MALT1 is a cysteine protease with both proteolytic and scaffolding functions that are key for the regulation of lymphocyte activation in response to antigen and TNF stimulation. The authors previously described a patient with combined immunodeficiency resulting from a homozygous W580S-MALT1 mutation that reduced levels of MALT1 (1). Here they show that Trp580 is required for protein stability, mediating interactions between the paracaspase and C-terminal immunoglobulin domains of MALT1.
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ONECUT2 Is a Driver of Neuroendocrine Prostate Cancer

Neuroendocrine prostate cancer (NEPC), a lethal form of the disease, is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, which results in resistance to AR-targeted therapy. Clinically, genomically and epigenetically, NEPC resembles other types of poorly differentiated neuroendocrine tumors (NETs). Through pan-NET analyses, we identified ONECUT2 as a candidate master transcriptional regulator of poorly differentiated NETs. ONECUT2…
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The incidence of many cancers continues to rise alongside the global obesity and type 2 diabetes epidemics. The metabolic disturbances associated with diabetes and obesity such as hyperinsulinemia, hyperglycemia, dyslipidemia, and elevated insulin-like growth factor have been implicated, alone or in combination, in cancer risk, especially for pancreatic cancer. This study is the first to separate the role of high insulin from high glucose, and directly test the insulin-cancer hypothesis in vivo.
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The mammary gland in adult women consists of biologically distinct cell types that differ in their surface phenotypes. Isolation and molecular characterization of these subpopulations of mammary cells have provided extensive insights into their different transcriptional programs and regulation. This information is now serving as a baseline for interpreting the heterogeneous features of human breast cancers. Examination of breast cancer…
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Recalibrating the Relevance of Adult Neurogenesis

Animal work has revealed that immature neurons born in the adult dentate gyrus have key cellular and behavioral functions. Recent reports are conflicted about whether adult neurogenesis occurs in humans. Discrepancies could arise from species differences in neurodevelopmental timing and differences in subject ages. Regardless of its extent, postnatally, an extended period of neurogenesis may produce a heterogeneous population of…
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Our research focus is the genomics of advanced prostate and bladder cancer. Utilizing a combination of standard tissue biopsies and blood-based liquid biopsies, we apply next-generation DNA sequencing techniques to characterize patient tumours. Ultimately, our goal is to enable precision medicine approaches in the clinic. We found that in men with prostate cancer who are metastatic at diagnosis, a blood test can detect tumour DNA shed into their bloodstream.
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Recent advances in single-cell molecular analytical methods and clonal growth assays are enabling more refined models of human hematopoietic lineage restriction processes to be conceptualized. Here, we report the results of integrating single-cell proteome measurements with clonally-determined lymphoid, neutrophilic/monocytic, and/or erythroid progeny outputs from over 1,000 index-sorted CD34+ human cord blood cells in short-term cultures with and without stromal cells. Surface…
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In addition to being the largest genomic study of paediatric Burkitt lymphoma (BL) to date, our paper sheds light on the poorly understood relationship between BL and the Epstein–Barr virus (EBV). Notably, EBV appears to induce AICDA expression, which encodes a mutator enzyme that is thought to be responsible for chromosomal rearrangements such as the oncogenic MYC translocation present in virtually all BL tumours. We also found that EBV-positive tumours lacked mutations in genes with roles in apoptosis, suggesting that...
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In this publication we explain the long-term effect of salt stress in the proteins that act as bridges between cellular organelles in leaf tissues. Our results shows that, in response to salt stress, proteins that act as molecular bridges are activated and create communication pathways between two plant organelles, the endoplasmic reticulum and the plasma membrane,. This mechanism is a specialized cellular adaption that, in plants, enables the cellular adaptation to sustained stress conditions commonly found during their life cycle...
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Domesticated plants and animals often display dramatic responses to selection, but the origins of the genetic diversity underlying these responses remain poorly understood. Despite domestication and improvement bottlenecks, the cultivated sunflower remains highly variable genetically, possibly due to hybridization with wild relatives. To characterize genetic diversity in the sunflower and to quantify contributions from wild relatives, we sequenced 287 cultivated…
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