723 research outputs found

    Impaired neurodevelopment by the low complexity domain of CPEB4 reveals a convergent pathway with neurodegeneration

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    CPEB4 is an RNA binding protein expressed in neuronal tissues including brain and spinal cord. CPEB4 has two domains: one that is structured for RNA binding and one that is unstructured and low complexity that has no known function. Unstructured low complexity domains (LCDs) in proteins are often found in RNA-binding proteins and have been implicated in motor neuron degenerative diseases such as amyotrophic lateral sclerosis, indicating that these regions mediate normal RNA processing as well as pathological events. While CPEB4 null knockout mice are normal, animals expressing only the CPEB4 LCD are neonatal lethal with impaired mobility that display defects in neuronal development such as reduced motor axon branching and abnormal neuromuscular junction formation. Although full-length CPEB4 is nearly exclusively cytoplasmic, the CPEB4 LCD forms nucleolar aggregates and CPEB4 LCD-expressing animals have altered ribosomal RNA biogenesis, ribosomal protein gene expression, and elevated levels of stress response genes such as the actin-bundling protein DRR1, which impedes neurite outgrowth. Some of these features share similarities with other LCD-related neurodegenerative disease. Most strikingly, DRR1 appears to be a common focus of several neurodevelopmental and neurodegenerative disorders. Our study reveals a possible molecular convergence between a neurodevelopmental defect and neurodegeneration mediated by LCDs

    Self-medications with potential abuse in the Middle East: a systematic literature review

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    Self-medication (SM) is highly prevalent in the Middle East. However, regulations in the Middle East are not always enforced and therefore many prescription medicines can be purchased as SM, resulting in potential abuse of many medicines. The aim of this article, therefore, was to undertake a comprehensive review to identify the different types of self-medications involved in abuse in the Middle East and to identify harms related to SM abuse. An extensive review of the published literature pertaining to the subject (1990–2015) was conducted using PubMed, Web of Science, Cochrane and Google Scholar databases for OTC medication abuse in the Middle East. Twenty two papers were identified. Medications involved in SM abuse included: psychoactive prescription-only medicines, codeine-containing products, tramadol, anabolic steroids, sedative antihistamines, decongestants and laxatives. Moreover, studies in the region rarely reported harms related to SM abuse and strategies to limit this abuse. Potential SM abuse involving a range of medicines is a public health problem in the Middle East. Future interventions and regulations should be applied to limit the expansion of SM use and potential abuse

    Domain walls at the spin density wave endpoint of the organic superconductor (TMTSF)2PF6 under pressure

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    We report the first comprehensive investigation of the organic superconductor (TMTSF)2PF6 in the vicinity of the endpoint of the spin density wave - metal phase transition where phase coexistence occurs. At low temperature, the transition of metallic domains towards superconductivity is used to reveal the various textures. In particular, we demonstrate experimentally the existence of 1D and 2D metallic domains with a cross-over from a filamentary superconductivity mostly along the c?-axis to a 2D superconductivity in the b?c-plane perpendicular to the most conducting direction. The formation of these domain walls may be related to the proposal of a soliton phase in the vicinity of the critical pressure of the (TMTSF)2PF6 phase diagram.Comment: 5 page

    Ab initio studies of electronic structure of defects in PbTe

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    Understanding the detailed electronic structure of deep defect states in narrow band-gap semiconductors has been a challenging problem. Recently, self-consistent ab initio calculations within density functional theory (DFT) using supercell models have been successful in tackling this problem. In this paper, we carry out such calculations in PbTe, a well-known narrow band-gap semiconductor, for a large class of defects: cationic and anionic substitutional impurities of different valence, and cationic and anionic vacancies. For the cationic defects, we study a series of compounds RPb2n-1Te2n, where R is vacancy or monovalent, divalent, or trivalent atom; for the anionic defects, we study compounds MPb2nTe2n-1, where M is vacancy, S, Se or I. We find that the density of states (DOS) near the top of the valence band and the bottom of the conduction band get significantly modified for most of these defects. This suggests that the transport properties of PbTe in the presence of impurities can not be interpreted by simple carrier doping concepts, confirming such ideas developed from qualitative and semi-quantitative arguments

    Recent and future trends in synthetic greenhouse gas radiative forcing

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    Atmospheric measurements show that emissions of hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons are now the primary drivers of the positive growth in synthetic greenhouse gas (SGHG) radiative forcing. We infer recent SGHG emissions and examine the impact of future emissions scenarios, with a particular focus on proposals to reduce HFC use under the Montreal Protocol. If these proposals are implemented, overall SGHG radiative forcing could peak at around 355 mW m[superscript −2] in 2020, before declining by approximately 26% by 2050, despite continued growth of fully fluorinated greenhouse gas emissions. Compared to “no HFC policy” projections, this amounts to a reduction in radiative forcing of between 50 and 240 mW m[superscript −2] by 2050 or a cumulative emissions saving equivalent to 0.5 to 2.8 years of CO2 emissions at current levels. However, more complete reporting of global HFC emissions is required, as less than half of global emissions are currently accounted for.Natural Environment Research Council (Great Britain) (Advanced Research Fellowship NE/I021365/1)United States. National Aeronautics and Space Administration (Upper Atmospheric Research Program Grant NNX11AF17G)United States. National Oceanic and Atmospheric Administratio

    Disruption of the Hippocampal and Hypothalamic Blood-Brain Barrier in a Diet-Induced Obese Model of Type II Diabetes: Prevention and Treatment by the Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate

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    Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. Methods: BBB and BRB permeability were assessed using 14C-sucrose and 99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. Results: High-fat feeding caused increased entry of 14C-sucrose and 99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to 14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to 99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of 99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for 14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. Conclusions: Blood–brain barrier and blood–retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in 14C-sucrose and 99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial carbonic anhydrase inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model

    AI Enabled-6G: Artificial Intelligence (AI) for Integration of 6G Wireless Communications

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    The research in wireless communication is rapidly shifting to the next generation mobile system, 6G. Fifth-generation mobile network standards are now in use. However, there are still some user criteria that are expected to be satisfied in the sixth-generation communication network. 6G is estimated to enable the unprecedented intelligence Internet of Things with extremely varied stimulating necessities. Currently, artificial intelligence (AI) is considered as a novel paradigm for the designing and optimizing intelligent 6G architectures, standards and functions. By 2030, all of the people would be using 6G. In this paper, we investigate 6G trends, requirements, challenges & potential solutions and how AI-enabled technique can integrate 6G communications. The analysis section provides the need and how AI-empowered technique efficiently and effectively enhances the performance of network. The 6G networks based on intelligent AI architecture used to understand automatic network adjustment, knowledge discovery, intelligent service provisioning, and smart resource management

    Revisiting the anatomy of the cephalic vein, its origin, course and possible clinical correlations in relation to the anatomical snuffbox among Jordanian

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    Background: The cephalic vein is one of the most distinguished superficial veins of the upper limb. Its clinical value lies in venous access. There is little known about the variation of its formation in relation to the anatomical snuffbox. Hence, anatomical variants in the origin of the cephalic vein are important in clinical practice. Subsequently, this study was designed to examine the variation of the cephalic vein formation in relation to the anatomical snuffbox. Materials and methods: A cross-sectional study of 438 subjects (722 hands), was prepared to study the cephalic vein among Jordanian students and staff of one of the major governmental Medical College in Jordan, by using infrared illumination system. The obtained data was analysed according to; gender, sidedness, and handedness. Results: Four sites for the formation of the cephalic vein in relation to the anatomical snuffbox were found. There was a significant relation between gender and sidedness, and the sites of formation of the cephalic vein (p < 0.0001 and p = 0.048, respectively). Conclusions: For the first time this study identified different sites for the formation of the cephalic vein in relation to the anatomical snuffbox. However, regardless of its sites of formation, the cephalic vein was running in 98% of the examined hands in the anatomical snuffbox

    The variability of methane, nitrous oxide and sulfur hexafluoride in Northeast India

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    High-frequency atmospheric measurements of methane (CH[subscript 4]), nitrous oxide (N[subscript 2]O) and sulfur hexafluoride (SF[subscript 6]) from Darjeeling, India are presented from December 2011 (CH[subscript 4])/March 2012 (N[subscript 2]O and SF[subscript 6]) through February 2013. These measurements were made on a gas chromatograph equipped with a flame ionization detector and electron capture detector, and were calibrated on the Tohoku University, the Scripps Institution of Oceanography (SIO)-98 and SIO-2005 scales for CH[subscript 4], N[subscript 2]O and SF[subscript 6], respectively. The observations show large variability and frequent pollution events in CH[subscript 4] and N[subscript 2]O mole fractions, suggesting significant sources in the regions sampled by Darjeeling throughout the year. By contrast, SF[subscript 6] mole fractions show little variability and only occasional pollution episodes, likely due to weak sources in the region. Simulations using the Numerical Atmospheric dispersion Modelling Environment (NAME) particle dispersion model suggest that many of the enhancements in the three gases result from the transport of pollutants from the densely populated Indo-Gangetic Plains of India to Darjeeling. The meteorology of the region varies considerably throughout the year from Himalayan flows in the winter to the strong south Asian summer monsoon. The model is consistent in simulating a diurnal cycle in CH[subscript 4] and N[subscript 2]O mole fractions that is present during the winter but absent in the summer and suggests that the signals measured at Darjeeling are dominated by large-scale (~100 km) flows rather than local (<10 km) flows.Massachusetts Institute of Technology. Center for Global Change Science (Director's Fund)Massachusetts Institute of Technology. Joint Program on the Science & Policy of Global ChangeMartin Family Society of Fellows for SustainabilityMIT Energy InitiativeMIT International Science and Technology InitiativeUnited States. National Aeronautics and Space Administration (Grant NNX11AF17G)United States. National Oceanic and Atmospheric Administration (Contract RA133R09CN0062
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