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rabindra.tharu.np@gmail.com
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Microbial colonization programs are structured by breastfeeding and guide healthy respiratory development
Breastfeeding and microbial colonization during infancy occur within a critical time window for development, and both are thought to influence the risk of respiratory illness. However, the mechanisms underlying the protective effects of breastfeeding and the regulation of microbial colonization are poorly understood. Here, we profiled the nasal and gut microbiomes, breastfeeding characteristics, and maternal…
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rabindra.tharu.np@gmail.com
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Intracellular Ebola virus nucleocapsid assembly revealed by in situ cryo-electron tomography
Filoviruses, including the Ebola and Marburg viruses, cause hemorrhagic fevers with up to 90% lethality. The viral nucleocapsid is assembled by polymerization of the nucleoprotein (NP) along the viral genome, together with the viral proteins VP24 and VP35. We employed cryo-electron tomography of cells transfected with viral proteins and infected with model Ebola virus to…
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rabindra.tharu.np@gmail.com
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Fine-grained descending control of steering in walking Drosophila
Locomotion involves rhythmic limb movement patterns that originate in circuits outside the brain. Purposeful locomotion requires descending commands from the brain, but we do not understand how these commands are structured. Here, we investigate this issue, focusing on the control of steering in walking Drosophila. First, we describe different limb “gestures” associated with different steering…
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rabindra.tharu.np@gmail.com
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A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes
Numerous eukaryotic toxins that accumulate in geophytic plants are valuable in the clinic, yet their biosynthetic pathways have remained elusive. A notable example is the >150 Amaryllidaceae alkaloids (AmAs), including galantamine, an FDA-approved treatment for Alzheimer’s disease. We show that while AmAs accumulate to high levels in many daffodil tissues, biosynthesis is localized to nascent,…
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rabindra.tharu.np@gmail.com
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Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles
Genetic medicines show promise for treating various diseases, yet clinical success has been limited by tolerability, scalability, and immunogenicity issues of current delivery platforms. To overcome these, we developed a proteolipid vehicle (PLV) by combining features from viral and non-viral approaches. PLVs incorporate fusion-associated small transmembrane (FAST) proteins isolated from fusogenic orthoreoviruses into a well-tolerated…
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rabindra.tharu.np@gmail.com
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Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity
Gasdermin-mediated inflammatory cell death (pyroptosis) can activate protective immunity in immunologically cold tumors. Here, we performed a high-throughput screen for compounds that could activate gasdermin D (GSDMD), which is expressed widely in tumors. We identified 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB) as a direct and selective GSDMD agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD. In…
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rabindra.tharu.np@gmail.com
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TGF-β and RAS jointly unmask primed enhancers to drive metastasis
Epithelial-to-mesenchymal transitions (EMTs) and extracellular matrix (ECM) remodeling are distinct yet important processes during carcinoma invasion and metastasis. Transforming growth factor β (TGF-β) and RAS, signaling through SMAD and RAS-responsive element-binding protein 1 (RREB1), jointly trigger expression of EMT and fibrogenic factors as two discrete arms of a common transcriptional response in carcinoma cells. Here,…
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rabindra.tharu.np@gmail.com
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Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates
In 2022, mpox virus (MPXV) spread worldwide, causing 99,581 mpox cases in 121 countries. Modified vaccinia Ankara (MVA) vaccine use reduced disease in at-risk populations but failed to deliver complete protection. Lag in manufacturing and distribution of MVA resulted in additional MPXV spread, with 12,000 reported cases in 2023 and an additional outbreak in Central…
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rabindra.tharu.np@gmail.com
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Unexplored microbial diversity from 2,500 food metagenomes and links with the human microbiome
Complex microbiomes are part of the food we eat and influence our own microbiome, but their diversity remains largely unexplored. Here, we generated the open access curatedFoodMetagenomicData (cFMD) resource by integrating 1,950 newly sequenced and 583 public food metagenomes. We produced 10,899 metagenome-assembled genomes spanning 1,036 prokaryotic and 108 eukaryotic species-level genome bins (SGBs), including…
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rabindra.tharu.np@gmail.com
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Cryo-EM-based discovery of a pathogenic parvovirus causing epidemic mortality by black wasting disease in farmed beetles
We use cryoelectron microscopy (cryo-EM) as a sequence- and culture-independent diagnostic tool to identify the etiological agent of an agricultural pandemic. For the past 4 years, American insect-rearing facilities have experienced a distinctive larval pathology and colony collapse of farmed Zophobas morio (superworm). By means of cryo-EM, we discovered the causative agent: a densovirus that…
