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rabindra.tharu.np@gmail.com
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Zebrafish Polymerase Theta and human Polymerase Theta: orthologues with homologous function
DNA Polymerase Theta (Pol θ) is a conserved an A-family polymerase that plays an essential role in repairing double strand breaks, through micro-homology end joining, and bypassing DNA lesions, through translesion synthesis, to protect genome integrity. Despite its essential role in DNA repair, Pol θ is inherently error-prone. Recently, key loop regions were identified to…
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rabindra.tharu.np@gmail.com
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Global Genotype by Environment Prediction Competition Reveals That Diverse Modeling Strategies Can Deliver Satisfactory Maize Yield Estimates
Predicting phenotypes from a combination of genetic and environmental factors is a grand challenge of modern biology. Slight improvements in this area have the potential to save lives, improve food and fuel security, permit better care of the planet, and create other positive outcomes. In 2022 and 2023 the first open-to-the-public Genomes to Fields (G2F)…
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rabindra.tharu.np@gmail.com
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A novel iPSC model of Bryant-Li-Bhoj neurodevelopmental syndrome demonstrates the role of histone H3.3 in neuronal differentiation and maturation
BACKGROUND Bryant-Li-Bhoj neurodevelopmental syndrome (BLBS) is neurogenetic disorder caused by variants in and the two genes that encode the histone H3.3 protein. Ninety-nine percent of individuals with BLBS show developmental delay/intellectual disability, but the mechanism by which variants in H3.3 result in these phenotypes is not yet understood. As a result, only palliative interventions are…
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rabindra.tharu.np@gmail.com
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Grin1 (Y) (647) (S/+) Mice: A Preclinical Model of GRIN1 -Related Neurodevelopmental Disorder
OBJECTIVE -related neurodevelopmental disorder ( -NDD) is characterized by clinically significant variation in the gene, which encodes the obligatory GluN1 subunit of N-methyl-D-aspartate receptors (NMDARs). The identified p.Tyr647Ser (Y647S) variant – carried by a 33-year-old female with seizures and intellectual disability – is located in the M3 helix in the GluN1 transmembrane domain. This study…
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rabindra.tharu.np@gmail.com
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Molecular and cellular dynamics of the developing human neocortex at single-cell resolution
The development of the human neocortex is a highly dynamic process and involves complex cellular trajectories controlled by cell-type-specific gene regulation. Here, we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and primary visual cortex. These samples span five main developmental stages, ranging from the…
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rabindra.tharu.np@gmail.com
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Nuclear Argonaute protein NRDE-3 switches small RNA partners during embryogenesis to mediate temporal-specific gene regulatory activity
RNA interference (RNAi) is a conserved gene regulation mechanism that utilizes the Argonaute protein and their associated small RNAs to exert regulatory function on complementary transcripts. While the majority of germline-expressed RNAi pathway components reside in perinuclear germ granules, it is unknown whether and how RNAi pathways are spatially organized in other cell types. Here…
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rabindra.tharu.np@gmail.com
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Structural transitions in kinesin minus-end directed microtubule motility
Kinesin motor proteins hydrolyze ATP to produce force for spindle assembly and vesicle transport, performing essential functions in cell division and motility, but the structural changes required for force generation are uncertain. We now report high-resolution structures showing new transitions in the kinesin mechanochemical cycle, including power stroke fluctuations upon ATP binding and a post-hydrolysis…
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rabindra.tharu.np@gmail.com
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Residual Microglia Following Short-term PLX5622 Treatment in 5xFAD Mice Exhibit Diminished NLRP3 Inflammasome and mTOR Signaling, and Enhanced Autophagy
Chronic neuroinflammation represents a prominent hallmark of Alzheimer’s disease (AD). While moderately activated microglia are pivotal in clearing amyloid beta (Aβ), hyperactivated microglia perpetuate neuroinflammation. Prior investigations have indicated that the elimination of ∼80% of microglia through a month-long inhibition of the colony-stimulating factor 1 receptor (CSF1R) during the advanced stage of neuroinflammation in 5xFamilial…
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rabindra.tharu.np@gmail.com
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Structures of Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus virions reveal species-specific tegument and envelope features
UNLABELLED Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are classified into the gammaherpesvirus subfamily of , which stands out from its alpha- and betaherpesvirus relatives due to the tumorigenicity of its members. Although structures of human alpha- and betaherpesviruses by cryogenic electron tomography (cryoET) have been reported, reconstructions of intact human gammaherpesvirus virions remain…
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rabindra.tharu.np@gmail.com
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Single-cell atlas of ABCA7 loss-of-function reveals impaired neuronal respiration via choline-dependent lipid imbalances
Loss-of-function (LoF) variants in the lipid transporter ABCA7 significantly increase the risk of Alzheimer’s disease (odds ratio ∼2), yet the pathogenic mechanisms and the neural cell types affected by these variants remain largely unknown. Here, we performed single-nuclear RNA sequencing of 36 human samples from the prefrontal cortex of 12 ABCA7 LoF carriers and 24…
