Androgen deprivation therapy is often the first-line therapy for high-risk and advanced PCa patients that initially leads to tumour regression with subsequent growth arrest and dormancy of prostate cancer. After this period of dormancy, however, most of these cases will progress to incurable castration-resistant prostate cancer (CRPC). The Wang lab reports that the GRB10 protein sustains androgen receptor activity in CRPC.
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Long non-coding RNAs (lncRNAs) have emerged as key modulators of tumour development, progression, and response to therapy across a variety of cancer types. The authors examined lncRNA expression in separate sequencing cohorts to characterize the landscape of lncRNAs expressed in tumour-infiltrating lymphocytes in a highly immunogenic tumour type.
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Whether accelerated aging develops over the course of chronic HIV infection or can be observed prior to significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) prior to the initiation of antiretroviral therapy. 378 antiretroviral therapy-naïve PLWH with CD4 T cell counts >500 cells/mm 3 enrolled in the Strategic Timing…
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Methicillin-resistant Staphylococcus aureus are resistant to beta-lactam antibiotics. Staphylococcal infections are mediated by a large array of secreted toxins including the phenol-soluble modulins (PSMs). PSMs are exported across the bacterial membrane by a specialized ATP–binding cassette transporter called PmtCD. The authors present the first atomic characterization using a combination of cryo-electron microscopy and x-ray crystallography.
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Worldwide increases in antibiotic resistance and the dearth of new antibiotics have created a global crisis in the treatment of infectious diseases. These concerns highlight the pressing need for novel antimicrobial agents. Natural clay minerals have a long history of therapeutic and biomedical applications and have lately received specific attention for their potent antimicrobial properties. In particular, Kisameet clay (KC)…
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Mesenchymal fibroblasts are ubiquitous cells that maintain the extracellular matrix of organs. Within the lung, airway and parenchymal fibroblasts are crucial for lung development and are altered with disease, but it has been difficult to understand their roles due to the lack of distinct molecular markers. We studied genome-wide DNA methylation and gene expression in airway and parenchymal lung fibroblasts…
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Many bacteria form spores in response to adverse environmental conditions. Several sporulation pathways have evolved independently and occur through distinctive mechanisms. Here, using cryo-electron tomography (cryo-ET), we examine all stages of growth and exospore formation in the model organism Streptomyces albus. Our data reveal the native ultrastructure of vegetative hyphae, including the likely structures of the polarisome and cytoskeletal filaments. In…
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The mutational landscape of grey zone lymphoma (GZL) has not yet been established and differences to related entities are largely unknown. Here, we studied coding sequence mutations of 50 EBV-negative GZL and 20 polymorphic EBV-positive DLBCL NOS (poly-EBV-L) in comparison to classical Hodgkin lymphoma (cHL), primary mediastinal large B cell lymphoma (PMBCL), and diffuse large B cell lymphoma (DLBCL). Exomes…
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The authors isolated hundreds of Nef clones representing four major HIV subtypes and tested their ability to counteract SERINC3 and SERINC5. They observed that Nef isolates differed markedly in SERINC antagonism activity, but overall, each viral subtype’s ability to counteract the more potent restriction factor correlated with its pathogenic potential, indicating that this Nef function likely contributes to disease.
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Reprogramming of the epigenome is a hallmark of cellular differentiation in mammals, but how the essential but distinct genomic imprints established in and oocytes remained unclear. The authors show that de novo DNA methylation, including at imprinted genes, is directed in the genome of prospermatogonia by a specific modification on the amino-terminus of histone H3, namely lysine 36 (H3K36).
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