Natural killer (NK) cells are primary defenders against cancer precursors, but cancer cells can persist by evading immune surveillance. To investigate the genetic mechanisms underlying this evasion, we perform a genome-wide CRISPR screen using B lymphoblastoid cells. SPPL3, a peptidase that cleaves glycosyltransferases in the Golgi, emerges as a top hit facilitating evasion from NK cytotoxicity.
View Article and Find Full Text PDFDiffuse large B cell lymphoma (DLBCL) is an aggressive, profoundly heterogeneous cancer, presenting a challenge for precision medicine. Bruton's tyrosine kinase (BTK) inhibitors block B cell receptor (BCR) signaling and are particularly effective in certain molecular subtypes of DLBCL that rely on chronic active BCR signaling to promote oncogenic NF-κB. The MCD genetic subtype, which often acquires mutations in the BCR subunit, CD79B, and in the innate immune adapter, MYD88, typically resists chemotherapy but responds exceptionally to BTK inhibitors.
View Article and Find Full Text PDFIn this study, 58 endophytic bacterial strains were isolated from pods of two hybrid vanilla plants from Madagascar, and . They were genetically characterized and divided into four distinct phylotypes. Three were associated to genus species, and the fourth to the genus .
View Article and Find Full Text PDFPeritoneal inclusion cyst is a rare benign tumor. It usually affects women of reproductive age. Its etiology is poorly understood; a history of endometriosis, pelvic inflammatory disease and pelvic surgery are sometimes implicated in its occurrence.
View Article and Find Full Text PDFBurkitt lymphoma (BL) is an aggressive lymphoma type that is currently treated by intensive chemoimmunotherapy. Despite the favorable clinical outcome for most patients with BL, chemotherapy-related toxicity and disease relapse remain major clinical challenges, emphasizing the need for innovative therapies. Using genome-scale CRISPR-Cas9 screens, we identified B-cell receptor (BCR) signaling, specific transcriptional regulators, and one-carbon metabolism as vulnerabilities in BL.
View Article and Find Full Text PDFIt was about a 61-year-old patient who presented an indurated and painless umbilical swelling surrounded by ulcerated plaque and an abdominal arch progressing for 8 months. Abdomino-pelvic ultrasound and abdominal-pelvic CT scan revealed in right ovarian the presence of a mass with a cystic's tissue, a thickness with a subcutaneous infiltration of the umbilical region and the diffuse infiltration of gastric parietal mesenteric fat. Histology of the ovarian mass confirmed Krükenberg's tumor and that of the Sister Marie-Joseph's nodule confirmed umbilical skin metastasis.
View Article and Find Full Text PDFThe development of precision medicine approaches for diffuse large B cell lymphoma (DLBCL) is confounded by its pronounced genetic, phenotypic, and clinical heterogeneity. Recent multiplatform genomic studies revealed the existence of genetic subtypes of DLBCL using clustering methodologies. Here, we describe an algorithm that determines the probability that a patient's lymphoma belongs to one of seven genetic subtypes based on its genetic features.
View Article and Find Full Text PDFSmall-conductance Ca-activated K (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2018
Heart failure (HF) following myocardial infarction (MI) is associated with high incidence of cardiac arrhythmias. Development of therapeutic strategy requires detailed understanding of electrophysiological remodeling. However, changes of ionic currents in ischemic HF remain incompletely understood, especially in translational large-animal models.
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