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rabindra.tharu.np@gmail.com
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Dramatic changes in mitochondrial subcellular location and morphology accompany activation of the CO(2) concentrating mechanism
Dynamic changes in intracellular ultrastructure can be critical for the ability of organisms to acclimate to environmental conditions. Microalgae, which are responsible for ~50% of global photosynthesis, compartmentalize their Ribulose 1,5 Bisphosphate Carboxylase/Oxygenase (Rubisco) into a specialized structure known as the pyrenoid when the cells experience limiting CO conditions; this compartmentalization is a component of…
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rabindra.tharu.np@gmail.com
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Identification of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has been responsible for numerous large-scale outbreaks in the last twenty years. Currently, there are no FDA-approved therapeutics for any alphavirus infection. CHIKV nonstructural protein 2 (nsP2), which contains a cysteine protease domain, is essential for viral replication, making it an attractive target for a drug discovery…
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rabindra.tharu.np@gmail.com
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Natural variation in age-related dopamine neuron degeneration is glutathione dependent and linked to life span
Aging is the biggest risk factor for Parkinson’s disease (PD), suggesting that age-related changes in the brain promote dopamine neuron vulnerability. It is unclear, however, whether aging alone is sufficient to cause significant dopamine neuron loss, and if so, how this intersects with PD-related neurodegeneration. Here, through examining a large collection of naturally varying strains,…
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rabindra.tharu.np@gmail.com
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Synaptic weight dynamics underlying memory consolidation: Implications for learning rules, circuit organization, and circuit function
Systems consolidation is a common feature of learning and memory systems, in which a long-term memory initially stored in one brain region becomes persistently stored in another region. We studied the dynamics of systems consolidation in simple circuit architectures with two sites of plasticity, one in an early-learning and one in a late-learning brain area.…
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rabindra.tharu.np@gmail.com
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Embers of autoregression show how large language models are shaped by the problem they are trained to solve
The widespread adoption of large language models (LLMs) makes it important to recognize their strengths and limitations. We argue that to develop a holistic understanding of these systems, we must consider the problem that they were trained to solve: next-word prediction over Internet text. By recognizing the pressures that this task exerts, we can make…
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rabindra.tharu.np@gmail.com
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A mismatch between striatal cholinergic pauses and dopaminergic reward prediction errors
Striatal acetylcholine and dopamine critically regulate movement, motivation, and reward-related learning. Pauses in cholinergic interneuron (CIN) firing are thought to coincide with dopamine pulses encoding reward prediction errors (RPE) to jointly enable synaptic plasticity. Here, we examine the firing of identified CINs during reward-guided decision-making in freely moving rats and compare this firing to dopamine…
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rabindra.tharu.np@gmail.com
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SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor
Inflammation is a protective response to pathogens and injury. To be effective it needs to be resolved by endogenous mechanisms in order to avoid prolonged and excessive inflammation, which can become chronic. Specialized pro-resolving mediators (SPMs) are a group of lipids derived from omega-3 fatty acids, which can induce the resolution of inflammation. How SPMs…
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rabindra.tharu.np@gmail.com
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Intestinal Lactobacillus murinus-derived small RNAs target porcine polyamine metabolism
Gut microbiota plays a vital role in host metabolism; however, the influence of gut microbes on polyamine metabolism is unknown. Here, we found germ-free models possess elevated polyamine levels in the colon. Mechanistically, intestinal -derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition,…
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rabindra.tharu.np@gmail.com
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A geometric-tension-dynamics model of epithelial convergent extension
Convergent extension of epithelial tissue is a key motif of animal morphogenesis. On a coarse scale, cell motion resembles laminar fluid flow; yet in contrast to a fluid, epithelial cells adhere to each other and maintain the tissue layer under actively generated internal tension. To resolve this apparent paradox, we formulate a model in which…
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rabindra.tharu.np@gmail.com
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Mechanically adaptive and deployable intracortical probes enable long-term neural electrophysiological recordings
Flexible intracortical probes offer important opportunities for stable neural interfaces by reducing chronic immune responses, but their advances usually come with challenges of difficult implantation and limited recording span. Here, we reported a mechanically adaptive and deployable intracortical probe, which features a foldable fishbone-like structural design with branching electrodes on a temperature-responsive shape memory polymer…
