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Master cell disease

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https://www.readbyqxmd.com/read/29344090/overexpression-of-the-proneural-transcription-factor-ascl1-in-chronic-lymphocytic-leukemia-with-a-t-12-14-q23-2-q32-3
#1
Theodora Malli, Melanie Rammer, Sabrina Haslinger, Jonathan Burghofer, Sonja Burgstaller, Hans-Christian Boesmueller, Renate Marschon, Wolfgang Kranewitter, Martin Erdel, Sabine Deutschbauer, Gerald Webersinke
Background: Translocations of the IGH locus on 14q32.3 are present in about 8% of patients with chronic lymphocytic leukemia (CLL) and contribute to leukemogenesis by deregulating the expression of the IGH-partner genes. Identification of these genes and investigation of the downstream effects of their deregulation can reveal disease-causing mechanisms. Case presentation: We report on the molecular characterization of a novel t(12;14)(q23.2;q32.3) in CLL. As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29320511/application-of-a-phenotypic-drug-discovery-strategy-to-identify-biological-and-chemical-starting-points-for-inhibition-of-tslp-production-in-lung-epithelial-cells
#2
Adelina Orellana, Vicente García-González, Rosa López, Sonia Pascual-Guiral, Estrella Lozoya, Julia Díaz, Daniel Casals, Antolín Barrena, Stephane Paris, Miriam Andrés, Victor Segarra, Dolors Vilella, Rajneesh Malhotra, Paul Eastwood, Anna Planagumà, Montserrat Miralpeix, Arsenio Nueda
Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation...
2018: PloS One
https://www.readbyqxmd.com/read/29319368/association-of-increased-eomesodermin-bcl6-and-granzyme-b-expression-with-major-clinical-manifestations-of-hashimoto-s-thyroiditis-an-observational-study
#3
Mario Štefanić, Stana Tokić, Mirjana Suver Stević, Ljubica Glavaš-Obrovac
PURPOSE: Studies of cytotoxic T cells and their respective lineage master regulators have been limited in Hashimoto's thyroiditis (HT). It is unclear whether their transcriptomes are changed in HT patients and how these changes are associated with the thyroid damage, major clinical manifestations, and disease progression. METHODS: We explored the gene expression patterns of selected transcription factors [eomesodermin (EOMES), BACH2, BCL6, TCF1] and cytolytic molecules [granzyme B (GZMB)] in peripheral blood (PB) T cells of 10 healthy controls and 30 HT patients of various subtypes (hypothyroid, untreated HT; L-thyroxine (T4)-treated HT, and spontaneously euthyroid HT) using real-time quantitative PCR...
January 10, 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29317536/golgi-stress-response-reprograms-cysteine-metabolism-to-confer-cytoprotection-in-huntington-s-disease
#4
Juan I Sbodio, Solomon H Snyder, Bindu D Paul
Golgi stress response is emerging as a physiologic process of comparable importance to endoplasmic reticulum (ER) and mitochondrial stress responses. However, unlike ER stress, the identity of the signal transduction pathway involved in the Golgi stress response has been elusive. We show that the Golgi stressor monensin acts via the PKR-like ER kinase/Activating Transcription Factor 4 pathway. ATF4 is the master regulator of amino acid metabolism, which is induced during amino acid depletion and other forms of stress...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29311280/an-algu-regulated-antisense-transcript-encoded-within-the-pseudomonas-syringae-fleq-gene-has-a-positive-effect-on-motility
#5
Eric Markel, Hollie Dalenberg, Caroline L Monteil, Boris A Vinatzer, Bryan Swingle
Production of bacterial flagella is controlled by a multi-tiered regulatory system that coordinates expression of 40-50 subunits and ordered assembly of these elaborate structures. Flagellar expression is environmentally controlled, presumably to optimize the benefits and liabilities of having these organelles with cell growth and survival. We recently reported a global survey of AlgU-dependent regulation and binding in Pseudomonas syringae pv. tomato DC3000 that included evidence for strong down-regulation of many flagellar and chemotaxis motility genes...
January 8, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29287724/paris-reprograms-glucose-metabolism-by-hif-1%C3%AE-induction-in-dopaminergic-neurodegeneration
#6
Hojin Kang, Areum Jo, Hyein Kim, Rin Khang, Ji-Yeong Lee, Hanna Kim, Chi-Hu Park, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Our previous study found that PARIS (ZNF746) transcriptionally suppressed transketolase (TKT), a key enzyme in pentose phosphate pathway (PPP) in the substantia nigra (SN) of AAV-PARIS injected mice. In this study, we revealed that PARIS overexpression reprogrammed glucose metabolic pathway, leading to the increment of glycolytic proteins along with TKT reduction in the SN of AAV-PARIS injected mice. Knock-down of TKT in differentiated SH-SY5Y cells led to an increase of glycolytic enzymes and decrease of PPP-related enzymes whereas overexpression of TKT restored PARIS-mediated glucose metabolic shift, suggesting that glucose metabolic alteration by PARIS is TKT-dependent...
December 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29282325/creation-of-disease-inspired-biomaterial-environments-to-mimic-pathological-events-in-early-calcific-aortic-valve-disease
#7
Ana M Porras, Jennifer A Westlund, Austin D Evans, Kristyn S Masters
An insufficient understanding of calcific aortic valve disease (CAVD) pathogenesis remains a major obstacle in developing treatment strategies for this disease. The aim of the present study was to create engineered environments that mimic the earliest known features of CAVD and apply this in vitro platform to decipher relationships relevant to early valve lesion pathobiology. Glycosaminoglycan (GAG) enrichment is a dominant hallmark of early CAVD, but culture of valvular interstitial cells (VICs) in biomaterial environments containing pathological amounts of hyaluronic acid (HA) or chondroitin sulfate (CS) did not directly increase indicators of disease progression such as VIC activation or inflammatory cytokine production...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29282317/distinctive-roles-of-age-sex-and-genetics-in-shaping-transcriptional-variation-of-human-immune-responses-to-microbial-challenges
#8
Barbara Piasecka, Darragh Duffy, Alejandra Urrutia, Hélène Quach, Etienne Patin, Céline Posseme, Jacob Bergstedt, Bruno Charbit, Vincent Rouilly, Cameron R MacPherson, Milena Hasan, Benoit Albaud, David Gentien, Jacques Fellay, Matthew L Albert, Lluis Quintana-Murci
The contribution of host genetic and nongenetic factors to immunological differences in humans remains largely undefined. Here, we generated bacterial-, fungal-, and viral-induced immune transcriptional profiles in an age- and sex-balanced cohort of 1,000 healthy individuals and searched for the determinants of immune response variation. We found that age and sex affected the transcriptional response of most immune-related genes, with age effects being more stimulus-specific relative to sex effects, which were largely shared across conditions...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29280568/cancer-associated-fibroblasts-the-architects-of-stroma-remodelling
#9
REVIEW
Alice Santi, Fernanda G Kugeratski, Sara Zanivan
Fibroblasts have exceptional phenotypic plasticity and capability to secrete vast amount of soluble factors, ECM components and extracellular vesicles. While in physiological conditions this makes fibroblasts master regulators of tissue homeostasis and healing of injured tissues, in solid tumours cancer-associated fibroblasts (CAFs) co-evolve with the disease, and alter the biochemical and physical structure of the tumour microenvironment, as well as the behaviour of the surrounding stromal and cancer cells...
December 27, 2017: Proteomics
https://www.readbyqxmd.com/read/29275836/a-cellular-and-molecular-view-of-t-helper-17%C3%A2-cell-plasticity-in-autoimmunity
#10
REVIEW
Ralph Stadhouders, Erik Lubberts, Rudi W Hendriks
Since the original identification of the T helper 17 (Th17) subset in 2005, it has become evident that these cells do not only contribute to host defence against pathogens, such as bacteria and fungi, but that they are also critically involved in the pathogenesis of many autoimmune diseases. In contrast to the classic Th1 and Th2 cells, which represent rather stably polarized subsets, Th17 cells display remarkable heterogeneity and plasticity. This has been attributed to the characteristics of the key transcription factor that guides Th17 differentiation, retinoic acid receptor-related orphan nuclear receptor gamma (RORγ)...
December 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29274248/stem-cell-education-for-medical-students-at-tongji-university-primary-cell-culture-and-directional-differentiation-of-rat-bone-marrow-mesenchymal-stem-cells
#11
Caixia Jin, Haibin Tian, Jiao Li, Song Jia, Siguang Li, Guo-Tong Xu, Lei Xu, Lixia Lu
Stem cells are cells that can self-renew and differentiate into a variety of cell types under certain conditions. Stem cells have great potential in regenerative medicine and cell therapy for the treatment of certain diseases. To deliver knowledge about this frontier in science and technology to medical undergraduate students, we designed an innovative practical experiment for freshmen in their second semester. The lab exercise focused on rat bone marrow mesenchymal stem cell (BMSC) isolation, cell culture and differentiation, and it aimed to help students master the aseptic techniques for cell culture, the basic methods and procedures for the primary culture and passage of BMSCs, the basic procedure for the directional differentiation of BMSCs into adipocytes and their subsequent identification by oil-red-O staining...
December 23, 2017: Biochemistry and Molecular Biology Education
https://www.readbyqxmd.com/read/29248493/tnfaip3-a20-acts-as-master-switch-in-tnf%C3%AE-blockade-driven-il-17a-expression
#12
Paulo Cm Urbano, Raúl Aguirre-Gamboa, Angel Ashikov, Bennie van Heeswijk, Anja Krippner-Heidenreich, Henk Tijssen, Yang Li, Valderilio F Azevedo, Lisa Jt Smits, Frank Hoentjen, Irma Joosten, Hans Jpm Koenen
BACKGROUND: Anti-TNF inhibitors successfully improve life quality of patients suffering from inflammatory disease. Unfortunately, not all patients respond to anti-TNF therapy and some patients show paradoxical immune side-effects, which is poorly understood. Surprisingly, anti-TNF agents were shown to promote IL-17A production, with as yet unknown clinical implications. OBJECTIVE: To investigate the molecular mechanism underlying anti-TNF driven IL-17A expression and the clinical implications of this phenomenon...
December 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29247688/caffeic-acid-and-resveratrol-ameliorate-cellular-damage-in-cell-and-drosophila-models-of-spinocerebellar-ataxia-type-3-through-upregulation-of-nrf2-pathway
#13
Yu-Ling Wu, Jui-Chih Chang, Wei-Yong Lin, Chien-Chun Li, Mingli Hsieh, Haw-Wen Chen, Tsu-Shing Wang, Wen-Tzu Wu, Chin-San Liu, Kai-Li Liu
Polyglutamine (polyQ)-expanded mutant ataxin-3 protein, which is prone to misfolding and aggregation, leads to cerebellar neurotoxicity in spinocerebellar ataxia type 3 (SCA3), an inherited PolyQ neurodegenerative disease. Although the exact mechanism is unknown, the pathogenic effects of mutant ataxin-3 are associated with dysregulation of transcription, protein degradation, mitochondrial function, apoptosis, and antioxidant potency. In the present study we explored the protective role and possible mechanism of caffeic acid (CA) and resveratrol (Res) in cells and Drosophila expressing mutant ataxin-3...
December 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29243807/microrna-as-a-systemic-intervention-in-the-specific-breast-cancer-subtypes-with-c-myc-impacts-introducing-subtype-based-appraisal-tool
#14
REVIEW
Vida Pourteimoor, Mahdi Paryan, Samira Mohammadi-Yeganeh
Breast cancer is indisputably a heterogeneous disease, in which a formidable combination of definitely dis-regulated C-MYC and microRNA (miRNA) profiles along with other factors are responsible to generate a specific type of breast cancer. C-MYC as a master regulator of more than 20,000 genes can modify the expression of genes underlying to perform diverse conflicting functional frameworks. The functional spectra of miRNA in the new areas of the evolution of cell behaviors are identified. Here, we endeavor to summarize some recent advances of miRNA applications that can be recruited as combinatorial targeted therapy for patients with breast cancer...
December 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29243212/controlling-centriole-numbers-geminin-family-members-as-master-regulators-of-centriole-amplification-and-multiciliogenesis
#15
REVIEW
Marina Arbi, Dafni-Eleftheria Pefani, Stavros Taraviras, Zoi Lygerou
To ensure that the genetic material is accurately passed down to daughter cells during mitosis, dividing cells must duplicate their chromosomes and centrosomes once and only once per cell cycle. The same key steps-licensing, duplication, and segregation-control both the chromosome and the centrosome cycle, which must occur in concert to safeguard genome integrity. Aberrations in genome content or centrosome numbers lead to genomic instability and are linked to tumorigenesis. Such aberrations, however, can also be part of the normal life cycle of specific cell types...
December 14, 2017: Chromosoma
https://www.readbyqxmd.com/read/29242678/keap1-and-done-targeting-the-nrf2-pathway-with-sulforaphane
#16
Albena T Dinkova-Kostova, Jed W Fahey, Rumen V Kostov, Thomas W Kensler
Background: Since the re-discovery of sulforaphane in 1992 and the recognition of the bioactivity of this phytochemical, many studies have examined its mode of action in cells, animals and humans. Broccoli, especially as young sprouts, is a rich source of sulforaphane and broccoli-based preparations are now used in clinical studies probing efficacy in health preservation and disease mitigation. Many putative cellular targets are affected by sulforaphane although only one, KEAP1-NRF2 signaling, can be considered a validated target at this time...
November 2017: Trends in Food Science & Technology
https://www.readbyqxmd.com/read/29234281/interleukin-6-induces-dec1-promotes-dec1-interaction-with-rxr%C3%AE-and-suppresses-the-expression-of-pxr-car-and-their-target-genes
#17
Rui Ning, Yunran Zhan, Shuangcheng He, Jinhua Hu, Zhu Zhu, Gang Hu, Bingfang Yan, Jian Yang, Wei Liu
Inflammatory burden is a primary cellular event in many liver diseases, and the overall capacity of drug elimination is decreased. PXR (pregnane X receptor) and CAR (constitutive androstane receptor) are two master regulators of genes encoding drug-metabolizing enzymes and transporters. DEC1 (differentiated embryonic chondrocyte-expressed gene 1) is a ligand-independent transcription factor and reportedly is induced by many inflammatory cytokines including IL-6. In this study, we used primary hepatocytes (human and mouse) as well as HepG2 cell line and demonstrated that IL-6 increased DEC1 expression and decreased the expressions of PXR, CAR, and their target genes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29231810/shigella-entry-unveils-a-calcium-calpain-dependent-mechanism-for-inhibiting-sumoylation
#18
Pierre Lapaquette, Sabrina Fritah, Nouara Lhocine, Alexandra Andrieux, Giulia Nigro, Joëlle Mounier, Philippe Sansonetti, Anne Dejean
Disruption of the sumoylation/desumoylation equilibrium is associated with several disease states such as cancer and infections, however the mechanisms regulating the global SUMO balance remain poorly defined. Here, we show that infection by Shigella flexneri, the causative agent of human bacillary dysentery, switches off host sumoylation during epithelial cell infection in vitro and in vivo and that this effect is mainly mediated by a calcium/calpain-induced cleavage of the SUMO E1 enzyme SAE2, thus leading to sumoylation inhibition...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29230372/integrated-downstream-regulation-by-the-quorum-sensing-controlled-transcription-factors-lrha-and-rcsa-impacts-phenotypic-outputs-associated-with-virulence-in-the-phytopathogen-pantoea-stewartii-subsp-stewartii
#19
Duy An Duong, Ann M Stevens
Pantoea stewartii subsp. stewartii is a Gram-negative proteobacterium that causes leaf blight and Stewart's wilt disease in corn. Quorum sensing (QS) controls bacterial exopolysaccharide production that blocks water transport in the plant xylem at high bacterial densities during the later stage of the infection, resulting in wilt. At low cell density the key master QS regulator in P. stewartii, EsaR, directly represses rcsA, encoding an activator of capsule biosynthesis genes, but activates lrhA, encoding a transcription factor that regulates surface motility...
2017: PeerJ
https://www.readbyqxmd.com/read/29229701/cody-mediated-c-di-gmp-dependent-inhibition-of-mammalian-cell-invasion-in-listeria-monocytogenes
#20
Ahmed M Elbakush, Kurt W Miller, Mark Gomelsky
Elevated levels of the second messenger c-di-GMP suppress virulence in diverse pathogenic bacteria, yet mechanisms are poorly characterized. In the food-borne pathogen Listeria monocytogenes, high c-di-GMP levels inhibit mammalian cell invasion. Here, we show that invasion is impaired because of the decreased expression of internalin genes whose products are involved in invasion. We further show that at high c-di-GMP levels, expression of the entire virulence regulon is suppressed and so is expression of the prfA gene encoding the master activator of the virulence regulon...
December 11, 2017: Journal of Bacteriology
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