pinecone/core-2020-05-10-deduplication huggingface dataset:
Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis

SummaryAlterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D
Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology

AbstractObjectiveCarpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray matter (GM) and white matter (WM) and whether such plasticity is linked to altered median nerve function in CTS.MethodsWe performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics.ResultsFor CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed.ConclusionsOur study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery
Reaction–diffusion systems for spatio-temporal intracellular protein networks: A beginner's guide with two examples

AbstractSpatio-temporal dynamics of a variety of proteins is, among other things, regulated by post-translational modifications of these proteins. Such modifications can thus influence stability and biochemical activities of the proteins, activity and stability of their upstream targets within specific signalling pathways. Commonly used mathematical tools for such protein–protein (and/or protein-mRNA) interactions in single cells, namely, Michaelis–Menten and Hill kinetics, yielding a system of ordinary differential equations, are extended here into (non-linear) partial differential equations by taking into account a more realistic spatial representation of the environment where these reactions occur. In the modelling framework under consideration, all interactions occur in a cell divided into two compartments, the nucleus and the cytoplasm, connected by the semipermeable nuclear membrane and bounded by the impermeable cell membrane. Passive transport mechanism, modelled by the so-called Kedem–Katchalsky boundary conditions, is used here to represent migration of species throughout the nuclear membrane. Nonlinear systems of partial differential equations are solved by the semi-implicit Rothe method. Examples of two spatial oscillators are shown. Namely, these are the circadian rhythm for concentration of the FRQ protein in Neurospora crassa and oscillatory dynamics observed in the activation and regulation of the p53 protein following DNA damage in mammalian cells
Hedgehog Partial Agonism Drives Warburg-like Metabolism in Muscle and Brown Fat

SummaryDiabetes, obesity, and cancer affect upward of 15% of the world’s population. Interestingly, all three diseases juxtapose dysregulated intracellular signaling with altered metabolic state. Exactly which genetic factors define stable metabolic set points in vivo remains poorly understood. Here, we show that hedgehog signaling rewires cellular metabolism. We identify a cilium-dependent Smo-Ca2+-Ampk axis that triggers rapid Warburg-like metabolic reprogramming within minutes of activation and is required for proper metabolic selectivity and flexibility. We show that Smo modulators can uncouple the Smo-Ampk axis from canonical signaling and identify cyclopamine as one of a new class of “selective partial agonists,” capable of concomitant inhibition of canonical and activation of noncanonical hedgehog signaling. Intriguingly, activation of the Smo-Ampk axis in vivo drives robust insulin-independent glucose uptake in muscle and brown adipose tissue. These data identify multiple noncanonical endpoints that are pivotal for rational design of hedgehog modulators and provide a new therapeutic avenue for obesity and diabetes
Special symmetries of the charged Kerr–AdS black hole of D=5 minimal gauged supergravity

AbstractIn this Letter we prove that the Hamilton–Jacobi equation in the background of the recently discovered charged Kerr–AdS black hole of D=5 minimal gauged supergravity is separable, for arbitrary values of the two rotation parameters. This allows us to write down an irreducible Killing tensor for the spacetime. As a result, we also show that the Klein–Gordon equation in this background is separable. We also consider the Dirac equation in this background in the special case of equal rotation parameters and show it has separable solutions. Finally, we discuss the near-horizon geometry of the supersymmetric limit of the black hole
Optimal construction of k-nearest-neighbor graphs for identifying noisy clusters

AbstractWe study clustering algorithms based on neighborhood graphs on a random sample of data points. The question we ask is how such a graph should be constructed in order to obtain optimal clustering results. Which type of neighborhood graph should one choose, mutual k-nearest-neighbor or symmetric k-nearest-neighbor? What is the optimal parameter k? In our setting, clusters are defined as connected components of the t-level set of the underlying probability distribution. Clusters are said to be identified in the neighborhood graph if connected components in the graph correspond to the true underlying clusters. Using techniques from random geometric graph theory, we prove bounds on the probability that clusters are identified successfully, both in a noise-free and in a noisy setting. Those bounds lead to several conclusions. First, k has to be chosen surprisingly high (rather of the order n than of the order logn) to maximize the probability of cluster identification. Secondly, the major difference between the mutual and the symmetric k-nearest-neighbor graph occurs when one attempts to detect the most significant cluster only
How the amyloid-β peptide and membranes affect each other: An extensive simulation study

AbstractThe etiology of Alzheimer's disease is thought to be linked to interactions between amyloid-β (Aβ) and neural cell membranes, causing membrane disruption and increased ion conductance. The effects of Aβ on lipid behavior have been characterized experimentally, but structural and causal details are lacking. We used atomistic molecular dynamics simulations totaling over 6μs in simulation time to investigate the behavior of Aβ42 in zwitterionic and anionic lipid bilayers. We simulated transmembrane β-sheets (monomer and tetramer) resulting from a global optimization study and a helical structure obtained from an NMR study. In all simulations Aβ42 remained embedded in the bilayer. It was found that the surface charge and the lipid tail type are determinants for transmembrane stability of Aβ42 with zwitterionic surfaces and unsaturated lipids promoting stability. From the considered structures, the β-sheet tetramer is most stable as a result of interpeptide interactions. We performed an in-depth analysis of the translocation of water in the Aβ42-bilayer systems. We observed that this process is generally fast (within a few nanoseconds) yet generally slower than in the peptide-free bilayers. It is mainly governed by the lipid type, simulation temperature and Aβ42 conformation. The rate limiting step is the permeation through the hydrophobic core, where interactions between Aβ42 and permeating H2O molecules slow the translocation process. The β-sheet tetramer allows more water molecules to pass through the bilayer compared to monomeric Aβ, allowing us to conclude that the experimentally observed permeabilization of membranes must be due to membrane-bound Aβ oligomers, and not monomers
Measurement of very forward neutron energy spectra for 7 TeV proton–proton collisions at the Large Hadron Collider

AbstractThe Large Hadron Collider forward (LHCf) experiment is designed to use the LHC to verify the hadronic-interaction models used in cosmic-ray physics. Forward baryon production is one of the crucial points to understand the development of cosmic-ray showers. We report the neutron-energy spectra for LHC s=7 TeV proton–proton collisions with the pseudo-rapidity η ranging from 8.81 to 8.99, from 8.99 to 9.22, and from 10.76 to infinity. The measured energy spectra obtained from the two independent calorimeters of Arm1 and Arm2 show the same characteristic feature before unfolding the detector responses. We unfolded the measured spectra by using the multidimensional unfolding method based on Bayesian theory, and the unfolded spectra were compared with current hadronic-interaction models. The QGSJET II-03 model predicts a high neutron production rate at the highest pseudo-rapidity range similar to our results, and the DPMJET 3.04 model describes our results well at the lower pseudo-rapidity ranges. However, no model perfectly explains the experimental results over the entire pseudo-rapidity range. The experimental data indicate a more abundant neutron production rate relative to the photon production than any model predictions studied here
Knowledge and risk perceptions of the Ebola virus in the United States

AbstractObjectivesThe Ebola epidemic has received extensive media coverage since the first diagnosed cases of the virus in the US. We investigated risk perceptions of Ebola among individuals living in the US and measured their knowledge of the virus.MethodUS residents completed an online survey (conducted 14–18 November 2014) that assessed their Ebola knowledge and risk perceptions.ResultsRespondents who were more knowledgeable of Ebola perceived less risk of contracting the virus and were less worried about the virus, but also regarded Ebola as more serious than less knowledgeable respondents. The internet served as a major source of additional information among knowledgeable respondents.ConclusionThe findings suggest that the provision of health information about Ebola may be effective in informing the public about Ebola risks and of preventive measures without curtailing the seriousness of the virus. Policymakers may seek to further exploit the internet as a means of delivering information about Ebola in the US and worldwide
The molybdenum isotopic compositions of I-, S- and A-type granitic suites

This study reports Mo isotopic compositions for fifty-two Palaeozoic granitic rocks with contrasting source affinities (A-, I- and S-type) from the Lachlan Fold Belt (LFB) and the New England Batholith (NEB), both in SE Australia, and three compositionally zoned plutons (Loch Doon, Criffell, and Fleet) located in the Southern Uplands of Scotland. The results show relatively large variations in δ98Mo for igneous rocks ranging from −1.73‰ to 0.59‰ with significant overlaps between different types. No relationships between δ98Mo and δ18O or ASI (Alumina Saturation Index) are observed, indicating that Mo isotopes do not clearly distinguish igneous vs. sedimentary source types. Instead, effects of igneous processes, source mixing, regional geology, as well as hydrothermal activity control the Mo isotope compositions in these granites. It is found that Mo is mainly accommodated in biotite and to a lesser extent in hornblende. Hornblende and Fe3+-rich minerals may preferentially incorporate light isotopes, as reflected by negative correlations between δ98Mo and K/Rb and [Fe2O3]. There is a positive correlation between initial 87Sr/86Sr and δ98Mo in I-type granitic rocks, reflecting the admixing of material from isotopically distinct sources. Granitic rocks from Scotland and Australia display strikingly similar curvilinear trends in δ98Mo vs. initial 87Sr/86Sr despite the differing regional geology. Localized hydrothermal effects can result in low δ98Mo in granite, as seen in three samples from Loch Doon and Criffell which have anomalously light δ98Mo of <−1‰. Based on this study, an estimate of δ98Mo = 0.14 ± 0.07‰ (95% s.e.) for the Phanerozoic upper crust is proposed. This is slightly heavier than basalts indicating an isotopically light lower crust and/or a systematic change to the crust resulting from subduction of isotopically light dehydrated slab and/or pelagic sediment over time
The effect of tissue surface modification with collagenase and addition of TGF-beta3 on the healing potential of meniscal tears repaired with tissue glues in vitro

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                  170599.pdf (publisher's version ) (Open Access)The aim of the current in vitro study was to investigate if tissue surface modification with collagenase and addition of the TGF-beta3 can increase the number of cells present in meniscus tears repaired with the use of newly developed tissue adhesives based on isocyanate-terminated block copolymers. Cylindrical explants were harvested from the inner part of bovine menisci. To simulate a full-thickness tear, the central core of the explants was removed and glued back into the defect, with or without incubation in collagenase solution prior to gluing. The repair constructs were then cultured with or without addition of TGF-beta3, and assessed for their histological appearance. The histological staining of the constructs confirmed that both developed adhesives were not cytotoxic. After 28 days, meniscus cells were present in direct contact with the glues. The addition of TGF-beta3 to the culture medium resulted in the presence of cells that formed a sheath inside the simulated tear and in increased cell numbers at the edges of annulus of the explants. In the group in which the tissue was incubated in collagenase and cultured in medium containing TGF-beta3, thicker layers of cells were observed. These results suggest that repairing the torn meniscus with tissue adhesives after pre-treatment of the tissue with collagenase and stimulation with TGF-beta3 is a very promising treatment method, especially when treating the inner avascular part of the meniscus. Nevertheless, longer-term in vitro and in vivo studies are needed to confirm the beneficial effects of this combination therapy
The SCUBA-2 Cosmology Legacy Survey :
                    ALMA resolves the bright-end of the sub-millimeter number counts

J. M. Simpson, et al., ???The SCUBA-2 Cosmology Legacy Survey: ALMA resolves the bright-end of the sub-millimetre number counts???, The Astrophysical Journal, Vol. 807(2), July 2015. ?? 2015. The American Astronomical Society.We present high-resolution 870-um ALMA continuum maps of 30 bright sub-millimeter sources in the UKIDSS UDS field. These sources are selected from deep, 1-square degrees 850-um maps from the SCUBA--2 Cosmology Legacy Survey, and are representative of the brightest sources in the field (median SCUBA2 flux S_850=8.7+/-0.4 mJy). We detect 52 sub-millimeter galaxies (SMGs) at >4-sigma significance in our 30 ALMA maps. In 61+/-17% of the ALMA maps the single-dish source comprises a blend of >=2 SMGs, where the secondary SMGs are Ultra--Luminous Infrared Galaxies (ULIRGs) with L_IR>10^12 Lo. The brightest SMG contributes on average 80+/-4% of the single-dish flux density, and in the ALMA maps containing >=2 SMGs the secondary SMG contributes 25+/-3% of the integrated ALMA flux. We construct source counts and show that multiplicity boosts the apparent single-dish cumulative counts by 20% at S_870>7.5mJy, and by 60% at S_870>12mJy. We combine our sample with previous ALMA studies of fainter SMGs and show that the counts are well-described by a double power-law with a break at 8.5+/-0.6mJy. The break corresponds to a luminosity of ~6x10^12Lsol or a star-formation rate of ~1000Mo/yr. For the typical sizes of these SMGs, which are resolved in our ALMA data with r=1.2+/-0.1kpc, this yields a limiting SFR density of ~100Msol/yr/kpc2. Finally, the number density of S_870>2mJy SMGs is 80+/-30 times higher than that derived from blank-field counts. An over-abundance of faint SMGs is inconsistent with line-of-sight projections dominating multiplicity in the brightest SMGs, and indicates that a significant proportion of these high-redshift ULIRGs must be physically associated
Sex differences in risk-based decision-making in adolescents with conduct disorder

Altered decision-making processes and excessive risk-seeking behaviours are key features of conduct disorder (CD). Previous studies have provided compelling evidence of abnormally increased preference for risky options, higher sensitivity to rewards, as well as blunted responsiveness to aversive outcomes in adolescents with CD. However, most studies published to date have focused on males only, thus it is not known whether females with CD show similar alterations in decision-making. The current study investigated potential sex differences in decision-making and risk-seeking behaviours in adolescents with CD. Forty-nine adolescents with CD (23 females) and 51 control subjects (27 females), aged 11-18 years, performed a computerised task assessing decision-making under risk - the Risky Choice Task. Participants made a series of decisions between two gamble options that varied in terms of their expected values and probability of gains and losses. This enabled the participants' risk preferences to be determined. Taking the sample as a whole, adolescents with CD exhibited increased risk-seeking behaviours compared to healthy controls. However, we found a trend towards a sex-by-group interaction, suggesting that these effects may vary by sex. Follow-up analyses showed that males with CD made significantly more risky choices than their typically-developing counterparts, while females with CD did not differ from typically-developing females in their risk-seeking behaviours. Our results provide preliminary evidence that sex may moderate the relationship between CD and alterations in risk attitudes and reward processing, indicating that there may be sex differences in the developmental pathways and neuropsychological deficits that lead to CD
Assessing peer review by gauging the fate of rejected manuscripts: the case of the Journal of Artificial Societies and Social Simulation

This paper investigates the fate of manuscripts that were rejected from JASSS-The Journal of Artificial Societies and Social Simulation, the flagship journal of social simulation. We tracked 456 manuscripts that were rejected from 1997 to 2011 and traced their subsequent publication as journal articles, conference papers or working papers. We compared the impact factor of the publishing journal and the citations of those manuscripts that were eventually published against the yearly impact factor of JASSS and the number of citations achieved by the JASSS mean and top cited articles. Only 10% of the rejected manuscripts were eventually published in a journal that was indexed in the Web of Science, although most of the rejected manuscripts were published elsewhere. Being exposed to more than one round of reviews before rejection, having received a more detailed reviewer report and being subjected to higher inter-reviewer disagreement were all associated with the number of citations received when the manuscript was eventually published. This indicates that peer review could contribute to increasing the quality even of rejected manuscript
European contribution to the study of ROS : a summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed