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https://www.readbyqxmd.com/read/29783050/disruption-of-ergosterol-and-tryptophan-biosynthesis-as-well-as-cell-wall-integrity-pathway-and-the-intracellular-ph-homeostasis-lead-to-mono-2-ethylhexyl-phthalate-toxicity-in-budding-yeast
#1
Linghuo Jiang, Litong Wang, Tianshu Fang, Vassilios Papadopoulos
Endocrine disrupting chemicals (EDCs) are substances in the environment, food, and consumer products that interfere with hormone homeostasis, metabolism or reproduction in humans and animals. One such EDC, the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), exerts its function through its principal bioactive metabolite, mono-(2-ethylhexyl)-phthalate (MEHP). To fully understand the effects of MEHP on cellular processes and metabolism as well as to assess the impact of genetic alteration on the susceptibility to MEHP-induced toxicity, we screened MEHP-sensitive mutations on a genome-scale in the eukaryotic model organism Saccharomyces cerevisiae...
May 15, 2018: Chemosphere
https://www.readbyqxmd.com/read/29783045/factors-affecting-gene-expression-and-activity-of-heme-and-manganese-dependent-catalases-in-lactobacillus-casei-strains
#2
Annamaria Ricciardi, Rocco Gerardo Ianniello, Eugenio Parente, Teresa Zotta
Catalases reduce oxidative stress by degrading hydrogen peroxide to molecular oxygen and water. The presence of heme-dependent or manganese-dependent catalases was observed for a long time in lactic acid bacteria (LAB) but, to date, knowledge on the factors affecting gene expression and enzymatic functionality are limited to a very few strains. In this study, the effect of atmosphere of incubation (not aerated static growth vs aerated shaken growth) and supplementation with Fe2+ , hemin, Mn2+ or their combinations on the catalase production of respiration-competent strain Lactobacillus casei N87 was evaluated using a 24 factorial design...
May 8, 2018: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/29782933/whole-genome-sequencing-and-analyses-identify-high-genetic-heterogeneity-and-diversity-of-rotavirus-genotype-p-6-strains-circulating-in-africa
#3
Martin M Nyaga, Yi Tan, Mapaseka L Seheri, Rebecca A Halpin, Asmik Akopov, Karla M Stucker, Nadia B Fedorova, Susmita Shrivastava, A Duncan Steele, Jason M Mwenda, Brett E Pickett, Suman R Das, M Jeffery Mphahlele
Rotavirus A (RVA) exhibits a wide genotype diversity globally. Little is known about the genetic composition of genotype P[6] from Africa. This study investigated possible evolutionary mechanisms leading to genetic diversity of genotype P[6] VP4 sequences. Phylogenetic analyses on 167 P[6] VP4 full-length sequences were conducted, which included six porcine-origin sequences. Of the 167 sequences, 57 were newly acquired through whole genome sequencing as part of this study. The other 110 sequences were all publicly-available global P[6] VP4 full-length sequences downloaded from GenBank...
May 18, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29782925/the-developmental-genetics-of-canalization
#4
REVIEW
Benedikt Hallgrimsson, Rebecca M Green, David Katz, Jennifer L Fish, Francois P J Bernier, Charles C Roseman, Nathan M Young, James M Cheverud, Ralph S Marcucio
Canalization, or robustness to genetic or environmental perturbations, is fundamental to complex organisms. While there is strong evidence for canalization as an evolved property that varies among genotypes, the developmental and genetic mechanisms that produce this phenomenon are very poorly understood. For evolutionary biology, understanding how canalization arises is important because, by modulating the phenotypic variation that arises in response to genetic differences, canalization is a determinant of evolvability...
May 18, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29782550/multiple-roles-of-core-protein-linker-in-hepatitis-b-virus-replication
#5
Kuancheng Liu, Laurie Luckenbaugh, Xiaojun Ning, Ji Xi, Jianming Hu
Hepatitis B virus (HBV) core protein (HBc) contains an N-terminal domain (NTD, assembly domain) and a C-terminal domain (CTD), which are linked by a flexible linker region. HBc plays multiple essential roles in viral replication, including capsid assembly, packaging of the viral pregenomic RNA (pgRNA) into nucleocapsids, viral reverse transcription that converts pgRNA to the genomic DNA, and secretion of DNA-containing (complete) virions or genome-free (empty) virions. The HBc linker is generally assumed to act merely as a spacer between NTD and CTD but some results suggest that the linker may affect NTD assembly...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782468/potential-role-of-gut-microbiota-in-als-pathogenesis-and-possible-novel-therapeutic-strategies
#6
Letizia Mazzini, Luca Mogna, Fabiola De Marchi, Angela Amoruso, Marco Pane, Irene Aloisio, Nicole Bozzi Cionci, Francesca Gaggìa, Ausiliatrice Lucenti, Enrica Bersano, Roberto Cantello, Diana Di Gioia, Giovanni Mogna
BACKGROUND: Recent preclinical studies suggest that dysfunction of gastrointestinal tract may play a role in amyotrophic lateral sclerosis (ALS) pathogenesis through a modification of the gut microbiota brain axis. Our study is the first focused on microbiota analysis in ALS patients. AIM: Our aim was to study the main human gut microbial groups and the overall microbial diversity in ALS and healthy subjects. Moreover we have examined the influence of a treatment with a specific bacteriotherapy composed of Lactobacillus strains (Lactobacillus fermentum, Lactobacillus delbrueckii, Lactobacillus plantarum, Lactobacillus salivarius) acting on the gastrointestinal barrier...
May 18, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29781996/replication-of-the-ordered-nonredundant-library-of-pseudomonas-aeruginosa-strain-pa14-transposon-insertion-mutants
#7
Eliana Drenkard, Rhianna M Hibbler, D Alina Gutu, Alexander D Eaton, Amy L Silverio, Frederick M Ausubel, Bryan P Hurley, Lael M Yonker
Pseudomonas aeruginosa is a phenotypically and genotypically diverse and adaptable Gram-negative bacterium ubiquitous in human environments. P. aeruginosa is able to form biofilms, develop antibiotic resistance, produce virulence factors, and rapidly evolve in the course of a chronic infection. Thus P. aeruginosa can cause both acute and chronic, difficult to treat infections, resulting in significant morbidity in certain patient populations. P. aeruginosa strain PA14 is a human clinical isolate with a conserved genome structure that infects a variety of mammalian and nonvertebrate hosts making PA14 an attractive strain for studying this pathogen...
May 4, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781598/instrumentation-for-xpcr-incorporating-qpcr-and-hrma
#8
Alexander R Jafek, Sean Harbertson, Hayden Brady, Raheel Samuel, Bruce K Gale
A microfluidic PCR device was developed that enables DNA amplification at speeds as fast as 2 seconds/cycle, with concurrent detection and amplification. Two targets were amplified from human genomic DNA. By observing the fluorescence emitted by a DNA dye while the sample is amplified, it is possible to obtain both qPCR and spatial melting information about the amplified product. The speed and integration of the device make it conducive to while-you-wait diagnostic tests that do not require post-PCR analysis...
May 21, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29780833/the-growing-genetic-and-functional-diversity-of-extended-spectrum-beta-lactamases
#9
REVIEW
Sadeeq Ur Rahman, Tariq Ali, Ijaz Ali, Nazir Ahmad Khan, Bo Han, Jian Gao
The β -lactams-a large class of diverse compounds-due to their excellent safety profile and broad antimicrobial spectrum are considered to be the most widely used therapeutic class of antibacterials prescribed in human and veterinary clinical practices. This, unfortunately, has also given rise to a continuous increased resistance globally in health care settings as well as in the community due to their permanent selective force driving diversification of the resistance mechanism. Resistance against β -lactams is increasing rapidly as novel β -lactamases, enzymes that degrade β -lactams, are being discovered each day such as recent emergence of extended spectrum β -lactamases (ESBL) that have the ability to inactivate most of the cephalosporins...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29780403/correlation-analyses-reveal-a-limited-role-of-transcription-in-genome-wide-differential-microrna-expression-in-mammals
#10
Xiaoxiao Zhang, Siling Hu, Jia Su, Zixuan Xie, Wenjing Li, Yan Zeng
Transcription initiates the cascade of gene expression and is often assumed to play a predominant role in determining how much gene products are ultimately expressed. The relationship between mRNA levels and protein levels has been studied extensively to reveal the degrees of transcriptional and post-transcriptional regulation of protein expression. The extent to which transcription globally controls the differential expression of non-coding RNAs, however, is poorly defined. MicroRNAs (miRNAs) are a class of small, non-coding RNAs whose biogenesis involves transcription followed by extensive processing...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29780036/revised-phylogeny-of-the-cellulose-synthase-gene-superfamily-insights-into-cell-wall-evolution
#11
Alan Little, Julian G Schwerdt, Neil J Shirley, Shi F Khor, Kylie Neumann, Lisa A O'Donovan, Jelle Lahnstein, Helen M Collins, Marilyn Henderson, Geoffrey B Fincher, Rachel A Burton
Cell walls are crucial for the integrity and function of all land plants, and are of central importance in human health, livestock production, and as a source of renewable bioenergy. Many enzymes that mediate the biosynthesis of cell wall polysaccharides are encoded by members of the large cellulose synthase (CesA) gene superfamily. Here, we analyzed 29 sequenced genomes and 17 transcriptomes to revise the phylogeny of the CesA gene superfamily in angiosperms. Our results identify ancestral gene clusters that predate the monocot-eudicot divergence and reveal several novel evolutionary observations, including the expansion of the Poaceae-specific cellulose synthase-like CslF family to the graminids and restiids and the characterisation of a previously unreported eudicot lineage, CslM, that forms a reciprocally monophyletic eudicot-monocot grouping with the CslJ clade...
May 20, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29780001/automated-typing-of-red-blood-cell-and-platelet-antigens-a-whole-genome-sequencing-study
#12
William J Lane, Connie M Westhoff, Nicholas S Gleadall, Maria Aguad, Robin Smeland-Wagman, Sunitha Vege, Daimon P Simmons, Helen H Mah, Matthew S Lebo, Klaudia Walter, Nicole Soranzo, Emanuele Di Angelantonio, John Danesh, David J Roberts, Nick A Watkins, Willem H Ouwehand, Adam S Butterworth, Richard M Kaufman, Heidi L Rehm, Leslie E Silberstein, Robert C Green
BACKGROUND: There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone...
May 17, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29779896/all-optical-electrophysiology-for-high-throughput-functional-characterization-of-a-human-ipsc-derived-motor-neuron-model-of-als
#13
Evangelos Kiskinis, Joel M Kralj, Peng Zou, Eli N Weinstein, Hongkang Zhang, Konstantinos Tsioras, Ole Wiskow, J Alberto Ortega, Kevin Eggan, Adam E Cohen
Human induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch-clamp electrophysiology. Here, we describe an optimized all-optical electrophysiology, "Optopatch," pipeline for high-throughput functional characterization of human iPSC-derived neuronal cultures. We demonstrate the method in a human iPSC-derived motor neuron (iPSC-MN) model of amyotrophic lateral sclerosis (ALS)...
May 11, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29779780/on-sunspots-click-science-and-molecular-iconography
#14
Igor Mokrousov
CRISPR-spoligotyping and MIRU-VNTR typing, SITVIT_WEB and MIRU-VNTRplus are the methods and online resources most widely used for Mycobacterium tuberculosis genotype family assignment and clustering analysis. They have been proven invaluable for molecular epidemiological studies of this important human pathogen in setting up the terminology and classification framework. However, they are inherently limited by insufficient knowledge of evolution of the targeted genome loci (especially, CRISPR). The situation is aggravated by the dogmatic, iconographic perception of these increasingly user-friendly online tools...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779585/translational-studies-provide-insights-for-the-etiology-and-treatment-of-cortical-bone-osteoporosis
#15
REVIEW
Robert Brommage, Claes Ohlsson
Increasing attention is being focused on the important contributions of cortical bone to bone strength, fractures and osteoporosis therapies. Recent progress in human genome wide association studies in combination with high-throughput mouse gene knockout phenotyping efforts of multiple genes and advanced conditional gene inactivation in mouse models have successfully identified genes with crucial roles in cortical bone homeostasis. Particular attention in this review is given to genes, such as WNT16, POSTN and SFRP4, that differentially affect cortical and trabecular bone architecture...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779582/animal-models-of-endocrine-disruption
#16
REVIEW
Heather B Patisaul, Suzanne E Fenton, David Aylor
Endocrine disrupting chemicals (EDCs) are compounds that alter the structure and function of the endocrine system and may be contributing to disorders of the reproductive, metabolic, neuroendocrine and other complex systems. Typically, these outcomes cannot be modeled in cell-based or other simple systems necessitating the use of animal testing. Appropriate animal model selection is required to effectively recapitulate the human experience, including relevant dosing and windows of exposure, and ensure translational utility and reproducibility...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779531/orphan-drugs-and-their-impact-on-pharmaceutical-development
#17
REVIEW
Misty M Attwood, Mathias Rask-Andersen, Helgi B Schiöth
High levels of productivity, with an increasing number of approvals for new molecular entities (NMEs) by the FDA during the past decade, have coincided with the emergence of innovative drugs for treatments of rare diseases that have utilized the FDA orphan drug program. Since 2000, NMEs with orphan designation encompass a significant portion of approved drugs and constitute about 80% of the approved drugs that have established novel human genome-encoded products in recent years. Biological approvals are also expanding, with 40% of the approved biological agents having orphan designation...
June 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29779058/genetics-of-resistant-hypertension-the-missing-heritability-and-opportunities
#18
REVIEW
Samantha K Teixeira, Alexandre C Pereira, Jose E Krieger
PURPOSE OF THE REVIEW: Blood pressure regulation in humans has long been known to be a genetically determined trait. The identification of causal genetic modulators for this trait has been unfulfilling at the least. Despite the recent advances of genome-wide genetic studies, loci associated with hypertension or blood pressure still explain a very low percentage of the overall variation of blood pressure in the general population. This has precluded the translation of discoveries in the genetics of human hypertension to clinical use...
May 19, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/29778942/transcriptomic-and-methylomic-analysis-reveal-the-toxicological-effect-of-2-3-7-8-tetrachlorodibenzodioxin-on-human-embryonic-stem-cell
#19
Keng Po Lai, Jing Woei Li, Ting Fung Chan, Andy Chen, Cherie Yin Lau Lee, William Shu Biu Yeung, Chris Kong Chu Wong
Cumulating epidemiological studies demonstrated that environmental exposure to endocrine disrupting chemicals (EDCs) during the early stages of fetal development is associated with the increase in disease susceptibility in later life. The fetal developmental plasticity is considered as a protective mechanism against an undesirable prenatal environment. Dioxin is one of the environmental contaminants and is considered a diabetogenic factor. Experimental animal and human epidemiological studies have revealed that dioxin exposure was associated with insulin resistance and altered beta cell function...
May 10, 2018: Chemosphere
https://www.readbyqxmd.com/read/29778836/interrogation-of-mammalian-protein-complex-structure-function-and-membership-using-genome-scale-fitness-screens
#20
Joshua Pan, Robin M Meyers, Brittany C Michel, Nazar Mashtalir, Ann E Sizemore, Jonathan N Wells, Seth H Cassel, Francisca Vazquez, Barbara A Weir, William C Hahn, Joseph A Marsh, Aviad Tsherniak, Cigall Kadoch
Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex...
May 14, 2018: Cell Systems
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