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https://www.readbyqxmd.com/read/29326336/arid5b-as-a-critical-downstream-target-of-the-tal1-complex-that-activates-the-oncogenic-transcriptional-program-and-promotes-t-cell-leukemogenesis
#1
Wei Zhong Leong, Shi Hao Tan, Phuong Cao Thi Ngoc, Stella Amanda, Alice Wei Yee Yam, Wei-Siang Liau, Zhiyuan Gong, Lee N Lawton, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells...
January 11, 2018: Genes & Development
https://www.readbyqxmd.com/read/29323491/g-quadruplex-identification-in-the-genome-of-protozoan-parasites-points-to-naphthalene-diimide-ligands-as-new-antiparasitic-agents
#2
Efres Belmonte-Reche, Marta Martínez-García, Aurore Guédin, Michela Zuffo, Matilde Arévalo-Ruiz, Filippo Doria, Jenny Campos-Salinas, Marjorie Maynadier, Jose-Juan Lopez-Rubio, Mauro Freccero, Jean-Louis Mergny, Jose María Perez-Victoria, Juan Carlos Morales
G-quadruplexes (G4) are DNA secondary structures which take part in the regulation of gene expression. Putative G4 forming sequences (PQS) have been reported in mammals, yeast, bacteria and viruses. Here, we present PQS searches on the genomes of T. brucei, L. major and P. falciparum. We found telomeric sequences and new PQS motifs. Biophysical experiments showed that EBR1, a 29 nucleotide long highly repeated PQS in T. brucei, forms a stable G4 structure. G4 ligands based on carbohydrate conjugated naphthalene diimides (carb-NDIs) which bind G4's including hTel, could bind EBR1 with selectivity versus dsDNA...
January 11, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29321375/highly-potent-visnagin-derivatives-inhibit-cyp1-and-prevent-doxorubicin-cardiotoxicity
#3
Aarti Asnani, Bahoui Zheng, Yan Liu, You Wang, Howard H Chen, Anita Vohra, An Chi, Ivan Cornella-Taracido, Huijun Wang, Douglas G Johns, David E Sosnovik, Randall T Peterson
Anthracyclines such as doxorubicin are highly effective chemotherapy agents used to treat many common malignancies. However, their use is limited by cardiotoxicity. We previously identified visnagin as protecting against doxorubicin toxicity in cardiac but not tumor cells. In this study, we sought to develop more potent visnagin analogs in order to use these analogs as tools to clarify the mechanisms of visnagin-mediated cardioprotection. Structure-activity relationship studies were performed in a zebrafish model of doxorubicin cardiomyopathy...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29311116/stim1-activation-of-adenylyl-cyclase-6-connects-ca2-and-camp-signaling-during-melanogenesis
#4
Rajender K Motiani, Jyoti Tanwar, Desingu Ayyappa Raja, Ayushi Vashisht, Shivangi Khanna, Sachin Sharma, Sonali Srivastava, Sridhar Sivasubbu, Vivek T Natarajan, Rajesh S Gokhale
Endoplasmic reticulum (ER)-plasma membrane (PM) junctions form functionally active microdomains that connect intracellular and extracellular environments. While the key role of these interfaces in maintenance of intracellular Ca2+ levels has been uncovered in recent years, the functional significance of ER-PM junctions in non-excitable cells has remained unclear. Here, we show that the ER calcium sensor protein STIM1 (stromal interaction molecule 1) interacts with the plasma membrane-localized adenylyl cyclase 6 (ADCY6) to govern melanogenesis...
January 8, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29282212/musclemotion-a-versatile-open-software-tool-to-quantify-cardiomyocyte-and-cardiac-muscle-contraction-in-vitro-and-in-vivo
#5
Luca Sala, Berend J van Meer, Leon T Tertoolen, Jeroen Bakkers, Milena Bellin, Richard P Davis, Chris N Denning, Michel A Dieben, Thomas Eschenhagen, Elisa Giacomelli, Catarina Grandela, Arne Hansen, Eduard Holman, Monique R Jongbloed, Sarah M Kamel, Charlotte D Koopman, Quentin Lachaud, Ingra Mannhardt, Mervyn P Mol, Diogo Mosqueira, Valeria V Orlova, Robert Passier, Marcelo C Ribeiro, Umber Saleem, Godfrey Smith, Francis L L Burton, Christine L Mummery
Rationale: There are several methods to measure cardiomyocyte (CM) and muscle contraction but these require customized hardware, expensive apparatus and advanced informatics or can only be used in single experimental models. Consequently, data and techniques have been difficult to reproduce across models and laboratories, analysis is time consuming and only specialist researchers can quantify data. Objective: Here we describe and validate an automated, open source software tool (MUSCLEMOTION) adaptable for use with standard laboratory- and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes and pharmacological responses...
December 27, 2017: Circulation Research
https://www.readbyqxmd.com/read/29249175/a-tool-compound-targeting-the-core-binding-factor-runt-domain-to-disrupt-binding-to-cbf%C3%AE-in-leukemic-cells
#6
Zaw Min Oo, Anuradha Illendula, Jolanta Grembecka, Charles Schmidt, Yunpeng Zhou, Virginie Esain, Wanda Kwan, Isaura Frost, Trista E North, Roger A Rajewski, Nancy A Speck, John H Bushweller
The core binding factor (CBF) gene RUNX1 is a target of chromosomal translocations in leukemia, including t(8;21) in acute myeloid leukemia (AML). Normal CBF function is essential for activity of AML1-ETO, product of the t(8;21), and for survival of several leukemias lacking RUNX1 mutations. Using virtual screening and optimization, we developed Runt domain inhibitors which bind to the Runt domain and disrupt its interaction with CBFβ. On-target activity was demonstrated by the Runt domain inhibitors' ability to depress hematopoietic cell formation in zebrafish embryos, reduce growth and induce apoptosis of t(8;21) AML cell lines, and reduce progenitor activity of mouse and human leukemia cells harboring the t(8;21), but not normal bone marrow cells...
December 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29236469/synthetic-phenolic-antioxidants-cause-perturbation-in-steroidogenesis-in-vitro-and-in-vivo
#7
Xiaoxi Yang, Wenting Song, Na Liu, Zhendong Sun, Ruirui Liu, Qian S Liu, Qunfang Zhou, Guibin Jiang
Synthetic phenolic antioxidants (SPAs) are closely correlated with human life due to their extensive usages, and increasing concerns have been raised on their biosafety. The previous controversial findings caused continuous debates on their potential endocrine disrupting effects. In the present study, four commonly used SPAs, including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butyl hydroquinone (TBHQ) and 2,2'-methylenebis(6-tert-butyl-4-methylphenol) (AO2246), were investigated for their estrogenic effects, and the results from in vitro screening assays showed SPAs themselves had negligible estrogen receptor binding affinities...
December 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29229770/rb1-promotes-t-cell-maturation-from-premature-apoptosis-by-inhibiting-e2f1
#8
Zili Zhang, Wei Liu, Lingfeng Zhao, Zhibin Huang, Xiaohui Chen, Ning Ma, Jin Xu, Wenqing Zhang, Yiyue Zhang
T lymphocytes are key cellular components of acquired immune system and play essential roles in cell-mediated immunity. T cell development occurs in the thymus where 95% of immature thymocytes are eliminated via apoptosis. It is known that mutation of Zeb1, one of RB1 target genes, resulted in immature T cell decrease in mice. E2F1, an RB1 interacting protein, has been shown to regulate mature T cell development by interfering with thymocyte apoptosis. However, whether Rb1 regulate thymocyte development in vivo is still need to be further investigated...
December 11, 2017: Development
https://www.readbyqxmd.com/read/29225165/cross-talk-between-tp53-and-c-myc-in-the-pathophysiology-of-diamond-blackfan-anemia-evidence-from-rpl11-deficient-in-vivo-and-in-vitro-models
#9
Anirban Chakraborty, Tamayo Uechi, Yukari Nakajima, Hanna T Gazda, Marie-Françoise O'Donohue, Pierre-Emmanuel Gleizes, Naoya Kenmochi
Mutations in genes encoding ribosomal proteins have been identified in Diamond-Blackfan anemia (DBA), a rare genetic disorder that presents with a prominent erythroid phenotype. TP53 has been implicated in the pathophysiology of DBA with ribosomal protein (RP) L11 playing a crucial role in the TP53 response. Interestingly, RPL11 also controls the transcriptional activity of c-Myc, an oncoprotein that positively regulates ribosome biogenesis. In the present study, we analyzed the consequences of rpl11 depletion on erythropoiesis and ribosome biogenesis in zebrafish...
December 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29204828/developmental-hsc-microenvironments-lessons-from-zebrafish
#10
Sara Nik, Joshua T Weinreb, Teresa V Bowman
Hematopoietic stem cells (HSCs) posses the ability to maintain the blood system of an organism from birth to adulthood. The behavior of HSCs is modulated by its microenvironment. During development, HSCs acquire the instructions to self-renew and differentiate into all blood cell fates by passing through several developmental microenvironments. In this chapter, we discuss the signals and cell types that inform HSC decisions throughout ontogeny with a focus on HSC specification, mobilization, migration, and engraftment...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29193635/inactivation-of-ammecr1-is-associated-with-growth-bone-and-heart-alterations
#11
Mariana Moysés-Oliveira, Giuliana Giannuzzi, Richard J Fish, Jill A Rosenfeld, Florence Petit, Maria de Fatima Soares, Leslie Domenici Kulikowski, Adriana Di Battista, Malú Zamariolli, Fan Xia, Thomas Liehr, Nadezda Kosyakova, Gianna Carvalheira, Michael Parker, Eleanor G Seaby, Sarah Ennis, Rodney D Gilbert, R Tanner Hagelstrom, Maria L Cremona, Wenhui L Li, Alka Malhotra, Anjana Chandrasekhar, Denise L Perry, Ryan J Taft, Julie McCarrier, Donald G Basel, Joris Andrieux, Taiza Stumpp, Fernanda Antunes, Gustavo José Pereira, Marguerite Neerman-Arbez, Vera Ayres Meloni, Margaret Drummond-Borg, Maria Isabel Melaragno, Alexandre Reymond
We report five individuals with loss-of-function of the X-linked AMMECR1: a girl with a balanced X-autosome translocation and inactivation of the normal X-chromosome; two boys with maternally-inherited and de novo nonsense variants; and two half-brothers with maternally inherited microdeletion variants. They present with short stature, cardiac and skeletal abnormalities and hearing loss. Variants of unknown significance in AMMECR1 in four male patients from two families with partially overlapping phenotypes were previously reported...
November 28, 2017: Human Mutation
https://www.readbyqxmd.com/read/29186449/the-thyroid-hormone-inactivating-type-3-deiodinase-is-essential-for-optimal-neutrophil-function-observations-from-3-species
#12
Anne H van der Spek, Kin Ki Jim, Aldona Karaczyn, Hermina C van Beeren, Mariëtte T Ackermans, Veerle M Darras, Christina M J E Vandenbroucke-Grauls, Arturo Hernandez, Matthijs C Brouwer, Eric Fliers, Diederik van de Beek, Anita Boelen
Neutrophils are essential effector cells of the innate immune system that have recently been recognized as thyroid hormone (TH) target cells. Cellular TH bioavailability is regulated by the deiodinase enzymes, which can activate or inactivate TH. We have previously shown that the TH inactivating enzyme type 3 deiodinase (D3) is present in neutrophils. Furthermore, D3KO mice show impaired bacterial killing upon infection. We hypothesized that D3 plays a role in neutrophil function during infection by actively regulating local TH availability...
November 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/29162696/expansion-microscopy-of-zebrafish-for-neuroscience-and-developmental-biology-studies
#13
Limor Freifeld, Iris Odstrcil, Dominique Förster, Alyson Ramirez, James A Gagnon, Owen Randlett, Emma K Costa, Shoh Asano, Orhan T Celiker, Ruixuan Gao, Daniel A Martin-Alarcon, Paul Reginato, Cortni Dick, Linlin Chen, David Schoppik, Florian Engert, Herwig Baier, Edward S Boyden
Expansion microscopy (ExM) allows scalable imaging of preserved 3D biological specimens with nanoscale resolution on fast diffraction-limited microscopes. Here, we explore the utility of ExM in the larval and embryonic zebrafish, an important model organism for the study of neuroscience and development. Regarding neuroscience, we found that ExM enabled the tracing of fine processes of radial glia, which are not resolvable with diffraction-limited microscopy. ExM further resolved putative synaptic connections, as well as molecular differences between densely packed synapses...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29127144/disruption-of-thrombocyte-and-t-lymphocyte-development-by-a-mutation-in-arpc1b
#14
Raz Somech, Atar Lev, Yu Nee Lee, Amos J Simon, Ortal Barel, Ginette Schiby, Camila Avivi, Iris Barshack, Michele Rhodes, Jiejing Yin, Minshi Wang, Yibin Yang, Jennifer Rhodes, Nufar Marcus, Ben-Zion Garty, Jerry Stein, Ninette Amariglio, Gideon Rechavi, David L Wiest, Yong Zhang
Regulation of the actin cytoskeleton is crucial for normal development and function of the immune system, as evidenced by the severe immune abnormalities exhibited by patients bearing inactivating mutations in the Wiskott-Aldrich syndrome protein (WASP), a key regulator of actin dynamics. WASP exerts its effects on actin dynamics through a multisubunit complex termed Arp2/3. Despite the critical role played by Arp2/3 as an effector of WASP-mediated control over actin polymerization, mutations in protein components of the Arp2/3 complex had not previously been identified as a cause of immunodeficiency...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29066577/identification-and-characterization-of-t-reg-like-cells-in-zebrafish
#15
Melissa Kasheta, Corrie A Painter, Finola E Moore, Riadh Lobbardi, Alysia Bryll, Eli Freiman, David Stachura, Arlin B Rogers, Yariv Houvras, David M Langenau, Craig J Ceol
Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that suppress autoreactive T cells. Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg-deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there...
October 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29059171/suppression-of-rac1-driven-malignant-melanoma-by-group-a-pak-inhibitors
#16
D Araiza-Olivera, Y Feng, G Semenova, T Y Prudnikova, J Rhodes, J Chernoff
Activating mutations in the RAC1 gene have recently been discovered as driver events in malignant melanoma. Expression of this gene is associated with melanocyte proliferation, and melanoma cells bearing this mutation are insensitive to BRAF inhibitors such as vemurafenib and dabrafenib, and also may evade immune surveillance due to enhanced expression of PD-L1. Activating mutations in RAC1 are of special interest, as small-molecule inhibitors for the RAC effector p21-activated kinase (PAK) are in late-stage clinical development and might impede oncogenic signaling from mutant RAC1...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29034215/the-proteome-of-biologically-active-membrane-vesicles-from-piscirickettsia-salmonis-lf-89-type-strain-identifies-plasmid-encoded-putative-toxins
#17
Cristian Oliver, Mauricio A Hernández, Julia I Tandberg, Karla N Valenzuela, Leidy X Lagos, Ronie E Haro, Patricio Sánchez, Pamela A Ruiz, Constanza Sanhueza-Oyarzún, Marcos A Cortés, María T Villar, Antonio Artigues, Hanne C Winther-Larsen, Ruben Avendaño-Herrera, Alejandro J Yáñez
Piscirickettsia salmonis is the predominant bacterial pathogen affecting the Chilean salmonid industry. This bacterium is the etiological agent of piscirickettsiosis, a significant fish disease. Membrane vesicles (MVs) released by P. salmonis deliver several virulence factors to host cells. To improve on existing knowledge for the pathogenicity-associated functions of P. salmonis MVs, we studied the proteome of purified MVs from the P. salmonis LF-89 type strain using multidimensional protein identification technology...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29030288/in-vitro-characterization-of-zebrafish-danio-rerio-organic-anion-transporters-oat2a-e
#18
Jelena Dragojević, Ivan Mihaljević, Marta Popović, Roko Zaja, Tvrtko Smital
OATS/Oats are transmembrane proteins that transport a variety of drugs, environmental toxins and endogenous metabolites into the cell. Zebrafish (Danio rerio) has seven OAT orthologs: Oat1, Oat2a-e and Oat3. In this study we specifically address Oat2 (Slc22a7) family. Conserved synteny analysis showed localization of zebrafish oat2 genes on two chromosomes, 11 and 17. All five zebrafish Oats were localized by live cell imaging in membranes of transiently transfected HEK293-T cells, and Oat2a, b, d, and e were confirmed using western blot analysis...
October 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29023774/transmission-of-a-common-intestinal-neoplasm-in-zebrafish-by-cohabitation
#19
A R Burns, V Watral, S Sichel, S Spagnoli, A V Banse, E Mittge, T J Sharpton, K Guillemin, M L Kent
Intestinal neoplasms are common in zebrafish (Danio rerio) research facilities. These tumours are most often seen in older fish and are classified as small cell carcinomas or adenocarcinomas. Affected fish populations always contain subpopulations with preneoplastic lesions, characterized by epithelial hyperplasia or inflammation. Previous observations indicated that these tumours are unlikely caused by diet, water quality or genetic background, suggesting an infectious aetiology. We performed five transmission experiments by exposure of naïve fish to affected donor fish by cohabitation or exposure to tank effluent water...
October 11, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28974514/diminished-prrx1-expression-is-associated-with-increased-risk-of-atrial-fibrillation-and-shortening-of-the-cardiac-action-potential
#20
Nathan R Tucker, Elena V Dolmatova, Honghuang Lin, Rebecca R Cooper, Jiangchuan Ye, William J Hucker, Heather S Jameson, Victoria A Parsons, Lu-Chen Weng, Robert W Mills, Moritz F Sinner, Maxim Imakaev, Jordan Leyton-Mange, Gus Vlahakes, Emelia J Benjamin, Kathryn L Lunetta, Steven A Lubitz, Leonid Mirny, David J Milan, Patrick T Ellinor
BACKGROUND: Atrial fibrillation (AF) affects over 33 million individuals worldwide. Genome-wide association studies have identified at least 30 AF loci, but the mechanisms through which individual variants lead to altered disease risk have remained unclear for the majority of these loci. At the 1q24 locus, we hypothesized that the transcription factor PRRX1 could be a strong candidate gene as it is expressed in the pulmonary veins, a source of AF in many individuals. We sought to identify the molecular mechanism, whereby variation at 1q24 may lead to AF susceptibility...
October 2017: Circulation. Cardiovascular Genetics
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