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rabindra.tharu.np@gmail.com
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Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates
Antiviral therapies with reduced frequencies of administration and high barriers to resistance remain a major goal. For HIV, theories have proposed that viral-deletion variants, which conditionally replicate with a basic reproductive ratio [R] > 1 (termed “therapeutic interfering particles” or “TIPs”), could parasitize wild-type virus to constitute single-administration, escape-resistant antiviral therapies. We report the engineering…
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rabindra.tharu.np@gmail.com
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The β-d-manno-heptoses are immune agonists across kingdoms
Bacterial small molecule metabolites such as adenosine-diphosphate-d–β-d–heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STT motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but…
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rabindra.tharu.np@gmail.com
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Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming
Late-onset Alzheimer’s disease (LOAD) is the most common form of Alzheimer’s disease (AD). However, modeling sporadic LOAD that endogenously captures hallmark neuronal pathologies such as amyloid-β (Aβ) deposition, tau tangles, and neuronal loss remains an unmet need. We demonstrate that neurons generated by microRNA (miRNA)-based direct reprogramming of fibroblasts from individuals affected by autosomal dominant…
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rabindra.tharu.np@gmail.com
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Convergent evolution of plant prickles by repeated gene co-option over deep time
An enduring question in evolutionary biology concerns the degree to which episodes of convergent trait evolution depend on the same genetic programs, particularly over long timescales. In this work, we genetically dissected repeated origins and losses of prickles-sharp epidermal projections-that convergently evolved in numerous plant lineages. Mutations in a cytokinin hormone biosynthetic gene caused at…
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rabindra.tharu.np@gmail.com
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A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut
Neuroimmune cross-talk participates in intestinal tissue homeostasis and host defense. However, the matrix of interactions between arrays of molecularly defined neuron subsets and of immunocyte lineages remains unclear. We used a chemogenetic approach to activate eight distinct neuronal subsets, assessing effects by deep immunophenotyping, microbiome profiling, and immunocyte transcriptomics in intestinal organs. Distinct immune perturbations…
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rabindra.tharu.np@gmail.com
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The anatomy of brainwashing
Glymphatic-lymphatic brain cleansing may reveal new therapeutic strategies.
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rabindra.tharu.np@gmail.com
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Operating semiconductor quantum processors with hopping spins
Qubits that can be efficiently controlled are essential for the development of scalable quantum hardware. Although resonant control is used to execute high-fidelity quantum gates, the scalability is challenged by the integration of high-frequency oscillating signals, qubit cross-talk, and heating. Here, we show that by engineering the hopping of spins between quantum dots with a…
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rabindra.tharu.np@gmail.com
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Chromatin plasticity predetermines neuronal eligibility for memory trace formation
Memories are encoded by sparse populations of neurons but how such sparsity arises remains largely unknown. We found that a neuron’s eligibility to be recruited into the memory trace depends on its epigenetic state prior to encoding. Principal neurons in the mouse lateral amygdala display intrinsic chromatin plasticity, which when experimentally elevated favors neuronal allocation…
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rabindra.tharu.np@gmail.com
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Tuning cohesin trajectories enables differential readout of the Pcdhα cluster across neurons
Expression of Protocadherin (Pcdh) genes is critical to the generation of neuron identity and wiring of the nervous system. Pcdhα genes are arranged in clusters and exhibit a range of expression profiles, from stochastic to deterministic. Because Pcdhα promoters have high sequence identity and share distal enhancers, how distinct neurons choose which gene to express…
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rabindra.tharu.np@gmail.com
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Multiscale photocatalytic proximity labeling reveals cell surface neighbors on and between cells
Proximity labeling proteomics (PLP) strategies are powerful approaches to yield snapshots of protein neighborhoods. Here, we describe a multiscale PLP method with adjustable resolution that uses a commercially available photocatalyst, Eosin Y, which upon visible light illumination activates different photo-probes with a range of labeling radii. We applied this platform to profile neighborhoods of the…
