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Master cell disease

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https://www.readbyqxmd.com/read/28346597/association-of-risk-of-viremia-immunosuppression-serious-clinical-events-and-mortality-with-increasing-age-in-perinatally-human-immunodeficiency-virus-infected-youth
#1
Anne M Neilan, Brad Karalius, Kunjal Patel, Russell B Van Dyke, Mark J Abzug, Allison L Agwu, Paige L Williams, Murli Purswani, Deborah Kacanek, James M Oleske, Sandra K Burchett, Andrew Wiznia, Miriam Chernoff, George R Seage, Andrea L Ciaranello
Importance: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. Objective: To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status...
March 27, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28344104/antimicrobial-medium-and-long-chain-free-fatty-acids-prevent-prfa-dependent-activation-of-virulence-genes-in-listeria-monocytogenes
#2
Eva Maria Sternkopf Lillebæk, Stine Lambert Nielsen, Rikke Scheel Thomasen, Nils J Færgeman, Birgitte H Kallipolitis
The foodborne pathogen Listeria monocytogenes is the causative agent of the invasive disease listeriosis. Infection by L. monocytogenes involves bacterial crossing of the intestinal barrier and intracellular replication in a variety of host cells. The PrfA protein is the master regulator of virulence factors required for bacterial entry, intracellular replication and cell-to-cell spread. PrfA-dependent activation of virulence genes occurs primarily in the blood and during intracellular infection. In contrast, PrfA does not play a significant role in regulation of virulence gene expression in the intestinal environment...
March 23, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/28342334/oncogene-addiction-in-non-small-cell-lung-cancer-focus-on-ros1-inhibition
#3
REVIEW
Francesco Facchinetti, Giulio Rossi, Emilio Bria, Jean-Charles Soria, Benjamin Besse, Roberta Minari, Luc Friboulet, Marcello Tiseo
Detection of molecular aberrations driving the biology and the clinical behavior of advanced non-small cell lung cancer (NSCLC) allows the adoption of specific therapeutic strategies dramatically impacting disease courses. Among these, ROS1 rearrangements are present in 1-2% of lung adenocarcinomas. Thanks to similarities between ALK and ROS1 oncogenes, lessons inferred from ALK can be applied to ROS1-positive NSCLC; nevertheless, disparities exist between diseases mastered by these two fusion genes. In the absence of more common genetic alterations detected in NSCLC (e...
March 12, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28333162/the-endoplasmic-reticulum-chaperone-grp78-bip-modulates-prion-propagation-in-vitro-and-in-vivo
#4
Kyung-Won Park, Gyoung Eun Kim, Rodrigo Morales, Fabio Moda, Ines Moreno-Gonzalez, Luis Concha-Marambio, Amy S Lee, Claudio Hetz, Claudio Soto
Prion diseases are fatal neurodegenerative disorders affecting several mammalian species, characterized by the accumulation of the misfolded form of the prion protein, which is followed by the induction of endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR). GRP78, also called BiP, is a master regulator of the UPR, reducing ER stress levels and apoptosis due to an enhancement of the cellular folding capacity. Here, we studied the role of GRP78 in prion diseases using several in vivo and in vitro approaches...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320635/safety-and-efficacy-of-multipotent-adult-progenitor-cells-in-acute-ischaemic-stroke-masters-a-randomised-double-blind-placebo-controlled-phase-2-trial
#5
David C Hess, Lawrence R Wechsler, Wayne M Clark, Sean I Savitz, Gary A Ford, David Chiu, Dileep R Yavagal, Ken Uchino, David S Liebeskind, Alexander P Auchus, Souvik Sen, Cathy A Sila, Jeffrey D Vest, Robert W Mays
BACKGROUND: Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. METHODS: We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA...
March 17, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#6
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28306143/mutant-eif2b-leads-to-impaired-mitochondrial-oxidative-phosphorylation-in-vanishing-white-matter-disease
#7
Gali Raini, Reut Sharet, Melisa Herrero, Andrea Atzmon, Anjana Shenoy, Tamar Geiger, Orna Elroy-Stein
Eukaryotic translation initiation factor 2B (eIF2B) is a master regulator of protein synthesis under normal and stress conditions. Mutations in any of the five genes encoding its subunits lead to Vanishing White Matter (VWM) disease, a recessive genetic deadly illness caused by progressive loss of white matter in the brain. In the current study we used fibroblasts, which are not involved in the disease, to demonstrate the involvement of eIF2B in mitochondrial function and abundance. Mass-spectrometry of total proteome of mouse embryonic fibroblasts (MEFs) isolated from Eif2b5(R132H/R132H) mice revealed unbalanced stoichiometry of proteins involved in oxidative phosphorylation and of mitochondrial translation machinery components, among others...
March 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28300213/effect-of-modulation-of-ppar-%C3%AE-activity-on-kupffer-cells-m1-m2-polarization-in-the-development-of-non-alcoholic-fatty-liver-disease
#8
Wenjing Luo, Qinyu Xu, Qi Wang, Huimin Wu, Jing Hua
Abnormal lipid-mediated hepatic inflammatory-immune dysfunction and chronic low grade inflammation play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Macrophage polarization is an important mechanism for the regulation of inflammatory response. Since PPAR-γ has emerged as a master regulator of macrophage polarization, we aimed to investigate the lipid-induced macrophage/Kupffer cell polarization in vivo and in vitro, and explore the association between PPAR-γ activity and macrophages M1/M2 polarization shifting...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297758/-role-of-master-transcriptional-factor-prox-1-in-lymphatic-endothelial-differentiation-of-kaposiform-hemangioendothelioma
#9
Z Y Ke, S J Yang
Objective: To analyze the clinical and pathological features of Kaposiform hemangioendothelioma (KHE), and to investigate the role of master transcriptional factor Prox-1 in the regulation of lymphatic differentiation. Methods: Nine cases of KHE (during the period from October 2009 to June 2016) were collected with clinical and pathological data. H&E stained section review and immunohistochemietry using the Dako EnVision method were performed. Results: There were 6 female and 3 male patients with age ranging from 2 months to 8 years (median 3 years and 4 months)...
March 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28292746/robust-generation-of-quiescent-porcine-valvular-interstitial-cell-cultures
#10
Ana M Porras, Nicole C A van Engeland, Evelyn Marchbanks, Ann McCormack, Carlijn V C Bouten, Magdi H Yacoub, Najma Latif, Kristyn S Masters
BACKGROUND: Valvular interstitial cells (VICs) in the healthy aortic valve leaflet exhibit a quiescent phenotype, with <5% of VICs exhibiting an activated phenotype. Yet, in vitro culture of VICs on tissue culture polystyrene surfaces in standard growth medium results in rapid transformation to an activated phenotype in >90% of cells. The inability to preserve a healthy VIC phenotype during in vitro studies has hampered the elucidation of mechanisms involved in calcific aortic valve disease...
March 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28292013/the-tumor-suppressor-p53-regulates-autophagosomal-and-lysosomal-biogenesis-in-lung-cancer-cells-by-targeting-transcription-factor-eb
#11
Zengli Zhang, Hongfeng Wang, Qifeng Ding, Yufei Xing, Delai Xu, Zhonghua Xu, Tong Zhou, Bin Qian, Chenghong Ji, Xue Pan, Anyuan Zhong, Zheng Ying, Caicun Zhou, Minhua Shi
The cellular protein degradation system, such as proteasomal or autophagy-lysosomal system plays an important role in the pathogenesis of a variety of human diseases including cancer. Transcription factor EB (TFEB) is a master transcriptional factor in the regulation of autophagy-lysosome pathway (ALP), and it has multiple biological functions including protein degradation, cell homeostasis and cell survival. In the present study we show that the tumor suppressor p53 can regulate TFEB nuclear translocation and activity in lung cancer cells...
March 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28289717/retinoic-acid-orphan-receptor-c-inhibition-suppresses-th17-cells-and-induces-thymic-aberrations
#12
Christine Guntermann, Alessandro Piaia, Marie-Laure Hamel, Diethilde Theil, Tina Rubic-Schneider, Alberto Del Rio-Espinola, Linda Dong, Andreas Billich, Klemens Kaupmann, Janet Dawson, Klemens Hoegenauer, David Orain, Samuel Hintermann, Rowan Stringer, Dhavalkumar D Patel, Arno Doelemeyer, Mark Deurinck, Jens Schümann
Retinoic-acid-orphan-receptor-C (RORC) is a master regulator of Th17 cells, which are pathogenic in several autoimmune diseases. Genetic Rorc deficiency in mice, while preventing autoimmunity, causes early lethality due to metastatic thymic T cell lymphomas. We sought to determine whether pharmacological RORC inhibition could be an effective and safe therapy for autoimmune diseases by evaluating its effects on Th17 cell functions and intrathymic T cell development. RORC inhibitors effectively inhibited Th17 differentiation and IL-17A production, and delayed-type hypersensitivity reactions...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288385/alphaviruses-suppress-host-immunity-by-preventing-myeloid-cell-replication-and-antagonizing-innate-immune-responses
#13
REVIEW
Derek W Trobaugh, William B Klimstra
Alphaviruses are medically important mosquito-borne viruses that cause a range of diseases in humans from febrile illness to arthritis or encephalitis. The innate immune response functions to suppress virus replication through upregulation of antiviral molecules and contributes to development of the adaptive immune response. Myeloid cells act as master regulators of virus infection by initiating both the innate and adaptive immune responses. Alphaviruses are capable of antagonizing individual components of these responses to increase replicative fitness in vivo...
March 10, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28286085/hspa5-gene-encoding-hsp70-chaperone-bip-in-the-endoplasmic-reticulum
#14
REVIEW
Jie Wang, Jessica Lee, David Liem, Peipei Ping
The HSPA5 gene (Ensembl ID: ENSG00000044574 (WTSI/EMBL-EBI, 2015)) encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca(2+) homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28283057/super-enhancer-mediated-rna-processing-revealed-by-integrative-microrna-network-analysis
#15
Hiroshi I Suzuki, Richard A Young, Phillip A Sharp
Super-enhancers are an emerging subclass of regulatory regions controlling cell identity and disease genes. However, their biological function and impact on miRNA networks are unclear. Here, we report that super-enhancers drive the biogenesis of master miRNAs crucial for cell identity by enhancing both transcription and Drosha/DGCR8-mediated primary miRNA (pri-miRNA) processing. Super-enhancers, together with broad H3K4me3 domains, shape a tissue-specific and evolutionarily conserved atlas of miRNA expression and function...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28275089/the-microtubule-network-and-cell-death-are-regulated-by-a-mir-34a-stathmin-1-betaiii-tubulin-axis
#16
Nancy S Vetter, E Anders Kolb, Valerie B Sampson, Christopher Mills
MicroRNA-34a (miR-34a) is a master regulator of signaling networks that maintain normal physiology and disease and is currently in development as a miRNA-based therapy for cancer. Prior studies have reported low miR-34a expression in osteosarcoma (OS); however, the molecular mechanisms underlying miR-34a activity in OS are not well defined. Therefore, this study evaluated the role of miR-34a in regulating signal transduction pathways that influence cell death in OS. Levels of miR-34a were attenuated in human OS cells and xenografts of the Pediatric Preclinical Testing Consortium (PPTC)...
March 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28266708/role-of-wnt-%C3%AE-catenin-signaling-regulatory-micrornas-in-the-pathogenesis-of-colorectal-cancer
#17
REVIEW
Farzad Rahmani, Amir Avan, Seyed Isaac Hashemy, Seyed Mahdi Hassanian
Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. In more than 90% of all CRC patients, the master oncogenic Ras-Wnt signaling axis is over-activated. MicroRNAs (miRNAs) are potential novel diagnostic and prognostic biomarkers as well as therapeutic targets for several cancers including lung, breast, gastric and colorectal cancers. Oncogenic or tumor suppressor miRNAs modulate tumor cells proliferation, cell cycle progression, angiogenesis, invasion and metastasis through regulating oncogenic pathways including Wnt/β-catenin signaling...
March 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28265786/precision-medicine-driven-by-cancer-systems-biology
#18
Fabian V Filipp
Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors...
March 7, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28261564/legionella-pneumophila-strain-130b-evades-macrophage-cell-death-independent-of-the-effector-sidf-in-the-absence-of-flagellin
#19
Mary Speir, Adam Vogrin, Azadeh Seidi, Gilu Abraham, Stéphane Hunot, Qingqing Han, Gerald W Dorn, Seth L Masters, Richard A Flavell, James E Vince, Thomas Naderer
The human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28260489/mechanisms-of-non-canonical-activation-of-ataxia-telangiectasia-mutated
#20
REVIEW
S V Khoronenkova
ATM is a master regulator of the cellular response to DNA damage. The classical mechanism of ATM activation involves its monomerization in response to DNA double-strand breaks, resulting in ATM-dependent phosphorylation of more than a thousand substrates required for cell cycle progression, DNA repair, and apoptosis. Here, new experimental evidence for non-canonical mechanisms of ATM activation in response to stimuli distinct from DNA double-strand breaks is discussed. It includes cytoskeletal changes, chromatin modifications, RNA-DNA hybrids, and DNA single-strand breaks...
December 2016: Biochemistry. Biokhimii︠a︡
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