Human APOBEC3 proteins can inhibit xenotropic murine leukemia virus-related virus infectivity

AbstractXenotropic murine leukemia virus-related virus (XMRV) is a novel retrovirus, related to murine leukemia virus (MLV), that has been implicated in human disease. If XMRV is indeed able to replicate in humans, then one might predict that XMRV would have developed resistance to human innate antiviral resistance factors such as APOBEC3G (hA3G). In fact, we observed that XMRV and MLV are both highly sensitive to inhibition by hA3G and equally resistant to inhibition by murine APOBEC3. While several human prostate cancer cell lines were found to lack hA3G, stable expression of physiological levels of hA3G rendered these cells refractory to XMRV replication. Few human tissues fail to express hA3G, and we therefore hypothesize that XMRV replicates in one or more hA3G-negative reservoir tissues and/or that human XMRV infections are likely to be rare and potentially of zoonotic origin

Urban blue space renovation and local resident and visitor well-being:A case study from Plymouth, UK

Observational studies have suggested that people with better access to attractive, safe, and inclusive blue spaces enjoy higher psychological well-being, with particular benefits for those living in deprived urban areas. However, intervention studies are scarce. To help bridge this gap we conducted a repeat cross-sectional study exploring local resident and visitor well-being before and after a small-scale intervention aimed at improving the quality of an urban beach area in a deprived neighbourhood in Plymouth, United Kingdom. Physical alterations were co-created with local stakeholders and residents, and accompanied by a series of on-site community events. Key outcomes were self-reported psychological well-being, satisfaction with personal safety and community belonging, and perceptions of site quality. Adjusted linear models showed that positive well-being (B = 7.42; 95% CI = 4.18–10.67) and life satisfaction (B = 0.40; 95% CI = 0.11–0.70) were both higher after the intervention compared to before, with associations for life satisfaction stronger among those who visited the site in the last four weeks. Associations with positive well-being were partially mediated by greater satisfaction with community belonging; and associations with life satisfaction were partially and independently mediated by greater satisfaction with personal safety and community belonging. Although caution needs to be taken due to the repeat cross-sectional design and the sampling of site visitors as well as local residents, the findings support the idea that environmental improvements to urban blue spaces can foster better psychological well-being, and underline the importance of community involvement in the process

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Internal and external cooling methods and their effect on body temperature, thermal perception and dexterity

© 2018 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0191416© 2018 Maley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective The present study aimed to compare a range of cooling methods possibly utilised by occupational workers, focusing on their effect on body temperature, perception and manual dexterity. Methods Ten male participants completed eight trials involving 30 min of seated rest followed by 30 min of cooling or control of no cooling (CON) (34C, 58% relative humidity). The cooling methods utilised were: ice cooling vest (CV0), phase change cooling vest melting at 14C (CV14), evaporative cooling vest (CVEV), arm immersion in 10C water (AI), portable water-perfused suit (WPS), heliox inhalation (HE) and ice slushy ingestion (SL). Immediately before and after cooling, participants were assessed for fine (Purdue pegboard task) and gross (grip and pinch strength) manual dexterity. Rectal and skin temperature, as well as thermal sensation and comfort, were monitored throughout. Results Compared with CON, SL was the only method to reduce rectal temperature (P = 0.012). All externally applied cooling methods reduced skin temperature (P0.05). Conclusion The present study observed that ice ingestion or ice applied to the skin produced the greatest effect on rectal and skin temperature, respectively. AI should not be utilised if workers require subsequent fine manual dexterity. These results will help inform future studies investigating appropriate pre-cooling methods for the occupational worker.This project is financially supported by the US Government through the Technical Support Working Group within the Combating Terrorism Technical Support Office.Published versio

Evolutionarily conserved and non-conserved retrovirus restriction activities of artiodactyl APOBEC3F proteins

The APOBEC3 proteins are unique to mammals. Many inhibit retrovirus infection through a cDNA cytosine deamination mechanism. HIV-1 neutralizes this host defense through Vif, which triggers APOBEC3 ubiquitination and degradation. Here, we report an APOBEC3F-like, double deaminase domain protein from three artiodactyls: cattle, pigs and sheep. Like their human counterparts, APOBEC3F and APOBEC3G, the artiodactyl APOBEC3F proteins are DNA cytosine deaminases that locate predominantly to the cytosol and can inhibit the replication of HIV-1 and MLV. Retrovirus restriction is attributable to deaminase-dependent and -independent mechanisms, as deaminase-defective mutants retain significant anti-retroviral activity. However, unlike human APOBEC3F and APOBEC3G, the artiodactyl APOBEC3F proteins have an active N-terminal DNA cytosine deaminase domain, which elicits a broader dinucleotide deamination preference, and they are resistant to HIV-1 Vif. These data indicate that DNA cytosine deamination; sub-cellular localization and retrovirus restriction activities are conserved in mammals, whereas active site location, local mutational preferences and Vif susceptibility are not. Together, these studies indicate that some properties of the mammal-specific, APOBEC3-dependent retroelement restriction system are necessary and conserved, but others are simultaneously modular and highly adaptable

INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio)

INSL3 (insulin-like peptide 3) is a relaxin peptide family member expressed by Leydig cells in the vertebrate testis. In mammals, INSL3 mediates testicular descent during embryogenesis but information on its function in adults is limited. In fish, the testes remain in the body cavity, although the insl3 gene is still expressed, suggesting yet undiscovered, evolutionary older functions. Anti-Müllerian hormone (Amh), in addition to inhibiting spermatogonial differentiation and androgen release, inhibits the Fsh (follicle-stimulating hormone)-induced increase in insl3 transcript levels in zebrafish testis. Therefore, the two growth factors might have antagonistic effects. We examine human INSL3 (hINSL3) effects on zebrafish germ cell proliferation/differentiation and androgen release by using a testis tissue culture system. hINSL3 increases the proliferation of type A undifferentiated (Aund) but not of type A differentiating (Adiff) spermatogonia, while reducing the proliferation of Sertoli cells associated with proliferating Aund. Since the area occupied by Aund decreases and that of Adiff increases, we conclude that hINSL3 recruits Aund into differentiation; this is supported by the hINSL3-induced down-regulation of nanos2 transcript levels, a marker of single Aund spermatogonia in zebrafish and other vertebrates. Pulse-chase experiments with a mitosis marker also indicate that hINSL3 promotes spermatogonial differentiation. However, hINSL3 does not modulate basal or Fsh-stimulated androgen release or growth factor transcript levels, including those of amh. Thus, hINSL3 seems to recruit Aund spermatogonia into differentiation, potentially mediating an Fsh effect on spermatogenesis

Work-Related Well-Being Among Dutch Cardiologists - A National Survey

This is the first study to provide a holistic examination of cardiologists' well-being, investigating positive and negative dimensions, and its determinants. We conducted a national, multicenter, self-administered web-based questionnaire. We used frequencies to depict scores on three well-being indicators (professional fulfillment, work exhaustion and interpersonal disengagement) and performed three multiple regression analyses to elucidate their determinants. Cardiologists' mean scores (scale 1 to 5) were 3.85 (SD = 0.62) for professional fulfillment, 2.25 (SD = 0.97) for work exhaustion and 2.04 (SD = 0.80) for interpersonal disengagement. Workload, work-home interference and team atmosphere predicted the negative dimensions of well-being. Autonomy predicted cardiologists' professional fulfillment. Physician-patient interactions, person-job fit and individual resilience affected both dimensions. Dutch cardiologists score relatively high on professional fulfillment and average on work exhaustion and interpersonal disengagement. In order to foster cardiologists' well-being it is critical to increase energy providing work- and individual aspects

Encapsidation of APOBEC3G into HIV-1 virions involves lipid raft association and does not correlate with APOBEC3G oligomerization

<p>Abstract</p> <p>Background</p> <p>The cellular cytidine deaminase APOBEC3G (A3G), when incorporated into the human immunodeficiency virus type 1 (HIV-1), renders viral particles non-infectious. We previously observed that mutation of a single cysteine residue of A3G (C100S) inhibited A3G packaging. In addition, several recent studies showed that mutation of tryptophan 127 (W127) and tyrosine 124 (Y124) inhibited A3G encapsidation suggesting that the N-terminal CDA constitutes a viral packaging signal in A3G. It was also reported that W127 and Y124 affect A3G oligomerization.</p> <p>Results</p> <p>Here we studied the mechanistic basis of the packaging defect of A3G W127A and Y124A mutants. Interestingly, cell fractionation studies revealed a strong correlation between encapsidation, lipid raft association, and genomic RNA binding of A3G. Surprisingly, the presence of a C-terminal epitope tag affected lipid raft association and encapsidation of the A3G W127A mutant but had no effect on wt A3G encapsidation, lipid raft association, and interaction with viral genomic RNA. Mutation of Y124 abolished A3G encapsidation irrespective of the presence or absence of an epitope tag. Contrasting a recent report, our co-immunoprecipitation studies failed to reveal a correlation between A3G oligomerization and A3G encapsidation. In fact, our W127A and Y124A mutants both retained the ability to oligomerize.</p> <p>Conclusion</p> <p>Our results confirm that W127 and Y124 residues in A3G are important for encapsidation into HIV-1 virions and our data establish a novel correlation between genomic RNA binding, lipid raft association, and viral packaging of A3G. In contrast, we were unable to confirm a role of W127 and Y124 in A3G oligomerization and we thus failed to confirm a correlation between A3G oligomerization and virus encapsidation.</p