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Sumedha Roy, Amanda J Moore, Cassandra Love, Anupama Reddy, Deepthi Rajagopalan, Sandeep S Dave, Leping Li, Cornelis Murre, Yuan Zhuang
A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion of innate-like αβ T cells known as invariant natural killer T (iNKT) cells. However, it remains to be determined whether Id proteins differentially regulate these distinct lineage choices in early stages of T cell development. In this manuscript, we report that in Id-deficient mice, uninhibited activity of the E protein family member E2A mediates activation of genes that support iNKT cell development and function...
2018: Frontiers in Immunology
Minu Singh, Prateek Bhatia, Amita Trehan, Neelam Varma, Manupdesh Singh Sachdeva, Deepak Bansal, Richa Jain, Shano Naseem
Copy number abnormalities (CNAs) and recurrent fusion transcripts are important genetic events which define and prognosticate B-Cell Acute Lymphoblastic Leukemia (B-ALL). We evaluated CNAs and fusion transcripts in 67 pediatric B-ALL cases and correlated the data with standard risk factors and early treatment outcome parameters. Common fusion transcripts ETV6-RUNX1, E2A-PBX, BCR-ABL1 and MLL-AF4 were examined by RT-PCR and noted in 15%, 15%, 13% and 1.4% of all cases respectively. CNAs in IKZF1, PAX5, EBF1, BTG1, RB1, CDKN2A/B and genes from PAR1 region viz...
February 2, 2018: Leukemia Research
Wenshuai Yu, Shengjie Zhao, Yongcui Wang, Brian Nlong Zhao, Weiling Zhao, Xiaobo Zhou
The rapid accumulation of cancer-related data owing to high-throughput technologies has provided unprecedented choices to understand the progression of cancer and discover functional networks in multiple cancers. Establishment of co-expression networks will help us to discover the systemic properties of carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we proposed a computational workflow to identify differentially co-expressed gene modules across 8 cancer types by using combined gene differential expression analysis methods and a higher-order generalized singular value decomposition...
December 22, 2017: Oncotarget
Andrew D Scott, Sonia Nielles-Vallespin, Pedro F Ferreira, Zohya Khalique, Peter D Gatehouse, Philip Kilner, Dudley J Pennell, David N Firmin
BACKGROUND: Stimulated-echo (STEAM) and, more recently, motion-compensated spin-echo (M2-SE) techniques have been used for in-vivo diffusion tensor cardiovascular magnetic resonance (DT-CMR) assessment of cardiac microstructure. The two techniques differ in the length scales of diffusion interrogated, their signal-to-noise ratio efficiency and sensitivity to both motion and strain. Previous comparisons of the techniques have used high performance gradients at 1.5 T in a single cardiac phase...
January 3, 2018: Journal of Cardiovascular Magnetic Resonance
I Gordiienko, L Shlapatska, V M Kholodniuk, L Kovalevska, T S Ivanivskaya, S P Sidorenko
BACKGROUND: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression...
December 2017: Experimental Oncology
Víctor Mayoral-Varo, Annarica Calcabrini, María Pilar Sánchez-Bailón, Jorge Martín-Pérez
miR205 has a dual activity, as tumor suppressor and as oncogene. Here we analyzed the impact of miR205 ectopic expression in the initial tumorigenic processes of SUM159PT, a triple negative breast cancer cell line with low endogenous levels of miR205. In SUM159PT, miR205 inhibited expression of its targets VEGFA, ErbB3, Zeb1, Fyn and Lyn A/B; it reduced cell proliferation, and Myc/cyclin D1 levels, while increased p27kip1 expression. miR205 abolished anchorage-independent growth, inhibited migration and invasion, Src-kinases/Stat3 axis activation, and levels of secreted MMP9...
2017: PloS One
Claudia Röwer, Christian George, Toralf Reimer, Bernd Stengel, Anngret Radtke, Bernd Gerber, Michael O Glocker
BACKGROUND: Lymph node metastasis status is a prognostic factor for further lymph node involvement and for patient survival in breast cancer patients. Frozen section analysis of lymph nodes is a reliable method for detection of macro-metastases. However, this method is far less effective in detecting micro-metastases, requesting improved diagnostic procedures. METHODS: We investigated expression and truncation of ezrin in (i) sentinel lymph node metastases, (ii) unaffected axillary lymph nodes, (iii) primary breast tumors, and (iv) healthy glandular breast tissues using 2D gel electrophoresis, SDS-PAGE, and mass spectrometry in addition to Western blotting...
November 10, 2017: Translational Oncology
Rohan Ameratunga, Wikke Koopmans, See-Tarn Woon, Euphemia Leung, Klaus Lehnert, Charlotte A Slade, Jessica C Tempany, Anselm Enders, Richard Steele, Peter Browett, Philip D Hodgkin, Vanessa L Bryant
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID...
October 2017: Clinical & Translational Immunology
Huan Zhou, Le Wang, Qing Xu, Qingquan Liu, Hui Liu, Wenhui Qiu, Tingyang Hu, Yongman Lv, Qian Zhang
Anti‑glomerular basement membrane glomerulonephritis (anti‑GBM GN) is an autoimmune disease that leads to severe and rapidly progressive renal injury. Inhibition of DNA‑binding factor 3 (ID3) serves a key role in autoimmune diseases, such as asthma and Sjögren's syndrome, and in experimental allergic encephalitis models. However, the role of ID3 in the progression of anti‑GBM GN remains unknown. In the present study, ID3 mRNA expression increased between 3‑ and 20‑fold in the renal tissues of anti‑GBM GN mice compared with the Control group, with a peak at day 14 post‑induction...
December 2017: Molecular Medicine Reports
Sabrina Pfurr, Yu-Hsuan Chu, Christian Bohrer, Franziska Greulich, Robert Beattie, Könül Mammadzada, Miriam Hils, Sebastian J Arnold, Verdon Taylor, Kristina Schachtrup, N Henriette Uhlenhaut, Christian Schachtrup
During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14...
November 1, 2017: Development
Cristina Scavone, Liberata Sportiello, Maria G Sullo, Carmen Ferrajolo, Rosanna Ruggiero, Maurizio Sessa, Pasquale M Berrino, Gabriella di Mauro, Liberato Berrino, Francesco Rossi, Concetta Rafaniello, Annalisa Capuano
Objectives: To investigate the occurrence of adverse events (AEs) in naïve patients receiving biotech drugs. Design: A prospective observational study. Setting: Onco-hematology, Hepato-gastroenterology, Rheumatology, Dermatology, and Neurology Units in Campania Region (Italy). Participants: 775 patients (53.81% female) with mean age 56.0 (SD 15.2). The mean follow-up/patient was 3.48 (95% confidence interval 3.13-3.84). Main outcome measures: We collected all AEs associated to biotech drugs, including serious infections and malignancies...
2017: Frontiers in Pharmacology
Zachary A Yochum, Jessica Cades, Lucia Mazzacurati, Neil M Neumann, Susheel K Khetarpal, Suman Chatterjee, Hailun Wang, Myriam A Attar, Eric H-B Huang, Sarah N Chatley, Katriana Nugent, Ashwin Somasundaram, Johnathan A Engh, Andrew J Ewald, Yoon-Jae Cho, Charles M Rudin, Phuoc T Tran, Timothy F Burns
TWIST1, an epithelial-mesenchymal transition (EMT) transcription factor, is critical for oncogene-driven non-small cell lung cancer (NSCLC) tumorigenesis. Given the potential of TWIST1 as a therapeutic target, a chemical-bioinformatic approach using connectivity mapping (CMAP) analysis was used to identify TWIST1 inhibitors. Characterization of the top ranked candidates from the unbiased screen revealed that harmine, a harmala alkaloid, inhibited multiple TWIST1 functions, including single-cell dissemination, suppression of normal branching in 3D epithelial culture, and proliferation of oncogene driver-defined NSCLC cells...
December 2017: Molecular Cancer Research: MCR
Christian T Stoeck, Constantin von Deuster, Thea Fleischmann, Miriam Lipiski, Nikola Cesarovic, Sebastian Kozerke
PURPOSE: To directly compare in vivo versus postmortem second-order motion-compensated spin-echo diffusion tensor imaging of the porcine heart. METHODS: Second-order motion-compensated spin-echo cardiac diffusion tensor imaging was performed during systolic contraction in vivo and repeated upon cardiac arrest by bariumchloride without repositioning of the study animal or replaning of imaging slices. In vivo and postmortem reproducibility was assessed by repeat measurements...
August 22, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Camille Malouf, Katrin Ottersbach
B cell leukaemia is one of the most frequent malignancies in the paediatric population, but also affects a significant proportion of adults in developed countries. The majority of infant and paediatric cases initiate the process of leukaemogenesis during foetal development (in utero) through the formation of a chromosomal translocation or the acquisition/deletion of genetic material (hyperdiploidy or hypodiploidy, respectively). This first genetic insult is the major determinant for the prognosis and therapeutic outcome of patients...
August 17, 2017: Cellular and Molecular Life Sciences: CMLS
Gabriella L Flacke, Franz Schwarzenberger, Linda M Penfold, Susan L Walker, Graeme B Martin, Robert Peter Millar, Monique C J Paris
The pygmy hippopotamus (Choeropsis liberiensis) is endangered in the wild and very little is known about its reproductive biology. In zoological facilities, this species experiences a number of reproductive issues that complicate breeding management, including a high rate of stillbirths and failure of many pairs to reproduce. We conducted a comprehensive study to evaluate reproductive cycles and pregnancy in this species using enzyme immunoassays (EIAs) for fecal hormone metabolite analysis. Fresh fecal samples were collected twice weekly for a one to three year period from 36 female pygmy hippos housed at 24 zoological institutions...
July 19, 2017: Theriogenology
Pedro F Ferreira, Sonia Nielles-Vallespin, Andrew D Scott, Ranil de Silva, Philip J Kilner, Daniel B Ennis, Daniel A Auger, Jonathan D Suever, Xiaodong Zhong, Bruce S Spottiswoode, Dudley J Pennell, Andrew E Arai, David N Firmin
PURPOSE: To evaluate the importance of strain-correcting stimulated echo acquisition mode echo-planar imaging cardiac diffusion tensor imaging. METHODS: Healthy pigs (n = 11) were successfully scanned with a 3D cine displacement-encoded imaging with stimulated echoes and a monopolar-stimulated echo-planar imaging diffusion tensor imaging sequence at 3 T during diastasis, peak systole, and strain sweet spots in a midventricular short-axis slice. The same diffusion tensor imaging sequence was repeated ex vivo after arresting the hearts in either a relaxed (KCl-induced) or contracted (BaCl2 -induced) state...
July 21, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Maiko Hirai, Hiroshi Yagasaki, Junya Fujimura, Masami Inoue, Katsuyoshi Shimozawa, Hirotsugu Okuma, Motoaki Chin, Shori Takahashi
No abstract text is available yet for this article.
July 21, 2017: Leukemia & Lymphoma
E A Shestakova, M Boutin, S Bourassa, E Bonneil, J J Bijl
Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox (HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations...
May 2017: Molekuliarnaia Biologiia
Bratati Saha, Robin J Parks
Adenovirus (Ad) vectors deleted of the early region 1 (E1) are widely used for transgene delivery in preclinical and clinical gene therapy studies. Although proteins encoded within the E1 region are required for efficient virus replication, previous studies have suggested that certain viral or cellular proteins can functionally compensate for E1, leading to expression of the early region 2 (E2)-encoded replicative proteins and subsequent virus replication. We have generated a series of E1-encoding and E1-deficient Ad vectors containing a FLAG-epitope tag on each of the E2-encoded proteins: DNA-binding protein (DBP), terminal protein (TP) and DNA polymerase (Pol)...
2017: PloS One
Maurizio Rossi, Martin Spichty, Lucilla Attorri, Chiara Distante, Clara Nervi, Serafina Salvati, Luigi Vitelli
The aim of this study was to investigate the molecular mechanism by which eicosapentaenoic acid (EPA) may exert neuroprotective effects through an "EPA-cyclic AMP response element-binding protein (CREB)" signaling pathway. The current study reveals that EPA modulates the exquisite interplay of interaction of CREB1 with the inhibitor of DNA binding (ID) and E2A family members, thereby delivering mechanistic insights into specific neural differentiation program. In this scenario, our work provides evidence for the capability of CREB1 to sequester ID:E2A family members in brain tissues and neural differentiating mouse embryonic stem cells (mESCs) through formation of a [CREB1]2:ID2:E47 tetrameric complex...
August 2017: Biochimica et Biophysica Acta
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