Biology subjects

Dey, J.

Publications and source records attributed to Dey, J..

6 recordsLinked to original sources

bioRxiv2026

Endocrinology shadows ecology: Characterization of Markhor (Capra falconeri heptneri) reproductive cycles through non-invasive hormone assessment

Markhor (Capra falconeri) is a charismatic, threatened, large, high-altitude bovid found in parts of central and south Asia. The species faces threats such as habitat loss, hunting, poaching, livestock competition, hybridisation, and disease, yet research on wild populations is challenging. Various biological aspects, including surveys, diet, population dynamics, interactions with livestock, hybridisation, and disease, have been studied locally, along with behavior and reproductive biology, but details such as pregnancy, oestrus, and parturition timing remain unestablished. We conducted the first systematic, detailed, and fine-scale characterization of the reproductive steroid profiles of two males and five female markhors (Capra falconeri heptneri) in a captive population at the Padmaja Naidu Himalayan Zoological Park (PNHZP), West Bengal, India. We collected weekly fecal samples, standardized and validated measurements of progesterone (fP4M) and testosterone (fTM) metabolites, and conducted reproductive profiling to assess reproductive stages in both sexes. Analyses of annual fP4M and fTM data from male and female markhor individuals showed similar profiles and synchronicity, with individual variation, and peaks and baselines were evident for both hormones. In both sexes, significantly higher hormone titres were observed during the sexually active and inactive phases. Non-invasive measurement of reproductive hormones accurately reflected ovarian function in females, helping establish mating, gestation, and parturition timelines in female markhors and determine the breeding season in males. These approaches support husbandry and breeding management by identifying optimal pairing, diagnosing pregnancy, and predicting parturition in both captive and wild populations. When applied correctly, these tools could greatly aid population monitoring of other endangered species across high-altitude regions worldwide.

physiology↗

bioRxiv2025

Statistically valid explainable black-box machine learning: applications in sex classification across species using brain imaging

Sex classification using neuroimaging data has the potential to revolutionize personalized diagnostics by revealing subtle structural brain differences that underlie sex-specific disease risks. Despite the promise of machine learning, traditional methods often fall short in providing both high classification accuracy and interpretable, statistically validated feature importance scores for high-dimensional imaging data. This gap is particularly evident when conventional techniques such as random forests, LIME, and SHAP are applied, as they struggle with complex feature interactions and managing noise in large datasets. We address this challenge by developing an integrated framework that combines Oblique Random Forests (ORFs) with a novel, permutation-based feature importance testing algorithm. ORFs extend traditional random forests by employing oblique decision boundaries through linear combinations of features, thereby capturing intricate interactions inherent in neuroimaging data. Our feature importance testing method, NEOFIT, rigorously quantifies the significance of each feature by generating null distributions and corrected p-values. We first validate our approach using simulated datasets, establishing its robustness and scalability under controlled conditions. We then apply our method to classify sex from both voxel-wise structural MRI and cortical thickness data in humans and macaques, facilitating direct cross-species comparisons. ORFs achieves AUC > 0.80 on human data, and > 0.70 on macaque data, while NEOFIT identifies statistically significant features aligned with sex-dimorphic neuroanatomy. Our results demonstrate that the proposed framework not only enhances classification performance but also provides clear, interpretable insights into the neuroanatomical features that distinguish sexes. These methodological advancements pave the way for improved diagnostic tools and contribute to a deeper understanding of the evolutionary basis of sex differences in brain structure.

neuroscience↗

bioRxiv2024

Wisteria floribunda agglutinin enhances Zaire ebolavirus entry through interactions at specific N-linked glycosylation sites on the virus glycoprotein complex

Entry of Zaire ebolavirus (EBOV) into a host cell is a complex process requiring interactions between the viral glycoproteins (GP) and cellular factors. These entry factors are cell-specific and can include cell surface lectins and phosphatidylserine receptors. NPC1 is critical to the late stage of the entry process. Entry has been demonstrated to be enhanced by interactions between the virion and surface-expressed lectins, which interact with carbohydrate moieties attached to the GP. In addition, soluble lectins, including mannose binding lectin (MBL), can enhance entry in vitro. However, the mechanism of lectin-mediated enhancement remains to be defined. This study investigated the potential of three plant lectins, Wisteria floribunda agglutinin (WFA), soybean agglutinin (SBA) and Galanthus nivalis agglutinin (GNA), which possess different carbohydrate binding specificities, to enhance EBOV entry by binding to the GP. WFA was observed to potently enhance entry of lentiviral pseudotype viruses (PVs) expressing the GP of three Ebolavirus species (Zaire, Sudan [SUDV] and Reston [RESTV]), with the greatest impact on EBOV. SBA had a modest enhancing effect on entry that was specific to EBOV, while GNA had no impact on entry of any of the Ebolavirus species. None of the lectins enhanced entry of control PVs expressing the surface proteins of other RNA viruses tested. WFA was demonstrated to bind directly with the EBOV-GP via the glycans, and mutational analysis implicated N238 as contributing to the interaction. Furthermore, enhancement was observed in both human and bat cell lines indicating a highly conserved mechanism of action. We conclude that binding of WFA to EBOV GP through interactions including the glycan at N238 results in GP alterations that enhance entry, providing evidence of a mechanism for lectin-mediated virus entry enhancement. Targeting lectin-ligand interactions presents a potential strategy for restricting Ebolavirus entry.

microbiology↗

bioRxiv2024

A STAT3 Degrader Demonstrates Pre-clinical Efficacy in Venetoclax resistant Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that continues to have poor prognosis despite recent therapeutic advances. Venetoclax (Ven), a BCL2-inhibitor has shown a high response rate in AML; however, relapse is invariable due to mitochondrial dysregulation that includes upregulation of the antiapoptotic protein MCL1, a central mechanism of Ven resistance (Ven-res). We have previously demonstrated that the transcription factor STAT3 is upregulated in AML hematopoietic stem and progenitor cells (HSPCs) and can be effectively targeted to induce apoptosis of these aberrant cells. We now show that overexpression of STAT3 alone is sufficient to initiate a strong AML phenotype in a transgenic murine model. Phospho-proteomic data from Ven treated AML patients show a strong correlation of high total STAT3 and phospho-STAT3 [both p-STAT3(Y705) and p-STAT3(S727)] expression with worse survival and reduced remission duration. Additionally, significant upregulation of STAT3 was observed in Ven-res cell lines, in vivo models and primary patient samples. A novel and specific degrader of STAT3 demonstrated targeted reduction of total STAT3 and resulting inhibition of its active p-STAT3(Y705) and p-STAT3(S727) forms. Treatment with the STAT3 degrader induced apoptosis in parental and Ven-res AML cell lines and decreased mitochondrial depolarisation, and thereby dependency on MCL1 in Ven-res AML cell line, as observed by BH3 profiling assay. STAT3 degrader treatment also enhanced differentiation of myeloid and erythroid colonies in Ven-res peripheral blood mononuclear cells (PBMNCs). Upregulation of p-STAT3(S727) was also associated with pronounced mitochondrial structural and functional dysfunction in Ven-res cell lines, that were restored by STAT3 degradation. Treatment with a clinical-stage STAT3 degrader, KT-333 resulted in a significant reduction in STAT3 and MCL1 protein levels within two weeks of treatment in a cell derived xenograft model of Ven-res AML. Additionally, this treatment significant improvement in the survival of a Ven-res patient-derived xenograft in-vivo study. Degradation of STAT3 resulting in downregulation of MCL1 and improvements in global mitochondrial dysfunction suggests a novel mechanism of overcoming Ven-res in AML. Statement of PurposeFive-year survival from AML is dismal at 30%. Our prior research demonstrated STAT3 over-expression in AML HSPCs to be associated with inferior survival. We now explore STAT3 over-expression in Ven-res AML, explain STAT3 mediated mitochondrial perturbations and describe a novel therapeutic strategy, STAT3 degradation to overcome Ven-res.

cancer biology↗

bioRxiv2023

Inferring B-cell derived T-cell receptor induced multi epitope-based vaccine candidate against enterovirus 71 (EV 71): A reverse vaccinology approach.

In addition to Coxsackie virus (CV), another pathogen that causes Hand-foot and mouth disease (HFMD), Enterovirus 71 (EV 71) is currently regarded as an increasing neurotropic virus in Asia and can cause severe complications in paediatric patients with blister like sores or rashes on the hand, feet and mouth. Not withstanding the significant burden of the disease, few treatments are currently available, and there is no authorised vaccine available for the disease prevention. Several vaccinations based on attenuated and inactivated vaccines have previously been identified, however they become worthless over time owing to changes in the viral genome. As a result, the goal of the study is to create an immunoinformatics and reverse vaccinology pipeline for predicting a multi epitope vaccine. A novel vaccine construct using B-cell derived T-cell epitopes from the virulent polyprotein and found the induction of possible immune response, in order to boost the immune system, aBeta-defensin 1 preproprotein adjuvant with EAAAK linker was added at the N-terminal end of the vaccine sequence. The immunogenicity of the designed, refined, and verified prospective 3D- structure of multi-epitope vaccine was found to be quite high with non-allergen, and antigenic property. The vaccine candidates bound to the TLR-3 in a molecular docking analysis and the efficacy of the potential vaccine to generate a strong immune response was assessed by means of an in silico immunological simulation. Computational analysis has shown that the proposed multi epitope vaccine possibility safe for use in humans and elicit an immune response, making it a promising tool against HFMD viral genome.

immunology↗

bioRxiv2019

Growth and rapid succession of methanotrophs effectively limit methane release during lake overturn

Lakes and reservoirs contribute substantially to atmospheric concentrations of the potent greenhouse gas methane. Lacustrine sediments produce large amounts of methane, which accumulate in oxygen-depleted hypolimnia of stratified lakes. Due to climate change and progressing eutrophication, the number of lakes with hypolimnetic methane storage may increase in the future. However, whether stored methane eventually reaches the atmosphere during lake overturn is a matter of controversy and depends critically on the response of the methanotroph assemblage. We show that the methanotroph assemblage in a mixing lake underwent both a substantial bloom and ecological succession. As a result, the methane oxidation capacity of the mixed layer kept pace with the methane supplied from the hypolimnion and most of the stored methane was oxidized. This previously unknown aspect of freshwater methanotroph ecology represents an effective mechanism limiting methane transfer from lakes to the atmosphere.

microbiology↗