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Article
Efficacy of sternocleidomastoid muscle flap in reducing anastomotic mediastinal/pleural cavity leak
Anastomotic mediastinal/pleural cavity leak (AMPCL) is a life-threatening postoperative complication after esophagectomy. The objective of this study was to find a safe and effective surgical method to reduce ...
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Article
Open AccessTMK-based cell-surface auxin signalling activates cell-wall acidification
The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for fi...
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Article
Open AccessPatient-derived models recapitulate heterogeneity of molecular signatures and drug response in pediatric high-grade glioma
Pediatric high-grade glioma (pHGG) is a major contributor to cancer-related death in children. In vitro and in vivo disease models reflecting the intimate connection between developmental context and pathogene...
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Article
Mutation of a single amino acid of pregnane X receptor switches an antagonist to agonist by altering AF-2 helix positioning
Pregnane X receptor (PXR) is activated by chemicals to transcriptionally regulate drug disposition and possibly decrease drug efficacy and increase resistance, suggesting therapeutic value for PXR antagonists....
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Article
Open AccessStructural basis for substrate recognition and chemical inhibition of oncogenic MAGE ubiquitin ligases
Testis-restricted melanoma antigen (MAGE) proteins are frequently hijacked in cancer and play a critical role in tumorigenesis. MAGEs assemble with E3 ubiquitin ligases and function as substrate adaptors that ...
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Article
LMDS-1, a potential TrkB receptor agonist provides a safe and neurotrophic effect for early-phase Alzheimer’s disease
The signaling pathways of tropomyosin-related kinase B (TrkB) receptor play a pivotal role in axonal sprouting, proliferation of dendritic arbor, synaptic plasticity, and neuronal differentiation. The levels o...
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Article
Open AccessAuxin-induced signaling protein nanoclustering contributes to cell polarity formation
Cell polarity is fundamental to the development of both eukaryotes and prokaryotes, yet the mechanisms behind its formation are not well understood. Here we found that, phytohormone auxin-induced, sterol-depen...
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Article
Open AccessA blood RNA transcript signature for TB exposure in household contacts
Current tools for diagnosing latent TB infection (LTBI) detect immunological memory of past exposure but are unable to determine whether exposure is recent. We sought to identify a whole-blood transcriptome si...
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Article
Open AccessGene expression responses to anti-tuberculous drugs in a whole blood model
There is a need for better tools to evaluate new or repurposed TB drugs. The whole blood bactericidal activity (WBA) assay has been advocated for this purpose. We investigated whether transcriptional responses...
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Article
Open AccessAdjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammat...
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Article
Open AccessAn unexpected protein interaction promotes drug resistance in leukemia
The overall survival of patients with acute myeloid leukemia (AML) is poor and identification of new disease-related therapeutic targets remains a major goal for this disease. Here we show that expression of M...
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Article
Open AccessSPA70 is a potent antagonist of human pregnane X receptor
Many drugs bind to and activate human pregnane X receptor (hPXR) to upregulate drug-metabolizing enzymes, resulting in decreased drug efficacy and increased resistance. This suggests that hPXR antagonists have...
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Article
Open AccessGlucose-dependent regulation of pregnane X receptor is modulated by AMP-activated protein kinase
Pregnane X receptor (PXR) is a xenobiotic receptor that regulates the detoxification and clearance of drugs and foreign compounds from the liver. There has been mounting evidence of crosstalk between the drug ...
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Article
Open AccesstRNA-mediated codon-biased translation in mycobacterial hypoxic persistence
Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence ...
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Article
Linear response eigenvalue problem solved by extended locally optimal preconditioned conjugate gradient methods
The locally optimal block preconditioned 4-d conjugate gradient method (LOBP4dCG) for the linear response eigenvalue problem was proposed by Bai and Li (2013) and later was extended to the generalized linear r...
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Article
Open AccessA phosphotyrosine switch regulates organic cation transporters
Membrane transporters are key determinants of therapeutic outcomes. They regulate systemic and cellular drug levels influencing efficacy as well as toxicities. Here we report a unique phosphorylation-dependent...
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Article
Open AccessFlavonoids activate pregnane × receptor-mediated CYP3A4 gene expression by inhibiting cyclin-dependent kinases in HepG2 liver carcinoma cells
The expression of the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is regulated by the pregnane × receptor (PXR), which is modulated by numerous signaling pathways, including the cyclin-dependent kina...
