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https://www.readbyqxmd.com/read/28099855/primary-cell-culture-of-live-neurosurgically-resected-aged-adult-human-brain-cells-and-single-cell-transcriptomics
#1
Jennifer M Spaethling, Young-Ji Na, Jaehee Lee, Alexandra V Ulyanova, Gordon H Baltuch, Thomas J Bell, Steven Brem, H Isaac Chen, Hannah Dueck, Stephen A Fisher, Marcela P Garcia, Mugdha Khaladkar, David K Kung, Timothy H Lucas, Donald M O'Rourke, Derek Stefanik, Jinhui Wang, John A Wolf, Tamas Bartfai, M Sean Grady, Jai-Yoon Sul, Junhyong Kim, James H Eberwine
Investigation of human CNS disease and drug effects has been hampered by the lack of a system that enables single-cell analysis of live adult patient brain cells. We developed a culturing system, based on a papain-aided procedure, for resected adult human brain tissue removed during neurosurgery. We performed single-cell transcriptomics on over 300 cells, permitting identification of oligodendrocytes, microglia, neurons, endothelial cells, and astrocytes after 3 weeks in culture. Using deep sequencing, we detected over 12,000 expressed genes, including hundreds of cell-type-enriched mRNAs, lncRNAs and pri-miRNAs...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28095325/peroxisome-proliferator-activated-receptor-%C3%AE-activation-inhibits-liver-growth-through-mir-122-mediated-downregulation-of-cmyc
#2
Andrei A Yarushkin, Yuliya A Kazantseva, Vyacheslav S Kobelev, Yuliya A Pustylnyak, Vladimir O Pustylnyak
Although NR1C3 agonists inhibit cell growth, the molecular mechanism of their action has not been thoroughly characterized to date. A recent study demonstrated that NR1C3 can regulate miR-122 by binding to its promoter. Given that miR-122 can indirectly regulate cMyc-mediated promitogenic signaling by targeting E2f1, we hypothesized that NR1C3 activation inhibits hepatocyte proliferation through miR-122-mediated cMyc downregulation. In the present study, we examined if liver hyperplasia induced by a strong chemical mitogen for the liver, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of NR1I3, can be repressed by NR1C3 activation through miR-122 upregulation...
January 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28092426/incomplete-reversibility-of-platelet-inhibition-following-prolonged-exposure-to-ticagrelor
#3
A J Gerrits, J A Jakubowski, A Sugidachi, A D Michelson, A L Frelinger
INTRODUCTION: Ticagrelor is described as a reversible P2Y12 antagonist. However, residual platelet inhibition persists after discontinuation of ticagrelor when plasma levels are undetectable. We assessed the reversibility of platelet inhibition by ticagrelor and its active metabolite (T-AM) in comparison with cangrelor and prasugrel's active metabolite (P-AM). METHODS: Whole blood was treated in vitro with ~50% inhibitory concentrations of ticagrelor, T-AM, cangrelor, P-AM and assessed for ADP-stimulated activated GPIIb-IIIa and P-selectin and vasodilator stimulated phosphoprotein (VASP) platelet reactivity index (PRI) before and after 100-fold dilution...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28087842/novel-determinants-of-mammalian-primary-microrna-processing-revealed-by-systematic-evaluation-of-hairpin-containing-transcripts-and-human-genetic-variation
#4
Christine Anne Roden, Jonathan Gaillard, Shaveta Kanoria, William Rennie, Syndi Barish, Jijun Cheng, Wen Pan, Jun Liu, Chris Cotsapas, Ye Ding, Jun Lu
Mature microRNAs (miRNAs) are processed from hairpin-containing primary miRNAs (pri-miRNAs). However, rules that distinguish pri-miRNAs from other hairpin-containing transcripts in the genome are incompletely understood. By developing a computational pipeline to systematically evaluate 30 structural and sequence features of mammalian RNA hairpins, we report several new rules that are preferentially utilized in miRNA hairpins and govern efficient pri-miRNA processing. We propose that a hairpin stem length of 36+/-3nt is optimal for pri-miRNA processing...
January 13, 2017: Genome Research
https://www.readbyqxmd.com/read/28075525/dynamic-remodeling-of-arteriolar-collaterals-after-acute-occlusion-in-chick-chorioallantoic-membrane
#5
Weiwei Xiang, Bettina Reglin, Bianca Nitzsche, Martin Maibier, Wenwei Rong, Björn Hoffmann, Alfredo Ruggeri, Pedro Guimarães, Timothy W Secomb, Axel R Pries
After arteriolar occlusion, collaterals enlarge and initially elevated wall shear stress (WSS) normalizes. While most previous studies focused on endpoints of such adaptive changes in larger collaterals the present investigation aimed to continuously determine the relation between WSS and diameter in microvascular collaterals during adaptive reactions METHODS: In Hamburger-Hamilton stage 40 chick chorioallantoic membranes (CAMs), junction points between arteriolar segments were identified and the third upstream segment on one side was occluded...
January 11, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28074552/validation-of-microrna-pathway-polymorphisms-in-esophageal-adenocarcinoma-survival
#6
Olusola O Faluyi, Lawson Eng, Xin Qiu, Jiahua Che, Qihuang Zhang, Dangxiao Cheng, Nanjiao Ying, Alvina Tse, Qin Kuang, Lorin Dodbiba, Daniel J Renouf, Sharon Marsh, Sevtap Savas, Helen J Mackay, Jennifer J Knox, Gail E Darling, Rebecca K S Wong, Wei Xu, Abul Kalam Azad, Geoffrey Liu
Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri-miRNA, 7 pre-miRNA) were genotyped and analyzed...
January 11, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28068184/antimicrobial-susceptibilities-of-flavobacterium-psychrophilum-isolates-from-the-great-lakes-basin-michigan
#7
Danielle Van Vliet, Thomas P Loch, Peter Smith, Mohamed Faisal
Flavobacterium psychrophilum is a serious pathogen of salmonids worldwide, a matter that is compounded by the lack of effective vaccine preparations. As a result, biosecurity measures and antimicrobial agents remain the only available methods to control diseases caused by F. psychrophilum. It is feared that antimicrobial use may have led to the development of F. psychrophilum strains with reduced susceptibility. Therefore, the primary objective of this study was to determine the antimicrobial susceptibility profiles of 50 F...
January 9, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28067243/association-of-polymorphisms-in-three-pri-mirnas-that-target-pepsinogen-c-with-the-risk-and-prognosis-of-gastric-cancer
#8
Ye-Feng Wu, Qian Xu, Cai-Yun He, Ying Li, Jing-Wei Liu, Na Deng, Li-Ping Sun, Yuan Yuan
We aimed to explore the associations of polymorphisms in three microRNAs (miRNAs) (let-7e rs8111742, miR-365b rs121224 and miR-4795 rs1002765) that target PGC with the risk and prognosis of gastric cancer/atrophic gastritis. Sequenom's MassArray was used to genotype the miRNA polymorphisms in 724 gastric cancer cases, 862 atrophic gastritis cases and 862 controls in a Chinese population. We found that let-7e rs8111742 and miR-4795 rs1002765 were associated with the risk of gastric cancer in the H. pylori-positive subgroup...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065907/platelet-reactivity-in-human-immunodeficiency-virus-infected-patients-on-dual-antiplatelet-therapy-for-an-acute-coronary-syndrome-the-evere2st-hiv-study
#9
Marie Hauguel-Moreau, Franck Boccara, Anders Boyd, Joe-Elie Salem, Delphine Brugier, Angélique Curjol, Jean-Sébastien Hulot, Mathieu Kerneis, Sophie Galier, Ariel Cohen, Gilles Montalescot, Jean-Philippe Collet, Johanne Silvain
AIM: To explore platelet reactivity on dual antiplatelet therapy (DAPT) of acute coronary syndrome (ACS) patients infected with HIV. METHODS AND RESULTS: Acute coronary syndrome patients infected with HIV (n = 80) were matched to ACS patients without HIV (n = 160) on age, sex, diabetes, and DAPT (aspirin 100%, clopidogrel 68%, prasugrel 31%, ticagrelor 1%). Platelet reactivity was evaluated after ACS (>30 days) by measuring residual platelet aggregation (RPA) to aspirin and to P2Y12 inhibitors with light transmission aggregometry (LTA), VerifyNow aspirin assay (ARU), and P2Y12 assay (PRU) and with the VASP platelet reactivity index (VASP-PRI)...
January 8, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#10
Robert Böscke, Eszter K Vladar, Michael Könnecke, Birgit Hüsing, Robert Linke, Ralph Pries, Norbert Reiling, Jeffrey D Axelrod, Jayakar V Nayak, Barbara Wollenberg
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28057565/development-and-validation-of-a-continuously-age-adjusted-measure-of-patient-condition-for-hospitalized-children-using-the-electronic-medical-record
#11
Michael J Rothman, Joseph J Tepas, Andrew J Nowalk, James E Levin, Joan M Rimar, Albert Marchetti, Allen L Hsiao
Awareness of a patient's clinical status during hospitalization is a primary responsibility for hospital providers. One tool to assess status is the Rothman Index (RI), a validated measure of patient condition for adults, based on empirically derived relationships between 1-year post-discharge mortality and each of 26 clinical measurements available in the electronic medical record. However, such an approach cannot be used for pediatrics, where the relationships between risk and clinical variables are distinct functions of patient age, and sufficient 1-year mortality data for each age group simply does not exist...
January 2, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28052101/defining-transcriptional-regulatory-mechanisms-for-primary-let-7-mirnas
#12
Xavier Gaeta, Luat Le, Ying Lin, Yuan Xie, William E Lowry
The let-7 family of miRNAs have been shown to control developmental timing in organisms from C. elegans to humans; their function in several essential cell processes throughout development is also well conserved. Numerous studies have defined several steps of post-transcriptional regulation of let-7 production; from pri-miRNA through pre-miRNA, to the mature miRNA that targets endogenous mRNAs for degradation or translational inhibition. Less-well defined are modes of transcriptional regulation of the pri-miRNAs for let-7...
2017: PloS One
https://www.readbyqxmd.com/read/27992670/dissection-of-the-effects-of-quercetin-on-mouse-myocardium
#13
Michel Santana Santos, Evaleide Diniz de Oliveira, Artur Santos-Miranda, Jader Santos Cruz, Antônio Nei Santana Gondim, José Evaldo Rodrigues de Menezes-Filho, Diego Santos de Souza, Leidiane Pinho-da-Silva, Itamar Couto Guedes de Jesus, Danilo Roman-Campos, Silvia Guatimosim, Aline Lara, Eduardo Antônio Conde-Garcia, Carla Maria Lins de Vasconcelos
Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 μM quercetin increased ICa,L at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V0...
December 19, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27991687/graphite-to-graphene-total-conversion
#14
Matat Buzaglo, Ilan Pri Bar, Maxim Varenik, Liran Shunak, Svetlana Pevzner, Oren Regev
The rush to develop graphene applications mandates mass production of graphene sheets. However, the currently available complex and expensive production technologies are limiting the graphene commercialization. Here, it is demonstrated that the addition of a protective diluent to graphite during ball-milling results in a game-changer yield (>90%) of defect-free graphene, whose size is controlled by the milling energy and the diluent type.
December 19, 2016: Advanced Materials
https://www.readbyqxmd.com/read/27988243/radiocarbon-concentration-in-tree-ring-samples-collected-in-the-south-west-slovakia-1974-2013
#15
I Kontuľ, M Ješkovský, J Kaizer, A Šivo, M Richtáriková, P P Povinec, P Čech, P Steier, R Golser
Radiocarbon measurements of tree-ring samples collected in Vysoká pri Morave were compared with tree-ring data of the Žlkovce monitoring station situated 5km south-east from the Jaslovské Bohunice Nuclear Power Plant (NPP). Radiocarbon concentrations in Vysoká pri Morave and in Žlkovce tree rings were decreasing exponentially with decay constants of 14.48±1.23 y and 17.96±1.97 y, respectively, in agreement with similar results obtained at other radiocarbon stations. The Suess effect, represented by a dilution in (14)C levels by fossil fuel CO2 emissions, was observed in both tree-ring data sets...
December 3, 2016: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/27987383/model-based-inference-from-microvascular-measurements-combining-experimental-measurements-and-model-predictions-using-a-bayesian-probabilistic-approach
#16
Peter M Rasmussen, Amy F Smith, Sava Sakadžić, David A Boas, Axel R Pries, Timothy W Secomb, Leif Østergaard
In vivo imaging of the microcirculation and network-oriented modeling have emerged as powerful means of studying microvascular function and understanding its physiological significance. Network-oriented modeling may provide the means of summarizing vast amounts of data produced by high-throughput imaging techniques in terms of key, physiological indices. To estimate such indices with sufficient certainty, however, network-oriented analysis must be robust to the inevitable presence of uncertainty due to measurement errors as well as model errors METHODS: We propose the Bayesian probabilistic data analysis framework as a means of integrating experimental measurements and network model simulations into a combined and statistically coherent analysis...
December 17, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/27983526/pri-mir-34b-c-rs4938723-polymorphism-increased-the-risk-of-prostate-cancer
#17
Mohammad Hashemi, Hiva Danesh, Fatemeh Bizhani, Bahzad Narouie, Mehdi Sotoudeh, Akbar Nouralizadeh, Farzaneh Sharifiaghdas, Gholamreza Bahari, Mohsen Taheri
The association studies between miR-34b/c rs4938723 polymorphism and cancer risk showed conflicting results. This study aimed to assess the impact of rs4938723 polymorphism on prostate cancer risk. This case-control study was done on 151 prostate cancer (PCa) patients and 152 benign prostate hyperplasia to examine whether rs4938723 polymorphism in the promoter of pri-miR-34b/c was linked to the carcinogenesis of PCa in a sample of Iranian population. Genotyping of Pri-miR-34 b/c rs4938723 polymorphism was performed by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method...
December 9, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27965755/screening-of-potential-free-radicals-scavenger-and-antibacterial-activities-of-purwoceng-pimpinella-alpina-molk
#18
Retno Wahyuningrum, Pri Iswati Utami, Binar Asrining Dhiani, Malikhah Kumalasari, Rizka Sari Kusumawardani
Purwoceng (Pimpinella alpina Molk) is a traditional medicinal plant used for its aphrodisiac values. This plant was originated Dieng Plateu, Central Java, Indonesia. Purwoceng has been reported to contain steroid, flavonoids, glycoside, saponins, tannins, and phenolic. Based on secondary metabolite compounds of Purwoceng herbs, a research need to be done to determine the other potential free radicals scavenger and antibacterial activities of Purwoceng. The objectives of this research are to screen the potential free radicals scavenger activity of in vitro using DPPH (1,1 diphenyl-2-picryl-hydrazil) radicals and NO• (nitric oxide) radicals, and antibacterial activity of Purwoceng...
November 2016: Tropical Life Sciences Research
https://www.readbyqxmd.com/read/27937053/association-of-pear1-rs12041331-polymorphism-and-pharmacodynamics-of-ticagrelor-in-healthy-chinese-volunteers
#19
Mupeng Li, Yaodong Hu, Zhipeng Wen, Huilan Li, Xiaolei Hu, Yanjiao Zhang, Zanling Zhang, Jian Xiao, Jie Tang, Xiaoping Chen
Genetic polymorphisms in platelet endothelial aggregation receptor 1 (PEAR1) were associated with responsiveness to aspirin and P2Y12 receptor antagonists. This study aimed to investigate whether PEAR1 polymorphism is associated with ticagrelor pharmacodynamics in healthy Chinese subjects. The in vitro inhibition of platelet aggregation (IPA) was evaluated before and after ticagrelor incubated with platelet rich plasma from 196 healthy Chinese male subjects. Eight polymorphisms at PEAR1 locus were genotyped...
December 12, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27907888/a-novel-role-for-gsk3%C3%AE-as-a-modulator-of-drosha-microprocessor-activity-and-microrna-biogenesis
#20
Claire E Fletcher, Jack D Godfrey, Akifumi Shibakawa, Martin Bushell, Charlotte L Bevan
Regulation of microRNA (miR) biogenesis is complex and stringently controlled. Here, we identify the kinase GSK3β as an important modulator of miR biogenesis at Microprocessor level. Repression of GSK3β activity reduces Drosha activity toward pri-miRs, leading to accumulation of unprocessed pri-miRs and reduction of pre-miRs and mature miRs without altering levels or cellular localisation of miR biogenesis proteins. Conversely, GSK3β activation increases Drosha activity and mature miR accumulation. GSK3β achieves this through promoting Drosha:cofactor and Drosha:pri-miR interactions: it binds to DGCR8 and p72 in the Microprocessor, an effect dependent upon presence of RNA...
October 23, 2016: Nucleic Acids Research
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