Biology subjects

Brown, V.

Publications and source records attributed to Brown, V..

4 recordsLinked to original sources

bioRxiv2025

The C. elegans WASH complex supports epithelial polarity by promoting endosomal sorting of Cadherin

Epithelial polarity requires polarized distribution of the apical adhesion complex that connects cells through the Cadherin transmembrane protein. Cadherin is intimately linked to the actin cytoskeleton through alpha catenin, which directly binds F-actin to set up the apical actin belt. Branched actin is formed when the Arp2/3 complex is activated by Nucleation Promoting Factors. C. elegans has three Nucleation Promoting Factors, WASP, WAVE and WASH. Our studies showed that WAVE-dependent branched actin promotes apical transport of Cadherin, including apically-directed transport of RAB-11-enriched endosomes. However, the contribution of other Nucleation Promoting Factors to Cadherin polarity has not been examined. The C. elegans WASH complex is not well described. Here we characterize components of the WASH complex, and confirm that CO5G5.2, despite being highly divergent, is the functional FAM21 component in C. elegans. We show that the WASH complex is enriched at early and recycling endosomes in the adult intestine, where it supports retrograde Cadherin transport. Our findings demonstrate that individual branched actin regulators promote specific transport steps, and identify WASH function at RME-1/EHD-enriched endosomes as an important contributor to Cadherin polarity and cargo sorting in a mature epithelium. Significance Statement*C. elegans has three known NPF (nucleation promoting factor) complexes to activate Arp2/3: WAVE, WASP and WASH. However, the role of C. elegans WASH complex in intracellular transport was unreported, and the essential component, FAM21, was not identified. *We show that C. elegans C05G5.2 is a likely FAM21 ortholog, since it functions in collaboration with other WASH components in retrograde transport. Loss of WASH components reduced epithelial polarity, while the cargo Cadherin was mis-sorted from early endosomes. *WASH branched actin polarizes epithelia using a functional FAM21 ortholog to promote sorting of retrograde cargo, including Cadherin.

cell biology↗

bioRxiv2019

Threat-Induced Anxiety During Goal Pursuit Disrupts Amygdala-Prefrontal Cortex Connectivity in Posttraumatic Stress Disorder

To investigate how unpredictable threat during goal pursuit impacts fronto-limbic activity and functional connectivity in posttraumatic stress disorder (PTSD), we compared military veterans with PTSD (n=25) versus trauma-exposed Control (n=25). Participants underwent functional magnetic resonance imaging (fMRI) while engaged in a computerized chase-and-capture game task that involved optimizing monetary rewards obtained from capturing virtual prey while simultaneously avoiding capture by virtual predators. The game was played under two alternating contexts - one involving exposure to unpredictable, task-irrelevant threat by randomly occurring electrical shocks, and a nonthreat control condition. Activation in and functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) was tested across threat and nonthreat task contexts with generalized psychophysiological interaction (gPPI) analyses. PTSD patients reported higher anxiety than controls across contexts. Better task performance represented by successfully avoiding capture by predators under threat than nonthreat contexts was associated with stronger left amygdala-vmPFC functional connectivity in controls and greater vmPFC activation in PTSD patients. PTSD symptom severity was negatively correlated with vmPFC activation in trauma-exposed controls and with right amygdala-vmPFC functional connectivity across all participants in the threat relative to nonthreat contexts. The findings showed that veterans with PTSD have disrupted amygdala-vmPFC functional connectivity and greater localized vmPFC processing under threat-modulation of goal-directed behavior, specifically related to successful task performance while avoiding loss of monetary rewards. In contrast, trauma survivors without PTSD rely on stronger threat-modulated left amygdala-vmPFC functional connectivity during goal-directed behavior, which may represent a resilience-related functional adaptation.

neuroscience↗

bioRxiv2018

3D Structural Connectivity In Healthy Adults: Detecting Structural Connections And Their Underlying Substrates For Olfactory Saccadic Pathway

This confirmatory study aimed to unravel the neural structural connectivity of Olfactory-Saccadic pathways extending between Piriform and Entorhinal Cortices to Frontal Eye Field (FEF), and to correlate its functional importance with possible clinical implications, using Diffusion Imaging fiber Tractography. The confirmatory observational analysis used thirty-two healthy adults, ultra-high b-value, diffusion imaging datasets from an Open access platform in Human Connectome Project (HCP). In all the datasets from both the sexes, fibers were traced and the neural structural connectivity was confirmed. The hemispheric differences between male and female subjects were anaNumber of tracts refers to a bundle of fibres having lysed using independent sample t-test. Thus, the study confirmed the structural existences of Olfactory-saccadic pathways that may be involved in influencing the movements of the neck and eyeball gaze (saccadic eye movement), towards the spatial orientation of olfactory stimulus.

neuroscience↗

bioRxiv2018

OLFACTORY SPATIAL ATTENTION: NEURAL STRUCTURAL CONNECTIVITY REVEALED

Different aspects of spatial neglect, the disability to locate the position of the source of an external stimulus, has been studied frequently especially with regards to lack of response to visual stimuli. A modicum of papers fails to elaborate on that of the auditory field and even less conducted on the extraction of spatial information from olfactory stimuli. In this study we attempted to find a structural connection between the Olfactory Cortex (OC) and Temporoparietal Junction (TPJ), in order to suggest that processed olfactory information is carried from OC to TPJ, where the spatial information of the odor maybe acquired. Positive results were attained in all subjects with a lateralization observed in the right hemisphere.\n\nOne Sentence SummaryExistence and hemispherical dominance.

neuroscience↗