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Hyun-Jin Kim, Jin-Young Min, Kyoung-Bok Min
OBJECTIVES: Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels...
September 2016: Journal of Preventive Medicine and Public Health, Yebang Ŭihakhoe Chi
Yeguang Hu, Zhihong Zhang, Mariko Kashiwagi, Toshimi Yoshida, Ila Joshi, Nilamani Jena, Rajesh Somasundaram, Akinola Olumide Emmanuel, Mikael Sigvardsson, Julien Fitamant, Nabeel El-Bardeesy, Fotini Gounari, Richard A Van Etten, Katia Georgopoulos
IKAROS is required for the differentiation of highly proliferative pre-B-cell precursors, and loss of IKAROS function indicates poor prognosis in precursor B-cell acute lymphoblastic leukemia (B-ALL). Here we show that IKAROS regulates this developmental stage by positive and negative regulation of superenhancers with distinct lineage affiliations. IKAROS defines superenhancers at pre-B-cell differentiation genes together with B-cell master regulators such as PAX5, EBF1, and IRF4 but is required for a highly permissive chromatin environment, a function that cannot be compensated for by the other transcription factors...
September 1, 2016: Genes & Development
Ruth Morona, José Luis Eduardo Ferran, Luis Puelles, Agustín González
Our previous analysis of progenitor domains in the pretectum of Xenopus revealed three molecularly distinct anteroposterior subdivisions identified as precommissural (PcP), juxtacommissural (JcP), and commissural (CoP) histogenetic domains (Morona et al. [2011] J Comp Neurol 519:1024-1050). Here we analyzed at later developmental stages the nuclei derived from these areas, attending to their gene expression patterns and histogenesis. Transcription-factor gene markers were used to selectively map derivatives of each domain: Pax7 and Pax6 (CoP); Foxp1 and Six3 (JcP); and Xiro1, VGlut2, Ebf1, and Ebf3 (PcP)...
August 19, 2016: Journal of Comparative Neurology
Elad Jacoby, Sang M Nguyen, Thomas J Fountaine, Kathryn Welp, Berkley Gryder, Haiying Qin, Yinmeng Yang, Christopher D Chien, Alix E Seif, Haiyan Lei, Young K Song, Javed Khan, Daniel W Lee, Crystal L Mackall, Rebecca A Gardner, Michael C Jensen, Jack F Shern, Terry J Fry
Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy...
2016: Nature Communications
Anton M Schwartz, Lidia V Putlyaeva, Milica Covich, Anna V Klepikova, Kseniya A Akulich, Ilya E Vorontsov, Kirill V Korneev, Sergey E Dmitriev, Oleg L Polanovsky, Svetlana P Sidorenko, Ivan V Kulakovskiy, Dmitry V Kuprash
Signaling lymphocytic activation molecule family member 1 (SLAMF1)/CD150 is a co-stimulatory receptor expressed on a variety of hematopoietic cells, in particular on mature lymphocytes activated by specific antigen, costimulation and cytokines. Changes in CD150 expression level have been reported in association with autoimmunity and with B-cell chronic lymphocytic leukemia. We characterized the core promoter for SLAMF1 gene in human B-cell lines and explored binding sites for a number of transcription factors involved in B cell differentiation and activation...
October 2016: Biochimica et Biophysica Acta
Sanjeev Kumar Gupta, Sameer Bakhshi, Lalit Kumar, Vineet Kumar Kamal, Rajive Kumar
The genes related to B-cell development are frequently altered in B-cell acute lymphoblastic leukemia (B-ALL). One hundred sixty-two newly diagnosed B-ALL cases, median age 8.5 years (2 months-67 years), were prospectively analyzed for copy number alterations (CNAs) in CDKN2A/B, IKZF1, PAX5, RB1, ETV6, BTG1, EBF1, and pseudoautosomal region genes (CRLF2, CSF2RA, IL3RA) using multiplex ligation-dependent probe amplification. The CNAs were detected in 114 (70.4%) cases; most commonly affected genes being CDKN2A/B-55 (34%), PAX5-51 (31...
June 24, 2016: Leukemia & Lymphoma
J J Zheng, S N Chen, A N Sun, D P Wu
No abstract text is available yet for this article.
May 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Hanfeng Guan, Linka Xie, Thomas Wirth, Alexey Ushmorov
Although Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) derived from germinal or post germinal B cells, they have lost the B cell phenotype in the process of lymphomagenesis. The phenomenon can be at least partially explained by repression of B-cell-specific transcription factors including TCF3, early B-cell factor 1 (EBF1), SPI1/PU.1, and FOXO1, which are down-regulated by genetic and epigenetic mechanisms. The unique phenotype has been suspected to be advantageous for survival of HRS cells...
May 6, 2016: Oncotarget
Irene M Shui, Chao-Jen Wong, Shanshan Zhao, Suzanne Kolb, Ericka M Ebot, Milan S Geybels, Rohina Rubicz, Jonathan L Wright, Daniel W Lin, Brandy Klotzle, Marina Bibikova, Jian-Bing Fan, Elaine A Ostrander, Ziding Feng, Janet L Stanford
BACKGROUND: DNA methylation has been hypothesized as a mechanism for explaining the association between smoking and adverse prostate cancer (PCa) outcomes. This study was aimed at assessing whether smoking is associated with prostate tumor DNA methylation and whether these alterations may explain in part the association of smoking with PCa recurrence and mortality. METHODS: A total of 523 men had radical prostatectomy as their primary treatment, detailed smoking history data, long-term follow-up for PCa outcomes, and tumor tissue profiled for DNA methylation...
July 15, 2016: Cancer
Sören Boller, Senthilkumar Ramamoorthy, Duygu Akbas, Robert Nechanitzky, Lukas Burger, Rabih Murr, Dirk Schübeler, Rudolf Grosschedl
Lymphopoiesis requires the activation of lineage-specific genes embedded in naive, inaccessible chromatin or in primed, accessible chromatin. The mechanisms responsible for de novo gain of chromatin accessibility, known as "pioneer" function, remain poorly defined. Here, we showed that the EBF1 C-terminal domain (CTD) is required for the regulation of a specific gene set involved in B cell fate decision and differentiation, independently of activation and repression functions. Using genome-wide analysis of DNaseI hypersensitivity and DNA methylation in multipotent Ebf1(-/-) progenitors and derivative EBF1wt- or EBF1ΔC-expressing cells, we found that the CTD promoted chromatin accessibility and DNA demethylation in previously naive chromatin...
March 15, 2016: Immunity
Ranjan Sen
In this issue of Immunity, Boller et al. (2016) show that a C-terminal domain of EBF1 is required for chromatin binding and induction of DNase I hypersensitive sites. These properties mark EBF1 as a pioneer factor in B cell development and demonstrate a role for non-DNA binding domains in this process.
March 15, 2016: Immunity
Yao Zou, Li Zhang, Xiaoming Liu, Ye Guo, Wenyu Yang, Jiayuan Zhang, Fang Liu, Tianfeng Liu, Shuchun Wang, Xiaojuan Chen, Min Ruan, Benquan Qi, Lixian Chang, Yumei Chen, Xiaofan Zhu
OBJECTIVE: To evaluate the copy number variations (CNVs) in pediatric ETV6/RUNX1 gene positive acute lymphoblastic leukemia(ALL) and its correlation with clinical features and prognosis. METHOD: Totally 141 children (<14 years of age) with newly diagnosed ETV6/RUNX1 positive ALL in Institute of Hematology and Blood Diseases Hospital, were included from January 2006 to November 2012. The CNVs were analyzed by multiplex ligation-dependent probe amplification (MLPA)...
March 2016: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Nicolas Duployez, Olivier Nibourel, Benoît Ducourneau, Nathalie Grardel, Thomas Boyer, Claire Bories, Stéphane Darre, Valérie Coiteux, Céline Berthon, Claude Preudhomme, Catherine Roche-Lestienne
We report a case of myeloproliferative neoplasm (MPN) with an atypical t(9;22;15)(p24;q11;q21) translocation, leading to a BCR-JAK2 fusion, associated with a trisomy of chromosome 8 in clonal evolution at karyotype. Patient's evolution was marked by an aggressive clinical course with rapid progression to blast phase within the first year after diagnosis. Examination of matched chronic phase and blast crisis samples by SNP-array karyotyping identified secondary acquired cryptic genetic events at the time of lymphoblastic transformation, including biallelic IKZF1 alteration and EBF1 and CDKN2A/B codeletions...
October 2016: European Journal of Haematology
Sang In Lee, Hyun June Jang, Mi-hyang Jeon, Mi Ock Lee, Jeom Sun Kim, Ik-Soo Jeon, Sung June Byun
Cathelicidins form a family of vertebrate-specific immune molecules with an evolutionarily conserved gene structure. We analyzed the expression patterns of cathelicidin genes (CAMP, CATH3, and CATHB1) in chicken bone marrow cells (BMCs) and chicken embryonic fibroblasts (CEFs). We found that CAMP and CATHB1 were significantly up-regulated in BMCs, whereas the expression of CATH3 did not differ significantly between BMCs and CEFs. To study the mechanism underlying the up-regulation of cathelicidin genes in BMCs, we predicted the transcription factors (TFs) that bind to the 5'-flanking regions of cathelicidin genes...
April 2016: Poultry Science
Nikki R Kong, Matthew Davis, Li Chai, Astar Winoto, Robert Tjian
Hematopoietic stem cells are capable of self-renewal or differentiation along three main lineages: myeloid, erythroid, and lymphoid. One of the earliest lineage decisions for blood progenitor cells is whether to adopt the lymphoid or myeloid fate. Previous work had shown that myocyte enhancer factor 2C (MEF2C) is indispensable for the lymphoid fate decision, yet the specific mechanism of action remained unclear. Here, we have identified early B cell factor-1 (EBF1) as a co-regulator of gene expression with MEF2C...
February 2016: PLoS Genetics
Claire Schwab, Sarra L Ryan, Lucy Chilton, Alannah Elliott, James Murray, Stacey Richardson, Christopher Wragg, John Moppett, Michelle Cummins, Oliver Tunstall, Catriona A Parker, Vaskar Saha, Nicholas Goulden, Ajay Vora, Anthony V Moorman, Christine J Harrison
The EBF1-PDGFRB gene fusion accounts for <1% of B-cell precursor acute lymphoblastic leukemia (ALL) cases and occurs within the Philadelphia-like ALL subtype. We report 15 EBF1-PDGFRB-positive patients from childhood ALL treatment trials (ALL 97/99, UKALL 2003, UKALL 2011) in the United Kingdom. The fusion arose from interstitial deletion of 5q33 (n = 11), balanced rearrangement (n = 2), or complex rearrangement (n = 2). There was a predominance of females (n = 11), median age of 12 years, and median white blood cell count of 48...
May 5, 2016: Blood
Karin von Wnuck Lipinski, Katherine Sattler, Susann Peters, Sarah Weske, Petra Keul, Hannes Klump, Gerd Heusch, Joachim R Göthert, Bodo Levkau
The hepatocyte NF (HNF) family of transcription factors regulates the complex gene networks involved in lipid, carbohydrate, and protein metabolism. In humans, HNF1A mutations cause maturity onset of diabetes in the young type 3, whereas murine HNF6 participates in fetal liver B lymphopoiesis. In this study, we have identified a crucial role for the prototypical member of the family HNF1A in adult bone marrow B lymphopoiesis. HNF1A(-/-) mice exhibited a clear reduction in total blood and splenic B cells and a further pronounced one in transitional B cells...
February 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Li Zhang, Xiao-Ming Liu, Ye Guo, Wen-Yu Yang, Jia-Yuan Zhang, Fang Liu, Tian-Feng Liu, Shu-Chun Wang, Xiao-Juan Chen, Min Ruan, Ben-Quan Qi, Li-Xian Chang, Yao Zou, Yu-Mei Chen, Xiao-Fan Zhu
OBJECTIVE: To investigate the application of multiplex ligation-dependent probe amplification (MLPA) in the detection of copy number variations (CNVs) in pediatric ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL), to compare this method with conventional karyotype analysis and fluorescence in situ hybridization (FISH), and to evaluate the value of MLPA. METHODS: The clinical data of 95 children with ETV6/RUNX1-positive ALL who were treated from January 2006 to November 2012 were analyzed retrospectively, including clinical features, results of karyotype analysis, and results of FISH...
January 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Juan R Acosta, Iyadh Douagi, Daniel P Andersson, Jesper Bäckdahl, Mikael Rydén, Peter Arner, Jurga Laurencikiene
AIMS/HYPOTHESIS: We aimed to elucidate the impact of fat cell size and inflammatory status of adipose tissue on the development of type 2 diabetes in non-obese individuals. METHODS: We characterised subcutaneous abdominal adipose tissue by examining stromal cell populations by 13 colour flow cytometry, measuring expression of adipogenesis genes in the progenitor cell fraction and determining lipolysis and adipose secretion of inflammatory proteins in 14 non-obese men with type 2 diabetes and 13 healthy controls matched for age, sex, body weight and total fat mass...
March 2016: Diabetologia
Monika Rataj-Baniowska, Anna Niewiadomska-Cimicka, Marie Paschaki, Monika Szyszka-Niagolov, Laura Carramolino, Miguel Torres, Pascal Dollé, Wojciech Krężel
The mammalian striatum controls sensorimotor and psychoaffective functions through coordinated activities of its two striatonigral and striatopallidal output pathways. Here we show that retinoic acid receptor β (RARβ) controls development of a subpopulation of GABAergic, Gad65-positive striatonigral projection neurons. In Rarb(-/-) knock-out mice, concomitant reduction of Gad65, dopamine receptor D1 (Drd1), and substance P expression at different phases of prenatal development was associated with reduced number of Drd1-positive cells at birth, in contrast to normal numbers of striatopallidal projection neurons expressing dopamine receptor D2...
October 28, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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