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rabindra.tharu.np@gmail.com
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Environment-independent distribution of mutational effects emerges from microscopic epistasis
Predicting how new mutations alter phenotypes is difficult because mutational effects vary across genotypes and environments. Recently discovered global epistasis, in which the fitness effects of mutations scale with the fitness of the background genotype, can improve predictions, but how the environment modulates this scaling is unknown. We measured the fitness effects of ~100 insertion…
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rabindra.tharu.np@gmail.com
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Targeting cancer with small-molecule pan-KRAS degraders
Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein are highly prevalent in cancer. However, small-molecule concepts that address oncogenic KRAS alleles remain elusive beyond replacing glycine at position 12 with cysteine (G12C), which is clinically drugged through covalent inhibitors. Guided by biophysical and structural studies of ternary complexes, we designed a heterobifunctional…
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rabindra.tharu.np@gmail.com
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Durably reducing conspiracy beliefs through dialogues with AI
Conspiracy theory beliefs are notoriously persistent. Influential hypotheses propose that they fulfill important psychological needs, thus resisting counterevidence. Yet previous failures in correcting conspiracy beliefs may be due to counterevidence being insufficiently compelling and tailored. To evaluate this possibility, we leveraged developments in generative artificial intelligence and engaged 2190 conspiracy believers in personalized evidence-based dialogues…
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rabindra.tharu.np@gmail.com
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H(2)O(2) sulfenylates CHE, linking local infection to the establishment of systemic acquired resistance
In plants, a local infection can lead to systemic acquired resistance (SAR) through increased production of salicylic acid (SA). For many years, the identity of the mobile signal and its direct transduction mechanism for systemic SA synthesis in initiating SAR have been debated. We found that in , after a local infection, the conserved cysteine…
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rabindra.tharu.np@gmail.com
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Spatial cognitive ability is associated with longevity in food-caching chickadees
Cognitive abilities are hypothesized to affect survival and life span in nonhuman animals. However, most tests of this hypothesis have relied on interspecific comparisons of indirect measures of cognitive ability, such as brain size. We present direct evidence that individual variation in cognitive abilities is associated with differences in life span in a wild food…
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rabindra.tharu.np@gmail.com
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Achieving optical transparency in live animals with absorbing molecules
Optical imaging plays a central role in biology and medicine but is hindered by light scattering in live tissue. We report the counterintuitive observation that strongly absorbing molecules can achieve optical transparency in live animals. We explored the physics behind this observation and found that when strongly absorbing molecules dissolve in water, they can modify…
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rabindra.tharu.np@gmail.com
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Returned samples indicate volcanism on the Moon 120 million years ago
There is extensive geologic evidence of ancient volcanic activity on the Moon, but it is unclear how long that volcanism persisted. Magma fountains produce volcanic glasses, which have previously been found in samples of the Moon’s surface. We investigated ~3000 glass beads in lunar soil samples collected by the Chang’e-5 mission and identified three as…
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rabindra.tharu.np@gmail.com
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Serotonin release in the habenula during emotional contagion promotes resilience
Negative emotional contagion-witnessing others in distress-affects an individual’s emotional responsivity. However, whether it shapes coping strategies when facing future threats remains unknown. We found that mice that briefly observe a conspecific being harmed become resilient, withstanding behavioral despair after an adverse experience. Photometric recordings during negative emotional contagion revealed increased serotonin (5-HT) release in the…
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rabindra.tharu.np@gmail.com
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Role of protein kinase PLK1 in the epigenetic maintenance of centromeres
The centromere, a chromosome locus defined by the histone H3-like protein centromeric protein A (CENP-A), promotes assembly of the kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A to be actively replenished by dedicated protein machinery in the early G phase of the cell cycle to compensate for its dilution after DNA replication.…
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rabindra.tharu.np@gmail.com
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In vivo dendritic cell reprogramming for cancer immunotherapy
Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to…
