Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

This is the final version. Available on open access from Wiley via the DOI in this recordA role for glial cells in brain circuits controlling feeding has begun to be identified with hypothalamic astrocyte signaling implicated in regulating energy homeostasis. The nucleus of the solitary tract (NTS), within the brainstem dorsal vagal complex (DVC), integrates vagal afferent information from the viscera and plays a role in regulating food intake. We hypothesized that astrocytes in this nucleus respond to, and influence, food intake. Mice fed high‐fat chow for 12 hr during the dark phase showed NTS astrocyte activation, reflected in an increase in the number (65%) and morphological complexity of glial‐fibrillary acidic protein (GFAP)‐immunoreactive cells adjacent to the area postrema (AP), compared to control chow fed mice. To measure the impact of astrocyte activation on food intake, we delivered designer receptors exclusively activated by designer drugs (DREADDs) to DVC astrocytes (encompassing NTS, AP, and dorsal motor nucleus of the vagus) using an adeno‐associated viral (AAV) vector (AAV‐GFAP‐hM3Dq_mCherry). Chemogenetic activation with clozapine‐N‐oxide (0.3 mg/kg) produced in greater morphological complexity in astrocytes and reduced dark‐phase feeding by 84% at 4 hr postinjection compared with vehicle treatment. hM3Dq‐activation of DVC astrocytes also reduced refeeding after an overnight fast (71% lower, 4 hr postinjection) when compared to AAV‐GFAP‐mCherry expressing control mice. DREADD‐mediated astrocyte activation did not impact locomotion. hM3Dq activation of DVC astrocytes induced c‐FOS in neighboring neuronal feeding circuits (including in the parabrachial nucleus). This indicates that NTS astrocytes respond to acute nutritional excess, are involved in the integration of peripheral satiety signals, and can reduce food intake when activated.Diabetes UKMedical Research Council (MRC

Two-season Atacama Cosmology Telescope polarimeter lensing power spectrum

© 2017 American Physical Society. We report a measurement of the power spectrum of cosmic microwave background (CMB) lensing from two seasons of Atacama Cosmology Telescope polarimeter (ACTPol) CMB data. The CMB lensing power spectrum is extracted from both temperature and polarization data using quadratic estimators. We obtain results that are consistent with the expectation from the best-fit Planck ΛCDM model over a range of multipoles L=80-2100, with an amplitude of lensing Alens=1.06±0.15(stat)±0.06(sys) relative to Planck. Our measurement of the CMB lensing power spectrum gives σ8Ωm0.25=0.643±0.054; including baryon acoustic oscillation scale data, we constrain the amplitude of density fluctuations to be σ8=0.831±0.053. We also update constraints on the neutrino mass sum. We verify our lensing measurement with a number of null tests and systematic checks, finding no evidence of significant systematic errors. This measurement relies on a small fraction of the ACTPol data already taken; more precise lensing results can therefore be expected from the full ACTPol data set.This work was supported by the U.S. National Science Foundation (NSF) through Grants. No. AST-1440226, No. AST-0965625 and No. AST-0408698 for the ACT project, as well as Grants No. PHY-1214379 and No. PHY-0855887. Funding was also provided by Princeton University, the University of Pennsylvania, and a Canada Foundation for Innovation (CFI) grant to U. B. C. A. C. T. operates in the Parque Astronómico Atacama in northern Chile under the auspices of the Comisión Nacional de Investigación Científica y Tecnológica de Chile (CONICYT). Computations were performed on the GPC supercomputer at the SciNet HPC Consortium. SciNetis funded bytheCFI under the auspices of Compute Canada, the Government of Ontario, the Ontario Research Fund Research Excellence, and the University of Toronto. The development of multichroic detectors and lenses was supported by NASA Grants No. NNX13AE56G and No. NNX14AB58G. N. S. acknowledges support from NSF Grant No. 1513618. A. K. has been supported by NSF Grant No. AST-1312380. R. D. and L. M. thank CONICYT for Grants No. ALMA-CONICYT 31140004, No. FONDECYT 1141113, No. Anillo ACT-1417 and BASAL CATA. We also thank the Mishrahi Fund and the Wilkinson Fund for their generous support of the project

Involvement of Skeletal Muscle Gene Regulatory Network in Susceptibility to Wound Infection Following Trauma

Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals

Streptococcal necrotising fasciitis from diverse strains of Streptococcus pyogenes in tropical northern Australia: case series and comparison with the literature

BACKGROUND: Since the mid-1980's there has been a worldwide resurgence of severe disease from group A streptococcus (GAS), with clonal clusters implicated in Europe and the United States. However GAS associated sepsis and rheumatic fever have always remained at high levels in many less developed countries. In this context we aimed to study GAS necrotising fasciitis (NF) in a region where there are high background rates of GAS carriage and disease. METHODS: We describe the epidemiology, clinical and laboratory features of 14 consecutive cases of GAS NF treated over a seven year period from tropical northern Australia. RESULTS: Incidence rates of GAS NF in the Aboriginal population were up to five times those previously published from other countries. Clinical features were similar to those described elsewhere, with 7/14 (50%) bacteremic and 9/14 (64%) having associated streptococcal toxic shock syndrome. 11/14 (79%) had underlying chronic illnesses, including all four fatalities (29% mortality overall). Important laboratory differences from other series were that leukocytosis was absent in 9/14 (64%) but all had substantial lymphopenia. Sequence typing of the 14 NF-associated GAS isolates showed no clonality, with only one emm type 1 and two emm type 3 strains. CONCLUSIONS: While NF clusters can occur from a single emergent GAS clone, this was not evident in our tropical region, where high rates of NF parallel high overall rates of GAS infection from a wide diversity of strains. The specific virulence factors of GAS strains which do cause NF and the basis of the inadequate host response in those patients who develop NF on infection with these GAS require further elucidation

Higgs lepton flavour violation: UV completions and connection to neutrino masses

We study lepton violating Higgs (HLFV) decays, first from the effective field theory (EFT) point of view, and then analysing the different high-energy realizations of the operators of the EFT, highlighting the most promising models. We argue why two Higgs doublet models can have a BR(h → τ μ) ∼ 0.01, and why this rate is suppressed in all other realizations including vector-like leptons. We further discuss HLFV in the context of neutrino mass models: in most cases it is generated at one loop giving always BR(h → τ μ) < 10−4 and typically much less, which is beyond experimental reach. However, both the Zee model and extended left-right symmetric models contain extra SU(2) doublets coupled to leptons and could in principle account for the observed excess, with interesting connections between HLFV and neutrino parameters

Mass Calibration of Optically Selected des Clusters Using a Measurement of CMB-cluster Lensing with SPTpol Data

We use cosmic microwave background (CMB) temperature maps from the 500 deg 2 SPTpol survey to measure the stacked lensing convergence of galaxy clusters from the Dark Energy Survey (DES) Year-3 redMaPPer (RM) cluster catalog. The lensing signal is extracted through a modified quadratic estimator designed to be unbiased by the thermal Sunyaev-Zel'dovich (tSZ) effect. The modified estimator uses a tSZ-free map, constructed from the SPTpol 95 and 150 GHz data sets, to estimate the background CMB gradient. For lensing reconstruction, we employ two versions of the RM catalog: a flux-limited sample containing 4003 clusters and a volume-limited sample with 1741 clusters. We detect lensing at a significance of 8.7σ(6.7σ) with the flux (volume)-limited sample. By modeling the reconstructed convergence using the Navarro-Frenk-White profile, we find the average lensing masses to be M 200m = (1.62 -0.25+0.32 [stat] ± 0.04 [sys.]) and (1.28 -0.18+0.14 [stat] ± 0.03[sys.])× 10 14 M ⊙ for the volume- and flux-limited samples, respectively. The systematic error budget is much smaller than the statistical uncertainty and is dominated by the uncertainties in the RM cluster centroids. We use the volume-limited sample to calibrate the normalization of the mass-richness scaling relation, and find a result consistent with the galaxy weak-lensing measurements from DES

The development of spontaneous facial responses to others’ emotions in infancy. An EMG study

Viewing facial expressions often evokes facial responses in the observer. These spontaneous facial reactions (SFRs) are believed to play an important role for social interactions. However, their developmental trajectory and the underlying neurocognitive mechanisms are still little understood. In the current study, 4- and 7-month old infants were presented with facial expressions of happiness, anger, and fear. Electromyography (EMG) was used to measure activation in muscles relevant for forming these expressions: zygomaticus major (smiling), corrugator supercilii (frowning), and frontalis (forehead raising). The results indicated no selective activation of the facial muscles for the expressions in 4-month-old infants. For 7-month-old infants, evidence for selective facial reactions was found especially for happy faces (leading to increased zygomaticus major activation) and fearful faces (leading to increased frontalis activation), while angry faces did not show a clear differential response. This suggests that emotional SFRs may be the result of complex neurocognitive mechanisms which lead to partial mimicry but are also likely to be influenced by evaluative processes. Such mechanisms seem to undergo important developments at least until the second half of the first year of life

Cell motility: the integrating role of the plasma membrane

The plasma membrane is of central importance in the motility process. It defines the boundary separating the intracellular and extracellular environments, and mediates the interactions between a motile cell and its environment. Furthermore, the membrane serves as a dynamic platform for localization of various components which actively participate in all aspects of the motility process, including force generation, adhesion, signaling, and regulation. Membrane transport between internal membranes and the plasma membrane, and in particular polarized membrane transport, facilitates continuous reorganization of the plasma membrane and is thought to be involved in maintaining polarity and recycling of essential components in some motile cell types. Beyond its biochemical composition, the mechanical characteristics of the plasma membrane and, in particular, membrane tension are of central importance in cell motility; membrane tension affects the rates of all the processes which involve membrane deformation including edge extension, endocytosis, and exocytosis. Most importantly, the mechanical characteristics of the membrane and its biochemical composition are tightly intertwined; membrane tension and local curvature are largely determined by the biochemical composition of the membrane and the biochemical reactions taking place; at the same time, curvature and tension affect the localization of components and reaction rates. This review focuses on this dynamic interplay and the feedbacks between the biochemical and biophysical characteristics of the membrane and their effects on cell movement. New insight on these will be crucial for understanding the motility process

Probing Galaxy Evolution in Massive Clusters Using ACT and DES: Splashback as a Cosmic Clock

We measure the projected number density profiles of galaxies and the splashback feature in clusters selected by the Sunyaev–Zel'dovich effect from the Advanced Atacama Cosmology Telescope (AdvACT) survey using galaxies observed by the Dark Energy Survey (DES). The splashback radius is consistent with CDM-only simulations and is located at ${2.4}_{-0.4}^{+0.3}\,\mathrm{Mpc}\,{h}^{-1}$. We split the galaxies on color and find significant differences in their profile shapes. Red and green-valley galaxies show a splashback-like minimum in their slope profile consistent with theory, while the bluest galaxies show a weak feature at a smaller radius. We develop a mapping of galaxies to subhalos in simulations and assign colors based on infall time onto their hosts. We find that the shift in location of the steepest slope and different profile shapes can be mapped to the average time of infall of galaxies of different colors. The steepest slope traces a discontinuity in the phase space of dark matter halos. By relating spatial profiles to infall time, we can use splashback as a clock to understand galaxy quenching. We find that red galaxies have on average been in clusters over 3.2 Gyr, green galaxies about 2.2 Gyr, while blue galaxies have been accreted most recently and have not reached apocenter. Using the full radial profiles, we fit a simple quenching model and find that the onset of galaxy quenching occurs after a delay of about a gigayear and that galaxies quench rapidly thereafter with an exponential timescale of 0.6 Gyr