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Biology subjects

Sagar, V.

Publications and source records attributed to Sagar, V..

5 recordsLinked to original sources

Demographic history, geographic distance, and landscape features shape the genetic divergence of wild tigers in northeast India

Habitat fragmentation creates small, isolated populations vulnerable to inbreeding, genetic drift, and high genetic load. For conservation management, it is essential to distinguish contemporary landscape resistance from historical demographic processes as drivers of these genetic patterns, especially for conservation priority regions such as northeast India which intersects two major tiger conservation landscapes. We studied the genetic structure and landscape connectivity of tigers across four protected areas in northeast India: Kaziranga, Manas, Orang, and Nameri, using faecal samples. From 741 samples collected over two field seasons, we identified 654 confirmed tiger specimens. Using methylation-based enrichment and ddRAD-seq of 176 samples, we generated a high-quality dataset of 3091 SNPs across 44 individuals. Population structure analyses identified three genetically distinct clusters: Kaziranga-Nameri, Manas, and Orang. Isolation-by-distance and landscape resistance explained 13% and 17% of the observed genetic divergence, respectively, with human settlements influencing gene flow. Orangs pronounced divergence from Kaziranga, despite geographic proximity and corridors, suggests a post-bottleneck founder effect, as evidenced by reduced heterozygosity (Ho = 0.24), nucleotide diversity (pi = 0.24), and effective population size (Ne = 1.3). These findings reveal that demographic and genetic recovery can decouple: Orangs population has recently grown, yet genome-wide evidence shows ongoing genetic erosion that monitoring has not detected. Similar patterns have been reported in other Indian tiger populations, indicating that such decoupling may be systemic. Target 4 of the Kunming-Montreal Global Biodiversity Framework requires explicit genetic diversity monitoring; this study demonstrates that non-invasive genomics can operationalise that mandate at a conservation-relevant scale.

evolutionary biology↗

Evaluating the efficacy of LUMPY-NIL herbal powder, dermal Spray and dermal ointment in treating Lumpy Skin Disease (LSD) in Bovines

BackgroundLumpy Skin Disease (LSD) lacks targeted treatment options and is managed using antibiotics and anti-inflammatory drugs. This study evaluated the efficacy of a polyherbal combination therapy in the management of LSD in affected bovines. Materials and Methods52 dairy cattle clinically diagnosed with LSD were enrolled in a field trial conducted under veterinary supervision. All animals received LUMPY-NIL Herbal Powder orally at 30 g twice daily, along with topical application of LUMPY-NIL Dermal Spray on closed nodules and LUMPY-NIL Ointment on open wounds. Daily monitoring included clinical signs, lesion progression, systemic symptoms, and milk yield recovery. ResultsTreatment duration varied from 7 to 21 days depending on severity of the disease. New lesion formation ceased within 2-4 days of treatment initiation. Systemic symptoms such as fever, lethargy, and inappetence resolved within 1-3 days. Open wounds showed progressive healing with no signs of infection, and nodules dried and sloughed off by day 15 in most animals. Milk yield showed partial recovery (20%) by day 7 and returned to baseline by day 15. The reduction in nodule size and number ranged from 81% to 94% by days 10-15. No adverse effects were observed during the treatment period. ConclusionThe polyherbal treatment combining demonstrated promising therapeutic benefits in managing clinical symptoms and accelerating recovery in LSD-infected cattle.

pharmacology and toxicology↗

Heterobifunctional proteomimetic polymers for targeted protein degradation

The burgeoning field of targeted protein degradation (TPD) has opened new avenues for modulating the activity of previously undruggable proteins of interest. To date, TPD has been dominated by small molecules containing separate linked domains for protein engagement and recruitment of cellular degradation machinery. The process of identifying active compounds has required tedious optimization and has been successful largely against a limited set of targets with well-defined, suitable docking pockets. Here we present a polymer chemistry approach termed the HYbrid DegRAding Copolymer (HYDRAC) to overcome standing challenges associated with the development of TPD. These copolymers densely display either peptide-based or small molecule-derived degradation inducers and target-binding peptide sequences for the selective degradation of disease-associated proteins. HYDRACs are synthesized in a facile manner, are modular in design, and are highly selective. Using the intrinsically disordered transcription factor MYC as an initial proof-of-concept, difficult to drug protein target, HYDRACs containing a MYC-inhibitory peptide copolymerized with a validated degron, showed robust and selective degradation of the target protein. Treatment of tumor-bearing mice with MYC-targeted HYDRACs showed decreased cell proliferation and increased tumor apoptosis, leading to significantly suppressed tumor growth in vivo. The versatility of the platform was demonstrated by substituting the degron for recruiters of three different E3 ligases (VHL, KEAP1, and CRBN), which all maintained MYC degradation. To demonstrate generalizability, HYDRACs were further designed against a second elusive target of clinical interest, KRAS, by employing a consensus RAS binding motif. RAS-targeted HYDRACs showed degradation in two cell lines harboring separate KRAS alleles, suggesting potential pan-KRAS activity. We envision the HYDRAC platform as a generalizable approach to developing degraders of proteins of interest, greatly expanding the therapeutic armamentarium for TPD.

bioengineering↗

Code for Collagen Folding Deciphered

Collagen triple helix folds in two steps: nucleation of three polypeptides at the C-termini followed by zip-chain like propagation. The triple helices found in all domains of life as well as viruses contain upto 6000 amino acids in each polypeptide that are also frequently interrupted with non-helical sequences that disrupt folding and reduce stability. Given the length of polypeptide and the disruptive interruptions, compensating mechanisms that stabilize against local unfolding during propagation and offset the entropic cost of folding the long polypeptides are not fully understood. Here, we show that the information for correct folding of collagen triple helices is encoded in their sequence as interchain electrostatic interactions. In case of humans, disrupting these interactions causes severe to lethal diseases. Key ResultCollagen triple helices found in all the three domains of life as well as viruses have converged on similar mechanism to fold correctly.

biochemistry↗

Exogenous attention facilitates performance through dissociable sensitivity and bias mechanisms

Selective attention enables prioritizing the most important information for differential sensory processing and decision-making. Here, we address an active debate regarding whether attention reflects a unitary phenomenon or involves the operation of dissociable sensory enhancement (perceptual sensitivity) and decisional gating (choice bias) processes. We developed a multialternative task in which participants detected and localized orientation changes in gratings at one of four spatial locations. Exogenous attention cues (high contrast flashes) preceded or followed the change events in close temporal proximity. Analysis of participants behavior with a multidimensional signal detection model revealed markedly distinct effects of exogenous cueing on perceptual sensitivity and choice bias. Whereas sensitivity enhancement was localized to the stimulus proximal to the exogenous cue, bias enhancement occurred even for distal stimuli in the cued hemifield. Modulations of sensitivity and bias were uncorrelated at both cued and uncued locations. Finally, exogenous cueing produced reaction time benefits only at the cued location and costs only at locations contralateral to the cue. These disparate effects of exogenous cueing on sensitivity, bias and reaction times could be parsimoniously explained within the framework of a diffusion-decision model, in which the drift rate was determined by a linear combination of sensitivity and bias at each location. Exogenous cueing effects on sensitivity and bias differed systematically from previously reported effects of endogenous cueing. We propose that the search for shared neural substrates of exogenous and endogenous attention would benefit from investigating neural correlates of their component sensory and decisional mechanisms.\n\nSignificance statementWhen we voluntarily direct attention \"endogenously\", we are able to better perceive stimuli at the attended location (sensitivity), and to prioritize information from that location for guiding behavioral decisions (bias). But when a salient stimulus, such as a flash of lightning, captures our attention \"exogenously\", does it also produce these same effects? To answer this question, we designed a multiple alternative task in which task events occurred in close conjunction with salient exogenous cues (high contrast flashes). We discovered that exogenous attention enhanced both sensitivity and bias for cued stimuli, but each of these changes followed distinct spatial patterns across locations. Our results provide novel insights into component processes of exogenous attention and motivate the search for their neural correlates.

neuroscience↗