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https://www.readbyqxmd.com/read/28434075/associations-of-self-reported-smoking-cotinine-levels-and-epigenetic-smoking-indicators-with-oxidative-stress-among-older-adults-a-population-based-study
#1
Xu Gao, Xīn Gào, Yan Zhang, Lutz Philipp Breitling, Ben Schöttker, Hermann Brenner
Tobacco smoking and oxidative stress (OS) are both related to a wide spectrum of adverse age-related health outcomes, but their association is not yet well-established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with two urinary proxy markers of OS, 8-isoprostane (8-iso) and 8-hydroxy-2'-deoxyguanosine (8-oxodG), in two independent subsets of older adults recruited in Germany (discovery set: n = 978, validation set: n = 531)...
April 22, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28433920/proteomic-analysis-of-sockeye-salmon-serum-as-a-tool-for-biomarker-discovery-and-new-insight-into-the-sublethal-toxicity-of-diluted-bitumen
#2
Sarah L Alderman, Laura A Dindia, Christopher J Kennedy, Anthony P Farrell, Todd E Gillis
Pipelines carrying diluted bitumen (dilbit) from Canada's oil sands traverse North America, including the freshwater habitat of Pacific salmon, posing a risk of environmental release and aquatic exposure. Swimming performance is impacted in juvenile sockeye (Oncorhynchus nerka) exposed to dilbit; therefore biomarkers of dilbit exposure will be valuable for monitoring at-risk salmon stocks. This study characterized changes in the serum proteome of sockeye exposed to a sub-lethal and environmentally relevant concentration of dilbit using isobaric tags for relative and absolute quantitation (iTRAQ), and included a range of experimental conditions to permit identification of biomarkers that are robust across time (1 and 4wk) and exercise level (at rest and following a swim test)...
April 12, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28433871/automatic-cumulative-sums-contour-detection-of-fbp-reconstructed-multi-object-nuclear-medicine-images
#3
Nicholas E Protonotarios, George M Spyrou, George A Kastis
The problem of determining the contours of objects in nuclear medicine images has been studied extensively in the past, however most of the analysis has focused on a single object as opposed to multiple objects. The aim of this work is to develop an automated method for determining the contour of multiple objects in positron emission tomography (PET) and single photon emission computed tomography (SPECT) filtered backprojection (FBP) reconstructed images. These contours can be used for computing body edges for attenuation correction in PET and SPECT, as well as for eliminating streak artifacts outside the objects, which could be useful in compressive sensing reconstruction...
April 14, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28433760/elucidation-of-the-dynamic-nature-of-interactome-networks-a-practical-tutorial
#4
Sandra I Anjo, Tania Martins-Marques, Paulo Pereira, Henrique Girão, Bruno Manadas
Considering that proteins are usually engaged in complex and dynamic networks of interactions to exert their activity, a way to understand proteins' functions and the molecular mechanisms in which those proteins are involved, is by studying their interactome. In this sense, this tutorial presents a simple pipeline for the analysis of the network of interactions of a protein in order to reach a biological interpretation of the mechanisms modulated by those interactions, and understand how these interactions are affected by the experimental conditions...
April 19, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28433698/adipose-crosstalk-with-other-cell-types-in-health-and-disease
#5
REVIEW
Chan Hee J Choi, Paul Cohen
In addition to storing and mobilizing energy, adipocytes secrete circulating factors to signal to other tissues and coordinate energy metabolism. These functions can become disrupted in the setting of obesity, contributing to the development of diabetes, cardiovascular disease, and cancer. Since the discovery of leptin and adiponectin, an increasing number of adipokines have been identified and their functions elucidated. More recent studies have highlighted other modes by which adipose tissue can participate in crosstalk with other cell types and tissues...
April 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28433643/green-light-for-lipid-fingerprinting
#6
Richard P Haslam, Ivo Feussner
The use of targeted lipidomic approaches for the analysis of plant lipids has steadily increased during recent years. We review recent developments of these methods and suggest the introduction of discovery lipidomics as additional approach through a new workflow, lipid fingerprinting, that integrates the advantages of shotgun lipidomics (quantitative data) with LC-MS-based strategies (higher resolution and/or coverage). This article is part of a Special Issue entitled:BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28433531/discovery-and-optimization-of-selective-fgfr4-inhibitors-via-scaffold-hopping
#7
Yikai Wang, Zhengxia Chen, Meibi Dai, Peipei Sun, Chunqiu Wang, Yang Gao, Haixia Zhao, Wenqin Zeng, Liang Shen, Weifeng Mao, Tian Wang, Guoping Hu, Jian Li, Shuhui Chen, Chaofeng Long, Xiaoxin Chen, Junhua Liu, Yang Zhang
Introduction of a Michael acceptor on a flexible scaffold derived from pan-FGFR inhibitors has successfully yielded a novel series of highly potent FGFR4 inhibitors with selectivity over FGFR1. Due to reduced lipophilicity and aromatic ring count, this series demonstrated improved solubility and permeability. However, plasma instability and fast metabolism limited its potential for in vivo studies. Efforts have been made to address these problems, which led to the discovery of compound (-)-11 with improved stability, CYP inhibition, and good activity/selectivity for further optimization...
April 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28433511/design-synthesis-and-pharmacological-evaluation-of-4-azolyl-benzamide-derivatives-as-novel-gpr52-agonists
#8
Kazuyuki Tokumaru, Yoshiteru Ito, Izumi Nomura, Takashi Nakahata, Yuji Shimizu, Emi Kurimoto, Kazunobu Aoyama, Kazuyoshi Aso
G protein-coupled receptor 52 (GPR52) agonists are expected to improve the symptoms of psychiatric disorders. During exploration for a novel class of GPR52 agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzamide (4u; half maximal effective concentration (EC50)=75nM, maximal response (Emax)=122%) starting from a high-throughput screening hit 3 (EC50=470nM, Emax=56%). The structural features of a reported GPR52 agonist were applied to 3, led to design 4-azolylbenzamides as novel GPR52 agonists...
April 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28433481/genetics-of-common-complex-diseases-a-view-from-iceland
#9
REVIEW
David O Arnar, Runolfur Palsson
In the past decade, large scale genotyping has led to discoveries of numerous sequence variants that confer increased risk of many common complex diseases. Interestingly, a substantial proportion of pioneering genetic work has originated from the small nation of Iceland and has been facilitated by an extensive genealogy database. We provide examples of relevant observations made so far in several major disease categories central to internal medicine practice. Some of these findings offer new mechanistic clues into the pathophysiology of common disorders and may suggest novel approaches in diagnosis and drug therapy...
April 19, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28433461/severely-impaired-adult-brain-neurogenesis-in-cyclin-d2-knock-out-mice-produces-very-limited-phenotypic-changes
#10
REVIEW
Robert K Filipkowski, Leszek Kaczmarek
The discovery of new neurons being produced in the brains of adult mammals (adult brain neurogenesis) began a quest to determine the function(s) of these cells. Major hypotheses in the field have assumed that these neurons play pivotal role, in particular, in learning and memory phenomena, mood control, and epileptogenesis. In our studies summarized herein, we used cyclin D2 knockout (KO) mice, as we have shown that cyclin D2 is the key factor in adult brain neurogenesis and thus its lack produces profound impairment of the process...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28433433/design-selection-and-development-of-cyclic-peptide-ligands-for-human-erythropoietin
#11
William S Kish, Hiroyuki Sachi, Amith D Naik, Matthew K Roach, Benjamin G Bobay, Robert K Blackburn, Stefano Menegatti, Ruben G Carbonell
This work presents the selection and characterization of erythropoietin (EPO)-binding cyclic peptide ligands. The sequences were selected by screening a focused library of cyclic depsipeptides cyclo[(Nα-Ac)Dap(A)-X1-X6-AE], whose structure and amino acid compositions were tailored to mimic the EPO receptor. The sequences identified through library screening were synthesized on chromatographic resin and characterized via binding-and-elution studies against EPO to select a pool of candidate ligands. Sequences with higher hydrophobicity consistently showed stronger binding to EPO, with the exception of FSLLSH, which was noted for its lower hydrophobicity and high EPO binding...
April 12, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28433422/postnatal-choline-supplementation-selectively-attenuates-hippocampal-microrna-alterations-associated-with-developmental-alcohol-exposure
#12
Sridevi Balaraman, Nirelia M Idrus, Rajesh C Miranda, Jennifer D Thomas
Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation...
January 3, 2017: Alcohol
https://www.readbyqxmd.com/read/28433076/identification-of-ntrk3-fusions-in-childhood-melanocytic-neoplasms
#13
Lu Wang, Klaus J Busam, Ryma Benayed, Robert Cimera, Jiajing Wang, Ryan Denley, Mamta Rao, Ruth Aryeequaye, Kerry Mullaney, Long Cao, Marc Ladanyi, Meera Hameed
Spitzoid neoplasms are a distinct group of melanocytic tumors. Genetically, they lack mutations in common melanoma-associated oncogenes. Recent studies have shown that spitzoid tumors may contain a variety of kinase fusions, including ROS1, NTRK1, ALK, BRAF, and RET fusions. We report herein the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or atypical features, based on genome-wide copy number analysis by single-nucleotide polymorphism array, which showed intragenic copy number changes in NTRK3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28433051/insect-specific-viruses-a-historical-overview-and-recent-developments
#14
Christopher M Roundy, Sasha R Azar, Shannan L Rossi, Scott C Weaver, Nikos Vasilakis
Arthropod-borne viruses (arboviruses) have in recent years become a tremendous global health concern resulting in substantial human morbidity and mortality. With the widespread utilization of molecular technologies such as next-generation sequencing and the advancement of bioinformatics tools, a new age of viral discovery has commenced. Many of the novel agents being discovered in recent years have been isolated from mosquitoes and exhibit a highly restricted host range. Strikingly, these insect-specific viruses have been found to be members of viral families traditionally associated with human arboviral pathogens, including but not limited to the families Flaviviridae, Togaviridae, Reoviridae, and Bunyaviridae...
2017: Advances in Virus Research
https://www.readbyqxmd.com/read/28433021/to-kink-or-not-a-search-for-long-chain-cumulenones-using-microwave-spectral-taxonomy
#15
Michael C McCarthy, Luyao Zou, Marie-Aline Martin-Drumel
A systematic search for carbon-chain cumulenones beyond H2C4O has been undertaken using microwave spectral taxonomy in combination with a pulsed jet discharge source. No evidence was found for the C2υ isomer of H2C5O or its longer derivatives, but HC(O)C4H, the longer variant of propynal, HC(O)CCH, was identified instead. Its rotational and leading centrifugal distortion constants have been derived to high accuracy from detection of both a- and b-type lines; those below 40 GHz were measured using a Fabry-Perot cavity, while lines between 40 and 72 GHz were recorded by double resonance techniques...
April 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28432980/discovery-of-potential-inhibitor-against-human-acetylcholinesterase-a-molecular-docking-and-molecular-dynamics-investigation
#16
Surya Pratap Singh, Dwijendra Gupta
Alzheimer's disease (AD) is a progressive neurodegenerative disease of central nervous system among elderly people. Human acetylcholinesterase (hAChE), an important enzyme in neuronal signaling, is responsible for the degradation of acetylcholine which in turn prevents the post synaptic signal transmissions. hAChE has been an attractive target of drug discovery for the search of therapeutics against AD. In the recent past hAChE has become hot target for the investigation of new potential therapeutics. We performed virtual screening of entire database against hAChE...
April 12, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28432840/detection-of-egfr-mutations-in-patients-with-non-small-cell-lung-cancer-by-high-resolution-melting-comparison-with-other-methods
#17
Carlos Martínez-Carretero, Fernando Iguaz Pascual, Antonio Rus, Ivan Bernardo
BACKGROUND: The discovery of mutations in the epidermal growth factor receptor gene (EGFR) related to the clinical response to tyrosine kinase inhibitors, has transformed the management of non-small cell lung cancer (NSCLC). Several methods have been developed for determination of mutations in EGFR, with different sensitivity and potential ability to detect a different number of mutations. METHODS: We developed a screening method by high resolution melting (HRM) to detect EGFR mutations, and compared the results of 123 fixed in formalin and paraffin embedded (FFPE) tumor tissue samples with the detection of mutations by allele-specific PCR...
April 22, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28432778/cross-species-studies-of-cognition-relevant-to-drug-discovery-a-translational-approach
#18
REVIEW
T W Robbins
This Review advances the case that bidirectional, cross-species translation of findings from experimental animals to and from humans is an important strategy for drug discovery. Animal models of mental disorders require appropriate behavioural or cognitive outcome variables that can be generalized cross-species. One example is the treatment of impulsive behaviour in attention deficit hyperactivity disorder (ADHD) with stimulant drugs. Performance on the stop signal reaction task as an index of impulsivity is improved both in healthy human volunteers and in patients with adult ADHD by stimulant drugs and also by the selective noradrenergic reuptake blocker atomoxetine...
April 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28432774/comprehensive-two-dimensional-pc-3-prostate-cancer-cell-membrane-chromatography-for-screening-anti-tumor-components-from-radix-sophorae-flavescentis
#19
Qiang Wang, Junnan Xu, Xiang Li, Dawei Zhang, Yong Han, Xu Zhang
Radix Sophorae flavescentis is generally used for the treatments of different stages of prostate cancer in China. It has ideal effects when combined with surgical treatment and chemotherapy. However, its active components are still ambiguous. We devised a comprehensive two-dimensional PC-3 prostate cancer cell membrane chromatography system for screening anti-prostate cancer components in Radix Sophorae flavescentis. Gefitinib and dexamethasone were chosen as positive and negative drugs respectively for validation and optimization the selectivity and suitability of the comprehensive two-dimensional chromatographic system...
April 22, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28432703/selective-calixarene-directed-synthesis-of-mxene-plates-crumpled-sheets-spheres-and-scrolls
#20
Arni Vaughn, Jeremy Ball, Tobias Heil, David Morgan, Giulio Lampronti, Gabija Maršalkaitė, Colin L Raston, Nicholas P Power, Suela Kellici
Fully exploiting the electronic and mechanical properties of 2D laminar materials not only requires efficient and effective means of their exfoliation into low dimensional layers, but also necessitates a means of changing their morphology so as to explore any enhancement that this may offer. MXenes are a rapidly emerging new class of such laminar materials with unique properties. However, access to other morphologies of MXenes has not yet been fully realised. To this end we have developed the synthesis of MXenes (Ti2C) as plates, crumpled sheets, spheres and scrolls, which involves selective intercalation of p-phosphonic calix[n]arenes, with control in morphology arising from the choice of the size of the macrocycle, n = 4, 5, 6 or 8...
April 21, 2017: Chemistry: a European Journal
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