Biology subjects

Bindokas, V. P.

Publications and source records attributed to Bindokas, V. P..

3 recordsLinked to original sources

bioRxiv2023

Three-dimensional spatial quantitative analysis of cardiac lymphatics in the mouse heart

Objective3D microscopy and image data analysis are necessary for studying the morphology of cardiac lymphatic vessels (LyVs) and association with other cell types. We aimed to develop a methodology for 3D multiplexed lightsheet microscopy and highly sensitive and quantitative image analysis to identify pathological remodeling in the 3D morphology of LyVs in young adult mouse hearts with familial hypertrophic cardiomyopathy (HCM). MethodsWe developed a 3D lightsheet microscopy workflow providing a quick turn-around (as few as 5-6 days), multiplex fluorescence detection, and preservation of LyV structure and epitope markers. Hearts from non-transgenic (NTG) and transgenic (TG) HCM mice were arrested in diastole, retrograde perfused, immunolabeled, optically cleared, and imaged. We built an image processing pipeline to quantify LyV morphological parameters at the chamber and branch levels. ResultsChamber-specific pathological alterations of LyVs were identified, but most significantly in the right atrium (RA). TG hearts had a higher volume fraction of ER-TR7+ fibroblasts and reticular fibers. In the RA, we found associations between ER-TR7+ volume fraction and both LyV segment density and median diameter. ConclusionsThis workflow and study enabled multi-scale analysis of pathological changes in cardiac LyVs of young adult mice, inviting ideas for research on LyVs in cardiac disease.

pathology↗

bioRxiv2022

Design of the mammalian cone photoreceptor to Off bipolar cell synapse

Graded synapses in sensory systems reliably transmit small signals in the presence of continuous quantal noise. To understand how signaling is optimized during graded transmission, we counted the number of vesicles released by a mammalian cone terminal and compared it to the simultaneous responses in each Off bipolar cell type. Off bipolar cells contacting the terminal base comprised two groups depending on how they sampled transmitter release. In both groups, responses initially grew non-linearly with the number of released vesicles implicating a role for cooperativity during sparse release. One group sampled release from most of a cones [~]20 ribbons and can exploit averaging to improve signal reliability. The other, less-sensitive group made 1-3 contacts at the terminal center and responded to pooled transmitter, a consequence of membrane depolarization, using an insensitive kainate receptor. Off bipolar cells use different strategies to minimize transmission noise and encode cone output over different ranges.

neuroscience↗

bioRxiv2020

Subcellular localization of the J-protein Sis1 regulates the heat shock response

Cells exposed to heat shock induce a conserved gene expression program - the heat shock response (HSR) - encoding chaperones like Hsp70 and other protein homeostasis (proteostasis) factors. Heat shock also triggers proteostasis factors to form subcellular quality control bodies, but the relationship between these spatial structures and the HSR is unclear. Here we show that localization of the J-protein Sis1 - a co-chaperone for Hsp70 - controls HSR activation in yeast. Under nonstress conditions, Sis1 is concentrated in the nucleoplasm where it promotes Hsp70 binding to the transcription factor Hsf1, repressing the HSR. Upon heat shock, Sis1 forms an interconnected network with other proteostasis factors that spans the nucleolus and the surface of the cortical ER. We propose that localization of Sis1 to this network directs Hsp70 activity away from Hsf1 in the nucleoplasm, leaving Hsf1 free to induce the HSR. In this manner, Sis1 couples HSR activation to the spatial organization of the proteostasis network. One sentence summaryLocalization of the J-protein Sis1 to a subcellular network of proteostasis factors activates the heat shock response.

cell biology↗