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https://www.readbyqxmd.com/read/27914109/bcor-upregulation-in-a-poorly-differentiated-synovial-sarcoma-with-ss18l1-ssx1-fusion-a-pathologic-and-molecular-pitfall
#1
Yu-Chien Kao, Yun-Shao Sung, Lei Zhang, Samuel Kenan, Samuel Singer, William D Tap, David Swanson, Brendan C Dickson, Cristina R Antonescu
The diagnosis of poorly differentiated synovial sarcoma (PD-SS) may be challenging due to overlapping morphologic features with other undifferentiated round cell sarcomas (URCS). Particularly relevant is the histologic overlap and shared BCOR overexpression between a subset of SS and URCS with various BCOR genetic abnormalities. Here we report a case of PD-SS lacking the canonical SS18-SSX gene fusion, but showing strong BCOR immunoreactivity and BCOR gene abnormalities by FISH which were misinterpreted as a URCS with BCOR gene rearrangements...
December 3, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27913725/in-vivo-expression-technology-and-5-end-mapping-of-the-borrelia-burgdorferi-transcriptome-identify-novel-rnas-expressed-during-mammalian-infection
#2
Philip P Adams, Carlos Flores Avile, Niko Popitsch, Ivana Bilusic, Renée Schroeder, Meghan Lybecker, Mollie W Jewett
Borrelia burgdorferi, the bacterial pathogen responsible for Lyme disease, modulates its gene expression profile in response to the environments encountered throughout its tick-mammal infectious cycle. To begin to characterize the B. burgdorferi transcriptome during murine infection, we previously employed an in vivo expression technology-based approach (BbIVET). This identified 233 putative promoters, many of which mapped to un-annotated regions of the complex, segmented genome. Herein, we globally identify the 5' end transcriptome of B...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27913309/sequence-determinants-of-the-caenhorhabditis-elegansdopamine-transporter-dictating-in-vivoaxonal-export-and-synaptic-localization
#3
Sarah B Robinson, J Andrew Hardaway, Shannon L Hardie, Jane Wright, Ryan M Glynn, Daniel P Bermingham, Qiao Han, Sarah M Sturgeon, Phyllis Freeman, Randy D Blakely
The monoamine neurotransmitter dopamine (DA) acts across phylogeny to modulate both simple and complex behaviors. The presynaptic DA transporter (DAT) is a major determinant of DA signaling capacity in ensuring efficient extracellular DA clearance. In humans, DAT is also a major target for prescribed and abused psychostimulants. Multiple structural determinants of DAT function and regulation have been defined, though largely these findings have arisen from heterologous expression or ex vivo cell culture studies...
November 29, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27910166/anchored-multiplex-pcr-for-targeted-next-generation-sequencing-reveals-recurrent-and-novel-usp6-fusions-and-upregulation-of-usp6-expression-in-aneurysmal-bone-cyst
#4
Natalya V Guseva, Omar Jaber, Munir R Tanas, Aaron A Stence, Ramakrishna Sompallae, Jenna Schade, Allison N Fillman, Benjamin J Miller, Aaron D Bossler, Deqin Ma
Primary aneurysmal bone cyst (ABC) is a neoplastic process due to recurrent translocations involving the USP6 gene. By fluorescence in situ hybridization, up to 69% of primary ABCs harbored USP6 translocations; no USP6 translocation was found in secondary ABC or giant cell tumor of bone (GCT). GCT can recur locally, metastasize to the lungs in some cases, and rarely undergo malignant transformation. Differentiating primary ABC from its mimics is important for treatment and prognosis. We evaluated USP6 fusion and expression in 13 cases of primary and 1 case of secondary ABC, and 9 cases of GCT using nucleic acid extracted from formalin-fixed, paraffin-embedded tissue and a next generation sequencing (NGS)-based assay...
November 7, 2016: Genes, Chromosomes & Cancer
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
#5
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/27907167/infusion-advancing-discovery-of-fusion-genes-and-chimeric-transcripts-from-deep-rna-sequencing-data
#6
Konstantin Okonechnikov, Aki Imai-Matsushima, Lukas Paul, Alexander Seitz, Thomas F Meyer, Fernando Garcia-Alcalde
Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found...
2016: PloS One
https://www.readbyqxmd.com/read/27903900/autoregulation-of-mbnl1-function-by-exon-1-exclusion-from-mbnl1-transcript
#7
Patryk Konieczny, Ewa Stepniak-Konieczna, Katarzyna Taylor, Łukasz J Sznajder, Krzysztof Sobczak
Muscleblind-like proteins (MBNLs) are regulators of RNA metabolism. During tissue differentiation the level of MBNLs increases, while their functional insufficiency plays a crucial role in myotonic dystrophy (DM). Deep sequencing of RNA molecules cross-linked to immunoprecipitated protein particles (CLIP-seq) revealed that MBNL1 binds to MBNL1 exon 1 (e1) encoding both the major part of 5'UTR and an amino-terminal region of MBNL1 protein. We tested several hypotheses regarding the possible autoregulatory function of MBNL1 binding to its own transcript...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903646/whole-transcriptome-sequencing-identified-a-distinct-subtype-of-acute-lymphoblastic-leukemia-with-predominant-genomic-abnormalities-of-ep300-and-crebbp
#8
Maoxiang Qian, Hui Zhang, Shirley Kow-Yin Kham, Shuguang Liu, Chuang Jiang, Xujie Zhao, Yi Lu, Charnise Goodings, Ting-Nien Lin, Ranran Zhang, Takaya Moriyama, Zhaohong Yin, Zhenhua Li, Thuan Chong Quah, Hany Ariffin, Ah Moy Tan, Shuhong Shen, Deepa Bhojwani, Shaoyan Hu, Suning Chen, Huyong Zheng, Ching-Hon Pui, Allen Eng-Juh Yeoh, Jun J Yang
Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54...
November 30, 2016: Genome Research
https://www.readbyqxmd.com/read/27900286/selective-and-efficient-elimination-of-vibrio-cholerae-with-a-chemical-modulator-that-targets-glucose-metabolism
#9
Young Taek Oh, Hwa Young Kim, Eun Jin Kim, Junhyeok Go, Wontae Hwang, Hyoung Rae Kim, Dong Wook Kim, Sang Sun Yoon
Vibrio cholerae, a Gram-negative bacterium, is the causative agent of pandemic cholera. Previous studies have shown that the survival of the seventh pandemic El Tor biotype V. cholerae strain N16961 requires production of acetoin in a glucose-rich environment. The production of acetoin, a neutral fermentation end-product, allows V. cholerae to metabolize glucose without a pH drop, which is mediated by the production of organic acid. This finding suggests that inhibition of acetoin fermentation can result in V...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27899926/bioinformatic-analyses-of-subgroup-a-members-of-the-wheat-bzip-transcription-factor-family-and-functional-identification-of-tabzip174-involved-in-drought-stress-response
#10
Xueyin Li, Biane Feng, Fengjie Zhang, Yimiao Tang, Liping Zhang, Lingjian Ma, Changping Zhao, Shiqing Gao
Extensive studies in Arabidopsis and rice have demonstrated that Subgroup-A members of the bZIP transcription factor family play important roles in plant responses to multiple abiotic stresses. Although common wheat (Triticum aestivum) is one of the most widely cultivated and consumed food crops in the world, there are limited investigations into Subgroup A of the bZIP family in wheat. In this study, we performed bioinformatic analyses of the 41 Subgroup-A members of the wheat bZIP family. Phylogenetic and conserved motif analyses showed that most of the Subgroup-A bZIP proteins involved in abiotic stress responses of wheat, Arabidopsis, and rice clustered in Clade A1 of the phylogenetic tree, and shared a majority of conserved motifs, suggesting the potential importance of Clade-A1 members in abiotic stress responses...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27899802/genomic-and-transcriptional-landscape-of-p2ry8-crlf2-positive-childhood-acute-lymphoblastic-leukemia
#11
C Vesely, C Frech, C Eckert, G Cario, A Mecklenbräuker, U Zur Stadt, K Nebral, F Kraler, S Fischer, A Attarbaschi, M Schuster, C Bock, H Cavé, A von Stackelberg, M Schrappe, M A Horstmann, G Mann, O A Haas, R Panzer-Grümayer
Children with P2RY8-CRLF2-positive ALL have an increased relapse risk. Their mutational and transcriptional landscape as well as the respective patterns at relapse remains largely elusive. We therefore performed an integrated analysis of whole-exome and RNA-sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway activating mutations in 76% of cases at diagnosis and virtually all relapses...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899596/chitars-3-1-the-enhanced-chimeric-transcripts-and-rna-seq-database-matched-with-protein-protein-interactions
#12
Alessandro Gorohovski, Somnath Tagore, Vikrant Palande, Assaf Malka, Dorith Raviv-Shay, Milana Frenkel-Morgenstern
Discovery of chimeric RNAs, which are produced by chromosomal translocations as well as the joining of exons from different genes by trans-splicing, has added a new level of complexity to our study and understanding of the transcriptome. The enhanced ChiTaRS-3.1 database (http://chitars.md.biu.ac.il) is designed to make widely accessible a wealth of mined data on chimeric RNAs, with easy-to-use analytical tools built-in. The database comprises 34 922: chimeric transcripts along with 11 714: cancer breakpoints...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27896439/characterization-of-pollen-expressed-bzip-protein-interactions-and-the-role-of-atbzip18-in-the-male-gametophyte
#13
Antónia Gibalová, Lenka Steinbachová, Said Hafidh, Veronika Bláhová, Zuzana Gadiou, Christos Michailidis, Karel Műller, Roman Pleskot, Nikoleta Dupľáková, David Honys
KEY MESSAGE : bZIP TF network in pollen. Transcriptional control of gene expression represents an important mechanism guiding organisms through developmental processes and providing plasticity towards environmental stimuli. Because of their sessile nature, plants require effective gene regulation for rapid response to variation in environmental and developmental conditions. Transcription factors (TFs) provide such control ensuring correct gene expression in spatial and temporal manner. Our work reports the interaction network of six bZIP TFs expressed in Arabidopsis thaliana pollen and highlights the potential functional role for AtbZIP18 in pollen...
November 28, 2016: Plant Reproduction
https://www.readbyqxmd.com/read/27890935/nup98-fusion-transcripts-characterize-different-biological-entities-within-acute-myeloid-leukemia-a-report-from-the-aieop-aml-group
#14
V Bisio, M Zampini, C Tregnago, E Manara, V Salsi, A Di Meglio, R Masetti, M Togni, D Di Giacomo, S Minuzzo, A Leszl, V Zappavigna, R Rondelli, C Mecucci, A Pession, F Locatelli, G Basso, M Pigazzi
Leukemia accepted article preview online, 28 November 2016. doi:10.1038/leu.2016.361.
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890927/the-ap-1-transcription-factor-junb-is-essential-for-multiple-myeloma-cell-proliferation-and-drug-resistance-in-the-bone-marrow-microenvironment
#15
F Fan, M H Bashari, E Morelli, G Tonon, S Malvestiti, S Vallet, M Jarahian, A Seckinger, D Hose, L Bakiri, C Sun, Y Hu, C R Ball, H Glimm, M Sattler, H Goldschmidt, E F Wagner, P Tassone, D Jaeger, K Podar
Despite therapeutic advances, multiple myeloma (MM) remains an incurable disease, predominantly due to the development of drug resistance. The activator protein-1 (AP-1) transcription factor family has been implicated in a multitude of physiologic processes and tumorigenesis; however, its role in MM is largely unknown. Here we demonstrate specific and rapid induction of the AP-1 family member JunB in MM cells when co-cultured with bone marrow stromal cells. Supporting a functional key role of JunB in MM pathogenesis, knockdown of JUNB significantly inhibited in vitro MM cell proliferation and survival...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27889468/mitochondrial-cristae-remodelling-is-associated-with-disrupted-opa1-oligomerisation-in-the-huntington-s-disease-r6-2-fragment-model
#16
Tanja Hering, Kerstin Kojer, Nathalie Birth, Jaqueline Hallitsch, Jan-Willem Taanman, Michael Orth
There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27888797/tumorigenicity-of-ewing-sarcoma-is-critically-dependent-on-the-trithorax-proteins-mll1-and-menin
#17
Laurie K Svoboda, Natashay Bailey, Raelene A Van Noord, Melanie A Krook, Ashley Harris, Cassondra Cramer, Brooke Jasman, Rajiv M Patel, Dafydd Thomas, Dmitry Borkin, Tomasz Cierpicki, Jolanta Grembecka, Elizabeth R Lawlor
Developmental transcription programs are epigenetically regulated by the competing actions of polycomb and trithorax (TrxG) protein complexes, which repress and activate genes, respectively. Ewing sarcoma is a developmental tumor that is associated with widespread de-regulation of developmental transcription programs, including HOX programs. Posterior HOXD genes are abnormally over-expressed by Ewing sarcoma and HOXD13, in particular, contributes to the tumorigenic phenotype. In MLL1 fusion-driven leukemia, aberrant activation of HOXA genes is epigenetically mediated by the TrxG complex and HOXA gene expression and leukemogenesis are critically dependent on the protein-protein interaction between the TrxG proteins MLL1 and menin...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27884323/the-toll-like-receptor-4-antagonist-transforming-growth-factor-%C3%AE-activated-kinase-tak-242-attenuates-taurocholate-induced-oxidative-stress-through-regulating-mitochondrial-function-in-mice-pancreatic-acinar-cells
#18
Long-Fei Pan, Lei Yu, Li-Ming Wang, Jun-Tao He, Jiang-Li Sun, Xiao-Bo Wang, Zheng-Hai Bai, Li-Juan Su, Hong-Hong Pei
BACKGROUND: Acute pancreatitis (AP) is a commonly occurring and potentially life-threatening disease. Recently, toll-like receptor 4 (TLR4) has been considered as a new clue for studying the pathogenesis of AP due to its important role in inflammatory response cascade. MATERIALS AND METHODS: The aim of this study was to investigate the potential protective effect of transforming growth factor-β-activated kinase (TAK)-242, a novel TLR4 antagonist, in taurocholate-treated mice pancreatic acinar cells...
December 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27882646/symb-and-symc-two-membrane-associated-proteins-are-required-for-epichlo%C3%A3-festucae-hyphal-cell-cell-fusion-and-maintenance-of-a-mutualistic-interaction-with-lolium-perenne
#19
Kimberly A Green, Yvonne Becker, Aiko Tanaka, Daigo Takemoto, Helen L Fitzsimons, Stephan Seiler, Hervé Lalucque, Philippe Silar, Barry Scott
Cell-cell fusion in fungi is required for colony formation, nutrient transfer and signal transduction. Disruption of genes required for hyphal fusion in Epichloë festucae, a mutualistic symbiont of Lolium grasses, severely disrupts the host interaction phenotype. We examined whether symB and symC, the E. festucae homologs of Podospora anserina self-signaling genes IDC2 and IDC3, are required for E. festucae hyphal fusion and host symbiosis. Deletion mutants of these genes were defective in hyphal cell fusion, formed intra-hyphal hyphae, and had enhanced conidiation...
November 23, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27875302/proteasomal-degradation-of-the-ews-fli1-fusion-protein-is-regulated-by-a-single-lysine-residue
#20
Maria E Gierisch, Franziska Pfistner, Laura A Lopez-Garcia, Lena Harder, Beat W Schäfer, Felix K Niggli
E-26 transformation specific (ETS) proteins are transcription factors directing gene expression through their conserved DNA-binding domain. They are implicated as truncated forms or interchromosomal rearrangements in a variety of tumors including Ewing sarcoma, a pediatric tumor of the bone. Tumor cells express the chimeric oncoprotein EWS-FLI1 from a specific t(22;11)(q24;12) translocation. EWS-FLI1 harbors a strong transactivation domain from EWSR1 and the DNA-binding ETS domain of FLI1 in the C-terminal part of the protein...
November 8, 2016: Journal of Biological Chemistry
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