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Emergency throughput

Liqin Wang, Miao Xu, Noel Southall, Wei Zheng, Shuishu Wang
Tuberculosis (TB) still kills over 1.5 million people per year despite available anti-TB drugs. The emergence of drug-resistant TB poses a major threat to public health and prompts for an urgent need for new and more effective drugs. The long duration needed to treat TB by the current TB drugs, which target the essential cellular activities, inevitably leads to the emergence of drug-resistance. PhoP of Mycobacterium tuberculosis (MTB), an essential virulence factor, is a novel target for drug development. Guided by the crystal structure of the PhoP-DNA complex, we designed and developed a robust high-throughput screening assay for identification of PhoP inhibitors that disrupt the PhoP-DNA binding...
October 10, 2016: Combinatorial Chemistry & High Throughput Screening
O F Ahmad, A Akbar
INTRODUCTION: Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal (GI) disorder. Increasing evidence implicates the GI microbiota in IBS pathogenesis and its modulation represents an emerging therapeutic strategy. SOURCES OF DATA: Original and review articles were identified through selective searches performed on PubMed and Google Scholar. AREAS OF AGREEMENT: The role of gut microbiota in IBS is supported by evidence from animal and human studies...
October 13, 2016: British Medical Bulletin
David Rizzo, Pierre-Julien Viailly, Sylvain Mareschal, Elodie Bohers, Jean-Michel Picquenot, Dominique Penther, Sydney Dubois, Vinciane Marchand, Philippe Bertrand, Catherine Maingonnat, Pascaline Etancelin, Jean Feuillard, Christian Bastard, Hervé Tilly, Fabrice Jardin, Philippe Ruminy
Little is known on the phylogenetic relationship between diagnostic and relapse clones of Diffuse Large B-Cell Lymphoma (DLBCL). We applied High Throughput Sequencing (HTS) of the VDJ locus of Immunoglobulin Heavy chain (IGHV) on fourteen DLBCL patients with serial samples, including tumor biopsies and/or peripheral blood mononuclear cells (PBMC). Phylogenetic data were consolidated with targeted sequencing and cytogenetics. Phylogeny clearly showed that DLBCL relapse could occur according either an early or a late divergent mode...
October 13, 2016: American Journal of Hematology
Eman M Hassan, William G Willmore, Maria C DeRosa
Circulating tumor cells (CTCs) are cells that shed from a primary tumor and freely circulate in the blood, retaining the ability to initiate metastasis and form a secondary tumor in distant organs in the body. CTCs reflect the molecular profile of the primary tumor, therefore studying CTCs can allow for an understanding of the mechanism of metastasis, and an opportunity to monitor the prognosis of cancer. Unfortunately, the detection of CTCs is a considerable challenge due to their low abundance in the bloodstream and the lack of consistent markers present to recognize these cells...
October 13, 2016: Nucleic Acid Therapeutics
Zhuoran Zhang, Enzhuo Yang, Chunmiao Hu, Han Cheng, Crystal Y Chen, Dan Huang, Richard Wang, Yue Zhao, Lijun Rong, Marco Vignuzzi, Hongbo Shen, Ling Shen, Zheng W Chen
While we are approaching the global eradication of circulating wild-type polioviruses(PV), vaccination with oral poliovirus vaccine (OPV) has led to emergence of circulating vaccine-derived poliovirus (cVDPV) and vaccine-associated paralytic poliomyelitis (VAPP). Complete cessation of all poliovirus infections may require stopping use of OPV and formulating improved vaccines and new antiviral drugs. Currently, no licensed drugs are available to treat chronically infected poliovirus excretors. Here, we created a modified PV expressing Gaussia Luciferase (PV-GLuc) and developed a cell-based high-throughput screening (HTS) antiviral assay...
October 12, 2016: ACS Infectious Diseases
Alan S L Wong, Gigi C G Choi, Timothy K Lu
High-order interactions among components of interconnected genetic networks regulate complex functions in biological systems, but deciphering these interactions is challenging. New strategies are emerging to decode these combinatorial genetic interactions across a wide range of organisms. Here, we review advances in multiplexed and combinatorial genetic perturbation technologies and high-throughput profiling platforms that are enabling the systematic dissection of complex genetic networks. These rapidly evolving technologies are being harnessed to probe combinatorial gene functions in functional genomics studies and have the potential to advance our understanding of how genetic networks regulate sophisticated biological phenotypes, to generate novel therapeutic strategies, and to enable the engineering of complex artificial gene networks...
October 6, 2016: Annual Review of Genetics
Liliana R Cisneros Castillo, Andrei-Dumitru Oancea, Christian Stüllein, Anne Régnier-Vigouroux
Multicellular tumor spheroids (MCTSs) embedded in a matrix are re-emerging as a powerful alternative to monolayer-based cultures. The primary information gained from a three-dimensional model is the invasiveness of treatment-exposed MCTSs through the acquisition of light microscopy images. The amount and complexity of the acquired data and the bias arisen by their manual analysis are disadvantages calling for an automated, high-throughput analysis. We present a universal algorithm we developed with the scope of being robust enough to handle images of various qualities and various invasion profiles...
October 12, 2016: Scientific Reports
Adam P Deveau, Victoria L Bentley, Jason N Berman
Current treatment strategies for acute leukemias largely rely on nonspecific cytotoxic drugs that result in high therapy-related morbidity and mortality. Cost effective, pertinent animal models are needed to link in vitro studies with the development of new therapeutic agents in clinical trials on a high-throughput scale. However, targeted therapies have had limited success moving from bench-to-clinic, often due to unexpected off-target effects. The zebrafish has emerged as a reliable in vivo tool for modeling human leukemia...
October 6, 2016: Experimental Hematology
Sandipan Datta, Sunil Sahdeo, Jennifer A Gray, Christophe Morriseau, Bruce D Hammock, Gino Cortopassi
Mitochondrial toxicity is emerging as a major mechanism underlying serious human health consequences. This work performs a high-throughput screen (HTS) of 176 environmental chemicals for mitochondrial toxicity utilizing a previously reported biosensor platform. This established HTS confirmed known mitochondrial toxins and identified novel mitotochondrial uncouplers such as 2, 2'-Methylenebis(4-chlorophenol) and pentachlorophenol. It also identified a mitochondrial 'structure activity relationship' (SAR) in the sense that multiple environmental chlorophenols are mitochondrial inhibitors and uncouplers...
October 4, 2016: Mitochondrion
Christopher E Slagle, Frank L Conlon
Congenital heart defects remain a leading cause of infant mortality in the western world, despite decades of research focusing on cardiovascular development and disease. With the recent emergence of several high-throughput technologies including RNA sequencing, chromatin-immunoprecipitation-coupled sequencing, mass-spectrometry-based proteomics analyses, and the numerous variations of these strategies, investigations into cardiac development have been transformed from candidate-based studies into whole-genome, -transcriptome, and -proteome undertakings...
October 4, 2016: Trends in Genetics: TIG
Myeong Chan Jo, Lidong Qin
The budding yeast Saccharomyces cerevisiae has been a powerful model for the study of aging and has enabled significant contributions to our understanding of basic mechanisms of aging in eukaryotic cells. However, the laborious low-throughput nature of conventional methods of performing aging assays limits the pace of discoveries in this field. Some of the technical challenges of conventional aging assay methods can be overcome by use of microfluidic systems coupled to time-lapse microscopy. One of the major advantages is the ability of a microfluidic system to perform long-term cell culture under well-defined environmental conditions while tracking individual yeast...
September 26, 2016: Small
Xin Zhang, Fei Xie, Baobei Lv, Pengxiang Zhao, Xuemei Ma
A simple and high-throughput assay to detect fungicide resistance is required for large-scale monitoring of the emergence of resistant strains of Botrytis cinerea. Using suspension array technology performed on a Bio-Plex 200 System, we developed a single-tube allele-specific primer extension assay that can simultaneously detect eight alleles in one reaction. These eight alleles include E198 and 198A of the β-Tubulin gene (BenA), H272 and 272Y of the Succinate dehydrogenase iron-sulfur subunit gene (SdhB), I365 and 365S of the putative osmosensor histidine kinase gene (BcOS1), and F412 and 412S of the 3-ketoreductase gene (erg27)...
2016: Frontiers in Microbiology
Yong Yang, Han Cheng, Hui Yan, Peng-Zhan Wang, Rong Rong, Ying-Ying Zhang, Cheng-Bo Zhang, Rui-Kun Du, Li-Jun Rong
Emerging viruses such as Ebola virus (EBOV), Lassa virus (LASV), and avian influenza virus H5N1 (AIV) are global health concerns. Since there is very limited options (either vaccine or specific therapy) approved for humans against these viruses, there is an urgent need to develop prophylactic and therapeutic treatments. Previously we reported a high-throughput screening (HTS) protocol to identify entry inhibitors for three highly pathogenic viruses (EBOV, LASV, and AIV) using a human immunodeficiency virus-based pseudotyping platform which allows us to perform the screening in a BSL-2 facility...
October 5, 2016: Journal of Medical Virology
Ralph S Baric, Sean Crosson, Blossom Damania, Samuel I Miller, Eric J Rubin
Host infection by microbial pathogens cues global changes in microbial and host cell biology that facilitate microbial replication and disease. The complete maps of thousands of bacterial and viral genomes have recently been defined; however, the rate at which physiological or biochemical functions have been assigned to genes has greatly lagged. The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function...
October 4, 2016: MBio
Huihui Chen, Jingjing Wan, Kaifei Chen, Gang Luo, Jiajun Fan, James Clark, Shicheng Zhang
Hydrothermal liquefaction (HTL) is an emerging and promising technology for the conversion of wet biomass into bio-crude, however, little attention has been paid to the utilization of hydrothermal liquefaction wastewater (HTLWW) with high concentration of organics. The present study investigated biogas production from wastewater obtained from HTL of straw for bio-crude production, with focuses on the analysis of the microbial communities and characterization of the organics. Batch experiments showed the methane yield of HTLWW (R-HTLWW) was 184 mL/g COD, while HTLWW after petroleum ether extraction (PE-HTLWW), to extract additional bio-crude, had higher methane yield (235 mL/g COD) due to the extraction of recalcitrant organic compounds...
September 27, 2016: Water Research
Guntram Suske
For long it has been recognized that CCAAT boxes and GC-rich elements co-occur in many human and murine promoters within 100bp upstream of the transcription start site. The trimeric transcription factor NF-Y is the major CCAAT box-binding factor, and members of the SP family of transcription factors are the major GC box-binding proteins. Recent chromatin immunoprecipitations coupled with high throughput sequencing (ChIP-seq) have examined binding of NF-Y and the ubiquitous SP factors SP1, SP2 and SP3 genome-wide, allowing for comprehensive comparison of NF-Y and SP factor actions in the context of chromatin...
September 30, 2016: Biochimica et Biophysica Acta
Salomon Manier, Karma Salem, Siobhan V Glavey, Aldo M Roccaro, Irene M Ghobrial
Multiple myeloma (MM) is a genetically complex disease. The past few years have seen an evolution in cancer research with the emergence of next-generation sequencing (NGS), enabling high throughput sequencing of tumors-including whole exome, whole genome, RNA, and single-cell sequencing as well as genome-wide association study (GWAS). A few inherited variants have been described, counting for some cases of familial disease. Hierarchically, primary events in MM can be divided into hyperdiploid (HDR) and nonhyperdiploid subtypes...
2016: Cancer Treatment and Research
Krishna Choudhary, Luyao Ruan, Fei Deng, Nathan Shih, Sharon Aviran
: To serve numerous functional roles, RNA must fold into specific structures. Determining these structures is thus of paramount importance. The recent advent of high-throughput sequencing-based structure profiling experiments has provided important insights into RNA structure and widened the scope of RNA studies. However, as a broad range of approaches continues to emerge, a universal framework is needed to quantitatively ensure consistent and high-quality data. We present SE-Qualyzer, a visual and interactive application that makes it easy and efficient to gauge data quality, screen for transcripts with high-quality information and identify discordant replicates in structure profiling experiments...
September 30, 2016: Bioinformatics
Sahir Kalim, Eugene P Rhee
The high-throughput, high-resolution phenotyping enabled by metabolomics has been applied increasingly to a variety of questions in nephrology research. This article provides an overview of current metabolomics methodologies and nomenclature, citing specific considerations in sample preparation, metabolite measurement, and data analysis that investigators should understand when examining the literature or designing a study. Furthermore, we review several notable findings that have emerged in the literature that both highlight some of the limitations of current profiling approaches, as well as outline specific strengths unique to metabolomics...
September 28, 2016: Kidney International
Alba Garin-Muga, Fernando J Corrales, Victor Segura
The integration of genomics and proteomics has led to the emergence of proteogenomics, a field of research successfully applied to the characterization of cancer samples. The diagnosis, prognosis and response to therapy of cancer patients will largely benefit from the identification of mutations present in their genome. The current state of the art of high throughput experiments for genome-wide detection of somatic mutations in cancer samples has allowed the development of projects such as the TCGA, in which hundreds of cancer genomes have been sequenced...
2016: Advances in Experimental Medicine and Biology
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