Broad Resistance to ACCase Inhibiting Herbicides in a Ryegrass Population Is Due Only to a Cysteine to Arginine Mutation in the Target Enzyme

BACKGROUND: The design of sustainable weed management strategies requires a good understanding of the mechanisms by which weeds evolve resistance to herbicides. Here we have conducted a study on the mechanism of resistance to ACCase inhibiting herbicides in a Lolium multiflorum population (RG3) from the UK. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of plant phenotypes and genotypes showed that all the RG3 plants (72%) that contained the cysteine to arginine mutation at ACCase codon position 2088 were resistant to ACCase inhibiting herbicides. Whole plant dose response tests on predetermined wild and mutant 2088 genotypes from RG3 and a standard sensitive population indicated that the C2088R mutation is the only factor conferring resistance to all ten ACCase herbicides tested. The associated resistance indices ranged from 13 for clethodim to over 358 for diclofop-methyl. Clethodim, the most potent herbicide was significantly affected even when applied on small mutant plants at the peri-emergence and one leaf stages. CONCLUSION/SIGNIFICANCE: This study establishes the clear and unambiguous importance of the C2088R target site mutation in conferring broad resistance to ten commonly used ACCase inhibiting herbicides. It also demonstrates that low levels "creeping", multigenic, non target site resistance, is not always selected before single gene target site resistance appears in grass weed populations subjected to herbicide selection pressure

Perceptions of HIV cure research among people living with HIV in Australia

Participation in HIV cure-related clinical trials that involve antiretroviral treatment (ART) interruption may pose substantial individual risks for people living with HIV (PLHIV) without any therapeutic benefit. As such, it is important that the views of PLHIV are considered in the design of HIV cure research trials. Examining the lived experience of PLHIV provides unique and valuable perspectives on the risks and benefits of HIV cure research. In this study, we interviewed 20 PLHIV in Australia about their knowledge and attitudes toward clinical HIV cure research and explored their views regarding participation in HIV cure clinical trials, including those that involve ART interruption. Data were analysed thematically, using both inductive and deductive coding techniques, to identity themes related to perceptions of HIV cure research and PLHIV’s assessment of the possible risks and benefits of trial participation. Study findings revealed interviewees were willing to consider participation in HIV cure research for social reasons, most notably the opportunity to help others. Concerns raised about ART interruption related to the social and emotional impact of viral rebound, including fear of onward HIV transmission and anxiety about losing control. These findings reveal the ways in which PLHIV perspectives deepen our understanding of HIV cure research, moving beyond a purely clinical assessment of risks and benefits in order to consider the social context

Loss of Toll-Like Receptor 4 Function Partially Protects against Peripheral and Cardiac Glucose Metabolic Derangements During a Long-Term High-Fat Diet

We would like to acknowledge Matt Priest for excellent technical assistance.Diabetes is a chronic inflammatory disease that carries a high risk of cardiovascular disease. However, the pathophysiological link between these disorders is not well known. We hypothesize that TLR4 signaling mediates high fat diet (HFD)-induced peripheral and cardiac glucose metabolic derangements. Mice with a loss-of-function mutation in TLR4 (C3H/HeJ) and age-matched control (C57BL/6) mice were fed either a high-fat diet or normal diet for 16 weeks. Glucose tolerance and plasma insulin were measured. Protein expression of glucose transporters (GLUT), AKT (phosphorylated and total), and proinflammatory cytokines (IL-6, TNF-α and SOCS-3) were quantified in the heart using Western Blotting. Both groups fed a long-term HFD had increased body weight, blood glucose and insulin levels, as well as impaired glucose tolerance compared to mice fed a normal diet. TLR4-mutant mice were partially protected against long-term HFD-induced insulin resistance. In control mice, feeding a HFD decreased cardiac crude membrane GLUT4 protein content, which was partially rescued in TLR4-mutant mice. TLR4-mutant mice fed a HFD also had increased expression of GLUT8, a novel isoform, compared to mice fed a normal diet. GLUT8 content was positively correlated with SOCS-3 and IL-6 expression in the heart. No significant differences in cytokine expression were observed between groups, suggesting a lack of inflammation in the heart following a HFD. Loss of TLR4 function partially restored a healthy metabolic phenotype, suggesting that TLR4 signaling is a key mechanism in HFD-induced peripheral and cardiac insulin resistance. Our data further suggest that TLR4 exerts its detrimental metabolic effects in the myocardium through a cytokine-independent pathway.Yeshttp://www.plosone.org/static/editorial#pee

The Role of Gay-Related Stigma in HIV-Risk Behavior Among Sexual Minority Men in Europe

Sexual orientation stigma stems from discriminatory social contexts and may ultimately impact the behavioral health of stigmatized individuals through stress-related pathways. Sexual minority stigma is of particular concern in Europe given the diversity of social contexts on the continent and sexual minority men's rapidly increasing risk of HIV infection, especially in Central and Eastern Europe, potentially rooted in stigma. This study assesses whether stigma in the ubiquitous social contexts surrounding sexual minority men (e.g., family, workplace, government) may place them at higher risk for HIV contraction across six countries. We utilized a large cross-sectional survey sample of HIV-negative sexual minority men (N\u2009=\u20092087; mean age\u2009=\u200931.6, SD\u2009=\u20099.7) from six European countries to test whether those who reported sexual orientation stigma also engaged in more HIV risk-related behaviors, including condomless sex with casual partners (in the absence of PrEP) and substance use before and during sex. Regression analyses were performed in Mplus. We found that a one standard deviation increase in reported sexual orientation stigma was significantly associated with the following during the last sexual encounter: a 19% increase in odds of sex under the influence of alcohol, 27% increase in odds of sex under the influence of cannabis, 49% increase in odds of sex under the influence of illicit drugs, an 11% increase in odds of condomless sex with casual partners in the past 6\ua0months, and a 26% increase in odds of knowing where to receive an HIV test. Sexual minority men who reported perceiving greater sexual orientation-related stigma within their ubiquitous social contexts were significantly more likely to report sexual risk and alcohol and drug use during their last sexual encounter, yet reported more knowledge of preventive services. Contextual stigma might serve as a precursor to behavioral risks of HIV infection, generating maladaptive stress responses capable of being modified through individually-focused interventions. Structural interventions are also needed to ultimately reduce stigma at its source

Network Influences on the Sexual Risk Behaviors of Gay, Bisexual and Other Men Who Have Sex with Men Using Geosocial Networking Applications

Geosocial networking applications (GSN apps) have become increasingly popular among gay, bisexual and other men who have sex with men (MSM). Our study sought to understand whether inclusion of individuals met via GSN apps in participants’ social networks was associated with increased HIV risk behaviors among a probability sample of GSN app using MSM (N=295) recruited in Los Angeles, California. Approximately 20% of participants included a GSN app-met individual as one of their top five closest social network members. Those with a GSN app-met network member had more recent (past 30-day) sexual partners (B=1.21, p<0.05), were nearly twice as likely to have engaged in unprotected anal intercourse (UAI) with their last sexual partner (AOR=2.02, p<0.05), and were nearly four times as likely to have engaged in UAI with their last GSN app-met sexual partner (AOR=3.98, p<0.001). Network-based interventions delivered via GSN apps may be useful in preventing the spread of HIV among MSM