The rockefeller university

All primates communicate. To dissect the neural circuits of social communication, we used fMRI to map non- human primate brain regions for social perception, second- person (interactive) social cognition, and orofacial movement generation. Face perception, second- person cognition, and face motor networks were largely non- overlapping and acted as distinct functional units rather than an integrated feedforward- processing pipeline. Whereas secondperson context selectively engaged a region of medial prefrontal cortex, production of orofacial movements recruited distributed subcortical and cortical areas in medial and lateral frontal and insular cortex. These areas exhibited some specialization, but not dissociation, of function along the mediolateral axis. Production of lipsmack movements recruited areas including putative homologs of Broca's area. These findings provide a new view of the neural architecture for social communication and suggest expressive orofacial movements generated by lateral premotor cortex as a putative evolutionary precursor to human speech.

Liver organogenesis requires complex cell-cell interactions between hepatic endoderm cells and adjacent cell niches. Endothelial cells are key players for endoderm hepatic fate decision. We previously demonstrated that the endothelial cell niche promotes hepatic specification of mouse embryonic stem cell(ESC)-derived endoderm through dual repression of Wnt and Notch pathways in endoderm cells. In the present study, we dissected further the mechanisms by which endothelial cells trigger endoderm hepatic specification. Using our previously established in vitro mouse ESC system mimicking the early hepatic specification process, endoderm cells were purified and co-cultured with endothelial cells to induce hepatic specification. The comparison of transcriptome profiles between hepatic endoderm cells isolated from co-cultures and endoderm cells cultured alone revealed that VEGF signaling instructs hepatic specification of endoderm cells through endothelial VEGFR2 activation. Additionally, epigenetic mark inhibition assays upon co-cultures uncovered that histone acetylation and DNA methylation promote hepatic specification while histone methylation inhibits it. This study provides an efficient 2D platform modelling the endothelial cell niche crosstalk with endoderm, and reveals mechanisms by which endothelial cells promote hepatic specification of mouse ESC-derived endoderm cells through endothelial VEGFR2 activation and endoderm epigenetic modifications.

Depressive disorders constitute a set of debilitating diseases with psychological, societal, economic and humanitarian consequences for millions of people worldwide. Scientists are beginning to understand the reciprocal communication between the brain and the rest of the body in the etiology of these diseases. In particular, scientists have noted a connection between depressive disorders, which are primarily seen as brain-based, and, insulin resistance (IR), a modifiable metabolic inflammatory state that is typically seen as peripheral. We highlight evidence showing how treating IR, with drugs or behavioral interventions, may ameliorate or possibly prevent, depressive disorders and their long-term consequences at various stages of the life course. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders. (C) 2017 Elsevier Ltd. All rights reserved.

A measurement of the electroweak (EW) production of two jets in association with a Z boson in proton-proton collisions at root s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lljj final state with l including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m(ll) > 50 GeV, m(jj) > 120 GeV, and transverse momenta P-Tj > 25 GeV is sigma(EW) (lljj) = 534 +/- 20 (stat) fb (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 < cwww/Lambda(2) < 2.6 TeV-2 and -8.4 < cw/Lambda(2) < 10.1 TeV-2. The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.

Neurons of the medullary reticular nucleus gigantocellularis (NGC) and their targets have recently been a focus of research on mechanisms supporting generalized CNS arousal (GA) required for proper cognitive functions. Using the retro-TRAP method, we characterized transcripts enriched in NGC neurons which have projections to the thalamus. The unique expression and activation of the endothelial nitric oxide (eNOS) signaling pathway in these cells and their intimate connections with blood vessels indicate that these neurons exert direct neurovascular coupling. Production of nitric oxide (NO) within eNOS-positive NGC neurons increases after environmental perturbations, indicating a role for eNOS/NO in modulating environmentally appropriate levels of GA. Inhibition of NO production causes dysregulated behavioral arousal after exposure to environmental perturbation. Further, our findings suggest interpretations for associations between psychiatric disorders and mutations in the eNOS locus.

Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 x 10(-7)), SMARCC1 (p = 8.15 x 10(-10)), and PTCH1 (p = 1.06 x 10(-6)). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 x 10(-4)). Together, these probands account for similar to 10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.

Objectives: Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) regulate food intake and body weight, glucose metabolism and convey the reward value of sucrose. In this report, we set out to establish the respective roles of MCH and conventional neurotransmitters in these neurons. Methods: MCH neurons were profiled using Cre-dependent molecular profiling technologies (vTRAP). MCHCre mice crossed to Vglut2(fl/fl)mice or to DTR(fl/fl)were used to identify the role of glutamate in MCH neurons. We assessed metabolic parameters such as body composition, glucose tolerance, or sucrose preference. Results: We found that nearly all MCH neurons in the LH are glutamatergic and that a loss of glutamatergic signaling from MCH neurons from a glutamate transporter (VGlut2) knockout leads to a reduced weight, hypophagia and hyperkinetic behavior with improved glucose tolerance and a loss of sucrose preference. These effects are indistinguishable from those seen after ablation of MCH neurons. These findings are in contrast to those seen in mice with a knockout of the MCH neuropeptide, which show normal glucose preference and do not have improved glucose tolerance. Conclusions: Overall, these data show that the vast majority of MCH neurons are glutamatergic, and that glutamate and MCH signaling mediate partially overlapping functions by these neurons, presumably by activating partially overlapping postsynaptic populations. The diverse functional effects of MCH neurons are thus mediated by a composite of glutamate and MCH signaling. Published by Elsevier GmbH.

Humans carry trillions of viruses that thrive because of their ability to exploit the host. In this exploitation, viruses promote their own replication by suppressing the host antiviral response and by inducing changes in host biosynthetic processes, often with extremely small genomes of their own. In the review, we discuss the phenomenon of histone mimicry by viral proteins and how this mimicry allows the virus to dial in to the cell's transcriptional processes and establish a cell state that promotes infection. We suggest that histone mimicry is part of a broader viral strategy to use intrinsic protein disorder as a means to overcome the size limitations of its own genome and to maximize its impact on host protein networks. In particular, we discuss how intrinsic protein disorder may enable viral proteins to interfere with phase-separated host protein condensates, including those that contribute to chromatin-mediated control of gene expression.

Addition of beta-lactam antibiotics to growing cultures of bacteria inhibit synthesis of the bacterial cell wall peptidoglycan accompanied by killing (loss of viable titer) and lysis (physical disintegration) of the cells. However, it has also been well established that these antibiotics are not effective in killing non-growing or slow-growing bacteria and the mechanism of this "antibiotic tolerance" is not well understood. In this study, we report on the genetic basis and phenotypic properties of an antibiotic tolerant derivative of the methicillin susceptible S. aureus strain 27s. Cultures were exposed to "pulses" of high concentrations of oxacillin followed by outgrowth of the surviving bacteria. This procedure quickly selected for antibiotic tolerant mutants with an increased ability to survive antibiotic treatment without increase in the MIC value for the antibiotic. Such mutants also exhibited longer lag phase, decreased lysis, virtually no change in antibiotic susceptibilities, cross tolerance to D-cycloserine and vancomycin, and increase in biofilm formation in the presence of high concentrations of oxacillin. Whole genome sequencing showed that these altered properties were linked to mutations in the atl and gdpP genes.

While studies of active nematics in two dimensions have shed light on various aspects of the flow regimes and topology of active matter, three-dimensional properties of topological defects and chaotic flows remain unexplored. By confining a film of active nematics between two parallel plates, we use continuum simulations and analytical arguments to demonstrate that the crossover from quasi-two-dimensional (quasi-2D) to three-dimensional (3D) chaotic flows is controlled by the morphology of the disclination lines. For small plate separations, the active nematic behaves as a quasi-2D material, with straight topological disclination lines spanning the height of the channel and exhibiting effectively 2D active turbulence. Upon increasing channel height, we find a crossover to 3D chaotic flows due to the contortion of disclinations above a critical activity. Above this critical activity highly contorted disclination lines and disclination loops are formed. We further show that these contortions are engendered by twist perturbations producing a sharp change in the curvature of disclinations.