1,256 research outputs found

    Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

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    TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations

    A pilot randomized controlled study of the mental health first aid elearning course with UK medical students

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    Background: Medical students face many barriers to seeking out professional help for their mental health, including stigma relating to mental illness, and often prefer to seek support and advice from fellow students. Improving medical students’ mental health literacy and abilities to support someone experiencing a mental health problem could reduce barriers to help seeking and improve mental health in this population. Mental Health First Aid (MHFA) is an evidence-based intervention designed to improve mental health literacy and ability to respond to someone with a mental health problem. This pilot randomised controlled trial aims to evaluate the MHFA eLearning course in UK medical students. Methods: Fifty-five medical students were randomised to receive six weeks access to the MHFA eLearning course (n = 27) or to a no-access control group (n = 28). Both groups completed baseline (pre-randomisation) and follow-up (six weeks post-randomisation) online questionnaires measuring recognition of a mental health problem, mental health first aid intentions, confidence to help a friend experiencing a mental health problem, and stigmatising attitudes. Course feedback was gathered at follow-up. Results: More participants were lost follow-up in the MHFA group (51.9%) compared to control (21.4%). Both intention-to-treat (ITT) and non-ITT analyses showed that the MHFA intervention improved mental health first aid intentions (p = <.001) and decreased stigmatising attitudes towards people with mental health problems (p = .04). While ITT analysis found no significant Group x Time interaction for confidence to help a friend, the non-ITT analysis did show the intervention improved confidence to help a friend with mental health problems (p =<.001), and improved mental health knowledge (p = .003). Medical students in the intervention group reported a greater number of actual mental health first aid actions at follow-up (p = .006). Feedback about the MHFA course was generally positive, with participants stating it helped improve their knowledge and confidence to help someone. Conclusion: This pilot study demonstrated the potential for the MHFA eLearning course to improve UK medical students’ mental health first aid skills, confidence to help a friend and stigmatising attitudes. It could be useful in supporting their own and others’ mental health while studying and in their future healthcare careers

    Factors associated with 2009 pandemic influenza A (H1N1) vaccination acceptance among university students from India during the post-pandemic phase

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    <p>Abstract</p> <p>Background</p> <p>There was a low adherence to influenza A (H1N1) vaccination program among university students and health care workers during the pandemic influenza in many parts of the world. Vaccination of high risk individuals is one of the recommendations of World Health Organization during the post-pandemic period. It is not documented about the student's knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period. We aimed to analyze the student's knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period in India.</p> <p>Methods</p> <p>Vaccine against H1N1 was made available to the students of Vellore Institute of Technology, India from September 2010. The data are based on a cross-sectional study conducted during October 2010 to January 2011 using a self-administered questionnaire with a representative sample of the student population (N = 802).</p> <p>Results</p> <p>Of the 802 respondents, only 102/802 (12.7%) had been vaccinated and 105/802 (13%) planned to do so in the future, while 595/802 (74%) would probably or definitely not get vaccinated in the future. The highest coverage was among the female (65/102, 63.7%) and non-compliance was higher among men in the group (384/595; 64.5%) (p < 0.0001). The representation of students from school of Bio-sciences and Bio-technology among vaccinees is significantly higher than that of other schools. Majority of the study population from the three groups perceived vaccine against H1N1 as the effective preventive measure when compared to other preventive measures. 250/595 (42%) of the responders argued of not being in the risk group. The risk perception was significantly higher among female (p < 0.0001). With in the study group, 453/802 (56.4%) said that they got the information, mostly from media.</p> <p>Conclusions</p> <p>Our study shows that the vaccination coverage among university students remains very low in the post-pandemic period and doubts about the safety and effectiveness of the vaccine are key elements in their rejection. Our results indicate a need to provide accessible information about the vaccine safety by scientific authorities and fill gaps and confusions in this regard.</p

    Surface Roughness of Commercial Composites after Different Polishing Protocols: An Analysis with Atomic Force Microscopy

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    Polishing may increase the surface roughness of composites, with a possible effect on bacterial growth and material properties. This preliminary in vitro study evaluates the effect of three different polishing systems (PoGo polishers, Enhance, Venus Supra) on six direct resin composites (Gradia Direct, Venus, Venus Diamond, Enamel Plus HFO, Tetric Evoceram, Filtek Supreme XT)

    The Antiviral Spectra of TRIM5α Orthologues and Human TRIM Family Proteins against Lentiviral Production

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    Rhesus monkey TRIM5α (TRIM5αrh) recognizes the incoming HIV-1 core through its C-terminal B30.2(PRYSPRY) domain and promotes its premature disassembly or degradation before reverse transcription. Previously, we have shown that TRIM5αrh blocks HIV-1 production through the N-terminal RBCC domain by the recognition of Gag polyproteins. Although all TRIM family proteins have RBCC domains, it remains elusive whether they possess similar late-restriction activities.We examined the antiviral spectra of TRIM5α orthologues and human TRIM family members which have a genetic locus proximal to human TRIM5α (TRIM5αhu), against primate lentiviral production. When HIV-1 virus-like particles (VLPs) were generated in the presence of TRIM5α proteins, rhesus, African green and cynomolgus monkey TRIM5α (TRIM5αag and TRIM5αcy), but not TRIM5αhu, were efficiently incorporated into VLPs, suggesting an interaction between HIV-1 Gag and TRIM5α proteins. TRIM5αrh potently restricted the viral production of HIV-1 groups M and O and HIV-2, but not simian lentiviruses including SIV(MAC)1A11, SIV(AGM)Tan-1 or SIV(AGM)SAB-1. TRIM5αhu did not show notable late restriction activities against these lentiviruses. TRIM5αag and TRIM5αcy showed intermediate restriction phenotypes against HIV-1 and HIV-2, but showed no restriction activity against SIV production. A series of chimeric TRIM5α constructs indicated that the N-terminal region of TRIM5αag and TRIM5αcy are essential for the late restriction activity, while the C-terminal region of TRIM5αcy negatively regulates the late restriction activity against HIV-1. When select human TRIM family proteins were examined, TRIM21 and 22 were efficiently incorporated into HIV-1 VLPs, while only TRIM22 reduced HIV-1 titers up to 5-fold. The antiviral activities and encapsidation efficiencies did not correlate with their relative expression levels in the producer cells.Our results demonstrated the variations in the late restriction activities among closely related TRIM5α orthologues and a subset of human TRIM family proteins, providing further insights into the late restriction activities of TRIM proteins
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