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https://www.readbyqxmd.com/read/28514688/the-e-id-protein-axis-specifies-adaptive-lymphoid-cell-identity-and-suppresses-thymic-innate-lymphoid-cell-development
#1
Masaki Miyazaki, Kazuko Miyazaki, Kenian Chen, Yi Jin, Jacob Turner, Amanda J Moore, Rintaro Saito, Kenichi Yoshida, Seishi Ogawa, Hans-Reimer Rodewald, Yin C Lin, Hiroshi Kawamoto, Cornelis Murre
Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28261265/new-insights-into-transcriptional-and-leukemogenic-mechanisms-of-aml1-eto-and-e2a-fusion-proteins
#2
Jian Li, Chun Guo, Nickolas Steinauer, Jinsong Zhang
BACKGROUND: Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins...
August 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28183509/assessment-of-myocardial-microstructural-dynamics-by-in%C3%A2-vivo-diffusion-tensor-cardiac-magnetic-resonance
#3
Sonia Nielles-Vallespin, Zohya Khalique, Pedro F Ferreira, Ranil de Silva, Andrew D Scott, Philip Kilner, Laura-Ann McGill, Archontis Giannakidis, Peter D Gatehouse, Daniel Ennis, Eric Aliotta, Majid Al-Khalil, Peter Kellman, Dumitru Mazilu, Robert S Balaban, David N Firmin, Andrew E Arai, Dudley J Pennell
BACKGROUND: Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. OBJECTIVES: This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM...
February 14, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28107608/the-increased-expression-of-tcf3-is-correlated-with-poor-prognosis-in-chinese-patients-with-nasopharyngeal-carcinoma
#4
X Shen, J Yuan, M Zhang, W Li, B Ni, Y Wu, L Jiang, W Fan, Z Tian
OBJECTIVES: Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote cancer growth and progression. B-cell-specific transcription factor 3 (TCF3/E2A) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family that is central to regulating epidermal and embryonic stem cell identity. It has been reported that TCF3 was connected with the development and progression of a number of human cancers...
January 20, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28056036/the-9aatad-is-exclusive-activation-domain-in-gal4
#5
Martin Piskacek, Marek Havelka, Martina Rezacova, Andrea Knight
The Gal4 protein is a well-known prototypic acidic activator that has multiple activation domains. We have previously identified a new activation domain called the nine amino acid transactivation domain (9aaTAD) in Gal4 protein. The family of the 9aaTAD activators currently comprises over 40 members including p53, MLL, E2A and other members of the Gal4 family; Oaf1, Pip2, Pdr1 and Pdr3. In this study, we revised function of all reported Gal4 activation domains. Surprisingly, we found that beside of the activation domain 9aaTAD none of the previously reported activation domains had considerable transactivation potential and were not involved in the activation of transcription...
2017: PloS One
https://www.readbyqxmd.com/read/28055272/rs12603332-is-associated-with-male-asthma-patients-specifically-in-urban-areas-of-lahore-pakistan
#6
Muhammad Farooq Sabar, Mariam Shahid, Iqbal Bano, Muhammad Usman Ghani, Muhammad Akram, Farheena Iqbal, Samra Kousar, Zafar Iqbal, Saba Altaf, Tayyab Husnain
OBJECTIVE: rs12603332, an important regulatory site variant, is known to alter the regulatory motif E2A that is involved in maturation of B-lymphocytes. The study was designed to check whether different environmental exposures alter its risk allele association with asthma or not. METHODS: 200 Physician diagnosed asthma patients and 108 healthy individuals were enrolled from hospitals of Lahore. After quantitation of DNA extracted from their peripheral blood samples, amplification of genomic region with rs12603332 was performed followed by single base extension...
January 5, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/27939672/dynamic-changes-in-chromatin-accessibility-occur-in-cd8-t-cells-responding-to-viral-infection
#7
James P Scott-Browne, Isaac F López-Moyado, Sara Trifari, Victor Wong, Lukas Chavez, Anjana Rao, Renata M Pereira
In response to acute infection, naive CD8(+) T cells expand, differentiate into effector cells, and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8(+) T cells acquire an "exhausted" phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8(+) T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq techniques. Acquisition of effector, memory, or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27929395/deficiency-in-the-ubiquitin-conjugating-enzyme-ube2a-in-alzheimer-s-disease-ad-is-linked-to-deficits-in-a-natural-circular-mirna-7-sponge-circrna-cirs-7
#8
Yuhai Zhao, Peter N Alexandrov, Vivian Jaber, Walter J Lukiw
Our understanding of the highly specialized functions for small non-coding single-stranded RNA (ssRNA) in the transcriptome of the human central nervous system (CNS) continues to evolve. Circular RNAs (circRNAs), a recently discovered class of ssRNA enriched in the brain and retina, are extremely stable and intrinsically resilient to degradation by exonuclease. Conventional methods of ssRNA, microRNA (miRNA), or messenger RNA (mRNA) detection and quantitation requiring free ribonucleotide ends may have considerably underestimated the quantity and significance of CNS circRNA in the CNS...
December 5, 2016: Genes
https://www.readbyqxmd.com/read/27920559/e2a-pbx1-exhibited-a-promising-prognosis-in-pediatric-acute-lymphoblastic-leukemia-treated-with-the-cclg-all2008-protocol
#9
Yixin Hu, Hailong He, Jun Lu, Yi Wang, Peifang Xiao, Jianqin Li, Jie Li, Yina Sun, Hui Lv, Junjie Fan, Yanhua Yao, Yihuan Chai, Shaoyan Hu
OBJECTIVE: The objective of this study was to observe the prognosis of pediatric patients with E2A-PBX1-positive acute lymphoblastic leukemia (ALL) from the treatment with the CCLG-ALL2008 protocol. DESIGN AND METHODS: Three hundred and forty-nine Chinese pediatric patients with pre-B-cell ALL were enrolled in this study from December 2008 to September 2013. Of these, 20 patients with E2A-PBX1 expression and 223 without the gene expression were stratified into two cohorts...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27894958/poly-adp-ribose-polymerase-inhibitors-selectively-induce-cytotoxicity-in-tcf3-hlf-positive-leukemic-cells
#10
Jinhua Piao, Shiori Takai, Takahiro Kamiya, Takeshi Inukai, Kanji Sugita, Kazuma Ohyashiki, Domenico Delia, Mitsuko Masutani, Shuki Mizutani, Masatoshi Takagi
Poly (ADP-ribose) polymerase (PARP) is an indispensable component of the DNA repair machinery. PARP inhibitors are used as cutting-edge treatments for patients with homologous recombination repair (HRR)-defective breast cancers harboring mutations in BRCA1 or BRCA2. Other tumors defective in HRR, including some hematological malignancies, are predicted to be good candidates for treatment with PARP inhibitors. Screening of leukemia-derived cell lines revealed that lymphoid lineage-derived leukemia cell lines, except for those derived from mature B cells and KMT2A (MLL)-rearranged B-cell precursors, were relatively sensitive to PARP inhibitors...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27869616/tet2-and-tet3-cooperate-with-b-lineage-transcription-factors-to-regulate-dna-modification-and-chromatin-accessibility
#11
Chan-Wang Lio, Jiayuan Zhang, Edahí González-Avalos, Patrick G Hogan, Xing Chang, Anjana Rao
Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igκ locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igκ 3' and distal enhancers that was mimicked by depletion of E2A or PU...
November 21, 2016: ELife
https://www.readbyqxmd.com/read/27855054/-pcr-detection-of-relevant-translocations-in-pediatric-acute-lymphoblastic-leukemia
#12
Francisco Xavier Guerra-Castillo, María Teresa Ramos-Cervantes, Cecilia Rosel-Pech, Elva Jiménez-Hernández, Vilma Carolina Bekker-Méndez
BACKGROUND: In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia. METHODS: 91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza"...
2016: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/27835756/regulated-localization-of-an-aid-complex-with-e2a-pax5-and-irf4-at-the-igh-locus
#13
Jannek Hauser, Christine Grundström, Ramesh Kumar, Thomas Grundström
Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates somatic hypermutation (SH) and class switch recombination (CSR) by deaminating cytosine to uracil. The targeting of AID and therefore SH and CSR to Ig genes is a central process of the immune system, but the trans-acting factors mediating the specific targeting have remained elusive. Here we show that defective calmodulin inhibition of the transcription factor E2A after activation of the B cell receptor (BCR) leads to reduced BCR, IL4 plus CD40 ligand stimulated CSR to IgE and instead CSR to other Ig classes...
December 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27784356/-clinicopathologic-characteristics-and-outcome-of-isolated-ovarian-relapse-in-adolescent-with-acute-lymphoblastic-leukemia
#14
Ya-Ping Yu, Ping Song, Jian-Gang Mei, Zhi-Ming An, Xiao-Gang Zhou, Feng Li, Li-Ping Wang, Yu-Mei Tang, Yong-Ping Zhai
OBJECTIVE: To investigate the clinicopathologic characteristics,diagnosis and treatment of isolated ovarian relapse of acute lymphoblastic leukemia(ALL). METHODS: A 16-year-old girl presented with complaints of bone and joint pain. The peripheral blood and bone marrow(BM) smears showed 32% and 72% blasts, respectively, which were myeloperoxidase-negative. The blasts were positive for HLA-DR, TdT, CD10, CD19, CD22 and cCD79a and negative for CD34, CD5, CD7, CD13, CD33, CD56 and MPO detected by flow cytometry...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27758892/e2a-pbx1-remodels-oncogenic-signaling-networks-in-b-cell-precursor-acute-lymphoid-leukemia
#15
Jesús Duque-Afonso, Chiou-Hong Lin, Kyuho Han, Michael C Wei, Jue Feng, Jason H Kurzer, Corina Schneidawind, Stephen Hon-Kit Wong, Michael C Bassik, Michael L Cleary
There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5%-7% of pediatric and 50% of pre-B-cell receptor (preBCR(+)) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL, which results in hyperactivation of the key oncogenic effector enzyme PLCγ2...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27506125/attenuation-of-thrombosis-and-bacterial-infection-using-dual-function-nitric-oxide-releasing-central-venous-catheters-in-a-9day-rabbit-model
#16
Elizabeth J Brisbois, Terry C Major, Marcus J Goudie, Mark E Meyerhoff, Robert H Bartlett, Hitesh Handa
UNLABELLED: Two major problems with implanted catheters are clotting and infection. Nitric oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet adhesion/activation and an antimicrobial agent, and NO-releasing polymers are expected to have similar properties. Here, NO-releasing central venous catheters (CVCs) are fabricated using Elast-eon™ E2As polymer with both diazeniumdiolated dibutylhexanediamine (DBHD/NONO) and poly(lactic-co-glycolic acid) (PLGA) additives, where the NO release can be modulated and optimized via the hydrolysis rate of the PLGA...
October 15, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27501245/follicular-cxcr5-expressing-cd8-t-cells-curtail-chronic-viral-infection
#17
Ran He, Shiyue Hou, Cheng Liu, Anli Zhang, Qiang Bai, Miao Han, Yu Yang, Gang Wei, Ting Shen, Xinxin Yang, Lifan Xu, Xiangyu Chen, Yaxing Hao, Pengcheng Wang, Chuhong Zhu, Juanjuan Ou, Houjie Liang, Ting Ni, Xiaoyan Zhang, Xinyuan Zhou, Kai Deng, Yaokai Chen, Yadong Luo, Jianqing Xu, Hai Qi, Yuzhang Wu, Lilin Ye
During chronic viral infection, virus-specific CD8(+) T cells become exhausted, exhibit poor effector function and lose memory potential. However, exhausted CD8(+) T cells can still contain viral replication in chronic infections, although the mechanism of this containment is largely unknown. Here we show that a subset of exhausted CD8(+) T cells expressing the chemokine receptor CXCR5 has a critical role in the control of viral replication in mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV)...
August 2, 2016: Nature
https://www.readbyqxmd.com/read/27493297/characterization-of-an-s-nitroso-n-acetylpenicillamine-based-nitric-oxide-releasing-polymer-from-a-translational-perspective
#18
Marcus J Goudie, Elizabeth J Brisbois, Jitendra Pant, Alex Thompson, Joseph A Potkay, Hitesh Handa
Due to the role of nitric oxide (NO) in regulating a variety of biological functions in humans, numerous studies on different NO releasing/generating materials have been published over the past two decades. Although NO has been demonstrated to be a strong antimicrobial and potent antithrombotic agent, NO-releasing (NOrel) polymers have not reached the clinical setting. While increasing the concentration of the NO donor in the polymer is a common method to prolong the NO-release, this should not be at the cost of mechanical strength or biocompatibility of the original material...
2016: International Journal of Polymeric Materials
https://www.readbyqxmd.com/read/27487330/cxcr5-follicular-cytotoxic-t-cells-control-viral-infection-in-b-cell-follicles
#19
Yew Ann Leong, Yaping Chen, Hong Sheng Ong, Di Wu, Kevin Man, Claire Deleage, Martina Minnich, Benjamin J Meckiff, Yunbo Wei, Zhaohua Hou, Dimitra Zotos, Kevin A Fenix, Anurag Atnerkar, Simon Preston, Jeffrey G Chipman, Greg J Beilman, Cody C Allison, Lei Sun, Peng Wang, Jiawei Xu, Jesse G Toe, Hao K Lu, Yong Tao, Umaimainthan Palendira, Alexander L Dent, Alan L Landay, Marc Pellegrini, Iain Comerford, Shaun R McColl, Timothy W Schacker, Heather M Long, Jacob D Estes, Meinrad Busslinger, Gabrielle T Belz, Sharon R Lewin, Axel Kallies, Di Yu
During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3...
October 2016: Nature Immunology
https://www.readbyqxmd.com/read/27467586/threshold-levels-of-gfi1-maintain-e2a-activity-for-b-cell-commitment-via-repression-of-id1
#20
Jennifer Fraszczak, Anne Helness, Riyan Chen, Charles Vadnais, François Robert, Cyrus Khandanpour, Tarik Möröy
A regulatory circuit that controls myeloid versus B lymphoid cell fate in hematopoietic progenitors has been proposed, in which a network of the transcription factors Egr1/2, Nab, Gfi1 and PU.1 forms the core element. Here we show that a direct link between Gfi1, the transcription factor E2A and its inhibitor Id1 is a critical element of this regulatory circuit. Our data suggest that a certain threshold of Gfi1 is required to gauge E2A activity by adjusting levels of Id1 in multipotent progenitors, which are the first bipotential myeloid/lymphoid-restricted progeny of hematopoietic stem cells...
2016: PloS One
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