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https://www.readbyqxmd.com/read/27911124/the-impact-of-interferon-alpha2-on-hla-genes-in-patients-with-polycythemia-vera-and-related-neoplasms
#1
Vibe Skov, Caroline Hasselbalch Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27911100/mitochondria-and-iron-current-questions
#2
Bibbin T Paul, David H Manz, Frank M Torti, Suzy V Torti
Mitochondria are cellular organelles that perform numerous bioenergetic, biosynthetic, and regulatory functions and play a central role in iron metabolism. Extracellular iron is taken up by cells and transported to the mitochondria, where it is utilized for synthesis of cofactors essential to the function of enzymes involved in oxidation-reduction reactions, DNA synthesis and repair, and a variety of other cellular processes. Areas Covered: This article reviews the trafficking of iron to the mitochondria and normal mitochondrial iron metabolism, including heme synthesis and iron-sulfur cluster biogenesis...
December 2, 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27910998/aurora-a-shines-on-t-cell-activation-through-the-regulation-of-lck
#3
Noelia Blas-Rus, Eugenio Bustos-Morán, Noa B Martín-Cófreces, Francisco Sánchez-Madrid
Different protein kinases control signaling emanating from the T cell receptor (TCR) during antigen-specific T cell activation. Mitotic kinases, e.g. Aurora-A, have been widely studied in the context of mitosis due to their role during microtubule (MT) nucleation, becoming critical regulators of cell cycle progression. We have recently described a specific role for Aurora-A kinase in antigenic T cell activation. Blockade of Aurora-A in T cells severely disrupts the dynamics of MTs and CD3ζ-bearing signaling vesicles during T cell activation...
December 2, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27910766/natural-igm-and-the-development-of-b-cell-mediated-autoimmune-diseases
#4
Trang T T Nguyen, Nicole Baumgarth
Most serum immunoglobulin M (IgM) is "natural IgM", which is produced apparently spontaneously by a distinct subset of B cells requiring no exogenous antigenic or microbial stimuli. Natural IgM is an evolutionarily conserved molecule and reacts with a variety of epitopes expressed on both self- and non-self antigens. It has long been understood that secreted (s) IgM contributes to the removal of altered self-antigens, such as apoptotic and dying cells. As we outline in this review, it is thought that this sIgM housekeeping function removes potential triggers of autoresponse induction...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910764/metabolic-regulation-of-natural-killer-cell-ifn-%C3%AE-production
#5
Annelise Y Mah, Megan A Cooper
Metabolism is critical for a host of cellular functions and provides a source of intracellular energy. It has been recognized recently that metabolism also regulates differentiation and effector functions of immune cells. Although initial work in this field has focused largely on T lymphocytes, recent studies have demonstrated metabolic control of innate immune cells, including natural killer (NK) cells. Here, we review what is known regarding the metabolic requirements for NK cell activation, focusing on NK cell production of interferon-gamma (IFN-γ)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27910206/balance-between-il-3-and-type-iinterferons-and-their-interrelationship-with-fasl-dictates-lifespan-and-effector-functions-of-human-basophils
#6
B R Hagmann, A Odermatt, T Kaufmann, C A Dahinden, M Fux
BACKGROUND: In contrast to eosinophils and neutrophils, the regulation of the lifespan of human basophils is poorly defined, with the exception of the potent anti-apoptotic effect of IL-3 that also promotes pro-inflammatory effector functions and phenotypic changes. Type I IFNs (IFN-α, IFN-β), which are well known for their anti-viral activities, have the capacity to inhibit allergic inflammation. OBJECTIVE: To elucidate whether type I IFNs have the potential to abrogate the lifespan and/or effector functions of human basophils...
November 5, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27909734/klf4-inhibits-tumor-growth-and-metastasis-by-targeting-microrna-31-in-human-hepatocellular-carcinoma
#7
Chuan Tian, Shanshan Yao, Li Liu, Youcheng Ding, Qingwang Ye, Xiao Dong, Yong Gao, Ning Yang, Qi Li
MicroRNAs (miRNAs or miRs) are short, endogenous non-coding RNA molecules, demonstrating abnormal expression in cancer initiation and progression. In this study, we profiled 18 differentially regulated miRNAs, including miRNA‑31, using miRNA array. Kruppel (or Krüppel)-like factor 4 (Klf4) is a transcription factor and putative tumor suppressor. Both were found to be significantly downregulated in liver cancer tissues and cells. However, little is known about the correlation between Klf4 and miRNA‑31 in hepatocellular carcinoma (HCC)...
November 24, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909336/c-terminal-truncated-hbv-x-promotes-hepato-oncogenesis-through-inhibition-of-tumor-suppressive-%C3%AE-catenin-bambi-signaling
#8
Seok Lee, Mi-Jin Lee, Jun Zhang, Goung-Ran Yu, Dae-Ghon Kim
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27909217/the-small-foxp1-isoform-predominantly-expressed-in-activated-b-cell-like-diffuse-large-b-cell-lymphoma-and-full-length-foxp1-exert-similar-oncogenic-and-transcriptional-activity-in-human-b-cells
#9
Martine van Keimpema, Leonie J Grüneberg, Esther J M Schilder-Tol, Monique E C M Oud, Esther Beuling, Paul J Hensbergen, Johann de Jong, Steven T Pals, Marcel Spaargaren
The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 (FOXP1-iso), rather than full-length FOXP1 (FOXP1-FL), may possess this oncogenic activity. Corroborating those studies, we here show that activated B cell-like diffuse large B-cell lymphoma cell-lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express FOXP1-iso and that the 5-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukaemia virus- and transposon-mediated insertional mutagenesis screens...
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27909060/cd6-regulates-intestinal-ischemia-reperfusion-induced-injury-by-modulating-natural-igm-producing-b1a-cell-self-renewal
#10
Gospel Enyindah-Asonye, Yan Li, Wei Xin, Nora Singer, Neetu Gupta, John Fung, Feng Lin
Intestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease is poorly understood, although it is established that circulating pathogenic natural IgM, which is primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as a marker for T cells and later found to be present on some subsets of B cells in humans, however, whether CD6 plays any role in intestinal I/R induced injury and if so, what are the underlying mechanisms, remain unknown...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909043/an-atlas-of-human-kinase-regulation
#11
David Ochoa, Mindaugas Jonikas, Robert T Lawrence, Bachir El Debs, Joel Selkrig, Athanasios Typas, Judit Villén, Silvia Dm Santos, Pedro Beltrao
The coordinated regulation of protein kinases is a rapid mechanism that integrates diverse cues and swiftly determines appropriate cellular responses. However, our understanding of cellular decision-making has been limited by the small number of simultaneously monitored phospho-regulatory events. Here, we have estimated changes in activity in 215 human kinases in 399 conditions derived from a large compilation of phosphopeptide quantifications. This atlas identifies commonly regulated kinases as those that are central in the signaling network and defines the logic relationships between kinase pairs...
December 1, 2016: Molecular Systems Biology
https://www.readbyqxmd.com/read/27908889/microrna-146a-induces-lineage-negative-bone-marrow-cell-apoptosis-and-senescence-by-targeting-polo-like-kinase-2-expression
#12
Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, Dushyantha T Jayaweera, Derek M Dykxhoorn, Chunming Dong
OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908728/activation-of-evi1-transcription-by-the-lef1-%C3%AE-catenin-complex-with-p53-alteration-in-myeloid-blast-crisis-of-chronic-myeloid-leukemia
#13
Nawin Manachai, Yusuke Saito, Shingo Nakahata, Avinash Govind Bahirvani, Tomomi Osato, Kazuhiro Morishita
The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blastic crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908295/dopamine-2-receptor-extracellular-n-terminus-regulates-receptor-surface-availability-and-is-the-target-of-human-pathogenic-antibodies-from-children-with-movement-and-psychiatric-disorders
#14
Nese Sinmaz, Fiona Tea, Deepti Pilli, Alicia Zou, Mazen Amatoury, Tina Nguyen, Vera Merheb, Sudarshini Ramanathan, Sandra T Cooper, Russell C Dale, Fabienne Brilot
Anti-Dopamine-2 receptor (D2R) antibodies have been recently identified in a subgroup of children with autoimmune movement and psychiatric disorders, however the epitope(s) and mechanism of pathogenicity remain unknown. Here we report a major biological role for D2R extracellular N-terminus as a regulator of receptor surface availability, and as a major epitope targeted and impaired in brain autoimmunity. In transfected human cells, purified anti-D2R antibody from patients specifically and significantly reduced human D2R surface levels...
December 1, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27908290/bile-acid-a-potential-inducer-of-colon-cancer-stem-cells
#15
Lulu Farhana, Pratima Nangia-Makker, Evan Arbit, Kathren Shango, Sarah Sarkar, Hamidah Mahmud, Timothy Hadden, Yingjie Yu, Adhip P N Majumdar
BACKGROUND: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. METHODS: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27907930/microrna-profiling-in-clear-cell-renal-cell-carcinoma-tissues-potentially-links-tumorigenesis-and-recurrence-with-obesity
#16
X Shu, M A Hildebrandt, J Gu, N M Tannir, S F Matin, J A Karam, C G Wood, X Wu
BACKGROUND: Twenty to 40% localised RCC patients may experience recurrence after curative surgery. Limited miRNA predictors have been identified for ccRCC recurrence. METHODS: Through a multi-phase study design, we analysed miRNAs in tissues obtained from 203 ccRCC patients. Paired t-test was used for tumour-normal comparisons and Cox regression model was performed to compute hazard ratios (HRs) and corresponding 95% CIs. RESULTS: A 17-miRNA signature was identified that can concordantly classify >95% of tumour/adjacent normal samples...
December 1, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27907175/p53-specifically-binds-triplex-dna-in-vitro-and-in-cells
#17
Marie Brázdová, Vlastimil Tichý, Robert Helma, Pavla Bažantová, Alena Polášková, Aneta Krejčí, Marek Petr, Lucie Navrátilová, Olga Tichá, Karel Nejedlý, Martin L Bennink, Vinod Subramaniam, Zuzana Bábková, Tomáš Martínek, Matej Lexa, Matej Adámik
Triplex DNA is implicated in a wide range of biological activities, including regulation of gene expression and genomic instability leading to cancer. The tumor suppressor p53 is a central regulator of cell fate in response to different type of insults. Sequence and structure specific modes of DNA recognition are core attributes of the p53 protein. The focus of this work is the structure-specific binding of p53 to DNA containing triplex-forming sequences in vitro and in cells and the effect on p53-driven transcription...
2016: PloS One
https://www.readbyqxmd.com/read/27907103/tbx20-is-an-essential-regulator-of-embryonic-heart-growth-in-zebrafish
#18
Steffen Just, Linda Raphel, Ina M Berger, Anja Bühler, Mirjam Keßler, Wolfgang Rottbauer
The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein...
2016: PloS One
https://www.readbyqxmd.com/read/27906627/oxidized-low-density-lipoproteins-enhance-expression-and-activity-of-cd39-and-cd73-in-the-human-aortic-valve-endothelium
#19
Ewa Kaniewska-Bednarczuk, Michał Mielcarek, Adrian H Chester, Ewa M Slominska, Magdi H Yacoub, Ryszard T Smolenski
Extracellular nucleotides regulate thrombosis, inflammation, and immune response. Ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5'-nucleotidase (CD73) convert extracellular nucleotides in a sequential order: ATP to ADP, AMP, and then to adenosine. In this study, we aimed to test an effect of oxidized low-density lipoprotein (ox-LDL) on CD39 and CD73 in endothelial cells. Human aortic valve endothelial cells were exposed to ox-LDL for 24-48 h. Next, the activity, protein expression, and mRNA transcripts level of CD39 and CD73 were characterized by an incubation with ATP or AMP followed by high-performance liquid chromatography analysis of media as well as western blots and qPCR...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906184/1-methyl-tryptophan-attenuates-regulatory-t-cells-differentiation-due-to-the-inhibition-of-estrogen-ido1-mrc2-axis-in-endometriosis
#20
Chunyan Wei, Jie Mei, Lingli Tang, Yukai Liu, Dajin Li, Mingqing Li, Xiaoyong Zhu
Foxp3(+) regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment...
December 1, 2016: Cell Death & Disease
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