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Relationship in between Intestinal tract Plants along with Serum Inflammatory Elements throughout Post-stroke Despression symptoms inside Ischemic Stroke.
© 2020, Fabig et al.Transient receptor potential canonical (TRPC) proteins form nonselective cation channels that play physiological roles in a wide variety of cells. Despite growing evidence supporting the therapeutic potential of TRPC6 inhibition in treating pathological cardiac and renal conditions, mechanistic understanding of TRPC6 function and modulation remains obscure. Here we report cryo-EM structures of TRPC6 in both antagonist-bound and agonist-bound states. The structures reveal two novel recognition sites for the small-molecule modulators corroborated by mutagenesis data. The antagonist binds to a cytoplasm-facing pocket formed by S1-S4 and the TRP helix, whereas the agonist wedges at the subunit interface between S6 and the pore helix. Conformational changes upon ligand binding illuminate a mechanistic rationale for understanding TRPC6 modulation. Furthermore, structural and mutagenesis analyses suggest several disease-related mutations enhance channel activity by disrupting interfacial interactions. Our results provide principles of drug action that may facilitate future design of small molecules to ameliorate TRPC6-mediated diseases. © 2020, Bai et al.Cryo-electron tomography (cryoET) has become a powerful technique at the interface of structural biology and cell biology, due to its unique ability for imaging cells in their native state and determining structures of macromolecular complexes in their cellular context. A limitation of cryoET is its restriction to relatively thin samples. Sample thinning by cryo-focused ion beam (cryoFIB) milling has significantly expanded the range of samples that can be analyzed by cryoET. Unfortunately, cryoFIB milling is low-throughput, time-consuming and manual. Here, we report a method for fully automated sequential cryoFIB preparation of high-quality lamellae, including rough milling and polishing. We reproducibly applied this method to eukaryotic and bacterial model organisms, and show that the resulting lamellae are suitable for cryoET imaging and subtomogram averaging. Since our method reduces the time required for lamella preparation and minimizes the need for user input, we envision the technique will render previously inaccessible projects feasible. © 2020, Zachs et al.Spermatozoa of marine invertebrates are attracted to their conspecific female gamete by diffusive molecules, called chemoattractants, released from the egg investments in a process known as chemotaxis. The information from the egg chemoattractant concentration field is decoded into intracellular Ca2+ concentration ([Ca2+]i) changes that regulate the internal motors that shape the flagellum as it beats. By studying sea urchin species-specific differences in sperm chemoattractant-receptor characteristics we show that receptor density constrains the steepness of the chemoattractant concentration gradient detectable by spermatozoa. Through analyzing different chemoattractant gradient forms, we demonstrate for the first time that Strongylocentrotus purpuratus sperm are chemotactic and this response is consistent with frequency entrainment of two coupled physiological oscillators i) the stimulus function and ii) the [Ca2+]i changes. We demonstrate that the slope of the chemoattractant gradients provides the coupling force between both oscillators, arising as a fundamental requirement for sperm chemotaxis. © 2020, Ramírez-Gómez et al.Depending on environmental demands, humans can learn and exploit multiple concurrent sets of stimulus-response associations. Mechanisms underlying the learning of such task-sets remain unknown. Here we investigate the hypothesis that task-set learning relies on unsupervised chunking of stimulus-response associations that occur in temporal proximity. We examine behavioral and neural data from a task-set learning experiment using a network model. We first show that task-set learning can be achieved provided the timescale of chunking is slower than the timescale of stimulus-response learning. Fitting the model to behavioral data on a subject-by-subject basis confirmed this expectation and led to specific predictions linking chunking and task-set retrieval that were borne out by behavioral performance and reaction times. Comparing the model activity with BOLD signal allowed us to identify neural correlates of task-set retrieval in a functional network involving ventral and dorsal prefrontal cortex, with the dorsal system preferentially engaged when retrievals are used to improve performance. © 2020, Bouchacourt et al.During spatial navigation, animals use self-motion to estimate positions through path integration. However, estimation errors accumulate over time and it is unclear how they are corrected. Here we report a new cell class ('cue cell') encoding visual cues that could be used to correct errors in path integration in mouse medial entorhinal cortex (MEC). During virtual navigation, individual cue cells exhibited firing fields only near visual cues and their population response formed sequences repeated at each cue. These cells consistently responded to cues across multiple environments. On a track with cues on left and right sides, most cue cells only responded to cues on one side. During navigation in a real arena, they showed spatially stable activity and accounted for 32% of unidentified, spatially stable MEC cells. These cue cell properties demonstrate that the MEC contains a code representing spatial landmarks, which could be important for error correction during path integration. © 2020, Kinkhabwala et al.Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. read more We present a method for maximum likelihood estimation of subunits by soft-clustering spike-triggered stimuli, and demonstrate its effectiveness in visual neurons. For parasol retinal ganglion cells in macaque retina, estimated subunits partitioned the receptive field into compact regions, likely representing aggregated bipolar cell inputs. Joint clustering revealed shared subunits between neighboring cells, producing a parsimonious population model. Closed-loop validation, using stimuli lying in the null space of the linear receptive field, revealed stronger nonlinearities in OFF cells than ON cells. Responses to natural images, jittered to emulate fixational eye movements, were accurately predicted by the subunit model. Finally, the generality of the approach was demonstrated in macaque V1 neurons.
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