Biology subjects

Mishra, C.

Publications and source records attributed to Mishra, C..

5 recordsLinked to original sources

bioRxiv2026

Snow leopard-mediated apparent competition between wild ungulates and domestic livestock in the Trans-Himalaya

Across High Asia, snow leopards Panthera uncia share habitats with pastoralists and consume both wild and domestic herbivores. Increasing wild prey is vital for predator conservation, but its effect on livestock depredation is unclear: it could decrease depredation through apparent facilitation or increase it through apparent competition. We investigated this association using a 13-year time series dataset from Upper Spiti Landscape in the Indian Trans-Himalaya. Long-term data on elusive carnivores are rare, making this time series especially valuable for testing predator-mediated interactions. We found higher wild ungulate density was accompanied by significantly greater depredation of free-ranging livestock, and this association remained positive after bootstrapping to account for uncertainty in density estimates. These results suggest snow leopard-mediated apparent competition between wild and domestic herbivores. We recommend conservation efforts that increase wild prey must also integrate effective livestock protection and support strategies to enhance coexistence between predators, prey and pastoralists.

ecology↗

bioRxiv2026

Hypothalamic Interleukin 6 linked to sex-specific behavioral deficits following adolescent social isolation

Social isolation refers to an extreme form of social deprivation that has enduring effects on the brain and behavior. Adolescents show selective vulnerability to such heightened social stress, displaying aberrant behavior and psychiatric ailments. The post-weaning social isolation rodent model has been widely used to recapitulate such behavioral anomalies and delineate their mechanistic bases. Here, we aim to identify how prolonged social isolation during adolescence affects neuroimmune responses in both sexes and the implications for behavioral outcomes, particularly aggression. While males subjected to adolescent isolation were hyper-aggressive with pathological signs, females showed reduced social exploration and inactivity. Cytokine profiling in core brain regions implicated in aggression revealed reduced interleukin 6 (IL6) levels, specifically in the hypothalamus, in both sexes. Other proinflammatory cytokines, including interferon-gamma and interleukin-1beta, were unaltered. IL6-responsive genes, SOCS3 and TIMP1, were also downregulated in the hypothalamus of both socially isolated males and females. The hypothalamus is crucial for stress responsiveness and the expression of excessive aggression. Despite behavioral dimorphism, reduced IL6 levels in both sexes may indicate differences in downstream signaling and roles beyond classical immune responses. Our findings suggest that hypothalamic IL6 may be a key mediator of adolescent social isolation, which is associated with aberrant behavior, including aggression.

neuroscience↗

bioRxiv2024

Simulating 500 million years of evolution with a language model

More than three billion years of evolution have produced an image of biology encoded into the space of natural proteins. Here we show that language models trained on tokens generated by evolution can act as evolutionary simulators to generate functional proteins that are far away from known proteins. We present ESM3, a frontier multimodal generative language model that reasons over the sequence, structure, and function of proteins. ESM3 can follow complex prompts combining its modalities and is highly responsive to biological alignment. We have prompted ESM3 to generate fluorescent proteins with a chain of thought. Among the generations that we synthesized, we found a bright fluorescent protein at far distance (58% identity) from known fluorescent proteins. Similarly distant natural fluorescent proteins are separated by over five hundred million years of evolution.

synthetic biology↗

bioRxiv2020

Spatial variation in population-density of snow leopards in a multiple use landscape in Spiti Valley, Trans-Himalaya

The endangered snow leopard Panthera uncia occurs in human use landscapes in the mountains of South and Central Asia. Conservationists generally agree that snow leopards must be conserved through a land-sharing approach, rather than land-sparing in the form of strictly protected areas. Effective conservation through land-sharing requires a good understanding of how snow leopards respond to human use of the landscape. Snow leopard density is expected to show spatial variation within a landscape because of variation in the intensity of human use and the quality of habitat. However, snow leopards have been difficult to enumerate and monitor. Variation in the density of snow leopards remains undocumented, and the impact of human use on their populations is poorly understood. We examined spatial variation in snow leopard density in Spiti Valley, an important snow leopard landscape in India, via spatially explicit capture recapture analysis of camera trap data. We camera trapped an area encompassing a minimum convex polygon of 953 km2. We estimated an overall density of 0.49 (95% CI: 0.39-0.73) adult snow leopards per 100 km2. Using AIC, our best model showed the density of snow leopards to depend on wild prey density, movement about activity centres to depend on altitude, and the expected number of encounters at the activity centre to depend on topography. Models that also used livestock biomass as a density covariate ranked second, but the effect of livestock was weak. Our results highlight the importance of maintaining high density pockets of wild prey populations in multiple use landscapes to enhance snow leopard conservation.

ecology↗

bioRxiv2018

First in-human PET study of 3 novel tau radiopharmaceuticals: RO6958948

Background[11C]RO-963, [11C]RO-643 and [18F]RO-948 (previously referred as [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948, respectively) have been reported as promising PET tracers for tau imaging based on in vitro and preclinical PET data (1,2). Here we describe the first human evaluation of these novel radiotracers.\n\nMethodsAmyloid PET positive Alzheimers disease (AD) patients and young healthy subjects (YC) each received two different tau tracers. Dynamic 90 min scans were obtained after bolus injection of [11C]RO-963, [11C]RO-643 or [18F]RO-948. Arterial blood sampling was performed in 11 healthy controls (HC) and 11 AD. Regions were defined on MRI, and PET data were quantified by plasma reference graphical analysis (for VT) and target cerebellum ratio (SUVR60-90). SUVR images were also analyzed voxelwise. Five older healthy subjects (OC) each received two scans with [18F]RO-948 for evaluation of test-retest variability. Four AD subjects received a repeat [18F]RO-948 scan over about 1 year. Six additional HC (3M: 3F; 41-67y) each received one whole body dosimetry scan with [18F]RO-948.\n\nResultsIn YC, peak SUV values were observed in the temporal lobe with values of approximately 3.0 for [11C]RO-963, 1.5 for [11C]RO-643 and 3.5 for [18F]RO-948. Over all brain regions and subjects, the trend was that [18F]RO-948 had the highest peak SUV value, followed by [11C]RO-963, and then [11C]RO-643. Regional analysis of SUVR and VT for [11C]RO-643 and [18F]RO-948 clearly discriminated AD and HC groups. Compartmental modeling confirmed that [11C]RO-643 had lower brain entry than both [18F]RO-963 and [18F]RO-948, and [18F]RO-948 showed a better contrast between (predicted) areas of high vs low tau accumulation. Thus, our subsequent analysis focused on [18F]RO-948. Both voxelwise and region-based analysis of [18F]RO-948 binding in HC vs AD revealed multiple areas where AD and HC significantly differed. Of 22 high-binding regions, 13 showed significant group difference (following ANOVA, F=45, p<10-5). Voxelwise analysis also revealed a set of symmetrical clusters where AD>HC (threshold of p<0.001, cluster size k>50).\n\nConclusions[18F]RO-948 demonstrates superior characteristics to [11C]RO-643 and [18F]RO-963 for characterization of tau pathology in AD. Regional binding data and kinetic properties of RO-948 compare favorably with existing other tau PET tracers.

neuroscience↗