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https://www.readbyqxmd.com/read/27911392/optogenetic-random-mutagenesis-using-histone-minisog-in-c-elegans
#1
Kentaro Noma, Yishi Jin
Forward genetic screening in model organisms is the workhorse to discover functionally important genes and pathways in many biological processes. In most mutagenesis-based screens, researchers have relied on the use of toxic chemicals, carcinogens, or irradiation, which requires designated equipment, safety setup, and/or disposal of hazardous materials. We have developed a simple approach to induce heritable mutations in C. elegans using germline-expressed histone-miniSOG, a light-inducible potent generator of reactive oxygen species...
November 14, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911380/method-for-identifying-small-molecule-inhibitors-of-the-protein-protein-interaction-between-hcn1-and-trip8b
#2
Ye Han, Kyle A Lyman, Matt Clutter, Gary E Schiltz, Quratul-Ain Ismail, Xiangying Cheng, Chi-Hao Luan, Dane M Chetkovich
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed ubiquitously throughout the brain, where they function to regulate the excitability of neurons. The subcellular distribution of these channels in pyramidal neurons of hippocampal area CA1 is regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit. Genetic knockout of HCN pore forming subunits or TRIP8b, both lead to an increase in antidepressant-like behavior, suggesting that limiting the function of HCN channels may be useful as a treatment for Major Depressive Disorder (MDD)...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911319/autotaxin-is-related-to-metabolic-dysfunction-and-predicts-alzheimer-s-disease-outcomes
#3
Kelsey E McLimans, Auriel A Willette
BACKGROUND: Obesity and insulin resistance are associated with neuropathology and cognitive decline in Alzheimer's disease (AD). OBJECTIVE: Ecto-nucleotide pyrophosphatase/phosphodiesterase 2, also called autotaxin, is produced by beige adipose tissue, regulates metabolism, and is higher in AD prefrontal cortex (PFC). Autotaxin may be a novel biomarker of dysmetabolism and AD. METHODS: We studied Alzheimer's Disease Neuroimaging Initiative participants who were cognitively normal (CN; n = 86) or had mild cognitive impairment (MCI; n = 135) or AD (n = 66)...
December 1, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911188/tuning-the-ribosome-the-influence-of-rrna-modification-on-eukaryotic-ribosome-biogenesis-and-function
#4
Katherine E Sloan, Ahmed S Warda, Sunny Sharma, Karl-Dieter Entian, Denis L J Lafontaine, Markus T Bohnsack
Ribosomal RNAs are extensively modified during their transcription and subsequent maturation in the nucleolus, nucleus and cytoplasm. RNA modifications, which are installed either by snoRNA-guided or by stand-alone enzymes, generally stabilise the structure of the ribosome. However, they also cluster at functionally important sites of the ribosome, such as the peptidyltransferase centre and the decoding site, where they facilitate efficient and accurate protein synthesis. The recent identification of sites of substoichiometric 2'-O-methylation and pseudouridylation has overturned the notion that all rRNA modifications are constitutively present on ribosomes, highlighting nucleotide modifications as an important source of ribosomal heterogeneity...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27911048/fluorescent-oligonucleotide-probes-for-screening-high-affinity-nucleobase-surrogates
#5
Asmo Aro-Heinilä, Tuomas Lönnberg
Double-helical oligonucleotide probes featuring a single-nucleotide gap opposed by one of the canonical nucleobases and flanked by the fluorescent nucleobase analogue pyrrolocytosine have been synthesized and titrated with PdII chelates of dipicolinamide and its N2,N6-dialkylated derivatives. The fluorometric titrations revealed greatly increased affinity of the PdII chelates for the nucleobases opposing the gap compared to the respective free nucleotides in solution. Owing to the constrained environment of the single-nucleotide gap, the relative stabilities of the various PdII mediated base pairs were also significantly different from those previously reported at monomer level...
December 2, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27910864/renin-angiotensin-aldosterone-system-gene-polymorphisms-in-gestational-hypertension-and-preeclampsia-a-case-control-gene-association-study
#6
Xun Li, Hongzhuan Tan, Shujin Zhou, Shimin Hu, Tianyi Zhang, Yangfen Li, Qianru Dou, Zhiwei Lai, Fenglei Chen
Pregnancy-induced hypertension (PIH, including preeclampsia [PE] and gestational hypertension [GH]) and cardiovascular diseases (CVDs) have some metabolic changes and risk factors in common. Many studies have reported associations between single nucleotide polymorphisms (SNPs) of renin-angiotensin-aldosterone system (RAAS) genes and CVDs (particularly hypertension), and their findings have provided candidate SNPs for research on genetic correlates of PIH. We explored the association between hypertension-related RAAS SNPs and PIH in a Chinese population...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910850/the-guanine-nucleotide-exchange-factor-net1-facilitates-the-specification-of-dorsal-cell-fates-in-zebrafish-embryos-by-promoting-maternal-%C3%AE-catenin-activation
#7
Shi Wei, Miaomiao Dai, Zhaoting Liu, Yuanqing Ma, Hanqiao Shang, Yu Cao, Qiang Wang
Wnt/β-catenin signaling is essential for the initiation of dorsal-ventral patterning during vertebrate embryogenesis. Maternal β-catenin accumulates in dorsal marginal nuclei during cleavage stages, but its critical target genes essential for dorsalization are silent until mid-blastula transition (MBT). Here, we find that zebrafish net1, a guanine nucleotide exchange factor, is specifically expressed in dorsal marginal blastomeres after MBT, and acts as a zygotic factor to promote the specification of dorsal cell fates...
December 2, 2016: Cell Research
https://www.readbyqxmd.com/read/27910745/a-new-second-messenger-bacterial-c-di-amp
#8
Tiwei Fu, Yuzhong Zhao, Jianping Xi
Nucleotide-based second messengers transduce signals originating from both outside and inside the cell to adaptive responses accordingly. c-di-AMP is a newly established second messenger employed by many organisms. We summarize recent advances in bacterial c-di-AMP-mediated signaling, especially the interaction between c-di-AMP signaling and the host.
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27910159/staphylococcus-aureus-derived-membrane-vesicles-exacerbate-skin-inflammation-in-atopic-dermatitis
#9
S H Jun, J H Lee, S I Kim, C W Choi, T I Park, H R Jung, J W Cho, S H Kim, J C Lee
BACKGROUND: Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD are unknown. OBJECTIVE: We investigated whether and how S. aureus-derived membrane vesicles (MVs) contribute to worsening of AD. METHODS: Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions...
November 5, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27910131/whole-exome-association-of-rare-deletions-in-multiplex-oral-cleft-families
#10
Jack Fu, Terri H Beaty, Alan F Scott, Jacqueline Hetmanski, Margaret M Parker, Joan E Bailey Wilson, Mary L Marazita, Elisabeth Mangold, Hasan Albacha-Hejazi, Jeffrey C Murray, Alexandre Bureau, Jacob Carey, Stephen Cristiano, Ingo Ruczinski, Robert B Scharpf
By sequencing the exomes of distantly related individuals in multiplex families, rare mutational and structural changes to coding DNA can be characterized and their relationship to disease risk can be assessed. Recently, several rare single nucleotide variants (SNVs) were associated with an increased risk of nonsyndromic oral cleft, highlighting the importance of rare sequence variants in oral clefts and illustrating the strength of family-based study designs. However, the extent to which rare deletions in coding regions of the genome occur and contribute to risk of nonsyndromic clefts is not well understood...
December 1, 2016: Genetic Epidemiology
https://www.readbyqxmd.com/read/27910058/gene-delivery-for-the-generation-of-bioartificial-pacemaker
#11
Patrick K W Chan, Ronald A Li
Electronic pacemakers have been used in patients with heart rhythm disorders for device-supported pacing. While effective, there are such shortcomings as limited battery life, permanent implantation of catheters, the lack of autonomic neurohumoral responses, and risks of lead dislodging. Here we describe protocols for establishing porcine models of sick sinus syndrome and complete heart block, and the generation of bioartificial pacemaker by delivering a strategically engineered form of hyperpolarization-activated cyclic nucleotide-gated pacemaker channel protein via somatic gene transfer to convert atrial or ventricular muscle cardiomyocytes into nodal-like cells that rhythmically fire action potentials...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909932/complete-nucleotide-sequences-of-seven-soybean-mosaic-viruses-smv-isolated-from-wild-soybeans-glycine-soja-in-china
#12
Yun-Xia Chen, Mian Wu, Fang-Fang Ma, Jian-Qun Chen, Bin Wang
Soybean mosaic virus (SMV) is a devastating plant virus classified in the family Potyviridae, and known to infect cultivated soybeans (Glycine max). In this study, seven new SMVs were isolated from wild soybean samples and analyzed by whole-genome sequencing. An updated SMV phylogeny was built with the seven new and 83 known SMV genomic sequences. Results showed that three northeastern SMV isolates were distributed in clade III and IV, while four southern SMVs were grouped together in clade II and all contained a recombinant BCMV fragment (~900 bp) in the upstream part of the genome...
December 1, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27909766/association-between-tlr2-tlr4-gene-polymorphisms-and-copd-phenotype-in-a%C3%A2-greek-cohort
#13
A Apostolou, T Kerenidi, A Michopoulos, K I Gourgoulianis, M Noutsias, A E Germenis, M Speletas
BACKGROUND: Considering that the innate immune system plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that functional single-nucleotide polymorphisms (SNPs) of innate immune genes affect the disease phenotype and prognosis. AIM: To elucidate the contribution of common functional TLR2 and TLR4 SNPs and genotypic deficiency of the mannose-binding lectin (MBL) protein, both as single parameters and in combination, in Greek COPD patients...
December 1, 2016: Herz
https://www.readbyqxmd.com/read/27909454/linkage-and-association-analyses-of-schizophrenia-with-genetic-variations-on-chromosome-22q11-in-koreans
#14
Se Chang Yoon, Yong Lee Jang, Jong-Won Kim, Eun-Young Cho, Dong Yeon Park, Kyung Sue Hong, Yu Sang Lee
OBJECTIVE: Chromosome 22q11 has been implicated as a susceptibility locus of schizophrenia. It also contains various candidate genes for which evidence of association with schizophrenia has been reported. To determine whether genetic variations in chromosome 22q11 are associated with schizophrenia in Koreans, we performed a linkage analysis and case-control association study. METHODS: Three microsatellite markers within a region of 4.35 Mb on 22q11 were genotyped for 47 multiplex schizophrenia families, and a non-parametric linkage analysis was applied...
November 2016: Psychiatry Investigation
https://www.readbyqxmd.com/read/27909439/the-a-allele-of-the-single-nucleotide-polymorphism-rs630923-creates-a-binding-site-for-mef2c-resulting-in-reduced-cxcr5-promoter-activity-in-b-cell-lymphoblastic-cell-lines
#15
Nikita A Mitkin, Alisa M Muratova, Anton M Schwartz, Dmitry V Kuprash
Chemokine receptor CXCR5 is highly expressed in B-cells and under normal conditions is involved in their migration to specific areas of secondary lymphoid organs. B-cells are known to play an important role in various autoimmune diseases including multiple sclerosis (MS) where areas of demyelinating lesions attract B-cells by overexpressing CXCL13, the CXCR5 ligand. In this study, we aimed to determine the functional significance of single-nucleotide polymorphism rs630923 (A/C), which is located in cxcr5 gene promoter, and its common allele is associated with increased risk of MS...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27909141/developing-a-risk-scoring-model-for-ankylosing-spondylitis-based-on-a-combination-of-hla-b27-single-nucleotide-polymorphism-and-copy-number-variant-markers
#16
Seung-Hyun Jung, Sung-Min Cho, Seon-Hee Yim, So-Hee Kim, Hyeon-Chun Park, Mi-La Cho, Seung-Cheol Shim, Tae-Hwan Kim, Sung-Hwan Park, Yeun-Jun Chung
OBJECTIVE: To develop a genotype-based ankylosing spondylitis (AS) risk prediction model that is more sensitive and specific than HLA-B27 typing. METHODS: To develop the AS genetic risk scoring (AS-GRS) model, 648 individuals (285 cases and 363 controls) were examined for 5 copy number variants (CNV), 7 single-nucleotide polymorphisms (SNP), and an HLA-B27 marker by TaqMan assays. The AS-GRS model was developed using logistic regression and validated with a larger independent set (576 cases and 680 controls)...
December 2016: Journal of Rheumatology
https://www.readbyqxmd.com/read/27908992/first-complete-genome-sequence-of-a-simian-foamy-virus-isolate-from-a-cynomolgus-macaque
#17
Koji Sakai, Yasushi Ami, Yuriko Suzaki, Tetsuro Matano
We report here the first complete proviral genome sequence (DDBJ/ENA/GenBank accession no. LC094267) of a simian foamy virus, SFVmfa/Cy5061, isolated from a cynomolgus macaque (Macaca fascicularis). This proviral genome consists of 12,965 nucleotides and has five open reading frames, gag, pol, env, tas, and bet, as with other foamy viruses.
December 1, 2016: Genome Announcements
https://www.readbyqxmd.com/read/27908959/rapid-screening-of-sugar-nucleotide-donor-specificities-of-putative-glycosyltransferases
#18
M Osman Sheikh, Stephanie M Halmo, Sneha Patel, Dustin Middleton, Hideyuki Takeuchi, Christopher M Schafer, Christopher M West, Robert S Haltiwanger, Fikri Y Avci, Kelley W Moremen, Lance Wells
Determining the correct enzymatic activity of putative glycosyltransferases (GTs) can be challenging as these enzymes can utilize multiple donor and acceptor substrates. Upon initial determination of the donor-sugar nucleotide(s), a GT utilizes various acceptor molecules that can then be tested. Here, we describe a quick method to screen sugar-nucleotide donor specificities of GTs utilizing a sensitive, nonradioactive, commercially available bioluminescent uridine diphosphate detection kit. This in vitro method allowed us to validate the sugar-nucleotide donor-substrate specificities of recombinantly expressed human, bovine, bacterial and protozoan GTs...
November 22, 2016: Glycobiology
https://www.readbyqxmd.com/read/27908825/egfr-mutation-subtypes-influence-survival-outcomes-following-first-line-gefitinib-therapy-in-advanced-asian-nsclc-patients
#19
Natalia Sutiman, Shao Weng Tan, Eng Huat Tan, Wan Teck Lim, Ravindran Kanesvaran, Quan Sing Ng, Amit Jain, Mei Kim Ang, Wan Ling Tan, Chee Keong Toh, Balram Chowbay
INTRODUCTION: Activating mutations in the EGFR gene have been shown to confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs) in advanced NSCLC patients. However, wide inter-patient variability in treatment outcomes to EGFR TKIs in these patients remains unaccounted for. This study aimed to evaluate the influence of EGFR mutation types and subtypes on survival outcomes in advanced Asian NSCLC patients receiving first-line gefitinib therapy. METHODS: Patients with stage IIIB/IV, harboring EGFR mutations, receiving first-line gefitinib treatment and of Asian descent (N=383) were evaluated...
November 28, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27908797/molecular-detection-and-characterization-of-respiratory-syncytial-virus-b-genotypes-circulating-in-pakistani-children
#20
Uzma Bashir, Nadia Nisar, Nayab Mahmood, Muhammad Masroor Alam, Hajra Sadia, Syed Sohail Zahoor Zaidi
Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infections in young children, but very little is known about its epidemiology and circulating genotypes in Pakistan. This study analyzed the epidemiological and molecular characteristics of RSV B genotypes in Pakistani children below 5years with acute respiratory tract infections (ARIs) during three consecutive winter seasons from 2010 to 2013. A total of 1941 samples were analyzed for RSV infection by real time PCR and 24% (472/1941) samples were found positive out of which 22...
November 28, 2016: Infection, Genetics and Evolution
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