Biology subjects

Sarkar, M.

Publications and source records attributed to Sarkar, M..

27 records · Page 2Linked to original sources

bioRxiv2023

Avifaunal Species diversity from Southern West part of West Bengal, India

Birds are essential for stabilizing the balance between various ecosystems. To estimate their diversity, we studied species distribution and made an annotated checklist along with their feeding habitats in the Southwest part of West Bengal, India. We studied the bird diversity using the point count method on various habitats, including agroforest, grassland, sub-tropical forest, and plateau forest regions. A total of 343 species were identified during our study period (2015-2019). We found high species diversity and sightings in the study sites, with 55 new records for the region. The whole study was conducted using a citizen science approach and amateur bird watchers community. This study will emphasize the future biodiversity conservation practice for the avifauna.

ecology↗

bioRxiv2023

Neural effects of TMS trains on the human prefrontal cortex

How does a train of TMS pulses modify neural activity in humans? Despite adoption of repetitive TMS (rTMS) for the treatment of neuropsychiatric disorders, we still do not understand how rTMS changes the human brain. This limited understanding stems in part from a lack of methods for noninvasively measuring the neural effects of a single TMS train -- a fundamental building block of treatment -- as well as the cumulative effects of consecutive TMS trains. Gaining this understanding would provide foundational knowledge to guide the next generation of treatments. Here, to overcome this limitation, we developed methods to noninvasively measure causal and acute changes in cortical excitability and evaluated this neural response to single and sequential TMS trains. In 16 healthy adults, standard 10 Hz trains were applied to the dorsolateral prefrontal cortex (dlPFC) in a randomized, sham-controlled, event-related design and changes were assessed based on the TMS-evoked potential (TEP), a measure of cortical excitability. We hypothesized that single TMS trains would induce changes in the local TEP amplitude and that those changes would accumulate across sequential trains, but primary analyses did not indicate evidence in support of either of these hypotheses. Exploratory analyses demonstrated non-local neural changes in sensor and source space and local neural changes in phase and source space. Together these results suggest that single and sequential TMS trains may not be sufficient to modulate local cortical excitability indexed by typical TEP amplitude metrics but may cause neural changes that can be detected outside the stimulation area or using phase or source space metrics. This work should be contextualized as methods development for the monitoring of transient noninvasive neural changes during rTMS and contributes to a growing understanding of the neural effects of rTMS.

neuroscience↗

bioRxiv2023

Mapping cortical excitability in the human dorsolateral prefrontal cortex

ObjectiveTo characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and that EL-TEP amplitude is inversely related to muscle artifact. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach. MethodsIn 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses. ResultsStimulation location significantly influenced EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%. SignificanceEarly local TMS-evoked potentials (EL-TEPs) can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols. HighlightsO_LIEarly local TMS-evoked potentials (EL-TEPs) varied significantly across the dlPFC as a function of TMS target. C_LIO_LITMS targets with less muscle artifact had significantly larger EL-TEPs. C_LIO_LISelection of a postero-medial target increased EL-TEPs by 102% compared to anterior targets. C_LI

neuroscience↗

bioRxiv2022

Experimental Suppression of TMS-EEG Sensory Potentials

BackgroundThe sensory experience of transcranial magnetic stimulation (TMS) evokes cortical responses measured in EEG that confound interpretation of TMS-evoked potentials (TEPs). Methods for sensory masking have been proposed to minimize sensory contributions to the TEP, but the most effective combination for suprathreshold TMS to dorsolateral prefrontal cortex (dlPFC) is unknown. ObjectiveWe applied sensory suppression techniques and quantified electrophysiology and perception from suprathreshold dlPFC TMS to identify the best combination to minimize the sensory TEP. MethodsIn 21 healthy adults, we applied single pulse TMS at 120% resting motor threshold (rMT) to the left dlPFC and compared EEG vertex N100-P200 and perception. Conditions included three protocols: No masking (no auditory masking, no foam, jittered inter-stimulus interval (ISI)), Standard masking (auditory noise, foam, jittered ISI), and our ATTENUATE protocol (auditory noise, foam, over-the-ear protection, unjittered ISI). ResultsATTENUATE reduced vertex N100-P200 by 56%, "click" loudness perception by 50%, and scalp sensation by 36%. We show that sensory prediction, induced with predictable ISI, has a suppressive effect on vertex N100-P200, and that combining standard suppression protocols with sensory prediction provides the best N100-P200 suppression. ATTENUATE was more effective than Standard masking, which only reduced vertex N100-P200 by 22%, loudness by 27%, and scalp sensation by 24%. ConclusionsWe introduce a sensory suppression protocol superior to Standard masking and demonstrate that using an unjittered ISI can contribute to minimizing sensory confounds. ATTENUATE provides superior sensory suppression to increase TEP signal-to-noise and contributes to a growing understanding of TMS-EEG sensory neuroscience. HighlightsO_LIATTENUATE is a novel sensory suppression protocol for suprathreshold dlPFC TMS C_LIO_LIATTENUATE is superior to standard masking for minimizing sensory confounds C_LIO_LIATTENUATE reduced vertex N100-P200 by 56% with no effect on the early TEP C_LIO_LIATTENUATE reduced "click" loudness rating by 50% and scalp sensation by 36% C_LIO_LIIndividual modifications are not sufficient to reduce vertex N100-P200 or perception C_LI

neuroscience↗

bioRxiv2021

Viroporin activity of SARS-CoV-2 Orf3a and Envelope protein impacts viral pathogenicity

COVID-19 is caused by SARS-CoV-2 which has so far affected more than 500 million people worldwide and killed over 6 million as of 1st May, 2022. The approved emergency-use vaccines were lifesaving to such a devastating pandemic. Viroporins are important players of the life cycle of SARS-CoV-2 and are primary to its pathogenesis. We studied the two prominent viroporins of SARS-CoV-2 (i) Orf3a and (ii) Envelope (E) protein from a sequential and structural point of view. Orf3a is a cation selective viral ion channel which has been shown to disrupt the endosomal pathways. E protein is one of the most conserved proteins among the SARS-CoV proteome which affects the ERGIC related pathways. The aqueous medium through the viroporins mediates the non-selective translocation of cations, affecting ionic homeostasis in the host cellular compartments. This ionic imbalance could potentially lead to increased inflammatory response in the host cell. Our results shed light into the mechanism of viroporin action, which can be potentially leveraged for the development of antiviral therapeutics. Our results corroborate with previously published transcriptomic data from COVID-19 infected lung alveolar cells where inflammatory responses and molecular regulators directly impacted by ion channelling were upregulated.

molecular biology↗

bioRxiv2020

Translation regulation of Japanese encephalitis virus revealed by ribosome profiling

Japanese encephalitis virus (JEV), a neurotropic flavivirus, is the leading cause of viral encephalitis in endemic regions of Asia. Although the mechanisms modulating JEV virulence and neuroinvasiveness are poorly understood, several acquired mutations in the live attenuated vaccine strain (SA14-14-2) point towards translation regulation as a key strategy. Using ribosome profiling, we identify multiple mechanisms including frameshifting, tRNA dysregulation and alternate translation initiation sites that regulate viral protein synthesis. A significant fraction (~ 40%) of ribosomes undergo frameshifting on NS1 coding sequence leading to early termination, translation of NS1' protein and modulation of viral protein stoichiometry. Separately, a tRNA subset (glutamate, serine, leucine and histidine) was found to be associated in high levels with the ribosomes upon JEV infection. We also report a previously uncharacterised translational initiation event from an upstream UUG initiation codon in JEV 5' UTR. A silent mutation at this start site in the vaccine strain has been shown to abrogate neuroinvasiveness suggesting the potential role of translation from this region. Together, our study sheds light on distinct mechanisms that modulate JEV translation with likely consequences for viral pathogenesis.

microbiology↗

bioRxiv2020

Structural insight into the putative role of Novel Coronavirus-2 E protein in viral infection via in silico approach: a potential target for LAV development and other therapeutic strategies

The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases. Using bioinformatics and structural modeling approach, we modeled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS-CoV-1, and is highly conserved in the N-terminal regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modeling, we found that the most favorable structure could function as a gated proton channel. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds. Additionally, two distinct “core” structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral proton channeling activity which may play a critical role in viral infection. In addition, it provides a structural basis and additional avenues for generating therapeutic interventions against the virus.One Sentence Summary Structural modeling of the novel coronavirus envelope proteins (E-proteins) demonstrating its possible proton channeling activity.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗

bioRxiv2019

A signaling axis involving CNOT3, Aurora B and ERK promotes mesendodermal differentiation of ES cells in response to FGF2 and BMP4

Mesendoderm cells are key intermediate progenitors that form at the early primitive streak (PrS) and give rise to mesoderm and endoderm in the gastrulating embryo. We have identified an interaction between CNOT3 and the cell cycle kinase Aurora B, which requires sequences in the NOT box domain of CNOT3, and regulates MAPK/ERK signalling during mesendoderm differentiation. Aurora B phosphorylates CNOT3 at two sites located close to a nuclear localization signal and promotes localization of CNOT3 to the nuclei of mouse ES cells (ESCs) and metastatic lung cancer cells. ESCs that have both sites mutated give rise to embryoid bodies that are largely devoid of mesoderm and endoderm and are composed mainly of ectoderm. The mutant ESCs are also compromised in their ability to differentiate into mesendoderm in response to FGF2, BMP4 and Wnt3. The double mutation affects interaction of CNOT3 with Aurora B and with ERK and reduces phosphorylation of ERK in response to FGF2, impacting on survival of the differentiated ME cells. Our results identify an adaptor function for CNOT3 that regulates a key pathway in embryogenesis and cancer.

developmental biology↗

bioRxiv2019

A role of cellular translation regulation associated with toxic Huntingtin protein

Huntingtons disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While the Htt amyloid aggregates are known to affect many cellular processes, its role in translation is not addressed. Here we report pathogenic Htt expression causes protein synthesis deficit in cells. We find a functional prion-like protein, the translation regulator Orb2 to be sequestered by Htt aggregates. Coexpression of Orb2 can partially rescue the lethality associated with poly Q expanded Htt. These findings can be relevant for HD as human homologs of Orb2 also can be sequestered by pathogenic Htt aggregates. Our work suggests that translation dysfunction could be one of the contributors in the pathogenesis of HD and new therapies targeting protein synthesis pathways might help alleviate disease symptoms.

cell biology↗