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rabindra.tharu.np@gmail.com
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Direct-bonded diamond membranes for heterogeneous quantum and electronic technologies
Diamond has superlative material properties for a broad range of quantum and electronic technologies. However, heteroepitaxial growth of single crystal diamond remains limited, impeding integration and evolution of diamond-based technologies. Here, we directly bond single-crystal diamond membranes to a wide variety of materials including silicon, fused silica, sapphire, thermal oxide, and lithium niobate. Our bonding…
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rabindra.tharu.np@gmail.com
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Structural basis of μ-opioid receptor targeting by a nanobody antagonist
The μ-opioid receptor (μOR), a prototypical G protein-coupled receptor (GPCR), is the target of opioid analgesics such as morphine and fentanyl. Due to the severe side effects of current opioid drugs, there is considerable interest in developing novel modulators of μOR function. Most GPCR ligands today are small molecules, however biologics, including antibodies and nanobodies,…
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rabindra.tharu.np@gmail.com
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A fair individualized polysocial risk score for identifying increased social risk in type 2 diabetes
Racial and ethnic minorities bear a disproportionate burden of type 2 diabetes (T2D) and its complications, with social determinants of health (SDoH) recognized as key drivers of these disparities. Implementing efficient and effective social needs management strategies is crucial. We propose a machine learning analytic pipeline to calculate the individualized polysocial risk score (iPsRS), which…
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rabindra.tharu.np@gmail.com
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Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors
The proteasome is a proteolytic enzyme complex essential for protein homeostasis in mammalian cells and protozoan parasites like Trichomonas vaginalis (Tv), the cause of the most common, non-viral sexually transmitted disease. Tv and other protozoan 20S proteasomes have been validated as druggable targets for antimicrobials. However, low yields and purity of the native proteasome have…
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rabindra.tharu.np@gmail.com
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Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma
Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8 T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in…
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rabindra.tharu.np@gmail.com
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Extinction cascades, community collapse, and recovery across a Mesozoic hyperthermal event
Mass extinctions are considered to be quintessential examples of Court Jester drivers of macroevolution, whereby abiotic pressures drive a suite of extinctions leading to huge ecosystem changes across geological timescales. Most research on mass extinctions ignores species interactions and community structure, limiting inference about which and why species go extinct, and how Red Queen processes…
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rabindra.tharu.np@gmail.com
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MDM2 induces pro-inflammatory and glycolytic responses in M1 macrophages by integrating iNOS-nitric oxide and HIF-1α pathways in mice
M1 macrophages induce protective immunity against infection, but also contribute to metabolic and inflammatory diseases. Here we show that the E3 ubiquitin ligase, MDM2, promotes the glycolytic and inflammatory activities of M1 macrophage by increasing the production of IL-1β, MCP-1 and nitric oxide (NO). Mechanistically, MDM2 triggers the ubiquitination and degradation of E3 ligase, SPSB2,…
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rabindra.tharu.np@gmail.com
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The double-edged role of FASII regulator FabT in Streptococcus pyogenes infection
In Streptococcus pyogenes, the type II fatty acid (FA) synthesis pathway FASII is feedback-controlled by the FabT repressor bound to an acyl-Acyl carrier protein. Although FabT defects confer reduced virulence in animal models, spontaneous fabT mutants arise in vivo. We resolved this paradox by characterizing the conditions and mechanisms requiring FabT activity, and those promoting…
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rabindra.tharu.np@gmail.com
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Reversible covalent c-Jun N-terminal kinase inhibitors targeting a specific cysteine by precision-guided Michael-acceptor warheads
There has been a surge of interest in covalent inhibitors for protein kinases in recent years. Despite success in oncology, the off-target reactivity of these molecules is still hampering the use of covalent warhead-based strategies. Herein, we disclose the development of precision-guided warheads to mitigate the off-target challenge. These reversible warheads have a complex and…
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rabindra.tharu.np@gmail.com
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Single-crystal hBN Monolayers from Aligned Hexagonal Islands
Hexagonal boron nitride (hBN), as one of the few two-dimensional insulators, holds strategic importance for advancing post-silicon electronic devices and circuits. Achieving wafer-scale, high-quality monolayer hBN is essential for its integration into the semiconductor industry. However, the physical mechanisms behind the chemical vapor deposition (CVD) synthesis of hBN are not yet well understood. Investigating morphology…
