Biology subjects

Mondal, R.

Publications and source records attributed to Mondal, R..

17 recordsLinked to original sources

bioRxiv2026

Sensitivity of stochastic growth rate and lifetime reproductive output to kin effects: A nonlinear feedback model

Humans exhibit a coevolutionary relationship between the trajectory of social evolution and senescence. A focal individual's kinship network is a function of his/her life history, while that network in turn shapes the focal individual's life history through kin effects on reproduction, generating a dynamic, nonlinear feedback loop across the population. Assessing directional selection on kin effects, therefore, requires explicitly modelling the feedback between the kinship network and life history. Here, we develop such a framework and apply it to examine selection pressures on the cooperative behaviour of closely related kin, including mothers, grandmothers, and older sisters. We hypothesise that the negative association of grandmothers, mothers, and older sisters (>10 years) with child mortality are under positive selection because increasing the absolute values of these kin effects would increase the stochastic growth rate. Furthermore, we hypothesise that the positive association of older sisters with child mortality is subject to negative selection, as increasing this effect would reduce the stochastic growth rate. We estimate kin-specific slope coefficients for child mortality using a Bayesian hierarchical model and solve a system of nonlinear equations linking kinship structure and survival to account for the nonlinear feedback between kinship and child survival. Thereafter, we compute stochastic sensitivities of both the stochastic growth rate and the mean lifetime reproductive output to these slope coefficients. Consistent with our hypotheses, all slope coefficients for kin presence on child mortality are negatively sensitive to both fitness metrics. We discuss the applications of our framework to examine the coevolution of social behaviours and senescence in age-structured populations.

evolutionary biology↗

bioRxiv2026

Modelling prodromal Parkinson's disease- gastrointestinal pathology and early motor deficits in mice after transient rotenone exposure

Early gastrointestinal (GI) dysfunction is a hallmark feature of Parkinson's disease (PD), yet models capturing prodromal gut and brain pathology in PD remain limited. Motivated by the increased PD risk associated with pesticide exposure, we monitored motor behavior, brain pathology, and GI structure and function over 9 months following 5 daily doses of rotenone in mice. Transient rotenone exposure induced significant nigrostriatal pathology, including {approx}48% loss of dopaminergic neurons and increased -synuclein aggregation in the substantia nigra, without significant changes in gross motor function. Notably, we identified pronounced GI dysfunction including reduced colonic transit velocity, altered motility dynamics, and delayed whole-gut transit. These functional changes were accompanied by enteric dopaminergic neurodegeneration, increased colonic -synuclein accumulation, increased colonic crypt depth, goblet cell hyperplasia with elevated mucin content per goblet cell. The findings are consistent with prodromal PD, suggesting the utility of this model for investigating early disease mechanisms and intervention strategies.

neuroscience↗

bioRxiv2026

Variability and persistence in inflation reshape human population dynamics by amplifying sensitivity and eroding demographic buffering

Inflation affects human fertility and survival; persistent inflation can translate into fluctuations in annual population growth rate. Existing studies have yet to systematically examine inflations impact on long-term growth rates across populations. Here, we examine whether high inflation variance and autocorrelation amplify long-term growth rates sensitivity to inflation, across 32 countries over 1971-2024. Additionally, we examine the effect of increasing inflation variance and autocorrelation on humans capacity for demographic buffering, i.e., reducing the temporal variance in vital rates most sensitive to growth. First, we construct inflation-dependent matrix population models using a hierarchical Bayesian framework. We then calculate the stochastic sensitivity and elasticity of population growth rate to inflation to quantify demographic buffering across a variance-autocorrelation parameter space. We find that the stochastic sensitivities of the growth rate increase with inflations variance and autocorrelation. However, we do not find support for the expected adverse effects of inflation variance and autocorrelation on humans capacity to buffer against inflation. Our framework provides a valuable tool for examining the impact of resource uncertainty on life history strategies in stochastic environments. We discuss how our framework can be extended to study the resource-dependent population dynamics within variable environments and across the tree of life.

ecology↗

bioRxiv2025

A brief exposure to rotenone alters microtubule dynamics resulting in aberrant elongation of primary cilia with impaired function

Rotenone, an environmental toxin, is widely used to model Parkinsons disease owing to its well-studied effect to inhibit mitochondrial complex I function and to increase Reactive Oxygen Species (ROS), thereby leading to dopaminergic neuron degeneration. Less appreciated is its impact on microtubules (MT), except for suggesting that it promotes microtubule depolymerization, raising the question of whether rotenone also impacts primary cilia (PC) that are microtubule-based signalling hubs, which are essential for neuronal function. Using hTERT-RPE1 (or RPE1) cells, which assemble PC upon serum starvation, we discovered that brief exposure to rotenone (2-6 h) at low concentration (100 nM) causes a striking elongation of PC and hyperacetylation of cytoskeletal microtubules. At this concentration, rotenone does not significantly alter mitochondrial dynamics or bioenergetics, and these phenotypes could not be reversed by pre-incubating cells with ROS scavenger NAC, or supplementing cells with NR. Thus, these observed effects of rotenone treatment in quiescent cells are predominantly independent of mitochondrial toxicity. Depletion of -TAT1, the -tubulin acetyltransferase, eliminated microtubule acetylation without preventing ciliary elongation, suggesting that rotenone drives PC extension through additional mechanisms. Importantly, rotenone increases soluble tubulin pools, owing to its microtubule destabilizing effect, which are likely the mechanism contributing to ciliary axoneme elongation as well as hyperacetylation of cytoskeletal microtubules. Critically, such aberrant increase in PC length impaired Sonic Hedgehog (SHH) signalling, which is exclusively transduced by PC during embryonic development and is critical for maintaining adult tissue homeostasis. Thus, our findings reveal that even brief, low-dose rotenone exposure induces aberrant elongation of PC in quiescent cells that assemble PC, while simultaneously disrupting the function of PC. Based on our observation and previous studies, we propose that such ciliary dysfunction represents an underappreciated mechanism by which rotenone contributes to the pathogenesis of neurodegenerative disease via affecting neuronal primary cilia.

cell biology↗

bioRxiv2025

Stretchable thin-film metal electronics enabled by multilayered nanomembranes

Metallic thin films are indispensable in flexible electronics, yet their brittleness under tensile strain has impeded their use in intrinsically stretchable devices. Here, we overcome this barrier with a multilayer platform of alternating nanomembranes of metal and porous elastomer assembled via exponential stacking. The porous elastomer layers anchor adjacent metal layers and facilitate vertical percolation. Under strain, they dissipate stress and laterally misalign cracks within successive metal layers, forming crack-bridging conductive pathways. This architecture achieves synergistic scaling of electrical and mechanical performance with increasing layer number, demonstrating bulk-like conductance at strains exceeding 700% across a wide range of metals. Using nanomembrane stacks of gold and platinum, we fabricated stretchable electrode arrays that enabled high-fidelity recordings and electrical stimulation of murine colonic electrophysiology in vivo.

physiology↗

bioRxiv2025

Multi-agent AI System for High Quality Metadata Curation at Scale

High-quality metadata is essential for downstream AI applications, yet metadata curation remains a persistent bottleneck in biomedical research. The core challenge lies in balancing quality and scalability. Manual curation delivers high quality, reliable annotations but is time-intensive and non-scalable; automated approaches, including those based on natural language processing, can scale but often fall short in accuracy and completeness. This tradeoff is particularly severe in public datasets, where metadata is frequently distributed across multiple sources for a single dataset. A notable example includes multi-omics datasets available on GEO and similar public repositories, which are often accompanied by associated publications. These supplementary sources can be leveraged to substantially enhance metadata quality, thereby supporting downstream applications such as classifier model development or the identification of biologically relevant cohorts, etc. We present a first-in-class multi-agent AI system that bridges the gap, achieving both high quality and scalability in metadata curation. Built on large-language models (LLMs), our system orchestrates a set of specialized agents that collaboratively extract, normalize, and infer critical metadata fields such as tissue, disease, cell line, sampling site, demographics, and experimental context from GEO entries, associated publications. A central orchestrator agent delegates tasks such as data retrieval, document parsing, ontology mapping, and context inference to expert sub-agents, enabling scalable, end-to-end automation. Applied to GEO data sets, a notoriously difficult metadata domain, our system achieves a 93% recall on average across 23 key fields (all original terms, normalized terms, and corresponding ontology ids) that include information about disease, tissue, treatment, donor-related information, outperforming existing automated baselines and approaches expert level quality. We also present a system that can easily scale to curate hundreds of metadata fields of interest with similar precision. This work demonstrates that an LLM-based multi-agent architecture can overcome traditional trade-offs in metadata curation, enabling both precision and scale, and offers a promising path forward for curating large public biomedical repositories for downstream AI applications.

scientific communication and education↗

bioRxiv2025

Magnetoelectric nanodiscs diminish motor deficits in a model of Parkinson's disease

Magnetoelectric nanodiscs (MENDs) offer a wireless, minimally invasive route to neuromodulation by converting weak magnetic fields into electric polarization, but their therapeutic applications have remained unrealized. Here, we report the therapeutic development of MENDs for deep brain stimulation (DBS) in the subthalamic nucleus (STN) to alleviate motor deficits in a mouse model of Parkinsons disease. To quantitatively assess therapeutic outcomes, we introduce GaitPattern, a computational pipeline that extracts DBS-induced alterations in salient gait features. Using GaitPattern, we demonstrate that MEND-mediated STN DBS induces motor improvements with precision comparable to clinical electrode-based DBS, while minimizing inflammatory responses associated with the implanted hardware. Notably, MEND-mediated DBS reduces oxidative stress in the brain, a key contributor to neurodegeneration. These findings position MEND-mediated STN DBS as an effective and minimally invasive neuromodulation strategy.

neuroscience↗

bioRxiv2025

Support for the social buffering hypothesis, especially under unpredictable precipitation regimes

Sociality is hypothesised to buffer populations against environmental stochasticity by stabilising key vital rates, yet this has rarely been tested across diverse taxa. We compiled demographic time series from 87 populations for 66 animal species spanning 12 taxonomic classes to test whether sociality promotes demographic buffering and whether this relationship depends on environmental context. Using stochastic elasticities and phylogenetically comparative analyses, we find broad support for the social buffering hypothesis: more social species exhibit lower sensitivity of population growth to vital rate variance (lower stochastic elasticity to vital rate variances, |T{sigma}|), particularly in juvenile survival and reproduction. Contrary to expectations, juvenile vital rates, but not adult survival, showed the strongest buffering patterns in social taxa, suggesting life-stage-specific social mechanisms. Furthermore, we show that social species invest more in maximising the average performance of adult survival and reproduction (higher stochastic elasticity to vital rate means, T), consistent with adaptive strategies favouring canalisation of fitness-related traits. This buffering benefit is especially relevant in highly unpredictable environments: in climates with erratic precipitation, social species have greater demographic advantages, exhibiting even lower T{sigma} values. Together, these findings provide support for the social buffering hypothesis, especially in highly stochastic environments. Social traits confer some demographic stability under moderate climatic conditions, but may become more relevant under extreme stochasticity--an insight particularly important for understanding population resilience in a rapidly changing world.

animal behavior and cognition↗

bioRxiv2024

Human populations with low survival at advanced ages and postponed fertility reduce long-term growth in high inflation environments

Temporal variability in inflation can lead to important fluctuations in the long-term growth rate of human populations via their differential impacts on vital rates like survival and fertility. However, historically, demographic studies have overlooked this time-dependent relationship. Here, we test whether human populations have higher stochastic population growth rates when exposed to lower levels of inflation. We also examine if lower survival rates at older ages (>60 years) and fertility rates at the later reproductive years (>30 years) among populations exposed to higher inflation rates determine their expected lower long-term growth rate compared to those exposed to lower inflation rates. To explore the impact of variability in inflation on vital rates response, we develop a quantitative pipeline with four steps, and parameterise it with high-resolution economic and demographic data across 76 countries from 1971-2021. The four steps are (1) defining treatment groups based on levels of trend inflation (creeping inflation (0-3%), walking inflation (3-10%), galloping inflation (10-50%), and hyperinflation (>50%)) among which the stochastic population growth rates will be compared; (2) constructing matrix population models for each environmental state under every treatment. The environmental states for each treatment are defined on the basis of the duration of inflation (e.g., 0, 2, 4, six years or above); (3) estimating the stochastic population growth rate for each treatment by considering a Markovian environment dictated by the long-term frequency (f) and temporal autocorrelation (p) of the treatment; and (4) decomposing the differences in the population growth rate between treatments into contributions from environmental variability and vital rate differences between environments to test how vital rates impact on population growth under varying environmental scenarios. In agreement with our hypothesis, we find that the stochastic population growth rate at lower levels of inflation is systematically higher than that at a higher level of inflation at all stationary frequencies and temporal autocorrelation of the inflation environment. Moreover, the disadvantage in survival at older ages (>60 years) and fertility at ages >30 years led to the lower stochastic growth rate among populations exposed to higher level of inflation such as walking inflation compared to lower level of inflation, such as creeping inflation. Our framework explicitly links human population performance and inflation environment by describing nonlinear feedback between inflation, human survival, fertility, population growth, and its age structure. We discuss the potential of our approach to study the life-history strategies and population dynamics of a wide range of drivers of environmental variability.

animal behavior and cognition↗

bioRxiv2024

Two liverworts from same habitats developed many similar but few distinct seasonal adaptive strategies: Insights from a transcriptomic approach

Liverworts are among the first land plants to experience seasonal changes after terrestrialization Therefore, we conducted a seasonal transcriptome analysis of two representative liverwort species from India, Dumortiera hirsuta and Plagiochasma appendiculatum, during their distinct growing seasons: the pre-monsoon, monsoon, post-monsoon, and fruiting season to understand the seasonal adaptations. Phylogenetic trees and evolutionary timescale analyses showed that D. hirsuta is primitive compared to P. appendiculatum. The RNA-seq analysis showed that D. hirsuta primarily modifies its transcriptome in the post-monsoon season but mainly induces specific genes in the fruiting season, most likely to develop reproductive organs and to adapt strategically by conserving energy in the fruiting season to deal with the harsh environmental conditions of both seasons. Conversely, P. appendiculatum exhibited significant transcriptome variability during both the fruiting and post-monsoon seasons, albeit to a lesser degree than D. hirsuta. This suggests that, to survive in the harsh conditions of both seasons, it strategically modulated its necessary gene expression levels over an extended period of time while taking energy conservation into consideration. This study offers the first comprehensive view of seasonal adaptive strategies employed by two liverworts that coexist in the same habitat but diverged at different stages in their evolutionary history.

genomics↗

bioRxiv2024

The impact of ERUPR on mitochondrial integrity mediated by PDK4

ER and mitochondrial stress are often interconnected and considered as major contributors to aging as well as neurodegeneration. Co-ordinated induction of ERUPR and mitoUPR has been observed in diabetes and pulmonary disorders. However, in the context of aging and neurodegeneration, regulation of this intra-organellar crosstalk has remained relatively elusive. Here, we demonstrate that pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial protein accumulates at the ER-mitochondrial contact sites (MAMs) during ER stress. Classically, PDK4 is known to phosphorylate PDHA1 (pyruvate dehydrogenase E1 subunit alpha 1), and plays a significant role in regulating the oxidative phosphorylation driven ATP production. In this study, we propose a non-canonical function of PDK4; we show that it acts as a connecting link between ERUPR and mitoUPR with significance in aging and neurodegeneration. Transcriptomics analyses show increased PDK4 levels upon drug induced ER stress. We detect elevated PDK4 levels in brain lysates of Alzheimers disease (AD) patients, as well as in in vivo and ex vivo AD models. Additionally, exogenous expression of PDK4 was found to refine ER-mitochondrial communication, significantly altering mitochondrial morphology and function. Further, we also observe defective autophagic clearance of mitochondria under such conditions. It is prudent to suggest that elevated PDK4 levels could be one of the key factors connecting ERUPR with mitoUPR, a phenotypic contributor in aging and at least some neurodegenerative diseases.

molecular biology↗

bioRxiv2023

The GIAB genomic stratifications resource for human reference genomes

Stratification of the genome into different genomic contexts is useful when developing bioinformatics software like variant callers, to assess performance in difficult regions in the human genome. Here we describe a set of genomic stratifications for the human reference genomes GRCh37, GRCh38, and T2T-CHM13v2.0. Generating stratifications for the new complete CHM13 reference genome is critical to understanding improvements in variant caller performance when using this new complete reference. The GIAB stratifications can be used when benchmarking variant calls to analyze difficult regions of the human genome in a standardized way. Here we present stratifications in the CHM13 genome in comparison to GRCh37 and GRCh38, highlighting expansions in hard-to-map and GC-rich stratifications which provide useful insight for accuracy of variants in these newly-added regions. To evaluate the reliability and utility of the new stratifications, we used the stratifications of the three references to assess accuracy of variant calls in diverse, challenging genomic regions. The means to generate these stratifications are available as a snakemake pipeline at https://github.com/ndwarshuis/giab-stratifications.

genomics↗

bioRxiv2023

Efficient Prohibitin 2 exposure during mitophagy depends on Voltage-dependent anion-selective channel protein 1.

Autophagic elimination of depolarized mitochondria (mitophagy) depends on Ubiquitin proteasome complex to expose the inner mitochondrial membrane-resident protein-Prohibitin 2 (PHB2). This uncovering facilitates its interaction with autophagosomal membrane-associated protein LC3. It remains unclear whether PHB2 is uncovered randomly through mitochondrial rupture sites. Prior knowledge and initial screening indicated that Voltage-dependent anion-selective channel protein 1 (VDAC1) might play a role in this process. Through in vitro biochemical assays and imaging, we have found that VDAC1-PHB2 interaction increases during mitochondrial depolarization. Subsequently, this interaction enhances the efficiency of PHB2 exposure and mitophagy. To investigate the relevance in vivo, we utilized a Porin (equivalent to VDAC1) knockout Drosophila line. Our findings demonstrate that during rotenone-induced mitochondrial stress, Porin is essential for PHB2 exposure, PHB2-LC3 interaction, and mitophagy. This study highlights that VDAC1 predominantly synchronizes efficient PHB2 exposure through mitochondrial rupture sites during mitophagy. These findings may provide insights to understand progressive neurodegeneration.

cell biology↗

bioRxiv2023

Protective intravenous BCG vaccination induces enhanced immune signaling in the airways

Intradermal (ID) Bacillus Calmette-Guerin (BCG) is the most widely administered vaccine in the world. However, ID-BCG fails to achieve the level of protection needed in adults to alter the course of the tuberculosis epidemic. Recent studies in non-human primates have demonstrated high levels of protection against Mycobacterium tuberculosis (Mtb) following intravenous (IV) administration of BCG. However, the protective immune features that emerge following IV BCG vaccination remain incompletely defined. Here we used single-cell RNA-sequencing (scRNAseq) to transcriptionally profile 157,114 unstimulated and purified protein derivative (PPD)-stimulated bronchoalveolar lavage (BAL) cells from 29 rhesus macaques immunized with BCG across routes of administration and doses to uncover cell composition-, gene expression-, and biological network-level signatures associated with IV BCG-mediated protection. Our analyses revealed that high-dose IV BCG drove an influx of polyfunctional T cells and macrophages into the airways. These macrophages exhibited a basal activation phenotype even in the absence of PPD-stimulation, defined in part by IFN and TNF- signaling up to 6 months following BCG immunization. Furthermore, intercellular immune signaling pathways between key myeloid and T cell subsets were enhanced following PPD-stimulation in high-dose IV BCG-vaccinated macaques. High-dose IV BCG also engendered quantitatively and qualitatively stronger transcriptional responses to PPD-stimulation, with a robust Th1-Th17 transcriptional phenotype in T cells, and augmented transcriptional signatures of reactive oxygen species production, hypoxia, and IFN-{gamma} response within alveolar macrophages. Collectively, this work supports that IV BCG immunization creates a unique cellular ecosystem in the airways, which primes and enables local myeloid cells to effectively clear Mtb upon challenge.

immunology↗

bioRxiv2023

A divide and conquer approach (DACA) to predict high fidelity structure of large multidomain protein BRWD1

Therapeutic importance in inhibiting Bromodomain and WD Repeat Domain containing BRWD1 against numerous human pathophysiological processes including cancers prompts prediction of a workable structure of this large protein. Here, a novel divide and conquer strategy was adopted to utilize smaller overlapping sequence-fragments of BRWD1 to further utilize their predicted structures as derived templates for prediction of complete BRWD1 structure in absence of its desired homologues in the template database. The novelty of this methodology stemmed from the requirement of templates of high sequence similarity in any comparative model based predictors whereas, the own fragments of the same target protein, BRWD1 could successfully fulfill this criteria. Additionally, the outputs of different high performing predictors including AlphaFold and RoseTTAFold were systematically integrated under the premise of Inductive Reasoning. The resultant structures were validated using existing validation parameters. Finally, a new validation paradigm was adopted to screen the best structure from the result presenting in-silico studies of known interactions of BRWD1 with various small molecules like, BD inhibitors, modified histone tails, DNA motifs and interacting proteins. The algorithm proposed in this work also paved the way for prediction of authentic structures of large size proteins.

bioinformatics↗

bioRxiv2023

Genome size, genetic diversity, and phenotypic variability imply the effect of genetic variation instead of ploidy on trait plasticity in the cross-pollinated tree species ofmulberry

Genome size, genetic diversity, and phenotypic vitiation were estimated to develop a model-based population structure and identify ploidy-associated traits of a wide collection of cross-pollinated, highly heterozygous tree species of Morus.Elucidation of genome size (GS), genetic and phenotypic variation is the fundamental aspect of crop improvement programs. Mulberry is a cross-pollinated, highly heterozygous tree eudicot, and comprised of huge ploidy variation with great adaptability across the world. However, because of inadequate information on GS, ploidy-associated traits, as well as the correlation between genetic and phenotypic variation hinder the further improvement of mulberry. In this present research, a core set of 157 germplasm accessions belonging to eight accepted species of Morus including promising functional varieties were chosen to represent the genetic spectrum from the whole germplasm collection. To estimate the GS, accessions were subjected to flow cytometry (FCM) analysis and the result suggested that four different ploidies (2n=2x, 3x, 4x, and 6x) with GS ranging from 0.72{+/-}0.005 (S-30) to 2.89{+/-}0.015 (M. serrata), accounting [~]4.01 fold difference. The predicted polyploidy was further confirmed with metaphase chromosome count. In addition, the genetic variation was estimated by selecting a representative morphologically, diverse population of 82 accessions comprised of all ploidy variations using simple sequence repeats (SSR). The estimated average Polymorphism Information Content (PIC) and expected heterozygosity showed high levels of genetic diversity. Additionally, three populations were identified by the model-based population structure (k=3) with a moderate level of correlation between the populations and different species of mulberry, which imply the effect of genetic variation instead of ploidy on trait plasticity that could be a consequence of the high level of heterozygosity imposed by natural cross-pollination. Further, the correlation between ploidies, especially diploid and triploid with selected phenotypic traits was identified, however, consistency could not be defined with higher ploidy levels (>3x). Moreover, incite gained here can serve as a platform for future omics approaches to the improvement of mulberry traits.

genetics↗

bioRxiv2022

The extracellular RNA pool within Zea mays apoplast: composition and differential expression during Ustilago maydis infection

The existence of an extracellular pool of RNA (exRNA) has been documented in both animal and plant cells in a number of instances. These exRNA species play important role in host response against different environmental stimuli. The mechanism of their function however remains largely unknown. In this study we report the composition of the exRNA pool within the leaf apoplast of Z. mays under normal growth condition. We could detect RNA transcripts originating from both the genic as well as the intergenic regions of the nuclear, mitochondrial and chloroplast genomes of maize in our exRNA sequencing data. Our data showed increased abundance of about 75% of the exRNA transcripts during infection with a basidiomycete smut fungi, Ustilago maydis. Functional classification of the differentially abundant exRNA transcripts within U. maydis SG200 WT infected maize apoplast with respect to uninfected apoplast revealed significant enrichment of the exRNA transcripts corresponding to the ribosome biogenesis pathway. Data related to the effect of two extracellular T2 type ribonucleases, Nuc1 and Nuc2 from U. maydis on the composition of exRNA pool of maize is also presented.

plant biology↗