniculus) for human consumption has a long tradition mainly in European and Asian countries. Infections that can affect the production of meat or even be transmitted from animals to humans are important to monitor, especially for public health reasons as well as for their impact on animals health. This study aimed to collect sera from rabbits bred in different conditions and test the presence of Toxoplasma gondii and Encephalitozoon cuniculi antibodies. Whether infections were active or latent was assessed by determining the occurrence of IgM or IgM together with IgG antibodies which indicated active infection whereas latent infection was characterized by finding IgG antibodies only. An ELISA test was performed with 1883 sera samples collected throughout the Czech and Slovak Republics. The seroprevalence of T. gondii in 902 samples from 6 commercial farms (CF) was very low with only 4 rabbits (0.4%) being positive. In total 99 (10.1%) individuals out of 981 samples from 29 household farms (HF) were positive for T. gondii antibodies. Only 2 (50%) of the T. gondii positive CF rabbits had active infections while the rest were latently infected. The serological results showed that 35 (35.4%) rabbits from the T. gondii positive HF group suffered from active infection. Out of CF samples 185 (20.5%) were positive for E. cuniculi. Antibodies of E. cuniculi were detected in 497 (50.7%) HF rabbits. Active E. cuniculi infections were determined in 85.9% of CF and 56.3% of HF rabbits; respectively. Interestingly, the E. cuniculi positive rabbits were significantly more often positive for anti-T. gondii antibodies in comparison to E. cuniculi negative individuals. Prevalence of T. gondii in CF rabbits was negligible. According to our results meat of HF rabbits still poses a risk of T. gondii infection. Nevertheless, the risk is on its lowest level in 20 years which is apparently caused due to changes in feeding practices. The

  5. Understanding Latent Heat of Vaporization.

    Science.gov (United States)

    Linz, Ed

    1995-01-01

    Presents a simple exercise for students to do in the kitchen at home to determine the latent heat of vaporization of water using typical household materials. Designed to stress understanding by sacrificing precision for simplicity. (JRH)

  6. Latent failures on biodiesel plants

    OpenAIRE

    Selva S. Rivera; Jorge E. Nunez Mc Leod; Daniela R. Calvo

    2016-01-01

    The process to obtain biodiesel is simple, however it is a chemical process in which toxic and flammable substances are used or variables like temperature or pressure should be controlled to avoid any kind of incident. Literature report accidents where most human errors are related to the confidence of operators by this simplicity. Much of these accidents are influenced by a number of factors involved constituting latent failures. This paper presents a summary of latent failures identified on...

  7. The Infinite Latent Events Model

    CERN Document Server

    Wingate, David; Roy, Daniel; Tenenbaum, Joshua

    2012-01-01

    We present the Infinite Latent Events Model, a nonparametric hierarchical Bayesian distribution over infinite dimensional Dynamic Bayesian Networks with binary state representations and noisy-OR-like transitions. The distribution can be used to learn structure in discrete timeseries data by simultaneously inferring a set of latent events, which events fired at each timestep, and how those events are causally linked. We illustrate the model on a sound factorization task, a network topology identification task, and a video game task.

  8. La sifilis latente vesical

    Directory of Open Access Journals (Sweden)

    Pablo Gómez Martínez

    1948-01-01

    Full Text Available Con este título me propongo presentar los conocimientos y experiencias sacados de la investigación cistoscópica llevada a cabo sobre un total de 400 enfermos examinados en el Departamento de Endoscopia del Hospital de la Samaritana, durante el año de 1946. El autor, describió y publicó por primera vez en Colombia en el año de 1944, 2 casos de sífilis vesical que se presentaron sobre un total de 3.323 pacientes sifilíticos examinados durante los años de 1939, 1940 Y parte de 1941, o sea una incidencia del 1/2 por mil. El porcentaje encontrado sobre enfermos que se quejaban de su aparato urinario fue de 0,30 (1. Entre la numerosa literatura consultada, figuran dos artículos de autores brasileros que nos llamaron mucho la atención, por la frecuencia con que ellos encontraron lesiones vesicales atribuibles a la sífilis y que denominaron "Sífilis latente de la Vejiga". Como sus idea no estaban de acuerdo con los hechos observados por nosotros, ni con la experiencia adquirida en varios años de continuos exámenes cistoscópicos, nos dimos al trabajo de investigar de una manera minuciosa, serena e imparcial, la presencia o ausencia de las lesiones vesicales descritas, lo mismo que la morfología que pudieran tener en nuestro medio.

  9. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

    OpenAIRE

    Burt, Sara A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; Poel, van der, J.J.

    2016-01-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60?% respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates. Dutch rabbits are unlikely to be a zoonotic source. Electronic supplementary material The online version of this article (doi:10.1007/s12560-016-9239-3) contains supplementary material, which is avail...

  10. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

    NARCIS (Netherlands)

    Burt, S.A.|info:eu-repo/dai/nl/140114432; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; van der Poel, Wim H.M.

    2016-01-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

  11. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

    NARCIS (Netherlands)

    Burt, Sara A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; Poel, van der Wim H.M.

    2016-01-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

  12. Rabbit Repellent Paint

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Five gallons of rabbit repellent paint were sent to George Wilson to be applied on the trees of the Tewaukon tree plot. Mr. Wilson requires a 3 or 4 in. brush for...

  13. Latent geometry of bipartite networks

    Science.gov (United States)

    Kitsak, Maksim; Papadopoulos, Fragkiskos; Krioukov, Dmitri

    2017-03-01

    Despite the abundance of bipartite networked systems, their organizing principles are less studied compared to unipartite networks. Bipartite networks are often analyzed after projecting them onto one of the two sets of nodes. As a result of the projection, nodes of the same set are linked together if they have at least one neighbor in common in the bipartite network. Even though these projections allow one to study bipartite networks using tools developed for unipartite networks, one-mode projections lead to significant loss of information and artificial inflation of the projected network with fully connected subgraphs. Here we pursue a different approach for analyzing bipartite systems that is based on the observation that such systems have a latent metric structure: network nodes are points in a latent metric space, while connections are more likely to form between nodes separated by shorter distances. This approach has been developed for unipartite networks, and relatively little is known about its applicability to bipartite systems. Here, we fully analyze a simple latent-geometric model of bipartite networks and show that this model explains the peculiar structural properties of many real bipartite systems, including the distributions of common neighbors and bipartite clustering. We also analyze the geometric information loss in one-mode projections in this model and propose an efficient method to infer the latent pairwise distances between nodes. Uncovering the latent geometry underlying real bipartite networks can find applications in diverse domains, ranging from constructing efficient recommender systems to understanding cell metabolism.

  14. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  15. Laparoscopic ovariectomy in rabbits

    Directory of Open Access Journals (Sweden)

    M. S. Al-Badrany

    2009-01-01

    Full Text Available A comparative evaluation of three different techniques of laparoscopic ovariectomy was carried out in 33 healthy female in rabbits, which included resection and removal of ovary after clip application, electrocautery of the ovary, then resection, and pulling ovary outside abdomen, ligation by silk, then ovary was removed. The ovaries and associated structures were better visualized by laparoscopy and all three techniques were carried out perfectly. All rabbits after operation were healthy and they were monitored for one month after operation. However, 3 of them died after operation, two of them died due to bleeding and the other of them died due to unknown causes. General anesthesia by using ketamine-xylazine i.m., was suitable for this technique, and the anesthesia provided good analgesia and good muscle relaxation. CO2 was used to establish pneumoperitoneum. In conclusion, resection and removal of the ovaries after clip application technique was found superior to the other two techniques.

  16. Rabbit renotropic system

    Energy Technology Data Exchange (ETDEWEB)

    Areas, J.; Yun, G.C.; Rahmat, J.; Gersten, D.; Goel, R.; Preuss, H.G.

    1988-04-01

    Elevated levels of a specific renal growth factor, renotropin, have been associated with spontaneous hypertension. To examine this association more closely, we have undertaken the development of a better assay system to characterize and purify renotropin. Sera from rabbits prior to operation (control) and at a specified time after unilateral nephrectomy (uni) were examined for renotropic activity. Comparing the effects of uni to control sera in the same rabbit, significant stimulation of 3H-thymidine incorporation into the DNA of primary rabbit kidney cultures incubated in D-valine medium to eliminate fibroblast growth was noted: at 3 days postoperatively 73% (n = 13), at 7 days 103% (n = 39), at 10 days 130% (n = 31), at 21 days 101% (n = 24), at 42 days 89% (n = 13). All values were at least P less than 0.01. The stimulatory properties were dose-dependent but reached a plateau at high serum concentrations. Comparing CPM/mg protein in uni/control in different concentrations of sera 7 days postoperatively, uni versus control were 67/44 at 5% v/v, 139/72 at 10% v/v, 261/161 at 20% v/v, and 243/136 at 40% v/v. The renotropic effect of uni sera remained after dialysis in incubation medium and after sera were heated in boiling water for 5 minutes. Renal extracts obtained from growing kidneys 7 days postnephrectomy augmented renotropic activity. Atrial natriuretic factor, ouabain, PGF2 alpha, PGE1, and cAMP did not possess renotropic activity. We conclude that the primary rabbit kidney culture assay for renotropin is highly sensitive and will be an important tool to comprehend the role of renotropin in the pathogenesis of hypertension.

  17. Proper elimination of latent variables

    NARCIS (Netherlands)

    Polderman, Jan W.

    1997-01-01

    We consider behaviors in which we distinguish two types of variables, manifest variables, the variables that are of interest to the user and latent variables, the variables that are introduced to obtain a first representation. The problem is to find a representation of the manifest behavior, that

  18. Indexing by Latent Semantic Analysis.

    Science.gov (United States)

    Deerwester, Scott; And Others

    1990-01-01

    Describes a new method for automatic indexing and retrieval called latent semantic indexing (LSI). Problems with matching query words with document words in term-based information retrieval systems are discussed, semantic structure is examined, singular value decomposition (SVD) is explained, and the mathematics underlying the SVD model is…

  19. A Latent Class Model for Rating Data.

    Science.gov (United States)

    Rost, Jurgen

    1985-01-01

    A latent class model for rating data is presented which provides an alternative to the latent trait approach of analyzing test data. It is the analog of Andrich's binomial Rasch model for Lazarsfeld's latent class analysis (LCA). Response probabilities for rating categories follow a binomial distribution and depend on class-specific item…

  20. A Multicomponent Latent Trait Model for Diagnosis

    Science.gov (United States)

    Embretson, Susan E.; Yang, Xiangdong

    2013-01-01

    This paper presents a noncompensatory latent trait model, the multicomponent latent trait model for diagnosis (MLTM-D), for cognitive diagnosis. In MLTM-D, a hierarchical relationship between components and attributes is specified to be applicable to permit diagnosis at two levels. MLTM-D is a generalization of the multicomponent latent trait…

  1. Ultrastructure of Reissner's membrane in the rabbit

    DEFF Research Database (Denmark)

    Qvortrup, K.; Rostgaard, Jørgen; Bretlau, P.

    1994-01-01

    Anatomy, Reissner's membrane, electron microscopy, tubulocisternal endoplasmic reticulum, subsurface cisterns, rabbit......Anatomy, Reissner's membrane, electron microscopy, tubulocisternal endoplasmic reticulum, subsurface cisterns, rabbit...

  2. Associations with rabbits and rabbit meat of three different ethnic ...

    African Journals Online (AJOL)

    Associations with rabbits and rabbit meat of three different ethnic groups in Stellenbosch, South Africa. LC Hoffman, C Vosloo, P Nkhabutlane, DW Schutte. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  3. Maintaining the Body's Immune System: Incidence of Latent Virus Shedding During Space Flight

    Science.gov (United States)

    Pierson, Duane; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

    2002-01-01

    Your body protects you from illness with its own security system - the immune system. This system keeps illness at bay not only by mounting a defense against foreign organisms, but also by controlling the population of bacteria and viruses that normally live in your body. But there's no need to panic: certain microbes can actually exist in your body without causing illness. Some bacteria are even beneficial - like the E. coli in the large intestine that are an important source of vitamin K. While viruses are not exactly considered beneficial, they can also inhabit the human body without causing immediate harm or infection. A good example is the herpes simplex virus type 1 (HSV1), more commonly known as cold sores or fever blisters. This virus infects 70 to 80 percent of all adults but remains latent much of the time. While latent, the virus within cells remains dormant. Activation of the dormant virus causes it to make copies of itself (known as replication) constantly detectable in body fluids such as urine or saliva in a process called shedding. When a person becomes sick or stressed, however, this weakened condition allows the virus to reactivate and multiply. These elevated levels may be enough to produce symptoms, but shedding can also occur without symptoms. This ability to shed without showing signs of infection, or asymptomatic shedding, is of great interest, as it increases the chances of infecting others. The stresses associated with space flight - adapting to microgravity, isolation from family and friends, living and working in a confined space, sleep deprivation, and busy schedules, to name but a few - may weaken astronauts' immune systems, leaving them at greater risk of viral reactivation. Members of the STS-107 crew will participate in this experiment, Incidence of Latent Viral Shedding in Space Flight, to help scientists understand how reactivation works in space, and at what level replication reaches before symptoms begin to show. This study also

  4. Analysis of latent structures in linear systems

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar

    2004-01-01

    In chemometrics the emphasis is on latent structure models. The latent structure is the part of the data that the modeling task is based upon. This paper is addressing some fundamental issues, when latent structures are used. The paper consists of three parts. The first part is concerned defining...... that are useful, when studying latent structures. It is shown how loading weight vectors are generated and how they can be interpreted in analyzing the latent structure. It is shown how the covariance can be used to get useful ‘apriori’ information on the modeling task. Also some simple methods are presented...

  5. Welfare assessment in pet rabbits

    NARCIS (Netherlands)

    Schepers, F.; Koene, P.; Beerda, B.

    2009-01-01

    One million pet rabbits are kept in The Netherlands, but there are no data available on their behaviour and welfare. This study seeks to assess the welfare of pet rabbits in Dutch households and is a first step in the development of a welfare assessment system. In an internet survey, housing

  6. Latent geometry of bipartite networks

    CERN Document Server

    Kitsak, Maksim; Krioukov, Dmitri

    2016-01-01

    Despite the abundance of bipartite networked systems, their organizing principles are less studied, compared to unipartite networks. Bipartite networks are often analyzed after projecting them onto one of the two sets of nodes. As a result of the projection, nodes of the same set are linked together if they have at least one neighbor in common in the bipartite network. Even though these projections allow one to study bipartite networks using tools developed for unipartite networks, one-mode projections lead to significant loss of information and artificial inflation of the projected network with fully connected subgraphs. Here we pursue a different approach for analyzing bipartite systems that is based on the observation that such systems have a latent metric structure: network nodes are points in a latent metric space, while connections are more likely to form between nodes separated by shorter distances. This approach has been developed for unipartite networks, and relatively little is known about its appli...

  7. The White Rabbit project

    CERN Document Server

    Serrano, J; Gousiou, E; van der Bij, E; Wlostowski, T; Daniluk, G; Lipinski, M

    2013-01-01

    White Rabbit (WR) is a multi-laboratory, multi- company collaboration for the development of a new Ethernet-based technology which ensures sub-nanosecond synchronisation and deterministic data transfer. The project uses an open source paradigm for the development of its hardware, gateware and software components. This article provides an introduction to the technical choices and an explanation of the basic principles underlying WR. It then describes some possible applications and the current status of the project. Finally, it provides insight on current developments and future plans.

  8. INFECTIOUS MYXOMATOSIS OF RABBITS

    Science.gov (United States)

    Smadel, Joseph E.; Ward, S. M.; Rivers, Thomas M.

    1940-01-01

    A second soluble antigen, separable from the virus, occurs in extracts of infected skin and in the serum of rabbits acutely ill with infectious myxomatosis. Like the first antigen (A), the second (B) is heat labile and has certain characteristics of a globulin. The two antigens precipitate in different concentrations of ammonium sulfate and can be separated by this method. Neither of the antigens after being heated at 56°C. precipitates in the presence of specific antibody but each is capable of inhibiting the activity of its antibody. PMID:19871012

  9. Latent heat of vehicular motion

    Science.gov (United States)

    Ahmadi, Farzad; Berrier, Austin; Habibi, Mohammad; Boreyko, Jonathan

    2016-11-01

    We have used the thermodynamic concept of latent heat, where a system loses energy due to a solid-to-liquid phase transition, to study the flow of a group of vehicles moving from rest. During traffic flow, drivers keep a large distance from the car in front of them to ensure safe driving. When a group of cars comes to a stop, for example at a red light, drivers voluntarily induce a "phase transition" from this "liquid phase" to a close-packed "solid phase." This phase transition is motivated by the intuition that maximizing displacement before stopping will minimize the overall travel time. To test the effects of latent heat on flow efficiency, a drone captured the dynamics of cars flowing through an intersection on a Smart Road where the initial spacing between cars at the red light was systematically varied. By correlating the experimental results with the Optimal Velocity Model (OVM), we find that the convention of inducing phase transitions at intersections offers no benefit, as the lag time (latent heat) of resumed flow offsets the initial increase in displacement. These findings suggest that in situations where gridlock is not an issue, drivers should not decrease their spacing during stoppages in order to maximize safety with no loss in flow efficiency.

  10. Spontaneous Latency in a Rabbit Model of Pulmonary Tuberculosis

    Science.gov (United States)

    Subbian, Selvakumar; Tsenova, Liana; O'Brien, Paul; Yang, Guibin; Kushner, Nicole L.; Parsons, Sven; Peixoto, Blas; Fallows, Dorothy; Kaplan, Gilla

    2013-01-01

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is an exquisitely adapted human pathogen capable of surviving for decades in the lungs of immune-competent individuals in the absence of disease. The World Health Organization estimates that 2 billion people have latent TB infection (LTBI), defined by a positive immunological response to Mtb antigens, with no clinical signs of disease. A better understanding of host and pathogen determinants of LTBI and subsequent reactivation would benefit TB control efforts. Animal models of LTBI have been hampered generally by an inability to achieve complete bacillary clearance. Herein, we have characterized a rabbit model of LTBI in which, similar to most humans, complete clearance of pulmonary Mtb infection and pathological characteristics occurs spontaneously. The evidence that Mtb-CDC1551–infected rabbits achieve LTBI, rather than sterilization, is based on the ability of the bacilli to be reactivated after immune suppression. These rabbits showed early activation of T cells and macrophages and an early peak in the TNFα level, which decreased in association with clearance of bacilli from the lungs. In the absence of sustained tumor necrosis factor-α production, no necrosis was seen in the evolving lung granulomas. In addition, bacillary control was associated with down-regulation of several metalloprotease genes and an absence of lung fibrosis. This model will be used to characterize molecular markers of protective immunity and reactivation. PMID:22960076

  11. Acupuncture analgesia in rabbits.

    Science.gov (United States)

    Galeano, C; Leung, C Y; Robitaille, R; Roy-Chabot, T

    1979-02-01

    The aim of this study was to verify the validity and reliability of analgesia elicited by acupuncture stimulation in rabbits. Ninety-five experiments were performed using 21 adult animals. The reaction time of the avoidance response elicited by noxious heat stimulation on the snout, and the presence or absence of the start response elicited by pin-prick and clamping of the skin were studied. Bilateral electric acupuncture stimulation in the area of Tsu-san-li and Shang-chu-hsu points in the hind legs was used. The animals were either held in a soft bag, loosely attached by cords, or suspended in a hammock; the eyes were either free of blindfolded. On the basis of operational behavioral measurements, it was found that acupuncture stimulation did not produce analgesia in undisturbed, placid animals. However, during agitated or fighting periods and the immobility reflex-like state, sometimes associated with acupuncture maneuvers, long reaction times were observed. Pin-pricking and clamping stimulation of the skin were not reliable methods of noxious stimulation in the rabbit.

  12. Subunit Vaccines Consisting of Antigens from Dormant and Replicating Bacteria Show Promising Therapeutic Effect against Mycobacterium Bovis BCG Latent Infection.

    Science.gov (United States)

    Li, F; Kang, H; Li, J; Zhang, D; Zhang, Y; Dannenberg, A M; Liu, X; Niu, H; Ma, L; Tang, R; Han, X; Gan, C; Ma, X; Tan, J; Zhu, B

    2017-06-01

    To screen effective antigens as therapeutic subunit vaccines against Mycobacterium latent infection, we did bioinformatics analysis and literature review to identify effective antigens and evaluated the immunogenicity of five antigens highly expressed in dormant bacteria, which included Rv2031c (HspX), Rv2626c (Hrp1), Rv2007c (FdxA), Rv1738 and Rv3130c. Then, several fusion proteins such as Rv2007c-Rv2626c (F6), Rv2031c-Rv1738-Rv1733c (H83), ESAT6-Rv1738-Rv2626c (LT40), ESAT6-Ag85B-MPT64 -Mtb8.4 (EAMM), and EAMM-Rv2626c (LT70) were constructed and their therapeutic effects were evaluated in pulmonary Mycobacterium bovis Bacilli Calmette-Guérin (BCG) - latently infected rabbit or mouse models. The results showed that EAMM and F6 plus H83 had therapeutic effect against BCG latent infection in the rabbit model, respectively, and that the combination of EAMM with F6 plus H83 significantly reduced the bacterial load. In addition, the fusion proteins LT40 and LT70 consisting of multistage antigens showed promising therapeutic effects in the mouse model. We conclude that subunit vaccines consisting of both latency and replicating-associated antigens show promising therapeutic effects in BCG latent infection animal models. © 2017 The Foundation for the Scandinavian Journal of Immunology.

  13. Oculoscopy in Rabbits and Rodents.

    Science.gov (United States)

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Ultraviolet luminescence from latent fingerprints.

    Science.gov (United States)

    Bramble, S K; Creer, K E; Qiang, W G; Sheard, B

    1993-04-01

    Illumination of latent fingerprints on white paper using 266-nm radiation from a Nd:YAG laser and photographic detection of their ultraviolet fluorescence, produces images with good ridge detail. The detection rate was 69% in a survey of fingerprints from 34 people compared with only 23% using an argon-ion laser at 514 nm. Prolonged exposure to UV light decreased the inherent UV fluorescence intensity but no adverse effects were observed on subsequent treatment with 1,8-diazafluoren-9-one or ninhydrin.

  15. Learning Latent Factor Models of Human Travel

    OpenAIRE

    Guerzhoy, Michael; Hertzmann, Aaron

    2012-01-01

    NIPS Workshop on Social Network and Social Media Analysis; International audience; This paper describes probability models for human travel, using latent factors learned from data. The latent factors represent interpretable properties: travel distance cost, desirability of destinations, and affinity between locations. Individuals are clustered into distinct styles of travel. The latent factors combine in a multiplicative manner, and are learned using Maximum Likelihood. The resulting models e...

  16. Tensor Decompositions for Learning Latent Variable Models

    Science.gov (United States)

    2012-12-08

    for several popular latent variable models Tensor Decompositions for Learning Latent Variable Models Anima Anandkumar1, Rong Ge2, Daniel Hsu3, Sham M...the ARO Award W911NF-12-1-0404. References [AFH+12] A. Anandkumar, D. P. Foster, D. Hsu, S. M. Kakade, and Y.-K. Liu . A spectral algorithm for latent...volume 13. Cambridge University Press, 2005. [PSX11] A. Parikh, L. Song , and E. P. Xing. A spectral algorithm for latent tree graphical models. In

  17. Optimization-Based Model Fitting for Latent Class and Latent Profile Analyses

    Science.gov (United States)

    Huang, Guan-Hua; Wang, Su-Mei; Hsu, Chung-Chu

    2011-01-01

    Statisticians typically estimate the parameters of latent class and latent profile models using the Expectation-Maximization algorithm. This paper proposes an alternative two-stage approach to model fitting. The first stage uses the modified k-means and hierarchical clustering algorithms to identify the latent classes that best satisfy the…

  18. Learning Latent Vector Spaces for Product Search

    NARCIS (Netherlands)

    Van Gysel, C.; de Rijke, M.; Kanoulas, E.

    2016-01-01

    We introduce a novel latent vector space model that jointly learns the latent representations of words, e-commerce products and a mapping between the two without the need for explicit annotations. The power of the model lies in its ability to directly model the discriminative relation between

  19. A Multinomial Probit Model with Latent Factors

    DEFF Research Database (Denmark)

    Piatek, Rémi; Gensowski, Miriam

    2017-01-01

    We develop a parametrization of the multinomial probit model that yields greater insight into the underlying decision-making process, by decomposing the error terms of the utilities into latent factors and noise. The latent factors are identified without a measurement system, and they can...

  20. Learning latent structure for activity recognition

    NARCIS (Netherlands)

    Hu, N.; Englebienne, G.; Lou, Z.; Kröse, B.

    2014-01-01

    We present a novel latent discriminative model for human activity recognition. Unlike the approaches that require conditional independence assumptions, our model is very flexible in encoding the full connectivity among observations, latent states, and activity states. The model is able to capture

  1. A Multinomial Probit Model with Latent Factors

    DEFF Research Database (Denmark)

    Piatek, Rémi; Gensowski, Miriam

    2017-01-01

    We develop a parametrization of the multinomial probit model that yields greater insight into the underlying decision-making process, by decomposing the error terms of the utilities into latent factors and noise. The latent factors are identified without a measurement system, and they can be mean...

  2. Prior Learning Assessment with Latent Semantic Analysis

    NARCIS (Netherlands)

    Kalz, Marco; Van Bruggen, Jan; Giesbers, Bas; Koper, Rob

    2007-01-01

    Kalz, M., Van Bruggen, J., Giesbers, B., & Koper, R. (2007). Prior Learning Assessment with Latent Semantic Analysis. In F. Wild, M. Kalz, J. Van Bruggen & R. Koper (Eds.). Proceedings of the First European Workshop on Latent Semantic Analysis in Technology Enhanced Learning (pp. 24-25). Heerlen,

  3. Prior Learning Assessment with Latent Semantic Analysis

    OpenAIRE

    Kalz, Marco; van Bruggen, Jan; Giesbers, Bas; Koper, Rob

    2007-01-01

    Kalz, M., Van Bruggen, J., Giesbers, B., & Koper, R. (2007). Prior Learning Assessment with Latent Semantic Analysis. In F. Wild, M. Kalz, J. Van Bruggen & R. Koper (Eds.). Proceedings of the First European Workshop on Latent Semantic Analysis in Technology Enhanced Learning (pp. 24-25). Heerlen, The Netherlands: Open University of the Netherlands.

  4. Introduction to Latent Class Analysis with Applications

    Science.gov (United States)

    Porcu, Mariano; Giambona, Francesca

    2017-01-01

    Latent class analysis (LCA) is a statistical method used to group individuals (cases, units) into classes (categories) of an unobserved (latent) variable on the basis of the responses made on a set of nominal, ordinal, or continuous observed variables. In this article, we introduce LCA in order to demonstrate its usefulness to early adolescence…

  5. Stability of latent class segments over time

    DEFF Research Database (Denmark)

    Mueller, Simone

    2011-01-01

    logit model suggests significant changes in the price sensitivity and the utility from environmental claims between both experimental waves. A pooled scale adjusted latent class model is estimated jointly over both waves and the relative size of latent classes is compared across waves, resulting...

  6. Exact tests for some latent traits

    NARCIS (Netherlands)

    de Gooijer, J.G.; Yuan, A.

    2008-01-01

    Item response theory is one of the modern test theory with many applications in the educational and psychological testing field. Recent developments made it possible to characterize some desired latent properties in terms of a collection of manifest ones, so that hypothesis tests on these latent

  7. Latent Class and Latent Transition Analysis With Applications in the Social, Behavioral, and Health Sciences

    CERN Document Server

    Collins, Linda M

    2010-01-01

    One of the few books on latent class analysis (LCA) and latent transition analysis (LTA) with a comprehensive treatment of longitudinal latent class models, Latent Class and Latent Transition Analysis reflects improvements in statistical computing as the most up-to-date reference for theoretical, technical, and practical issues in cross-sectional and longitudinal data. Plentiful examples enable the reader to acquire a thorough conceptual and technical understanding and to apply techniques to address empirical research questions. Researchers seeking an advanced introduction to LCA and LTA and g

  8. Latent semantics as cognitive components

    DEFF Research Database (Denmark)

    Petersen, Michael Kai; Mørup, Morten; Hansen, Lars Kai

    2010-01-01

    emotional responses can be encoded in words, we propose a simplified cognitive approach to model how we perceive media. Representing song lyrics in a vector space of reduced dimensionality using LSA, we combine bottom-up defined term distances with affective adjectives, that top-down constrain the latent......Cognitive component analysis, defined as an unsupervised learning of features resembling human comprehension, suggests that the sensory structures we perceive might often be modeled by reducing dimensionality and treating objects in space and time as linear mixtures incorporating sparsity...... semantics according to the psychological dimensions of valence and arousal. Subsequently we apply a Tucker tensor decomposition combined with re-weighted L1 regularization and a Bayesian ARD automatic relevance determination approach to derive a sparse representation of complementary affective mixtures...

  9. Epstein–Barr virus latent genes

    Science.gov (United States)

    Kang, Myung-Soo; Kieff, Elliott

    2015-01-01

    Latent Epstein–Barr virus (EBV) infection has a substantial role in causing many human disorders. The persistence of these viral genomes in all malignant cells, yet with the expression of limited latent genes, is consistent with the notion that EBV latent genes are important for malignant cell growth. While the EBV-encoded nuclear antigen-1 (EBNA-1) and latent membrane protein-2A (LMP-2A) are critical, the EBNA-leader proteins, EBNA-2, EBNA-3A, EBNA-3C and LMP-1, are individually essential for in vitro transformation of primary B cells to lymphoblastoid cell lines. EBV-encoded RNAs and EBNA-3Bs are dispensable. In this review, the roles of EBV latent genes are summarized. PMID:25613728

  10. The White Rabbit Project

    CERN Document Server

    Serrano, J; Cattin, M; Garcia Cota, E; Lewis, J; Moreira, P; Wlostowski, T; Gaderer, G; Loschmidt, P; Dedic, J; Bär, R; Fleck, T; Kreider, M; Prados, C; Rauch, S

    2009-01-01

    Reliable, fast and deterministic transmission of control information in a network is a need formany distributed systems. One example is timing systems, where a reference frequency is used to accurately schedule time-critical messages. TheWhite Rabbit (WR) project is a multi-laboratory and multi-company effort to bring together the best of the data transfer and timing worlds in a completely open design. It takes advantage of the latest developments for improving timing over Ethernet, such as IEEE 1588 (Precision Time Protocol) and Synchronous Ethernet. The presented approach aims for a general purpose, fieldbus-like transmission system, which provides deterministic data and timing (sub-ns accuracy and ps jitter) to around 1000 stations. It automatically compensates for fiber lengths in the order of 10 km. This paper describes the WR design goals and the specification used for the project. It goes on to describe the central component of the WR system structure - the WR switch - with theoretical considerations a...

  11. Production of Polyclonal Antibodies in Rabbits

    Science.gov (United States)

    1995-10-01

    Increased hemosiderin pigment within splenic macrophages was seen in four of the rabbits. The reports by the histopathologist are included in Appendix A...hypoplasia in the spleens of all five rabbits and varying levels of increased U I I Page 21 hemosiderin pigment within splenic macrophages in four of the...99 and 443. Increased hemosiderin pigment within splenic macrophages was noted in 5/6 rabbits and was especially prominent in rabbit #99. I

  12. Learning Harmonium models with infinite latent features.

    Science.gov (United States)

    Chen, Ning; Zhu, Jun; Sun, Fuchun; Zhang, Bo

    2014-03-01

    Undirected latent variable models represent an important class of graphical models that have been successfully developed to deal with various tasks. One common challenge in learning such models is to determine the number of hidden units that are unknown a priori. Although Bayesian nonparametrics have provided promising results in bypassing the model selection problem in learning directed Bayesian Networks, very little effort has been made toward applying Bayesian nonparametrics to learn undirected latent variable models. In this paper, we present the infinite exponential family Harmonium (iEFH), a bipartite undirected latent variable model that automatically determines the number of latent units from an unbounded pool. We also present two important extensions of iEFH to 1) multiview iEFH for dealing with heterogeneous data, and 2) infinite maximum-margin Harmonium (iMMH) for incorporating supervising side information to learn predictive latent features. We develop variational inference algorithms to learn model parameters. Our methods are computationally competitive because of the avoidance of selecting the number of latent units. Our extensive experiments on real image datasets and text datasets appear to demonstrate the benefits of iEFH and iMMH inherited from Bayesian nonparametrics and max-margin learning. Such results were not available until now and contribute to expanding the scope of Bayesian nonparametrics to learn the structures of undirected latent variable models.

  13. European Rabbits as Reservoir for Coxiella burnetii.

    Science.gov (United States)

    González-Barrio, David; Maio, Elisa; Vieira-Pinto, Madalena; Ruiz-Fons, Francisco

    2015-06-01

    We studied the role of European rabbits (Oryctolagus cuniculus) as a reservoir for Coxiella burnetii in the Iberian region. High individual and population seroprevalences observed in wild and farmed rabbits, evidence of systemic infections, and vaginal shedding support the reservoir role of the European rabbit for C. burnetii.

  14. Extraction of latent images from printed media

    Science.gov (United States)

    Sergeyev, Vladislav; Fedoseev, Victor

    2015-12-01

    In this paper we propose an automatic technology for extraction of latent images from printed media such as documents, banknotes, financial securities, etc. This technology includes image processing by adaptively constructed Gabor filter bank for obtaining feature images, as well as subsequent stages of feature selection, grouping and multicomponent segmentation. The main advantage of the proposed technique is versatility: it allows to extract latent images made by different texture variations. Experimental results showing performance of the method over another known system for latent image extraction are given.

  15. Retrieved Latent Heating from TRMM

    Science.gov (United States)

    Tao, Wei-Kuo; Smith, Eric A.; Houze Jr, Robert

    2008-01-01

    The global hydrological cycle is central to the Earth's climate system, with rainfall and the physics of precipitation formation acting as the key links in the cycle. Two-thirds of global rainfall occurs in the tropics with the associated latent heating (LH) accounting for three-fourths of the total heat energy available to the Earth's atmosphere. In addition, fresh water provided by tropical rainfall and its variability exerts a large impact upon the structure and motions of the upper ocean layer. In the last decade, it has been established that standard products of LH from satellite measurements, particularly TRMM measurements, would be a valuable resource for scientific research and applications. Such products would enable new insights and investigations concerning the complexities of convection system life cycles, the diabatic heating controls and feedbacks related to meso-synoptic circulations and their forecasting, the relationship of tropical patterns of LH to the global circulation and climate, and strategies for improving cloud parameterizations in environmental prediction models. The status of retrieved TRMM LH products, TRMM LH inter-comparison and validation project, current TRMM LH applications and critic issues/action items (based on previous five TRMM LH workshops) is presented in this article.

  16. Disorders of the Reproductive Tract of Rabbits.

    Science.gov (United States)

    Harcourt-Brown, Frances Margaret

    2017-05-01

    Disorders of the reproductive tract are common in rabbits. Conditions are different in rabbits that are farmed for their meat or fur and those that are kept as pets. Farmed rabbits suffer from infections and diseases associated with pregnancy. Congenital abnormalities are more likely to be recognized and treated in pet rabbits. Pet rabbits suffer from age-related changes to their genital tract (hyperplasia, neoplasia, or hernias). Neutering is an important part of prevention and treatment of reproductive disorders. Knowledge of normal male and female reproductive anatomy is essential to prevent complications. These are described and illustrated. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  17. Evidence-Based Advances in Rabbit Medicine.

    Science.gov (United States)

    Summa, Noémie M; Brandão, João

    2017-09-01

    Rabbit medicine has been continuously evolving over time with increasing popularity and demand. Tremendous advances have been made in rabbit medicine over the past 5 years, including the use of imaging tools for otitis and dental disease management, the development of laboratory testing for encephalitozoonosis, or determination of prognosis in rabbits. Recent pharmacokinetic studies have been published, providing additional information on commonly used antibiotics and motility-enhancer drugs, as well as benzimidazole toxicosis. This article presents a review of evidence-based advances for liver lobe torsions, thymoma, and dental disease in rabbits and controversial and new future promising areas in rabbit medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Use of latent semantic analysis at Otec

    NARCIS (Netherlands)

    Van Bruggen, Jan

    2006-01-01

    Van Bruggen, J. (2006). Use of latent semantic analysis at Otec. Presentations discusses the applications of LSA in the Otec RTD program and a number of methodological issues. May, 18, 2006, Hannover, Germany.

  19. Respiratory and neurological disease in rabbits experimentally infected with equid herpesvirus 1.

    Science.gov (United States)

    Kanitz, Fábio A; Cargnelutti, Juliana F; Anziliero, Deniz; Gonçalves, Kelley V; Masuda, Eduardo K; Weiblen, Rudi; Flores, Eduardo F

    2015-10-01

    Equid herpesvirus type 1 (EHV-1) is an important pathogen of horses worldwide, associated with respiratory, reproductive and/or neurological disease. A mouse model for EHV-1 infection has been established but fails to reproduce some important aspects of the viral pathogenesis. Then, we investigated the susceptibility of rabbits to EHV-1 aiming at proposing this species as an alternative model for EHV-1 infection. Weanling rabbits inoculated intranasal with EHV-1 Kentucky D (10(7) TCID50/animal) shed virus in nasal secretions up to day 8-10 post-inoculation (pi), presented viremia up to day 14 pi and seroconverted to EHV-1 (virus neutralizing titers 4 to 64). Most rabbits (75%) developed respiratory disease, characterized by serous to hemorrhagic nasal discharge and mild to severe dyspnea. Some animals (20%) presented neurological signs as circling, bruxism and opisthotonus. Six animals died during acute disease (days 3-6); infectious virus and/or viral DNA were detected in the lungs, trigeminal ganglia (TG), olfactory bulbs (OBs) and cerebral cortex/brain (CC). Histological examination showed necrohemorrhagic, multifocal to coalescent bronchointerstitial pneumonia and diffuse alveolar edema. In two rabbits euthanized at day 50 pi, latent EHV-1 DNA was detected in the OBs. Dexamethasone administration at day 50 pi resulted in virus reactivation, demonstrated by virus shedding, viremia, clinical signs, and increase in VN titers and/or by detection of virus DNA in lungs, OBs, TGs and/or CC. These results demonstrate that rabbits are susceptible to EHV-1 infection and develop respiratory and neurological signs upon experimental inoculation. Thus, rabbits may be used to study selected aspects of EHV-1 biology and pathogenesis, extending and complementing the mouse model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. El silenciamiento de la proteína priónica celular (PrPC mediante RNA de interferencia (siRNA reduce la infección por HSV-1 y HSV-2 en células SK-SY5Y

    Directory of Open Access Journals (Sweden)

    Elizabeth Ortega-Soto

    2012-01-01

    Full Text Available Las encefalopatías espongiformes transmisibles (EETs son enfermedades neurodegenerativas fatales que afectan a humanos y ciertas especies animales. La hipótesis más aceptada indica que el agente infeccioso, denotado como prion y compuesto principalmente por la Proteína Priónica Scrapie (PrPSc, corresponde a una conformación anormal de una proteína codificada por el huésped denominada Proteína Priónica Celular (PrPC, cuya función es aún desconocida; sin embargo, la expresión ubicua de PrPC así como su elevado grado de conservación entre especies, sugieren un papel importante para esta proteína. En este trabajo se detectó a la PrPC en diferentes tipos celulares incluyendo un cultivo primario de células de peces (Tilapia, Oreochromis spp.. Además, basándonos en la secuencia de la PrPC humana, se diseñó un RNA de interferencia (siRNA con el fin de silenciar el gen PRNP en células neuronales SK-SY5Y. El siRNA diseñado inhibió la expresión de PrPC a lo largo de las 96 h post-transfección y las células silenciadas fueron menos susceptibles a la infección por HSV-1 y HSV-2, en comparación con células no transfectadas con el siRNA.

  1. Thermally Stable, Latent Olefin Metathesis Catalysts

    OpenAIRE

    Thomas, Renee M.; Fedorov, Alexey; Keitz, Benjamin K.; Grubbs, Robert H.

    2011-01-01

    Highly thermally stable N-aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium catalysts were designed and synthesized for latent olefin metathesis. These catalysts showed excellent latent behavior toward metathesis reactions, whereby the complexes were inactive at ambient temperature and initiated at elevated temperatures, a challenging property to achieve with second generation catalysts. A sterically hindered N-tert-butyl substituent on the NHC ligand of the ruthenium complex was found to i...

  2. Handbook of latent variable and related models

    CERN Document Server

    Lee, Sik-Yum

    2011-01-01

    This Handbook covers latent variable models, which are a flexible class of models for modeling multivariate data to explore relationships among observed and latent variables.- Covers a wide class of important models- Models and statistical methods described provide tools for analyzing a wide spectrum of complicated data- Includes illustrative examples with real data sets from business, education, medicine, public health and sociology.- Demonstrates the use of a wide variety of statistical, computational, and mathematical techniques.

  3. Adverse fetal outcomes in pregnant rabbits experimentally infected with rabbit hepatitis E virus.

    Science.gov (United States)

    Ahn, Hee-Seop; Han, Sang-Hoon; Kim, Yong-Hyun; Park, Byung-Joo; Kim, Dong-Hwi; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Choi, Changsun; Myoung, Jinjong; Choi, In-Soo

    2017-12-01

    Hepatitis E virus (HEV) causes severe hepatitis in pregnant women, with associated poor fetal outcomes. To study HEV viral pathogenesis, pregnant rabbits were infected with low- and high-dose rabbit HEV at 2 weeks gestation. HEV was identified in the serum, feces, and liver tissue of infected rabbits, and dose-dependent fetal mortality rates ranging from 67% to 80% were observed. The aspartate transaminase (AST)/alanine transaminase ratio was significantly higher (P rabbits than low-dose infected and negative control rabbits 14 days post infection (dpi). Tumor necrosis factor-α (TNF-α) was significantly higher in low-dose (P rabbits (P rabbits produced significantly more interferon-γ (IFN-γ; P rabbits at 7 and 14 dpi. High levels of AST, TNF-α, and IFN-γ may substantially influence adverse fetal outcomes in pregnant rabbits infected with high-dose HEV. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Model of evoked rabbit phonation.

    Science.gov (United States)

    Ge, Ping Jiang; French, Lesley C; Ohno, Tsunehisa; Zealear, David L; Rousseau, Bernard

    2009-01-01

    We describe a method for eliciting phonation in an in vivo rabbit preparation using low-frequency, bipolar pulsed stimulation of the cricothyroid muscles with airflow delivered to the glottis. Ten New Zealand White breeder rabbits weighing 3 to 5 kg were used in this study. The cricothyroid muscles were isolated bilaterally, and separate pairs of anode-cathode hooked-wire electrodes were inserted into each muscle. A Grass S-88 stimulator and 2 constant-current PSIU6 isolation units were used to deliver bipolar square wave pulses to each cricothyroid muscle, with airflow delivered to the glottis through a cuffed endotracheal tube. Phonation was evoked with a 50-Hz, 4-mA stimulus train of 1-ms pulses delivered to each cricothyroid muscle. The pulse trains were on for 2 seconds and were repeated every 5 seconds over a period of 180 minutes. Airflow was delivered at 143 cm3/s, producing phonation measuring 71 to 85 dB sound pressure level. Evoked phonation is feasible in rabbits by use of bipolar stimulation of the cricothyroid muscles with airflow delivered to the glottis. The in vivo rabbit preparation described may provide a useful small animal option for studies of evoked phonation. From the level and consistency of the adduction observed, we hypothesize that current spreading to the underlying adductor muscles and nerves resulted in neural pathway involvement beyond discrete activation of the cricothyroid muscle, providing sufficient approximation of the vocal folds for phonation.

  5. Latent nystagmus: vestibular nystagmus with a twist.

    Science.gov (United States)

    Brodsky, Michael C; Tusa, Ronald J

    2004-02-01

    Latent nystagmus is a horizontal binocular oscillation that is evoked by unequal visual input to the 2 eyes. It develops primarily in humans with congenital esotropia. To investigate the interrelationship between latent and peripheral vestibular nystagmus and their corollary neuroanatomical pathways. Examination of subcortical neuroanatomical pathways producing latent nystagmus and review of the neurophysiological mechanisms by which they become activated in congenital esotropia. The vestibular nucleus presides over motion input from the eyes and labyrinths. Latent nystagmus corresponds to the optokinetic component of ocular rotation that is driven monocularly by nasal optic flow during a turning movement of the body in lateral-eyed animals. Congenital esotropia alters visual pathway development from the visual cortex to subcortical centers that project to the vestibular nucleus, allowing this primitive subcortical motion detection system to generate latent nystagmus under conditions of monocular fixation. Latent nystagmus is the ocular counterpart of peripheral vestibular nystagmus. Its clinical expression in humans proclaims the evolutionary function of the eyes as sensory balance organs.

  6. Effect of a lytic bacteriophage on rabbits experimentally infected with pathogenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    J. Zhao

    2017-09-01

    Full Text Available Pathogenic Escherichia coli (E. coli is severely threatening the rabbit industry in China, and the concern over antibiotic-resistant bacteria has given rise to an urgent need for antibiotic alternatives. In this study, a member (ZRP1 of the Myoviridae family was isolated from rabbit faeces using a strain of rabbit atypical enteropathogenic E. coli (ZR1 as host. The one-step growth curve indicated that the latent period was around 25 to 30 min and the burst size was 144±31 plaque-forming unit/cell. The rate of phage-resistant mutation was 7×10–5±4×10–5. When the bacteriophage input at the multiplicity of infection (MOI was 0.1, 1 or 10, the growth of host E. coli in broth was inhibited for 5 h. A single intravenous injection of ZRP1 at MOI 0.1, 1 or 10 significantly prolonged the survival time of rabbits which simultaneously received a lethal dose of ZR1.

  7. Power-Law Distributions Based on Exponential Distributions: Latent Scaling, Spurious Zipf's Law, and Fractal Rabbits

    Science.gov (United States)

    Chen, Yanguang

    2015-03-01

    The difference between the inverse power function and the negative exponential function is significant. The former suggests a complex distribution, while the latter indicates a simple distribution. However, the association of the power-law distribution with the exponential distribution has been seldom researched. This paper is devoted to exploring the relationships between exponential laws and power laws from the angle of view of urban geography. Using mathematical derivation and numerical experiments, I reveal that a power-law distribution can be created through a semi-moving average process of an exponential distribution. For the distributions defined in a one-dimension space (e.g. Zipf's law), the power exponent is 1; while for those defined in a two-dimension space (e.g. Clark's law), the power exponent is 2. The findings of this study are as follows. First, the exponential distributions suggest a hidden scaling, but the scaling exponents suggest a Euclidean dimension. Second, special power-law distributions can be derived from exponential distributions, but they differ from the typical power-law distributions. Third, it is the real power-law distributions that can be related with fractal dimension. This study discloses an inherent link between simplicity and complexity. In practice, maybe the result presented in this paper can be employed to distinguish the real power laws from spurious power laws (e.g. the fake Zipf distribution).

  8. Power-law distributions based on exponential distributions: Latent scaling, spurious Zipf's law, and fractal rabbits

    CERN Document Server

    Chen, Yanguang

    2013-01-01

    The different between the inverse power function and the negative exponential function is significant. The former suggests a complex distribution, while the latter indicates a simple distribution. However, the association of the power-law distribution with the exponential distribution has been seldom researched. Using mathematical derivation and numerical experiments, I reveal that a power-law distribution can be created through averaging an exponential distribution. For the distributions defined in a 1-dimension space, the scaling exponent is 1; while for those defined in a 2-dimension space, the scaling exponent is 2. The findings of this study are as follows. First, the exponential distributions suggest a hidden scaling, but the scaling exponents suggest a Euclidean dimension. Second, special power-law distributions can be derived from exponential distributions, but they differ from the typical power-law distribution. Third, it is the real power-law distribution that can be related with fractal dimension. ...

  9. EXPERIMENTAL LIPEMIA IN RABBITS

    Science.gov (United States)

    Boggs, Thomas R.; Morris, Roger S.

    1909-01-01

    In reviewing the literature, no description of a lipemia occurring in relation to simple hemorrhage was found, so that the observation of the phenomenon here recorded would seem to be new. Very high percentages of fat have been found in the blood of diabetics. Fischer's case showed 18.1 per cent total ether extract. Of this very little was free fat (0.0018 gm. potassium hydroxide per gram of fat); iodine absorption was 60.6 per cent.; cholesterin, 2.6 per cent. Chatin's case, cited by Fischer, showed 1.2 per cent. cholesterin, 66.5 per cent. olein, 32.2 per cent. margarin in the fat. Neisser and Derlin in the ether extract of blood from a patient with diabetic coma found 19.7 per cent. fat, with melting point of from 39° to 41° C.; iodine absorption was 53.6 per cent. Javal in a similar case found 25.4 per cent. of fat in ether extract of dry serum (perhaps by Soxhlet method); 21 per cent. of the fat was lecithin. Bleibtreu produced alimentary lipemia in geese by feeding barley and butter. Ether extract of serum showed 6 per cent. of fat. The serum was milky with invisible droplets. Iodine absorption was 57 to 58 per cent. The fat was quite different, chemically, from the fat in the food. Lipemia disappeared a few days after discontinuing the forced feeding. Our experiments suggest, by analogy, the possible occurrence of lipemia in human anemias. In this connection it is of interest to note that we have recently demonstrated a moderate lipemia in a case of marked secondary anemia from hemorrhoids. The emaciation in such cases, as contrasted with the well-recognized conservation of the fat in pernicious anemia, suggests in human pathology a still further analogy which we now have under investigation. The fat in our lipemic rabbits differs from fats described above in its insolubility, as well as in its "constants." The change after precipitation of calcium from the serum suggests that the fat may be present in the serum as a protein-calcium-lecithin combination

  10. A survey exploring factors associated with 2890 companion-rabbit owners' knowledge of rabbit care and the neuter status of their companion rabbit.

    Science.gov (United States)

    Welch, Tasha; Coe, Jason B; Niel, Lee; McCobb, Emily

    2017-02-01

    Pet owners' knowledge of pet care has been shown to affect the human-animal relationship and the welfare of companion animals. With rabbits being the third most common companion animal in many regions, and evidence of owners' lack of awareness for the standards of care required to care for companion rabbits, it is important to understand the knowledge level of rabbit owners and determine how companion rabbits are being cared for. The purpose of this study was to survey rabbit owners in order to explore factors associated with their knowledge of rabbit care, and the neuter status of their companion rabbit. Current rabbit owners (n=2890) completed an online survey investigating acquisition of their companion rabbit, husbandry and care of their current rabbit, neuter status of their rabbit, owners' knowledge of rabbit care and owners' attachment to their current rabbit. An approximation of logistic regression modeling revealed increasing attachment (powners, the current study suggests acquisition sources, veterinarians, and companion-animal professionals can have an important role in the development of companion-rabbit owners' knowledge of rabbit care and in promoting the importance of neutering companion rabbits. Efforts to develop accessible resources to assist with educating companion-rabbit owners is important to ensuring successful rabbit-owner relationships. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Healthy rabbits are susceptible to Epstein-Barr virus infection and infected cells proliferate in immunosuppressed animals.

    Science.gov (United States)

    Khan, Gulfaraz; Ahmed, Waqar; Philip, Pretty S; Ali, Mahmoud H; Adem, Abdu

    2015-02-18

    Epstein-Barr virus (EBV) is an oncogenic virus implicated in the pathogenesis of several human malignancies. However, due to the lack of a suitable animal model, a number of fundamental questions pertaining to the biology of EBV remain poorly understood. Here, we explore the potential of rabbits as a model for EBV infection and investigate the impact of immunosuppression on viral proliferation and gene expression. Six healthy New Zealand white rabbits were inoculated intravenously with EBV and blood samples collected prior to infection and for 7 weeks post-infection. Three weeks after the last blood collection, animals were immunosuppressed with daily intramuscular injections of cyclosporin A at doses of 20 mg/kg for 15 days and blood collected twice a week from each rabbit. The animals were subsequently sacrificed and tissues from all major organs were collected for subsequent analysis. Following intravenous inoculation, all 6 rabbits seroconverted with raised IgG and IgM titres to EBV, but viral DNA in peripheral blood mononuclear cells (PBMCs) could only be detected intermittently. Following immunosuppression however, EBV DNA could be readily detected in PBMCs from all 4 rabbits that survived the treatment. Quantitative PCR indicated an increase in EBV viral load in PBMCs as the duration of immunosuppression increased. At autopsy, splenomegaly was seen in 3/4 rabbits, but spleens from all 4 rabbit were EBV PCR positive. EBER-in situ hybridization and immunoshistochemistry revealed the presence of a large number of EBER-positive and LMP-1 positive lymphoblasts in the spleens of 3/4 rabbits. To a lesser extent, EBER-positive cells were also seen in the portal tract regions of the liver of these rabbits. Western blotting indicated that EBNA-1 and EBNA-2 were also expressed in the liver and spleen of infected animals. EBV can infect healthy rabbits and the infected cells proliferate when the animals are immunocompromised. The infected cells expressed several EBV-latent

  12. Human Cytomegalovirus Manipulation of Latently Infected Cells

    Science.gov (United States)

    Sinclair, John H.; Reeves, Matthew B.

    2013-01-01

    Primary infection with human cytomegalovirus (HCMV) results in the establishment of a lifelong infection of the host which is aided by the ability of HCMV to undergo a latent infection. One site of HCMV latency in vivo is in haematopoietic progenitor cells, resident in the bone marrow, with genome carriage and reactivation being restricted to the cells of the myeloid lineage. Until recently, HCMV latency has been considered to be relatively quiescent with the virus being maintained essentially as a “silent partner” until conditions are met that trigger reactivation. However, advances in techniques to study global changes in gene expression have begun to show that HCMV latency is a highly active process which involves expression of specific latency-associated viral gene products which orchestrate major changes in the latently infected cell. These changes are argued to help maintain latent infection and to modulate the cellular environment to the benefit of latent virus. In this review, we will discuss these new findings and how they impact not only on our understanding of the biology of HCMV latency but also how they could provide tantalising glimpses into mechanisms that could become targets for the clearance of latent HCMV. PMID:24284875

  13. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD)

    Science.gov (United States)

    2014-01-01

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection. PMID:24490832

  14. Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses

    OpenAIRE

    Ma, H. X.; Zheng, L.; Liu, Y. B.; Zhao, C. Y.; Harrison, T. J.; Ma, Y. Y.; Sun, S. H.; Zhang, J. G.; Wang, Y. C.

    2010-01-01

    BACKGROUND: A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77-79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection. METHODS: Forty-two SPF rabbits were divided randomly in...

  15. White Rabbit Status and Prospects

    CERN Document Server

    Serrano, J; Cattin, M; van der Bij, E; Wlostowski, T; Daniluk, G; Lipinski, M; Beck, D; Hoffmann, J; Kreider, M; Prados, C; Rauch, S; Terpstra, W W; Zweig, M

    2014-01-01

    The White Rabbit (WR) project started off to provide a sequencing and synchronisation solution for the needs of CERN and GSI. Since then, many other users have adopted it to solve problems in the domain of distributed hard realtime systems. The paper discusses the current performance of WR hardware, along with present and foreseen applications. It also describes current efforts to standardise WR under IEEE 1588 and recent developments on reliability of timely data distribution, finishing with an outline of future plans.

  16. Role of Households in Rabbit Production in Enugu-North ...

    African Journals Online (AJOL)

    North Agricultural Zone of Enugu State. It determined rabbit management and breeding practices of respondents, roles of households in rabbit production and constraints associated with rabbit production in the area. Multistage sampling technique ...

  17. Text Categorization with Latent Dirichlet Allocation

    Directory of Open Access Journals (Sweden)

    ZLACKÝ Daniel

    2014-05-01

    Full Text Available This paper focuses on the text categorization of Slovak text corpora using latent Dirichlet allocation. Our goal is to build text subcorpora that contain similar text documents. We want to use these better organized text subcorpora to build more robust language models that can be used in the area of speech recognition systems. Our previous research in the area of text categorization showed that we can achieve better results with categorized text corpora. In this paper we used latent Dirichlet allocation for text categorization. We divided initial text corpus into 2, 5, 10, 20 or 100 subcorpora with various iterations and save steps. Language models were built on these subcorpora and adapted with linear interpolation to judicial domain. The experiment results showed that text categorization using latent Dirichlet allocation can improve the system for automatic speech recognition by creating the language models from organized text corpora.

  18. Geographic pathology of latent prostatic carcinoma.

    Science.gov (United States)

    Yatani, R; Chigusa, I; Akazaki, K; Stemmermann, G N; Welsh, R A; Correa, P

    1982-06-15

    Prostates obtained at autopsy from black and white males in the United States of America, from Colombians, from Japanese migrants in Hawaii, and from Japanese in Japan (all over 50 years old) were serially step-sectioned and examined microscopically using identical techniques and diagnostic criteria. The age-adjusted overall prevalence of latent carcinoma was significantly higher in US blacks (36.9%), in US whites (34.6%) and in Colombians (31.5%) than in Japanese in Japan (20.5%). There was no significant difference in prevalence between Japanese migrants in Hawaii (25.6%) and Japanese in Japan. When the carcinomas were subdivided into latent infiltrative type (LIT) and latent non-infiltrative type (LNT), the LIT component reflected upon the overall prevalence of latent carcinoma. There was an increase in the overall prevalence of latent carcinoma and in the prevalence of LIT tumors with age in Japanese migrants to Hawaii and in Japanese of Japan but only a suggestive increase in blacks and whites in the United States. There was no significant relation between age and prevalence in Colombia. In LNT tumors, there was no consistent trend related to race or age. The size of LIT tumors was significantly greater than that of LNT tumors in all races or in each decade of total material. There were many large LIT tumors in blacks and whites in the United States. These results suggest that the prevalence of LIT tumors shows a race variation similar to the incidence of clinical carcinoma of the prostate, and that LNT tumors probably remain latent during the individual's life span.

  19. Rabbit model for Chlamydia pneumoniae infection.

    OpenAIRE

    Fong, I W; Chiu, B.; Viira, E; Fong, M W; Jang, D.; Mahony, J

    1997-01-01

    A rabbit model was established for Chlamydia pneumoniae infection that may be helpful to understand the pathogenesis of disease in humans. Twelve, pathogen-free, 1-month-old New Zealand White rabbits were inoculated with 1.0 x 10(7) to 5.0 x 10(7) CFU of purified C. pneumoniae (ATCC strain VR 1310) via the nasopharynx (1 rabbit died immediately postinoculation, and 11 were available for study). Five controls were inoculated with the carrier buffer. Ten of the 11 study rabbits demonstrated ser...

  20. Fibronectin promotes epithelial migration of cultured rabbit cornea in situ

    OpenAIRE

    1983-01-01

    We investigated the effect of fibronectin on epithelial migration onto the stroma in cultured rabbit cornea. Rabbit plasma fibronectin was purified by affinity chromatography using gelatin-Sepharose 4B, and its purity was confirmed by SDS polyacrylamide slab gel electrophoresis. Antibody against rabbit plasma fibronectin raised in guinea pigs formed a single precipitin line against rabbit plasma and purified rabbit plasma fibronectin by Ouchterlony double diffusion test. When rabbit cornea wa...

  1. Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses

    Science.gov (United States)

    Ma, Hongxia; Zheng, Lin; Liu, Yunbo; Zhao, Chenyan; Harrison, Tim J.; Ma, Yuyuan; Sun, Shuhua; Zhang, Jingang; Wang, Youchun

    2010-01-01

    Background A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77–79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection. Methods Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination. Findings Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation. Conclusions These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis. PMID:20161794

  2. Experimental infection of rabbits with rabbit and genotypes 1 and 4 hepatitis E viruses.

    Science.gov (United States)

    Ma, Hongxia; Zheng, Lin; Liu, Yunbo; Zhao, Chenyan; Harrison, Tim J; Ma, Yuyuan; Sun, Shuhua; Zhang, Jingang; Wang, Youchun

    2010-02-11

    A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77-79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection. Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination. Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation. These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis.

  3. Experimental infection of rabbits with rabbit and genotypes 1 and 4 hepatitis E viruses.

    Directory of Open Access Journals (Sweden)

    Hongxia Ma

    Full Text Available BACKGROUND: A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV genotype. Although the rabbit HEV isolate had 77-79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection. METHODS: Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination. FINDINGS: Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents, with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation. CONCLUSIONS: These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis.

  4. Variable importance in latent variable regression models

    NARCIS (Netherlands)

    Kvalheim, O.M.; Arneberg, R.; Bleie, O.; Rajalahti, T.; Smilde, A.K.; Westerhuis, J.A.

    2014-01-01

    The quality and practical usefulness of a regression model are a function of both interpretability and prediction performance. This work presents some new graphical tools for improved interpretation of latent variable regression models that can also assist in improved algorithms for variable

  5. Essay Assessment with Latent Semantic Analysis

    Science.gov (United States)

    Miller, Tristan

    2003-01-01

    Latent semantic analysis (LSA) is an automated, statistical technique for comparing the semantic similarity of words or documents. In this article, I examine the application of LSA to automated essay scoring. I compare LSA methods to earlier statistical methods for assessing essay quality, and critically review contemporary essay-scoring systems…

  6. An Introduction to Latent Semantic Analysis.

    Science.gov (United States)

    Landauer, Thomas K; Foltz, Peter W.; Laham, Darrell

    1998-01-01

    Offers an introduction to the theory and implementation of Latent Semantic Analysis (LSA), a theory and method for extracting and representing the contextual-usage meaning of words by statistical computations applied to a large corpus of text. Gives an overview of applications and modeling of human knowledge to which LSA has been applied. (SR)

  7. On identifiability of certain latent class models.

    NARCIS (Netherlands)

    van Wieringen, W.N.

    2005-01-01

    Blischke [1962. Moment estimators for the parameters of a mixture of two binomial distributions. Ann. Math. Statist. 33, 444-454] studies a mixture of two binomials, a latent class model. In this article we generalize this model to a mixture of two products of binomials. We show when this

  8. Forensic Chemistry: The Revelation of Latent Fingerprints

    Science.gov (United States)

    Friesen, J. Brent

    2015-01-01

    The visualization of latent fingerprints often involves the use of a chemical substance that creates a contrast between the fingerprint residues and the surface on which the print was deposited. The chemical-aided visualization techniques can be divided into two main categories: those that chemically react with the fingerprint residue and those…

  9. Latent Structure of Self-Monitoring.

    Science.gov (United States)

    Hoyle, Rick H.; Lennox, Richard D.

    1991-01-01

    The latent structure of the Self-Monitoring Scale of M. Snyder (1974) is evaluated by comparing several measurement models suggested by previous factor analysis of the scale using sample data from 1,113 college students. Implications of results are discussed in relation to self-monitoring and the use of factor analysis. (SLD)

  10. Saharan Africa: A Latent Class Analysis

    African Journals Online (AJOL)

    AJRH Managing Editor

    1University of Southern California School of Social Work, 669 W. 34th Street, Los Angeles, CA 90089, USA; 2University of ... Abstract. While studies have examined factors associated with condom use behaviors, few have assessed risk perception and condom use among SSA .... approach (latent class analysis) to identify.

  11. Thermally Stable, Latent Olefin Metathesis Catalysts.

    Science.gov (United States)

    Thomas, Renee M; Fedorov, Alexey; Keitz, Benjamin K; Grubbs, Robert H

    2011-12-26

    Highly thermally stable N-aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium catalysts were designed and synthesized for latent olefin metathesis. These catalysts showed excellent latent behavior toward metathesis reactions, whereby the complexes were inactive at ambient temperature and initiated at elevated temperatures, a challenging property to achieve with second generation catalysts. A sterically hindered N-tert-butyl substituent on the NHC ligand of the ruthenium complex was found to induce latent behavior toward cross-metathesis reactions, and exchange of the chloride ligands for iodide ligands was necessary to attain latent behavior during ring-opening metathesis polymerization (ROMP). Iodide-based catalysts showed no reactivity toward ROMP of norbornene-derived monomers at 25 °C, and upon heating to 85 °C gave complete conversion of monomer to polymer in less than 2 hours. All of the complexes were very stable to air, moisture, and elevated temperatures up to at least 90 °C, and exhibited a long catalyst lifetime in solution at elevated temperatures.

  12. Incorporating direct marketing activity into latent attrition models

    NARCIS (Netherlands)

    Schweidel, David A.; Knox, George

    2013-01-01

    When defection is unobserved, latent attrition models provide useful insights about customer behavior and accurate forecasts of customer value. Yet extant models ignore direct marketing efforts. Response models incorporate the effects of direct marketing, but because they ignore latent attrition,

  13. Mapping superficial lymphatic territories in the rabbit.

    Science.gov (United States)

    Soto-Miranda, Miguel A; Suami, Hiroo; Chang, David W

    2013-06-01

    Little is known about the anatomy of the lymphatic system in the rabbit with regard to relationships between the lymphatic vessel and lymph node. According to our previous studies in human cadavers and canines, the superficial lymphatic system could be divided into lymphatic territories. The aim of this study was to completely map the superficial lymphatic system in the rabbit. We used our microinjection technique and histological analysis for dissecting studies and recently developed indocyanine green (ICG) fluorescent lymphography for demonstrating dynamic lymph flow in living rabbits. Real-time ICG fluorescent lymphography was performed in two living New Zealand White rabbits, and direct dye microinjection of the lymphatic vessels was performed in eight dead rabbits. To assess the relationships between the vascular and lymphatic systems in rabbits, we performed radiocontrast injection into arteries in two dead rabbits prior to the lymphatic injection. The ICG fluorescent lymphography revealed eight lymphatic territories in the preauricular, submandibular, root of the lateral neck, axillary, lumbar, inguinal, root of the tail, and popliteal regions. We injected blue acrylic dye into every lymphatic vessel 0.1 mm in diameter or larger. We then dissected and chased the stained lymphatic vessels proximally until the vessels connected to the first tier lymph node. This procedure was repeated throughout the body until all the relationships between the lymphatic vessels and lymph nodes were defined. The lymphatic system of the rabbit could be defined as eight lymphatic territories, each with its own lymphatic vessels and lymph node. Copyright © 2013 Wiley Periodicals, Inc.

  14. VASCULAR EFFECTS OF KETAMINE IN ISOLATED RABBIT ...

    African Journals Online (AJOL)

    Daniel Owu

    Summary: The precise mechanism by which ketamine induces relaxation of vascular smooth muscle is not clear. The goal of this study was to further characterize the vascular actions of ketamine in rabbit aortic smooth muscles. Ring segments (2mm) of rabbit aortae were suspended in 20ml organ baths containing ...

  15. Uterine disorders in 50 pet rabbits.

    Science.gov (United States)

    Künzel, Frank; Grinninger, Petra; Shibly, Sarina; Hassan, Jasmin; Tichy, Alexander; Berghold, Petra; Fuchs-Baumgartinger, Andrea

    2015-01-01

    Although the incidence of uterine disorders in pet rabbits is high there are only a few retrospective studies and case reports on genital tract disease in female rabbits. Uterine disorders were assessed in 50 pet rabbits. In 31 pet rabbits with suspected clinical uterine disease, medical records were further reviewed regarding clinical signs, diagnostic workup, treatment as well as the outcome itself. Uterine adenocarcinoma (54%) was most frequently diagnosed, followed by endometrial hyperplasia (26%). Serosanguineous vaginal discharge was the predominant clinical sign observed by the rabbit owners. In approximately 50% of the rabbits with suspected uterine disorders, abdominal palpation revealed enlarged and/or irregular masses in the caudoventral abdomen indicating uterine lesions. Out of 23 rabbits undergoing ovariohysterectomy, four were either euthanized or died shortly after surgery because they were clinically unstable. Overall, 80% of the ovariohysterectomized animals were still alive 6 mo after surgery. In female pet rabbits that are not breeding, either ovariohysterectomy should be performed at an early age or routine checks including ultrasonography of the abdomen are recommended on a regular basis.

  16. Viral skin diseases of the rabbit.

    Science.gov (United States)

    Meredith, Anna L

    2013-09-01

    This article describes the viral skin diseases affecting the domestic rabbit, the most important being myxomatosis. Transmission and pathogenesis, clinical signs, diagnosis, treatment, and control are described and the article will be of interest to veterinary practitioners who treat rabbits. Shope fibroma virus, Shope papilloma virus, and rabbitpox are also discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Welfare and the intensive production of rabbits.

    Science.gov (United States)

    Morisse, J P; Maurice, R

    1994-03-01

    Rabbit production in Europe is concentrated largely in the "Latin" countries of Italy, France and Spain, in which animal protectionist attitudes are considered moderate. However, in the case of rabbits, the intensification of husbandry necessitates strict observance of physiological, behavioural and health requirements, in view of the very special needs of the species and the sensitivity of rabbits to environmental conditions. Rabbits are described as anxious, timid and emotional, with unusual arrangements for reproduction (induced ovulation) and digestion (caecotrophy). Therefore, these animals could not be reared intensively until the completion of extensive research, which has been conducted over the past twenty years, into the environmental and nutritional needs of rabbits, and the selection of lines having a calm temperament and maternal aptitude. This research was required to meet the welfare needs of this species. These concepts are perfectly integrated into the current operation of intensive units, and should not be brought into question on the basis of fragmentary observations by some researchers who would wish to see a return to rearing on litter. A discussion of rabbit welfare conducted in 1992 by specialists of the German branch of the World Rabbit Science Association approved modern methods of keeping rabbits on wire grids, provided that some changes were made to current procedures.

  18. Experimental Infections Of Domestic Rabbits ( Oryctolagus cuniculus ...

    African Journals Online (AJOL)

    Nigerian Journal of Animal Production ... Comparative study of single infections of domestic rabbits (Oryctolagus cuniculus) with Nigerian isolates of Trypanosoma brucei (Gboko strain), and Trypanosoma congolense (Binchi ... Eighteen rabbits of 10-14 weeks old weighing between 600-1200 grams were used for the study.

  19. Kafka versus RabbitMQ

    OpenAIRE

    Dobbelaere, Philippe; Esmaili, Kyumars Sheykh

    2017-01-01

    Publish/subscribe is a distributed interaction paradigm well adapted to the deployment of scalable and loosely coupled systems. Apache Kafka and RabbitMQ are two popular open-source and commercially-supported pub/sub systems that have been around for almost a decade and have seen wide adoption. Given the popularity of these two systems and the fact that both are branded as pub/sub systems, two frequently asked questions in the relevant online forums are: how do they compare against each other...

  20. Bayesian Adaptive Lasso for Ordinal Regression with Latent Variables

    Science.gov (United States)

    Feng, Xiang-Nan; Wu, Hao-Tian; Song, Xin-Yuan

    2017-01-01

    We consider an ordinal regression model with latent variables to investigate the effects of observable and latent explanatory variables on the ordinal responses of interest. Each latent variable is characterized by correlated observed variables through a confirmatory factor analysis model. We develop a Bayesian adaptive lasso procedure to conduct…

  1. Behavioral fever in newborn rabbits

    Science.gov (United States)

    Satinoff, E.; Mcewen, G. N., Jr.; Williams, B. A.

    1976-01-01

    New Zealand white rabbit pups aged 12 to 72 hr were divided into three groups and given an intraperitoneal injection of Pseudomonas polysaccharide, a saline vehicle alone, and no treatment, respectively. The animals injected with pyrogen and maintained at an ambient temperature of 32 C for 2 hr did not develop fever. When placed in a thermally graded alleyway, the animals injected with pyrogen selected gradient positions that represented significantly higher temperatures than controls injected with saline. Further stay at selected positions for 5 min caused a considerable increase in the rectal temperature of the pyrogen-injected pups but not that of controls. The results support the hypothesis that newborn rabbits will develop a fever by behavioral means after a single injection of an exogenous pyrogen if the opportunity for thermoregulatory behavior is present. No fever develops if the pups must rely solely on internal thermoregulatory mechanisms. The behavioral system for producing a fever is mature at birth, but an adequate system of internal reflexes does not appear to develop for some days.

  2. Assessment of handedness using latent class factor analysis.

    Science.gov (United States)

    Merni, Franco; Di Michele, Rocco; Soffritti, Gabriele

    2014-01-01

    Recently several studies in which handedness was evaluated as a latent construct have been performed. In those studies, handedness was modelled using a qualitative latent variable (latent class models), a continuous latent variable (factor models), or both a qualitative latent variable and a continuous latent trait (mixed Rasch models). The aim of this study was to explore the usefulness and effectiveness of an approach in which handedness is treated as a qualitatively scaled latent variable with ordered categories (latent class factor models). This aim was pursued through an exploratory analysis of a dataset containing information on the hand used by 2236 young Italian sportspeople to perform 10 tasks. For comparison purposes, a latent class analysis was carried out. A cross-validation procedure was implemented. The results of all the analyses revealed that the best fit to the observed handedness patterns was obtained using a latent class factor model. Through this model, individuals were assigned to one of four ordered levels of handedness, and a quantitative index of left-handedness for each individual was computed by taking into account the different effect of the 10 tasks. These results provide support for the use of the latent class factor approach for handedness assessment.

  3. Biomedical Literature Exploration through Latent Semantics

    Directory of Open Access Journals (Sweden)

    Hugo ARAÚJO

    2013-08-01

    Full Text Available The fast increasing amount of articles published in the biomedical field is creating difficulties in the way this wealth of information can be efficiently exploited by researchers. As a way of overcoming these limitations and potentiating a more efficient use of the literature, we propose an approach for structuring the results of a literature search based on the latent semantic information extracted from a corpus. Moreover, we show how the results of the Latent Semantic Analysis method can be adapted so as to evidence differences between results of different searches. We also propose different visualization techniques that can be applied to explore these results. Used in combination, these techniques could empower users with tools for literature guided knowledge exploration and discovery.

  4. Parasitic infections of wild rabbits and hares

    Directory of Open Access Journals (Sweden)

    Ilić Tamara

    2014-01-01

    Full Text Available The paper presents the most important parasitic infections of wild rabbits and hares, which harmful effect in this animal population is manifested as a gradual weakening of the immune system, reduction in fertility, weight loss and constant exhaustion. Order of Lagomorpha (hares or lagomorphs belongs to superorder of higher mammals which includes the family of rabbits (Leporidae which are represented in Europe as well as the family of whistleblowers (Ochotonidae which live only in North America and Northern regions of Asia. The most important representatives of Leporidae family are European hare (Lepus europeus and wild rabbit (Oryctolagus cuniculus. The most important endoparasitosis of hares and wild rabbits are: coccidiosis, encephalitozoonosis (nosemosis, toxoplasmosis, sarcocystosis, giardiasis, cryptosporidiosis, protostrongylosis, trichostrngylodosis, passalurosis, anoplocephalidosis, cysticercosis and fasciolosis. The most frequent ectoparasites of rabbits and wild hares are fleas, lice and ticks. Reduction in hare population, which is noticed in whole Europe including Serbia, is caused by changed living conditions, quantitatively and qualitatively insufficient nutrition, increased use of herbicides as well as various infectious diseases and the diseases of parasitic etiology. Since wild rabbits and hares pose a threat to health of domestic rabbits and people, knowledge of parasitic fauna of these wild animals is of extreme epizootiological and epidemiological importance.

  5. Welfare aspects in rabbit rearing and transport

    Directory of Open Access Journals (Sweden)

    Claudio Cavani

    2010-01-01

    Full Text Available The review starts with the description of the rabbits’ (Oryctolagus cuniculus main habits and the current situation concerning the rabbit husbandry and management systems, as well as their effects on the welfare of these animals. As far as the intensive rabbit husbandry systems are concerned, the main problems are related to the time since rabbits have been domesticated and their adaptive capacity and coping styles as respects the farming environment and management systems. Both these aspects have implications in the present and future of rabbit rearing for different purposes. Examples are given on the effects of different housing and management systems on rabbit welfare, as well as examples of the ethological, physiological and productive indicators used to evaluate these effects. Transportation and, more generally, preslaughter phases including catching, fasting and lairage at the abattoir are considered major stressors for farmed rabbits and might have deleterious effects on health, well-being, performance, and finally, product quality. A general statement of the recent scientific studies considering the effects of pre-slaughter factors on physiological and productive measurements are reported. Finally, some indications in order to improve rabbit welfare, already present at the European level, are also outlined, together with the European Food Safety Authority opinions.

  6. Latent Semantic Indexing for Patent Information

    OpenAIRE

    Ryley, Dr. James

    2007-01-01

    Latent Semantic Indexing (LSI) promises more accurate retrieval of information by incorporating statistical information on term meaning and frequency while retrieving documents as a result of a search. LSI’s precision and accuracy has been proven many times on test corpora, but the world’s patent literature poses a significant challenge in effectively implementing an LSI search engine due the size and heterogeneity of the patent corpus. Some of the factors which must be addressed to realize...

  7. Review of Inferring Latent Attributes from Twitter

    OpenAIRE

    Ludu, Surabhi Singh

    2015-01-01

    This paper reviews literature from 2011 to 2013 on how Latent attributes like gender, political leaning etc. can be inferred from a person's twitter and neighborhood data. Prediction of demographic data can bring value to businesses, can prove instrumental in legal investigation. Moreover, political leanings can be inferred from the wide variety of user data available on-line. The motive of this review is to understand how large data sets can be made from available twitter data. The tweeting ...

  8. Latent variables and route choice behavior

    DEFF Research Database (Denmark)

    Prato, Carlo Giacomo; Bekhor, Shlomo; Pronello, Cristina

    2012-01-01

    In the last decade, a broad array of disciplines has shown a general interest in enhancing discrete choice models by considering the incorporation of psychological factors affecting decision making. This paper provides insight into the comprehension of the determinants of route choice behavior...... results illustrate that considering latent variables (i.e., memory, habit, familiarity, spatial ability, time saving skills) alongside traditional variables (e.g., travel time, distance, congestion level) enriches the comprehension of route choice behavior....

  9. New Treatment Regimen for Latent Tuberculosis Infection

    Centers for Disease Control (CDC) Podcasts

    2012-03-15

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses the December 9, 2011 CDC guidelines for the use of a new regimen for the treatment of persons with latent tuberculosis infection.  Created: 3/15/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 3/15/2012.

  10. Barcelona - Talent Latent 09 / Ahto Sooaru

    Index Scriptorium Estoniae

    Sooaru, Ahto

    2010-01-01

    Fotonäitusest "Talent Latent 09" Barcelonas Arts Santa Monica kunstikeskuses. Loetletud näitusel eksponeeritud fotode autorid. Pikemalt Rafael Milach'i (sünd. 1978), Lucia Ganieva, Javier Marquerie Thomas'i (sünd. 1986), Amaury da Cunha (sünd. 1976) töödest. Lühidalt ka teistest näitustest Arts Santa Monica kunstikeskuses

  11. Probabilistic Latent Variable Models as Nonnegative Factorizations

    Directory of Open Access Journals (Sweden)

    Madhusudana Shashanka

    2008-05-01

    Full Text Available This paper presents a family of probabilistic latent variable models that can be used for analysis of nonnegative data. We show that there are strong ties between nonnegative matrix factorization and this family, and provide some straightforward extensions which can help in dealing with shift invariances, higher-order decompositions and sparsity constraints. We argue through these extensions that the use of this approach allows for rapid development of complex statistical models for analyzing nonnegative data.

  12. Emerging latent fingerprint technologies: a review

    OpenAIRE

    Jasuja, Om Prakash; Bumbrah, Gurvinder Singh; Sharma, Rakesh Mohan

    2016-01-01

    Gurvinder Singh Bumbrah, Rakesh Mohan Sharma, Om Prakash Jasuja Department of Forensic Science, Punjabi University, Patiala, Punjab, India Abstract: Information regarding state of the art technology is accessible by searching in a systematic manner, and is the preferred way of keeping up to date. In this review, we present the recent developments in the field of latent fingerprint detection. Recent developments in processing methods including optical, physical, and chemical ...

  13. Factors associated with latent fingerprint exclusion determinations.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2017-06-01

    Exclusion is the determination by a latent print examiner that two friction ridge impressions did not originate from the same source. The concept and terminology of exclusion vary among agencies. Much of the literature on latent print examination focuses on individualization, and much less attention has been paid to exclusion. This experimental study assesses the associations between a variety of factors and exclusion determinations. Although erroneous exclusions are more likely to occur on some images and for some examiners, they were widely distributed among images and examiners. Measurable factors found to be associated with exclusion rates include the quality of the latent, value determinations, analysis minutia count, comparison difficulty, and the presence of cores or deltas. An understanding of these associations will help explain the circumstances under which errors are more likely to occur and when determinations are less likely to be reproduced by other examiners; the results should also lead to improved effectiveness and efficiency of training and casework quality assurance. This research is intended to assist examiners in improving the examination process and provide information to the broader community regarding the accuracy, reliability, and implications of exclusion decisions. Published by Elsevier B.V.

  14. Clinical implication of latent myofascial trigger point.

    Science.gov (United States)

    Celik, Derya; Mutlu, Ebru Kaya

    2013-08-01

    Myofascial trigger points (MTrPs) are hyperirritable points located within a taut band of skeletal muscle or fascia, which cause referred pain, local tenderness and autonomic changes when compressed. There are fundamental differences between the effects produced by the two basic types of MTrPs (active and latent). Active trigger points (ATrPs) usually produce referred pain and tenderness. In contrast, latent trigger points (LTrPs) are foci of hyperirritability in a taut band of muscle, which are clinically associated with a local twitch response, tenderness and/or referred pain upon manual examination. LTrPs may be found in many pain-free skeletal muscles and may be "activated" and converted to ATrPs by continuous detrimental stimuli. ATrPs can be inactivated by different treatment strategies; however, they never fully disappear but rather convert to the latent form. Therefore, the diagnosis and treatment of LTrPs is important. This review highlights the clinical implication of LTrPs.

  15. Benign Rabbit Calicivirus in New Zealand.

    Science.gov (United States)

    Nicholson, Leila J; Mahar, Jackie E; Strive, Tanja; Zheng, Tao; Holmes, Edward C; Ward, Vernon K; Duckworth, Janine A

    2017-06-01

    The Czech v351 strain of rabbit hemorrhagic disease virus (RHDV1) is used in Australia and New Zealand as a biological control agent for rabbits, which are important and damaging introduced vertebrate pests in these countries. However, nonpathogenic rabbit caliciviruses (RCVs) can provide partial immunological cross-protection against lethal RHDV infection and thus interfere with effective rabbit biocontrol. Antibodies that cross-reacted against RHDV antigens were found in wild rabbits before the release of RHDV1 in New Zealand in 1997, suggesting that nonpathogenic RCVs were already present in New Zealand. The aim of this study was to confirm the presence of nonpathogenic RCV in New Zealand and describe its geographical distribution. RCV and RHDV antibody assays were used to screen serum samples from 350 wild rabbits from 14 locations in New Zealand. The serological survey indicated that both RCV and RHDV are widespread in New Zealand wild rabbits, with antibodies detected in 10 out of 14 and 12 out of 14 populations, respectively. Two closely related RCV strains were identified in the duodenal tissue from a New Zealand wild rabbit (RCV Gore-425A and RCV Gore-425B). Both variants are most closely related to Australian RCV strains, but with 88% nucleotide identity, they are genetically distinct. Phylogenetic analysis revealed that the New Zealand RCV strains fall within the genetic diversity of the Australian RCV isolates, indicating a relatively recent movement of RCVs between Australia and New Zealand. IMPORTANCE Wild rabbits are important and damaging introduced vertebrate pests in Australia and New Zealand. Although RHDV1 is used as a biological control agent, some nonpathogenic RCVs can provide partial immunological cross-protection against lethal RHDV infection and thus interfere with its effectiveness for rabbit control. The presence of nonpathogenic RCVs in New Zealand wild rabbits has been long hypothesized, but earlier attempts to isolate a New Zealand

  16. A Review of Rabbit Diseases in Egypt

    Directory of Open Access Journals (Sweden)

    Hamed A Mohammed

    2016-02-01

    Full Text Available Promising approaches of the Egyptian governmental as well as non-governmental society to rabbit industry to overcome the unemployment of youth in the society required more efforts from scientific institutes to help in development of such industry. Epidemiological studies are of outmost importance to highlight disease nature and to help in meantime implement of successful preventive and control measures. The aim of this paper is to review the situation of rabbit diseases of economic impact in Egypt (1952 to 2013. The review will highlight the viral infection of rabbit hemorrhagic disease, bacterial disease of colibacillosis, clostridiosis, salmonellosis, pasteurellosis, staphylococcosis and listeriosis and parasitic infection of coccidiosis and mange.

  17. First Versus Second Order Latent Growth Curve Models: Some Insights From Latent State-Trait Theory.

    Science.gov (United States)

    Geiser, Christian; Keller, Brian; Lockhart, Ginger

    2013-07-01

    First order latent growth curve models (FGMs) estimate change based on a single observed variable and are widely used in longitudinal research. Despite significant advantages, second order latent growth curve models (SGMs), which use multiple indicators, are rarely used in practice, and not all aspects of these models are widely understood. In this article, our goal is to contribute to a deeper understanding of theoretical and practical differences between FGMs and SGMs. We define the latent variables in FGMs and SGMs explicitly on the basis of latent state-trait (LST) theory and discuss insights that arise from this approach. We show that FGMs imply a strict trait-like conception of the construct under study, whereas SGMs allow for both trait and state components. Based on a simulation study and empirical applications to the CES-D depression scale (Radloff, 1977) we illustrate that, as an important practical consequence, FGMs yield biased reliability estimates whenever constructs contain state components, whereas reliability estimates based on SGMs were found to be accurate. Implications of the state-trait distinction for the measurement of change via latent growth curve models are discussed.

  18. Rabbit muscle proteomics: a great leap forward.

    Science.gov (United States)

    de Almeida, André Martinho

    2013-08-01

    The rabbit is an important species as both a production animal and as a model organism in physiology, pharmaceutical, and numerous other studies. Similar to other species, the rabbit skeletal muscle proteome has been characterized, first using 2DE mapping and more recently using high-throughput shotgun proteomics. This article is a commentary on "Shotgun proteomics analysis of the sarcoplasmic reticulum preparations from rabbit skeletal muscle" (Z. Liu et al., Proteomics, 2013, 13, 2335-2338). Herein, we present the reasons why the manuscript is of high relevance to three major fields: farm animal, rabbit, and muscle/meat proteomics. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. TOXIC EFFECTS OF CYPERMETHRIN IN FEMALE RABBITS

    Directory of Open Access Journals (Sweden)

    M. S. ULLAH, M. AHMAD, N. AHMAD, M. Z. KHAN1 AND I. AHMAD

    2006-10-01

    Full Text Available The aim of the present study was to explore the fetotoxic effects of cypermethrin (CY in female rabbits with low and high doses. For this purpose, 32 adult female rabbits were divided in to four equal groups A, B, C and D. Rabbits of groups A, B and C were treated with different levels of CY at the dose rate of 25, 50 and 75 mg/kg body weight intraperitoneally, while the group D served as a control and was given equal volume of normal saline intraperitoneally. The clinical signs exhibited by the rabbits treated with CY included salivation, licking of different body parts, muscular tremors, ataxia and convulsions. There was a significant difference in the numbers of CL and number of fetuses which mean the early embryonic death and post implantation loses at the high dose. There were microscopic changes in the ovaries and uteri of animals treated with CY.

  20. Knowledge of reproduction management practices among rabbit ...

    African Journals Online (AJOL)

    Forty-four (44) commercial rabbit farmers from two urban centers (Abeokuta and Ijebu-Ode) in Ogun State were studied in this research. Majority (63.64%) are small-scale farmers with a stock size of between 20 and 50 animals. About 27% of the farmers have a stock size of 52-100 rabbits while only 9.09% have a stock size ...

  1. INFECTIOUS MYXOMATOSIS (SANARELLI) IN PREGNANT RABBITS

    Science.gov (United States)

    Sprunt, Douglas H.

    1932-01-01

    Pregnancy in rabbits alters the reactivity of the tissues to the virus of infectious myxomatosis. The livers of pregnant animals with the myxoma have a central acidophilic necrosis. Secondary lesions in the lungs are much more numerous and larger in the pregnant than in the non-gravid animals. In like manner the lesions in the spleen are more extensive in the pregnant rabbit. On the other hand the skin lesions of the pregnant animal are decreased in size. PMID:19870088

  2. Encephalitozoon cuniculi in rabbits: Serological screening and histopathological findings.

    Science.gov (United States)

    Maestrini, Giovanni; Ricci, Emanuele; Cantile, Carlo; Mannella, Riccardo; Mancianti, Francesca; Paci, Gisella; D'Ascenzi, Carlo; Perrucci, Stefania

    2017-02-01

    Serological prevalence of E. cuniculi infection was assessed in 183 rabbits from central Italy. In seropositive deceased rabbits, histopathological lesions were also evaluated. Sera from 118 rabbits from 6 intensive farms, 10 rabbits from 6 family farms, 16 rabbits from a zoo, 30 rabbits from 5 research laboratories and 9 pet rabbits from 9 different owners, were tested by an enzyme-linked immunosorbent assay. Data were statistically analysed. Tissue samples from brain and kidney of 10 deceased rabbits were formalin-fixed and subsequently analysed by histopathology and immunohistochemistry. Anti-E. cuniculi antibodies were found in 129/183 (70.5%) analysed sera. At statistical analysis, E. cuniculi seropositivity was significantly higher (prabbits. At histology, different degrees of pathological lesions were found in serological positive (9) deceased animals. In three rabbits deceased after showing neurological signs, the severity of the lesions was interpreted as a likely cause for their death. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Endotoxemia accelerates diaphragm dysfunction in ventilated rabbits.

    Science.gov (United States)

    Yang, Yi; Yu, Tao; Pan, Chun; Longhini, Federico; Liu, Ling; Huang, Yingzi; Guo, Fengmei; Qiu, Haibo

    2016-12-01

    Ventilators may induce diaphragm dysfunction, and most of the septic population who are admitted to the intensive care unit require mechanical ventilation. However, there is no evidence that sepsis accelerates the onset of ventilator-induced diaphragm dysfunction or affects the microcirculation. Our study investigated whether lipopolysaccharide (LPS)-induced endotoxemia accelerated diaphragm dysfunction in ventilated rabbits by evaluating microcirculation, lipid accumulation, and diaphragm contractility. After anesthesia and tracheostomy, 25 invasively monitored and mechanically ventilated New Zealand white rabbits were randomized to control (n = 5), controlled mechanical ventilation (CMV) (n = 5), pressure support ventilation (PSV; n = 5), CMV or PSV with LPS-induced endotoxemia (CMV-LPS and PSV-LPS, respectively; n = 5 for each). Rabbits were anesthetized and ventilated for 24 h, except the control rabbits (30 min). Diaphragmatic contractility was evaluated using neuromechanical and neuroventilatory efficiency. We evaluated the following at the end of the protocol: (1) diaphragm microcirculation; (2) lipid accumulation; and (3) diaphragm muscular fibers structure. Diaphragm contractility, microcirculation, lipid accumulation, and fiber structures were severely compromised in endotoxemic animals after 24 h compared to nonendotoxemic rabbits. Moreover, a slight but significant increase in lipid accumulation was observed in CMV and PSV groups compared with controls (P rabbits, affects the microcirculation, and results in diaphragmatic lipid accumulation and contractility impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Light colour preference of growing rabbits

    Directory of Open Access Journals (Sweden)

    Zsolt Szendrő

    2010-01-01

    Full Text Available The objective of the experiment was to evaluate the light colour preference of growing rabbits placed in a free-choice cage. The experiment was carried out on 128 Pannon White growing rabbits weaned at the age of 5 weeks and placed into blocks (2m2 of four cages. The rabbits could move freely among the four cages (0.5m2 each through swing doors. The cages differed only in the colour of the light applied (white, yellow, green or blue. The lighting schedule was 16L: 8D. From 6 until 10 weeks of age, infrared video recording was performed once a week (24 hours. The number of rabbits in each cage was counted every 15 minutes. Feed consumption was measured weekly. Between 6 and 10 weeks of age the rabbits significantly preferred white light (28.0%. The preference order was the following: yellow (26.3%, blue (23.4% and green (22.3% (P<0.001. No significant differences were recorded in the feed consumption among the cages. In conclusion, the cage preference of the rabbits was slightly affected by the light colour.

  5. Latent Viruses: A Space Travel Hazard??

    Science.gov (United States)

    Ling, P. D.; Peng, R. S.; Pierson, D.; Lednicky, J.; Butel, J. S.

    1999-01-01

    A major issue associated with long-duration space flight is the possibility of infectious disease causing an unacceptable medical risk to crew members. Our proposal is designed to gain information that addresses several issues outlined in the Immunology/Infectious disease critical path. The major hypothesis addressed is that space flight causes alterations in the immune system that may allow latent viruses which are endogenous in the human population to reactivate and shed to higher levels than normal which can affect the health of crew members during a long term space-flight mission. We will initially focus our studies on the human herpesviruses and human polyomaviruses which are important pathogens known to establish latent infections in the human population. Both primary infection and reactivation from latent infection with this group of viruses can cause a variety of illnesses that result in morbidity and occasionally mortality of infected individuals. Effective vaccines exist for only one of the eight known human herpesviruses and the vaccine itself can still reactivate from latent infection. Available antivirals are of limited use and are effective against only a few of the human herpesviruses. Although most individuals display little if any clinical consequences from latent infection, events which alter immune function such as immunosuppressive therapy following solid organ transplantation are known to increase the risk of developing complications as a result of latent virus reactivation. This proposal will measure both the frequency and magnitude of viral shedding and genome loads in the blood from humans participating in activities that serve as ground based models of space flight conditions. Our initial goal is to develop sensitive quantitative competitive PCR- based assays (QC-PCR) to detect the herpesvirus Epstein-Barr virus (EBV), and the polyomaviruses SV40, BKV, and JCV. Using these assays we will establish baseline patterns of viral genome load in

  6. On updating problems in latent semantic indexing

    Energy Technology Data Exchange (ETDEWEB)

    Simon, H.D. [Lawrence Berkeley National Lab., CA (United States); Zha, H. [Pennsylvania State Univ., University Park, PA (United States). Dept. of Computer Science and Engineering

    1997-11-01

    The authors develop new SVD-updating algorithms for three types of updating problems arising from Latent Semantic Indexing (LSI) for information retrieval to deal with rapidly changing text document collections. They also provide theoretical justification for using a reduced-dimension representation of the original document collection in the updating process. Numerical experiments using several standard text document collections show that the new algorithms give higher (interpolated) average precisions than the existing algorithms and the retrieval accuracy is comparable to that obtained using the complete document collection.

  7. Multilevel Latent Class Models with Dirichlet Mixing Distribution

    OpenAIRE

    Di, Chong-Zhi; Bandeen-Roche, Karen

    2011-01-01

    Latent class analysis (LCA) and latent class regression (LCR) are widely used for modeling multivariate categorical outcomes in social science and biomedical studies. Standard analyses assume data of different respondents to be mutually independent, excluding application of the methods to familial and other designs in which participants are clustered. In this paper, we consider multilevel latent class models, in which subpopulation mixing probabilities are treated as random effects that vary ...

  8. Latent mnemonic strengths are latent : A comment on Mickes, Wixted, and Wais

    NARCIS (Netherlands)

    Rouder, J.N.; Pratte, M.S.; Morey, R.D.

    2007-01-01

    Mickes, Wixted, and Wais (2007) proposed a simple test of latent strength variability in recognition memory. They asked participants to rate their confidence using either a 20-point or a 99-point strength scale and plotted distributions of the resulting ratings. They found 25% more variability in

  9. Infrared Spectroscopic Imaging of Latent Fingerprints and Associated Forensic Evidence

    OpenAIRE

    Chen, Tsoching; Schultz, Zachary D.; Levin, Ira W.

    2009-01-01

    Fingerprints reflecting a specific chemical history, such as exposure to explosives, are clearly distinguished from overlapping, and interfering latent fingerprints using infrared spectroscopic imaging techniques and multivariate analysis.

  10. A Framework for Reproducible Latent Fingerprint Enhancements.

    Science.gov (United States)

    Carasso, Alfred S

    2014-01-01

    Photoshop processing of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology.

  11. Latent heat of traffic moving from rest

    Science.gov (United States)

    Farzad Ahmadi, S.; Berrier, Austin S.; Doty, William M.; Greer, Pat G.; Habibi, Mohammad; Morgan, Hunter A.; Waterman, Josam H. C.; Abaid, Nicole; Boreyko, Jonathan B.

    2017-11-01

    Contrary to traditional thinking and driver intuition, here we show that there is no benefit to ground vehicles increasing their packing density at stoppages. By systematically controlling the packing density of vehicles queued at a traffic light on a Smart Road, drone footage revealed that the benefit of an initial increase in displacement for close-packed vehicles is completely offset by the lag time inherent to changing back into a ‘liquid phase’ when flow resumes. This lag is analogous to the thermodynamic concept of the latent heat of fusion, as the ‘temperature’ (kinetic energy) of the vehicles cannot increase until the traffic ‘melts’ into the liquid phase. These findings suggest that in situations where gridlock is not an issue, drivers should not decrease their spacing during stoppages in order to lessen the likelihood of collisions with no loss in flow efficiency. In contrast, motion capture experiments of a line of people walking from rest showed higher flow efficiency with increased packing densities, indicating that the importance of latent heat becomes trivial for slower moving systems.

  12. Performance of rabbits fed diets containing graded levels of ...

    African Journals Online (AJOL)

    Chinchilla x New Zealand white) weaned rabbits with average initial weights of 540g to evaluate the performance of rabbits fed diets containing graded ... Only ash content was affected by the processing method in the result of nutrient digestibility.

  13. Simple suture and anchor in rabbit hips

    Science.gov (United States)

    Garcia Filho, Fernando Cal; Guarniero, Roberto; de Godoy Júnior, Rui Maciel; Pereira, César Augusto Martins; Matos, Marcos Almeida; Garcia, Lucas Cortizo

    2012-01-01

    Objective Using biomechanical studies, this research aims to compare hip capsulorrhaphy in rabbits, carried out with two different techniques: capsulorrhaphy with simple sutures and with anchors. Method Thirteen New Zealand Albino (Oryctolaguscuniculus) male rabbits, twenty-six hip joints, were used. First, a pilot project was performed with three rabbits (six hip joints). This experiment consisted of ten rabbits divided into two groups: group 1 underwent capsulorrhaphy on both right and left hips with simple suture using polyglycolic acid absorbable thread, and group 2 underwent capsulorrhaphy with titanium anchors. After a four-week postoperative period, the animals were euthanized and the hip joints were frozen. On the same day of the biomechanical studies, after the hip joints were previously unfrozen, the following parameters were evaluated: rigidity, maximum force, maximum deformity and energy. Results There was no relevant statistical difference in rigidity, maximum force, maximum deformity and energy between the simple suture and anchor groups. Conclusion Through biomechanical analyses, using parameters of rigidity, maximum force, maximum deformity and energy, it has been shown that capsulorrhaphy with simple suture and with anchors has similar results in rabbit hip joints. Level of Evidence II, Prospective Comparative Study. PMID:24453618

  14. Rabbit meat processing: historical perspective to future directions

    OpenAIRE

    Petracci, Massimiliano; Cavani, Claudio

    2013-01-01

    In past centuries, because rabbits are relatively small, animals slaughtered for consumption were generally eaten immediately. However, since a single rabbit would offer little more product than could be consumed at one sitting, little effort was devoted to developing preserved rabbit products (such as salted or dried meat, sausages, etc.). For this reason, although there is a rich history of recipes using rabbit meat in the Mediterranean area, there are few traditional further-processed prod...

  15. A LATENT TRAIT MODEL FOR DICHOTOMOUS CHOICE DATA

    NARCIS (Netherlands)

    HOIJTINK, H

    1990-01-01

    The PARELLA model is a probabilistic parallelogram model that can be used for the measurement of latent attitudes or latent preferences. The data analyzed are the dichotomous responses of persons to stimuli, with a one (zero) indicating agreement (disagreement) with the content of the stimulus. The

  16. Prevalence and risk factors of latent Tuberculosis among ...

    African Journals Online (AJOL)

    Background: Latent Tuberculosis treatment is a key tuberculosis control intervention. Adolescents are a high risk group that is not routinely treated in low income countries. Knowledge of latent Tuberculosis (TB) burden among adolescents may influence policy. Objectives: We determined the prevalence and risk factors of ...

  17. Gene Variants Associated with Antisocial Behaviour: A Latent Variable Approach

    Science.gov (United States)

    Bentley, Mary Jane; Lin, Haiqun; Fernandez, Thomas V.; Lee, Maria; Yrigollen, Carolyn M.; Pakstis, Andrew J.; Katsovich, Liliya; Olds, David L.; Grigorenko, Elena L.; Leckman, James F.

    2013-01-01

    Objective: The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Methods: Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a…

  18. Spurious Latent Classes in the Mixture Rasch Model

    Science.gov (United States)

    Alexeev, Natalia; Templin, Jonathan; Cohen, Allan S.

    2011-01-01

    Mixture Rasch models have been used to study a number of psychometric issues such as goodness of fit, response strategy differences, strategy shifts, and multidimensionality. Although these models offer the potential for improving understanding of the latent variables being measured, under some conditions overextraction of latent classes may…

  19. Classification criteria of syndromes by latent variable models

    DEFF Research Database (Denmark)

    Petersen, Janne

    2010-01-01

    The thesis has two parts; one clinical part: studying the dimensions of human immunodeficiency virus associated lipodystrophy syndrome (HALS) by latent class models, and a more statistical part: investigating how to predict scores of latent variables so these can be used in subsequent regression...

  20. The Latent Variable Approach as Applied to Transitive Reasoning

    Science.gov (United States)

    Bouwmeester, Samantha; Vermunt, Jeroen K.; Sijtsma, Klaas

    2012-01-01

    We discuss the limitations of hypothesis testing using (quasi-) experiments in the study of cognitive development and suggest latent variable modeling as a viable alternative to experimentation. Latent variable models allow testing a theory as a whole, incorporating individual differences with respect to developmental processes or abilities in the…

  1. A Latent Class Approach to Estimating Test-Score Reliability

    Science.gov (United States)

    van der Ark, L. Andries; van der Palm, Daniel W.; Sijtsma, Klaas

    2011-01-01

    This study presents a general framework for single-administration reliability methods, such as Cronbach's alpha, Guttman's lambda-2, and method MS. This general framework was used to derive a new approach to estimating test-score reliability by means of the unrestricted latent class model. This new approach is the latent class reliability…

  2. Item Response Theory, Latent Classes and Rule Space.

    Science.gov (United States)

    1987-07-15

    1968) and Latent Class ( Lazarsfeld p.M 5 & Henry, 1968) will be discussed with respect to the demands of modern measurement theory and their...Paper presented at the 22nd International Congress of Psychology, Leipzig. Lazarsfeld , P. F. & Henry, N. W. (1968). Latent structure analysis. Boston

  3. Transforming Selected Concepts into Dimensions in Latent Semantic Analysis

    Science.gov (United States)

    Olmos, Ricardo; Jorge-Botana, Guillermo; León, José Antonio; Escudero, Inmaculada

    2014-01-01

    This study presents a new approach for transforming the latent representation derived from a Latent Semantic Analysis (LSA) space into one where dimensions have nonlatent meanings. These meanings are based on lexical descriptors, which are selected by the LSA user. The authors present three analyses that provide examples of the utility of this…

  4. Higher-Order Item Response Models for Hierarchical Latent Traits

    Science.gov (United States)

    Huang, Hung-Yu; Wang, Wen-Chung; Chen, Po-Hsi; Su, Chi-Ming

    2013-01-01

    Many latent traits in the human sciences have a hierarchical structure. This study aimed to develop a new class of higher order item response theory models for hierarchical latent traits that are flexible in accommodating both dichotomous and polytomous items, to estimate both item and person parameters jointly, to allow users to specify…

  5. The latent variable approach as applied to transitive reasoning

    NARCIS (Netherlands)

    Bouwmeester, S.; Vermunt, J.K.; Sijtsma, K.

    2012-01-01

    We discuss the limitations of hypothesis testing using (quasi-) experiments in the study of cognitive development and suggest latent variable modeling as a viable alternative to experimentation. Latent variable models allow testing a theory as a whole, incorporating individual differences with

  6. PROC LCA: A SAS Procedure for Latent Class Analysis

    Science.gov (United States)

    Lanza, Stephanie T.; Collins, Linda M.; Lemmon, David R.; Schafer, Joseph L.

    2007-01-01

    Latent class analysis (LCA) is a statistical method used to identify a set of discrete, mutually exclusive latent classes of individuals based on their responses to a set of observed categorical variables. In multiple-group LCA, both the measurement part and structural part of the model can vary across groups, and measurement invariance across…

  7. Early innate immunity determines outcome of Mycobacterium tuberculosis pulmonary infection in rabbits

    Science.gov (United States)

    2013-01-01

    Background Pulmonary infection of humans by Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), results in active disease in 5-10% of individuals, while asymptomatic latent Mtb infection (LTBI) is established in the remainder. The host immune responses that determine this differential outcome following Mtb infection are not fully understood. Using a rabbit model of pulmonary TB, we have shown that infection with the Mtb clinical isolate HN878 (a hyper-virulent W-Beijing lineage strain) leads to progressive cavitary disease similar to what is seen in humans with active TB. In contrast, infection with Mtb CDC1551 (a hyper-immunogenic clinical isolate) is efficiently controlled in rabbit lungs, with establishment of LTBI, which can be reactivated upon treatment with immune-suppressive drugs. We hypothesize that the initial interaction of Mtb with the cells of the host response in the lungs determine later outcome of infection. Results To test this hypothesis, we used our rabbit model of pulmonary TB and infected the animals with Mtb HN878 or CDC1551. At 3 hours, with similar lung bacillary loads, HN878 infection caused greater accumulation of mononuclear and polymorphonuclear leukocytes (PMN) in the lungs, compared to animals infected with CDC1551. Using whole-genome microarray gene expression analysis, we delineated the early transcriptional changes in the lungs of HN878- or CDC1551-infected rabbits at this time and compared them to the differential response at 4 weeks of Mtb-infection. Our gene network and pathway analysis showed that the most significantly differentially expressed genes involved in the host response to HN878, compared to CDC1551, at 3 hours of infection, were components of the inflammatory response and STAT1 activation, recruitment and activation of macrophages, PMN, and fMLP (N-formyl-Methionyl-Leucyl-Phenylalanine)-stimulation. At 4 weeks, the CDC1551 bacillary load was significantly lower and the granulomatous

  8. Spermatological Parameters of Extended Rabbit Semen in 5 ...

    African Journals Online (AJOL)

    USER

    These problems range from nutritional challenges to availability of assisted reproductive techniques, most especially artificial insemination (AI) technique. Despite the use of AI in the large rabbit farms of several European countries, rabbit AI has certainly not become a common practice in the rabbit meat producing areas of.

  9. Energy partitioning for growth by rabbits fed groundnut and stylo ...

    African Journals Online (AJOL)

    Forty eight crossbred (California X New Zealand White) rabbits were used to evaluate energy partitioning of rabbits fed forages supplemented with concentrate. The rabbits were randomly allocated to three treatments consisting of sole Stylosanthes hamata (stylo),sole Arachis hypogea (groundnut) haulms and 50:50 mixture ...

  10. Performance characteristics of Weaner rabbits fed Moringa oleifera ...

    African Journals Online (AJOL)

    This study was designed to investigate the utilization of Moringa oleifera (MO) and Moringa stenopetala (MS) by weaner rabbit. In a twelve week feeding trial, forty eight weaner rabbits of about five weeks old were allotted into three treatments with each treatment consisting of sixteen rabbits in a completely randomized ...

  11. Effect of genotype on growth traits of rabbits | Oke | International ...

    African Journals Online (AJOL)

    Genotype effect on growth traits of rabbits were investigated in a randomised complete block design using one hundred and twenty - 10-week-old breeding rabbits. The breeds of rabbits used were New Zealand white, Dutch, chinchilla and were characterized using body weight (BW), heart girth (HG), shoulder to tail (ST), ...

  12. Determination of the Tetramer-Dimer Equilibrium Constant of Rabbit ...

    African Journals Online (AJOL)

    ... derivatives of rabbit hemoglobin. The constant has been found to be the same for all the derivatives of rabbit hemoglobin, implying that the ligand bound on the heme has no significant effect on the tetramer-dimer dissociation of rabbit hemoglobin. African Journal of Educational Studies in Mathematics and Sciences Vol.

  13. Problems and prospects of rabbit production in Nigeria - a review ...

    African Journals Online (AJOL)

    It is apparent that in many areas in developing countries, rabbit production could be an effective means of converting forages and by-products into high quality animal protein for human consumption. The study provides a benchmark for the understanding of prospects of rabbit production in Nigeria. Keywords: Rabbit ...

  14. Effect of Cigarette Smoke on Rabbit Testicular Lipid Peroxidation ...

    African Journals Online (AJOL)

    The effect of cigarette smoke on oxidative status of liver and testis was evaluated. Three groups of male weaned rabbits (1.0 – 1.5kg) were used. Group 1, the basal control group consisted of 2 rabbits which were sacrificed immediately after one week acclimatization (week O). Group 2 – (S) group consisted of 6 rabbits.

  15. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY... Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which are... inspection shall be made, and all rabbits found to be, or which are suspected of being, affected with the...

  16. Performance and nutrient digestibility of rabbits fed urea treated ...

    African Journals Online (AJOL)

    The study was conducted to investigate the effect of varying levels of urea treated and untreated cowpea husk on the performance of weaner rabbits. Thirty-two mongrel weaner rabbits of both sexes, 6 – 8 weeks old with an average weight of 822g were randomly distributed to four dietary treatments with four rabbits per ...

  17. A Preliminary internet survey of pet rabbit owners’ characteristics

    Directory of Open Access Journals (Sweden)

    J.A. Oxley

    2015-12-01

    Full Text Available This study aimed to conduct a preliminary survey to investigate basic ownership factors, frequency of microchipping and insurance and views of pet rabbit owners  n these areas and general rabbit management. More specifically, we aimed to investigate whether owners possess insurance, whether their rabbits are microchipped, and owners’ views on the recommendations relating to rabbits (e.g. recommended enclosure sizes and the law. A questionnaire was designed and promulgated through social media sites and rabbit forums. A total of 1183 responses were received. Just over 29% of respondents sourced their rabbits through rescue centres. 73.9% (867/1174 of owners stated that they had no pet insurance for their rabbits. Concerning microchips, 78.3% (919/1173 of rabbits were not microchipped, while 21.7% (254/1173 were. This preliminary study found that the majority of individuals are of the opinion that the relevant law is insufficiently publicised. A more detailed study would be beneficial to investigate and provide further insight into rabbit owners and their views and concerns for rabbits. The results of such a study could help formulate rabbit-related information and guidelines which in turn could have a direct impact on pet rabbit welfare.

  18. General intravenous anesthesia for brachial plexus surgery in the rabbit.

    Science.gov (United States)

    Reichert, P; Rutowski, R; Kielbowicz, Z; Kuryszko, J; Kielbowicz, M

    2013-01-01

    The rabbit is a good experimental model for brachial plexus surgery. The risks of death during anesthesia were significantly greater in rabbits than cats or dogs. This article presents the protocol of injectable anesthesia for a short surgical procedure, safe for the rabbit patient and convenient for the surgeon.

  19. Performance and digestibility of weaner rabbits fed graded levels of ...

    African Journals Online (AJOL)

    Weaner crossbred rabbits were allocated to five treatment groups in a completely randomized design. The treatments consisted of 100, 75, 50 and 25% levels of soybean cheese waste/maize offal diet (SBW). 100% rabbit meal served as control. Each rabbit received chopped Bracharia decumbens hay ad libitum. Water was ...

  20. Amino acid and mineral composition of meat from rabbits ...

    African Journals Online (AJOL)

    Eighty one weaned composite breeds of rabbits (males and females) were randomly allotted to nine treatment groups with nine rabbits per treatment. Each treatment had three replicates with three rabbits per replicate. Processed tallow meal was included in the diets as a source of protein which was set at 16 % CP.

  1. Performance evaluation and nutrient digestibility of rabbits fed ...

    African Journals Online (AJOL)

    A total of 32 weaned rabbits (56 days old; 586 ± 60.31g body weight) were selected to investigate the effect of dietary growth promoters on the growth performance, nutrient digestibility and carcass characteristics of rabbits. The rabbits were randomly assigned to four dietary treatments (n = 8) including a basal diet (control), ...

  2. Hematology and Serum Biochemistry of Rabbits Fed Dried Sweet ...

    African Journals Online (AJOL)

    ... were within the normal range for rabbits. The sweet orange fruit pulp meal based diets were nutritionally adequate to meet rabbit requirements for accretion and safe consumption at 25% level of maize replacement. This shows that sweet orange fruit pulp meal is a possible feed resource for rabbit production.

  3. Multiphoton microscopic imaging of rabbit dorsal skin.

    Science.gov (United States)

    Zhu, Xiaoqin; Xu, Yahao; Hong, Zhipeng; Chen, Jing; Zhuo, Shuangmu; Chen, Jianxin

    2015-01-01

    Rabbits are often preferred to be experimental animals during the skin research. The visualizing and understanding the full-thickness structure of rabbit skin has significance in biology, medicine, and animal husbandry. In this study, multiphoton microscopy (MPM) was employed to examine the rabbit skin on the back, which was based on second harmonic generation and two-photon excited fluorescence. High-resolution images were achieved from the fresh, unfixed, and unstained tissues, showing detailed microstructure of the skin without the administration of exogenous contrast agents. The morphology and distribution of the main components of epidermis and dermis, such as keratin, collagen fibers, elastic fibers, and hair follicles, can be distinctly identified in MPM images. Since the changes in these components are tightly related to skin diseases and wound healing, the noninvasive nature of MPM enables it become a valuable tool in skin research for detecting and monitoring. © Wiley Periodicals, Inc.

  4. Ovarian lesions in 44 rabbits (Oryctolagus cuniculus)

    Science.gov (United States)

    BERTRAM, Christof Albert; KLOPFLEISCH, Robert; MÜLLER, Kerstin

    2017-01-01

    The clinical and pathological records of 44 domestic, female rabbits with an age ranging from 6–124 months (median age: 63.5 month) were assessed retrospectively for ovarian lesions. Included were all rabbits that underwent an ovariohysterectomy with a subsequent pathological examination of the genital tract between March 1997 and June 2016. Pathological examination revealed ovarian lesions in 12 of the 44 rabbits including follicular cysts (n=7), cystic rete ovarii (n=3), widespread ovarian necrosis with dystrophic calcification (n=2), ovarian adenoma (n=1). Clinical examination including radiographs only suggested ovarian disorders in two cases of ovarian necrosis with dystrophic calcification and in two cases of cystic rete ovarii. Clinical significance was only conclusive in a case of cystic rete ovarii. PMID:29057758

  5. Rabbit tissue model (RTM) harvesting technique.

    Science.gov (United States)

    Medina, Marelyn

    2002-01-01

    A method for creating a tissue model using a female rabbit for laparoscopic simulation exercises is described. The specimen is called a Rabbit Tissue Model (RTM). Dissection techniques are described for transforming the rabbit carcass into a small, compact unit that can be used for multiple training sessions. Preservation is accomplished by using saline and refrigeration. Only the animal trunk is used, with the rest of the animal carcass being discarded. Practice exercises are provided for using the preserved organs. Basic surgical skills, such as dissection, suturing, and knot tying, can be practiced on this model. In addition, the RTM can be used with any pelvic trainer that permits placement of larger practice specimens within its confines.

  6. Tweets clustering using latent semantic analysis

    Science.gov (United States)

    Rasidi, Norsuhaili Mahamed; Bakar, Sakhinah Abu; Razak, Fatimah Abdul

    2017-04-01

    Social media are becoming overloaded with information due to the increasing number of information feeds. Unlike other social media, Twitter users are allowed to broadcast a short message called as `tweet". In this study, we extract tweets related to MH370 for certain of time. In this paper, we present overview of our approach for tweets clustering to analyze the users' responses toward tragedy of MH370. The tweets were clustered based on the frequency of terms obtained from the classification process. The method we used for the text classification is Latent Semantic Analysis. As a result, there are two types of tweets that response to MH370 tragedy which is emotional and non-emotional. We show some of our initial results to demonstrate the effectiveness of our approach.

  7. Endogenous Opioid-Masked Latent Pain Sensitization

    DEFF Research Database (Denmark)

    Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B

    2015-01-01

    UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development...... of chronic pain, but LS has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous mild heat injury (MHI) we demonstrated a dose-dependent reinstatement of pain sensitization, assessed as primary (P ... naloxone dose (0.021 mg/kg). However, while LS was consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This difference is likely due to selection bias since the C57BL/6 mouse strain exhibits markedly enhanced pain sensitivity in assays of acute thermal nociception. Future...

  8. Using existing questionnaires in latent class analysis

    DEFF Research Database (Denmark)

    Nielsen, Anne Molgaard; Vach, Werner; Kent, Peter

    2016-01-01

    BACKGROUND: Latent class analysis (LCA) is increasingly being used in health research, but optimal approaches to handling complex clinical data are unclear. One issue is that commonly used questionnaires are multidimensional, but expressed as summary scores. Using the example of low back pain (LBP......), the aim of this study was to explore and descriptively compare the application of LCA when using questionnaire summary scores and when using single items to subgrouping of patients based on multidimensional data. MATERIALS AND METHODS: Baseline data from 928 LBP patients in an observational study were....... The resulting subgroups were descriptively compared using statistical measures and clinical interpretability. RESULTS: For each health domain, the preferred model solution ranged from five to seven subgroups for the summary-score strategy and seven to eight subgroups for the single-item strategy...

  9. Latent factors and route choice behaviour

    DEFF Research Database (Denmark)

    Prato, Carlo Giacomo

    A behaviourally realistic description of the route choice process should consider variables that are both observable, such as travel time and cost, and unobservable, such as attitudes, perceptions, spatial abilities and network knowledge. This manuscript focuses on automotive route choice behaviour...... by proposing a methodology for collecting and analyzing behavioural indicators and modelling route choices of individuals driving habitually from home to their workplace. A web-based survey was designed to collect attitudinal data and observed route choices among faculty and staff members of Turin Polytechnic....... A reliable dataset was prepared through measures of internal consistency and sampling adequacy, and data were analyzed with a proper application of factor analysis to the route choice context. For the dataset obtained from the survey, six latent constructs affecting driver behaviour were extracted and scores...

  10. Learning Latent Structure in Complex Networks

    DEFF Research Database (Denmark)

    Mørup, Morten; Hansen, Lars Kai

    Latent structure in complex networks, e.g., in the form of community structure, can help understand network dynamics, identify heterogeneities in network properties, and predict ‘missing’ links. While most community detection algorithms are based on optimizing heuristic clustering objectives...... prediction performance of the learning based approaches and other widely used link prediction approaches in 14 networks ranging from medium size to large networks with more than a million nodes. While link prediction is typically well above chance for all networks, we find that the learning based mixed...... membership stochastic block model of Airoldi et al., performs well and often best in our experiments. The added complexity of the LD model improves link predictions for four of the 14 networks....

  11. Latent profile approach to duration of stalking.

    Science.gov (United States)

    Björklund, Katja; Häkkänen-Nyholm, Helinä; Sheridan, Lorraine; Roberts, Karl; Tolvanen, Asko

    2010-07-01

    Stalking behavior and victim-stalker relationship are often the principal known factors in a stalking case. Thus, they are of great importance when trying to identify factors contributing to stalking duration. The present study aims to identify distinct subgroups of stalking victims based on measures of behavioral stalking dimensions. These victim subgroups, stalking dimensions, and victim-stalker relationship are examined in relation to stalking duration. Using a sample of 137 university students, latent profile analysis (LPA) revealed five distinct victim subgroups based on stalker behavior dimensions: surveillance, low-profile, social lurker, wide scope, and baseline stalkers. The subgroups were significantly related to stalking duration and explained a considerable amount of the variance along with the stalking dimensions and victim-stalker relationship. Connections to stalking literature and utility of person-orientated methods in stalking research are discussed.

  12. Pretreatment of Latent Prints for Laser Development.

    Science.gov (United States)

    Menzel, E R

    1989-06-01

    The pretreatment procedures for laser detection of latent fingerprints is reviewed. The general features of laser detection and the operational aspects of the examination of physical evidence for laser fingerprint detection are enumerated in the initial sections. The literature review is divided into various pretreatment approaches. Cited studies prior to 1981 are primarily concerned with the demonstration of the viability of laser fingerprint detection, whereas work post-1981 addresses issues of compatibility with the traditional methods of fingerprint development, examination of difficult surfaces, and the routine implementation of laser detection by law enforcement agencies. Related topics of research, review articles, conference reports, case examinations, the research support climate, and future trends are also briefly addressed. Copyright © 1989 Central Police University.

  13. Classification criteria of syndromes by latent variable models

    DEFF Research Database (Denmark)

    Petersen, Janne

    2010-01-01

    analyses. Part 1: HALS engages different phenotypic changes of peripheral lipoatrophy and central lipohypertrophy.  There are several different definitions of HALS and no consensus on the number of phenotypes. Many of the definitions consist of counting fulfilled criteria on markers and do not include......, although this is often desired. I have proposed a new method for predicting class membership that, in contrast to methods based on posterior probabilities of class membership, yields consistent estimates when regressed on explanatory variables in a subsequent analysis. There are four different basic models...... within latent variable models: factor analysis, latent class analysis, latent profile analysis and latent trait analysis. I have given a general overview of how to predict scores of latent variables so these can be used in subsequent regression models. Two different principles of predicting scores...

  14. Latent Virus Reactivation in Space Shuttle Astronauts

    Science.gov (United States)

    Mehta, S. K.; Crucian, B. E.; Stowe, R. P.; Sams, C.; Castro, V. A.; Pierson, D. L.

    2011-01-01

    Latent virus reactivation was measured in 17 astronauts (16 male and 1 female) before, during, and after short-duration Space Shuttle missions. Blood, urine, and saliva samples were collected 2-4 months before launch, 10 days before launch (L-10), 2-3 hours after landing (R+0), 3 days after landing (R+14), and 120 days after landing (R+120). Epstein-Barr virus (EBV) DNA was measured in these samples by quantitative polymerase chain reaction. Varicella-zoster virus (VZV) DNA was measured in the 381 saliva samples and cytomegalovirus (CMV) DNA in the 66 urine samples collected from these subjects. Fourteen astronauts shed EBV DNA in 21% of their saliva samples before, during, and after flight, and 7 astronauts shed VZV in 7.4% of their samples during and after flight. It was interesting that shedding of both EBV and VZV increased during the flight phase relative to before or after flight. In the case of CMV, 32% of urine samples from 8 subjects contained DNA of this virus. In normal healthy control subjects, EBV shedding was found in 3% and VZV and CMV were found in less than 1% of the samples. The circadian rhythm of salivary cortisol measured before, during, and after space flight did not show any significant difference between flight phases. These data show that increased reactivation of latent herpes viruses may be associated with decreased immune system function, which has been reported in earlier studies as well as in these same subjects (data not reported here).

  15. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement

    NARCIS (Netherlands)

    Mack, U.; Migliori, G. B.; Sester, M.; Rieder, H. L.; Ehlers, S.; Goletti, D.; Bossink, A.; Magdorf, K.; Hölscher, C.; Kampmann, B.; Arend, S. M.; Detjen, A.; Bothamley, G.; Zellweger, J. P.; Milburn, H.; Diel, R.; Ravn, P.; Cobelens, F.; Cardona, P. J.; Kan, B.; Solovic, I.; Duarte, R.; Cirillo, D. M.

    2009-01-01

    Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected

  16. Rabbit model for Chlamydia pneumoniae infection.

    Science.gov (United States)

    Fong, I W; Chiu, B; Viira, E; Fong, M W; Jang, D; Mahony, J

    1997-01-01

    A rabbit model was established for Chlamydia pneumoniae infection that may be helpful to understand the pathogenesis of disease in humans. Twelve, pathogen-free, 1-month-old New Zealand White rabbits were inoculated with 1.0 x 10(7) to 5.0 x 10(7) CFU of purified C. pneumoniae (ATCC strain VR 1310) via the nasopharynx (1 rabbit died immediately postinoculation, and 11 were available for study). Five controls were inoculated with the carrier buffer. Ten of the 11 study rabbits demonstrated serological evidence of acute infection (immunoglobulin G antibodies, 1:8 to > 1:16), with the weakest response at 7 days and the strongest response at 28 days, whereas none of the controls showed any seroconversion. Study animals were sacrificed in batches of three, on days 7, 14, 21, and 28, but controls were sacrificed on days 7 and 28. Two-thirds of the animals demonstrated evidence of bronchiolitis and pneumonia on days 7 and 14 and resolution by day 21. Two study rabbits demonstrated, on histology, early and intermediate lesions of atherosclerosis: one animal (day 7) showed the accumulation of foamy macrophages (fatty streak) in the arch of the aorta, and the other animal (day 14) showed spindle cell proliferation of smooth muscle cells (intermediate lesion). Focal periaortitis was seen in the same animal (day 7). C. pneumoniae elementary bodies were demonstrated by immunocytochemical stain in the lungs (n = 2), liver (n = 3), spleen (n = 5), and aorta (n = 2), one of which corresponded to the intermediate lesion. C. pneumoniae was cultured from the lungs (n = 2), liver (n = 2), spleen (n = 2), and aortic arch (n = 1). All histopathological, immunocytochemical, and cultural studies were negative in the controls. Hence, the rabbit provides a useful animal model for the study of C. pneumoniae infection and its complications, particularly atherosclerosis.

  17. The Genetic Structure of Domestic Rabbits

    Science.gov (United States)

    Carneiro, Miguel; Afonso, Sandra; Geraldes, Armando; Garreau, Hervé; Bolet, Gerard; Boucher, Samuel; Tircazes, Aurélie; Queney, Guillaume; Nachman, Michael W.; Ferrand, Nuno

    2011-01-01

    Understanding the genetic structure of domestic species provides a window into the process of domestication and motivates the design of studies aimed at making links between genotype and phenotype. Rabbits exhibit exceptional phenotypic diversity, are of great commercial value, and serve as important animal models in biomedical research. Here, we provide the first comprehensive survey of nucleotide polymorphism and linkage disequilibrium (LD) within and among rabbit breeds. We resequenced 16 genomic regions in population samples of both wild and domestic rabbits and additional 35 fragments in 150 rabbits representing six commonly used breeds. Patterns of genetic variation suggest a single origin of domestication in wild populations from France, supporting historical records that place rabbit domestication in French monasteries. Levels of nucleotide diversity both within and among breeds were ∼0.2%, but only 60% of the diversity present in wild populations from France was captured by domestic rabbits. Despite the recent origin of most breeds, levels of population differentiation were high (FST = 17.9%), but the majority of polymorphisms were shared and thus transferable among breeds. Coalescent simulations suggest that domestication began with a small founding population of less than 1,200 individuals. Taking into account the complex demographic history of domestication with two successive bottlenecks, two loci showed deviations that were consistent with artificial selection, including GPC4, which is known to be associated with growth rates in humans. Levels of diversity were not significantly different between autosomal and X-linked loci, providing no evidence for differential contributions of males and females to the domesticated gene pool. The structure of LD differed substantially within and among breeds. Within breeds, LD extends over large genomic distances. Markers separated by 400 kb typically showed r2 higher than 0.2, and some LD extended up to 3,200 kb

  18. A Probability Distribution over Latent Causes, in the Orbitofrontal Cortex.

    Science.gov (United States)

    Chan, Stephanie C Y; Niv, Yael; Norman, Kenneth A

    2016-07-27

    The orbitofrontal cortex (OFC) has been implicated in both the representation of "state," in studies of reinforcement learning and decision making, and also in the representation of "schemas," in studies of episodic memory. Both of these cognitive constructs require a similar inference about the underlying situation or "latent cause" that generates our observations at any given time. The statistically optimal solution to this inference problem is to use Bayes' rule to compute a posterior probability distribution over latent causes. To test whether such a posterior probability distribution is represented in the OFC, we tasked human participants with inferring a probability distribution over four possible latent causes, based on their observations. Using fMRI pattern similarity analyses, we found that BOLD activity in the OFC is best explained as representing the (log-transformed) posterior distribution over latent causes. Furthermore, this pattern explained OFC activity better than other task-relevant alternatives, such as the most probable latent cause, the most recent observation, or the uncertainty over latent causes. Our world is governed by hidden (latent) causes that we cannot observe, but which generate the observations we see. A range of high-level cognitive processes require inference of a probability distribution (or "belief distribution") over the possible latent causes that might be generating our current observations. This is true for reinforcement learning and decision making (where the latent cause comprises the true "state" of the task), and for episodic memory (where memories are believed to be organized by the inferred situation or "schema"). Using fMRI, we show that this belief distribution over latent causes is encoded in patterns of brain activity in the orbitofrontal cortex, an area that has been separately implicated in the representations of both states and schemas. Copyright © 2016 the authors 0270-6474/16/367817-12$15.00/0.

  19. Sensitivity of rabbit fibrochondrocytes to mycoplasmas

    Directory of Open Access Journals (Sweden)

    Nascimento Carlos Manuel de Oliveira

    2002-01-01

    Full Text Available Primary cell culture from rabbit meniscus (fibrochondrocytes-FcrC was infected for 24 hours with different inocula (10² to 10(7 Colony Forming Units-CFU of Mycoplasma hominis PG-21, M. pneumoniae FH and 1428 or M. arthritidis PG-6. The severity of the different obtained cytophatic effects-CPE was inoculum, Mycoplasma species and strain dependant. These bacteria were recovered from all infected FcrC and the SP4 medium for mycoplasmas also caused toxic effect on the FcrC. It was concluded that rabbit fibrochondrocytes were sensitive to mycoplasma infection, as well as to the SP4 mycoplasma medium.

  20. BIORESORBABLE POLYMERIC MENISCAL PROSTHESIS: STUDY IN RABBITS

    OpenAIRE

    Cardoso, Tulio Pereira; de Rezende Duek, Eliana Aparecida; Amatuzzi,Marco Martins; Caetano, Edie Benedito

    2010-01-01

    Objective: To induce growth of a neomeniscus into the pores of a prosthesis in order to protect the knee joint cartilage. Methods: 70 knees of 35 New Zealand rabbits were operated. The rabbits were five to seven months old, weighed 2 to 3.8 kilograms, and 22 were male and 13 were female. Each animal underwent medial meniscectomy in both knees during a single operation. A bioabsorbable polymeric meniscal prosthesis composed of 70% polydioxanone and 30% L-lactic acid polymer was implanted in on...

  1. Ultrastructure of Reissner's membrane in the rabbit

    DEFF Research Database (Denmark)

    Qvortrup, K; Rostgaard, J; Bretlau, P

    1994-01-01

    The ultrastructure of Reissner's membrane in the rabbit is described following vascular perfusion-fixation of live, anesthetized and artificially respirated healthy animals. A new and improved technique of fixation is employed that includes a pressure feedback controlled peristaltic pump and an o......The ultrastructure of Reissner's membrane in the rabbit is described following vascular perfusion-fixation of live, anesthetized and artificially respirated healthy animals. A new and improved technique of fixation is employed that includes a pressure feedback controlled peristaltic pump...

  2. Trichostatin A (TSA) improves the development of rabbit-rabbit intraspecies cloned embryos, but not rabbit-human interspecies cloned embryos.

    Science.gov (United States)

    Shi, Li-Hong; Miao, Yi-Liang; Ouyang, Ying-Chun; Huang, Jun-Cheng; Lei, Zi-Li; Yang, Ji-Wen; Han, Zhi-Ming; Song, Xiang-Fen; Sun, Qing-Yuan; Chen, Da-Yuan

    2008-03-01

    The interspecies somatic cell nuclear transfer (iSCNT) technique for therapeutic cloning gives great promise for treatment of many human diseases. However, the incomplete nuclear reprogramming and the low blastocyst rate of iSCNT are still big problems. Herein, we observed the effect of TSA on the development of rabbit-rabbit intraspecies and rabbit-human interspecies cloned embryos. After treatment with TSA for 6 hr during activation, we found that the blastocyst rate of rabbit-rabbit cloned embryos was more than two times higher than that of untreated embryos; however, the blastocyst rate of TSA-treated rabbit-human interspecies cloned embryos decreased. We also found evident time-dependent histone deacetylation-reacetylation changes in rabbit-rabbit cloned embryos, but not in rabbit-human cloned embryos from fusion to 6 hr after activation. Our results suggest that TSA-treatment does not improve blastocyst development of rabbit-human iSCNT embryos and that abnormal histone deacetylation-reacetylation changes in iSCNT embryos may account for their poor blastocyst development. (c) 2008 Wiley-Liss, Inc.

  3. Assessing Trust and Effectiveness in Virtual Teams: Latent Growth Curve and Latent Change Score Models

    Directory of Open Access Journals (Sweden)

    Michael D. Coovert

    2017-08-01

    Full Text Available Trust plays a central role in the effectiveness of work groups and teams. This is the case for both face-to-face and virtual teams. Yet little is known about the development of trust in virtual teams. We examined cognitive and affective trust and their relationship to team effectiveness as reflected through satisfaction with one’s team and task performance. Latent growth curve analysis reveals both trust types start at a significant level with individual differences in that initial level. Cognitive trust follows a linear growth pattern while affective trust is overall non-linear, but becomes linear once established. Latent change score models are utilized to examine change in trust and also its relationship with satisfaction with the team and team performance. In examining only change in trust and its relationship to satisfaction there appears to be a straightforward influence of trust on satisfaction and satisfaction on trust. However, when incorporated into a bivariate coupling latent change model the dynamics of the relationship are revealed. A similar pattern holds for trust and task performance; however, in the bivariate coupling change model a more parsimonious representation is preferred.

  4. Data on the interexaminer variation of minutia markup on latent fingerprints.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2016-09-01

    The data in this article supports the research paper entitled "Interexaminer variation of minutia markup on latent fingerprints" [1]. The data in this article describes the variability in minutia markup during both analysis of the latents and comparison between latents and exemplars. The data was collected in the "White Box Latent Print Examiner Study," in which each of 170 volunteer latent print examiners provided detailed markup documenting their examinations of latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. Each examiner examined 22 latent-exemplar pairs; an average of 12 examiners marked each latent.

  5. Data on the interexaminer variation of minutia markup on latent fingerprints

    Directory of Open Access Journals (Sweden)

    Bradford T. Ulery

    2016-09-01

    Full Text Available The data in this article supports the research paper entitled “Interexaminer variation of minutia markup on latent fingerprints” [1]. The data in this article describes the variability in minutia markup during both analysis of the latents and comparison between latents and exemplars. The data was collected in the “White Box Latent Print Examiner Study,” in which each of 170 volunteer latent print examiners provided detailed markup documenting their examinations of latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. Each examiner examined 22 latent-exemplar pairs; an average of 12 examiners marked each latent.

  6. Possible interaction between myxomatosis and calicivirosis related to rabbit haemorrhagic disease affecting the European rabbit.

    Science.gov (United States)

    Marchandeau, S; Bertagnoli, S; Peralta, B; Boucraut-Baralon, C; Letty, J; Reitz, F

    2004-11-06

    Serological data on myxoma virus, rabbit haemorrhagic disease (RHD) virus and RHD-like viruses in juvenile rabbits (Oryctolagus cuniculus) trapped in 1995, 1996 and 1997 in two areas of France were analysed. For each disease, the effects of bodyweight, year, month and seropositivity for the other disease were modelled by using logistic regressions. In one area, a model including RHD seropositivity was selected to explain the myxoma virus seropositivity. Models including myxoma virus seropositivity were selected to explain the RHD seropositivity in both areas, and the odds of a rabbit being seropositive to both viruses were 5.1 and 8.4 times higher than the odds of a rabbit being seronegative to myxoma virus and seropositive to RHD. The year and bodyweight had significant effects for myxomatosis in one area and for RHD in both areas.

  7. Tropical Gravity Wave Momentum Fluxes and Latent Heating Distributions

    Science.gov (United States)

    Geller, Marvin A.; Zhou, Tiehan; Love, Peter T.

    2015-01-01

    Recent satellite determinations of global distributions of absolute gravity wave (GW) momentum fluxes in the lower stratosphere show maxima over the summer subtropical continents and little evidence of GW momentum fluxes associated with the intertropical convergence zone (ITCZ). This seems to be at odds with parameterizations forGWmomentum fluxes, where the source is a function of latent heating rates, which are largest in the region of the ITCZ in terms of monthly averages. The authors have examined global distributions of atmospheric latent heating, cloud-top-pressure altitudes, and lower-stratosphere absolute GW momentum fluxes and have found that monthly averages of the lower-stratosphere GW momentum fluxes more closely resemble the monthly mean cloud-top altitudes rather than the monthly mean rates of latent heating. These regions of highest cloud-top altitudes occur when rates of latent heating are largest on the time scale of cloud growth. This, plus previously published studies, suggests that convective sources for stratospheric GW momentum fluxes, being a function of the rate of latent heating, will require either a climate model to correctly model this rate of latent heating or some ad hoc adjustments to account for shortcomings in a climate model's land-sea differences in convective latent heating.

  8. Characterization of Pasteurella multocida involved in rabbit infections

    DEFF Research Database (Denmark)

    Massacci, Francesca Romana; Magistrali, Chiara Francesca; Cucco, Lucilla

    2018-01-01

    In rabbit, P. multocida is considered a predominant pathogenic agent; despite this, few data on the molecular epidemiology are available so far. The aim of this work was to characterize P. multocida isolates from rabbit affected by various diseases in Italy. Comparison was made to reference strains...... belonged to the LPS genotypes 3 (22/39) or 6 (17/39). The clonal relationships of the Italian strains from rabbit had similarity to previously reported rabbit isolates that belonged to ST9, ST74, ST204 and ST206, however, they differed from other rabbit references strains that belonged to six other STs....... In particular, ST9 with capsular type F has been previously reported from diseased rabbit in Czech Republic and ST74 has been observed for older rabbit isolates. ST50 has probably been reported from Spain. ST9 and ST50 have previously also been reported from birds and pig, respectively, whereas ST74 has...

  9. An individual-based model of rabbit viral haemorrhagic disease on European wild rabbits (Oryctolagus cuniculus)

    Science.gov (United States)

    Fa, John E.; Sharples, Colin M.; Bell, Diana J.; DeAngelis, Donald L.

    2001-01-01

    We developed an individual-based model of Rabbit Viral Hemorrhagic Disease (RVHD) for European wild rabbits (Oryctolagus cuniculus L.), representing up to 1000 rabbits in four hectares. Model output for productivity and recruitment matched published values. The disease was density-dependent and virulence affected outcome. Strains that caused death after several days produced greater overall mortality than strains in which rabbits either died or recovered very quickly. Disease effect also depended on time of year. We also elaborated a larger scale model representing 25 km2 and 100,000+ rabbits, split into a number of grid-squares. This was a more traditional model that did not represent individual rabbits, but employed a system of dynamic equations for each grid-square. Disease spread depended on probability of transmission between neighboring grid-squares. Potential recovery from a major population crash caused by the disease relied on disease virulence and frequency of recurrence. The model's dependence on probability of disease transmission between grid-squares suggests the way that the model represents the spatial distribution of the population affects simulation. Although data on RVHD in Europe are lacking, our models provide a basis for describing the disease in realistic detail and for assessing influence of various social and spatial factors on spread.

  10. Strategies for rearing of rabbit does

    NARCIS (Netherlands)

    Rommers, J.M.

    2003-01-01

    This thesis describes the effects of different rearing strategies for young rabbit does on body development and reproduction performance. In current rearing, does are often fed to appetite from weaning to first insemination. First insemination is applied when 75 to 80% of mature body weight (BW) is

  11. Eyeblink conditioning in the developing rabbit.

    Science.gov (United States)

    Brown, Kevin L; Woodruff-Pak, Diana S

    2012-05-01

    Eyeblink classical conditioning in pre-weanling rabbits was examined in the present study. Using a custom lightweight headpiece and restrainer, New Zealand white littermates were trained once daily in 400 ms delay eyeblink classical conditioning from postnatal days (PD) 17-21 or PD 24-28. These ages were chosen because eyeblink conditioning emerges gradually over PD 17-24 in rats [Stanton et al., (1992) Behavioral Neuroscience, 106(4):657-665], another altricial species with neurodevelopmental features similar to those of rabbits. Consistent with well-established findings in rats, rabbits trained from PD 24-28 showed greater conditioning relative to littermates trained from PD 17-21. Both age groups displayed poor retention of eyeblink conditioning at retraining 1 month after acquisition. These findings are the first to demonstrate eyeblink conditioning in the developing rabbit. With further characterization of optimal conditioning parameters, this preparation may have applications to neurodevelopmental disease models as well as research exploring the ontogeny of memory. Copyright © 2011 Wiley Periodicals, Inc.

  12. Enhanced Phenylephrine Contractions in Rabbit Carotid Arteries ...

    African Journals Online (AJOL)

    Carotid arteries were isolated from rabbits and cut into 2mm rings, suspended in 20ml organ baths and bubbled with 95% O2, 5% CO2 and isometric ... There were no significant differences in PE contractions following exposure to intact erythrocytes and ghosts from subjects with different Hb genotypes; however, exposure ...

  13. ALANINE - VALINE DYNAMICS IN PREGNANT RABBITS

    African Journals Online (AJOL)

    USER

    [15N]-alanine and [15N]–valine dynamics were studied in 29 -30 days pregnant New-Zealand rabbits. Over the experimental period, there was no detectable significant difference of mean ± SD of alanine concentrations within the sampling intervals in maternal, umbilical venous and arterial blood samples suggesting that ...

  14. Measures For Achieving Sustainable Rabbit Production In ...

    African Journals Online (AJOL)

    A study was conducted to ascertain ways of achieving sustainable rabbits production in Ogba/Egbema/Ndoni Local Government Area of Rivers State. The study population involved 120 respondents comprising 40 students and 80 farmers. Two sets of structured questionnaire designed with a 4-point Likert type rating scale ...

  15. Postanaesthetic tracheal strictures in three rabbits.

    Science.gov (United States)

    Grint, N J; Sayers, I R; Cecchi, R; Harley, R; Day, M J

    2006-07-01

    Within an 11-day period, three rabbits were anaesthetized for neutering. All were endotracheally intubated with 12 cm long, 2.5 mm (inner diameter [ID]) polyvinylchloride (PVC) tubes. All rabbits developed clinical signs of dyspnoea and upper respiratory tract obstruction, 17-21 days later. One rabbit was found dead; the other two were treated, but one was euthanized and one died. At necropsy examination, focal chronic inflammation and significant localized narrowing of the tracheal lumen was found in all cases. The affected sites corresponded to the position of the bevel of the endotracheal tube (ETT) during anaesthesia. Histopathology could not differentiate between a traumatic or chemical cause for the narrowing. Possible causes include trauma by the bevel of the ETT when turning the rabbit or preparing the surgical site or a chemical burn from incorrect disinfection or inadequate rinsing of the tubes. Iatrogenic tracheitis should be considered as a cause of dyspnoea, when clinical signs arise 2-3 weeks after anaesthesia.

  16. Ficus mucoso and Senna occidentalis in rabbits.

    African Journals Online (AJOL)

    Rev Olaleye

    ABSTRACT: A total of 20 domestic rabbits divided into 4 groups of 5 animals per group were used in this study to assess the haematinic potencies of the aqueous crude extracts of Ficus mucoso and Senna occidentalis and this was then compared with that of a proprietary haematinic, Haematopan B12®. Group A animals ...

  17. Muscle weakness causes joint degeneration in rabbits.

    Science.gov (United States)

    Rehan Youssef, A; Longino, D; Seerattan, R; Leonard, T; Herzog, W

    2009-09-01

    The objective of this study was to investigate the effects of botulinum toxin type-A (BTX-A) induced quadriceps weakness on micro-structural changes in knee cartilage of New Zealand White (NZW) rabbits. Fifteen rabbits were divided randomly into an experimental and a sham control group. Each group received a unilateral single quadriceps muscle injection either with saline (sham control; n=4) or BTX-A (experimental; n=11). BTX-A injection produced significant quadriceps muscle weakness (Pmuscle mass (Pknee cartilage, assessed with the Mankin grading system, were the same for the injected and non-injected hind limbs of the experimental group animals. Sham injection had no effect on joint degeneration but all control animals showed some degenerative changes in the knee. Degenerative changes of the retro-patellar cartilage were more severe in the experimental compared to sham control group rabbits (P0.05). Quadriceps muscle weakness caused increased degeneration in the retro-patellar cartilage of NZW rabbits, providing evidence that muscle weakness might be a risk factor for the onset and progression of osteoarthritis (OA). Future work needs to delineate whether muscle weakness directly affects joint degeneration, or if changes in function and movement execution associated with muscle weakness are responsible for the increased rate of OA onset and progression observed here.

  18. Ultrastructural researches on rabbit myxomatosis. Lymphnodal lesions.

    Science.gov (United States)

    Marcato, P S; Simoni, P

    1977-07-01

    Ultrastructural examination of head and neck lymph nodes in rabbits with spontaneous subacute myxomatosis showed fusion of immature reticuloendothelial cells which lead to the formation of polykarocytes. There was no ultrastructural evidence of viral infection of these polykaryocytes. Histiosyncytial lymphadenitis can be considered a specific lesion of myxomatosis.

  19. Immunostimulant Effect of Egyptian Propolis in Rabbits

    Science.gov (United States)

    Nassar, Somya A.; Mohamed, Amira H.; Soufy, Hamdy; Nasr, Soad M.; Mahran, K. M.

    2012-01-01

    The present experiment was conducted to study the effect of ethanolic extract of Egyptian propolis given alone or in combination with inactivated Pasteurella multocida vaccine on rabbits challenged with a virulent strain of Pasteurella multocida. Fifty-six New-Zealand rabbits, 6–8 weeks old and non-vaccinated against pasteurellosis, were randomly divided into eight equal groups. The first group was kept as a control for the experiment. The other groups received different treatments with propolis extract, inactivated vaccine, or both. The experiment continued for seven weeks during which clinical signs, body weight, and mortality rate were monitored, and blood samples were collected weekly for evaluating the leukogram, serum biochemistry, and immune response in all groups of animals. At the end of the seventh week, the animals were subjected to challenge with a virulent strain of Pasteurella multocida. Two weeks later, tissue specimens were collected from different organs for histopathological examination. Results showed that rabbits of the groups treated with both propolis and the vaccine by different routes appeared healthy after challenge. It has been concluded that alcoholic extract of propolis administrated in combination with inactivated Pasteurella multocida vaccine has no adverse effects on the general health conditions and enhances immune response in rabbits. PMID:22654648

  20. Immunostimulant Effect of Egyptian Propolis in Rabbits

    Directory of Open Access Journals (Sweden)

    Somya A. Nassar

    2012-01-01

    Full Text Available The present experiment was conducted to study the effect of ethanolic extract of Egyptian propolis given alone or in combination with inactivated Pasteurella multocida vaccine on rabbits challenged with a virulent strain of Pasteurella multocida. Fifty-six New-Zealand rabbits, 6–8 weeks old and non-vaccinated against pasteurellosis, were randomly divided into eight equal groups. The first group was kept as a control for the experiment. The other groups received different treatments with propolis extract, inactivated vaccine, or both. The experiment continued for seven weeks during which clinical signs, body weight, and mortality rate were monitored, and blood samples were collected weekly for evaluating the leukogram, serum biochemistry, and immune response in all groups of animals. At the end of the seventh week, the animals were subjected to challenge with a virulent strain of Pasteurella multocida. Two weeks later, tissue specimens were collected from different organs for histopathological examination. Results showed that rabbits of the groups treated with both propolis and the vaccine by different routes appeared healthy after challenge. It has been concluded that alcoholic extract of propolis administrated in combination with inactivated Pasteurella multocida vaccine has no adverse effects on the general health conditions and enhances immune response in rabbits.

  1. histopathological changes in female rabbits adminstered

    African Journals Online (AJOL)

    SWEET

    2016-03-23

    Mar 23, 2016 ... generalised cell necrosis and erosion of the villi of the small intestine. All the rabbits that survived gained weight, which is .... photometer, (AAS, Unicam Solar 969 - Unicam), (Haswell, 1991). Phytochemical screening ..... Haswell SJ (1991). Atomic Absorption Spectrometry; Theory, Design and Applications.

  2. International Conference on Immunogenetics of the Rabbit.

    Science.gov (United States)

    1983-12-09

    crowded cell cultures and is removed by extensive dialysis of the CCSup. We concluded that the GM present in rabbit lymphoid cell cultures maintained in...inbred species. We were confronted with the expected marked decline in fertility and fecundity, but the persistence of hetero- zygosis for blood group

  3. Anesthetic protocol for videolaparoscopic surgery in rabbits.

    Science.gov (United States)

    Balbinotto, Rosi Pereira; Trindade, Manoel Roberto Maciel; Meyer, Fabíola Schons; Muller, Ana Lucia Letti; Rosa, Arlindo da; Nunes, André Gorgen; da Silva, Rodrigo

    2010-02-01

    To describe the anesthetic protocol and the intubation technique without visualizing the trachea in rabbits, in order to enable the videolaparoscopic surgical procedure. The experiment was performed on 33 female rabbits (Oryctolagus cuniculus), aged from 5 to 7 months. It consisted of general anesthesia and endotracheal intubation by manual palpation of the trachea of the rabbits, without using the laryngoscope, orally, for later videolaparoscopic surgical access to the abdominal cavity. The mean values and standard deviation of vital parameters of the animals were 223.8 + or - 15.61 beats per minute for heart rate; 35 + or - 9 movements per minute for respiratory rate; 96.94 + or - 0.99% of oxymetry and 42.82 + or - 4.02 mmHg for capnometry; 16.7 + or - 4.3 minutes for pneumoperitoneum (duration of surgery) and 1 hour and 14 + or - 8.52 minutes for time of observation (from induction to recovery from anesthesia). All animals were intubated in at most three attempts. No animals were lost after the introduction of this anesthetic technique. This protocol proved adequate, safe and easy to perform, on rabbits submitted to videolaparoscopic surgery.

  4. The latent rationality of risky decisions

    Energy Technology Data Exchange (ETDEWEB)

    Japp, K.P. [Bielefeld Univ. (Germany). Faculty for Sociology

    1999-12-01

    . So rationality will stay latent as the operation of re-entry. It may become manifest as legitimating of something else, for instance as rational choice. In everyday life re-entries emerge as compromise. But compromises conceal the relevant difference. In scientific life re-entries emerge as mixed scanning. But mixed scanning displays a mix, not a difference. And it is always a difference which makes a difference. This remains latent.

  5. Sensory intolerance: latent structure and psychopathologic correlates.

    Science.gov (United States)

    Taylor, Steven; Conelea, Christine A; McKay, Dean; Crowe, Katherine B; Abramowitz, Jonathan S

    2014-07-01

    Sensory intolerance refers to high levels of distress evoked by everyday sounds (e.g., sounds of people chewing) or commonplace tactile sensations (e.g., sticky or greasy substances). Sensory intolerance may be associated with obsessive-compulsive (OC) symptoms, OC-related phenomena, and other forms of psychopathology. Sensory intolerance is not included as a syndrome in current diagnostic systems, although preliminary research suggests that it might be a distinct syndrome. First, to investigate the latent structure of sensory intolerance in adults; that is, to investigate whether it is syndrome-like in nature, in which auditory and tactile sensory intolerance co-occur and are associated with impaired functioning. Second, to investigate the psychopathologic correlates of sensory intolerance. In particular, to investigate whether sensory intolerance is associated with OC-related phenomena, as suggested by previous research. A sample of 534 community-based participants were recruited via Amazon.com's Mechanical Turk program. Participants completed measures of sensory intolerance, OC-related phenomena, and general psychopathology. Latent class analysis revealed two classes of individuals: those who were intolerant of both auditory and tactile stimuli (n=150), and those who were relatively undisturbed by auditory or tactile stimuli (n=384). Sensory-intolerant individuals, compared to those who were comparatively sensory tolerant, had greater scores on indices of general psychopathology, more severe OC symptoms, a higher likelihood of meeting caseness criteria for OC disorder, elevated scores on measures of OC-related dysfunctional beliefs, a greater tendency to report OC-related phenomena (e.g., a greater frequency of tics), and more impairment on indices of social and occupational functioning. Sensory-intolerant individuals had significantly higher scores on OC symptoms even after controlling for general psychopathology. Consistent with recent research, these findings

  6. Latent Herpes Viruses Reactivation in Astronauts

    Science.gov (United States)

    Mehta, Satish K.; Pierson, Duane L.

    2008-01-01

    Space flight has many adverse effects on human physiology. Changes in multiple systems, including the cardiovascular, musculoskeletal, neurovestibular, endocrine, and immune systems have occurred (12, 32, 38, 39). Alterations in drug pharmacokinetics and pharmacodynamics (12), nutritional needs (31), renal stone formation (40), and microbial flora (2) have also been reported. Evidence suggests that the magnitude of some changes may increase with time in space. A variety of changes in immunity have been reported during both short (.16 days) and long (>30 days) space missions. However, it is difficult to determine the medical significance of these immunological changes in astronauts. Astronauts are in excellent health and in superb physical condition. Illnesses in astronauts during space flight are not common, are generally mild, and rarely affect mission objectives. In an attempt to clarify this issue, we identified the latent herpes viruses as medically important indicators of the effects of space flight on immunity. This chapter demonstrates that space flight leads to asymptomatic reactivation of latent herpes viruses, and proposes that this results from marked changes in neuroendocrine function and immunity caused by the inherent stressfullness of human space flight. Astronauts experience uniquely stressful environments during space flight. Potential stressors include confinement in an unfamiliar, crowded environment, isolation, separation from family, anxiety, fear, sleep deprivation, psychosocial issues, physical exertion, noise, variable acceleration forces, increased radiation, and others. Many of these are intermittent and variable in duration and intensity, but variable gravity forces (including transitions from launch acceleration to microgravity and from microgravity to planetary gravity) and variable radiation levels are part of each mission and contribute to a stressful environment that cannot be duplicated on Earth. Radiation outside the Earth

  7. Photoacoustic and Colorimetric Visualization of Latent Fingerprints.

    Science.gov (United States)

    Song, Kai; Huang, Peng; Yi, Chenglin; Ning, Bo; Hu, Song; Nie, Liming; Chen, Xiaoyuan; Nie, Zhihong

    2015-12-22

    There is a high demand on a simple, rapid, accurate, user-friendly, cost-effective, and nondestructive universal method for latent fingerprint (LFP) detection. Herein, we describe a combination imaging strategy for LFP visualization with high resolution using poly(styrene-alt-maleic anhydride)-b-polystyrene (PSMA-b-PS) functionalized gold nanoparticles (GNPs). This general approach integrates the merits of both colorimetric imaging and photoacoustic imaging. In comparison with the previous methods, our strategy is single-step and does not require the signal amplification by silver staining. The PSMA-b-PS functionalized GNPs have good stability, tunable color, and high affinity for universal secretions (proteins/polypeptides/amino acids), which makes our approach general and flexible for visualizing LFPs on different substrates (presumably with different colors) and from different people. Moreover, the unique optical property of GNPs enables the photoacoustic imaging of GNPs-deposited LFPs with high resolution. This allows observation of level 3 hyperfine features of LFPs such as the pores and ridge contours by photoacoustic imaging. This technique can potentially be used to identify chemicals within LFP residues. We believe that this dual-modality imaging of LFPs will find widespread use in forensic investigations and medical diagnostics.

  8. Predicting Component Failures Using Latent Dirichlet Allocation

    Directory of Open Access Journals (Sweden)

    Hailin Liu

    2015-01-01

    Full Text Available Latent Dirichlet Allocation (LDA is a statistical topic model that has been widely used to abstract semantic information from software source code. Failure refers to an observable error in the program behavior. This work investigates whether semantic information and failures recorded in the history can be used to predict component failures. We use LDA to abstract topics from source code and a new metric (topic failure density is proposed by mapping failures to these topics. Exploring the basic information of topics from neighboring versions of a system, we obtain a similarity matrix. Multiply the Topic Failure Density (TFD by the similarity matrix to get the TFD of the next version. The prediction results achieve an average 77.8% agreement with the real failures by considering the top 3 and last 3 components descending ordered by the number of failures. We use the Spearman coefficient to measure the statistical correlation between the actual and estimated failure rate. The validation results range from 0.5342 to 0.8337 which beats the similar method. It suggests that our predictor based on similarity of topics does a fine job of component failure prediction.

  9. Crossbreeding effects on rabbit reproduction from four maternal lines of rabbits.

    Science.gov (United States)

    Ragab, M; Sánchez, J P; Mínguez, C; Baselga, M

    2016-07-01

    Litter size is essential for an efficient production of rabbit meat. A diallel cross between four maternal lines was carried out and the analysis of the components of litter size has been already done. This paper presents the analysis of litter size traits themselves (total born (TB), number born alive (NBA), number weaned (NW)) and kindling interval (KI), that complete the analysis of the reproductive performance. The 16 genetic groups were distributed in four Spanish farms. The V line was present in all farms in order to be used as reference group. A total of 34 546 parities from 7111 does, were analysed. The crossbreeding parameters were estimated according to Dickerson model. The differences between lines performance were of low magnitude and not significant for litter size traits. The LP line showed the shortest KI followed by H respect to lines A and V. These differences reflected the differences between direct and maternal genetic effects. The differences between the average of all crosses and line V were found to be significant and seemed to be important, being 0.46 for TB, 0.56 for NBA, 0.75 for NW and -2.21 days for KI. The differences between reciprocal crosses for litter size were of low magnitude and non-significant, which indicate that the maternal effects are not important between these lines. In general, the lines did not show significant differences in direct and maternal genetic effects for TB, NBA and NW but there were some significant differences for KI, which ranged from 1.54 to 6.85 days in direct effects and from 0.63 to 3.38 days for maternal effects. A positive and, in some cases, relevant heterosis was found. The largest heterosis was for TB in the HV cross (1.05 rabbits), followed by the AH (0.74 rabbits), AV (0.57 rabbits) and LH (0.55 rabbits) crosses. For NBA, significant heterosis was found in HV (1.11 rabbits) and AV (0.49 rabbits) and for NW in AV (0.90 rabbits), LH (0.70 rabbits) and LV (0.58 rabbits). Favourable and significant

  10. Latent Work and Latent Heat of the Liquid/Vapor Transformation

    Science.gov (United States)

    2014-08-01

    vapor under pressure or in differential form dM1(t) dt + dM2 (t) dt = 0 . (7) We define the latent heat of condensation Lx (t) in the process “x” by the...as (η1 − η2) dM1 dt + ∑ I MI dηI dt = 1 T dQ dt . (40) 10 The variable dM2 /dt can be eliminated between Eqs. 34 and 35 to read ∑ I MI ρ2I dρI dt + ( 1

  11. A Non-Gaussian Spatial Generalized Linear Latent Variable Model

    KAUST Repository

    Irincheeva, Irina

    2012-08-03

    We consider a spatial generalized linear latent variable model with and without normality distributional assumption on the latent variables. When the latent variables are assumed to be multivariate normal, we apply a Laplace approximation. To relax the assumption of marginal normality in favor of a mixture of normals, we construct a multivariate density with Gaussian spatial dependence and given multivariate margins. We use the pairwise likelihood to estimate the corresponding spatial generalized linear latent variable model. The properties of the resulting estimators are explored by simulations. In the analysis of an air pollution data set the proposed methodology uncovers weather conditions to be a more important source of variability than air pollution in explaining all the causes of non-accidental mortality excluding accidents. © 2012 International Biometric Society.

  12. Classification criteria of syndromes by latent variable models

    DEFF Research Database (Denmark)

    Petersen, Janne

    2010-01-01

    displaying isolated peripheral lipoatrophy and another displaying both peripheral lipoatrophy and central lipohypertrophy. When patient characteristics were included the results indicated that smoking status is an essential variable in explaining why some patients do not get the central lipohypertrophy part...... of the syndrome. Thus, the results suggested that peripheral lipoatrophy and central lipohypertophy are interrelated phenotypes rather than two independent phenotypes. Part 2: Latent class regression relates explanatory variables to latent classes. In this model no measure of the latent class variable is obtained...... are shown to be superior depending on whether the latent variable is a dependent or an independent variable. Both these types of scores are extended to the situation of differential item functioning. Analytically I have showed that the scores result in consistent estimates when used properly in subsequent...

  13. A developmental study of latent absolute pitch memory.

    Science.gov (United States)

    Jakubowski, Kelly; Müllensiefen, Daniel; Stewart, Lauren

    2017-03-01

    The ability to recall the absolute pitch level of familiar music (latent absolute pitch memory) is widespread in adults, in contrast to the rare ability to label single pitches without a reference tone (overt absolute pitch memory). The present research investigated the developmental profile of latent absolute pitch (AP) memory and explored individual differences related to this ability. In two experiments, 288 children from 4 to12 years of age performed significantly above chance at recognizing the absolute pitch level of familiar melodies. No age-related improvement or decline, nor effects of musical training, gender, or familiarity with the stimuli were found in regard to latent AP task performance. These findings suggest that latent AP memory is a stable ability that is developed from as early as age 4 and persists into adulthood.

  14. Understanding the sufficiency of information for latent fingerprint value determinations.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Kiebuzinski, George I; Roberts, Maria Antonia; Buscaglia, Joann

    2013-07-10

    A latent print examiner's assessment of the value, or suitability, of a latent impression is the process of determining whether the impression has sufficient information to make a comparison. A "no value" determination preemptively states that no individualization or exclusion determination could be made using the impression, regardless of quality of the comparison prints. Factors contributing to a value determination include clarity and the types, quantity, and relationships of features. These assessments are made subjectively by individual examiners and may vary among examiners. We modeled the relationships between value determinations and feature annotations made by 21 certified latent print examiners on 1850 latent impressions. Minutia count was strongly associated with value determinations. None of the models resulted in a stronger intraexaminer association with "value for individualization" determinations than minutia count alone. The association between examiner annotation and value determinations is greatly limited by the lack of reproducibility of both annotation and value determinations. Published by Elsevier Ireland Ltd.

  15. Localized Dictionaries Based Orientation Field Estimation for Latent Fingerprints.

    Science.gov (United States)

    Xiao Yang; Jianjiang Feng; Jie Zhou

    2014-05-01

    Dictionary based orientation field estimation approach has shown promising performance for latent fingerprints. In this paper, we seek to exploit stronger prior knowledge of fingerprints in order to further improve the performance. Realizing that ridge orientations at different locations of fingerprints have different characteristics, we propose a localized dictionaries-based orientation field estimation algorithm, in which noisy orientation patch at a location output by a local estimation approach is replaced by real orientation patch in the local dictionary at the same location. The precondition of applying localized dictionaries is that the pose of the latent fingerprint needs to be estimated. We propose a Hough transform-based fingerprint pose estimation algorithm, in which the predictions about fingerprint pose made by all orientation patches in the latent fingerprint are accumulated. Experimental results on challenging latent fingerprint datasets show the proposed method outperforms previous ones markedly.

  16. A solar air collector with integrated latent heat thermal storage

    Science.gov (United States)

    Charvat, Pavel; Ostry, Milan; Mauder, Tomas; Klimes, Lubomir

    2012-04-01

    Simulations of the behaviour of a solar air collector with integrated latent heat thermal storage were performed. The model of the collector was created with the use of coupling between TRNSYS 17 and MATLAB. Latent heat storage (Phase Change Material - PCM) was integrated with the solar absorber. The model of the latent heat storage absorber was created in MATLAB and the model of the solar air collector itself was created in TRNSYS with the use of TYPE 56. The model of the latent heat storage absorber allows specification of the PCM properties as well as other parameters. The simulated air collector was the front and back pass collector with the absorber in the middle of the air cavity. Two variants were considered for comparison; the light-weight absorber made of sheet metal and the heat-storage absorber with the PCM. Simulations were performed for the climatic conditions of the Czech Republic (using TMY weather data).

  17. Appropriate handling of pet rabbits: a literature review.

    Science.gov (United States)

    Bradbury, A G; Dickens, G J E

    2016-10-01

    Many rabbits show fear behaviours when lifted off the ground. Estimates from owner surveys suggest that around 60% of pet rabbits struggle when lifted and fear-related aggression is common. This article integrates information from both laboratory and pet rabbit studies to formulate a list of recommendations for appropriate handling of rabbits. Reduction of the frequency of the stressor can be achieved by educating owners on alternative management practices to reduce the need to carry their rabbits. However, in some situations, it is unavoidable that a rabbit is lifted. Amelioration of the stress in these instances can be achieved by a 2 pronged strategy. First, the population of rabbits can be made more resilient to infrequent stressors by selectively breeding for confident rabbits and by better socialisation of unweaned kits, and, where possible, training of individual animals to permit handling. Secondly, any unavoidable lifting can be made less stressful by educating veterinary staff in appropriate methods of holding rabbits during both consultations and inpatient care. Better understanding of appropriate interactions with rabbits will improve welfare. © 2016 British Small Animal Veterinary Association.

  18. Poikilocytosis in Rabbits: Prevalence, Type, and Association with Disease

    Science.gov (United States)

    Christopher, Mary M.; Hawkins, Michelle G.; Burton, Andrew G.

    2014-01-01

    Rabbits (Oryctolagus cuniculus) are a popular companion animal, food animal, and animal model of human disease. Abnormal red cell shapes (poikilocytes) have been observed in rabbits, but their significance is unknown. The objective of this study was to investigate the prevalence and type of poikilocytosis in pet rabbits and its association with physiologic factors, clinical disease, and laboratory abnormalities. We retrospectively analyzed blood smears from 482 rabbits presented to the University of California-Davis Veterinary Medical Teaching Hospital from 1990 to 2010. Number and type of poikilocytes per 2000 red blood cells (RBCs) were counted and expressed as a percentage. Acanthocytes (>3% of RBCs) were found in 150/482 (31%) rabbits and echinocytes (>3% of RBCs) were found in 127/482 (27%) of rabbits, both healthy and diseased. Thirty-three of 482 (7%) rabbits had >30% acanthocytes and echinocytes combined. Mild to moderate (>0.5% of RBCs) fragmented red cells (schistocytes, microcytes, keratocytes, spherocytes) were found in 25/403 (6%) diseased and 0/79 (0%) healthy rabbits (P = 0.0240). Fragmentation and acanthocytosis were more severe in rabbits with inflammatory disease and malignant neoplasia compared with healthy rabbits (Prabbits. Our findings support the need to carefully document poikilocytes in research investigations and in clinical diagnosis and to determine their diagnostic and prognostic value. PMID:25402479

  19. Innate resistance to myxomatosis in wild rabbits in England*

    Science.gov (United States)

    Ross, J.; Sanders, M. F.

    1977-01-01

    Wild rabbits (Oryctolagus cuniculus) from one study area in England have been used over a period of 11 years to investigate the possible appearance of innate resistance to myxomatosis. Rabbits of 4-6 weeks old were captured alive, retained in the laboratory until at least 4 months old, and then infected with a type of myxoma virus which kills 90-95% of laboratory rabbits. Observations were made of symptoms, mortality rate and survival times. In the first 4 years of the study (1966-9), mortality rates were not significantly different from those of laboratory rabbits, although survival times of wild rabbits were appreciably longer. In 1970, the mortality rate amongst wild rabbits was 59%, in 1974 it was 17%, and in 1976 it was 20%, thus showing that a considerable degree of inherited resistance to myxomatosis has developed. The types of myxoma virus most commonly isolated from wild rabbits in Great Britain in recent years have been those which cause 70-95% mortality in laboratory rabbits. Therefore, if the degree of innate resistance demonstrated is widespread in Great Britain, there are serious implications regarding the size of the rabbit population, because myxomatosis has been an important factor in holding rabbit numbers at a relatively low level. PMID:270526

  20. Innate resistance to myxomatosis in wild rabbits in England.

    Science.gov (United States)

    Ross, J; Sanders, M F

    1977-12-01

    Wild rabbits (Oryctolagus cuniculus) from one study area in England have been used over a period of 11 years to investigate the possible appearance of innate resistance to myxomatosis. Rabbits of 4-6 weeks old were captured alive, retained in the laboratory until at least 4 months old, and then infected with a type of myxoma virus which kills 90-95% of laboratory rabbits. Observations were made of symptoms, mortality rate and survival times.In the first 4 years of the study (1966-9), mortality rates were not significantly different from those of laboratory rabbits, although survival times of wild rabbits were appreciably longer. In 1970, the mortality rate amongst wild rabbits was 59%, in 1974 it was 17%, and in 1976 it was 20%, thus showing that a considerable degree of inherited resistance to myxomatosis has developed.The types of myxoma virus most commonly isolated from wild rabbits in Great Britain in recent years have been those which cause 70-95% mortality in laboratory rabbits. Therefore, if the degree of innate resistance demonstrated is widespread in Great Britain, there are serious implications regarding the size of the rabbit population, because myxomatosis has been an important factor in holding rabbit numbers at a relatively low level.

  1. Latent tuberculosis infection in health care workers: review article

    Directory of Open Access Journals (Sweden)

    Davood Mansury

    2018-01-01

    Full Text Available The members of Mycobacterium tuberculosis complex (MTBC known as causative agents of human tuberculosis. Tuberculosis infection is one of the most important occupational risks for healthcare workers (HCWs in most countries, such as Iran. In general, there are two types of tuberculosis, they include: latent infection and active TB. Latent tuberculosis infection (LTBI means: a patient is infected with Mycobacterium tuberculosis but, the patient does not have active tuberculosis, clinical symptoms and radiological findings. According to studies, TB infection from patients to health care workers, depending on geographic region and economic situation is two to five times more than general population. The lowest incidence and the highest rates of LTBI prevalence among HCWs were 7% in Mashhad and 82.8% in Zahedan respectively. The risk factor acquisition of TB infection was a significant relationship with certain hospital wards (lung disease unit, laboratory, etc., Increasing age and duration of employment. And results of this study show that TB is a significant problem among HCWs in Iran. Infection control and personal protective measures with training programs to patients and HCW is required to reduce the occupational risk of TB. Early detection of Mycobacterium tuberculosis and prevention treatment in people with latent TB are key elements in control of tuberculosis. Until now, different methods for detection of latent tuberculosis infection has been introduced that are not gold standard none of them. However, the most important methods, tuberculin skin test and the tests that based on measuring the production of interferon gamma are recommended, but each one of them has advantages and disadvantages. However, in all the articles of the tuberculin skin test is used for screening and early diagnosis of latent tuberculosis infection. So, the aim of this study was to Incidence and prevalence of latent tuberculosis infection in health care workers and

  2. Latent-failure risk estimates for computer control

    Science.gov (United States)

    Dunn, William R.; Folsom, Rolfe A.; Green, Owen R.

    1991-01-01

    It is shown that critical computer controls employing unmonitored safety circuits are unsafe. Analysis supporting this result leads to two additional, important conclusions: (1) annual maintenance checks of safety circuit function do not, as widely believed, eliminate latent failure risk; (2) safety risk remains even if multiple, series-connected protection circuits are employed. Finally, it is shown analytically that latent failure risk is eliminated when continuous monitoring is employed.

  3. The rabbit meat quality after different feeding

    Directory of Open Access Journals (Sweden)

    Adriana Pavelková

    2017-01-01

    Full Text Available The goal of this present work was to evaluation the effect of feeding on selected chemical and physical parameters rabbit meat. For testing was used rabbits incurred by the crossing of two breeds: the mother - Nitriansky králik and father - Nemecký obrovitý strakoš. Rabbits came from domestic breeding and were 8 weeks old separated from the mother. We created two groups: group A was fed by feed wheat and group B was fed by granulated fodder Králik gold forte. During all the time of fattening, rabbits were fed with hay, respectively green fodder. Rabbits were slaughtered at the age of 19 weeks. After slaughtering was dissection obtained fresh rabbit meat for analysis. From chemical parameters were determined: dry matter, fat, protein, ash, energy value and biogenic amines as putrescine, cadaverine, tyramine, spermidine and spermine. From physical parameter was measured pH of meat. The initial value of pH in group A was 6.12 and after 48 hours was 6.38 and in group B was 7.32 and 6.40, respectively.Dry matter in group A was 24.86 g.100 g-1 and in group B was 24.70 g.100 g-1, content of fat was 1.44 g.100g-1 and 1.33 g.100 g-1, protein was 20.94 g.100 g-1 and 21.12 g.100 g-1, ash was 1.18 g.100 g-1 and 1.25 g.100 g-1, energy value was 461.89 kJ.100 g-1 and 440.27 kJ.100 g-1, respectively. Statistical evaluation of all results we found statistically significant differences (p <0.05 only between the groups A and B only in biogenic amine - spermidine. Experiment was shown a high correlation between biogenic amines putrescine and tyramine, putrescine and spermine, cadaverine and tyramine. Normal 0 21 false false false EN-GB X-NONE X-NONE

  4. A bladder diverticulum model in rabbits.

    Science.gov (United States)

    Çelebi, Süleyman; Kuzdan, Özgür; Özaydın, Seyithan; Başdaş, Cemile Beşik; Özaydın, İpek; Erdoğan, Cankat; Sander, Serdar

    2016-10-01

    Shuttling of some of the bladder volume into the bladder diverticulum (BD) can cause urinary retention, lower urinary tract dysfunction, infection, and stone formation. This experimental study is the first to create a rabbit BD to study micturition physiology (urodynamics and pathology) that mimics clinical findings. The study included 16 New Zealand adult male rabbits in the BD group and 16 sham-operated controls. BD creation consisted of a lower midline laparotomy and bladder entry via the spacing between the detrusor muscle fibers and the mucosa, posterolaterally from the bladder wall. The detrusor was excised to provide a mucosal prolapsus, creating a narrow BD neck (Figure). The sham group underwent bladder exposure with a midline incision. All rabbits underwent urodynamic study preoperatively and postoperatively, consisting of postmicturition residue (PMR), maximum bladder capacity (MBC), voiding detrusor pressure (VPdet), filling detrusor pressure (FPdet), compliance, and urine flow (Qflow). The animals were then sacrificed and their bladders assessed for pathology and stone formation. Preoperative MBC, Pdet, and Qmax were within reference ranges. No animals had PMR or urinary tract infections (UTIs). The BD group showed urodynamic and pathologic bladder changes, including decreased (28%) cystometric bladder capacity and compliance (Sham: 26.8 ± 0.4; BD: 4.46 ± 1.08, p = 0.0001) and increased post-void residual PMR (8.3 ± 2.4 mL). Pathology revealed increased bladder detrusor thickness correlated with urodynamic findings of increased filling detrusor pressures (Sham: 1.58 ± 0.2; BD: 4.89 ± 0.93, p = 0.0001). Urodynamics revealed intermittent BD bladder contraction during the filling phases. Eight BD group rabbits had UTIs; five had stone formation (4-9 mm). In the literature, it has not been determined whether lower urinary tract disorders (LUTD) could cause diverticula, or if a congenital diverticula could be reason for LUTD. Anatomical

  5. Latent Transition Analysis with a Mixture Item Response Theory Measurement Model

    Science.gov (United States)

    Cho, Sun-Joo; Cohen, Allan S.; Kim, Seock-Ho; Bottge, Brian

    2010-01-01

    A latent transition analysis (LTA) model was described with a mixture Rasch model (MRM) as the measurement model. Unlike the LTA, which was developed with a latent class measurement model, the LTA-MRM permits within-class variability on the latent variable, making it more useful for measuring treatment effects within latent classes. A simulation…

  6. A Flexible Latent Class Approach to Estimating Test-Score Reliability

    Science.gov (United States)

    van der Palm, Daniël W.; van der Ark, L. Andries; Sijtsma, Klaas

    2014-01-01

    The latent class reliability coefficient (LCRC) is improved by using the divisive latent class model instead of the unrestricted latent class model. This results in the divisive latent class reliability coefficient (DLCRC), which unlike LCRC avoids making subjective decisions about the best solution and thus avoids judgment error. A computational…

  7. Mode Choice Model for Public Transport with Categorized Latent Variables

    Directory of Open Access Journals (Sweden)

    Jian Chen

    2017-01-01

    Full Text Available Mode choice model for public transport, which integrates structural equation model (SEM and discrete choice model (DCM with categorized latent variables, was presented in this paper. Apart from identifying those important latent variables that affect mode choice for public transport, the objective of this study was also to develop an improved disaggregative model that better explains travel behavior of those decision-makers in choosing public transport. After extensive observations, selective latent variable sets which consist of latent variable components were chosen together with explicit variables in formulating the utility functions. Data collected in Chengdu city, China, were used to calibrate and validate the model. Results showed that the impact of fare on mode choice of public transport escalated in the SEM-DCM integrated model compared with the traditional logit model. The goodness of fit for the integrated model with latent variable sets is 0.201 higher than that of the traditional logit model, which proves that latent variables have an obvious impact on mode choice behavior, and the SEM-DCM integrated model has higher accuracy and stronger explanatory ability. The results are especially helpful for public transport operators to achieve higher mode share split by improving the service quality of public transport in terms of providing more convenience and better service environment for public transport users.

  8. Comparing the context specificity of extinction and latent inhibition.

    Science.gov (United States)

    Miller, Ralph R; Laborda, Mario A; Polack, Cody W; Miguez, Gonzalo

    2015-12-01

    Exposure to a cue alone either before (i.e., latent inhibition treatment) or after (i.e., extinction) the cue is paired with an unconditioned stimulus results in attenuated conditioned responding to the cue. Here we report two experiments in which potential parallels between the context specificity of the effects of extinction and latent inhibition treatments were directly compared in a lick suppression preparation with rats. The reversed ordering of conditioning and nonreinforcement in extinction and latent inhibition designs allowed us to examine the effect of training order on the context specificity of what is learned given phasic reinforcement and nonreinforcement of a target cue. Experiment 1 revealed that when conditioned-stimulus (CS) conditioning and CS nonreinforcement were administered in the same context, both extinction and latent inhibition treatments had reduced impacts on test performance, relative to excitatory conditioning when testing occurred outside the treatment context. Similarly, Experiment 2 showed that when conditioning was administered in one context and nonreinforcement was administered in a second context, the effects of both extinction and latent inhibition treatments were attenuated when testing occurred in a neutral context, relative to the context in which the CS was nonreinforced. The observed context specificity of extinction and latent inhibition treatments has been previously reported in both cases, but not in a single experiment under otherwise identical conditions. The results of the two experiments convergently suggest that memory of nonreinforcement becomes context dependent after a cue is both reinforced and nonreinforced, independent of the order of training.

  9. Accelerated muscle fatigability of latent myofascial trigger points in humans.

    Science.gov (United States)

    Ge, Hong-You; Arendt-Nielsen, Lars; Madeleine, Pascal

    2012-07-01

    Muscle fatigue is prevalent in acute and chronic musculoskeletal pain conditions in which myofascial trigger points (MTPs) are involved. The aim of this study was to investigate the association of latent MTPs with muscle fatigue. Intramuscular electromyographic (EMG) recordings were obtained from latent MTPs and non-MTPs together with surface EMG recordings from the upper trapezius muscles during sustained isometric muscle contractions in 12 healthy subjects. Normalized root mean square (RMS) EMG amplitude and mean power frequency (MNF) were analyzed. The rate of perceived exertion and pain intensity from MTP side and non-MTP side were recorded. Pain intensity on the MTP side was significantly higher than the non-MTP side (P latent MTPs showed an early onset of decrease in MNF and a significant decrease at the end of fatiguing contraction as compared with non-MTPs (P latent MTPs presented with an early onset of the increase in RMS amplitude and the increase was significantly higher than that from non-MTPs at the end of sustained isometric contraction (P latent MTP is associated with an accelerated development of muscle fatigue and simultaneously overloading active motor units close to an MTP. Elimination of latent MTPs and inactivation of active MTPs may effectively reduce accelerated muscle fatigue and prevent overload spreading within a muscle. Wiley Periodicals, Inc.

  10. Ocular herpes simplex virus type 1: is the cornea a reservoir for viral latency or a fast pit stop?

    Science.gov (United States)

    Kennedy, David P; Clement, Christian; Arceneaux, Richard L; Bhattacharjee, Partha S; Huq, Tashfin S; Hill, James M

    2011-03-01

    To present a review supporting and refuting evidence from mouse, rabbit, nonhuman primate, and human studies of herpes simplex virus type 1 (HSV-1) concerning corneal latency. More than 50 research articles on HSV-1 published in peer-reviewed journals were examined. Infectious HSV-1 has been found in mouse denervated tissues and in tissues with negative cultures from the corresponding ganglion. However, the different mouse strains have shown varied responses to different strains of HSV, making it difficult to relate such findings to humans. Rabbit studies provide excellent evidence for HSV-1 corneal latency including data on HSV-1 migration from the cornea into the corneoscleral rim and on the distribution of HSV-1 DNA in the cornea. However, the available methods for the detection of infectious HSV-1 may not be sensitive enough to detect low-level infection. Infectious HSV-1 has been successfully isolated from the tears of nonhuman primates in the absence of detectable corneal lesions. The recurrence of corneal ulcers in nonhuman primates before the appearance of infectious HSV-1 in tears suggests that the origin of the HSV-1 is the cornea, rather than the trigeminal ganglion. Human studies presented evidence of both ganglion and corneal latency. Understanding HSV-1 disease progression and the possibility of corneal latency could lead to more effective treatments for herpetic keratitis. However, it is unlikely that operational latency in the cornea will be definitively proven unless a new method with higher sensitivity for the detection of infectious virus is developed.

  11. The Oct4 promoter-EGFP transgenic rabbit: a new model for monitoring the pluripotency of rabbit stem cells.

    Science.gov (United States)

    Yin, Mingru; Fang, Zhenfu; Jiang, Weihua; Xing, Fengying; Jiang, Manxi; Kong, Pengcheng; Li, Yao; Zhou, Xiaomei; Tang, Lan; Li, Shangang; Chen, Xuejin

    2013-01-01

    The rabbit has long been used as a laboratory animal model for developing reproductive and stem cell-related technologies, as well as for studying human disease. The Oct4 transcription factor plays a crucial role in the maintenance and regulation of pluripotency in embryos and stem cells. We constructed a reporter plasmid containing the gene encoding the enhanced green fluorescent protein (EGFP) under the control of the rabbit Oct4 promoter (prOG) and transfected it into E14 mouse stem cells and rabbit ESCs. In addition, prOG transgenic fibroblasts were derived and prOG transgenic rabbits were produced by somatic cell nuclear transfer (SCNT). The pattern of expression of ectopic EGFP was similar in E14 mouse stem cells whether under the control of the rabbit (prOG) or mouse Oct4 promoter (pmOG). EGFP expression was observed in rabbit ESCs following prOG transfection. Both prOG transgenic SCNT embryos and F1 prOG transgenic embryos derived from adult transgenic rabbits expressed green fluorescence at the morula and blastocyst stages. EGFP was clearly detected in gonads isolated from fetuses at 27 dpc. The prOG transgenic rabbit represents a new model for studying the derivation and maintenance of rabbit pluripotent cells, and for investigating rabbit embryo development.

  12. Dietary supplementation of butyrate in growing rabbits

    Directory of Open Access Journals (Sweden)

    G. Radaelli

    2010-01-01

    Full Text Available The UE restrictions imposed on the antibiotic utilization in animal husbandry have increased the interest on alternative additives capable of improving animal digestive health. Among the numerous tested products, short chain fatty acids stimulated intestinal mucus production at different level and intestinal cells proliferation in rats (Meslin et al., 2001; Moreau et al., 2003. Short and medium chain fatty acids could also modulate intestinal microflora: in rabbits, the antimicrobial activity of caprilic and capric acids was proved on various strains of Clostridium perfringens and Escherichia coli (Marounek et al., 2002. The present trial aimed to evaluate the effect of butyrate inclusion and level on growth performance, health status, digestive physiology and slaughter traits in growing rabbits.

  13. Fusiform aneurysm model in rabbit carotid artery.

    Science.gov (United States)

    Reinald, Nicoleta; Fournier, Benjamin; Naveau, Adrien; Couty, Ludovic; Lemitre, Mathilde; Seguier, Sylvie; Coulomb, Bernard; Gogly, Bruno; Lafont, Antoine; Durand, Eric

    2010-01-01

    To develop a reproducible and accessible model of elastase-induced fusiform aneurysm in carotid rabbit arteries. Elastase, at a concentration of 1-30 U, was incubated into the lumen of carotid rabbit arteries. Four weeks later, angiography, histomorphometry, immunohistochemistry and zymography were performed. The optimal concentration of elastase in this model was 3 U according to the balance between mortality and thrombosis rates. Indeed, at 3 U, external carotid diameter increased from 1.9 +/- 0.1 to 3.1 +/- 0.4 mm (p < 0.0001) associated with degradation of elastic fibers, matrix metalloproteinase-9 secretion, apoptosis and macrophage infiltration. Our study underlines that abdominal aortic aneurysm can be reliably duplicated in an elastase-induced aneurysm in carotid artery, a much more accessible vessel. Copyright 2009 S. Karger AG, Basel.

  14. Lactate metabolism in the fetal rabbit lung

    Energy Technology Data Exchange (ETDEWEB)

    Engle, M.J.; Brown, D.J.; Dooley, M.

    1986-05-01

    Lactate is frequently overlooked as a potential substrate for the fetal lung, even though it is present in the fetal circulation in concentrations as high as 8 mM. These high concentrations, coupled with the relatively low levels of glucose in the fetal blood, may indicate that lactate can substitute for glucose in pulmonary energy generation and phospholipid synthesis. A series of experiments was therefore undertaken in order to investigate the role of lactate in perinatal pulmonary development. Explants from 30 day gestation fetal rabbit lungs were incubated in Krebs-Ringer bicarbonate buffer supplemented with 3 mM (U-/sup 14/C)-glucose and varying levels of lactate. In the absence of medium lactate, fetal rabbit lung explants were capable of producing lactate at a rate of approximately 200 etamoles/mg protein/hour. The addition of lactate to the bathing medium immediately reduced net lactate production and above 4 mM, fetal rabbit lung explants became net utilizers of lactate. Media lactate concentrations of 2.5 mM, 5 mM and 10 mM also decreased glucose incorporation into total tissue disaturated phosphatidylcholine by approximately 20%, 35%, and 45%, respectively. Glucose incorporation into surfactant phosphatidylcholine was also reduced by approximately 50%, when lactate was present in the incubation medium at a concentration of 5 mM. Additional experiments also revealed that fetal lung lactate dehydrogenase activity was almost twice that found in the adult rabbit lung. These data indicate that lactate may be an important carbon source for the developing lung and could be a significant component in the manufacture of surfactant phosphatidylcholine during late gestation.

  15. Usefulness of high-resolution sonography in early diagnosis of rabbit clonorchiasis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Hoon; Choi, Don Gil; Chung, Il Gyu; Phyun, Lae Hyun; Pyeun, Yong Seon [Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of); Hong, Sung Tae; Lee, Me Jeong [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1999-09-15

    To determine the role of high-resolution sonography in the early diagnosis of experimentally induced clonorchiasis in rabbits. We performed sonographic examination weekly in 22 lightly-infected rabbits (10 rabbits infected with 10 metacercariae, 6 rabbits infected with 20 metacercariae, and 6 rabbits infected with 40 metacercariae), and 10 heavily-infected rabbits (500 metacercariae). The sonographic criterion of diagnosis with dilatation of the intrahepatic ducts. We sacrificed lightly-infected rabbits and counted numbers of adult worms of clonorchis sinensis 9 weeks after infection. Sonographic abnormalities were found 3 weeks after infection in 2 lightly-infected rabbits and 5 heavily-infected rabbits. On sonography at 9 weeks after infection, we observed dilatation of the intrahepatic ducts in 11 (65%) of 17 lightly-infected rabbits and all of 10 heavily-infected rabbits. High-resolution sonography is very useful in early diagnosis of rabbits clonorchiasis.

  16. Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities

    OpenAIRE

    Philip Maseghe Mwachaka; Hassan Saidi; Paul Ochieng Odula; Pamela Idenya Mandela

    2015-01-01

    Purpose: To describe the effect of monocular deprivation on densities of neural retinal cells in rabbits. Methods: Thirty rabbits, comprised of 18 subject and 12 control animals, were included and monocular deprivation was achieved through unilateral lid suturing in all subject animals. The rabbits were observed for three weeks. At the end of each week, 6 experimental and 3 control animals were euthanized, their retinas was harvested and processed for light microscopy. Photomicrographs of ...

  17. Toxicity of staphylococcal toxic shock syndrome toxin 1 in rabbits.

    OpenAIRE

    de Azavedo, J C; Arbuthnott, J P

    1984-01-01

    Strains of Staphylococcus aureus associated with toxic shock syndrome produce toxic shock syndrome toxin 1 (TSST 1), which is lethal to conventional rabbits and acts synergistically with gram-negative lipopolysaccharide. The lethal effect of TSST 1 was examined in specific-pathogen-free rabbits on the basis that these rabbits, being less colonized by gram-negative bacteria, would be less susceptible than conventional animals. Although there was no significant difference in mortality between s...

  18. Myxomatosis in farmland rabbit populations in England and Wales.

    OpenAIRE

    Ross, J; Tittensor, A. M.; Fox, A P; Sanders, M. F.

    1989-01-01

    The overall pattern and consequences of myxomatosis in wild rabbit populations were studied at three farmland sites in lowland southern England and upland central Wales between 1971 and 1978. When results from all years were combined, the disease showed a clear two-peaked annual cycle, with a main autumn peak between August and January, and a subsidiary spring peak during February to April. Rabbit fleas, the main vectors of myxomatosis in Britain, were present on full-grown rabbits in suffici...

  19. Welfare Impacts of Pindone Poisoning in Rabbits (Oryctolagus cuniculus)

    OpenAIRE

    Fisher, Penny; Brown, Samantha; Arrow, Jane

    2016-01-01

    Simple Summary The nature and duration of the effects of pindone poisoning in rabbits were evaluated through observational monitoring of affected animals and necropsy. Using the resulting data in a formal assessment framework, the welfare impacts of pindone poisoning were ranked as relatively higher than other vertebrate toxic agents currently used for rabbit control. Abstract Control methods used to manage unwanted impacts of the European rabbit in Australia and New Zealand include the use o...

  20. Field Trial of a Pasteurella multocida Extract Vaccine in Rabbits

    OpenAIRE

    Suckow, Mark A; Haab, Rudolph W; Miloscio, Lawrence J; Guilloud, Norman B

    2008-01-01

    Pasteurella multocida is a bacterial pathogen that can cause significant disease and subsequent effects on research activities involving rabbits. Although several vaccines have been tested under laboratory conditions, field trials of vaccines for the control of P. multocida in rabbits are few. We used a potassium thiocyanate extract (PTE) produced from P. multocida serotype D:3,12,15 to vaccinate Pasteurella-free rabbits at their introduction into a colony having endemic infection with P. mul...

  1. Erythrocyte Osmotic Fragility and Excitability Score in Rabbit fed ...

    African Journals Online (AJOL)

    olayemitoyin

    of excitability score shows that rabbit on diet 1 and 2 had a lower value which was significantly (P < 0.05) lower than rabbits on ... heat stress in poultry (Minka et al. .... An excitability score of 4 was recorded in 70.00 ± 5.50 % in rabbit. Table 1: Composition of Experimental Diets. Ingredients. Dietary Treatment. T1. T2. T3. T4.

  2. BIORESORBABLE POLYMERIC MENISCAL PROSTHESIS: STUDY IN RABBITS

    Science.gov (United States)

    Cardoso, Tulio Pereira; de Rezende Duek, Eliana Aparecida; Amatuzzi, Marco Martins; Caetano, Edie Benedito

    2015-01-01

    Objective: To induce growth of a neomeniscus into the pores of a prosthesis in order to protect the knee joint cartilage. Methods: 70 knees of 35 New Zealand rabbits were operated. The rabbits were five to seven months old, weighed 2 to 3.8 kilograms, and 22 were male and 13 were female. Each animal underwent medial meniscectomy in both knees during a single operation. A bioabsorbable polymeric meniscal prosthesis composed of 70% polydioxanone and 30% L-lactic acid polymer was implanted in one side. The animals were sacrificed after different postoperative time intervals. The femoral condyles and neomeniscus were subjected to histological analysis. Histograms were used to measure the degradation and absorption of the prosthesis, the growth of meniscal tissue in the prosthesis and the degree of degradation of the femoral condyle joint cartilage. Results: The data obtained showed that tissue growth histologically resembling a normal meniscus occurred, with gradual absorption of the prosthesis, and the percentages of chondrocytes on the control side and prosthesis side. Conclusion: Tissue growth into the prosthesis pores that histologically resembled the normal rabbit meniscus was observed. The joint cartilage of the femoral condyles on the prosthesis side presented greater numbers of chondrocytes in all its layers. PMID:27022549

  3. Sodium nitroprusside induces apoptosis of rabbit chondrocytes

    Science.gov (United States)

    Liang, Qian; Wang, Xiao-Ping; Chen, Tong-Sheng

    2013-02-01

    Osteoarthritis (OA) is characterized by a slowly progressing degradation of the matrix and destruction of articular cartilage. Apoptosis of chondrocyte is accounted for the mechanism of OA. Nitric oxide (NO), as a stimulus, has been shown to induce chondrocyte apoptosis by activating the matrix metalloproteinases (MMPs), increasing the expression of cyclooxygenase 2 (COX-2) and the level of prostaglandin E2 (PGE2), inhibiting the proteoglycan synthesis and type II collagen expression. In this study, sodium nitroprusside (SNP) was administered to be the NO donor to explore the mechanism of NO-induced apoptosis of rabbit chondrocytes obtained from six weeks old New Zealand rabbits. CCK-8 assay revealed the inhibitory effect of SNP on cell viability. We used flow cytometry (FCM) to assess the form of cell death by Annexin-V/propidium iodide (PI) double staining, and evaluate the change of mitochondrial membrane potential (ΔΨm). We found that the SNP induced chondrocyte apoptosis in a dose- and time-dependent manner and an observable reduction of ΔΨm. In conclusion, our findings indicate that SNP induces apoptosis of rabbit chondrocytes via a mitochondria-mediated pathway.

  4. Reproductive activity and welfare of rabbit does

    Directory of Open Access Journals (Sweden)

    C. Castellini

    2010-04-01

    Full Text Available This paper reviews the relationships between reproductive performance and welfare of the rabbit does. In the last 10 years the profitability of rabbit farms has increased mainly due to improvements in management and genetic selection but several problems mainly related to animal welfare have also occurred. The mortality and rates of female replacement per year are very high and the replaced females often show poor body condition and low performance. The effect of kindling order, litter size, genetic strain, weaning age and reproduction rhythm on the reproductive performance and welfare of females and some mechanisms implicated in these effects are discussed. Modern rabbit does produce a lot of milk which have a high energetic value which leads to a mobilization of body fat which results in an energy deficit. In the current reproductive rhythms, there is an extensive overlap between lactation and gestation. The resulting energetic and hormonal antagonism reduces the fertility rate and lifespan of the doe. Strategies to improve the fertility, lifespan and welfare of does are discussed. An approach which combines various strategies seems to be required to meet these objectives. Since the factors involved in this productive system are fixed (genetic strain, environment the most powerful way to improve doe welfare is to choose a reproductive rhythm that is adapted to the physiology of the does.

  5. Sildenafil Stimulates Aqueous Humor Turnover in Rabbits

    Science.gov (United States)

    Alvarez, Lawrence J.; Zamudio, Aldo C.; Candia, Oscar A.

    2013-01-01

    Sildenafil citrate increases ocular blood flow and accelerates the rate of anterior chamber refilling after paracentesis. The latter effect could have resulted from a reduction in outflow facility or from an increase in aqueous humor (AH) production. In this study, we used scanning ocular fluorophotometry to examine the effects of sildenafil on AH turnover, and thus, AH production in eyes of live normal rabbits. For this, the rate of aqueous humor flow (AHF) was quantified with a commercially available fluorophotometer that measured the rate of fluorescein clearance from the anterior segment, which predominantly occurs via the trabecular meshwork. After ≈ 2 hrs of control scans to determine the baseline rate of AHF, the rabbits were fed 33 mg of sildenafil and allowed ≈ 45 min for the drug to enter the systemic circulation. Thereafter, fluorescence scans were retaken for an additional 90–120 min. Sildenafil ingestion increased AHF by about 36%, from 2.31 μL/min to 3.14 μL/min (PViagra, Revatio), stimulates AHF in rabbits. Our results seem consistent with reports indicating that the drug dilates intraocular arteries and augments intraocular vascular flow. These physiological responses to the agent apparently led to increased fluid entry into the anterior chamber. As such, the drug might have utility in patients with ocular hypotony resulting from insufficient AH formation. PMID:23562660

  6. Abstracts of the 24th Hungary conference on rabbit production

    Directory of Open Access Journals (Sweden)

    24TH Conference on rabbit production Kaposvár, Hungary. 30th May, 2012

    2014-09-01

    Full Text Available Some 100 guests took part in the 24th Hungarian Conference on Rabbit Production in Kaposvár, organised by the University of Kaposvár, the Hungarian Branch of the WRSA and the Rabbit Production Board. This is the largest and most popular event for rabbit breeders in Hungary. Seventeen papers were presented, both by senior and young scientists. Topics of the papers covered all fields of rabbit production (production, housing and welfare, reproduction, genetics, nutrition, meat quality and pathology. Full papers are available from the organiser (matics.zsolt@ke.hu on request.

  7. PHARMACOKINETIC VARIATIONS OF OFLOXACIN IN NORMAL AND FEBRILE RABBITS

    Directory of Open Access Journals (Sweden)

    M. AHMAD, H. RAZA, G. MURTAZA AND N. AKHTAR

    2008-12-01

    Full Text Available The influence of experimentally Escherichia coli-induced fever (EEIF on the pharmacokinetics of ofloxacin was evaluated. Ofloxacin was administered @ 20 mg.kg-1 body weight intravenously to a group of eight healthy rabbits and compared these results to values in same eight rabbits with EEIF. Pharmacokinetic parameters of ofloxacin in normal and febrile rabbits were determined by using two compartment open kinetic model. Peak plasma level (Cmax and area under the plasma concentration-time curve (AUC0-α in normal and febrile rabbits did not differ (P>0.05. However, area under first moment of plasma concentration-time curve (AUMC0-α in febrile rabbits was significantly (P<0.05 higher than that in normal rabbits. Mean values for elimination rate constant (Ke, elimination half life (t1/2β and apparent volume of distribution (Vd were significantly (P<0.05 lower in febrile rabbits compared to normal rabbits, while mean residence time (MRT and total body clearance (Cl of ofloxacin did not show any significant difference in the normal and febrile rabbits. Clinical significance of the above results can be related to the changes in the volume of distribution and elimination half life that illustrates an altered steady state in febrile condition; hence, the need for an adjustment of dosage regimen in EEIF is required.

  8. Human Handling Promotes Compliant Behavior in Adult Laboratory Rabbits

    Science.gov (United States)

    Swennes, Alton G; Alworth, Leanne C; Harvey, Stephen B; Jones, Carolyn A; King, Christopher S; Crowell-Davis, Sharon L

    2011-01-01

    Routine laboratory procedures can be stressful for laboratory animals. We wanted to determine whether human handling of adult rabbits could induce a degree of habituation, reducing stress and facilitating research-related manipulation. To this end, adult New Zealand white rabbits were handled either frequently or minimally. After being handled over 3 wk, these rabbits were evaluated by novel personnel and compared with minimally handled controls. Evaluators subjectively scored the rabbits for their relative compliance or resistance to being scruffed and removed from their cages, being transported to a treatment room, and their behavior at all stages of the exercise. Upon evaluation, handled rabbits scored significantly more compliant than nontreated controls. During evaluation, behaviors that the rabbits displayed when they were approached in their cages and while being handled outside their cages were recorded and compared between study groups. Handled rabbits displayed behavior consistent with a reduction in human-directed fear. This study illustrates the potential for handling to improve compliance in laboratory procedures and reduce fear-related behavior in laboratory rabbits. Such handling could be used to improve rabbit welfare through the reduction of stress and exposure to novel stimuli. PMID:21333162

  9. Effect of feed restriction on performance of growing rabbits

    Directory of Open Access Journals (Sweden)

    Maria Cristina de Oliveira

    2012-06-01

    Full Text Available This experiment assessed the effect of feed restriction in rabbits on performance and economic viability of the activity. Sixty New Zealand White rabbits, weaned at 33 days and slaughtered at 81 days of age, were used. The design was of randomized blocks with four treatments and five replications. The treatments were, as follows: 1 - free feeding, 2 - feed restriction from 35 to 40 days of age (50 g/d/rabbit, 3 - feed restriction from 54 to 61 days of age (90 g/d/rabbit and 4 - feed restriction from 33 to 40 days (50 g/d/rabbit and from 54 to 61 days of age (90 g/d/rabbit. There was no difference in the performance and carcass parameters, indicating that there was compensatory growth in the rabbits that suffered feed restriction. The best gross margin was obtained with feed restriction from 54 to 61 days age. Feed restriction in growing rabbits can be adopted at different ages because it does not interfere negatively in the performance and carcass parameters. In two periods and from 51 to 61 days, feed restriction was more economically viable for the sale of live and slaughtered rabbits, respectively.

  10. Latent autoimmune diabetes of adulthood: case report.

    Science.gov (United States)

    Page, Cristen P; Fitzgerald, Brian; Hawes, Emily M

    2017-01-01

    polyglandular autoimmune syndrome type IIIa. It serves as a reminder that clinicians should remember that patients with one autoimmune disease (in this case, h/o Graves' disease) are at higher risk for diabetes and other endocrine autoimmune diseases and should be screened appropriately. Clinicians should keep latent type 1 diabetes in the differential in adulthood to ensure proper and timely treatment.

  11. Intracutaneous DNA Vaccination with the E8 Gene of Cottontail Rabbit Papillomavirus Induces Protective Immunity against Virus Challenge in Rabbits

    OpenAIRE

    Hu, Jiafen; Han, Ricai; Cladel, Nancy M.; Pickel, Martin D; Christensen, Neil D.

    2002-01-01

    The cottontail rabbit papillomavirus (CRPV)-rabbit model has been used in several studies for testing prophylactic and therapeutic papillomavirus vaccines. Earlier observations had shown that the CRPV nonstructural genes E1, E2, and E6 induced strong to partial protective immunity against CRPV infection. In this study, we found that CRPV E8 immunization eliminated virus-induced papillomas in EIII/JC inbred rabbits (100%) and provided partial protection (55%) against virus challenge in outbred...

  12. Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

    OpenAIRE

    Bertagnoli, Stéphane; Gelfi, Jacqueline; Le Gall, Ghislaine; Boilletot, Eric; Vautherot, Jean-François; Rasschaert, Denis; Laurent, Sylvie; Petit, Frédérique; Boucraut-Baralon, Corine; Milon, Alain

    1996-01-01

    Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma vir...

  13. The Biological Effects of Sex Hormones on Rabbit Articular Chondrocytes from Different Genders

    National Research Council Canada - National Science Library

    Chang, Shwu Jen; Kuo, Shyh Ming; Lin, Yen Ting; Yang, Shan-Wei

    2014-01-01

    ...-estradiol and testosterone) on rabbit articular chondrocytes from different genders. We cultured primary rabbit articular chondrocytes from both genders with varying concentration of sex hormones...

  14. Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

    Science.gov (United States)

    Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

    1996-08-01

    Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

  15. Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits.

    Science.gov (United States)

    Bertó-Moran, Alejandro; Pacios, Isabel; Serrano, Emmanuel; Moreno, Sacramento; Rouco, Carlos

    2013-01-01

    The interaction among several parasites in European rabbits (Oryctolagus cuniculus) is crucial to host fitness and to the epidemiology of myxomatosis and rabbit hemorrhagic disease. These diseases have caused significant reductions in rabbit populations on the Iberian Peninsula. Most studies have focused on the epidemiology and pathogenesis of these viruses individually, and little is known about interactions between these viruses and other parasites. Taking advantage of an experimental restocking program in Spain, the effects of coccidian and nematode infections on the probability of having detectable antibody to myxoma and rabbit hemorrhagic disease viruses were tested in European wild rabbits. For 14 mo, we monitored rabbit abundance and parasite loads (coccidia and nematodes) in three reintroduced rabbit populations. While coccidian and nematode loads explained seasonal antibody prevalences to myxoma virus, the pattern was less clear for rabbit hemorrhagic disease. Contrary to expectations, prevalence of antibody to myxoma virus was inversely proportional to coccidian load, while nematode load seemed to play a minor role. These results have implications for viral disease epidemiology and for disease management intended to increase rabbit populations in areas where they are important for ecosystem conservation.

  16. Accuracy and reliability of forensic latent fingerprint decisions

    Science.gov (United States)

    Ulery, Bradford T.; Hicklin, R. Austin; Buscaglia, JoAnn; Roberts, Maria Antonia

    2011-01-01

    The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. The National Research Council of the National Academies and the legal and forensic sciences communities have called for research to measure the accuracy and reliability of latent print examiners’ decisions, a challenging and complex problem in need of systematic analysis. Our research is focused on the development of empirical approaches to studying this problem. Here, we report on the first large-scale study of the accuracy and reliability of latent print examiners’ decisions, in which 169 latent print examiners each compared approximately 100 pairs of latent and exemplar fingerprints from a pool of 744 pairs. The fingerprints were selected to include a range of attributes and quality encountered in forensic casework, and to be comparable to searches of an automated fingerprint identification system containing more than 58 million subjects. This study evaluated examiners on key decision points in the fingerprint examination process; procedures used operationally include additional safeguards designed to minimize errors. Five examiners made false positive errors for an overall false positive rate of 0.1%. Eighty-five percent of examiners made at least one false negative error for an overall false negative rate of 7.5%. Independent examination of the same comparisons by different participants (analogous to blind verification) was found to detect all false positive errors and the majority of false negative errors in this study. Examiners frequently differed on whether fingerprints were suitable for reaching a conclusion. PMID:21518906

  17. Variation in amino acid and lipid composition of latent fingerprints.

    Science.gov (United States)

    Croxton, Ruth S; Baron, Mark G; Butler, David; Kent, Terry; Sears, Vaughn G

    2010-06-15

    The enhancement of latent fingerprints, both at the crime scene and in the laboratory using an array of chemical, physical and optical techniques, permits their use for identification. Despite the plethora of techniques available, there are occasions when latent fingerprints are not successfully enhanced. An understanding of latent fingerprint chemistry and behaviour will aid the improvement of current techniques and the development of novel ones. In this study the amino acid and fatty acid content of 'real' latent fingerprints collected on a non-porous surface was analysed by gas chromatography-mass spectrometry. Squalene was also quantified in addition. Hexadecanoic acid, octadecanoic acid and cis-9-octadecenoic acid were the most abundant fatty acids in all samples. There was, however, wide variation in the relative amounts of each fatty acid in each sample. It was clearly demonstrated that touching sebum-rich areas of the face immediately prior to fingerprint deposition resulted in a significant increase in the amount of fatty acids and squalene deposited in the resulting 'groomed' fingerprints. Serine was the most abundant amino acid identified followed by glycine, alanine and aspartic acid. The significant quantitative differences between the 'natural' and 'groomed' fingerprint samples seen for fatty acids were not observed in the case of the amino acids. This study demonstrates the variation in latent fingerprint composition between individuals and the impact of the sampling protocol on the quantitative analysis of fingerprints. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  18. Differentiation of active and latent trigger points by thermography.

    Science.gov (United States)

    Diakow, P R

    1992-09-01

    This study tested whether two distinct thermographic patterns attributed to myofascial trigger points could distinguish between active and latent trigger points. A retrospective chart survey was undertaken with thermographic data divided into two groups: a) increased thermal emission only over the trigger point and b) over the area of pain referral. The criterion standard used in a blinded comparison was physical examination findings separating active from latent trigger points. All cases were drawn from a private practice referral center for thermographic evaluation of neck and low back injuries. A sample of 65 cases showing physical examination findings of trigger points was chosen from 229 consecutive motor vehicle accident case files. There was moderate agreement between the two methods of differentiating active from latent latent trigger points (Kappa = 0.44) with a specificity of 0.70 and a sensitivity of 0.74. When cases in which spinal segmental dysfunction were eliminated, the agreement increased (Kappa = 0.54) with specificity of 0.82 and sensitivity of 0.74. Thermography may be a useful tool in distinguishing active from latent trigger points, but the thermal imaging of spinal joint dysfunction may be a compounding factor.

  19. Skin Resistivity Value of Upper Trapezius Latent Trigger Points.

    Science.gov (United States)

    Skorupska, Elżbieta; Zawadziński, Jarosław; Bednarek, Agata; Samborski, Włodzimierz

    2015-01-01

    The skin resistivity (SkR) measurement is commonly recommended for acupoints measurement, but for trigger points (TrPs) only one study is available. The purpose of the study was to evaluate SkR for latent TrPs compared to non-TrPs and the surrounding tissue. Forty-two healthy volunteers with unilateral latent upper trapezius TrPs (12 men, 30 women) aged 21-23 (mean age: 22.1 ± 0.6 y) participated in the study. Keithley electrometer 610B was used for measuring SkR (Ag/AgCl self-adhesive, disposable ground electrode: 30 mm diameter). SkR was measured for latent TrPs and compared to opposite non-TrPs sites and the surrounding tissue. The SkR decrease of TrPs-positive sites as compared to TrPs-negative sites and the surrounding tissue was confirmed. However, no statistically significant difference in the SkR value occurred when all data were analyzed. The same was confirmed after gender division and for TrPs-positive subjects examined for referred pain and twitch response presence. SkR reactive changes at latent TrPs are possible but the results were not consistent with the previous study. Thus, caution in applying SkR to latent TrPs isolation is recommended and its clinical use should not be encouraged yet. Further studies, especially on active TrPs, are yet required.

  20. Study of noninvasive detection of latent fingerprints using UV laser

    Science.gov (United States)

    Li, Hong-xia; Cao, Jing; Niu, Jie-qing; Huang, Yun-gang; Mao, Lin-jie; Chen, Jing-rong

    2011-06-01

    Latent fingerprints present a considerable challenge in forensics, and noninvasive procedure that captures a digital image of the latent fingerprints is significant in the field of criminal investigation. The capability of photography technologies using 266nm UV Nd:YAG solid state laser as excitation light source to provide detailed images of unprocessed latent fingerprints is demonstrated. Unprocessed latent fingerprints were developed on various non-absorbent and absorbing substrates. According to the special absorption, reflection, scattering and fluorescence characterization of the various residues in fingerprints (fatty acid ester, protein, and carbosylic acid salts etc) to the UV light to weaken or eliminate the background disturbance and increase the brightness contrast of fingerprints with the background, and using 266nm UV laser as excitation light source, fresh and old latent fingerprints on the surface of four types of non-absorbent objects as magazine cover, glass, back of cellphone, wood desktop paintwork and two types of absorbing objects as manila envelope, notebook paper were noninvasive detected and appeared through reflection photography and fluorescence photography technologies, and the results meet the fingerprint identification requirements in forensic science.

  1. Market Driving to Develop Rabbit Meat Products in Indonesia

    Directory of Open Access Journals (Sweden)

    Atien Priyanti

    2012-09-01

    Full Text Available Rabbit meat is a nutritional food containing high protein and low cholesterol, fat and sodium. Current research in rabbit production is aimed for developing production strategies to increase the nutritional and economic values of rabbit meat products as functional food. Nowadays, producing rabbit is a popular farming activity in many parts of Indonesia as a small and medium scale operation for food security and cash income. Rabbit farming is to produce meat, skin and hides, fur, organic fertilizers and pet or fancy animals. Consumption of rabbit meat is considered very low, due partly to low meat supply and inavailability of marketing. In some tourist areas, such as Lembang (West Java, Tawangmangu (Central Java, Sarangan and Batu (East Java rabbit meat is a specific food. Attempt to create and drive rabbit markets will simultaneously increase meat production to fulfill the demand and meet economic scale of farming. Hence, this will give significant impact to the farmers’ welfare. Availability of good quality meat, dissemination and diversification of meat products, production efficiency toward competitive price along with its proper marketing strategy will drive consumers’ preferences to consume more rabbit meat. Market driving needs to be created in order to promote rabbit meat products by establishing food outlets. This program has been developed by a farmers group in Magelang, Central Java. During the period of 2006 – 2007 the food outlets had increased to 5 outlets, and in 2012 become 9 outlets. This market driving will also have an impact on changing orientation of rabbit farming from traditional to a small and medium economic scale that will influence the production efficiency.

  2. Myxomatosis in farmland rabbit populations in England and Wales.

    Science.gov (United States)

    Ross, J; Tittensor, A M; Fox, A P; Sanders, M F

    1989-10-01

    The overall pattern and consequences of myxomatosis in wild rabbit populations were studied at three farmland sites in lowland southern England and upland central Wales between 1971 and 1978. When results from all years were combined, the disease showed a clear two-peaked annual cycle, with a main autumn peak between August and January, and a subsidiary spring peak during February to April. Rabbit fleas, the main vectors of myxomatosis in Britain, were present on full-grown rabbits in sufficient numbers for transmission to occur throughout the year, but the observed seasonal pattern of the disease appeared to be influenced by seasonal mass movements of these fleas. However other factors were also important including the timing and success of the main rabbit breeding season, the proportion of rabbits which had recovered from the disease and the timing and extent of autumn rabbit mortality from other causes. Significantly more males than females, and more adults and immatures than juveniles, were observed to be infected by myxomatosis. Only 25-27% of the total populations were seen to be infected during outbreaks. Using two independent methods of calculation, it was estimated that between 47 and 69% of infected rabbits died from the disease (much lower than the expected 90-95% for fully susceptible rabbits with the partly attenuated virus strains that predominated). Thus it was estimated that 12-19% of the total rabbit populations were known to have died directly or indirectly from myxomatosis. Although the effects of myxomatosis were much less than during the 1950s and 1960s, it continued to be an important mortality factor. It may still have a regulatory effect on rabbit numbers, with autumn/winter peaks of disease reducing the numbers of rabbits present at the start of the breeding season.

  3. Latent Tuberculosis in Pregnancy: A Systematic Review.

    Science.gov (United States)

    Malhamé, Isabelle; Cormier, Maxime; Sugarman, Jordan; Schwartzman, Kevin

    2016-01-01

    In countries with low tuberculosis (TB) incidence, immigrants from higher incidence countries represent the major pool of individuals with latent TB infection (LTBI). The antenatal period represents an opportunity for immigrant women to access the medical system, and hence for potential screening and treatment of LTBI. However, such screening and treatment during pregnancy remains controversial. In order to further understand the prevalence, natural history, screening and management of LTBI in pregnancy, we conducted a systematic literature review addressing the screening and treatment of LTBI, in pregnant women without known HIV infection. A systematic review of 4 databases (Embase, Embase Classic, Medline, Cochrane Library) covering articles published from January 1st 1980 to April 30th 2014. Articles in English, French or Spanish with relevant information on prevalence, natural history, screening tools, screening strategies and treatment of LTBI during pregnancy were eligible for inclusion. Articles were excluded if (1) Full text was not available (2) they were case series or case studies (3) they focused exclusively on prevalence, diagnosis and treatment of active TB (4) the study population was exclusively HIV-infected. Of 4,193 titles initially identified, 208 abstracts were eligible for review. Of these, 30 articles qualified for full text review and 22 were retained: 3 cohort studies, 2 case-control studies, and 17 cross-sectional studies. In the USA, the estimated prevalence of LTBI ranged from 14 to 48% in women tested, and tuberculin skin test (TST) positivity was associated with ethnicity. One study suggested that incidence of active TB was significantly increased during the 180 days postpartum (Incidence rate ratio, 1.95 (95% CI 1.24-3.07). There was a high level of adherence with both skin testing (between 90-100%) and chest radiography (93-100%.). In three studies from low incidence settings, concordance between TST and an interferon-gamma release

  4. Latent Tuberculosis in Pregnancy: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Isabelle Malhamé

    Full Text Available In countries with low tuberculosis (TB incidence, immigrants from higher incidence countries represent the major pool of individuals with latent TB infection (LTBI. The antenatal period represents an opportunity for immigrant women to access the medical system, and hence for potential screening and treatment of LTBI. However, such screening and treatment during pregnancy remains controversial.In order to further understand the prevalence, natural history, screening and management of LTBI in pregnancy, we conducted a systematic literature review addressing the screening and treatment of LTBI, in pregnant women without known HIV infection.A systematic review of 4 databases (Embase, Embase Classic, Medline, Cochrane Library covering articles published from January 1st 1980 to April 30th 2014. Articles in English, French or Spanish with relevant information on prevalence, natural history, screening tools, screening strategies and treatment of LTBI during pregnancy were eligible for inclusion. Articles were excluded if (1 Full text was not available (2 they were case series or case studies (3 they focused exclusively on prevalence, diagnosis and treatment of active TB (4 the study population was exclusively HIV-infected.Of 4,193 titles initially identified, 208 abstracts were eligible for review. Of these, 30 articles qualified for full text review and 22 were retained: 3 cohort studies, 2 case-control studies, and 17 cross-sectional studies. In the USA, the estimated prevalence of LTBI ranged from 14 to 48% in women tested, and tuberculin skin test (TST positivity was associated with ethnicity. One study suggested that incidence of active TB was significantly increased during the 180 days postpartum (Incidence rate ratio, 1.95 (95% CI 1.24-3.07. There was a high level of adherence with both skin testing (between 90-100% and chest radiography (93-100%.. In three studies from low incidence settings, concordance between TST and an interferon

  5. Current management options for latent tuberculosis: a review

    Directory of Open Access Journals (Sweden)

    Norton BL

    2012-11-01

    Full Text Available Brianna L Norton, David P HollandDepartment of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USAAbstract: Tuberculosis remains the world’s second leading infectious cause of death, with nearly one-third of the global population latently infected. Treatment of latent tuberculosis infection is a mainstay of tuberculosis-control efforts in low-to medium-incidence countries. Isoniazid monotherapy has been the standard of care for decades, but its utility is impaired by poor completion rates. However, new, shorter-course regimens using rifamycins improve completion rates and are cost-saving compared with standard isoniazid monotherapy. We review the currently available therapies for latent tuberculosis infection and their toxicities and include a brief economic comparison of the different regimens.Keywords: isoniazid, rifampin, rifapentine, tuberculin skin test, interferon-gamma release assay

  6. Rare Earth Fluorescent Nanomaterials for Enhanced Development of Latent Fingerprints.

    Science.gov (United States)

    Wang, Meng; Li, Ming; Yu, Aoyang; Wu, Jian; Mao, Chuanbin

    2015-12-30

    The most commonly found fingerprints at crime scenes are latent and, thus, an efficient method for detecting latent fingerprints is very important. However, traditional developing techniques have drawbacks such as low developing sensitivity, high background interference, complicated operation, and high toxicity. To tackle this challenge, we have synthesized two kinds of rare earth fluorescent nanomaterials, including the fluoresce red-emitting YVO4:Eu nanocrystals and green-emitting LaPO4:Ce,Tb nanobelts, and then used them as fluorescent labels for the development of latent fingerprints with high sensitivity, high contrast, high selectivity, high efficiency, and low background interference, on various substrates including noninfiltrating materials, semi-infiltrating materials, and infiltrating materials.

  7. A combined feature latent semantic model for scene classification

    Science.gov (United States)

    Jiang, Yue; Wang, Runsheng

    2009-10-01

    Due to vast growth of image databases, scene image classification methods have become increasingly important in computer vision areas. We propose a new scene image classification framework based on combined feature and a latent semantic model which is based on the Latent Dirichlet Allocation (LDA) in the statistical text literature. Here the model is applied to visual words representation for images. We use Gibbs sampling for parameter estimation and use several different numbers of topics at the same time to obtain the latent topic representation of images. We densely extract multi-scale patches from images and get the combined feature on these patches. Our method is unsupervised. It can also well represent semantic characteristic of images. We demonstrate the effectiveness of our approach by comparing it to those used in previous work in this area. Experiments were conducted on three often used image databases, and our method got better results than the others.

  8. Surface Ig on rabbit lymphocytes. Rabbit B and T cells are distinct populations

    NARCIS (Netherlands)

    Bast, B J; Catty, D; Manten-Slingerland, R; Jansen, J T; Veldhuis, Dick H.; Roholl, P; Ballieux, R E

    1979-01-01

    Rabbit peripheral blood lymphocytes (PBL) were analyzed by immunofluorescence using anti-T cell conjugates and anti-Fab, anti-a1 allotype, anti-IgM and anti-IgA conjugates. In addition, T cells were demonstrated by rosetting with papain-treated homologous erythrocytes. Control experiments, using

  9. [Association between single nucleotide polymorphism of MC4R gene and carcass traits in rabbits].

    Science.gov (United States)

    Jiang, Mei-Shan; Chen, Shi-Yi; Lai, Song-Jia; Deng, Xiao-Song; Chen, Yun; Wan, Jie

    2008-12-01

    Single nucleotide polymorphisms in the coding sequence of melanoeortin-4 receptor (MC4R) gene were detected by PCR-SSCP and DNA sequencing method in Harbin white rabbit, Tianfu black rabbit, Belgian hare, ZIKA rabbit, and California rabbit breeds. A-->G conversion mutation at base position 237 was found with high frequency in Harbin white rabbit, Belgian hare, and Zika rabbit and low frequency in Tianfu black rabbit and California rabbit. The allele A was pre-dominant allele for each of meat rabbit breeds. AA genotype frequency was higher than AG genotype in the five studied rabbit breeds. GLM analysis for the effect of genotypes on performance traits demonstrated that AG genotype was significantly associated with body weight, eviscerated weight and feed conversion efficiency (P0.05). It was concluded from the results that MC4R gene could be a candidate modifier gene that affects or controls body weight and carcass traits of rabbit.

  10. Effects of Latent Toxoplasmosis on Autoimmune Thyroid Diseases in Pregnancy

    Science.gov (United States)

    Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

    2014-01-01

    Background Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Methods Cross-sectional study in 1248 consecutive pregnant women in the 9–12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Results Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Conclusions Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases. PMID:25350671

  11. Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy.

    Science.gov (United States)

    Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

    2014-01-01

    Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Cross-sectional study in 1248 consecutive pregnant women in the 9-12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases.

  12. Interexaminer variation of minutia markup on latent fingerprints.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2016-07-01

    Latent print examiners often differ in the number of minutiae they mark during analysis of a latent, and also during comparison of a latent with an exemplar. Differences in minutia counts understate interexaminer variability: examiners' markups may have similar minutia counts but differ greatly in which specific minutiae were marked. We assessed variability in minutia markup among 170 volunteer latent print examiners. Each provided detailed markup documenting their examinations of 22 latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. An average of 12 examiners marked each latent. The primary factors associated with minutia reproducibility were clarity, which regions of the prints examiners chose to mark, and agreement on value or comparison determinations. In clear areas (where the examiner was "certain of the location, presence, and absence of all minutiae"), median reproducibility was 82%; in unclear areas, median reproducibility was 46%. Differing interpretations regarding which regions should be marked (e.g., when there is ambiguity in the continuity of a print) contributed to variability in minutia markup: especially in unclear areas, marked minutiae were often far from the nearest minutia marked by a majority of examiners. Low reproducibility was also associated with differences in value or comparison determinations. Lack of standardization in minutia markup and unfamiliarity with test procedures presumably contribute to the variability we observed. We have identified factors accounting for interexaminer variability; implementing standards for detailed markup as part of documentation and focusing future training efforts on these factors may help to facilitate transparency and reduce subjectivity in the examination process. Published by Elsevier Ireland Ltd.

  13. Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy.

    Directory of Open Access Journals (Sweden)

    Šárka Kaňková

    Full Text Available BACKGROUND: Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. METHODS: Cross-sectional study in 1248 consecutive pregnant women in the 9-12th gestational weeks. Serum thyroid-stimulating hormone (TSH, thyroperoxidase antibodies (TPOAb, and free thyroxine (FT4 were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA. RESULTS: Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004, and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049. Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033, which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014, as well as a positive correlation between FT4 and log2 CFT (p = 0.009. CONCLUSIONS: Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases.

  14. Fortification of cassava peel meals in balanced diets for rabbits ...

    African Journals Online (AJOL)

    The diets were fortified with palm oil for energy and soyabean and palm kernel cake for protein. Each diet was fed to four replicates of rabbits consisting of one rabbit per replicate and water was supplied ad libitum. Feed intake, weight-gain and feed cost/unit weight-gain were significantly affected by dietary treatments ...

  15. Performance of growing rabbits fed graded levels of sugarcane peel ...

    African Journals Online (AJOL)

    Twenty five growing rabbits of mixed breeds and average weight of 894g were used in a seven week feeding trial. Five experimental diets were formulated in which sugarcane peels (SCP) was included at 0, 10, 20, 30 and 40% levels to replace maize offal. The rabbits were balanced for weight and allotted to the treatments ...

  16. Immunogenic Response of Rabbits to Monovalent and Polyvalent ...

    African Journals Online (AJOL)

    Slide agglutination and indirect haemagglutination tests were used for detecting and measuring specific antibodies against the strains used. Antisera against polyvalent immunogens protected 83-100% of rabbits against A1, A7 and 50% of rabbits against A2 challenge while the lowest protection (16- 33%) was seen in ...

  17. Haematological profile in salt loaded experimental rabbits treated ...

    African Journals Online (AJOL)

    This study evaluates the haematological profile of salt loaded rabbits treated with Acalypha wilkesiana ethanolic leaf extract. Twenty-four rabbits were randomized into four groups (A - D) of six animals each. Group A-C were fed salt-loaded diet for 35 days, subsequently group B were treated with extract for 7 days. Group C ...

  18. Response of growing rabbits to graded levels of fermented and ...

    African Journals Online (AJOL)

    No significant (P>0.05) difference was observed in daily feed intake of rabbits as a result of dietary inclusion level or processing type of PPM. Better (P<0.05) feed efficiency was recorded in rabbits fed PPM at 12.5% dietary inclusion level than those fed at 25%. Fermentation enhanced the nutritional value of feedstuff and ...

  19. Rabbit droppings as an organic fertilizer in earthen ponds, to ...

    African Journals Online (AJOL)

    cntaganda

    Preliminary results obtained in Cameroon pointed to the promising effect of rabbit manure as a water fertilizer for Oreochromis niloticus ponds and as a food-source for the catfish Heterobranchus longifilis (Breine et al., 1995). (Franco, 1991), using dried rabbit dung to feed tilapia O. niloticus in mesocosms, reported that the ...

  20. The reservoir status of rabbits for the maintenance of Ehrlichia ...

    African Journals Online (AJOL)

    The reservoir status of rabbits for a strain of Ehrlichia ruminantium was investigated using six experimental and four controlled rabbits. Each of the experimental animals was intraperitoneally inoculated with 1.5 ml of infective blood from a febrile goat. The effect of the parasite on body weight, packed cell volume, total protein ...

  1. Doe productivity indices and sire effects of a heterogeneous rabbit ...

    African Journals Online (AJOL)

    IJAAAR

    forest zone. Animal, housing and reproductive management. Rabbits for this study were obtained from composite populations reared in Ibadan,. Osogbo and Ile-Ife in Southwestern Nigeria. The heterogeneous rabbit stocks are products of non-specific crosses of New Zealand White,. California, Chinchilla and Flemish Giant.

  2. Biochemical polymorphism in New Zealand white x Chinchilla rabbit ...

    African Journals Online (AJOL)

    The study evaluated diversity within New Zealand white and Chinchilla rabbit crosses using four structural protein loci: Hemoglobin (Hb), Albumin (Alb), Transferin (Tf) and Carbonic anhydrase (CA). Blood (4mls) was sampled from a total of 49 rabbits through ocular venipuncture. The samples collected were analysed using ...

  3. Tear film break-up time in rabbits.

    Science.gov (United States)

    Wei, Xiaojia E; Markoulli, Maria; Zhao, Zhenjun; Willcox, Mark D P

    2013-01-01

    Rabbits have a longer inter-blink time (approximately 10 minutes) compared with humans (five to eight seconds), suggesting that rabbits have a much more stable tear film. Using fluorescein, the tear break-up time of rabbits has been reported to be similar to that of humans. This study set out to measure the tear break-up time in rabbits using non-invasive methods and to establish the pattern of tear break-up compared to humans. The tear break-up time was measured and the pattern of tear break-up was observed in six New Zealand White rabbits on two separate occasions using both the Keeler Tearscope-plus(TM) and a slitlamp biomicroscope. The mean rabbit tear break-up time was 29.8 ± 3.4 (SD) minutes. This contrasts with the reports of human tear break-up time of eight to 30 seconds. The tear breaking spread very slowly and was often restricted to the area of the initial break. Rabbit tears have a significantly higher tear break-up time than humans and this aligns with previously demonstrated differences in inter-blink time between rabbits and humans. Understanding the underlying mechanisms of tear stability may lead to novel ways of increasing human tear film stability. © 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

  4. Comparison of radiation effects on weight of rabbits after ...

    African Journals Online (AJOL)

    This study, investigated the effects of radiation on weight change in rabbit following consumption of diets mixed with fresh and thermoxidised palm oil, common diets among the people in the tropics. Two groups of rabbits each were fed with normal diets (Control group 1), Fresh palm oil diets (FPOD) and thermoxidised palm ...

  5. Optimum rabbit density over fish ponds to optimise Nile tilapia ...

    African Journals Online (AJOL)

    Although previous studies have suggested that rabbit excreta can be used as high-quality manure for sustaining plankton production due to their gradual nutrient release, integrated rabbit–fish production systems are still not widely used. Between 2006 and 2010 optimal rabbit densities for sustainable integrated rabbit–Nile ...

  6. Characterization of a Heterogeneous Population of Rabbits for ...

    African Journals Online (AJOL)

    This study was conducted to describe prolificacy and litter characteristics of a Nigerian heterogeneous population of rabbits. Data on 535 kits sired by 10 bucks and 48 does across three parities were used to characterize this population of rabbits for prolificacy, pre-weaning litter traits and kit survival under on-station ...

  7. Genital tract morphometry and haematology of male rabbits fed ...

    African Journals Online (AJOL)

    A study was conducted to investigate the effects of feeding graded levels of cassava leaf meal (CLM) on genital tract morphometry and haematology of twenty 8-week old male rabbits weighing between 815 to 910g. The rabbits were randomly assigned to four dietary treatments viz: T (control), T , T and T with CLM inclusion ...

  8. Supplemental value of avizyme in diets of rabbits containing graded ...

    African Journals Online (AJOL)

    Growth performance, nutrient retention and hematological parameters of rabbits fed graded levels of wheat offal supplemented with Avizyme were studied. A total of 24, 9-week old New Zealand rabbits were fed for 49 days (7 weeks) on four experimental diets. Avizyme was added at the rate of 1 g kg-1 of wheat offal based ...

  9. Wildlife of southern forests habitat & management (Chapter 15): Rabbits

    Science.gov (United States)

    James G. Dickson

    2003-01-01

    Rabbits, or lagomorphs, resemble rodents. But unlike rodents they have relatively large hind legs, large ears, a short fluffy tail, and 2 sets of upper incisors. Like rodents their incisors grow continually. They can either walk or hop, and are fleet and elusive when evading predators. They normally are silent but are capable of several different vocalizations. Rabbits...

  10. Growth Indices and Apparent Nutrient Digestibility in Rabbits Fed ...

    African Journals Online (AJOL)

    The chemical composition of moringa leaf meal, growth performance and nutrient digestibility of growing rabbits fed graded levels of moringa leaf meal (MLM) were investigated. The MLM was incorporated in rabbit diet at 0, 5, 10 and 15% levels as replacement for soyabean meal (SBM) which constituted treatments ...

  11. Response of rabbits to varying levels of cassava and Leucaena ...

    African Journals Online (AJOL)

    An experiment was carried out to determine the performance, haematology, carcass characteristics and sensory evaluation of meat from rabbits (n = 30) fed varying levels of cassava and Leucaena leaf meal diets. Rabbits were randomly allocated to five dietary treatments of 0, 10, 20, 30 and 40% CLM replaced with LLM for ...

  12. Microhabitat Characteristics of sites used by swamp rabbits

    Science.gov (United States)

    Patrick A. Zollner; Winston P. Smith; Leonard A. Brennan

    2000-01-01

    The swamp rabbit (Sylvilagus aquaticus) is one of the least studied North American lagomorphs; a better understanding of the habitat types it uses will improve management of this species. We studied microhabitat characteristics of sites associated with specific behaviors of the swamp rabbit. During spring-summer (15 April-1 October) and fall-winter (...

  13. Growth Performance and Nutrients Digestibility of Weanling Rabbits ...

    African Journals Online (AJOL)

    An experiment was conducted to determine the effects of various levels of sesame seed meal inclusion on the performance and apparent nutrient digestibility of weanling rabbits. Sixteen, (New Zealand White) rabbits of mixed sexes were used for the experiment. They were weighed and randomly allotted to four dietary ...

  14. Growth response and nutrient digestibility of pre-pubertal rabbit ...

    African Journals Online (AJOL)

    A study was conducted to investigate the growth response and nutrient digestibility in rabbit bucks fed cottonseed cake (CSC)-based diets supplemented with vitamin E. 64 weanling rabbit bucks, aged five to six weeks and weighing averagely 511.28 g were involved in the study. The bucks were randomly allocated to eight ...

  15. Effects of Charcoal Inclusion on the Performance of Growing Rabbits ...

    African Journals Online (AJOL)

    An experiment was carried out to study the effects of charcoal inclusion in the diet of growing rabbits fed Acacia pod meal (APM) diet. Eighteen (18) growing rabbits of mixed breeds (give the crosses) and sexes with an average initial weight of 5202±0.25g were used for this study in a completely randomized design, ...

  16. Spontaneous Lung Lesions in Aging Laboratory Rabbits ( Oryctolagus cuniculus).

    Science.gov (United States)

    Cooper, T K; Griffith, J W; Chroneos, Z C; Izer, J M; Willing, L B; Peng, X

    2017-01-01

    Spontaneous age-related lesions of laboratory rabbits are not well documented in the contemporary scientific literature. A retrospective study of diagnostic necropsies of 36 rabbits >2 years of age found a number of common lung lesions. Fibromuscular intimal hyperplasia affected medium and to a lesser extent large pulmonary arteries and was present to a variable extent in all 36 rabbits >2 years of age. The lesions were characterized by fragmentation and/or reduplication of the internal elastic lamina (IEL), proliferation of smoothelin+/alpha-smooth muscle actin (α-SMA)+/vimentin- smooth muscle cells and fewer smoothelin-/α-SMA+/vimentin+ myofibroblasts, and intimal deposition of collagen without thrombosis, embolism, or evidence of pulmonary hypertension. Pulmonary emphysema, present in 30/36 rabbits, was characterized by the loss of alveolar septa; most affected rabbits did not have clinical signs of respiratory disease. In 8/13 rabbits of the inbred EIII/JC audiogenic strain, we identified a unique syndrome of granulomatous pneumonia containing hyaline brown to gray, globular to ring-like acellular material that was Alcian blue and periodic acid-Schiff positive. The material was immunoreactive for surfactant protein-A and had the ultrastructural appearance of multilamellar vesicles, suggesting a genetic defect in surfactant metabolism. Additionally, we found small benign primary lung tumors (fibropapillomas, 5 rabbits) not previously described. Other findings included heterotopic bone (5 rabbits), subacute to chronic suppurative bronchopneumonia, pyogranulomatous pneumonia with plant material, and pulmonary artifacts from barbiturate euthanasia solution.

  17. Cutaneous lymphomas in European pet rabbits (Oryctolagus cuniculus).

    Science.gov (United States)

    Ritter, J M; von Bomhard, W; Wise, A G; Maes, R K; Kiupel, M

    2012-09-01

    Cutaneous lymphoma is a common skin neoplasm of pet rabbits in Europe but is rarely reported in pet rabbits in North America. These neoplasms have not been previously characterized, nor has the cause for the apparent predilection for cutaneous lymphoma in European pet rabbits compared with North American pet rabbits been investigated. In this retrospective study, the authors morphologically and immunohistochemically characterized 25 cutaneous lymphomas in European pet rabbits according to the World Health Organization classification. Tumors were classified as diffuse large B cell lymphomas, with 14 lymphomas exhibiting a centroblastic/centrocytic subtype and 11 tumors exhibiting a T cell-rich B cell subtype. To investigate a potential viral etiology of these lymphomas, 3 diffuse large B cell and 3 T cell-rich B cell lymphomas were evaluated by polymerase chain reaction for retroviral and herpesviral genes. Neither virus was detected. In contrast to other domestic animals, cutaneous lymphomas in European pet rabbits were highly pleomorphic and frequently contained multinucleated giant cells. Unexpectedly, the second most common subtype was T cell-rich B cell lymphoma, a subtype that is rare in species other than horses. Based on a limited number of samples, there was no support for a viral etiology that would explain the higher incidence of lymphoma in European pet rabbits compared with American pet rabbits. Further investigation into genetic and extrinsic factors associated with the development of these tumors is warranted.

  18. Connections of the vestibular nuclei in the rabbit

    NARCIS (Netherlands)

    A.H. Epema

    1990-01-01

    textabstractThis thesis descnbes the afferent, efferent and intrinsic connections of the vestibular nuclei in the Dutch belted rabbit. Different anatomical tracing techniques were used to study these projections. A description of the vestibular complex was added, since recent data for the rabbit

  19. Performance and carcass characteristics of growing rabbits fed ...

    African Journals Online (AJOL)

    In an 84 days feeding trial, the effect of feeding bacterial protein meal (BPM) either as a replacement for fish meal or for groundnut cake meal in growing rabbits was examined. A total of 20 growing rabbits having an initial body weight of 617.2 (standard error 25) g were randomly assigned to five dietary treatments. A control ...

  20. the assessment of fasciola gigantica infection in the rabbit ...

    African Journals Online (AJOL)

    In this study, the rabbit was assessed as a laboratory host for the helminthes parasite, Fasciola gigantica. Three groups of rabbits were Infected experimentally with 5, 10 end 15 metacercariae of F. gigantica respectively. Clinical signs found included pale mucous membrane, progressive emaciation and rough hair coat.

  1. Performance characteristics of growing rabbits fed diet based on a ...

    African Journals Online (AJOL)

    A feeding trial using twenty four cross bred 8-9 weeks old rabbits was conducted to investigate the effect of feeding cerelac waste - CW (a by-product of the infant food industry considered as waste) on the performance and organ characteristics of growing rabbits. Three experimental diets were formulated with diet 1 serving ...

  2. Tolerance study of aqueous extract of Mitracarpus scaber in rabbits ...

    African Journals Online (AJOL)

    The study was to evaluate the cardiac safety of Mitracarpus scaber (Rubiaceae) in rabbit. In this study, different batches of rabbits were injected with increasing doses of aqueous extract of Mitracarpus scaber (encoded) and changes in the activities of serum glutamic oxaloacetic transaminase (GOT), lactate deshydrogenase ...

  3. Incomplete bone regeneration of rabbit calvarial defects using different membranes

    DEFF Research Database (Denmark)

    Aaboe, M; Pinholt, E M; Schou, S

    1998-01-01

    The present study describes the use of a degradable and a non-degradable material for guided bone regeneration. Forty rabbits were divided into 5 groups. Bicortical defects 15 mm in diameter were prepared in rabbit calvaria. A titanium microplate was placed over the defect to prevent collapse...

  4. Response of weaner rabbits to diets containing graded levels of ...

    African Journals Online (AJOL)

    An 8-week study was conducted to investigate the effect of feeding graded levels of cooked velvet beans (Mucuna pruriens) on growth performance and blood of weaner rabbits. 24, 6 week-old hybrid (Chinchilla x New Zealand white) weaner rabbits with initial average weight of 0.52 kg were housed in a hutch which ...

  5. Rabbit management and occurrences of mange mite infestations in ...

    African Journals Online (AJOL)

    A cross-sectional study was conducted in Morogoro Municipality between September and December 2015 to explore the rabbit farming and assess the common health problems with a focus on epidemiology of mange infestation. A total of 18 rabbit farms with 622 animals from 9 wards were investigated. A questionnaire ...

  6. Environmental bacteria associated with an institutional rabbit house ...

    African Journals Online (AJOL)

    A bacteriological investigation of microorganisms of public health importance associated with rabbit houses was undertaken to determine the occurrence of bacteria in rabbit house in Ibadan. A total of 144 swab samples were collected from which 160 bacterial isolates were recovered. E. coli, (20%) showed the highest ...

  7. Growth response and nutrient digestibility of pre- pubertal rabbit ...

    African Journals Online (AJOL)

    DR 'JIDE AMAO

    2012-09-20

    Sep 20, 2012 ... A study was conducted to investigate the growth response and nutrient digestibility in rabbit bucks fed cottonseed cake (CSC)-based diets supplemented with vitamin E. 64 weanling rabbit bucks, aged five to six weeks and weighing averagely 511.28 g were involved in the study. The bucks were randomly.

  8. Effect of Garlic on Perfusion Scintigraphy of Rabbit's Lungs ...

    African Journals Online (AJOL)

    Purpose: To study of the effect of garlic on rabbit's lungs, with the aid of perfusion scintigraphy, after experimentally-induced pulmonary embolism. Methods: Twelve adult rabbits were anesthetized. Prepared macroaggregated albumin- technetium 99m (99mTc-MAA) radiopharmaceutical was injected into the ear vein at a ...

  9. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced ...

    African Journals Online (AJOL)

    olayemitoyin

    lipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim of these experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet induced hyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= ...

  10. Growth and Reproductive Performance of Rabbits Fed Mistletoe ...

    African Journals Online (AJOL)

    Ten (10) rabbit does of mixed breeds aged between 5 – 6 months were used to study the effect of feeding mistletoe on feed intake, body weight and reproductive performance of rabbits. Following a pre - treatment period of two weeks during which the does were allowed to acclimatize to the environment, they were randomly ...

  11. Effect of Hibiscus sabdariffa calyx extract on stressed rabbit plasma ...

    African Journals Online (AJOL)

    Hibiscus sabdariffa aqueous extract has been shown to have antioxidant and lipid lowering effects in animal studies. This study is aimed at investigating the effects of the aqueous extract of Hibiscus sabdariffa calyx on the lipid profile of rabbits subjected to stress. The rabbits were stressed by suspension for 2 minutes, twice ...

  12. Castration causes progressive reduction of length of the rabbit penis ...

    African Journals Online (AJOL)

    Understanding of the alterations of the penile size in hypogonadism is important in clinical examination of hypogonadic patients. The aim of this study was to describe the changes in the rabbit penile length after castration. Fifteen adult male rabbits were used for the study. Nine of these were castrated under local anesthesia ...

  13. Growth indices and economic implications of weaned rabbits fed ...

    African Journals Online (AJOL)

    This study assessed the performance and economic implications of rabbits fed Leucaena leucocephala leaf protein concentrate (LLPC) as protein source to replace soybean meal in rabbit diet. Five experimental diets were formulated in which LLPC replaced soybean meal at 0, 5, 10, 15 and 20% (representing 0, 1.20, 2.40, ...

  14. Occurrence of Gastrointestinal Helminths in rabbits with special ...

    African Journals Online (AJOL)

    The aim of this study was to detect Giardia spp. as zoonotic helminth as Giardiosis has been recognised as the one of the important parasitic diarrhoea among children as cross transmission may occur between human and rabbits. Other helminths in rabbits may causes ill health and sometimes proved fatal. Faecal samples ...

  15. Skin Resistivity Value of Upper Trapezius Latent Trigger Points

    OpenAIRE

    Elżbieta Skorupska; Jarosław Zawadziński; Agata Bednarek; Włodzimierz Samborski

    2015-01-01

    Introduction. The skin resistivity (SkR) measurement is commonly recommended for acupoints measurement, but for trigger points (TrPs) only one study is available. The purpose of the study was to evaluate SkR for latent TrPs compared to non-TrPs and the surrounding tissue. Material and Methods. Forty-two healthy volunteers with unilateral latent upper trapezius TrPs (12 men, 30 women) aged 21–23 (mean age: 22.1 ± 0.6 y) participated in the study. Keithley electrometer 610B was used for measuri...

  16. Hippocampus NMDA receptors selectively mediate latent extinction of place learning.

    Science.gov (United States)

    Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

    2016-09-01

    Extinction of maze learning may be achieved with or without the animal performing the previously acquired response. In typical "response extinction," animals are given the opportunity to make the previously acquired approach response toward the goal location of the maze without reinforcement. In "latent extinction," animals are not given the opportunity to make the previously acquired response and instead are confined to the previous goal location without reinforcement. Previous evidence indicates that the effectiveness of these protocols may depend on the type of memory being extinguished. Thus, one aim of the present study was to further examine the effectiveness of response and latent extinction protocols across dorsolateral striatum (DLS)-dependent response learning and hippocampus-dependent place learning tasks. In addition, previous neural inactivation experiments indicate a selective role for the hippocampus in latent extinction, but have not investigated the precise neurotransmitter mechanisms involved. Thus, the present study also examined whether latent extinction of place learning might depend on NMDA receptor activity in the hippocampus. In experiment 1, adult male Long-Evans rats were trained in a response learning task in a water plus-maze, in which animals were reinforced to make a consistent body-turn response to reach an invisible escape platform. Results indicated that response extinction, but not latent extinction, was effective at extinguishing memory in the response learning task. In experiment 2, rats were trained in a place learning task, in which animals were reinforced to approach a consistent spatial location containing the hidden escape platform. In experiment 2, animals also received intra-hippocampal infusions of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (AP5; 5.0 or 7.5 ug/0.5 µg) or saline vehicle immediately before response or latent extinction training. Results indicated that both extinction protocols were

  17. Investigating design: A comparison of manifest and latent approaches

    DEFF Research Database (Denmark)

    Cash, Philip; Snider, Chris

    2014-01-01

    them together and explicitly investigating their complementarity in the design domain. This is realised using an example artificial observation study. In addition to discussing underlying relationships between the approaches, this paper identifies key opportunities for improving design research methods......This paper contributes to the on-going focus on improving design research methods, by exploring and synthesising two key interrelated research approaches e manifest and latent. These approaches are widely used individually in design research, however, this paper represents the first work bringing...... by more explicitly combining both manifest and latent elements. Finally, a number of combinatory approaches are proposed based on a conceptual framework. © 2014 Elsevier Ltd. All rights reserved....

  18. Latent Semantic Analysis of the Languages of Life

    Science.gov (United States)

    Rossi, Ryan Anthony

    We use Latent Semantic Analysis as a basis to study the languages of life. Using this approach we derive techniques to discover latent relationships between organisms such as significant motifs and evolutionary features. Doubly Singular Value Decomposition is defined and the significance of this adaptation is demonstrated by finding a phylogeny of twenty prokaryotes. Minimal Killer Words are used to define families of organisms from negative information. The application of these words makes it possible to automatically retrieve the coding frame of a sequence from any organism.

  19. Multimodal visual dictionary learning via heterogeneous latent semantic sparse coding

    Science.gov (United States)

    Li, Chenxiao; Ding, Guiguang; Zhou, Jile; Guo, Yuchen; Liu, Qiang

    2014-11-01

    Visual dictionary learning as a crucial task of image representation has gained increasing attention. Specifically, sparse coding is widely used due to its intrinsic advantage. In this paper, we propose a novel heterogeneous latent semantic sparse coding model. The central idea is to bridge heterogeneous modalities by capturing their common sparse latent semantic structure so that the learned visual dictionary is able to describe both the visual and textual properties of training data. Experiments on both image categorization and retrieval tasks demonstrate that our model shows superior performance over several recent methods such as K-means and Sparse Coding.

  20. Gene variants associated with antisocial behaviour: a latent variable approach.

    Science.gov (United States)

    Bentley, Mary Jane; Lin, Haiqun; Fernandez, Thomas V; Lee, Maria; Yrigollen, Carolyn M; Pakstis, Andrew J; Katsovich, Liliya; Olds, David L; Grigorenko, Elena L; Leckman, James F

    2013-10-01

    The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15-year follow-up of a randomized trial of a prenatal and infancy nurse-home visitation programme in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed. Eight single-nucleotide polymorphisms (SNPs) from eight genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all eight genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid and cholinergic signalling as well as stress response pathways in mediating susceptibility to antisocial behaviour. This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential 'co-action' of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the aetiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a