Biology subjects

Mahdavi, S.

Publications and source records attributed to Mahdavi, S..

3 recordsLinked to original sources

bioRxiv2025

Optic Ataxia in Patients with Thalamic Lesions

Lesions in parietal cortex can strongly impair visually guided reach-grasping behaviour. A specific reaching deficit termed Optic Ataxia (OA) occurs when eye and hand position are dissociated. Optic ataxia has typically been studied in patients with lesions in parietal cortex, neglecting potential thalamic contributions. We here examined 28 acute stroke patients (age 58.9 {+/-} 12.6 years) with circumscribed thalamic lesions for the presence of optic ataxia. We leveraged MRI-based lesion-symptom mapping to address the contributions of specific thalamic nuclei to visually-guided reaching deficits under foveal and peripheral viewing conditions. Based on the cortical literature, we hypothesized that lesions in thalamic nuclei with strong connections to the inferior and superior parietal cortex, such as the ventrolateral nucleus and pulvinar might lead to optic ataxia. In comparison with aged-matched healthy subjects (n = 40, age 60.6 {+/-} 9.1 years), we identified five thalamic patients with optic ataxia, most pronounced for reaches with the contralesional hand into the contralesional space. While motor and grasping deficits and optic ataxia occurred frequently together, they did not always co-occur, and visual attention deficits could not account for the optic ataxia either. Comparing the lesion maps of patients with and without optic ataxia, the critical lesion site for optic ataxia was not restricted to one circumscribed thalamic region within the Morel atlas. Instead, it encompassed several medial and lateral nuclei within and around the internal medullary laminar (IML) complex. Interestingly, this region matches the so-called central thalamus, a functionally defined thalamic region that is considered a higher-order nucleus complex. It receives afferent inputs from the cerebellum and brainstem regions and connects to fronto-parietal regions involved in eye movement control. Taken together, our results suggest the critical importance of thalamic nuclei for the spatial transformation from eye-into body-centered coordinates.

neuroscience↗

bioRxiv2023

Flexibility and sensitivity in gene regulation out of equilibrium

Cells adapt to environments and tune gene expression by controlling the concentrations of proteins and their kinetics in regulatory networks. In both eukaryotes and prokaryotes, experiments and theory increasingly attest that these networks can and do consume bio-chemical energy. How does this dissipation enable cellular behaviors unobtainable in equilibrium? This open question demands quantitative models that transcend thermodynamic equilibrium. Here we study the control of a simple, ubiquitous gene regulatory motif to explore the consequences of departing equilibrium in kinetic cycles. Employing graph theory, we find that dissipation unlocks nonmonotonicity and enhanced sensitivity of gene expression with respect to a transcription factors concentration. These features allow a single transcription factor to act as both a repressor and activator at different levels or achieve outputs with multiple concentration regions of locally-enhanced sensitivity. We systematically dissect how energetically-driving individual transitions within regulatory networks, or pairs of transitions, generates more adjustable and sensitive phenotypic responses. Our findings quantify necessary conditions and detectable consequences of energy expenditure. These richer mathematical behaviors--feasibly accessed using biological energy budgets and rates--may empower cells to accomplish sophisticated regulation with simpler architectures than those required at equilibrium. Significance StatementGrowing theoretical and experimental evidence demonstrates that cells can (and do) spend biochemical energy while regulating their genes. Here we explore the impact of departing from equilibrium in simple regulatory cycles, and learn that beyond increasing sensitivity, dissipation can unlock more flexible input-output behaviors that are otherwise forbidden without spending energy. These more complex behaviors could enable cells to perform more sophisticated functions using simpler systems than those needed at equilibrium.

biophysics↗

bioRxiv2021

Peptimetric: Quantifying and visualizing differences in peptidomic data

Finding new sustainable means of diagnosing and treating diseases is one of the most pressing issues of our time. In recent years, several endogenous peptides have been found to be both excellent biomarkers for many diseases and to possess important physiological roles which may be utilized in treatments. The detection of peptides has been facilitated by the rapid development of biological mass spectrometry and now the combination of fast and sensitive high resolution MS instruments and stable nano HP-LC equipment sequences thousands of peptides in one single experiment. In most research conducted with these advanced systems, proteolytically cleaved proteins are analyzed and the specific peptides are identified by software dedicated for protein quantification using different proteomics workflows. Analysis of endogenous peptides with peptidomics workflows also benefit from the novel sensitive and advanced instrumentation, however, the generated peptidomic data is vast and subsequently laborious to visualize and examine, creating a bottleneck in the analysis. Therefore, we have created Peptimetric, an application designed to allow researchers to investigate and discover differences between peptidomic samples. Peptimetric allows the user to dynamically and interactively investigate the proteins, peptides, and some general characteristics of multiple samples, and is available as a web application at https://peptimetric.herokuapp.com. To illustrate the utility of Peptimetric, weve applied it to a peptidomic dataset of 15 urine samples from diabetic patients and corresponding data from healthy subjects.

bioinformatics↗