Biology subjects

Dar, S. A.

Publications and source records attributed to Dar, S. A..

4 recordsLinked to original sources

bioRxiv2026

Searching for a New Home or Rare Dispersal? Habitat Suitability and Landscape Connectivity of the Tibetan Brown Bear across the Indian Cold Deserts and the Tibetan Plateau

Understanding habitat suitability and landscape connectivity is essential for conserving wide-ranging carnivores in climate-sensitive high-altitude mountain ecosystems. The first occurrence record of the Tibetan brown bear (Ursus arctos pruinosus) from the Changthang region of Ladakh, India, has raised questions about whether this individual represents an isolated dispersal event or reflects functional connectivity with source populations on the Tibetan Plateau. To evaluate potential habitat suitability and transboundary connectivity, we compiled species occurrence records and associated environmental predictors and developed an ensemble species distribution model using biomod2. We then assessed landscape connectivity using circuit theory implemented in Circuitscape to identify potential ecological corridors. Our models indicate that approximately 1,011,818 km{superscript 2} (21.34%) of the combined Ladakh (India) and the Tibetan Plateau landscape is currently suitable for the species, of which only [~]207,000 km{superscript 2} represents highly suitable habitat. Annual precipitation, precipitation of the wettest month, and precipitation of the warmest quarter were the most influential predictors of habitat suitability. Connectivity analysis identified potential corridors linking the eastern Changthang region of Ladakh with suitable habitat on the Tibetan Plateau, suggesting plausible transboundary ecological connectivity. These results indicate that the recent record from Changthang is more likely driven by landscape-scale functional connectivity than by an isolated dispersal event. Although the mapped corridors represent probable connectivity pathways rather than confirmed movement routes, this study provides the first spatially explicit assessment of habitat suitability and potential transboundary connectivity for the Tibetan brown bear across the Ladakh and Tibetan Plateau landscape.

ecology↗

bioRxiv2025

Cell-specific RNA isoform remodeling in the aging mouse brain

Aging is associated with increases in risk of multiple chronic diseases and at the cellular level, with disruptions in RNA homeostasis. Single-cell transcriptomic studies have revealed RNA abundance heterogeneity across brain cell types but the more complex changes in RNA processing such as alternative splicing, isoform usage, transcription start and polyadenylation site selection remain uncharacterized. Here, we combine single-cell analysis with long-read nanopore sequencing to capture full-length RNA isoforms and uncover temporal changes in RNA transcription, processing, and alternative splicing in the aging mouse cortex and hippocampus. By profiling transcriptomes from young adult to very old mice, we identify non-linear, cell-type-specific isoform expression changes and isoform usage shifts, primarily driven by transcription start site selection. These aging-associated isoform changes alter the coding potential and poly(A) site position of genes. Our data also reveal a high proportion of senescence in immune cells, far exceeding that of other cell types. We also identify isoform markers that, when applied to a machine learning model, distinguish senescent from normal immune cells. This study provides a full-length RNA isoform-based atlas of the aging mouse brain, offering insights into RNA metabolism remodeling across brain cell types throughout the lifespan.

genomics↗

bioRxiv2023

Full-length direct RNA sequencing reveals widespread RNA decay upon cellular stress

Cells react to stress by triggering response pathways, leading to extensive alterations in the transcriptome to restore cellular homeostasis. The role of RNA metabolism in shaping the cellular response to stress is vital, yet the global changes in RNA stability under these conditions remain unclear. In this work, we employ direct RNA sequencing with nanopores, enhanced by 5 end adaptor ligation, to comprehensively interrogate the human transcriptome at single-molecule and nucleotide resolution. By developing a statistical framework to identify robust RNA length variations in nanopore data, we find that cellular stress induces prevalent 5 end RNA decay that is coupled to translation and ribosome occupancy. Unlike typical RNA decay models in normal conditions, we show that stress-induced RNA decay is dependent on XRN1 but does not depend on deadenylation or decapping. We observed that RNAs undergoing decay are predominantly enriched in the stress granule transcriptome while inhibition of stress granule formation via genetic ablation of G3BP1 and G3BP2 rescues RNA length. Our findings reveal RNA decay as a key determinant of RNA metabolism upon cellular stress and dependent on stress-granule formation.

cell biology↗

bioRxiv2023

Senescence-specific translation dysregulation desensitizes cells to stress by inhibiting activation of the integrated stress response

Senescence is a state of indefinite cell cycle arrest associated with aging, cancer, and age-related diseases. Here, using label-based mass spectrometry, ribosome profiling and nanopore direct RNA sequencing, we explore the coordinated interaction of translational and transcriptional programs of human cellular senescence. We find that translational deregulation and a corresponding maladaptive integrated stress response (ISR) is a hallmark of senescence that desensitizes senescent cells to stress. We present evidence that senescent cells maintain high levels of eIF2 phosphorylation, typical of ISR activation, but translationally repress production of the stress response transcription factor 4 (ATF4) by ineffective bypass of the inhibitory upstream open reading frames. Surprisingly, ATF4 translation remains inhibited even after acute proteotoxic and amino acid starvation stressors, resulting in a highly diminished stress response. Furthermore, absent a response, stress augments the senescence secretory phenotype, thus intensifying a proinflammatory state that exacerbates disease. Our results reveal a novel mechanism that senescent cells exploit to evade an adaptive stress response and remain viable.

molecular biology↗