4,149 research outputs found

    Gi- and Gs-coupled GPCRs show different modes of G-protein binding.

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    More than two decades ago, the activation mechanism for the membrane-bound photoreceptor and prototypical G protein-coupled receptor (GPCR) rhodopsin was uncovered. Upon light-induced changes in ligand-receptor interaction, movement of specific transmembrane helices within the receptor opens a crevice at the cytoplasmic surface, allowing for coupling of heterotrimeric guanine nucleotide-binding proteins (G proteins). The general features of this activation mechanism are conserved across the GPCR superfamily. Nevertheless, GPCRs have selectivity for distinct G-protein family members, but the mechanism of selectivity remains elusive. Structures of GPCRs in complex with the stimulatory G protein, Gs, and an accessory nanobody to stabilize the complex have been reported, providing information on the intermolecular interactions. However, to reveal the structural selectivity filters, it will be necessary to determine GPCR-G protein structures involving other G-protein subtypes. In addition, it is important to obtain structures in the absence of a nanobody that may influence the structure. Here, we present a model for a rhodopsin-G protein complex derived from intermolecular distance constraints between the activated receptor and the inhibitory G protein, Gi, using electron paramagnetic resonance spectroscopy and spin-labeling methodologies. Molecular dynamics simulations demonstrated the overall stability of the modeled complex. In the rhodopsin-Gi complex, Gi engages rhodopsin in a manner distinct from previous GPCR-Gs structures, providing insight into specificity determinants

    Influence of coach encouragement on technical demand of an small-sided games in football-7.

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    El objetivo del presente estudio ha sido analizar el efecto de la motivación del entrenador sobre la demanda técnica de un juego reducido (JR) 3 contra 3, realizado por futbolistas de categoría alevín, observando el nivel de aprendizaje técnico adquirido a través de estas tareas. Se han cuantificado el número de acciones técnicas que se producen en un JR de 3 contra 3 sin intervención del entrenador (JRSIE) y las que se producen en el mismo JR con la intervención del entrenador (JRCME). Se ha realizado en cada una de las 4 sesiones del programa de entrenamiento con JR dos test de valoración del dominio técnico en situaciones pre y post sesión. Los resultados confirman que aparecen diferencias en el número de acciones técnicas que el jugador realiza durante el JR, siendo significativamente mayor en el JRCME, generándose además mayor nivel de aprendizaje

    Continuous Spatiotemporal Transformers

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    Modeling spatiotemporal dynamical systems is a fundamental challenge in machine learning. Transformer models have been very successful in NLP and computer vision where they provide interpretable representations of data. However, a limitation of transformers in modeling continuous dynamical systems is that they are fundamentally discrete time and space models and thus have no guarantees regarding continuous sampling. To address this challenge, we present the Continuous Spatiotemporal Transformer (CST), a new transformer architecture that is designed for the modeling of continuous systems. This new framework guarantees a continuous and smooth output via optimization in Sobolev space. We benchmark CST against traditional transformers as well as other spatiotemporal dynamics modeling methods and achieve superior performance in a number of tasks on synthetic and real systems, including learning brain dynamics from calcium imaging data.Comment: Updated version, after review

    Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog.

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    The Silent Corticotroph Adenoma (SCA) is a pituitary adenoma variant characterized by the immunoreactivity for adrenocorticotropic hormone (ACTH) and related peptides, without the clinical signs of Cushing's disease. SCA has been postulated to either secrete structurally abnormal ACTH that is inactive but detectable by immunohistochemistry or radioimmunoassay, or to secrete ACTH intermittently or at low levels continuously. Excess of ACTH has been associated to type II muscle atrophy. We describe a case of type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. The dog showed moderate to severe proximal muscle wasting and weakness with normal levels of muscle-associated enzymes. In the limb muscle biopsies, type II fibers were uniformly smaller than type I fibers. In temporalis muscles, there were few atrophic fibers, and several irregular areas of loss of enzymatic activity observed in NADH, SDH and COX stains. The tumour showed a trabecular growth pattern and immunohistochemical analysis demonstrated the presence of cytoplasmic immunoreactivity for ACTH. The muscle atrophy was considered to be related to an excess of inactive ACTH. Studying spontaneous occurring rare diseases in animals could help to understand the mechanism of similar diseases in human has well

    Surveillance of nosocomial infections: a preliminary study on hand hygiene compliance of healthcare workers

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    The observance of hand hygiene compliance is important to reduce cross-infection by micro-organisms. The aim of this preliminary study was to evaluate the level of hand hygiene in healthcare workers from different departments, with particular emphasis on transient flora. The study was conducted in three departments (Surgery, Intensive Care Unit, Obstetrics and Gynecology) of a hospital in Campania, southern Italy. Over a six-month period, 50 healthcareworkers wererandomly tested. Imprints of palms and fingertips were taken monthly during the morning shift. The number of colonies per plate was counted and transient pathogens were identified. Risk factors for hand contamination were determined. Total flora was found in the following CFU means per palm and per five fingertips (95% CI): Obstetrics and Gynecology [palms 130 CFUs (95% CI 85-180); fingertips 125 CFUs (95% CI 92-160)]; ICU [palms 80 CFUs (95% CI 58-99); fingertips 62 CFUs (95% CI 45-82)]; Surgery [palms 75 CFUs (95% CI 41-120); fingertips 70 CFUs (95% CI 52-90)] Transient flora was found on 39% of healthcare workers?hands. The only factor associated with hand contamination by transient flora was the absence of gloving during healthcare procedure(P=0.02)

    Leucocyte-and platelet-rich fibrin block: Its use for the treatment of a large cyst with implant-based rehabilitation

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    The management of critical-size bone defects is still demanding. Recently, autologous platelet concentrates in combination with bone substitute have been applied and reported in a few studies. Our aim is to report the healing of a critical-size alveolar bone defect treated with a new bone regeneration technique by means of L-PRF and L-PRF blocks. A 45-year-old woman presented a large cystic lesion; the extraction of three teeth, a cyst removal procedure, and bone regeneration procedures with L-PRF and L-PRF blocks were planned. The L-PRF block was prepared by mixing a bone substitute with a piece of L-PRF membrane and liquid fibrinogen. Additionally, after bone healing an implant-based rehabilitation was optimally performed. On the basis of the positive results, in terms of bone healing and tissue regeneration in a large bone defect, the application of LPRF and L-PRF blocks, in agreement with the scarce literature, is suggested as a feasible procedure in selected cases

    Recent expansion of dengue virus serotype 3 in West Africa

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    Due to non-existing or limited surveillance in Africa, little is known about the epidemiology of dengue illness in the continent. Serological and virological data obtained from returning European travellers is a key complement to this often flawed information. In the past years, dengue 3 virus has emerged in West Africa and has been detected in travellers returning to Europe. The first dengue epidemic in Cape Verde with more than 17,000 cases from September to December 2009 demonstrated that dengue virus is still expanding worldwide to new territories.S
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