Albaghdadi, M. | bioRxiv Science

bioRxiv2020

Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry

Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.

cell biology↗

bioRxiv2017

Gaze Behaviour During Sensorimotor Adaptation Parcellates the Explicit and Implicit Contributions to Learning

Successful motor performance relies on our ability to adapt to changes in the environment by learning novel mappings between motor commands and sensory outcomes. Such adaptation is thought to involve two distinct mechanisms: An implicit, error-based component linked to slow learning and an explicit, strategic component linked to fast learning and savings (i.e., faster relearning). Because behaviour, at any given moment, is the resultant combination of these two processes, it has remained a challenge to parcellate their relative contributions to performance. The explicit component to visuomotor rotation (VMR) learning has recently been measured by having participants verbally report their aiming strategy used to counteract the rotation. However, this procedure has been shown to magnify the explicit component. Here we tested whether task-specific eye movements, a natural component of reach planning--but poorly studied in motor learning tasks--can provide a direct read-out of the state of the explicit component during VMR learning. We show, by placing targets on a visible ring and including a delay between target presentation and reach onset, that individual differences in gaze patterns during sensorimotor adaptation are linked to participants rates of learning and can predict the expression of savings. Specifically, we find that participants who, during reach planning, naturally fixate an aimpoint, rotated away from the target location, show faster initial adaptation and readaptation 24 hrs. later. Our results demonstrate that gaze behaviour can not only uniquely identify individuals who implement cognitive strategies during learning, but also how their implementation is linked to differences in learning.

neuroscience↗