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https://www.readbyqxmd.com/read/27923063/control-of-gene-expression-by-rna-binding-protein-action-on-alternative-translation-initiation-sites
#1
Angela Re, Levi Waldron, Alessandro Quattrone
Transcript levels do not faithfully predict protein levels, due to post-transcriptional regulation of gene expression mediated by RNA binding proteins (RBPs) and non-coding RNAs. We developed a multivariate linear regression model integrating RBP levels and predicted RBP-mRNA regulatory interactions from matched transcript and protein datasets. RBPs significantly improved the accuracy in predicting protein abundance of a portion of the total modeled mRNAs in three panels of tissues and cells and for different methods employed in the detection of mRNA and protein...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27922124/convex-analysis-of-mixtures-for-separating-non-negative-well-grounded-sources
#2
Yitan Zhu, Niya Wang, David J Miller, Yue Wang
Blind Source Separation (BSS) is a powerful tool for analyzing composite data patterns in many areas, such as computational biology. We introduce a novel BSS method, Convex Analysis of Mixtures (CAM), for separating non-negative well-grounded sources, which learns the mixing matrix by identifying the lateral edges of the convex data scatter plot. We propose and prove a sufficient and necessary condition for identifying the mixing matrix through edge detection in the noise-free case, which enables CAM to identify the mixing matrix not only in the exact-determined and over-determined scenarios, but also in the under-determined scenario...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920723/sex-dependent-anti-stress-effect-of-an-%C3%AE-5-subunit-containing-gabaa-receptor-positive-allosteric-modulator
#3
Sean C Piantadosi, Beverly J French, Michael M Poe, Tamara Timić, Bojan D Marković, Mohan Pabba, Marianne L Seney, Hyunjung Oh, Beverley A Orser, Miroslav M Savić, James M Cook, Etienne Sibille
Rationale: Current first-line treatments for stress-related disorders such as major depressive disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2'F-R-CH3 (denoted "α5-PAM"), a positive allosteric modulator selective for α5-subunit containing GABAA receptors found predominantly on cortical pyramidal cell dendrites, has anti-stress effects...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27919501/soluble-serum-vcam-1-whole-blood-mrna-expression-and-treatment-response-in-natalizumab-treated-multiple-sclerosis
#4
E R Petersen, H B Søndergaard, A B Oturai, Peh Jensen, P S Sorensen, F Sellebjerg, L Börnsen
BACKGROUND: Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood. OBJECTIVE: We aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27918628/phenotypic-and-genome-wide-association-analysis-of-spike-ethylene-in-diverse-wheat-genotypes-under-heat-stress
#5
Ravi Valluru, Matthew P Reynolds, William J Davies, Sivakumar Sukumaran
The gaseous phytohormone ethylene plays an important role in spike development in wheat (Triticum aestivum). However, the genotypic variation and the genomic regions governing spike ethylene (SET) production in wheat under long-term heat stress remain unexplored. We investigated genotypic variation in the production of SET and its relationship with spike dry weight (SDW) in 130 diverse wheat elite lines and landraces under heat-stressed field conditions. We employed an Illumina iSelect 90K single nucleotide polymorphism (SNP) genotyping array to identify the genetic loci for SET and SDW through a genome-wide association study (GWAS) in a subset of the Wheat Association Mapping Initiative (WAMI) panel...
December 5, 2016: New Phytologist
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#6
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27917695/nanostring-a-novel-digital-color-coded-barcode-technology-current-and-future-applications-in-molecular-diagnostics
#7
Hin-Fung Tsang, Vivian Weiwen Xue, Su-Pin Koh, Ya-Ming Chiu, Lawrence Po-Wah Ng, Sze-Chuen Cesar Wong
Formalin-fixed, paraffin-embedded (FFPE) tissue sample is a gold mine of resources for molecular diagnosis and retrospective clinical studies. Although molecular technologies have expanded the range of mutations identified in FFPE samples, the applications of existing technologies are limited by the low nucleic acids yield and poor extraction quality. As a result, the routine clinical applications of molecular diagnosis using FFPE samples has been associated with many practical challenges. NanoString technologies utilize a novel digital color-coded barcode technology based on direct multiplexed measurement of gene expression and offer high levels of precision and sensitivity...
December 3, 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27917594/a-novel-two-nucleotide-deletion-in-hps6-affects-mepacrine-uptake-and-platelet-dense-granule-secretion-in-a-family-with-hermansky-pudlak-syndrome
#8
Oliver Andres, Verena Wiegering, Eva-Maria König, Anna Lena Schneider, Daniela Semeniak, Simon Stritt, Eva Klopocki, Harald Schulze
BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by oculocutaneous albinism and platelet dysfunction. We report on a novel HPS6 homozygous frameshift variant (c.1919_1920delTC; p.Val640Glyfs*29) in a nonconsanguineous Caucasian family with two affected siblings (index patients) who presented with oculocutaneous albinism at birth and a mild bleeding phenotype during childhood and adolescence. PROCEDURE: Genetic analysis was conducted by panel-based next-generation sequencing (NGS) and Sanger sequencing...
December 4, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27917192/mining-centuries-old-in-situ-conserved-turkish-wheat-landraces-for-grain-yield-and-stripe-rust-resistance-genes
#9
Deepmala Sehgal, Susanne Dreisigacker, Savaş Belen, Ümran Küçüközdemir, Zafer Mert, Emel Özer, Alexey Morgounov
Wheat landraces in Turkey are an important genetic resource for wheat improvement. An exhaustive 5-year (2009-2014) effort made by the International Winter Wheat Improvement Programme (IWWIP), a cooperative program between the Ministry of Food, Agriculture and Livestock of Turkey, the International Center for Maize and Wheat Improvement (CIMMYT) and the International Center for Agricultural Research in the Dry Areas (ICARDA), led to the collection and documentation of around 2000 landrace populations from 55 provinces throughout Turkey...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27917186/expression-level-of-the-dreb2-type-gene-identified-with-amplifluor-snp-markers-correlates-with-performance-and-tolerance-to-dehydration-in-bread-wheat-cultivars-from-northern-kazakhstan
#10
Yuri Shavrukov, Aibek Zhumalin, Dauren Serikbay, Makpal Botayeva, Ainur Otemisova, Aiman Absattarova, Grigoriy Sereda, Sergey Sereda, Vladimir Shvidchenko, Arysgul Turbekova, Satyvaldy Jatayev, Sergiy Lopato, Kathleen Soole, Peter Langridge
A panel of 89 local commercial cultivars of bread wheat was tested in field trials in the dry conditions of Northern Kazakhstan. Two distinct groups of cultivars (six cultivars in each group), which had the highest and the lowest grain yield under drought were selected for further experiments. A dehydration test conducted on detached leaves indicated a strong association between rates of water loss in plants from the first group with highest grain yield production in the dry environment relative to the second group...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27915305/dna-barcoding-coupled-with-high-resolution-melting-analysis-enables-rapid-and-accurate-distinction-of-aspergillus-species
#11
Gabor Fidler, Sandor Kocsube, Eva Leiter, Sandor Biro, Melinda Paholcsek
We describe a high-resolution melting (HRM) analysis method that is rapid, reproducible, and able to identify reference strains and further 40 clinical isolates of Aspergillus fumigatus (14), A. lentulus (3), A. terreus (7), A. flavus (8), A. niger (2), A. welwitschiae (4), and A. tubingensis (2). Asp1 and Asp2 primer sets were designed to amplify partial sequences of the Aspergillus benA (beta-tubulin) genes in a closed-, single-tube system. Human placenta DNA, further Aspergillus (3), Candida (9), Fusarium (6), and Scedosporium (2) nucleic acids from type strains and clinical isolates were also included in this study to evaluate cross reactivity with other relevant pathogens causing invasive fungal infections...
December 3, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27913932/almost-2-of-spanish-breast-cancer-families-are-associated-to-germline-pathogenic-mutations-in-the-atm-gene
#12
A Tavera-Tapia, L Pérez-Cabornero, J A Macías, M I Ceballos, G Roncador, M de la Hoya, A Barroso, V Felipe-Ponce, R Serrano-Blanch, C Hinojo, M D Miramar-Gallart, M Urioste, T Caldés, S Santillan-Garzón, J Benitez, A Osorio
PURPOSE: There is still a considerable percentage of hereditary breast and ovarian cancer (HBOC) cases not explained by BRCA1 and BRCA2 genes. In this report, next-generation sequencing (NGS) techniques were applied to identify novel variants and/or genes involved in HBOC susceptibility. METHODS: Using whole exome sequencing, we identified a novel germline mutation in the moderate-risk gene ATM (c.5441delT; p.Leu1814Trpfs*14) in a family negative for mutations in BRCA1/2 (BRCAX)...
December 2, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27913859/complex-genetics-architecture-contributes-to-salmonella-resistance-in-acb60-mice
#13
Sean Beatty, Leïla Rached-D'Astous, Danielle Malo
Human infection with Salmonella is of global public health concern. In low- and middle-income countries, Salmonella infection is a major source of disease in terms of both mortality and morbidity, while in high-income nations, the pathogen is an ongoing threat to food security. The outcome of infection with Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) in mouse models is dependent upon a coordinated and complex immune response. A panel of recombinant congenic strains (RCS) derived from the reciprocal double backcross of A/J and C57BL/6J mice has been screened for their susceptibility to Salmonella infection, and the RCS AcB60 was identified to be the most resistant strain to Salmonella infection, more resistant than the parental strain A/J...
December 2, 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/27913812/association-between-cytokines-and-their-receptor-antagonist-gene-polymorphisms-and-clinical-risk-factors-and-acute-rejection-following-renal-transplantation
#14
SIqing Ding, Jianfei Xie, Qiquan Wan
BACKGROUND Acute rejection (AR) after renal transplantation affects both patient and graft survival. There is growing evidence of the genetic association between cytokine or its receptor antagonist and AR in solid organ transplantation. The objectives of this study were to investigate the role of recipient TNF β, IL-10, IL-1β, and IL-1 receptor antagonist (ra) gene polymorphism, as well as traditional clinical variables such as panel-reactive antibody (PRA) levels, donor type, and HLA mismatches in AR following renal transplantation...
December 3, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27913567/drug-repositioning-screens-identify-triamterene-as-a-selective-drug-for-the-treatment-of-dna-mismatch-repair-deficient-cells
#15
Delphine Guillotin, Philip Austin, Rumena Begum, Marta O Freitas, Ashirwad Merve, Tim Brend, Susan C Short, Silvia Marino, Sarah A Martin
PURPOSE: The DNA Mismatch repair (MMR) pathway is required for the maintenance of genome stability. Unsurprisingly, mutations in MMR genes occur in a wide range of different cancers. Studies thus far have largely focused on specific tumor types or MMR mutations, however it is becoming increasingly clear that a therapy targeting MMR-deficiency in general would be clinically very beneficial. EXPERIMENTAL DESIGN: Based on a drug-repositioning approach, we screened a large panel of cell lines with various MMR deficiencies from a range of different tumor types with a compound drug library of previously approved drugs...
December 2, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27913155/early-molecular-stratification-of-high-risk-primary-biliary-cholangitis
#16
Claire Hardie, Kile Green, Laura Jopson, Ben Millar, Barbara Innes, Sarah Pagan, Dina Tiniakos, Jessica Dyson, Muzlifah Haniffa, Venetia Bigley, David E Jones, John Brain, Lucy J Walker
High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel...
November 21, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27913132/rapid-identification-of-candida-spp-frequently-involved-in-invasive-mycoses-by-using-flow-through-hybridization-and-gene-chip-fhgc-technology
#17
Chen Li, Xiurong Ding, Zhizhong Liu, Juanjuan Zhu
The incidence of invasive fungal infections in immunocompromised patients has increased in recent decades. Rapid and accurate identification of these pathogenic fungi is crucial for initiating a timely, safe, and effective antifungal therapy. Here we developed a microarray based on flow-through hybridization gene chip technology. The microarray was tested for its specificity using a panel of reference and blinded clinical isolates. The results proved that this microarray was highly discriminative, leading to the unequivocal identification of each species, including Candida famata and the highly related species Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis...
November 29, 2016: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/27913065/hpv-status-cancer-stem-cell-marker-expression-hypoxia-gene-signatures-and-tumour-volume-identify-good-prognosis-subgroups-in-patients-with-hnscc-after-primary-radiochemotherapy-a-multicentre-retrospective-study-of-the-german-cancer-consortium-radiation-oncology
#18
Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E Aust, Gustavo B Baretton, Howard D Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann
OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed...
November 29, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27913044/clinical-validation-of-the-50-gene-ampliseq-cancer-panel-v2-for-use-on-a-next-generation-sequencing-platform-using-formalin-fixed-paraffin-embedded-and-fine-needle-aspiration-tumour-specimens
#19
Vivek Rathi, Gavin Wright, Diana Constantin, Siok Chang, Huong Pham, Kerryn Jones, Atha Palios, Sue-Anne Mclachlan, Matthew Conron, Penny McKelvie, Richard Williams
The advent of massively parallel sequencing has caused a paradigm shift in the ways cancer is treated, as personalised therapy becomes a reality. More and more laboratories are looking to introduce next generation sequencing (NGS) as a tool for mutational analysis, as this technology has many advantages compared to conventional platforms like Sanger sequencing. In Australia all massively parallel sequencing platforms are still considered in-house in vitro diagnostic tools by the National Association of Testing Authorities (NATA) and a comprehensive analytical validation of all assays, and not just mere verification, is a strict requirement before accreditation can be granted for clinical testing on these platforms...
November 29, 2016: Pathology
https://www.readbyqxmd.com/read/27911494/determining-functional-aptamer-protein-interaction-by-biolayer-interferometry
#20
Xinhui Lou, Martin Egli, Xianbin Yang
Short single-stranded nucleic acids called aptamers are widely being explored as recognition molecules of high affinity and specificity for binding a wide range of target molecules, particularly protein targets. In biolayer interferometry (BLI), a simple Dip-and-Read approach in which the aptamer-coated biosensors are dipped into microplate wells is used to study the interactions between an aptamer and its target protein. Here we describe the protocol for the analysis of the interaction between a well-characterized anti-thrombin RNA aptamer with thrombin (Basic Protocol)...
December 1, 2016: Current Protocols in Nucleic Acid Chemistry
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