Albrechtsenallison7313

The physiological significance of the coherent cellular response to a molecularly complex matrix is discussed. This article has an associated First Person interview with the first author of the paper.The α-arrestin domain containing protein 3 (ARRDC3) is a tumor suppressor in triple-negative breast carcinoma (TNBC), a highly metastatic subtype of breast cancer that lacks targeted therapies. Thus, understanding the mechanisms and targets of ARRDC3 in TNBC is important. ARRDC3 regulates trafficking of protease-activated receptor 1 (PAR1, also known as F2R), a G-protein-coupled receptor (GPCR) implicated in breast cancer metastasis. Loss of ARRDC3 causes overexpression of PAR1 and aberrant signaling. Moreover, dysregulation of GPCR-induced Hippo signaling is associated with breast cancer progression. However, the mechanisms responsible for Hippo dysregulation remain unknown. AZD1480 order Here, we report that the Hippo pathway transcriptional co-activator TAZ (also known as WWTR1) is the major effector of GPCR signaling and is required for TNBC migration and invasion. Additionally, ARRDC3 suppresses PAR1-induced Hippo signaling via sequestration of TAZ, which occurs independently of ARRDC3-regulated PAR1 trafficking. The ARRDC3 C-terminal PPXY motifs and TAZ WW domain are crucial for this interaction and are required for suppression of TNBC migration and lung metastasis in vivo. These studies are the first to demonstrate a role for ARRDC3 in regulating GPCR-induced TAZ activity in TNBC and reveal multi-faceted tumor suppressor functions of ARRDC3. This article has an associated First Person interview with the first author of the paper.Rab5 is required for macropinosome formation, but its site and mode of action remain unknown. We report that Rab5 acts at the plasma membrane, downstream of ruffling, to promote macropinosome sealing and scission. Dominant-negative Rab5, which obliterates macropinocytosis, had no effect on the development of membrane ruffles. However, Rab5-containing vesicles were recruited to circular membrane ruffles, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent endomembrane fusion was necessary for the completion of macropinocytosis. This fusion event coincided with the disappearance of PtdIns(4,5)P2 that accompanies macropinosome closure. Counteracting the depletion of PtdIns(4,5)P2 by expression of phosphatidylinositol-4-phosphate 5-kinase impaired macropinosome formation. Importantly, we found that the removal of PtdIns(4,5)P2 is dependent on Rab5, through the Rab5-mediated recruitment of the inositol 5-phosphatases OCRL and Inpp5b, via APPL1. Knockdown of OCRL and Inpp5b, or APPL1, prevented macropinosome closure without affecting ruffling. We therefore propose that Rab5 is essential for the clearance of PtdIns(4,5)P2 needed to complete the scission of macropinosomes or to prevent their back-fusion with the plasmalemma.Fast-adapting type 1 (FA-1) and slowly-adapting type 1 (SA-1) first-order tactile neurons provide detailed spatiotemporal tactile information when we touch objects with fingertips. The distal axon of these neuron types branches in the skin and innervates many receptor organs associated with fingerprint ridges (Meissner corpuscles and Merkel cell neurite complexes, respectively), resulting in heterogeneous receptive fields whose sensitivity topography includes many highly sensitive zones or "subfields." In experiments on humans of both sexes, using raised dots that tangentially scanned the receptive field we examined the spatial acuity of the subfields of FA-1 and SA-1 neurons and its constancy across scanning speed and direction. We report that the sensitivity of the subfield arrangement for both neuron types on average corresponds to a spatial period of ∼0.4 mm and provide evidence that a subfield's spatial selectivity arises because its associated receptor organ measures mechanical events limited to a singlnical events at individual ridges. That neurons receive convergent input from multiple subfields does not preclude the possibility that spatial details can be resolved on the scale of single fingerprint ridges by a population code.Many species from diverse and often distantly related animal groups (e.g. monkeys, crows, fish and bees) have a sense of number. This means that they can assess the number of items in a set - its 'numerosity'. The brains of these phylogenetically distant species are markedly diverse. This Review examines the fundamentally different types of brains and neural mechanisms that give rise to numerical competence across the animal tree of life. Neural correlates of the number sense so far exist only for specific vertebrate species the richest data concerning explicit and abstract number representations have been collected from the cerebral cortex of mammals, most notably human and nonhuman primates, but also from the pallium of corvid songbirds, which evolved independently of the mammalian cortex. In contrast, the neural data relating to implicit and reflexive numerical representations in amphibians and fish is limited. The neural basis of a number sense has not been explored in any protostome so far. However, promising candidate regions in the brains of insects, spiders and cephalopods - all of which are known to have number skills - are identified in this Review. A comparative neuroscientific approach will be indispensable for identifying evolutionarily stable neuronal circuits and deciphering codes that give rise to a sense of number across phylogeny.

There remains major uncertainty regarding the optimal therapy for symptomatic nonacute extracranial vertebral artery occlusion (EVAO). Endovascular recanalization for EVAO is technically challenging, and limited data are available. This research aimed to report a multicenter clinical experience of endovascular recanalization for symptomatic nonacute EVAO and establish a novel angiographic classification.

From June 2011 to December 2019, 50 symptomatic nonacute EVAO patients treated with endovascular recanalization in three regional referral stroke centers were retrospectively analyzed. All patients were categorized into four groups based on the angiographic classification. The rates of technical success, periprocedural complications, any stroke or death within 1 month, and follow-up data were assessed.

The rates of technical success, periprocedural complications, and any stroke or death within 1 month were 86.0% (43/50), 12.0% (6/50), and 4.0% (2/50), respectively. The recanalization rates gradually decreased from Type A to Type D (100%, 94.