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https://www.readbyqxmd.com/read/29149504/mybl1-rearrangements-and-myb-amplification-in-breast-adenoid-cystic-carcinomas-lacking-the-myb-nfib-fusion-gene
#1
Jisun Kim, Felipe C Geyer, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Anqi Li, Fresia Pareja, Nicola Fusco, Marcia Edelweiss, Rahul Kumar, Rodrigo Gularte-Merida, Andre N Forbes, Ekta Khurana, Odette Mariani, Sunil Badve, Anne Vincent-Salomon, Larry Norton, Jorge S Reis-Filho, Britta Weigelt
Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer (TNBC), has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression...
November 17, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29148366/involvement-of-the-ytfk-gene-from-the-phob-regulon-in-stationary-phase-h2o2-stress-tolerance-in-escherichia-coli
#2
Yumi Iwadate, Jun-Ichi Kato
The Escherichia coli PhoB-PhoR two-component system responds to phosphate starvation and induces the expression of many genes. Previous studies suggested that phosphate starvation induces oxidative stress, but the involvement of the PhoB regulon in oxidative stress tolerance has not been clarified. Here, we showed that ytfK, one of the PhoB regulon genes, is involved in cell tolerance to a redox-cycling drug, menadione, and H2O2 in stationary-phase cells. A ytfK deletion mutant was sensitive to H2O2 when the cells were grown anaerobically or micro-aerobically in the presence of nitrate...
November 17, 2017: Microbiology
https://www.readbyqxmd.com/read/29148086/novel-gene-fusion-of-prcc-mitf-defines-a-new-member-of-mit-family-translocation-renal-cell-carcinoma-clinicopathologic-analysis-and-detection-of-the-gene-fusion-by-rna-sequencing-and-fish
#3
Qiu-Yuan Xia, Xiao-Tong Wang, Sheng-Bing Ye, Xuan Wang, Rui Li, Shan-Shan Shi, Ru Fang, Ru-Song Zhang, Heng-Hui Ma, Zhen-Feng Lu, Qin Shen, Wei Bao, Xiao-Jun Zhou, Qiu Rao
AIMS: MITF, TFE3, TFEB and TFEC belong to the same microphthalmia-associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harboring TFE3 gene fusions and t(6;11) RCC harboring a MALAT1-TFEB gene fusion. The 2016 World Health Organization classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported...
November 17, 2017: Histopathology
https://www.readbyqxmd.com/read/29147589/%C3%AE-%C3%AE-t-cell-acute-lymphoblastic-leukemia-lymphoma-discussion-of-two-pediatric-cases-and-its-distinction-from-other-mature-%C3%AE-%C3%AE-t-cell-malignancies
#4
Eric X Wei, Vasiliki Leventaki, John K Choi, Susana C Raimondi, Elizabeth M Azzato, Sheila A Shurtleff, Menchu G Ong, Diana M Veillon, James D Cotelingam, Rodney E Shackelford
Gamma delta (γδ) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Here we report two pediatric T-ALL cases and present their clinical features, histology, immunophenotypes, cytogenetics, and molecular diagnostic findings. The first patient is a two-year-old girl with leukocytosis, circulating lymphoblasts, and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23 resulting in an MLL and AF10 fusion transcript, which may be the first reported in γδ T-ALL...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29146937/tfeb-regulates-lysosomal-positioning-by-modulating-tmem55b-expression-and-jip4-recruitment-to-lysosomes
#5
Rose Willett, José A Martina, James P Zewe, Rachel Wills, Gerald R V Hammond, Rosa Puertollano
Lysosomal distribution is linked to the role of lysosomes in many cellular functions, including autophagosome degradation, cholesterol homeostasis, antigen presentation, and cell invasion. Alterations in lysosomal positioning contribute to different human pathologies, such as cancer, neurodegeneration, and lysosomal storage diseases. Here we report the identification of a novel mechanism of lysosomal trafficking regulation. We found that the lysosomal transmembrane protein TMEM55B recruits JIP4 to the lysosomal surface, inducing dynein-dependent transport of lysosomes toward the microtubules minus-end...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146205/pax3-foxo1-zooming-in-on-an-undruggable-target
#6
REVIEW
Marco Wachtel, Beat W Schäfer
Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets...
November 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29144506/soluble-p-selectin-promotes-retinal-ganglion-cell-survival-through-activation-of-nrf2-signaling-after-ischemia-injury
#7
Kishan Kapupara, Yao-Tseng Wen, Rong-Kung Tsai, Shun-Ping Huang
Retinal ischemic injuries play an important role in the pathogenesis of several eye disorders. Inflammation and oxidative stress are key players in ischemic injuries. Following retinal ischemia, vascular endothelial cells and leukocytes express several inflammatory adhesion receptors, such as selectins and cell adhesion molecules. P-selectin stimulates leukocyte recruitment to platelet aggregates and has an important role in vascular homeostasis and inflammatory leukocyte extravasation. Soluble P-selectin can be neuroprotective through competitive binding to the receptors of endogenous P-selectin molecules...
November 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29143810/next-generation-pacemakers-from-small-devices-to-biological-pacemakers
#8
REVIEW
Eugenio Cingolani, Joshua I Goldhaber, Eduardo Marbán
Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator...
November 16, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29140457/genistein-specific-g6dt-gene-for-the-inducible-production-of-wighteone-in-lotus-japonicus
#9
Jinyue Liu, Wenbo Jiang, Yaying Xia, Xuemin Wang, Guoan Shen, Yongzhen Pang
Prenylated isoflavonoids were found in several legume plants, and they possess various biological activities that play important roles in both plant defense and human health. However, it is still unknown whether prenylated isoflavonoids are present in the model legume plant L. japonicus. In the present study, we found that the prenylated isoflavonoid wighteone was produced in L. japonicus when the leaf was supplemented with genistein. Furthermore, a novel prenyltransferase gene LjG6DT was identified, which shared high similarity and was closely related with several known prenyltransferase genes involved in isoflavonoid biosynthesis...
November 10, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29140244/subcellular-analysis-of-pigeon-hair-cells-implicates-vesicular-trafficking-in-cuticulosome-formation-and-maintenance
#10
Simon Nimpf, Erich Pascal Malkemper, Mattias Lauwers, Lyubov Ushakova, Gregory Nordmann, Andrea Wenninger-Weinzierl, Thomas R Burkard, Sonja Jacob, Thomas Heuser, Guenter P Resch, David A Keays
Hair cells are specialized sensors located in the inner ear that enable the transduction of sound, motion, and gravity into neuronal impulses. In birds some hair cells contain an iron-rich organelle, the cuticulosome, that has been implicated in the magnetic sense. Here, we exploit histological, transcriptomic and tomographic methods to investigate the development of cuticulosomes, as well as the molecular and subcellular architecture of cuticulosome positive hair cells. We show that this organelle forms rapidly after hatching in a process that involves vesicle fusion and nucleation of ferritin nanoparticles...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29139541/characterization-of-the-autophagy-related-gene-8a-atg8a-promoter-in-drosophila-melanogaster
#11
Arundhati Bali, Bhupendra V Shravage
Autophagy is an evolutionarily conserved process which is upregulated under various stress conditions, including nutrient stress and oxidative stress. Amongst autophagy related genes (Atgs), Atg8a (LC3 in mammals) is induced several-fold during nutrient limitation in Drosophila. The minimal Atg8a cis-regulatory module (CRM) which mediates transcriptional upregulation under various stress conditions is not known. Here, we describe the generation and analyses of a series of Atg8a promoter deletions which drive the expression of an mCherry-Atg8a fusion cassette...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/29134701/overexpression-of-a-newly-identified-d-amino-acid-transaminase-in-mycobacterium-smegmatis-complements-glutamate-racemase-deletion
#12
Roman Mortuza, Htin Lin Aung, George Taiaroa, Helen K Opel-Reading, Torsten Kleffmann, Gregory M Cook, Kurt L Krause
Glutamate racemase (MurI) has been proposed as a target for anti-tuberculosis drug development based on the inability of ΔmurI mutants of Mycobacterium smegmatis to grow in the absence of d-glutamate. In this communication, we identify ΔmurI suppressor mutants that are detected during prolonged incubation. Whole genome sequencing of these ΔmurI suppressor mutants identified the presence of a SNP, located in the promoter region of MSMEG_5795. RT-qPCR and transcriptional fusion analyses revealed that the ΔmurI suppressor mutant overexpressed MSMEG_5795 14-fold compared to the isogenic wild-type...
November 14, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29133799/hit-and-run-epigenetic-editing-prevents-senescence-entry-in-primary-breast-cells-from-healthy-donors
#13
Emily A Saunderson, Peter Stepper, Jennifer J Gomm, Lily Hoa, Adrienne Morgan, Michael D Allen, J Louise Jones, John G Gribben, Tomasz P Jurkowski, Gabriella Ficz
Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation is not clear. To investigate this question, we use a CRISPR-dCas9 epigenetic editing tool, where an inactive form of Cas9 is fused to DNA methyltransferase effectors. Using this system, here we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary breast cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct, and this prevents cells from engaging senescence arrest...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29133595/targeted-next-gen-sequencing-for-detecting-mll-gene-fusions-in-leukemia
#14
Sadia Afrin, Christine Rc Zhang, Claus Meyer, Caedyn L Stinson, Thy Pham, Timothy Jc Bruxner, Nicola C Venn, Toby N Trahair, Rosemary Sutton, Rolf Marschalek, J Lynn Fink, Andrew S Moore
Mixed Lineage Leukemia (MLL) gene rearrangements characterize approximately 70% of infant and 10% of adult and therapy-related leukemia. Conventional clinical diagnostics, including cytogenetics and fluorescence in situ hybridization (FISH) fail to detect MLL translocation partner genes (TPGs) in many patients. Long-Distance Inverse (LDI)-PCR, the 'gold standard' technique that is used to characterize MLL breakpoints is laborious and requires a large input of genomic DNA (gDNA). To overcome the limitations of current techniques, a targeted Next-Generation Sequencing (NGS) approach that requires low RNA input was tested...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133374/the-rin-mc-fusion-of-mads-box-transcription-factors-has-transcriptional-activity
#15
Shan Li, Huijinlan Xu, Zheng Ju, Dongyan Cao, Hongliang Zhu, Daqi Fu, Donald Grierson, Guozheng Qin, Yunbo Luo, Benzhong Zhu
Fruit development and ripening is regulated by genetic and environmental factors and is of critical importance for seed dispersal, reproduction and fruit quality. Tomato rin mutant fruit have a classic ripening-inhibited phenotype, which is attributed to a genomic DNA deletion resulting in the fusion of two truncated transcription factors, RIN and MC. In wild-type fruit, RIN, a MADS-box transcription factor, is a key regulator of the ripening gene expression network with hundreds of gene targets controlling changes in color, flavor, texture and taste during tomato fruit ripening; MC, on the other hand, has low expression in fruit, and the potential functions of the RIN-MC fusion gene in ripening remain unclear...
November 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29130105/tumor-molecular-profiling-of-nsclc-patients-using-next-generation-sequencing
#16
Nikolaos Tsoulos, Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Georgios Tsaousis, Chrisoula Efstathiadou, Georgia Tounta, Aikaterini Scapeti, Eugenia Bourkoula, Pavlos Zarogoulidis, George Pentheroudakis, Stylianos Kakolyris, Ioannis Boukovinas, Pavlos Papakotoulas, Elias Athanasiadis, Theofanis Floros, Anna Koumarianou, Vasileios Barbounis, Anca Dinischiotu, George Nasioulas
Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29130101/the-recombinant-egfr-cd13-bi-targeted-fusion-protein-induces-apoptosis-and-blocks-tube-formation
#17
Weijin Sheng, Jianhua Gong, Min Jiang, Yongsu Zhen
Previously it was shown that the recombinant EGFR/CD13 bi-targeted fusion protein ER(Fv)‑LDP-NGR which consists of an anti‑EGFR scFv antibody fragment, a tri‑cyclic NGR peptide, and a lidamycin-derived apoprotein, inhibited the proliferation of cancer cells and markedly suppressed tumor growth of breast carcinoma MCF-7 xenografts in athymic mice. This study investigated the mechanism of action of the fusion protein. Human breast cancer MCF-7 cells, lung adenocarcinoma A549 cells, and microvascular endothelial HMEC‑1 cells were used for a series of assays and determinations...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29129207/fusion-pore-in-exocytosis-more-than-an-exit-gate-a-%C3%AE-cell-perspective
#18
REVIEW
Benoit Hastoy, Anne Clark, Patrik Rorsman, Jochen Lang
Secretory vesicle exocytosis is a fundamental biological event and the process by which hormones (like insulin) are released into the blood. Considerable progress has been made in understanding this precisely orchestrated sequence of events from secretory vesicle docked at the cell membrane, hemifusion, to the opening of a membrane fusion pore. The exact biophysical and physiological regulation of these events implies a close interaction between membrane proteins and lipids in a confined space and constrained geometry to ensure appropriate delivery of cargo...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29128369/inhibition-of-poly-adp-ribose-polymerase-1-alters-expression-of-mitochondria-related-genes-in-pc12-cells-relevance-to-mitochondrial-homeostasis-in-neurodegenerative-disorders
#19
Grzegorz A Czapski, Magdalena Cieślik, Przemysław L Wencel, Sylwia Wójtowicz, Robert P Strosznajder, Joanna B Strosznajder
Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Aβ) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Aβ peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29127011/rational-design-of-small-molecules-that-modulate-the-transcriptional-function-of-the-response-regulator-phop
#20
Xiaoyu Qing, Ami De Weerdt, Marc De Maeyer, Hans Steenackers, Arnout Voet
The response regulator PhoP, which is part of the PhoP/PhoQ two-component system, regulates the expression of multiple genes involved in controlling virulence in Salmonella enterica serovar Typhimurium and other species of Gram-negative bacteria. Modulating the phosphorylation-mediated dimerization in the receiver domain may interfere with the transcriptional function of PhoP. In this study, we analyzed the therapeutic potential of the PhoP receiver domain by exploring it as a potential target for drug design...
November 7, 2017: Biochemical and Biophysical Research Communications
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