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https://www.readbyqxmd.com/read/29165835/the-function-of-contactin-2-tag-1-in-oligodendrocytes-in-health-and-demyelinating-pathology
#1
Lida Zoupi, Maria Savvaki, Katerina Kalemaki, Ilias Kalafatakis, Kyriaki Sidiropoulou, Domna Karagogeos
The oligodendrocyte maturation process and the transition from the pre-myelinating to the myelinating state are extremely important during development and in pathology. In the present study, we have investigated the role of the cell adhesion molecule CNTN2/TAG-1 on oligodendrocyte proliferation, differentiation, myelination, and function during development and under pathological conditions. With the combination of in vivo, in vitro, ultrastructural, and electrophysiological methods, we have mapped the expression of CNTN2 protein in the oligodendrocyte lineage during the different stages of myelination and its involvement on oligodendrocyte maturation, branching, myelin-gene expression, myelination, and axonal function...
November 22, 2017: Glia
https://www.readbyqxmd.com/read/29165790/physician-interpretation-of-genomic-test-results-and-treatment-selection
#2
Lauren L Brusco, Chetna Wathoo, Kenna R Mills Shaw, Vijaykumar R Holla, Ann M Bailey, Amber M Johnson, Yekaterina B Khotskaya, Beate C Litzenburger, Nora S Sanchez, Jia Zeng, Elmer V Bernstam, Cathy Eng, Bryan K Kee, Rodabe N Amaria, Mark J Routbort, Gordon B Mills, John Mendelsohn, Funda Meric-Bernstam
BACKGROUND: Genomic testing is increasingly performed in oncology, but concerns remain regarding the clinician's ability to interpret results. In the current study, the authors sought to determine the agreement between physicians and genomic annotators from the Precision Oncology Decision Support (PODS) team at The University of Texas MD Anderson Cancer Center in Houston regarding actionability and the clinical use of test results. METHODS: On a prospective protocol, patients underwent clinical genomic testing for hotspot mutations in 46 or 50 genes...
November 22, 2017: Cancer
https://www.readbyqxmd.com/read/29165716/targeting-bcr-abl-independent-tki-resistance-in-chronic-myeloid-leukemia-by-mtor-and-autophagy-inhibition
#3
Rebecca Mitchell, Lisa E M Hopcroft, Pablo Baquero, Elaine K Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V Melo, Edmond Chan, Kevin M Ryan, Véronique Maguer-Satta, Brian J Druker, Richard E Clark, Subir Mitra, Pawel Herzyk, Franck E Nicolini, Paolo Salomoni, G Vignir Helgason
Background: Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment...
November 20, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29165700/epigenetic-therapy-novel-translational-implications-for-arrest-of-environmental-dioxin-induced-disease-in-females
#4
Zaraq Khan, Ye Zheng, Tiffanny L Jones, Abigail A Delaney, Luiz F Correa, Chandra C Shenoy, Khashayarsha Khazaie, Gaurang S Daftary
Increased toxicant exposure and resultant environmentally-induced diseases are a tradeoff of industrial productivity. Dioxin (TCDD: 2,3,7,8 tetrachlorodibenzo-p-dioxin), a ubiquitous by-product is associated with a spectrum of diseases including endometriosis, a common, chronic disease in women. TCDD activates cytochrome p450 (CYP) metabolic enzymes, which alters organ function to cause disease. In contrast, the transcription factor, Krüppel-Like Factor (KLF) 11 represses these enzymes via epigenetic mechanisms...
November 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/29165698/nuclear-mrna-degradation-tunes-the-gain-of-the-unfolded-protein-response-in-saccharomyces-cerevisiae
#5
Debasish Sarkar, Sunirmal Paira, Biswadip Das
Unfolded protein response (UPR) is triggered by the accumulation of unfolded proteins in the endoplasmic reticulum (ER), which is accomplished by a dramatic induction of genes encoding ER chaperones. Activation of these genes involves their rapid transcription by Hac1p, encoded by the HAC1 precursor transcript harboring an intron and a bipartite element (3'-BE) in the 3'-UTR. ER stress facilitates intracellular targeting and recruitment of HAC1 pre-mRNA to Ire1p foci (requiring 3'-BE), leading to its non-spliceosomal splicing mediated by Ire1p/Rlg1p...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165687/investigation-of-the-relationship-between-radiation-dose-and-gene-mutations-and-fusions-in-post-chernobyl-thyroid-cancer
#6
Alexey A Efanov, Alina V Brenner, Tetiana I Bogdanova, Lindsey M Kelly, Pengyuan Liu, Mark P Little, Abigail I Wald, Maureen Hatch, Liudmyla Y Zurnadzy, Marina N Nikiforova, Vladimir Drozdovitch, Kiyohiko Mabuchi, Mykola D Tronko, Stephen J Chanock, Yuri E Nikiforov
Background: Exposure to ionizing radiation during childhood is a well-established risk factor for thyroid cancer. However, the genetic mechanisms of radiation-associated carcinogenesis remain not fully understood. Methods: In this study, we used targeted next-generation sequencing and RNA-Seq to study 65 papillary thyroid cancers (PTCs) from patients in the Ukrainian-American cohort with measurement-based iodine-131 (I-131) thyroid doses received as a result of the Chernobyl accident...
November 18, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29165665/novel-structural-features-drive-dna-binding-properties-of-cmr-a-crp-family-protein-in-tb-complex-mycobacteria
#7
Sridevi Ranganathan, Jonah Cheung, Michael Cassidy, Christopher Ginter, Janice D Pata, Kathleen A McDonough
Mycobacterium tuberculosis (Mtb) encodes two CRP/FNR family transcription factors (TF) that contribute to virulence, Cmr (Rv1675c) and CRPMt (Rv3676). Prior studies identified distinct chromosomal binding profiles for each TF despite their recognizing overlapping DNA motifs. The present study shows that Cmr binding specificity is determined by discriminator nucleotides at motif positions 4 and 13. X-ray crystallography and targeted mutational analyses identified an arginine-rich loop that expands Cmr's DNA interactions beyond the classical helix-turn-helix contacts common to all CRP/FNR family members and facilitates binding to imperfect DNA sequences...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165655/expression-atlas-gene-and-protein-expression-across-multiple-studies-and-organisms
#8
Irene Papatheodorou, Nuno A Fonseca, Maria Keays, Y Amy Tang, Elisabet Barrera, Wojciech Bazant, Melissa Burke, Anja Füllgrabe, Alfonso Muñoz-Pomer Fuentes, Nancy George, Laura Huerta, Satu Koskinen, Suhaib Mohammed, Matthew Geniza, Justin Preece, Pankaj Jaiswal, Andrew F Jarnuczak, Wolfgang Huber, Oliver Stegle, Juan Antonio Vizcaino, Alvis Brazma, Robert Petryszak
Expression Atlas (http://www.ebi.ac.uk/gxa) is an added value database that provides information about gene and protein expression in different species and contexts, such as tissue, developmental stage, disease or cell type. The available public and controlled access data sets from different sources are curated and re-analysed using standardized, open source pipelines and made available for queries, download and visualization. As of August 2017, Expression Atlas holds data from 3,126 studies across 33 different species, including 731 from plants...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165391/micrornas-associated-with-von-hippel-lindau-pathway-in-renal-cell-carcinoma-a-comprehensive-review
#9
REVIEW
Lisa-Maria Schanza, Maximilian Seles, Michael Stotz, Johannes Fosselteder, Georg C Hutterer, Martin Pichler, Verena Stiegelbauer
Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor. One of the major problems with RCC treatment strategies is inherent or acquired resistance towards therapeutic agents over time...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165356/fast-detection-of-a-brca2-large-genomic-duplication-by-next-generation-sequencing-as-a-single-procedure-a-case-report
#10
Marcella Nunziato, Flavio Starnone, Barbara Lombardo, Matilde Pensabene, Caterina Condello, Francesco Verdesca, Chiara Carlomagno, Sabino De Placido, Lucio Pastore, Francesco Salvatore, Valeria D'Argenio
The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. BRCA molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative genomic hybridization (CGH) array was used as confirmatory method...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165337/mirnome-profiling-in-bicuspid-aortic-valve-associated-aortopathy-by-next-generation-sequencing
#11
Andrea Borghini, Ilenia Foffa, Silvia Pulignani, Cecilia Vecoli, Lamia Ait-Ali, Maria Grazia Andreassi
The molecular mechanisms underlying thoracic aortic aneurysm (TAA) in patients with bicuspid aortic valve (BAV) are incompletely characterized. MicroRNAs (miRNAs) may play a major role in the different pathogenesis of aortopathy. We sought to employ next-generation sequencing to analyze the entire miRNome in TAA tissue from patients with BAV and tricuspid aortic valve (TAV). In the discovery stage, small RNA sequencing was performed using the Illumina MiSeq platform in 13 TAA tissue samples (seven patients with BAV and six with TAV)...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165314/towards-natural-mimetics-of-metformin-and-rapamycin
#12
Alexander Aliper, Leslie Jellen, Franco Cortese, Artem Artemov, Darla Karpinsky-Semper, Alexey Moskalev, Andrew G Swick, Alex Zhavoronkov
Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals-safer, naturally-occurring compounds-that mimic the anti-aging effects of metformin and rapamycin without adverse effects...
November 15, 2017: Aging
https://www.readbyqxmd.com/read/29165235/synthesis-of-n-acetyl-d-quinovosamine-in-rhizobium-etli-ce3-is-completed-after-its-4-keto-precursor-is-linked-to-a-carrier-lipid
#13
Tiezheng Li, K Dale Noel
Bacterial O-antigens are synthesized on lipid carriers before being transferred to lipopolysaccharide core structures. Rhizobium etli CE3 lipopolysaccharide is a model for understanding O-antigen biological function. CE3 O-antigen structure and genetics are known. However, proposed enzymology for CE3 O-antigen synthesis has been examined very little in vitro, and even the sugar added to begin the synthesis is uncertain. A model based on mutagenesis studies predicts that 2-acetamido-2,6-dideoxy-d-glucose (QuiNAc) is the first O-antigen sugar and that genes wreV, wreQ and wreU direct QuiNAc synthesis and O-antigen initiation...
November 22, 2017: Microbiology
https://www.readbyqxmd.com/read/29165073/recent-progress-in-delivery-of-therapeutic-and-imaging-agents-utilizing-organic-inorganic-hybrid-nanoparticles
#14
Haque Sheikh Tanzina, Ezharul Chowdhury
Delivery of conventional small molecule drugs and currently evolving nucleic acid-based therapeutics, such as small interfering RNAs (siRNAs) and genes, and contrast agents for high resolution imaging, to the target site of action is highly demanding to increase the therapeutic and imaging efficacy while minimizing the off-target effects of the delivered molecules, as well as develop novel therapeutic and imaging approaches. Organic-inorganic hybrid nanoparticles offer a number of advantages by combining the unique properties of the organic and inorganic counterparts, thus improving the pharmacokinetic behavior and targetability of drugs and contrast agents, and conferring the exclusive optical and magnetic properties for both therapeutic and imaging purposes...
November 19, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29165068/identifying-candidates-for-breast-cancer-using-interactions-of-chemicals-and-proteins
#15
Jing Lu, Kangle Shang, Yi Bi
Breast cancer is one of the major cause of cancer death in women worldwide. Therefore, it is urgent to discovery novel drugs or design effective treatments for this disease. However, the research and development of drugs by using only experimental methods is always time-consuming and expensive. With the development of computer science, some advanced computational methods can make full use of known knowledge to design candidate drugs, thereby reducing the cost and time of experimental testing. In this study, a computational method was proposed to identify novel candidates for breast cancer...
November 20, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/29165010/dnmt3a-co-mutation-is-required-for-flt3-itd-as-an-adverse-prognostic-indicator-in-intermediate-risk-cytogenetic-group-aml
#16
Juan Ma, Jennifer Dunlap, Aleksandra Paliga, Elie Traer, Richard Press, Lisong Shen, Guang Fan
This single institution cohort study of 132 AML patients investigated the clinical implications of co-mutations detected with a 42-gene NGS panel. In the intermediate-risk cytogenetic group, FLT3-ITD is an adverse prognostic indicator only in the presence of a DNMT3A co-mutation, regardless of NPM1 mutation status. In the absence of a concomitant DNMT3A mutation, there was no significant difference in overall survival between FLT3-ITD positive and FLT3-ITD negative patients. Furthermore, mutation analysis on post-induction specimens showed that residual FLT3-ITD and/or DNMT3A mutations were associated with a high frequency of therapy resistance or relapse in AML...
November 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29164822/a-transposon-mutant-library-of-bacillus-cereus-atcc-10987-reveals-novel-genes-required-for-biofilm-formation-and-implicates-motility-as-an-important-factor-for-pellicle-biofilm-formation
#17
Mira Okshevsky, Matilde Greve Louw, Elena Otero Lamela, Martin Nilsson, Tim Tolker-Nielsen, Rikke Louise Meyer
Bacillus cereus is one of the most common opportunistic pathogens causing foodborne illness, as well as a common source of contamination in the dairy industry. B. cereus can form robust biofilms on food processing surfaces, resulting in food contamination due to shedding of cells and spores. Despite the medical and industrial relevance of this species, the genetic basis of biofilm formation in B. cereus is not well studied. In order to identify genes required for biofilm formation in this bacterium, we created a library of 5000 +  transposon mutants of the biofilm-forming strain B...
November 22, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/29164808/a-universal-approach-to-correct-various-hbb-gene-mutations-in-human-stem-cells-for-gene-therapy-of-beta-thalassemia-and-sickle-cell-disease
#18
Liuhong Cai, Hao Bai, Vasiliki Mahairaki, Yongxing Gao, Chaoxia He, Yanfei Wen, You-Chuan Jin, You Wang, Rachel L Pan, Armaan Qasba, Zhaohui Ye, Linzhao Cheng
Beta-thalassemia is one of the most common recessive genetic diseases, caused by mutations in the HBB gene. Over 200 different types of mutations in the HBB gene containing three exons have been identified in patients with β-thalassemia (β-thal) whereas a homozygous mutation in exon 1 causes sickle cell disease (SCD). Novel therapeutic strategies to permanently correct the HBB mutation in stem cells that are able to expand and differentiate into erythrocytes producing corrected HBB proteins are highly desirable...
November 21, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29164800/the-generation-of-human-%C3%AE-%C3%AE-t-cell-derived-induced-pluripotent-stem-cells-from-whole-peripheral-blood-mononuclear-cell-culture
#19
Daisuke Watanabe, Michiyo Koyanagi-Aoi, Mariko Taniguchi-Ikeda, Yukiko Yoshida, Takeshi Azuma, Takashi Aoi
γδT cells constitute a small proportion of lymphocytes in peripheral blood. Unlike αβT cells, the anti-tumor activities are exerted through several different pathways in a MHC-unrestricted manner. Thus, immunotherapy using γδT cells is considered to be effective for various types of cancer. Occasionally, however, ex vivo expanded cells are not as effective as expected due to cell exhaustion. To overcome the issue of T-cell exhaustion, researchers have generated induced pluripotent stem cells (iPSCs) that harbor the same T-cell receptor (TCR) genes as their original T-cells, which provide nearly limitless sources for antigen-specific cytotoxic T lymphocytes (CTLs)...
November 21, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29164771/functional-self-assembled-peptide-scaffold-inhibits-tnf-alpha-induced-inflammation-and-apoptosis-in-nucleus-pulposus-cells-by-suppressing-nf-%C3%AE%C2%BAb-signaling
#20
Xiaochuan Li, Shi Cheng, Yaohong Wu, Jingwei Ying, Chaofeng Wang, Tianyong Wen, Xuedong Bai, Wei Ji, Deli Wang, Dike Ruan
Although nucleus pulposus (NP) tissue engineering has achieved tremendous success, researches still face the huge obstacles in maintaining cell survival and function. A novel functional self-assembled peptide RADA-KPSS was constructed by conjugating BMP-7 short active fragment (KPSS) to the C-terminus of RADA16-I that displays anti-inflammatory and anti-apoptosis effects. However, whether this functional self-assembled RADA-KPSS peptide can alleviate inflammation and NPC apoptosis induced by TNF-α has not been studied...
November 22, 2017: Journal of Biomedical Materials Research. Part A
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