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https://www.readbyqxmd.com/read/29786562/application-of-hepatocyte-like-cells-to-enhance-hepatic-safety-risk-assessment-in-drug-discovery
#1
REVIEW
Dominic P Williams
Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29782156/combining-high-throughput-sequencing-of-sedadna-and-traditional-palaeolimnological-techniques-to-infer-historical-trends-in-cyanobacterial-communities
#2
Timothy J Tse, Lorne E Doig, Song Tang, Xiaohui Zhang, Weimin Sun, Steve B Wiseman, Cindy Xin Feng, Hongling Liu, John P Giesy, Markus Hecker, Paul D Jones
Freshwaters worldwide are under increasing pressure from anthropogenic activities and changing climate. Unfortunately, many inland waters lack sufficient long-term monitoring to assess environmental trends. Analysis of sedimentary ancient DNA (sedaDNA) is emerging as a means to reconstruct the past occurrence of microbial communities of inland waters. The purpose of this study was to assess a combination of high-throughput sequencing (16S rRNA) of sedaDNA and traditional palaeolimnological analyses to explore multidecadal relationships among cyanobacterial community composition, the potential for cyanotoxin production and palaeoenvironmental proxies...
May 21, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29781014/cat-elcca-catalyzing-drug-discovery-through-click-chemistry
#3
Amanda L Garner
Click chemistry has emerged as a powerful tool in our arsenal for unlocking new biology. This includes its utility in both chemical biology and drug discovery. An emerging application of click chemistry is in the development of biochemical assays for high-throughput screening to identify new chemical probes and drug leads. This Feature Article will discuss the advancements in click chemistry that were necessary for the development of a new class of biochemical assay, catalytic enzyme-linked click chemistry assay or cat-ELCCA...
May 21, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29779155/prioritising-risk-factors-for-type-2-diabetes-causal-inference-through-genetic-approaches
#4
REVIEW
Laura B L Wittemans, Luca A Lotta, Claudia Langenberg
PURPOSE OF THE REVIEW: Causality has been demonstrated for few of the many putative risk factors for type 2 diabetes (T2D) emerging from observational epidemiology. Genetic approaches are increasingly being used to infer causality, and in this review, we discuss how genetic discoveries have shaped our understanding of the causal role of factors associated with T2D. RECENT FINDINGS: Genetic discoveries have led to the identification of novel potential aetiological factors of T2D, including the protective role of peripheral fat storage capacity and specific metabolic pathways, such as the branched-chain amino acid breakdown...
May 19, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29778532/non-alcoholic-fatty-liver-disease-insights-from-sphingolipidomics
#5
David J Montefusco, Jeremy C Allegood, Sarah Spiegel, L Ashley Cowart
Non-alcoholic fatty liver disease (NAFLD) is a major clinical concern and its treatment consumes abundant resources. While accumulation of lipids in hepatocytes initiates the disease, this in itself is not necessarily harmful; rather, initiation of inflammation and subsequent fibrosis and cirrhosis are critical steps in NAFLD pathology. Mechanisms linking lipid overload to downstream disease progression are not fully understood; however, bioactive lipid metabolism may underlie instigation of proinflammatory signaling...
May 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29776627/introduction-molecular-medicine-in-the-common-era-applications-and-impact-of-molecular-pathology-in-health-and-disease
#6
REVIEW
Martin H Bluth
The unprecedented expansion of molecular pathology continues to affect and influence the clinical laboratory. Technological advances in high-throughput automation, cost containment, and refined methodology have improved the understanding of pathobiology through application of molecular pathology to multiple disease spaces. Incorporation of this field to emerging omics platforms, pharmacovigilance and biomarker discovery, and accessibility by lay consumers demonstrates the widespread reach of molecular pathology in the clinical marketplace...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29774042/assessing-the-efficiency-of-phenotyping-early-traits-in-a-greenhouse-automated-platform-for-predicting-drought-tolerance-of-soybean-in-the-field
#7
Laura S Peirone, Gustavo A Pereyra Irujo, Alejandro Bolton, Ignacio Erreguerena, Luis A N Aguirrezábal
Conventional field phenotyping for drought tolerance, the most important factor limiting yield at a global scale, is labor-intensive and time-consuming. Automated greenhouse platforms can increase the precision and throughput of plant phenotyping and contribute to a faster release of drought tolerant varieties. The aim of this work was to establish a framework of analysis to identify early traits which could be efficiently measured in a greenhouse automated phenotyping platform, for predicting the drought tolerance of field grown soybean genotypes...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29772236/identification-and-characterization-of-circular-rnas-in-rapid-atrial-pacing-dog-atrial-tissue
#8
Wenfeng Shangguan, Xue Liang, Wen Shi, Tong Liu, Manman Wang, Guangping Li
Circular RNAs (circRNAs) have emerged as novel molecules of interest in gene regulation as other noncoding RNAs, and participating in the process of many diseases. However, the expression and functions of circRNAs in Rapid atrial pacing (RAP) dog atrial tissue still unknown. 12 canines were randomly assigned to control and pacing group. RAP at 500 beats per minute was maintained 14 days in the pacing group. The expression characterization of circRNAs were revealed by high-throughput sequencing. We totally predicted 15,990 circRNAs in dog atrial tissues...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29767369/high-throughput-sequencing-based-approaches-for-gene-expression-analysis
#9
R Raja Sekhara Reddy, M V Ramanujam
Next-generation sequencing has emerged as the method of choice to answer fundamental questions in biology. The massively parallel sequencing technology for RNA-Seq analysis enables better understanding of gene expression patterns in model and nonmodel organisms. Sequencing per se has reached the stage of commodity level while analyzing and interpreting huge amount of data has been a significant challenge. This chapter is aimed at discussing the complexities involved in sequencing and analysis, and tries to simplify sequencing based gene expression analysis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29767365/current-and-future-methods-for-mrna-analysis-a-drive-toward-single-molecule-sequencing
#10
Anthony Bayega, Somayyeh Fahiminiya, Spyros Oikonomopoulos, Jiannis Ragoussis
The transcriptome encompasses a range of species including messenger RNA, and other noncoding RNA such as rRNA, tRNA, and short and long noncoding RNAs. Due to the huge role played by mRNA in development and disease, several methods have been developed to sequence and characterize mRNA, with RNA sequencing (RNA-Seq) emerging as the current method of choice particularly for large high-throughput studies. Short-read RNA-Seq which involves sequencing of short cDNA fragments and computationally assembling them to reconstruct the transcriptome, or aligning them to a reference is the most widely used approach...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29766788/microbial-genetic-screens-for-monitoring-protein-misfolding-associated-with-neurodegeneration-tools-for-identifying-disease-relevant-genes-and-for-screening-synthetic-and-natural-compound-libraries-for-the-discovery-of-potential-therapeutics
#11
Kalliopi Kostelidou, Ilias Matis, Georgios Skretas
Neurodegenerative diseases (ND) are a major threat to the aging population and the lack of a single preventive or disease-modifying agent only serves to increase their impact. In the past few years, protein misfolding and the subsequent formation of neurotoxic oligomeric/aggregated protein species have emerged as a unifying theme underlying the pathology of these complex diseases. Recently developed microbial genetic screens and selection systems for monitoring ND-associated protein misfolding have allowed the establishment of high-throughput assays for the identification of cellular factors and processes that are important mediators of ND-associated proteotoxicities...
May 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29766737/identification-of-small-molecule-egfr-allosteric-inhibitors-by-high-throughput-docking
#12
Fabiana Caporuscio, Annachiara Tinivella, Valentina Restelli, Marta S Semrau, Luca Pinzi, Paola Storici, Massimo Broggini, Giulio Rastelli
AIM: The EGFR inhibitors represent the first-line treatment of non-small-cell lung cancer. However, the emergence of resistance urgently requires the development of new inhibitors targeting drug-resistant mutants. METHODOLOGY: A recently released structure of an EGFR kinase domain in complex with an allosteric inhibitor and a mutant protein model derived from it were used to set up a low-cost high-throughput docking protocol for the fast identification of EGFR allosteric inhibitors...
May 16, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29766503/transcriptome-analysis-of-potential-mirna-involved-in-adipogenic-differentiation-of-c2c12-myoblasts
#13
Ye Hou, Liangliang Fu, Jingjin Li, Jingxuan Li, Yunxia Zhao, Yu Luan, An Liu, Huiying Liu, Xinyun Li, Shuhong Zhao, Changchun Li
>Emerging evidence indicates that microRNA (miRNA) plays an important role in adipogenesis and disease pathogenesis. To investigate the miRNA involved in regulating different periods of adipogenesis, we performed a comprehensive study on microRNAome during the stimulation of adipogenesis by an adipogenic differentiation cocktail in C2C12 myoblasts at 0, 2, 4, and 7 days using the Solexa sequencing technology. In this study, we identified 52 differentially expressed (DE) miRNA. Functional annotation indicated that the target genes of DE miRNA were mostly enriched in adipogenic transdifferentiation and fat metabolism-related pathways, including Wnt, mitogen-activated protein kinase (MAPK), and insulin signaling...
May 16, 2018: Lipids
https://www.readbyqxmd.com/read/29765865/a-protocatechuate-biosensor-for-pseudomonas-putida-kt2440-via-promoter-and-protein-evolution
#14
Ramesh K Jha, Jeremy M Bingen, Christopher W Johnson, Theresa L Kern, Payal Khanna, Daniel S Trettel, Charlie E M Strauss, Gregg T Beckham, Taraka Dale
Robust fluorescence-based biosensors are emerging as critical tools for high-throughput strain improvement in synthetic biology. Many biosensors are developed in model organisms where sophisticated synthetic biology tools are also well established. However, industrial biochemical production often employs microbes with phenotypes that are advantageous for a target process, and biosensors may fail to directly transition outside the host in which they are developed. In particular, losses in sensitivity and dynamic range of sensing often occur, limiting the application of a biosensor across hosts...
June 2018: Metabolic Engineering Communications
https://www.readbyqxmd.com/read/29765365/human-activity-determines-the-presence-of-integron-associated-and-antibiotic-resistance-genes-in-southwestern-british-columbia
#15
Miguel I Uyaguari-Díaz, Matthew A Croxen, Zhiyao Luo, Kirby I Cronin, Michael Chan, Waren N Baticados, Matthew J Nesbitt, Shaorong Li, Kristina M Miller, Damion Dooley, William Hsiao, Judith L Isaac-Renton, Patrick Tang, Natalie Prystajecky
The dissemination of antibiotic resistant bacteria from anthropogenic sources into the environment poses an emerging public health threat. Antibiotic resistance genes (ARGs) and gene-capturing systems such as integron-associated integrase genes ( intI ) play a key role in alterations of microbial communities and the spread of antibiotic resistant bacteria into the environment. In order to assess the effect of anthropogenic activities on watersheds in southwestern British Columbia, the presence of putative antibiotic resistance and integrase genes was analyzed in the microbiome of agricultural, urban influenced, and protected watersheds...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29765036/a-crispri-screen-in-e-coli-reveals-sequence-specific-toxicity-of-dcas9
#16
Lun Cui, Antoine Vigouroux, François Rousset, Hugo Varet, Varun Khanna, David Bikard
High-throughput CRISPR-Cas9 screens have recently emerged as powerful tools to decipher gene functions and genetic interactions. Here we use a genome-wide library of guide RNAs to direct the catalytically dead Cas9 (dCas9) to block gene transcription in Escherichia coli. Using a machine-learning approach, we reveal that guide RNAs sharing specific 5-nucleotide seed sequences can produce strong fitness defects or even kill E. coli regardless of the other 15 nucleotides of guide sequence. This effect occurs at high dCas9 concentrations and can be alleviated by tuning the expression of dCas9 while maintaining strong on-target repression...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764945/a-mechanism-of-unidirectional-transformation-leading-to-antibiotic-resistance-occurs-within-nasopharyngeal-pneumococcal-biofilm-consortia
#17
Santiago M Lattar, Xueqing Wu, Jennifer Brophy, Fuminori Sakai, Keith P Klugman, Jorge E Vidal
Streptococcus pneumoniae acquires genes for resistance to antibiotics such as streptomycin (Str) or trimethoprim (Tmp) by recombination via transformation of DNA released by other pneumococci and closely related species. Using naturally transformable pneumococci, including strain D39 serotype 2 (S2) and TIGR4 (S4), we studied whether pneumococcal nasopharyngeal transformation was symmetrical, asymmetrical, or unidirectional. Incubation of S2Tet and S4Str in a bioreactor simulating the human nasopharynx led to the generation of SpnTet/Str recombinants...
May 15, 2018: MBio
https://www.readbyqxmd.com/read/29764461/characterization-of-a-new-apple-luteovirus-identified-by-high-throughput-sequencing
#18
Huawei Liu, Liping Wu, Ekaterina Nikolaeva, Kari Peter, Zongrang Liu, Dimitre Mollov, Mengji Cao, Ruhui Li
BACKGROUND: 'Rapid Apple Decline' (RAD) is a newly emerging problem of young, dwarf apple trees in the Northeastern USA. The affected trees show trunk necrosis, cracking and canker before collapse in summer. In this study, we discovered and characterized a new luteovirus from apple trees in RAD-affected orchards using high-throughput sequencing (HTS) technology and subsequent Sanger sequencing. METHODS: Illumina NextSeq sequencing was applied to total RNAs prepared from three diseased apple trees...
May 15, 2018: Virology Journal
https://www.readbyqxmd.com/read/29762535/leveraging-energy-harvesting-and-wake-up-receivers-for-long-term-wireless-sensor-networks
#19
Fayçal Ait Aoudia, Matthieu Gautier, Michele Magno, Olivier Berder, Luca Benini
Wireless sensor nodes are traditionally powered by individual batteries, and a significant effort has been devoted to maximizing the lifetime of these devices. However, as the batteries can only store a finite amount of energy, the network is still doomed to die, and changing the batteries is not always possible. A promising solution is to enable each node to harvest energy directly in its environment, using individual energy harvesters. Moreover, novel ultra-low power wake-up receivers, which allow continuous listening of the channel with negligible power consumption, are emerging...
May 15, 2018: Sensors
https://www.readbyqxmd.com/read/29761826/computational-discovery-of-potent-drugs-to-improve-the-treatment-of-pyrazinamide-resistant-mycobacterium-tuberculosis-mutants
#20
Manaswini Jagadeb, Surya N Rath, Avinash Sonawane
Emergence of multi-drug resistance tuberculosis has become a serious health problem globally. Accumulation of mutations in the drug target led to the development of multi-drug resistant mycobacterial strains that have made most of the conventional drugs ineffective. Hence, there is desperate need for the development of new therapeutic strategies. Here, we focused on the analysis of mutations in Mycobacterium tuberculosis (Mtb) PncA (pyrazinamidase) that is responsible for resistance against first-line anti-tuberculosis pyrazinamide (PZA) drug...
May 15, 2018: Journal of Cellular Biochemistry
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