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Chowdhury, P.

Publications and source records attributed to Chowdhury, P..

11 recordsLinked to original sources

An Open-Source End-to-End Pipeline for Large-Scale EEG-Based Brain Age Modelling

Aging affects individuals at varying biological rates, prompting the development of the Brain Age Index (BAI) to quantify neurobiological health relative to chronological age and disease risk. While structural MRI has dominated brain age prediction, its high cost, immobility, and low temporal resolution restrict its clinical scalability and responsiveness to transient neurophysiological changes. Electroencephalography (EEG) offers a highly scalable, portable, and temporally precise alternative capable of capturing dynamic brain states. However, the transition of EEG-based models to clinical biomarkers is impeded by methodological limitations, including small or biased datasets, inconsistent preprocessing pipelines, and a distinct lack of interpretable machine learning approaches. To address these persistent challenges, this paper presents a comprehensive, open-source, end-to-end pipeline for large-scale EEG-based brain age modeling. Developed using the Temple University Hospital EEG Corpus (TUEG) the largest publicly available resting-state EEG dataset. The pipeline encompasses rigorous data engineering, reproducible preprocessing, and robust feature extraction. Following quality control and subject-level dataset partitioning to definitively prevent data leakage, exactly 41,181 recordings were successfully retained. Two independent feature sets were extracted: the Catch22 time-series characteristics and a comprehensive set of spectral, aperiodic, and non-linear dynamics from the CCS toolbox. The methodology evaluates seven regression models, optimized via Optuna for hyperparameter tuning, and integrates SHAP (SHapley Additive exPlanations) for transparent feature importance analysis. By making this infrastructure publicly available, this work lowers the barrier to entry for large-cohort studies, fostering reproducible development and clinical validation of dynamic brain age biomarkers.

neuroscience↗

The Neurodynamic Core of Meditation: Dissociating Meditation from Rest and Task in a Reliability-based EEG study

BackgroundElectroencephalographic (EEG) studies attempting to characterise the neural signature of meditation typically rely on contrasts with passive rest or comparisons among practitioners based on experience. However, these approaches rarely include active control states and seldom establish the reliability and robustness of identified quantitative EEG features. Consequently, the validity of proposed neurophysiological markers of meditative state remains uncertain. The present study addressed these limitations by using a reliability-informed, multi-session within-subject design to characterise distinct state-dependent EEG dynamics in experienced meditators from the Brahmakumaris Rajayoga tradition. MethodsThirty long-term meditators underwent repeated EEG recordings over two days, comprising two meditation sessions per day. Each meditation block was flanked by rest periods, with a cognitive task between sessions to reduce carryover effects. We quantified broadband spectral power, aperiodic slope and intercept, and nonlinear dynamical measures, including detrended fluctuation analysis (DFA), Higuchi fractal dimension, and permutation entropy (PE), across meditation, rest, and task conditions. ResultsCompared with both rest and task states, meditation was associated with increased theta-alpha power, an elevated aperiodic intercept, and systematic modulation of nonlinear indices (DFA, Higuchi, PE). Further meditative core features demonstrated high inter-session test-retest reliability, strong inter-individual consistency, stability across guided and silent meditation states, and were not moderated by years of meditative experience. ConclusionThe present framework identifies a reproducible neurodynamic core of meditation, distinct from passive and active control states, spanning spectral, aperiodic, and nonlinear EEG domains in long-term meditators. These findings enhance the construct validity and measurement reliability of meditation-specific neural markers.

neuroscience↗

Lysine Demethylase 4A (KDM4A) Maintains Basal Body Architecture and Protects Against Ciliary Destabilization

Primary cilia are sensory organelles essential for signaling and defects in formation, maintenance or structure underlie diverse ciliopathies. Here, we identify lysine demethylase 4A (KDM4A) as a previously unrecognized mediator of ciliogenesis. Using genetic depletion and pharmacologic inhibition, we show that KDM4A is required for cilia assembly and maintenance. Super-resolution imaging reveals KDM4A localization at the basal body, where it distinctively wraps around the centrioles. We uncover a direct interaction between KDM4A and Rootletin (CROCC), a structural protein mediating centriole cohesion, and demonstrate that KDM4A loss increases inter-centriolar distances, implicating basal body architecture in ciliary failure. Together, these findings define a demethylase-centrosome axis that integrates KDM4A activity with organelle biology, revealing new mechanisms underlying ciliogenesis.

cell biology↗

Early Inflammation and Interferon Signaling Direct Enhanced Intestinal Crypt Regeneration after Proton FLASH Radiotherapy

Ultra-high dose rate ("FLASH") radiotherapy ([≥]40-60 Gy/s) is a promising new radiation modality currently in human clinical trials. Previous studies showed that FLASH proton radiotherapy (FR) improves toxicity of normal tissues compared to standard proton radiotherapy (SR) without compromising anti-tumor effects. Understanding this normal tissue sparing effect may offer insight into how toxicities from cancer therapy can be improved. Here, we show that compared to SR, FR resulted in improved acute weight recovery and survival in mice after whole-abdomen irradiation. Improved morbidity and mortality after FR were associated with greater proliferation of damage-induced epithelial progenitor cells followed by improved tissue regeneration. FR led to the accelerated differentiation of revival stem cells (revSCs), a rare damage-induced stem cell required for intestinal regeneration, and to qualitative and quantitative changes in activity of signaling pathways important for revSC differentiation and epithelial regeneration. Specifically, FR resulted in greater infiltration of macrophages producing TGF-{beta}, a cytokine important for revSC induction, that was coupled to augmented TGF-{beta} signaling in revSCs. In pericryptal fibroblasts, FR resulted in greater type I IFN (IFN-I) signaling, which directly stimulates production of FGF growth factors supporting revSC proliferation. Accordingly, the ability of FR to improve epithelial regeneration and morbidity was dependent on IFN-I signaling. In the context of SR, however, IFN-I had a detrimental effect and promoted toxicity. Thus, a tissue-level signaling network coordinated by differences in IFN-I signaling and involving stromal cells, immune cells, and revSCs underlies the ability of FLASH to improve normal tissue toxicity without compromising anti-tumor efficacy. One Sentence SummaryFLASH radiation improves normal tissue toxicity without compromising anti-tumor efficacy through a stroma, immune, and revSC signaling network coordinated by IFN-I.

cell biology↗

Lysine Demethylase 4A is a Centrosome Associated Protein Required for Centrosome Integrity and Genomic Stability

Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. The lysine demethylase 4A (KDM4A) is an epigenetic eraser of chromatin methyl marks, which we show also localizes to the centrosome with single molecule resolution. We additionally discovered KDM4A demethylase enzymatic activity is required to maintain centrosome homeostasis, and is required for centrosome integrity, a new functionality unlinked to altered expression of genes regulating centrosome number. We find rather, that KDM4A interacts with both mother and daughter centriolar proteins to localize to the centrosome in all stages of mitosis. Loss of KDM4A results in supernumerary centrosomes and accrual of chromosome segregation errors including chromatin bridges and micronuclei, markers of genomic instability. In summary, these data highlight a novel role for an epigenetic eraser regulating centrosome integrity, mitotic fidelity, and genomic stability at the centrosome.

cell biology↗

Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation

The rapid emergence of artemisinin resistance (ART-R) poses a challenge to global malaria control efforts. ART potency is triggered by ferrous iron- and/or heme-mediated cleavage of the endoperoxide bond to generate reactive heme-ART alkoxy radicals and covalent heme-ART adducts that alkylate parasite targets or inhibit the detoxification of heme into {beta}-hematin crystals; both of which lead to parasite death. Mutations in the P. falciparum Kelch-containing protein Kelch13 (PfKekch13) confer clinical ART-R, in which the resistant parasites exhibit impaired hemoglobin uptake, reduced heme yield, and thus decreased ART activation. However, a more direct involvement of PfKelch13 in heme-mediated ART activation has not been reported. Here, we show that recombinant, purified PfKelch13 wild-type (WT) protein displays measurable binding affinity for both iron and heme, the main effectors for ART activation. Comparative biochemical analyses further indicate weaker heme-binding affinities in the two Southeast Asian ART-R PfKelch13 mutants C580Y and R539T compared to the ART-sensitive WT and A578S mutant proteins, which ultimately translates into reduced yield of heme-ART derivatives. In conclusion, this study provides the first evidence for regulated ART activation via the heme-binding propensity of PfKelch13, which may contribute towards modulating the level of ART-R in malaria parasites with PfKelch13 mutations.

biochemistry↗

An essential mechanosensitive channel Pkd2 modulates the assembly of type II myosin and actin filaments in the cytokinetic contractile ring

Cytokinesis, the last step in cell division, separate daughter cells through the force produced by an actomyosin contractile ring assembled at the equatorial plane. In fission yeast cells, the ring helps recruit a mechanosensitive ion channel Pkd2 to the cleavage furrow, whose activation by membrane tension promotes calcium influx and daughter cell separation. However, it is unclear how the activities of Pkd2 may affect the actomyosin ring. Here, through both microscopic and genetic analyses of a hypomorphic mutant of the essential pkd2 gene, we examine its potential role in assembling and constricting the contractile ring. The pkd2-81KD mutation significantly increased the number of type II myosin heavy chain Myo2 (+20%), its regulatory light chain Rlc1 (+37%) and actin (+20%) molecules in the ring, compared to the wild type. Consistent with a regulatory role of Pkd2 in the ring assembly, we identified a strong negative genetic interaction between pkd2-81KD and the temperature-sensitive mutant myo2-E1. The pkd2-81KD myo2-E1 cells often failed to assemble a complete contractile ring. We conclude that Pkd2 modulates the recruitment of type II myosin and actin to the contractile ring, suggesting a novel calcium- dependent mechanism regulating the actin cytoskeletal structures during cytokinesis.

cell biology↗

Cytoplasmic tail of the putative polycystin channel Pkd2 regulates its clustering in the fission yeast eisosomes

Polycystins are a family of conserved ion channels, mutations of which lead to human genetic disorder Autosomal Dominant Polycystic Kidney Disease. The unicellular model organism fission yeast Schizosacchromyces pombe possesses single essential polycystin Pkd2 that localizes to the plasma membrane and is required for cell proliferation. Here, we carried out a functional analysis of Pkd2 based on its Alphafold predicted structure. It consisted of N-terminal lipid-binding (LBD), central transmembrane (TMD) and C-terminal cytoplasmic (CCD) domains. LBD assumes a unique immunoglobulin-fold, while TMD contains nine transmembrane helices. Both were essential. Although the mostly disordered CCD was not, its removal led to clustering of Pkd2 in eisosomes, a microdomain of the plasma membrane. Inhibiting eisosome assembly prevented the clustering but disrupting ER-PM contacts further increased it. Pkd2 shared similar structure with two other putative channels Trp663 and Trp1322, but their intracellular localization and function diverged from each other. Replacing LBD with that of Trp663 partially restored the function of Pkd2, but TMD could not be replaced by either that of Trp663 or human polycystins. We concluded that both the plasma membrane microdomains and cytoplasmic tail of Pkd2 regulate the cell surface clustering of this putative ion channel.

cell biology↗

Tracing the Indian Population Ancestry by cis-linked Mutations in HBB Gene

BackgroundHuman left their genetic footprints during the time of migration throughout the different countries all over the world. Human evolution was studied through various markers. India is a country of rich heritage and cultural diversity. The modern Indian population is derived from two ancestral groups, viz.-Ancestral North Indians (ANI) and Ancestral South Indians (ASI). AimFinding out the migratory route of the modern Indian population by studying cis acting mutations of human beta-globin (HBB) genes. Subjects and methodsA total of 120 thalassemia subjects were enrolled. DNA sequencing was done for mutation detection in the HBB gene. Some previous literature reviews were gone through for tracing mutations, all over the world and in the Indian subcontinent. ResultsNine thalassemia patients were found where HBB:c.92G>C and HBB:c.-92C>G mutations co-exist together in cis condition. Only one patient had HBB:c.51delC and HBB:c.33C>A. The pedigree analysis confirmed the presence of these mutations in cis condition and vertical transmission from one generation to the next. Literature reviews also reassure the co-existence of these mutations from different countries. ConclusionThe co-existence of these cis acting mutations helps to point out the possible migratory route of ANI population after venturing out of Africa.

evolutionary biology↗

The genetic basis of Drosophila melanogaster defense against Beauveria bassiana explored through evolve and resequence and quantitative trait locus mapping

Many of the molecular mechanisms for antifungal immunity in Drosophila melanogaster have been defined, but relatively little is known about the genetic basis for variation in antifungal immunity in natural populations. Using two population genetic approaches, Quantitative Trait Locus (QTL) Mapping and Evolve and Resequence (E&R), we explored the genetics underlying D. melanogaster immune defense against infection with the fungus Beauveria bassiana. Immune defense was highly variable both in the recombinant inbred lines from the Drosophila Synthetic Population Resource used for our QTL Mapping and in the synthetic outbred populations used in our E&R study. Survivorship of infection improved dramatically over just 10 generations in the E&R study, and continued to increase for an additional 9 generations, revealing a trade-off with uninfected longevity. Populations selected for increased defense against B. bassiana evolved cross resistance to a second, distinct B. bassiana strain but not to bacterial pathogens. The QTL mapping study revealed that sexual dimorphism in defense depends on host genotype, and the E&R study indicated that dimorphism also depends on the specific pathogen to which the host is exposed. Both the QTL Mapping and E&R experiments generated lists of potentially causal candidate genes, although these lists were non-overlapping.

genomics↗

Theaflavins, polyphenols of black tea, inhibit entry of hepatitis C virus

The treatment of hepatitis C virus (HCV) infection by combination of direct acting antivirals (DAA), with different mode of action, has made substantial progress in the past few years. However, appearance of resistance and high cost of the therapy is still an obstacle in the achievement of the therapy, more specifically in developing countries. In this context, search for affordable antivirals with new mechanisms of action is still needed. Tea, after water, is the most popular drink worldwide. Polyphenols extracted from green tea have already shown anti-HCV activity as entry inhibitors. Here, three different theaflavins, theaflavin (TF1), theaflavin-3-monogallate (TF2), and theaflavin-3-3-digallate (TF3), which are major polyphenols from black tea, were tested against HCV in cell culture. The results showed that all theaflavins inhibit HCV infection in a dose-dependent manner in an early step of infection. Results obtained with HCV pseudotyped virions confirmed their activity on HCV entry and demonstrated their pan-genotypic action. No effect on HCV replication was observed by using HCV replicon. Investigation on the mechanism of action of black tea theaflavins showed that they act directly on the virus particle and are able to inhibit cell-to-cell spread. Combination study with inhibitors most widely used in anti-HCV treatment regimen demonstrated that TF3 exerts additive effect. In conclusion, theaflavins, that are present in high quantity in black tea, are new inhibitors of HCV entry and hold promise for developing in therapeutic arsenal for HCV infection.

microbiology↗