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rabindra.tharu.np@gmail.com
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AI-powered omics-based drug pair discovery for pyroptosis therapy targeting triple-negative breast cancer
Due to low success rates and long cycles of traditional drug development, the clinical tendency is to apply omics techniques to reveal patient-level disease characteristics and individualized responses to treatment. However, the heterogeneous form of data and uneven distribution of targets make drug discovery and precision medicine a non-trivial task. This study takes pyroptosis therapy…
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rabindra.tharu.np@gmail.com
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Potassium channel TASK-5 forms functional heterodimers with TASK-1 and TASK-3 to break its silence
TASK-5 (KCNK15) belongs to the acid-sensitive subfamily of two-pore domain potassium (K) channels, which includes TASK-1 and TASK-3. TASK-5 stands out as K channel for which there is no functional data available, since it was reported in 2001 as non-functional and thus “silent”. Here we show that TASK-5 channels are indeed non-functional as homodimers, but…
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rabindra.tharu.np@gmail.com
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scCAD: Cluster decomposition-based anomaly detection for rare cell identification in single-cell expression data
Single-cell RNA sequencing (scRNA-seq) technologies have become essential tools for characterizing cellular landscapes within complex tissues. Large-scale single-cell transcriptomics holds great potential for identifying rare cell types critical to the pathogenesis of diseases and biological processes. Existing methods for identifying rare cell types often rely on one-time clustering using partial or global gene expression. However,…
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rabindra.tharu.np@gmail.com
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Molecular recognition of an odorant by the murine trace amine-associated receptor TAAR7f
There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are distinct, with the TAARs being most similar to the aminergic receptors such as those activated by adrenaline, serotonin, dopamine and histamine. To elucidate the structural determinants…
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rabindra.tharu.np@gmail.com
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DNA methylation governs the sensitivity of repeats to restriction by the HUSH-MORC2 corepressor
The human silencing hub (HUSH) complex binds to transcripts of LINE-1 retrotransposons (L1s) and other genomic repeats, recruiting MORC2 and other effectors to remodel chromatin. How HUSH and MORC2 operate alongside DNA methylation, a central epigenetic regulator of repeat transcription, remains largely unknown. Here we interrogate this relationship in human neural progenitor cells (hNPCs), a…
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rabindra.tharu.np@gmail.com
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Ultraconformable cuff implants for long-term bidirectional interfacing of peripheral nerves at sub-nerve resolutions
Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios.…
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rabindra.tharu.np@gmail.com
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Comparison of AI-integrated pathways with human-AI interaction in population mammographic screening for breast cancer
Artificial intelligence (AI) readers of mammograms compare favourably to individual radiologists in detecting breast cancer. However, AI readers cannot perform at the level of multi-reader systems used by screening programs in countries such as Australia, Sweden, and the UK. Therefore, implementation demands human-AI collaboration. Here, we use a large, high-quality retrospective mammography dataset from Victoria,…
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rabindra.tharu.np@gmail.com
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A catalog of small proteins from the global microbiome
Small open reading frames (smORFs) shorter than 100 codons are widespread and perform essential roles in microorganisms, where they encode proteins active in several cell functions, including signal pathways, stress response, and antibacterial activities. However, the ecology, distribution and role of small proteins in the global microbiome remain unknown. Here, we construct a global microbial…
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rabindra.tharu.np@gmail.com
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Sde proteins coordinate ubiquitin utilization and phosphoribosylation to establish and maintain the Legionella replication vacuole
The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification of Reticulon 4 (Rtn4). Sde proteins have two additional activities of unclear relevance to the infection process: K63 linkage-specific deubiquitination and phosphoribosyl modification of polyubiquitin (pR-Ub). We show here that the deubiquitination…
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rabindra.tharu.np@gmail.com
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Phosphoribosyl modification of poly-ubiquitin chains at the Legionella-containing vacuole prohibiting autophagy adaptor recognition
Ubiquitination is a posttranslational modification in eukaryotes that plays a significant role in the infection of intracellular microbial pathogens, such as Legionella pneumophila. While the Legionella-containing vacuole (LCV) is coated with ubiquitin (Ub), it avoids recognition by autophagy adaptors. Here, we report that the Sdc and Sde families of effectors work together to build ubiquitinated…
