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901.
Anna Mondini Francesca Sassone Davide Antonio Civello Maria Lisa Garavaglia Claudia Bazzini Simona Rodighiero Valeria Vezzoli Fabio Conti Lucia Torielli Giovanbattista Capasso Markus Paulmichl Giuliano Meyer 《PloS one》2012,7(12)
The CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) activity and localization are influenced by the cytoskeleton, in particular by actin and its polymerization state. In this study we investigated whether the expression of the hypertensive mutations of α-adducin (G460W-S586C in humans, F316Y in rats), an actin capping protein, led to a functional modification of CFTR activity and surface expression. The experiments were performed on HEK293 T cells cotransfected with CFTR and the human wild type (WT) or G460W mutated α-adducin. In whole-cell patch-clamp experiments, both the CFTR chloride current and the slope of current activation after forskolin addition were significantly higher in HEK cells overexpressing the G460W adducin. A higher plasma membrane density of active CFTR channels was confirmed by cell-attached patch-clamp experiments, both in HEK cells and in cultured primary DCT cells, isolated from MHS (Milan Hypertensive Strain, a Wistar rat (Rattus norvegicus) hypertensive model carrying the F316Y adducin mutation), compared to MNS (Milan Normotensive Strain) rats. Western blot experiments demonstrated an increase of the plasma membrane CFTR protein expression, with a modification of the channel glycosylation state, in the presence of the mutated adducin. A higher retention of CFTR protein in the plasma membrane was confirmed both by FRAP (Fluorescence Recovery After Photobleaching) and photoactivation experiments. The present data indicate that in HEK cells and in isolated DCT cells the presence of the G460W-S586C hypertensive variant of adducin increases CFTR channel activity, possibly by altering its membrane turnover and inducing a retention of the channel in the plasmamembrane. Since CFTR is known to modulate the activity of many others transport systems, the increased surface expression of the channel could have consequences on the whole network of transport in kidney cells. 相似文献
902.
Atherothrombosis is a leading cause of death in patients with diabetes mellitus. Among factors contributing to the diabetic prothrombotic state, platelet activation plays a pivotal role. Numerous studies have investigated the benefits of antiplatelet therapy for primary and secondary cardiovascular prevention in diabetic patients. However, there are limited evidences that low-dose aspirin may be effective in this clinical setting. Several disease-specific factors have been identified as potential determinants of aspirin treatment failure. In this review, the main determinants of interindividual variability in response to antiplatelet agents are discussed, with particular emphasis on the pharmacokinetic and pharmacodynamic mechanisms of clinical efficacy and safety of antiplatelet drugs in patients with diabetes mellitus. 相似文献
903.
904.
Colomba C Saporito L Ciufolini MG Marchi A Rotolo V De Grazia S Titone L Giammanco GM 《The new microbiologica》2012,35(2):161-165
Toscana sandfly fever virus (TOSV) is an arthropod-borne virus transmitted to humans by sandfly vectors. It has been associated with human cases of meningitis and meningo-encephalitis mainly occurring during the warm season. We performed a retrospective serological study to evaluate TOSV circulation in Palermo, Sicily, and to compare TOSV seroprevalence in patients with neurological symptoms and in a control group of patients without neurological symptoms. When sera from 155 patients with and without neurological symptoms were evaluated, the rate of overall TOSV IgG reactivity was 17.4%. Patients with neurological symptoms showed a higher percentage of TOSV IgG positivity than control patients (25% versus 10.8%). TOSV exposure was confirmed by virus neutralization tests which also detected a Naples virus (SFNV) infection. TOSV should be considered as an etiologic agent in the differential diagnosis of fever and meningo-encephalitis in Sicily. 相似文献
905.
Viaggi CD Cavani S Pierluigi M Antona V Piro E Corsello G Mogni M Piccione M Malacarne M 《Journal of applied genetics》2012,53(3):285-288
Complex chromosomal rearrangements (CCRs) are structural aberrations involving more than two chromosomes with at least three breakpoints. CCRs can be divided into familial and de novo. Balanced CCR are extremely rare in humans and are at high risk of producing unbalanced gametes. Individuals with balanced CCR are usually phenotipically normal but report fertility problems, recurrent miscarriages or congenital anomalies in newborn offsprings as consequence of either meiotic failure or imbalanced chromosomes segregation.We describe the case of an unbalanced CCR involving chromosomes 1, 4 and 8 found in a girl with developmental delay, hexadactilia and microcephaly. The rearrangement, apparently balanced at a standard karyotype analysis and of maternal origin, was demonstrated to be unbalanced by array-CGH and FISH. In conclusion our study underlines the importance of the combined use of a quantitative technique, as array-CGH, to detect criptic segmental aneuploidies, and a qualitative tool, as FISH analysis, to physically map the localization of the chromosome segments involved, in order to realize the exact nature that underlies a chromosomal rearrangement. 相似文献
906.
907.
During developmental critical periods, external stimuli are crucial for information processing, acquisition of new functions or functional recovery after CNS damage. These phenomena depend on the capability of neurons to modify their functional properties and/or their connections, generally defined as "plasticity". Although plasticity decreases after the closure of critical periods, the adult CNS retains significant capabilities for structural remodelling and functional adaptation. At the molecular level, structural modifications of neural circuits depend on the balance between intrinsic growth properties of the involved neurons and growth-regulatory cues of the extracellular milieu. Interestingly, experience acts on this balance, so as to create permissive conditions for neuritic remodelling. Here, we present an overview of recent findings concerning the effects of experience on cellular and molecular processes responsible for producing structural plasticity of neural networks or functional recovery after an insult to the adult CNS (e.g. traumatic injury, ischemia or neurodegenerative disease). Understanding experience-dependent mechanisms is crucial for the development of tailored rehabilitative strategies, which can be exploited alone or in combination with specific therapeutic interventions to improve neural repair after damage. 相似文献
908.
Caraci F Spampinato S Sortino MA Bosco P Battaglia G Bruno V Drago F Nicoletti F Copani A 《Cell and tissue research》2012,347(1):291-301
Alzheimer’s disease (AD) is a neurodegenerative disorder that affects about 35 million people worldwide. Current drugs for
AD only treat the symptoms and do not interfere with the underlying pathogenic mechanisms of the disease. AD is characterized
by the presence of β-amyloid (Aβ) plaques, neurofibrillary tangles, and neuronal loss. Identification of the molecular determinants
underlying Aβ-induced neurodegeneration is an essential step for the development of disease-modifying drugs. Recently, an
impairment of the transforming growth factor-β1 (TGF-β1) signaling pathway has been demonstrated to be specific to the AD
brain and, particularly, to the early phase of the disease. TGF-β1 is a neurotrophic factor responsible for the initiation
and maintenance of neuronal differentiation and synaptic plasticity. The deficiency of TGF-β1 signaling is associated with
Aβ pathology and neurofibrillary tangle formation in AD animal models. Reduced TGF-β1 signaling seems to contribute both to
microglial activation and to ectopic cell-cycle re-activation in neurons, two events that contribute to neurodegeneration
in the AD brain. The neuroprotective features of TGF-β1 indicate the advantage of rescuing TGF-β1 signaling as a means to
slow down the neurodegenerative process in AD. 相似文献
909.
910.
Barbara Casati Genciana Terova Anna Giulia Cattaneo Simona Rimoldi Eleonora Franzetti Magda de Eguileor Gianluca Tettamanti 《Gene》2012
Atg1 is a Serine/Threonine protein kinase that plays a pivotal role in autophagy. A complete coding sequence of ATG1 is not available for the silkworm, Bombyx mori which is a good model for studying the autophagic process. 相似文献