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https://www.readbyqxmd.com/read/29793215/in-silico-insight-into-voltage-gated-sodium-channel-1-7-inhibition-for-anti-pain-drug-discovery
#1
Mingxing Wang, Wei Li, Ying Wang, Yongbo Song, Jian Wang, Maosheng Cheng
Studies on human genetics have implicated the voltage-gated sodium channel Nav1.7 as an appealing target for the treatment of pain. In this study, we put forward a ligand-based pharmacophore for the first time, which was generated by a set of multiple chemical scaffolds including sulfonamide and non-sulfonamide derivatives and consisted of four chemical features: an aromatic ring, a hydrophobic group and two hydrogen acceptors. The active cavity was divided into three regions according to the properties of the amino acids surrounded and was used for the docking of 16 known active inhibitors...
May 18, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29793141/new-contributions-to-gruberia-lanceolata-gruber-1884-kahl-1932-based-on-analyses-of-multiple-populations-and-genes-ciliophora-heterotrichea-gruberiidae
#2
Xiangrui Chen, Shahed Uddin Ahmed Shazib, Ji Hye Kim, Min Seok Kim, Mann Kyoon Shin
Gruberia Kahl, 1932 is a species-poor genus comprising only seven named species. Most of these species have not been reinvestigated since the original reports. In the present work, we investigated the taxonomy and phylogeny of Gruberia lanceolata (Gruber, 1884) Kahl, 1932 based on analyses of morphology and multiple gene sequences from four South Korean populations. This species is mainly characterized by a well-developed peristome region, segmented paroral membrane, and moniliform macronucleus. Some morphological features were not stable among the four populations investigated, such as body shape and size, cell color, and the ratio of oral length to body length...
May 9, 2018: European Journal of Protistology
https://www.readbyqxmd.com/read/29792989/novel-genotypes-and-multilocus-genotypes-of-enterocytozoon-bieneusi-in-pigs-in-northwestern-china-a-public-health-concern
#3
Sha-Sha Wang, Jun-Qiang Li, Yun-Hui Li, Xiang-Wei Wang, Xian-Chen Fan, Xin Liu, Zi-Juan Li, Jun-Ke Song, Long-Xian Zhang, Guang-Hui Zhao
Enterocytozoon bieneusi, the most important and common microsporidian species, inhabits in most animals and humans causing diarrhea and systemic diseases. The objectives of the present study were to examine the prevalence and genetic variability of E. bieneusi in pigs in Shaanxi province, northwestern China. A total of 560 pig faecal samples were collected from five different farms in Shaanxi province and molecularly characterized using multilocus genotyping (MLST) technology. High E. bieneusi infection rate (78...
May 21, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29792923/high-throughput-sequencing-identifies-chilling-responsive-genes-in-sweetpotato-ipomoea-batatas-lam-during-storage
#4
Zeyi Xie, Zhilin Zhou, Hongmin Li, Jingjing Yu, Jiaojiao Jiang, Zhonghou Tang, Daifu Ma, Baohong Zhang, Yonghua Han, Zongyun Li
Sweetpotato (Ipomoea batatas L.) is a globally important economic food crop. It belongs to Convolvulaceae family and origins in the tropics; however, sweetpotato is sensitive to cold stress during storage. In this study, we performed transcriptome sequencing to investigate the sweetpotato response to chilling stress during storage. A total of 110,110 unigenes were generated via high-throughput sequencing. Differentially expressed genes (DEGs) analysis showed that 18,681 genes were up-regulated and 21,983 genes were down-regulated in low temperature condition...
May 21, 2018: Genomics
https://www.readbyqxmd.com/read/29792895/pharmacogenomics-of-drug-induced-liver-injury-dili-molecular-biology-to-clinical-applications
#5
REVIEW
Kalaiyarasi Kaliyaperumal, Jane I Grove, Robin M Delahay, William J H Griffiths, Adam Duckworth, Guruprasad P Aithal
A number of drug-specific and host-related factors contribute to the development of drug-induced liver injury (DILI). Investigations focused on genetic susceptibility to DILI have advanced our understanding of the pathogenesis of this rare, yet potentially life-threatening adverse reaction. Candidate gene studies involving well-characterized patients with DILI and drug-exposed controls have identified single nucleotide polymorphisms (SNPs) affecting the metabolism and clearance of specific drugs and hence, influencing individual's susceptibility to DILI...
May 21, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29792880/molecular-alterations-during-larval-development-of-haemonchus-contortus-in-vitro-are-under-tight-post-transcriptional-control
#6
Guangxu Ma, Tao Wang, Pasi K Korhonen, Ching-Seng Ang, Nicholas A Williamson, Neil D Young, Andreas J Stroehlein, Ross S Hall, Anson V Koehler, Andreas Hofmann, Robin B Gasser
In this study, we explored the molecular alterations in the developmental switch from the L3 to the exsheathed L3 (×L3) and to the L4 stage of Haemonchus contortus in vitro using an integrated transcriptomic, proteomic and bioinformatic approach. Totals of 9,754 mRNAs, 88 microRNAs (miRNAs) and 1,591 proteins were identified, and 6,686 miRNA-mRNA pairs inferred in all larval stages studied. Approximately 16% of transcripts in the combined transcriptome (representing all three larval stages) were expressed as proteins, and there were positive correlations (r = 0...
May 22, 2018: International Journal for Parasitology
https://www.readbyqxmd.com/read/29792781/is-bla-ctx-m-1-riding-the-same-plasmid-among-horses-in-sweden-and-france
#7
Agnese Lupo, Marisa Haenni, Estelle Saras, Joanna Gradin, Jean-Yves Madec, Stefan Börjesson
A predominance of the blaCTX-M-1 /IncHI1 plasmid combination in horses has been reported in Czech-Republic, Denmark, and The Netherlands. To clarify a possible specific plasmid epidemiology of blaCTX-M-1 in horses in a European perspective, a collection of 74 extended-spectrum beta-lactamase-producing Escherichia coli recovered from diseased horses in France and Sweden during the period 2009-2014 was investigated in respect of their genetic relatedness, plasmid content, and molecular features. Overall, 80% of E...
May 24, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29792777/dismantling-a-complex-of-anther-smuts-microbotryum-on-carnivorous-plants-in-the-genus-pinguicula
#8
Rebekka Ziegler, Matthias Lutz, Jolanta Piątek, Marcin Piątek
The anther smuts of the genus Microbotryum are known from host plant species belonging to the Caryophyllaceae, Dipsacaceae, Lamiaceae, Lentibulariaceae, Montiaceae, and Primulaceae. Of these, the anther smuts on Caryophyllaceae, in particular on Silene spp., are best known because they include model organisms studied in many disciplines of fungal biology. For Microbotryum species parasitic on Caryophyllaceae, a high degree of host specificity was revealed and several cryptic species were described. In contrast, the host specificity within Microbotryum pinguiculae occurring in anthers of different Pinguicula species (Lentibulariaceae) has not been investigated in detail until now...
March 15, 2018: Mycologia
https://www.readbyqxmd.com/read/29792762/genetic-profiling-in-acute-myeloid-leukemia-a-path-to-predicting-treatment-outcome
#9
Giuseppe Visani, Federica Loscocco, Alessandro Isidori, Pier Paolo Piccaluga
Despite substantial progresses in acute myeloid leukemia (AML) diagnosis and treatment, at least half of patient will eventually die for the disease. In the last decades, the use of genetic and genomic approaches allowed the identification of patients with higher risk of recurrence after and/or resistance to CHT. However, though many novel drugs have been proposed and tested, only little clinical improvements have been made concerning the treatment of the so called 'high risk' patients. Areas covered: In this article, the authors, based on their own experience and the most updated literature, review the basic knowledge of AML prognostication and treatment prediction developed throughout genetic and genomic profiling, and focus on the use of gene expression profiling as a promising predictive tool...
May 24, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29792591/comprehensive-evolutionary-and-phylogenetic-analysis-of-hepacivirus-n-hnv
#10
M S da Silva, D M Junqueira, L F Baumbach, S P Cibulski, A C S Mósena, M N Weber, S Silveira, G M de Moraes, R D Maia, V C S Coimbra, C W Canal
Hepaciviruses (HVs) have been detected in several domestic and wild animals and present high genetic diversity. The actual classification divides the genus Hepacivirus into 14 species (A-N), according to their phylogenetic relationships, including the bovine hepacivirus [Hepacivirus N (HNV)]. In this study, we confirmed HNV circulation in Brazil and sequenced the whole genome of two strains. Based on the current classification of HCV, which is divided into genotypes and subtypes, we analysed all available bovine hepacivirus sequences in the GenBank database and proposed an HNV classification...
May 24, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29792310/bet-inhibition-overcomes-receptor-tyrosine-kinase-mediated-cetuximab-resistance-in-hnscc
#11
Brandon Leonard, Toni M Brand, Rachel A O'Keefe, Eliot Lee, Yan Zang, Jacquelyn D Kemmer, Hua Li, Jennifer R Grandis, Neil E Bhola
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29792158/landraces-of-snake-melon-an-ancient-middle-eastern-crop-reveal-extensive-morphological-and-dna-diversity-for-potential-genetic-improvement
#12
Samer Omari, Yuri Kamenir, Jennifer I C Benichou, Sarah Pariente, Hanan Sela, Rafael Perl-Treves
BACKGROUND: Snake melon (Cucumis melo var. flexuosus, "Faqqous") is a traditional and ancient vegetable in the Mediterranean area. A collection of landraces from 42 grower fields in Israel and Palestinian territories was grown and characterized in a "Common Garden" rain-fed experiment, at the morphological-horticultural and molecular level using seq-DArT markers. RESULTS: The different landraces ("populations") showed extensive variation in morphology and quantitative traits such as yield and femaleness, and clustered into four horticultural varieties...
May 23, 2018: BMC Genetics
https://www.readbyqxmd.com/read/29791872/gene-expression-in-cord-blood-links-genetic-risk-for-neurodevelopmental-disorders-with-maternal-psychological-distress-and-adverse-childhood-outcomes
#13
Michael S Breen, Aliza P Wingo, Nastassja Koen, Kirsten A Donald, Mark Nicol, Heather J Zar, Kerry J Ressler, Joseph D Buxbaum, Dan J Stein
Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n=20), depression (n=31) and PTSD with comorbid depression (n=13), compared to carefully matched trauma exposed controls (n=23) and healthy mothers (n=62)...
May 20, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29791871/network-based-disease-module-discovery-by-a-novel-seed-connector-algorithm-with-pathobiological-implications
#14
Rui-Sheng Wang, Joseph Loscalzo
Understanding the genetic basis of complex diseases is challenging. Prior work shows that disease-related proteins do not typically function in isolation. Rather, they often interact with each other to form a network module that underlies dysfunctional mechanistic pathways. Identifying such disease modules will provide insights into a systems-level understanding of molecular mechanisms of diseases. Owing to the incompleteness of our knowledge of disease proteins and limited information on the biological mediators of pathobiological processes, the key proteins (seed proteins) for many diseases appear scattered over the human protein-protein interactome and form a few small branches, rather than coherent network modules...
May 20, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29791608/hiv-1-genetic-diversity-and-resistance-to-antiretroviral-drugs-among-pregnant-women-in-ribeir%C3%A3-o-preto-sp-brazil-cross-sectional-study
#15
Ana Teresa Mancini Pimenta, Isadora Alonso Correa, Patricia Pereira Dos Santos Melli, Renata Abduch, Geraldo Duarte, José Carlos Couto-Fernandez, Silvana Maria Quintana
BACKGROUND: Increasing genetic diversity of HIV-1 and emergence of drug-resistant mutations may reduce the efficacy of antiretroviral therapy and prophylaxis that are used to prevent mother-to-child transmission. The aim of this study was to assess the genetic diversity and prevalence of drug-resistant mutations among HIV-infected pregnant women. DESIGN AND SETTING: Cross-sectional study at an outpatient clinic for infectious diseases within gynecology and obstetrics...
March 2018: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/29791171/-diagnosis-of-mody-brief-overview-for-clinical-practice
#16
Jana Urbanová, Ludmila Brunerová, Jan Brož
Maturity Onset Diabetes of the Young (MODY) comprises inherited forms of diabetes mellitus caused by the mutations in the genes involved in the development, differentiation and function of beta-cells. The majority of patients with MODY remains misdiagnosed and erroneously classified as type 1 or type 2 diabetic patients. Correct MODY diagnosis is, however, essential since it enables individualization of treatment, assessment of the prognosis and identification of diabetes among patient´s relatives. Clinical presentation of MODY is highly variable and it could resemble other types of diabetes, thus identification of MODY patients might be difficult...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29791133/design-construction-and-validation-of-histone-binding-effectors-in-vitro-and-in-cells
#17
Stefan J Tekel, Cassandra M Barrett, Daniel A Vargas, Karmella A Haynes
Chromatin is a system of nuclear proteins and nucleic acids that plays a pivotal role in gene expression and cell behavior, and is therefore the subject of intense study for cell development and cancer research. Biochemistry, crystallography, and reverse genetics have elucidated the macromolecular interactions that drive chromatin regulation. One of the central mechanisms is the recognition of post translational modifications (PTMs) on histone proteins by a family of nuclear proteins known as "readers...
May 23, 2018: Biochemistry
https://www.readbyqxmd.com/read/29790873/diversity-of-genetic-events-associated-with-mlh1-promoter-methylation-in-lynch-syndrome-families-with-heritable-constitutional-epimutation
#18
Julie Leclerc, Cathy Flament, Tonio Lovecchio, Lucie Delattre, Emilie Ait Yahya, Stéphanie Baert-Desurmont, Nelly Burnichon, Myriam Bronner, Odile Cabaret, Sophie Lejeune, Rosine Guimbaud, Gilles Morin, Jacques Mauillon, Philippe Jonveaux, Pierre Laurent-Puig, Thierry Frébourg, Nicole Porchet, Marie-Pierre Buisine
PurposeConstitutional epimutations are an alternative to genetic mutations in the etiology of genetic diseases. Some of these epimutations, termed secondary, correspond to the epigenetic effects of cis-acting genetic defects transmitted to the offspring following a Mendelian inheritance pattern. In Lynch syndrome, a few families with such apparently heritable MLH1 epimutations have been reported so far.MethodsWe designed a long-range polymerase chain reaction next-generation sequencing strategy to screen MLH1 entire gene and applied it to 4 French families with heritable epimutations and 10 additional patients with no proven transmission of their epimutations...
April 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29790871/phenotypic-expansion-illuminates-multilocus-pathogenic-variation
#19
Ender Karaca, Jennifer E Posey, Zeynep Coban Akdemir, Davut Pehlivan, Tamar Harel, Shalini N Jhangiani, Yavuz Bayram, Xiaofei Song, Vahid Bahrambeigi, Ozge Ozalp Yuregir, Sevcan Bozdogan, Gozde Yesil, Sedat Isikay, Donna Muzny, Richard A Gibbs, James R Lupski
PurposeMultilocus variation-pathogenic variants in two or more disease genes-can potentially explain the underlying genetic basis for apparent phenotypic expansion in cases for which the observed clinical features extend beyond those reported in association with a "known" disease gene.MethodsAnalyses focused on 106 patients, 19 for whom apparent phenotypic expansion was previously attributed to variation at known disease genes. We performed a retrospective computational reanalysis of whole-exome sequencing data using stringent Variant Call File filtering criteria to determine whether molecular diagnoses involving additional disease loci might explain the observed expanded phenotypes...
April 26, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29790687/expression-profiles-of-selected-genes-in-tumors-and-matched-surgical-margins-in-oral-cavity-cancer-do-we-have-to-pay-attention-to-the-molecular-analysis-of-the-surgical-margins
#20
Joanna K Strzelczyk, Łukasz Krakowczyk, Karolina Gołąbek, Aleksander J Owczarek
BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are associated with an interplay between genetics and the environment; they account for 3% of all diagnosed malignant tumors in men and 2% of those in women. OBJECTIVES: The aim of the study was to analyze the significance of TIMP3, SFRP1, SFRP2, CDH1, RASSF1, RORA, and DAPK1 gene expression in head and neck squamous cell carcinoma tumors, and in matching surgical margin samples. We also analyzed the association between clinical parameters and the expression of the selected genes...
April 24, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
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