bioRxiv Science⌕ Search

Biology subjects

Gorji, A.

Publications and source records attributed to Gorji, A..

2 recordsLinked to original sources

Over-Reliance on Prior Expectations in Relapsing-Remitting Multiple Sclerosis

Cognitive impairment is a common and disabling feature of multiple sclerosis (MS). Bayesian models of perception and action provide a powerful framework to better understand how cognitive processes are altered in MS. In this case-control study, we employed a time reproduction paradigm within a Bayesian framework to investigate the underlying mechanisms of cognitive dysfunction in patients with relapsing-remitting MS. We applied a modified Bayesian observer model, which partitions time reproduction into three stages: sensory measurement, time estimation, and motor response. We found that both MS and control groups showed a systematic bias in reproducing time, overestimating short intervals and underestimating long intervals. This bias was significantly larger in patients with MS compared with controls, reflecting an over-reliance on prior expectations relative to sensory-motor information. Computational modeling indicated that this increased bias in the MS group was driven by greater measurement noise during the sensory stage. Moreover, central tendency bias increases with age in healthy participants as reliance on prior expectations becomes stronger than sensory-motor evidence. Interestingly, we found that this age-related effect on bias was absent in patients with MS. Further analysis showed both younger and older patients performed equally biased, and their performance was similar to older healthy participants.

neuroscience↗

Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

RationaleFailure of small synthetic vascular grafts is largely due to late endothelialization and has been an ongoing challenge in the treatment of cardiovascular diseases.\n\nObjectivePrevious strategies developed to promote graft endothelialization include surface topographical modulation and biochemical modifications. However, these have been met with limited success. Importantly, although the integrity of Endothelial Cell (EC) monolayer is crucial for endothelialization, the crosstalk between surface topography and cell-cell connectivity is still not well understood. Here we explored a combined strategy that utilizes both topographical features and pharmacological perturbations.\n\nMethods and resultWe characterized EC behaviors in response to micron-scale grating topography in conjunction with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We studied the EA.hy 926 cell-cell junctions and monolayer integrity using the junctional markers upon the inhibitory effect of EAJ regulator on both planar and grating topographies substrates.\n\nWe identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of EAJ stability. Next, we studied the physiologically relevant behaviors of EC using primary human coronary arterial endothelial cells (HCAEC). Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration to promote endothelialization.\n\nOur results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration and proliferation.\n\nConclusionThe synergistic effect of PTP1B inhibition and grating topographies could be useful for the promotion of endothelialization by enhancing EC migration and proliferation.

cell biology↗