As an environment-dependent pleiotropic gene regulator in Gram-negative bacteria, the H-NS protein is crucial for adaptation and toxicity control of human pathogens such as Salmonella, Vibrio cholerae or enterohaemorrhagic Escherichia coli. Changes in temperature affect the capacity of H-NS to form multimers that condense DNA and restrict gene expression. However, the molecular mechanism through which H-NS senses temperature and other physiochemical parameters remains unclear and controversial. Combining structural, biophysical and computational analyses, we show that human body temperature promotes unfolding of the central dimerization domain, breaking up H-NS multimers. This unfolding event enables an autoinhibitory compact H-NS conformation that blocks DNA binding. Our integrative approach provides the molecular basis for H-NS–mediated environment-sensing and may open new avenues for the control of pathogenic multi-drug resistant bacteria.

While virtual reality (VR) is emerging as an interactive tool for chemical education, its application and assessment for chemical education are still limited. Thus, an educational VR activity based on interactive molecular dynamics in virtual reality (iMD-VR), which allows for realtime, immersive interactions with a dynamic molecular world, was now designed and executed to demonstrate chemical concepts and engage students in exploring molecular structures, motions, and interactions. There were 70 students in the first semester of an introductory organic chemistry course asked to complete an example task to pull a methane molecule through a carbon nanotube with iMD-VR software originally designed for research purposes by Glowacki and coworkers. Our assessments of this activity have shown valuable motivational impacts and measurable learning gains. The VR activity can be further tailored to many different levels by varying the topics and tasks, with affordable hardware and software.

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BackgroundYears of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting.MethodsClinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD.ResultsSubjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide.LimitationsFindings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample.ConclusionsThe relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD.

The G protein-coupled pituitary adenylate cyclase-activating polypeptide receptor (PAC1R) is a potential therapeutic target for endocrine, metabolic and stress-related disorders. However, many questions regarding the protein structure and dynamics of PAC1R remain largely unanswered. Using microsecond-long simulations, we examined the open and closed PAC1R conformations interconnected within an ensemble of transitional states. The open-to-closed transition can be initiated by “unzipping” the extracellular domain and the transmembrane domain, mediated by a unique segment within the β3-β4 loop. Transitions between different conformational states range between microseconds to milliseconds, which clearly implicate allosteric effects propagating from the extracellular face of the receptor to the intracellular G protein-binding site. Such allosteric dynamics provides structural and mechanistic insights for the activation and modulation of PAC1R and related class B receptors.