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https://www.readbyqxmd.com/read/29452228/a-bach2-gene-variant-is-associated-with-postoperative-recurrence-of-crohn-s-disease
#1
Michael R Laffin, Richard N Fedorak, Eytan Wine, Bryan Dicken, Karen L Madsen
BACKGROUND: Crohn's disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in over half of the patients following their initial operation. Although many genetic loci are implicated in Crohn's disease, few have been associated with post-resection recurrence. STUDY DESIGN: A cohort of Crohn's disease subjects who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence...
February 13, 2018: Journal of the American College of Surgeons
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
#2
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/29230020/snp-co-association-and-network-analyses-identify-e2f3-kdm5a-and-bach2-as-key-regulators-of-the-bovine-milk-fatty-acid-profile
#3
Sara Pegolo, Christos Dadousis, Núria Mach, Yuliaxis Ramayo-Caldas, Marcello Mele, Giuseppe Conte, Stefano Schiavon, Giovanni Bittante, Alessio Cecchinato
The fatty acid (FA) profile has a considerable impact on the nutritional and technological quality of milk and dairy products. The molecular mechanism underlying the regulation of fat metabolism in bovine mammary gland have been not completely elucidated. We conducted genome-wide association studies (GWAS) across 65 milk FAs and fat percentage in 1,152 Brown Swiss cows. In total, we identified 175 significant single nucleotide polymorphism (SNPs) spanning all chromosomes. Pathway analyses revealed that 12:0 was associated with the greatest number of overrepresented categories/pathways (e...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29216925/silencing-of-mir-193a-5p-increases-the-chemosensitivity-of-prostate-cancer-cells-to-docetaxel
#4
Zhan Yang, Jin-Suo Chen, Jin-Kun Wen, Hai-Tao Gao, Bin Zheng, Chang-Bao Qu, Kai-Long Liu, Man-Li Zhang, Jun-Fei Gu, Jing-Dong Li, Yan-Ping Zhang, Wei Li, Xiao-Lu Wang, Yong Zhang
BACKGROUND: Docetaxel-based chemotherapy failure in advanced prostate carcinoma has partly been attributed to the resistance of prostate cancer (PC) cells to docetaxel-induced apoptosis. Hence, there is an urgent need to identify mechanisms of docetaxel chemoresistance and to develop new combination therapies. METHODS: miR-193a-5p level was evaluated by qPCR in prostate tissues and cell lines, and its expression in the tissues was also examined by in situ hybridization...
December 8, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29154209/external-signals-regulate-germinal-center-fate-determining-transcription-factors-in-the-a20-lymphoma-cell-line
#5
Juan Feng, Xin Liu, Xingya Ni, Hai Qi
Due to the apoptosis-prone nature of primary germinal center B (GCB) cells, it remains a huge challenge to dissect signals that guide their differentiation towards memory B cells and plasma cells in vitro. Here we show that the murine lymphoma cell line A20 resembles primary GCB cells in expression of GC-specific surface markers and the master transcription factor BCL6 and may serve as a useful system to model certain GCB cell behaviors in vitro. Using these cells, we found that both CD40 and B cell receptor (BCR) signaling are able to drive BCL6 downregulation, which is a prerequisite of post-GC B-cell differentiation...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29129929/il-2-imprints-human-naive-b-cell-fate-towards-plasma-cell-through-erk-elk1-mediated-bach2-repression
#6
Nicolas Hipp, Hannah Symington, Cédric Pastoret, Gersende Caron, Céline Monvoisin, Karin Tarte, Thierry Fest, Céline Delaloy
Plasma cell differentiation is a tightly regulated process that requires appropriate T cell helps to reach the induction threshold. To further understand mechanisms by which T cell inputs regulate B cell fate decision, we investigate the minimal IL-2 stimulation for triggering human plasma cell differentiation in vitro. Here we show that the timed repression of BACH2 through IL-2-mediated ERK/ELK1 signalling pathway directs plasma cell lineage commitment. Enforced BACH2 repression in activated B cells unlocks the plasma cell transcriptional program and induces their differentiation into immunoglobulin M-secreting cells...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28993481/mtor-bach2-cascade-controls-cell-cycle-and-class-switch-recombination-during-b-cell-differentiation
#7
Toru Tamahara, Kyoko Ochiai, Akihiko Muto, Yukinari Kato, Nicolas Sax, Mitsuyo Matsumoto, Takeyoshi Koseki, Kazuhiko Igarashi
The transcription factor Bach2 regulates both acquired and innate immunity at multiple steps including antibody class switching and regulatory T cell development in activated B and T cells, respectively. However, little is known about the molecular mechanisms of Bach2 regulation in response to signaling of cytokines and antigen. We show here that mammalian target of rapamycin (mTOR) controls Bach2 along B cell differentiation with two distinct mechanisms in pre-B cells. Firstly, mTOR complex 1 (mTORC1) inhibited accumulation of Bach2 protein in nuclei and reduced its stability...
October 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28924457/bach2-promotes-indolent-clinical-presentation-in-waldenstr%C3%A3-m-macroglobulinemia
#8
Charles Herbaux, Elisabeth Bertrand, Guillemette Marot, Christophe Roumier, Nicolas Poret, Valérie Soenen, Olivier Nibourel, Catherine Roche-Lestienne, Natacha Broucqsault, Sylvie Galiègue-Zouitina, Eileen M Boyle, Guillemette Fouquet, Aline Renneville, Sabine Tricot, Franck Morschhauser, Claude Preudhomme, Bruno Quesnel, Stephanie Poulain, Xavier Leleu
Approximately 30% of the patients who fulfil the criteria of Waldenström's macroglobulinemia (WM) are diagnosed while asymptomatic (indolent), and will not require immediate therapy. Conversely, patients with a disease-related event will be considered for therapy. The physiopathology of these 2 groups remains unclear, and the mechanisms of progression from indolent to symptomatic WM have yet to be fully understood. Seventeen patients diagnosed with WM were included in this study, 8 asymptomatic WM (A-WM) and 9 symptomatic WM (S-WM)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28916727/inflammatory-responses-induce-an-identity-crisis-of-alveolar-macrophages-leading-to-pulmonary-alveolar-proteinosis
#9
COMPARATIVE STUDY
Risa Ebina-Shibuya, Mitsuyo Matsumoto, Makoto Kuwahara, Kyoung-Jin Jang, Manabu Sugai, Yoshiaki Ito, Ryo Funayama, Keiko Nakayama, Yuki Sato, Naoto Ishii, Yasunobu Okamura, Kengo Kinoshita, Kohei Kometani, Tomohiro Kurosaki, Akihiko Muto, Masakazu Ichinose, Masakatsu Yamashita, Kazuhiko Igarashi
Pulmonary alveolar proteinosis (PAP) is a severe respiratory disease characterized by dyspnea caused by accumulation of surfactant protein. Dysfunction of alveolar macrophages (AMs), which regulate the homeostasis of surfactant protein, leads to the development of PAP; for example, in mice lacking BTB and CNC homology 2 (Bach2). However, how Bach2 helps prevent PAP is unknown, and the cell-specific effects of Bach2 are undefined. Using mice lacking Bach2 in specific cell types, we found that the PAP phenotype of Bach2-deficient mice is due to Bach2 deficiency in more than two types of immune cells...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28887441/hiv-1-mediated-insertional-activation-of-stat5b-and-bach2-trigger-viral-reservoir-in-t-regulatory-cells
#10
Daniela Cesana, Francesca R Santoni de Sio, Laura Rudilosso, Pierangela Gallina, Andrea Calabria, Stefano Beretta, Ivan Merelli, Elena Bruzzesi, Laura Passerini, Silvia Nozza, Elisa Vicenzi, Guido Poli, Silvia Gregori, Giuseppe Tambussi, Eugenio Montini
HIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these insertions provide such selective advantage to infected cell clones. Here, we show that in 30/87 (34%) patients under combination antiretroviral therapy, BACH2, and STAT5B are activated by insertions triggering the formation of mRNAs that contain viral sequences fused by splicing to their first protein-coding exon. These chimeric mRNAs, predicted to express full-length proteins, are enriched in T regulatory and T central memory cells, but not in other T lymphocyte subsets or monocytes...
September 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28855027/bach2-represses-the-ap-1-driven-induction-of-interleukin-2-gene-transcription-in-cd4%C3%AF-t-cells
#11
Eunkyeong Jang, Hye Rim Lee, Geon Hee Lee, Ah-Reum Oh, Ji-Young Cha, Kazuhiko Igarashi, Jeehee Youn
The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed CD4+ T cells, Bach2 overexpression counteracted T cell receptor/CD28- or PMA/ionomycin-driven induction of interleukin-2 expression, and silencing of Bach2 had the opposite effect...
September 2017: BMB Reports
https://www.readbyqxmd.com/read/28837395/nightshift-work-chronotype-and-genome-wide-dna-methylation-in-blood
#12
Charleen D Adams, Kristina M Jordahl, Wade Copeland, Dana K Mirick, Xiaoling Song, Cassandra L Sather, Karl Kelsey, Andres Houseman, Scott Davis, Timothy Randolph, Parveen Bhatti
Molecular mechanisms underlying the negative health effects of shift work are poorly understood, which remains a barrier to developing intervention strategies to protect the long-term health of shift workers. We evaluated genome-wide differences in DNA methylation (measured in blood) between 111 actively employed female nightshift and 86 actively employed female dayshift workers from the Seattle metropolitan area. We also explored the effect of chronotype (i.e., measure of preference for activity earlier or later in the day) on DNA methylation among 110 of the female nightshift workers and an additional group of 131 male nightshift workers...
August 24, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28798058/let-s-give-bach2-a-breath-of-fresh-air
#13
Francesco Bertoni
No abstract text is available yet for this article.
August 10, 2017: Blood
https://www.readbyqxmd.com/read/28704388/the-mir-23a-27a-24-2-microrna-cluster-buffers-transcription-and-signaling-pathways-during-hematopoiesis
#14
Jeffrey L Kurkewich, Justin Hansen, Nathan Klopfenstein, Helen Zhang, Christian Wood, Austin Boucher, Joseph Hickman, David E Muench, H Leighton Grimes, Richard Dahl
MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28695611/prediction-of-type-1-diabetes-using-a-genetic-risk-model-in-the-diabetes-autoimmunity-study-in-the-young
#15
Brigitte I Frohnert, Michael Laimighofer, Jan Krumsiek, Fabian J Theis, Christiane Winkler, Jill M Norris, Anette-Gabriele Ziegler, Marian J Rewers, Andrea K Steck
BACKGROUND: Genetic predisposition for type 1 diabetes (T1D) is largely determined by human leukocyte antigen (HLA) genes; however, over 50 other genetic regions confer susceptibility. We evaluated a previously reported 10-factor weighted model derived from the Type 1 Diabetes Genetics Consortium to predict the development of diabetes in the Diabetes Autoimmunity Study in the Young (DAISY) prospective cohort. Performance of the model, derived from individuals with first-degree relatives (FDR) with T1D, was evaluated in DAISY general population (GP) participants as well as FDR subjects...
July 11, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28646072/genetic-and-environmental-interactions-modify-the-risk-of-diabetes-related-autoimmunity-by-6-years-of-age-the-teddy-study
#16
Jeffrey P Krischer, Kristian F Lynch, Åke Lernmark, William A Hagopian, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Anette-G Ziegler, Beena Akolkar
OBJECTIVE: We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes. RESEARCH DESIGN AND METHODS: Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. Single nucleotide polymorphisms (SNPs) came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years. RESULTS: Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children)...
September 2017: Diabetes Care
https://www.readbyqxmd.com/read/28601984/persistent-coxsackievirus-b4-infection-induces-microrna-dysregulation-in-human-pancreatic-cells
#17
Ilka Engelmann, Enagnon K Alidjinou, Antoine Bertin, Johann Bossu, Céline Villenet, Martin Figeac, Famara Sane, Didier Hober
Enterovirus infections are implicated in the development of type 1 diabetes (T1D). MicroRNAs as regulators of gene expression are involved in many physiological and pathological processes. Given that viral infections dysregulate cellular microRNAs, we investigated the impact of persistent coxsackievirus B4 infection on microRNA expression of human pancreatic cells. Next-generation sequencing was used to determine microRNA expression in PANC-1 cells persistently infected (for several weeks) with coxsackievirus B4 and uninfected control cells...
June 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28592433/bifurcated-bach2-control-coordinates-mantle-cell-lymphoma-survival-and-dispersal-during-hypoxia
#18
Han Zhang, Zheng Chen, Roberto N Miranda, L Jeffrey Medeiros, Nami McCarty
BACH2, a B-cell-specific transcription factor, plays a critical role in oxidative stress-mediated drug resistance in mantle cell lymphoma (MCL); however, the biological functions of BACH2 and its regulation of B-cell malignancies in chronic hypoxic microenvironment have not been studied. Here, we found that silencing BACH2 led to not only increased tumor formation and colony formation but also increased tumor dispersal to spleen and bone marrow. Decreased BACH2 levels in patients were also correlated with bone marrow and gastrointestinal dispersal of MCL and blastoid subtypes of MCL...
August 10, 2017: Blood
https://www.readbyqxmd.com/read/28530713/bach2-immunodeficiency-illustrates-an-association-between-super-enhancers-and-haploinsufficiency
#19
Behdad Afzali, Juha Grönholm, Jana Vandrovcova, Charlotte O'Brien, Hong-Wei Sun, Ine Vanderleyden, Fred P Davis, Ahmad Khoder, Yu Zhang, Ahmed N Hegazy, Alejandro V Villarino, Ira W Palmer, Joshua Kaufman, Norman R Watts, Majid Kazemian, Olena Kamenyeva, Julia Keith, Anwar Sayed, Dalia Kasperaviciute, Michael Mueller, Jason D Hughes, Ivan J Fuss, Mohammed F Sadiyah, Kim Montgomery-Recht, Joshua McElwee, Nicholas P Restifo, Warren Strober, Michelle A Linterman, Paul T Wingfield, Holm H Uhlig, Rahul Roychoudhuri, Timothy J Aitman, Peter Kelleher, Michael J Lenardo, John J O'Shea, Nichola Cooper, Arian D J Laurence
The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28487475/mir-130a-3p-inhibits-the-viability-proliferation-invasion-and-cell-cycle-and-promotes-apoptosis-of-nasopharyngeal-carcinoma-cells-by-suppressing-bach2-expression
#20
Xin Chen, Bo Yue, Changming Zhang, Meihao Qi, Jianhua Qiu, Ye Wang, Jun Chen
The aim of the present study was to explore the mechanism through which miR-130a-3p affects the viability, proliferation, migration, and invasion of nasopharyngeal carcinoma (NPC). Tissue samples were collected from the hospital department. NPC cell lines were purchased to conduct the in vitro and in vivo assays. A series of biological assays including MTT, Transwell, and wound healing assays were conducted to investigate the effects of miR-130a-3p and BACH2 on NPC cells. MiR-130a-3p was down-regulated in both NPC tissues and cell lines, whereas BACH2 was up-regulated in both tissues and cell lines...
June 30, 2017: Bioscience Reports
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