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Inhibition of autophagy by bafilomycin rendered consistent expression of p62 indicating a defect in the final process of autophagy. Further, electron microscopic studies also confirmed massive vacuole overload and a sign of apoptotic cell death in PBMCs of diabetic patients, whereas metformin treatment reduced the number of autophagic vacuoles perhaps by lysosomal fusion. Thus, our results indicate that defective autophagy in T2D is associated with the fusion process of lysosomes which could be overcome by metformin. © 2020 International Federation for Cell Biology.Microtubule-associated protein (MAP) 2 has been perceived as a static cytoskeletal protein enriched in neuronal dendritic shafts. Emerging evidence indicates dynamic functions for various MAPs in activity-dependent synaptic plasticity. However, it is unclear how MAP2 is associated with synaptic plasticity mechanisms. Here, we demonstrate that specific silencing of high-molecular-weight MAP2 in vivo abolished induction of long-term potentiation (LTP) in the Schaffer collateral pathway of CA1 pyramidal neurons and in vitro blocked LTP-induced surface delivery of AMPA receptors and spine enlargement. In mature hippocampal neurons, we observed rapid translocation of a subpopulation of MAP2, present in dendritic shafts, to spines following LTP stimulation. Time-lapse confocal imaging showed that spine translocation of MAP2 was coupled with LTP-induced spine enlargement. Consistently, immunogold electron microscopy revealed that LTP stimulation of the Schaffer collateral pathway promoted MAP2 labeling in spine heads of CA1 neurons. This translocation depended on NMDA receptor activation and Ras-MAPK signaling. Furthermore, LTP stimulation led to an increase in surface-expressed AMPA receptors specifically in the neurons with MAP2 spine translocation. Altogether, this study indicates a novel role for MAP2 in LTP mechanisms and suggests that MAP2 participates in activity-dependent synaptic plasticity in mature hippocampal networks. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.Astrocytes are vital for preserving correct brain functioning by continuously sustaining neuronal activity and survival. They are in contact with multiple synapses at once allowing the expansion of local synaptic events into activity changes in neuronal networks. Furthermore, cortical astrocytes integrate local sensory inputs and behavioral state. From an anatomical, molecular, and functional perspective, astrocytes are thus ideal candidates to influence complex large-scale brain mechanisms such as plasticity. GNE-7883 YAP inhibitor We collected evidence for the astrocytic potential for plasticity modulation, using the monocular enucleation (ME) mouse model of visual cortex plasticity. The impact of one-eyed vision involves the functional recruitment of the deprived visual cortex by the spared senses within a 7-week time frame, reflecting a substantial change in sensory information processing. In visually deprived cortex, a swift upregulation in Aldh1l1-positive astrocyte density lasts until maximal functional recovery is reached. Transient metabolic silencing of visual cortex astrocytes at the time of ME induction, through intracranial fluorocitrate injections, reveals that astrocytes are required on site to achieve adequate long-term neuronal reactivation. In addition, chronic stimulation by Gi but not Gq G-protein coupled receptor activation of local astrocytes boosts the cortical plasticity phenomenon. Hence, functional manipulation of protoplasmic astrocytes has long-lasting effects on the functional recovery of cortical neurons upon sensory loss, possibly by influencing the neuronal threshold to reactivate. Together, our results highlight an integral role for astrocytes in mediating adult cortical plasticity and unmask astrocyte specific Gi signaling as an interesting therapeutic pathway for brain plasticity regulation. © 2020 Wiley Periodicals, Inc.PURPOSE Poorer short-term outcomes have been described for females after cardiovascular surgery. We examined the influence of sex on the outcomes after aortic root replacement (ARR). METHODS Medical records of 848 patients (females, n = 159/848, 19%) who underwent ARR at our center from 2005 to 2018 were retrospectively reviewed. Sex differences of the following outcomes were analyzed the primary end point (in-hospital mortality or stro111ke), secondary end point (new requirement for permanent pacemaker), and long-term survival (median follow-up 21.4 months [interquartile range,1.3-60.0]). RESULTS Females were significantly older (61.3 vs 58.7 [male]) with higher rates of pre-existing cerebrovascular disease (14% [22/159] vs 7% [52/689]) and previous valve intervention (20% [32/159] vs 13% [89/689]) but less myocardial infarction [1%(1/159) vs 7%(48/689)]. The surgical indication was different (aneurysm 75% [120/159] vs 87% [602/689], dissection 13% [21/159] vs 6% [41/689]; P  less then  .01]). Females had ladicals, Inc.The stable deposition of reactive nanostructures on metal electrodes is a key process for modern technologies including energy conversion / storage, electrocatalysis or sensing. Here we report a facile, scalable route which allows the bulk nanostructuring of copper foam electrodes with metal, metal oxide or metal hydroxide nanostructures. A concentration-gradient driven synthetic approach enables the fabrication of Janus-type electrodes where one face features Cu(OH)2 nanowires, while the other face features CuO nanoflowers. Thermal or chemical conversion of the nanostructured surfaces into copper oxide or copper metal is possible whilst retaining the respective nanostructure morphologies. As proof of concept, the functionalized electrodes are in electrocatalytic water oxidation and water reduction reactions. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Most oncology trainees are not taught about the needs of older patients, who make up the majority of patients with cancer. Training of health care providers is critical to improve the care of older adults with cancer. There is no consensus about which geriatric oncology (GO) competencies are important for medical oncology trainees. Our objective was to identify GO competencies medical oncology trainees should acquire during training. MATERIALS AND METHODS A modified Delphi consensus of experts in oncology medical education and GO was conducted. Experts categorized at what training stage proposed competencies should be attained internal medicine, oncology, or GO training. Consensus was obtained if two thirds of experts agreed on the training stage at which the competency should be attained. RESULTS A total of 78 potential competencies were identified, of which 35 (44.9%) proposed competencies were felt to be appropriate to be acquired during oncology training. The majority of the identified competencies pertained to prescribing of systemic therapy (n = 12) and psychosocial and supportive care (n = 13).
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