Glutamate prevents altered mitochondrial function following recurrent low glucose in hypothalamic but not cortical primary rat astrocytes.

This is the final version. Available from MDPI via the DOI in this record. Data Availability Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.Astrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglycaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metabolic responses of cortical (CRTAS) and hypothalamic (HTAS) primary rat astrocytes were measured in acute and recurrent low glucose using extracellular flux analyses. RLG caused mitochondrial adaptations in both HTAS and CRTAS, many of which were attenuated by glutamate exposure during low glucose (LG) treatments. We observed an increase in capacity of HTAS to metabolise glutamine after RLG exposure. Demonstrating astrocytic heterogeneity in the response to LG, CRTAS increased cellular acidification, a marker of glycolysis in LG, whereas this decreased in HTAS. The directional change in intracellular Ca2+ levels of each cell type, correlated with the change in extracellular acidification rate (ECAR) during LG. Further examination of glutamate-induced Ca2+ responses in low glucose treated CRTAS and HTAS identified sub-populations of glucose-excited- and glucose-inhibited-like cells with differing responses to glutamate. Lastly, release of the gliotransmitter ATP by HTAS was elevated by RLG, both with and without concurrent glutamate exposure. Therefore, hypothalamic astrocytes adapt to RLG by increasing glutamate uptake and oxidation in a manner that prevents RLG-induced mitochondrial adaptations.Diabetes UKJuvenile Diabetes Research FoundationEuropean Federation for the Study of DiabetesNovo Nordisk Research Foundatio

Detection of the pairwise kinematic Sunyaev-Zel'dovich effect with BOSS DR11 and the Atacama Cosmology Telescope

We present a new measurement of the kinematic Sunyaev-Zeldovich effect using data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area, we evaluate the mean pairwise baryon momentum associated with the positions of 50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A non-zero signal arises from the large-scale motions of halos containing the sample galaxies. The data fits an analytical signal model well, with the optical depth to microwave photon scattering as a free parameter determining the overall signal amplitude. We estimate the covariance matrix of the mean pairwise momentum as a function of galaxy separation, using microwave sky simulations, jackknife evaluation, and bootstrap estimates. The most conservative simulation-based errors give signal-to-noise estimates between 3.6 and 4.1 for varying galaxy luminosity cuts. We discuss how the other error determinations can lead to higher signal-to-noise values, and consider the impact of several possible systematic errors. Estimates of the optical depth from the average thermal Sunyaev-Zeldovich signal at the sample galaxy positions are broadly consistent with those obtained from the mean pairwise momentum signal.Comment: 15 pages, 8 figures, 2 table

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ

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

Anthrax Toxin Receptor Drives Protective Antigen Oligomerization and Stabilizes the Heptameric and Octameric Oligomer by a Similar Mechanism

Anthrax toxin is comprised of protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins are individually nontoxic; however, when PA assembles with LF and EF, it produces lethal toxin and edema toxin, respectively. Assembly occurs either on cell surfaces or in plasma. In each milieu, PA assembles into a mixture of heptameric and octameric complexes that bind LF and EF. While octameric PA is the predominant form identified in plasma under physiological conditions (pH 7.4, 37°C), heptameric PA is more prevalent on cell surfaces. The difference between these two environments is that the anthrax toxin receptor (ANTXR) binds to PA on cell surfaces. It is known that the extracellular ANTXR domain serves to stabilize toxin complexes containing the PA heptamer by preventing premature PA channel formation--a process that inactivates the toxin. The role of ANTXR in PA oligomerization and in the stabilization of toxin complexes containing octameric PA are not understood.Using a fluorescence assembly assay, we show that the extracellular ANTXR domain drives PA oligomerization. Moreover, a dimeric ANTXR construct increases the extent of and accelerates the rate of PA assembly relative to a monomeric ANTXR construct. Mass spectrometry analysis shows that heptameric and octameric PA oligomers bind a full stoichiometric complement of ANTXR domains. Electron microscopy and circular dichroism studies reveal that the two different PA oligomers are equally stabilized by ANTXR interactions.We propose that PA oligomerization is driven by dimeric ANTXR complexes on cell surfaces. Through their interaction with the ANTXR, toxin complexes containing heptameric and octameric PA oligomers are similarly stabilized. Considering both the relative instability of the PA heptamer and extracellular assembly pathway identified in plasma, we propose a means to regulate the development of toxin gradients around sites of infection during anthrax pathogenesis

Sonographic evaluation of the shoulder in asymptomatic elderly subjects with diabetes

<p>Abstract</p> <p>Background</p> <p>The prevalence of rotator cuff tears increases with age and several studies have shown that diabetes is associated with symptomatic shoulder pathologies. Aim of our research was to evaluate the prevalence of shoulder lesions in a population of asymptomatic elderly subjects, normal and with non insulin - dependent diabetes mellitus.</p> <p>Methods</p> <p>The study was performed on 48 subjects with diabetes and 32 controls (mean age: 71.5 ± 4.8 and 70.7 ± 4.5, respectively), who did not complain shoulder pain or dysfunction. An ultrasound examination was performed on both shoulders according to a standard protocol, utilizing multiplanar scans.</p> <p>Results</p> <p>Tendons thickness was greater in diabetics than in controls (Supraspinatus Tendon: 6.2 ± 0.09 mm <it>vs </it>5.2 ± 0.7 mm, p < 0.001; Biceps Tendon: 4 ± 0.8 mm <it>vs </it>3.2 ± 0.4 mm, p < 0.001). Sonographic appearances of degenerative features in the rotator cuff and biceps were more frequently observed in diabetics (Supraspinatus Tendon: 42.7% <it>vs </it>20.3%, p < 0.003; Biceps Tendon: 27% <it>vs </it>7.8%, p < 0.002).</p> <p>Subjects with diabetes exhibited more tears in the Supraspinatus Tendon (Minor tears: 15 (15.8%) <it>vs </it>2 (3.1%), p < 0.03; Major tears: 15 (15.8%) <it>vs </it>5 (7.8%), p = ns), but not in the long head of Biceps. More effusions in subacromial bursa were observed in diabetics (23.9% <it>vs </it>10.9%, p < 0.03) as well as tenosynovitis in biceps tendon (33.3% <it>vs </it>10.9%, p < 0.001).</p> <p>In both groups, pathological findings were prevalent on the dominant side, but no difference related to duration of diabetes was found.</p> <p>Conclusions</p> <p>Our results suggest that age - related rotator cuff tendon degenerative changes are more common in diabetics.</p> <p>Ultrasound is an useful tool for discovering in pre - symptomatic stages the subjects that may undergo shoulder symptomatic pathologies.</p

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

Charge-separated atmospheric neutrino-induced muons in the MINOS far detector

14 pages, 15 figuresWe found 140 neutrino-induced muons in 854.24 live days in the MINOS far detector. We looked for evidence of neutrino disappearance in this data set by computing the ratio of the number of low momentum muons to the sum of the number of high momentum and unknown momentum muons for both data and Monte Carlo expectation in the absence of neutrino oscillations. The ratio of data and Monte Carlo ratios is consistent with an oscillation signal. A fit to the data for the oscillation parameters excludes the null oscillation hypothesis at the 94% confidence level. We separated the muons by charge sign in both the data and Monte Carlo events and found the ratio of the total number of negative to positive muons in both samples. The ratio of those ratios is a test of CPT conservation. The result is consistent with CPT conservation