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Although further studies are needed, these findings indicate that for the purpose of mitigating rises in core temperature exceeding recommended limits (&gt;1 °C), ACGIH guidelines have comparable effectiveness in non-heat acclimatized men and women during moderate-intensity work. Novelty Sex did not appreciably influence thermal strain nor the proportion of participants with core temperatures exceeding recommended limits. Sex did not significantly influence tolerance to uncompensable heat stress. Despite originating from data obtained in only men, current occupational heat stress guidance offered comparable effectiveness in men and women.This study examined whether the attitudinal responses toward child sexual abuse (CSA) differ due to the person's relationship with the victim (intrafamilial vs. extrafamilial) and/or proximity to the victim (close vs. distant). An online sample of 292 participants completed a measure assessing pre-existing attitudes toward people who commit sexual offenses, before being randomly presented with a vignette describing a CSA case committed by a biological father, biological uncle, babysitter, stranger, or stepfather. Participants then rated the perpetrator's level of dangerousness and pedophilic interest, their own feelings of disgust, and their punitive judgments. Controlling for pre-existing attitudes, the extrafamilial cases (stranger and babysitter) were perceived to be more dangerous (large effects; ds &gt; .50) and more pedophilic than the stepfather (large effects; ds &gt; .60). Also, participants reported greater levels of disgust toward the stranger than both the babysitter and uncle (medium effects; ds &gt; .30). The findings demonstrate the need to account for the established heterogeneity of men who commit CSA when studying the public's attitudinal responses. Methodological limitations and suggestions for future research are also discussed.<br /><br /> Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects many organs of the body including the peripheral nervous system (PNS) which has potential significant impact. Plexopathy is rare but one of the serious PNS manifestations of lupus.<br /><br /> A 41-year-old female presented with recurrent attacks of painful brachial plexopathy and right hemi-diaphragmatic paralysis. After extensive workup, she was diagnosed with SLE and started on hydroxychloroquine and mycophenolate mofetil. The frequency and severity of the attacks of plexopathy has significantly improved after starting the immune suppressive therapy for SLE. Whole exome sequencing unveiled previously unreported mutations encoding non-synonymous amino acids in titin and minichromosome maintenance 3-associated protein.<br /><br /> Recurrent attacks of painful brachial plexopathy may warrant careful evaluation for underlying SLE with a premise of therapeutic benefit.<br /><br />Recurrent attacks of painful brachial plexopathy may warrant careful evaluation for underlying SLE with a premise of therapeutic benefit.Sexual violence in sport is prevalent and represents a serious public health concern. The social-ecological model for health promotion has been used successfully as a framework to identify individual-to-policy level factors aimed at health promotion or disease prevention. The purpose of this review was to examine both published and non-published (publicly available) SVP efforts conducted within the context of sport and make recommendations for future practice. Grey literature search methods were utilized to conduct a review of publicly available documents. This included (a) a comprehensive Google search using unique search terms that would identify SVP efforts within sport settings and (b) a review of the publicly accessible websites identified in the previous step. Following the grey literature search, and using the SVP practices identified in step one, we conducted a supplementary literature search using scientific publication search engines to identify whether the SVP practices identified in step one had associated peer-reviewed publications. Finally, we assessed various characteristics of each SVP practice including the target population, age range of intended participants, and whether the SVP had associated peer review publications. This led to the identification of 35 unique SVP practices 25 (71%) SVP practices were assigned to the Intrapersonal level, 6 (17%) were assigned to the Interpersonal level, 9 (26%) were assigned to the Organizational level, 3 (9%) were assigned to the Community, and 2 (6%) were assigned to the Policy level. This review uncovered several important findings including a lack of multi-level SVP practices within sport, a lack of SVP practices that target children, minimal programming aimed at specifically preventing perpetration, the need to elevate policy level action, and a lack of peer-reviewed literature. Ultimately findings suggest that sport organizations ought to prioritize sexual violence prevention using national organizations for guidance.SignificanceThe study provided a long-sought molecular mechanism that could explain the link between fatty acid metabolism and cancer metastasis. Further understanding may lead to new strategies to inhibit cancer metastasis. The chemical proteomic approach developed here will be useful for discovering other regulatory mechanisms of protein function by small molecule metabolites.SignificanceWe directly visualize DNA translocation and lesion recognition by the O6-alkylguanine DNA alkyltransferase (AGT). Our data show bidirectional movement of AGT monomers and clusters on undamaged DNA that depended on Zn2+ occupancy of AGT. A role of cooperative AGT clusters in enhancing lesion search efficiencies by AGT has previously been proposed. Surprisingly, our data show no enhancement of DNA translocation speed by AGT cluster formation, suggesting that AGT clusters may serve a different role in AGT function. Our data support preferential cluster formation by AGT at alkyl lesions, suggesting a role of these clusters in stabilizing lesion-bound complexes. From our data, we derive a new model for the lesion search and repair mechanism of AGT.SignificanceJuvenile hormone (JH), a sesquiterpenoid, regulates many aspects of insect development, including maintenance of the larval stage by preventing metamorphosis. In contrast, ecdysteroids promote metamorphosis by inducing the E93 transcription factor, which triggers apoptosis of larval cells and remodeling of the larval midgut. We discovered that JH suppresses precocious larval midgut-remodeling by inducing an epigenetic modifier, histone deacetylase 3 (HDAC3). [https://www.selleckchem.com/products/gsk126.html click here] JH-induced HDAC3 deacetylates the histone H4 localized at the promoters of proapoptotic genes, resulting in the suppression of these genes. This eventually prevents programmed cell death of midgut cells and midgut-remodeling during larval stages. These studies identified a previously unknown mechanism of JH action in blocking premature remodeling of the midgut during larval feeding stages.SignificancePARP is an important target in the treatment of cancers, particularly in patients with breast, ovarian, or prostate cancer that have compromised homologous recombination repair (i.e., BRCA-/-). This review about inhibitors of PARP (PARPi) is for readers interested in the development of next-generation drugs for the treatment of cancer, providing insights into structure-activity relationships, in vitro vs. in vivo potency, PARP trapping, and synthetic lethality.SignificanceHosts often target the relatively conserved regions in rapidly mutating retroviruses to inhibit their replication. One of these regions is called a primer binding site (PBS), which has to be complementary to the host tRNA to initiate reverse transcription. By analyzing endogenous retroviral elements, we found that host cells use this sequence as a target in efforts to block the expression of viral elements. A specific type of zinc finger protein targets the PBS in a host genome, which not only inhibits the transcription of endogenous viruses but also inhibits the replication of exogenous retroviruses with the same PBS. Thus, our study sheds light on a strategy for searching for host restriction factors targeting retroviruses.SignificanceIntracellular gradients have essential roles in cell and developmental biology, but their formation is not fully understood. We have developed a computational approach facilitating interpretation of protein dynamics and gradient formation. We have combined this computational approach with experiments to understand how Polo-Like Kinase 1 (PLK-1) forms a cytoplasmic gradient in Caenorhabditis elegans embryos. Although the PLK-1 gradient depends on the Muscle EXcess-5/6 (MEX-5/6) proteins, we reveal differences in PLK-1 and MEX-5 gradient formation that can be explained by a model with two components, PLK-1 bound to MEX-5 and unbound PLK-1. Our combined approach suggests that a weak coupling between PLK-1 and MEX-5 reaction-diffusion mechanisms dictates the dynamic exchange of PLK-1 with the cytoplasm, explaining PLK-1 high diffusivity and smooth gradient.SignificanceNeurodegenerative diseases are poorly understood and difficult to treat. One common hallmark is lysosomal dysfunction leading to the accumulation of aggregates and other undegradable materials, which cause damage to brain resident cells. Lysosomes are acidic organelles responsible for breaking down biomolecules and recycling their constitutive parts. In this work, we find that the antiinflammatory and neuroprotective compound, discovered via a phenotypic screen, imparts its beneficial effects by targeting the lysosome and restoring its function. This is established using a genome-wide CRISPRi target identification screen and then confirmed using a variety of lysosome-targeted studies. The resulting small molecule from this study represents a potential treatment for neurodegenerative diseases as well as a research tool for the study of lysosomes in disease.SignificanceWe first observed a transient chirality inversion on a simple unimolecular platform during the racemization of a chiral helical complex [LCo3A6]3+, i.e., the helicity changed from P-rich (right-handed) to M-rich (left-handed), which then racemized to a P/M equimolar mixture in spite of the absence of a reagent that could induce the M helix. This transient chirality inversion was observed only in the forward reaction, whereas the reverse reaction showed a simple monotonic change with an induction time. Consequently, the M helicity appeared only in the forward reaction. These forward and reverse reactions constitute a hysteretic cycle. Compounds showing such unique time responses would be useful for developing time-programmable switchable materials that can control the physical/chemical properties in a time-dependent manner.SignificanceThe GGGGCC hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS). Despite myriad studies on the toxic effects of poly-dipeptides produced from the C9orf72 repeats, the mechanisms underlying the selective hyperexcitability of motor cortex that characterizes the early stages of C9orf72 ALS patients remain elusive. Here, we show that the proline-arginine poly-dipeptides cause hyperexcitability in cortical motor neurons by increasing persistent sodium currents conducted by the Nav1.2/β4 sodium channel complex, which is highly expressed in the motor cortex. These findings provide the basis for understanding how the C9orf72 mutation causes motor neuron hyperactivation that can lead to the motor neuron death in C9orf72 ALS.