Biology subjects

Ghosh, N.

Publications and source records attributed to Ghosh, N..

14 recordsLinked to original sources

bioRxiv2026

Warmth shifts rather than speeds transcriptomic ageing in the malaria mosquito Anopheles gambiae

Only older mosquitoes transmit malaria, so how warming changes mosquito ageing matters for disease. Warmer temperatures are known to make mosquitoes age faster, but 'faster' can mean two different things: the ageing clock ticks more quickly, or it is simply set forward. We distinguished these by reanalysing 115 whole-body RNA-sequencing libraries from female Anopheles gambiae kept at 27, 30 or 32 {degrees}C and sampled 1-15 days after emergence. A transcriptomic clock trained on 27 {degrees}C mosquitoes (error {+/-}0.9 days) read 32 {degrees}C mosquitoes as 2.4 days older (95% CI 1.9-2.9) and 30 {degrees}C mosquitoes as 1.1 days older. The gap opened by day 5 and then stopped growing: between days 5 and 15, warmth added 0.01 extra days per day (95% CI -0.16 to 0.19), well below the 0.29-0.45 expected if the clock ran faster. Genome-wide, warmth advanced genes that change late in life, notably melanisation and digestive genes, but moved early-maturation genes the opposite way. Many responses bent at 30 {degrees}C, and immune genes held until 30 {degrees}C before falling. Warmth therefore shifts mosquitoes to an older transcriptional state without accelerating its pace.

bioinformatics↗

bioRxiv2026

Evolutionary replay of duplicate-gene retention across independent whole-genome duplications

Whole-genome duplication repeatedly exposes ancestral gene lineages to duplicate retention and loss. Although preferential retention is established, whether lineage identity carries transferable information, and which biological properties account for that information, remain separate questions. We compared retention ranks across independent duplications using orthology coordinates constructed independently of target outcomes. Three plant events showed replay (Treplay = 0.210; bootstrap 95% confidence interval, 0.172 to 0.248; permutation P = 1/100,001). A frozen plant score prospectively predicted Apple/Pear retention ({rho} = 0.169; n = 373; 95% confidence interval, 0.069 to 0.262; P = 0.000470). Transfer to yeast was supported, whereas teleost transfer remained unresolved. Independent teleost-Stylommatophora replay was positive but below its prespecified strong-effect threshold; a strict plant-animal scalar comparison remained unresolved. We then prospectively defined tests of dosage-related response, protein-sequence constraint, expression magnitude and expression breadth, followed by a frozen multivariate analysis. Dosage-related proxies, sequence constraint and expression breadth were unsupported under their tested definitions. Conserved expression magnitude was associated with retention across the reference plant events, but its attenuation of replay was unresolved. The multivariate model did not establish reliable prediction of held-out events superior to all single-property models. Thus, gene-lineage identity carries partially transferable retention information, but the tested conserved properties do not demonstrably account for it. Predicting retention and explaining replay are distinct biological problems.

evolutionary biology↗

bioRxiv2026

Microbiome-to-Nigrostriatal Vulnerability Mapping Prioritizes SCFA-Linked Gut-Brain Axes in Parkinson's Disease

BackgroundParkinsons disease (PD) is increasingly recognized as a multisystem neurodegenerative disorder in which gastrointestinal dysfunction, microbial ecology, immune signaling, and nigrostriatal vulnerability intersect. Microbiome studies have identified PD-associated gut microbial alterations, but translating these observations into host-relevant biological axes requires integration across microbial functions, metabolites, host genes, and brain-region transcriptomic context. MethodsMiNi-PD was developed as a lightweight, fully in silico, table-level prioritization workflow integrating processed PD microbiome features, curated microbe-metabolite-host-gene associations from gutMGene v2.0, and processed substantia nigra and putamen transcriptomic support from GSE136666. The framework ranks microbe-metabolite-host-gene axes using exact-curated metabolite-mediated evidence, brain-region support, and a normalized Nigrostriatal Gut-Brain Convergence Score (NGBCS). ResultsStrict evidence filtering retained 639 primary exact-curated metabolite-mediated axes. Of these, 12 had FDR-level brain transcriptomic support and 65 had nominal-or-stronger support. IL1B emerged as the principal FDR-level host-gene convergence point. SCFA-linked metabolites dominated the primary exact-curated set, including 387 butyrate axes and 5 3-indolepropionic-acid axes. The FDR-supported axes reached the maximum NGBCS value of 5.0, while the top nominally supported axes reached the high-priority NGBCS value of 4.5. ConclusionMiNi-PD identifies a focused SCFA-linked gut-brain signature in PD, highlighting butyrate- and 3-indolepropionic-acid-associated links to IL1B as a biologically meaningful substantia nigra-supported inflammatory axis. The NGBCS framework provides an accessible and interpretable route for prioritizing metabolite-mediated gut-brain mechanisms for downstream validation.

neuroscience↗

bioRxiv2026

Curli Carrier Burden: a quantitative trait-level microbiome index for amyloidogenic bacterial signals in Parkinsons disease gut metagenomes

BackgroundParkinsons disease (PD) gut metagenomic studies have repeatedly reported disease-associated shifts in microbial taxa, genes, and pathways. However, the field still lacks transparent trait-level indices that summarize biologically coherent microbial exposures. Curli fibres are extracellular bacterial amyloids produced by several Enterobacteriaceae and related taxa, and they provide a plausible microbiological bridge between gut microbial ecology, epithelial/immune interfaces, and alpha-synuclein-centered gut-brain-axis hypotheses. We introduced Curli Carrier Burden (CCB), a mathematically explicit, taxon-informed index that estimates the aggregate abundance of curated curli-carrier bacterial taxa in processed metagenomic profiles. MethodsA curated curli-carrier candidate panel was converted into an evidence-weighted taxon set. For sample s, CCB was defined as [Formula], where ais is the processed relative abundance of matched curli-carrier taxon i and wi is an evidence weight reflecting curli-carrier confidence. We evaluated CCB in five main PD gut metagenomic evidence streams: Wallen 2022, Integrated-US, Mao Central China, Romano non-Wallen, and DuruIC 2024. Results were interpreted cohort-wise rather than as a formal meta-analysis. ResultsThe CCB framework generated a reproducible sample-level microbial trait variable and enabled cohort-wise comparison of amyloidogenic bacterial burden. Wallen showed discovery-stage PD-associated elevation (724 samples; 31 matched curli taxa; Mann-Whitney p = 0.0020). Integrated-US provided supportive independent evidence (244 samples; 18 matched taxa; p = 0.0079). Mao Central China and DuruIC 2024 showed the same PD-greater-than-control direction by mean and median CCB, although their individual comparisons were not nominally significant. Romano non-Wallen provided a large multi-study analysis (600 samples; 29 matched curli-associated mOTUs taxa), with higher PD mean and median CCB in pooled analysis (p = 0.0036, Cliffs{delta} = 0.137) and cohort-sensitive behavior under study-stratified permutation (p = 0.1974). Additional processed-cohort checks indicated that CCB interpretability depends on taxonomic representation and matched curli-candidate coverage, reinforcing the value of explicit compatibility reporting. ConclusionsCCB is a novel, extensible, microbiology-informed index for quantifying amyloidogenic curli-carrier bacterial burden in processed gut metagenomic profiles. The current results support CCB as a useful exploratory trait-level variable for PD microbiome research and provide a principled route toward future raw-read, csg-operon, strain-resolved, and phenotype-aware studies of the curli-vagal PD axis.

neuroscience↗

bioRxiv2026

NeuroFate: endpoint-locked transcriptomic axis scoring for neurodegeneration risk research

MotivationAD and PD transcriptomic cohorts can reveal disease-associated neuronal, glial, mitochondrial, myelin, proteostasis, vascular, and immune programs, but these signals are difficult to compare reproducibly across studies without endpoint-locked, sample-level biological summaries. ResultsWe present NeuroFate, a command-line research package that converts compact transcriptomic cohorts into curated neurodegeneration-axis scores, exploratory research-use risk scores, and conservative evidence reports. The software locks disease-state endpoints before scoring, maps genes or probes onto a 10-axis NeuroFate panel, records axis-gene coverage, and grades external cohort evidence by direction, effect size, nominal/FDR support, and claim-safety rules. Demonstrations across AD and PD resources show nominal independent AD support for a neuronal vulnerability axis, mixed PD convergence, and a PD-divergent synuclein-mitochondrial example while avoiding clinical or mechanism-overstating claims. Availability and implementationNeuroFate is implemented in Python and available at https://github.com/sinhakrishnendu/NeuroFate.git. Contactnabanitaghosh89@gmail.com; dr.krishnendusinha@gmail.com. Supplementary informationDocumentation, examples, tests, and reproducibility notes are included in the repository.

bioinformatics↗

bioRxiv2025

Epoxyazadiradione ameliorates Parkinson's disease by upregulating heat shock factor 1 and protein degradation pathways in mice.

Parkinsons disease (PD) is a major debilitating health concern for millions of the elderly population all over the world. This progressive neurodegenerative disorder also poses a severe mental and financial burden to caregivers and society. Despite a major thrust on research for therapy development, no significant progress has been made; only temporary management options are currently available. To this end, we have reported azadiradione (AZD), a triterpenoid that we isolated from neem seed extract using a cell-based assay. AZD showed high efficacy in ameliorating protein aggregation-induced pathology and symptoms in fruit flies and mice. Current evidence suggests that AZD functions through activating the transcriptional function of heat shock factor 1 (HSF1), a master regulator of protein quality control pathways, without modulating the cellular redox balance. To better understand the pharmacophore of AZD, a triterpenoid in its observed function, we have analysed various structural derivatives, focusing on their HSF1-activating function in vitro and their efficacies in ameliorating protein aggregation-induced toxicities in cell and mouse models. Our analyses, based on real-time PCR, immunoblots, fluorescent anisotropy, and a mouse model of MPTP-induced PD, highlighted Epoxy-azadiradione (Epoxy) as being as efficient as AZD in in vivo functional tests, albeit activating the promoter binding activity of HSF1 with at least two-fold higher efficacy in vitro. Notably, similar to AZD, Epoxy did not induce cellular redox imbalance. We also incorporated molecular docking analyses involving the published crystal structure of the DNA-binding domain of HSF1 bound to its DNA recognition element to study molecular dynamics-based energy estimation. The analysis revealed a higher energy stability of the epoxy-bound complexes, as indicated by a significant decrease in binding free energy ({Delta}G) estimated from an ensemble of intermediate docked complex structures.

pharmacology and toxicology↗

bioRxiv2025

Pre-treatment naive T cells are associated with severe irAE following PD-1/CTLA4 checkpoint blockade for melanoma

Immune checkpoint inhibitors (ICIs) such as anti-PD-1 and anti-CTLA-4 antibodies are used to induce an immune response against many types of tumors. However, ICIs often also induce autoimmune responses, referred to as immune-related adverse events (irAEs), which occur unpredictably and at varying levels of severity in ICI-treated patients. The immunologic factors that predispose patients to the development of severe irAE are largely unclear. Here, we utilized high dimensional mass cytometry immunophenotyping of longitudinal blood samples from patients with metastatic melanoma treated with combination anti-PD-1/CTLA4 ICI therapy in the context of a clinical trial to characterize alterations in immune profiles induced by combination ICI therapy and to identify immune features associated with development of severe irAEs. Deep T cell profiling highlighted that ICI therapy induces prominent expansions of activated, CD38hi CD4+ and CD8+ T cells, which are frequently bound by the therapeutic anti-PD-1 antibody, as well as substantial changes in regulatory T cell phenotypes. However, neither the baseline frequency nor the extent of expansion of these cell populations was associated with development of severe irAEs. Rather, single cell-association testing revealed naive CD4+ T cell abundance pre-treatment as significantly associated with the development of severe irAEs. Biaxial gating of naive CD4+ T cells confirmed a significant positive association of naive CD4+ T cell proportion and development of a severe irAE and with the number of irAEs developed in this cohort. Results from this broad profiling study indicate the abundance of naive CD4+ T cells as a predictive feature for the development of severe irAEs following combination anti-PD-1/CTLA4 ICI therapy.

immunology↗

bioRxiv2025

Corneal lens curvature depends on localized chitin secretion

The Drosophila corneal lens is an apical extracellular matrix structure with a biconvex shape that enables it to focus light. Here we investigated how this shape is influenced by the source of one of its major components, the polysaccharide chitin. Knocking down the chitin synthase Krotzkopf verkehrt reduced corneal lens thickness and curvature. Conversely, enhancing chitin export by overexpressing Rebuf expanded the corneal lens. We found that the cone and primary pigment cells in the center of each ommatidium produce most of the chitin, and preventing chitin synthesis by these central cells reduced corneal lens curvature. Increasing chitin export from central cells increased the thickness of the central corneal lens, while increasing export from peripheral lattice cells expanded its edges. The biconvex shape thus results from high levels of chitin production by central cells relative to peripheral cells, indicating that localized chitin secretion is critical for normal corneal lens curvature.

developmental biology↗

bioRxiv2025

Transcription Factor Driven Gene Regulation in Autism Spectrum Disorder

Autism Spectrum Disorders (ASD) encompass a group of neurodevelopmental disorders in which an affected individual faces challenges in social interaction and communication, along with restricted and repetitive stereotypic behavioral patterns and interests. In this work, we have studied the differential gene regulation between patients and controls, mediated by Transcription Factors (TFs), of key genes involved in ASD. Nine and seven TFs have been identified as potential regulators of the set of syndromic and non-syndromic key high confident genes retrieved by the Simons Foundation Autism Research Initiative (SFARI) database. We have also identified significant couples of Transcription Factor - Target Gene potentially associated with an altered regulation in ASD patients. Consistently, many identified couples are involved in processes associated with brain morphogenesis and development. In this regard, this biased regulation could be the target of some experimental design in order to 1) test this hypothesis and 2) try to target this altered regulation pattern in ASD samples. In conclusion, we would like to emphasize that the present work proposes an effective and reliable computational approach that could be applied to any disease with known key genes and available gene expression data.

bioinformatics↗

bioRxiv2024

Unveiling epigenetic regulatory elements associated with breast cancer development

Breast cancer is the most common cancer in women and the 2nd most common cancer worldwide, yearly impacting over 2 million females and causing 650 thousand deaths. It has been widely studied, but its epigenetic variation is not entirely unveiled. We aimed to identify epigenetic mechanisms impacting the expression of breast cancer related genes to detect new potential biomarkers and therapeutic targets. We considered The Cancer Genome Atlas database with over 800 samples and several omics datasets such as mRNA, miRNA, DNA methylation, which we used to select 2701 features that were statistically significant to differ between cancer and control samples using the Monte Carlo Feature Selection and Interdependency Discovery algorithm, from an initial total of 417,486. Their biological impact on cancerogenesis was confirmed using: statistical analysis, natural language processing, linear and machine learning models as well as: transcription factors identification, drugs and 3D chromatin structure analyses. Classification of cancer vs control samples on the selected features returned high classification weighted Accuracy from 0.91 to 0.98 depending on feature-type: mRNA, miRNA, DNA methylation, and classification algorithm. In general, cancer samples showed lower expression of differentially expressed genes and increased {beta}-values of differentially methylated sites. We identified mRNAs whose expression is well explained by miRNA expression and differentially methylated sites {beta}-values. We recognized differentially methylated sites possibly affecting NRF1 and MXI1 transcription factors binding, causing a disturbance in NKAPL and PITX1 expression, respectively. Our 3D models showed more loosely packed chromatin in cancer. This study successfully points out numerous possible regulatory dependencies.

cancer biology↗

bioRxiv2024

The antimicrobial potential of traditional remedies of Indigenous Peoples from Canada against MRSA planktonic and biofilm bacteria in wound-infection mimetic conditions

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of wound infections, often progressing into serious invasive bloodstream infections. MRSA disproportionately affects Indigenous peoples in Canada with higher rates of skin and wound infections, an example of persistent gaps in health outcomes between Indigenous and non-Indigenous peoples precipitated by the legacy of colonialism. Conversely, Indigenous peoples have long used natural remedies for infections and other diseases; however, their knowledge was rarely considered for modern medicine. The stagnant antibiotic discovery pipeline and alarming rise of resistance to current antibiotics prompted us to turn to Indigenous medicine as an untapped source of antimicrobials. As such, we collected and prepared 85 extracts of medicinal plants of value to Indigenous Peoples spanning the Canadian Prairies. We explored the antimicrobial potential of these extracts against MRSA under wound infection-mimetic conditions compared to culture media typically used to study bacterial antibiotic responses and biofilms but not adequately representative of infection sites. We identified extracts with MRSA growth inhibitory [e.g., bergamot, dock, gaillardia, and dandelion extracts] and biofilm prevention and eradication [e.g., gumweed extracts] activities. Extracts, including those of chokecherry, hoary puccoon, and Northern bedstraw, were only active under wound infection-mimetic conditions, highlighting the relevance of antibiotic discovery under host-relevant conditions. Testing growth inhibitory extracts against an S. aureus cross-resistance platform suggested that they act through mechanisms likely distinct from known antibiotic classes. Together, through an interdisciplinary partnership leveraging Western approaches and traditional Indigenous knowledge, we identified plant extracts with promising antimicrobial potential for drug-resistant MRSA wound infections.

microbiology↗

bioRxiv2024

Apical cell expansion maintained by Dusky-like establishes a scaffold for corneal lens morphogenesis

The biconvex shape of the Drosophila corneal lens, which enables it to focus light onto the retina, arises by organized assembly of chitin and other apical extracellular matrix components. We show here that the Zona Pellucida domain-containing protein Dusky-like is essential for normal corneal lens morphogenesis. Dusky-like transiently localizes to the expanded apical surfaces of the corneal lens-secreting cells, and in its absence, these cells undergo apical constriction and apicobasal contraction. Dusky-like also controls the arrangement of two other Zona Pellucida-domain proteins, Dumpy and Piopio, external to the developing corneal lens. Loss of either dusky-like or dumpy delays chitin accumulation and disrupts the outer surface of the corneal lens. Artificially inducing apical constriction with constitutively active Myosin light chain kinase is sufficient to similarly alter chitin deposition and corneal lens morphology. These results demonstrate the importance of cell shape for the morphogenesis of overlying apical extracellular matrix structures.

developmental biology↗

bioRxiv2023

Developmental stability and segregation of Theory of Mind and Pain networks carry distinct temporal signatures during naturalistic viewing

Temporally stable large-scale functional brain connectivity among distributed brain regions is crucial during brain development. Recently, many studies highlighted an association between temporal dynamics during development and their alterations across various time scales. However, systematic characterization of temporal stability patterns of brain networks that represent the bodies and minds of others in children remains unexplored. To address this, we apply an unsupervised approach to reduce high-dimensional dynamic functional connectivity (dFC) features via low-dimensional patterns and characterize temporal stability using quantitative metrics across neurodevelopment. This study characterizes the development of temporal stability of the Theory of Mind (ToM) and Pain networks to address the functional maturation of these networks. The dataset used for this investigation comprised 155 subjects (children (n=122, 3-12 years) and adults (n=33)) watching engaging movie clips while undergoing fMRI data acquisition. The movie clips highlighted cartoon characters and their bodily sensations (often pain) and mental states (beliefs, desires, emotions) of others, activating ToM and Pain network regions of young children. Our findings demonstrate that ToM and pain networks display distinct temporal stability patterns by age 3 years. Finally, the temporal stability and specialization of the two functional networks increase with age and predict ToM behavior.

neuroscience↗

bioRxiv2022

Role of mucin gene for growth in Anas platyrynchos - a novel report

Mucin gene is expressed at the mucous membrane of the inner layer of the internal organs. Intestinal mucin 2 (MUC2), a major gel-forming mucin, represents a primary barrier component of mucus layers. This is the first report of role of mucin gene in growth traits in animals. In the current study, we had randomly studied Bengal ducks (Anas platyrynchos) reared from day old to 10 weeks of age under organized farm and studied the growth parameters as well as body weight and average daily body weight gain. We had characterized mucin gene for Bengal duck and observed glycosylation and EGF1 (EGF like domain signature) as important domain for growth traits in duck. We observed better expression profile for mucin gene in high growing ducks in comparison to that of lower growing ducks with real time PCR. Hence mucin gene may be employed as a marker for growth traits.

genomics↗