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Sample records for single mi population

  1. Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci.

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    Dorota M Nowak

    Full Text Available Despite numerous studies, the causes of both development and progression of keratoconus remain elusive. Previous studies of this disorder focused mainly on one or two genetic factors only. However, in the analysis of such complex diseases all potential factors should be taken into consideration. The purpose of this study was a comprehensive analysis of known keratoconus loci to uncover genetic factors involved in this disease causation in the general population, which could be omitted in the original studies. In this investigation genomic data available in various databases and experimental own data were assessed. The lists of single nucleotide variants and miRNA genes localized in reported keratoconus loci were obtained from Ensembl and miRBase, respectively. The potential impact of nonsynonymous amino acid substitutions on protein structure and function was assessed with PolyPhen-2 and SIFT. For selected protein genes the ranking was made to choose those most promising for keratoconus development. Ranking results were based on topological features in the protein-protein interaction network. High specificity for the populations in which the causative sequence variants have been identified was found. In addition, the possibility of links between previously analyzed keratoconus loci was confirmed including miRNA-gene interactions. Identified number of genes associated with oxidative stress and inflammatory agents corroborated the hypothesis of their effect on the disease etiology. Distribution of the numerous sequences variants within both exons and mature miRNA which forces you to search for a broader look at the determinants of keratoconus. Our findings highlight the complexity of the keratoconus genetics.

  2. Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci.

    Science.gov (United States)

    Nowak, Dorota M; Gajecka, Marzena

    2015-01-01

    Despite numerous studies, the causes of both development and progression of keratoconus remain elusive. Previous studies of this disorder focused mainly on one or two genetic factors only. However, in the analysis of such complex diseases all potential factors should be taken into consideration. The purpose of this study was a comprehensive analysis of known keratoconus loci to uncover genetic factors involved in this disease causation in the general population, which could be omitted in the original studies. In this investigation genomic data available in various databases and experimental own data were assessed. The lists of single nucleotide variants and miRNA genes localized in reported keratoconus loci were obtained from Ensembl and miRBase, respectively. The potential impact of nonsynonymous amino acid substitutions on protein structure and function was assessed with PolyPhen-2 and SIFT. For selected protein genes the ranking was made to choose those most promising for keratoconus development. Ranking results were based on topological features in the protein-protein interaction network. High specificity for the populations in which the causative sequence variants have been identified was found. In addition, the possibility of links between previously analyzed keratoconus loci was confirmed including miRNA-gene interactions. Identified number of genes associated with oxidative stress and inflammatory agents corroborated the hypothesis of their effect on the disease etiology. Distribution of the numerous sequences variants within both exons and mature miRNA which forces you to search for a broader look at the determinants of keratoconus. Our findings highlight the complexity of the keratoconus genetics.

  3. Dissecting miRNA gene repression on single cell level with an advanced fluorescent reporter system

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    Lemus-Diaz, Nicolas; Böker, Kai O.; Rodriguez-Polo, Ignacio; Mitter, Michael; Preis, Jasmin; Arlt, Maximilian; Gruber, Jens

    2017-01-01

    Despite major advances on miRNA profiling and target predictions, functional readouts for endogenous miRNAs are limited and frequently lead to contradicting conclusions. Numerous approaches including functional high-throughput and miRISC complex evaluations suggest that the functional miRNAome differs from the predictions based on quantitative sRNA profiling. To resolve the apparent contradiction of expression versus function, we generated and applied a fluorescence reporter gene assay enabling single cell analysis. This approach integrates and adapts a mathematical model for miRNA-driven gene repression. This model predicts three distinct miRNA-groups with unique repression activities (low, mid and high) governed not just by expression levels but also by miRNA/target-binding capability. Here, we demonstrate the feasibility of the system by applying controlled concentrations of synthetic siRNAs and in parallel, altering target-binding capability on corresponding reporter-constructs. Furthermore, we compared miRNA-profiles with the modeled predictions of 29 individual candidates. We demonstrate that expression levels only partially reflect the miRNA function, fitting to the model-projected groups of different activities. Furthermore, we demonstrate that subcellular localization of miRNAs impacts functionality. Our results imply that miRNA profiling alone cannot define their repression activity. The gene regulatory function is a dynamic and complex process beyond a minimalistic conception of “highly expressed equals high repression”. PMID:28338079

  4. Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers.

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    Rawlings-Goss, Renata A; Campbell, Michael C; Tishkoff, Sarah A

    2014-08-28

    MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes. Genetic variation in 1524 miRNA genes was examined using whole genome sequencing (60x coverage) in a panel of 69 unrelated individuals from 14 global populations, including European, Asian and African populations. We identified 33 previously undescribed miRNA variants, and 31 miRNA containing variants that are globally population-differentiated in frequency between African and non-African populations (PD-miRNA). The top 1% of PD-miRNA were significantly enriched for regulation of genes involved in glucose/insulin metabolism and cell division (p < 10(-7)), most significantly the mitosis pathway, which is strongly linked to cancer onset. Overall, we identify 7 PD-miRNAs that are currently implicated as cancer biomarkers or diagnostics: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908. Notably, hsa-mir-202, a potential breast cancer biomarker, was found to show significantly high allele frequency differentiation at SNP rs12355840, which is known to affect miRNA expression levels in vivo and subsequently breast cancer mortality. MiRNA expression profiles represent a promising new category of disease biomarkers. However, population specific genetic variation can affect the prevalence and baseline expression of these miRNAs in diverse populations. Consequently, miRNA genetic and expression level variation among ethnic groups may be contributing in

  5. Association of a miRNA-137 Polymorphism with Schizophrenia in a Southern Chinese Han Population

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    Guoda Ma

    2014-01-01

    Full Text Available Both genome wide association study (GWAS and biochemical studies of Caucasian populations indicate a robust association between the miR-137 genetic variant rs1625579 and schizophrenia, but inconsistent results have been reported. To assay the association between this variant and schizophrenia, we genotyped 611 schizophrenic patients from Southern Chinese Han population for the risk single nucleotide polymorphism (SNP rs1625579 using the SNaPshot technique and compared the clinical profiles of different genotypes. Additionally, a meta-analysis was performed using the combined sample groups from five case-control publications and the present study. Both the genotype and allele distributions of the rs1625579 SNP were significantly different between patients and controls (P=0.036 and 0.026, SNP. TT genotype carriers showed slightly lower Brief Assessment of Cognition in Schizophrenia- (BACS- derived working memory performance than G carriers (15.58 ± 9.56 versus 19.71 ± 8.18, P=0.045. In the meta-analysis, we observed a significant association between rs1625579 and schizophrenia under different genetic models (all P<0.05. The results of our study and meta-analysis provide convincing evidence that rs1625579 is significantly associated with schizophrenia. Furthermore, the miR-137 polymorphism influences the working memory performance of schizophrenic patients in a Chinese Han population.

  6. Measurement of the Single Top Quark Production Cross Section and |<mi>Vmi><mi>tb>| in Events with One Charged Lepton, Large Missing Transverse Energy, and Jets at CDF

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    Aaltonen, T.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Auerbach, B.; Aurisano, A.; Azfar, F.; Badgett, W.; Bae, T.; Barbaro-Galtieri, A.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartos, P.; Bauce, M.; Bedeschi, F.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Bhatti, A.; Bland, K. R.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brigliadori, L.; Bromberg, C.; Brucken, E.; Budagov, J.; Budd, H. S.; Burkett, K.; Busetto, G.; Bussey, P.; Butti, P.; Buzatu, A.; Calamba, A.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cerri, A.; Cerrito, L.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Chokheli, D.; Clark, A.; Clarke, C.; Convery, M. E.; Conway, J.; Corbo, M.; Cordelli, M.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; d’Ascenzo, N.; Datta, M.; de Barbaro, P.; Demortier, L.; Deninno, M.; D’Errico, M.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Dittmann, J. R.; Donati, S.; D’Onofrio, M.; Dorigo, M.; Driutti, A.; Ebina, K.; Edgar, R.; Elagin, A.; Erbacher, R.; Errede, S.; Esham, B.; Farrington, S.; Fernández Ramos, J. P.; Field, R.; Flanagan, G.; Forrest, R.; Franklin, M.; Freeman, J. C.; Frisch, H.; Funakoshi, Y.; Galloni, C.; Garfinkel, A. F.; Garosi, P.; Gerberich, H.; Gerchtein, E.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Giokaris, N.; Giromini, P.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grosso-Pilcher, C.; Group, R. C.; Guimaraes da Costa, J.; Hahn, S. R.; Han, J. Y.; Happacher, F.; Hara, K.; Hare, M.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hays, C.; Heinrich, J.; Herndon, M.; Hirschbuehl, D.; Hocker, A.; Hong, Z.; Hopkins, W.; Hou, S.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jang, D.; Jayatilaka, B.; Jeon, E. J.; Jindariani, S.; Jones, M.; Joo, K. K.; Jun, S. Y.; Junk, T. R.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Kasmi, A.; Kato, Y.; Ketchum, W.; Keung, J.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. H.; Kim, S. B.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Knoepfel, K.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kurata, M.; Laasanen, A. T.; Lammel, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lee, H. S.; Lee, J. S.; Leo, S.; Leone, S.; Lewis, J. D.; Limosani, A.; Lipeles, E.; Lister, A.; Liu, H.; Liu, Q.; Liu, T.; Lockwitz, S.; Loginov, A.; Lucchesi, D.; Lucà, A.; Lueck, J.; Lujan, P.; Lukens, P.; Lungu, G.; Lys, J.; Lysak, R.; Madrak, R.; Maestro, P.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Marchese, L.; Margaroli, F.; Marino, P.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Mesropian, C.; Miao, T.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nakano, I.; Napier, A.; Nett, J.; Neu, C.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Ortolan, L.; Pagliarone, C.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parker, W.; Pauletta, G.; Paulini, M.; Paus, C.; Phillips, T. J.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pondrom, L.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ristori, L.; Robson, A.; Rodriguez, T.; Rolli, S.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sakumoto, W. K.; Sakurai, Y.; Santi, L.; Sato, K.; Saveliev, V.; Savoy-Navarro, A.; Schlabach, P.; Schmidt, E. E.; Schwarz, T.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Semenov, A.; Sforza, F.; Shalhout, S. Z.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simonenko, A.; Sliwa, K.; Smith, J. R.; Snider, F. D.; Song, H.; Sorin, V.; St. Denis, R.; Stancari, M.; Stentz, D.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Ukegawa, F.; Uozumi, S.; Vázquez, F.; Velev, G.; Vellidis, C.; Vernieri, C.; Vidal, M.; Vilar, R.; Vizán, J.; Vogel, M.; Volpi, G.; Wagner, P.; Wallny, R.; Wang, S. M.; Waters, D.; Wester, W. C.; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wolbers, S.; Wolfe, H.; Wright, T.; Wu, X.; Wu, Z.; Yamamoto, K.; Yamato, D.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W. -M.; Yeh, G. P.; Yi, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G. B.; Yu, I.; Zanetti, A. M.; Zeng, Y.; Zhou, C.; Zucchelli, S.

    2014-12-31

    We report a measurement of single top quark production in proton-antiproton collisions at a center-of-mass energy of mi>smi>=1.96 mi>TeVmi> using a data set corresponding to 7.5 mi>fbmi>-1 of integrated luminosity collected by the Collider Detector at Fermilab. We select events consistent with the single top quark decay process mi>t>mi>Wmi>b>mi>νmi>b> by requiring the presence of an electron or muon, a large imbalance of transverse momentum indicating the presence of a neutrino, and two or three jets including at least one originating from a bottom quark. An artificial neural network is used to discriminate the signal from backgrounds. We measure a single top quark production cross section of 3.04-0.53+0.57 mi>pb> and set a lower limit on the magnitude of the coupling between the top quark and bottom quark |

  7. Which Sámi? Sámi inclusion criteria in population-based studies of Sámi health and living conditions in Norway - an exploratory study exemplified with data from the SAMINOR study.

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    Pettersen, Torunn; Brustad, Magritt

    2013-01-01

    In a situation where national censuses do not record information on ethnicity, studies of the indigenous Sámi people's health and living conditions tend to use varying Sámi inclusion criteria and categorizations. Consequently, the basis on which Sámi study participants are included and categorized when Sámi health and living conditions are explored and compared differs. This may influence the results and conclusions drawn. To explore some numerical consequences of applying principles derived from Norway's Sámi Act as a foundation for formalized inclusion criteria in population-based Sámi studies in Norway. We established 1 geographically based (G1) and 3 individual-based Sámi example populations (I1-I3) by applying diverse Sámi inclusion criteria to data from 17 rural municipalities in Norway north of the Arctic Circle. The data were collected for a population-based study of health and living conditions in 2003-2004 (the SAMINOR study). Our sample consisted of 14,797 participants aged 36-79 years. The size of the individual-based populations varied significantly. I1 (linguistic connection Sámi) made up 35.5% of the sample, I2 (self-identified Sámi) made up 21.0% and I3 (active language Sámi) 17.7%. They were also noticeably unevenly distributed between the 5 Sámi regions defined for this study. The differences for the other characteristics studied were more ambiguous. For the population G1 (residents in the Sámi language area) the only significant difference found between the Sámi and the corresponding non-Sámi population was for household income (OR=0.69, 95% CI: 0.63-0.74). For the populations I1-I3 there were significant differences on all measures except for I2 and education (OR=1.09, 95% CI: 0.99-1.21). The choice of Sámi inclusion criterion had a clear impact on the size and geographical distribution of the defined populations but lesser influence on the selected characteristics for the Sámi populations relative to the respective non-Sámi

  8. miRNA as potential biomarkers of breast cancer in the Lebanese population and in young women: a pilot study.

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    Farah J Nassar

    Full Text Available Relative to western populations, the percentage of women diagnosed with breast cancer at a young age in Lebanon is high. While the younger age of the Lebanese population compared to the West certainly contributes to this difference, potential genetic, reproductive and/or biological factors likely play an important role. The objective of this study is to investigate the contribution of miRNAs in this setting through the analysis of the expression of five reported dysregulated miRNAs, miR-148b, miR-10b, miR-21, miR-221, and miR-155 in 20 normal and 57 cancerous breast tissues from Lebanese breast cancer patients. After finding their relative expression by quantitative reverse transcription real time PCR, the results were analyzed with respect to the patients' clinical and histopathology presentations. Compared to normal breast tissues, significant upregulation of miR-155, miR-21 and miR-148b, notable downregulation of miR-10b and non-significant expression of miR-221 were observed in tumor tissues. Moreover, miR-10b was significantly underexpressed in estrogen/progesterone receptor (ER/PR negative tumors relative to ER/PR positive tumor tissues. miR-155 was also significantly overexpressed in postmenopausal patients and in those of age at diagnosis greater than 40 years old as well as in PR negative or in human epidermal growth factor 2 (Her2 positive tissues. This study is the first one to report miRNA expression patterns in Lebanese breast cancer patients. We found that differential miRNA expression in breast cancer could be variable between Lebanese and Western populations. miR-10b was positively correlated with the ER and PR status and miR-155 could be a noteworthy biomarker for the menopausal state, age at diagnosis, PR and Her2 status. Hence, miRNA can be used as biomarkers for early breast cancer detection.

  9. miRNA Expression Profiles of HPV-Infected Patients with Cervical Cancer in the Uyghur Population in China.

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    Dongmei Gao

    Full Text Available The study aimed to investigate the state of human papillomavirus (HPV infection in patients with cervical cancer in the Uyghur population in China and to identify miRNA as biomarker for cervical cancer and HPV infection. We also performed genotyping to determine the variation in the types of HPV. Using microRNA (miRNA microarray technology, differential miRNA expression between HPV-infected cervical cancer and uninfected normal cervical tissues was determined; the microarray results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR using 20 samples of both the tissues. The infection rate of HPV in patients with cervical cancer was 96.7% (29 of 30, and the main subtype identified was HPV16 (29 of 29. HPV16 integration assay demonstrated that the majority of infectious cases were of the integrated form (26 of 29. Analysis of 140 miRNAs demonstrated greater than two-fold change in miRNA expression in HPV-infected cervical cancer tissue as compared to that in uninfected cervical tissue. The qRT-PCR analysis verified that the expression of miR-15a-5p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-96, miR-106b-5p, and miR-3653 was higher, while the expression of miR-497-5p was lower in cancer tissues than in normal tissues. The results demonstrate significant changes in miRNA expression in cervical cancer tissues associated with HPV infection as compared to that in normal tissues. These molecular markers may be useful for an early diagnosis and prognosis of cervical cancer in specific human populations.

  10. Effect of a single nucleotide polymorphism in miR-146a on COX-2 protein expression and lung function in smokers with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Wang, Ran; Li, Min; Zhou, Sijing; Zeng, Daxiong; Xu, Xuan; Xu, Rui; Sun, Gengyun

    2015-01-01

    To evaluate the effect of a single nucleotide polymorphism (rs2910164) in the miR-146a precursor on the expression level of miR-146a, cyclooxygenase-2 (COX2), and production of prostaglandin E2 (PGE2) in lung tissue harvested from smokers with chronic obstructive pulmonary disease, as well as the lung function and disease stages from the same patient population. One-hundred and sixty-eight smokers with diagnosed chronic obstructive pulmonary disease were recruited. The patients were genotyped for rs2910164 polymorphism using Sanger sequencing, and their lung function/disease stages were evaluated following Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Meanwhile, messenger ribonucleic acid and protein expression levels of miR-146a and COX2 as well as PGE2 production were determined in 66 lung tissue samples collected in the patients who received surgical treatment. We confirmed that COX2 is a validated target of miR-146a in human fibroblast cells, and identified the differential expression patterns of miR-146a and COX2 in each rs2910164 genotype group. We observed a significant association between rs2910164 in miR-146a and the levels of either COX2 or PGE2 using real-time polymerase chain reaction and Western blot. Consistently, we were able to demonstrate that the rs2910164 single nucleotide polymorphism has a functional effect on the baseline lung function in the study population. In the present study, the rs2910164 CC and GC genotype was found to be associated with an improved lung function and milder disease stages, at least partially, mediated by its ability to increase in COX2 expression and PGE2 production.

  11. A Functional Variant at the miR-214 Binding Site in the Methylenetetrahydrofolatereductase Gene Alters Susceptibility to Gastric Cancer in a Chinese Han Population

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    Qiaoyun Chen

    2015-05-01

    Full Text Available Background and Aims: Single nucleotide polymorphisms in miRNA binding sites, which are located in mRNA 3' untranslated regions (3'-UTRs, were recently found to influence microRNA-target interactions. Specifically, such polymorphisms can modulatebinding affinity or create or destroy miRNA-binding sites; such variants have also been found to be associated with cancer risk. In this study, we explored the effect of a functional variant at the miR-214 binding site in the methylenetetrahydrofolate reductase gene (rs114673809 on gastric cancer (GC risk in a hospital-based case-control study in a Chinese Han population. Methods and Results: We genotyped the rs114673809 polymorphism in 345 gastric cancer patients and 376 cancer-free controls using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP technique. The functions of rs114673809 were investigated using a luciferase activity assay and validated by immunoblotting. We found that participants carrying the rs114673809 AA genotype or A allele had a significantly increased risk of gastric cancer (OR = 1.667, 95% CI = 1.044-2.660, P = 0.034; OR = 1.261, 95% CI = 1.017-1.563, P = 0.037, respectively compared to those carrying the GG genotype and G allele. In addition, rs114673809 modified the binding of hsa-miR-214 to MTHFR as well as MTHFR protein levels in gastric cancer patients. Conclusion: Our data suggested that rs114673809, which is located at the miR-214 binding site in the 3'-UTR of MTHFR, may play an important role in the development of gastric cancer in a Chinese Han population.

  12. Thermodynamics of Meissner effect and flux pinning behavior in the bulk of single-crystal <mi>La>2-<mi>xmi><mi>Srmi><mi>xCuO>4 ( <mi>x>=0.09 )

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    Dhiman, I.; Ziesche, R.; Anand, V. K.; Riik, L.; Song, Gian; Islam, A. T. M. N.; Tanaka, Isao; Treimer, W.

    2017-09-01

    We have studied the magnetic flux pinning behavior and Meissner effect for the high-$T_{\\rm c}$ single crystal La$_{2-x}$Sr$_{x}$CuO$_{4}$ ($x$ = 0.09) superconductor using the polarized neutron imaging method with varying magnetic field and temperature. In the Meissner state expulsion of magnetic field (switched on during the measurements) is visualized, and the signatures of mixed state with increasing temperature are observed. While, for flux pinning behavior between 5 K $\\leq$ $T$ $\\leq$ 15 K and $H_{\\rm ext}$ = 63.5 mT (switched off during the measurements), the evolution of fringe pattern for both 0$^{o}$ and 90$^{o}$ sample orientation indicates magnetic flux pinning inside the bulk of the sample. At 25 K $\\leq$ $T$ $\\leq$ 32 K, a continuous decrease of inhomogeneously distribution pinned magnetic flux is observed, with the sample reaching a normal conducting state at $T_{\\rm c}$ ($\\approx$ 32 K). The flux pinning behavior is also explored as a function of $H_{\\rm ext}$, at $T$ = 5 K. As expected, with increasing $H_{\\rm ext}$ an increase in fringe density is observed, indicating an increase in magnetic flux pinning in the bulk of the sample. Therefore, in the present work for the first time we report bulk visualization of Meissner effect and flux pinning behavior in high-$T_{\\rm c}$ La$_{2-x}$Sr$_{x}$CuO$_{4}$ ($x$ = 0.09) superconductor. This study clearly demonstrates the potential of real space polarized neutron imaging technique for the visualization of the superconducting mixed state, particularly in the field of high-$T_{\\rm c}$ superconductors.

  13. Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population.

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    Enjiao Zhang

    Full Text Available MicroRNAs play important roles in the development of human cancers. This case-control study is to evaluate the roles of the polymorphisms in pre-miRNAs on risk of oral cancer in a Chinese population.The genotypes of three polymorphisms were determined in 340 patients with oral squamous cell cancer and 340 healthy controls who were frequency matched for age and sex. Odds ratios (ORs and 95% confidence intervals (95%CIs were calculated to assess the association. All analyses were performed using the SPSS software. 3.154( 0.001.For miR-499 rs3746444, individuals carrying homozygous CC genotype had increased risks of oral cancer compared with the homozygous wild TT genotype (adjusted OR was 3.154, 95%CI was 1.555-6.397, P value was 0.001. The C allele of miR-499 rs3746444 was associated with a higher risk of oral cancer with significant odds ratio of 1.453. In the stratified analyses by sex, the associations between miR-499 rs3746444 and miR-146a rs2910164 polymorphisms with the susceptibility of oral squamous cell cancer were significant in males. However, with 1/4 as many subjects there were no significant associations between the three polymorphisms and oral cancer risks in females. The joint effects of miRNA polymorphisms and smoking on the risk of OSCC were analyzed and the results suggested that the association between microRNA genetic variants and OSCC risk was modified by smoking.These findings suggest that miR-499 rs3746444 and miR-146a rs2910164 polymorphisms may contribute to genetic susceptibility to oral squamous cell cancer.

  14. Magnetic Beads-Based Sensor with Tailored Sensitivity for Rapid and Single-Step Amperometric Determination of miRNAs

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    Eva Vargas

    2017-11-01

    Full Text Available This work describes a sensitive amperometric magneto-biosensor for single-step and rapid determination of microRNAs (miRNAs. The developed strategy involves the use of direct hybridization of the target miRNA (miRNA-21 with a specific biotinylated DNA probe immobilized on streptavidin-modified magnetic beads (MBs, and labeling of the resulting heteroduplexes with a specific DNA–RNA antibody and the bacterial protein A (ProtA conjugated with an horseradish peroxidase (HRP homopolymer (Poly-HRP40 as an enzymatic label for signal amplification. Amperometric detection is performed upon magnetic capture of the modified MBs onto the working electrode surface of disposable screen-printed carbon electrodes (SPCEs using the H2O2/hydroquinone (HQ system. The magnitude of the cathodic signal obtained at −0.20 V (vs. the Ag pseudo-reference electrode demonstrated linear dependence with the concentration of the synthetic target miRNA over the 1.0 to 100 pM range. The method provided a detection limit (LOD of 10 attomoles (in a 25 μL sample without any target miRNA amplification in just 30 min (once the DNA capture probe-MBs were prepared. This approach shows improved sensitivity compared with that of biosensors constructed with the same anti-DNA–RNA Ab as capture instead of a detector antibody and further labeling with a Strep-HRP conjugate instead of the Poly-HRP40 homopolymer. The developed strategy involves a single step working protocol, as well as the possibility to tailor the sensitivity by enlarging the length of the DNA/miRNA heteroduplexes using additional probes and/or performing the labelling with ProtA conjugated with homopolymers prepared with different numbers of HRP molecules. The practical usefulness was demonstrated by determination of the endogenous levels of the mature target miRNA in 250 ng raw total RNA (RNAt extracted from human mammary epithelial normal (MCF-10A and cancer (MCF-7 cells and tumor tissues.

  15. High throughput detection of miRNAs and gene-specific mRNA at the single-cell level by flow cytometry

    Science.gov (United States)

    Porichis, Filippos; Hart, Meghan G.; Griesbeck, Morgane; Everett, Holly L.; Hassan, Muska; Baxter, Amy E.; Lindqvist, Madelene; Miller, Sara M.; Soghoian, Damien Z.; Kavanagh, Daniel G.; Reynolds, Susan; Norris, Brett; Mordecai, Scott K.; Nguyen, Quan; Lai, Chunfai; Kaufmann, Daniel E.

    2014-01-01

    Fluorescent in situ hybridization (FISH) is a method that uses fluorescent probes to detect specific nucleic acid sequences at the single cell level. Here we describe optimized protocols that exploit a highly sensitive FISH method based on branched DNA technology to detect mRNA and miRNA in human leukocytes. This technique can be multiplexed and combined with fluorescent antibody protein staining to addressa variety of questions in heterogeneous cell populations. We demonstrate antigen-specific upregulation of IFNγ and IL-2 mRNAs in HIV- and CMV-specific T cells. We show simultaneous detection of cytokine mRNA and corresponding protein in single cells. We apply this method to detect mRNAs for which flow antibodies against the corresponding proteins are poor or are not available. We use this technique to show modulation of a microRNA critical for T cell function, miR-155. We adapt this assay for simultaneous detection of mRNA and proteins by Image Stream technology. PMID:25472703

  16. Study of <mi>CP> -violating charge asymmetries of single muons and like-sign dimuons in <mi>p><mi>p>¯ collisions

    Energy Technology Data Exchange (ETDEWEB)

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Agnew, J. P.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Askew, A.; Atkins, S.; Augsten, K.; Avila, C.; Badaud, F.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bazterra, V.; Bean, A.; Begalli, M.; Bellantoni, L.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Blazey, G.; Blessing, S.; Bloom, K.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Brandt, A.; Brandt, O.; Brock, R.; Bross, A.; Brown, D.; Bu, X. B.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Buszello, C. P.; Camacho-Pérez, E.; Casey, B. C. K.; Castilla-Valdez, H.; Caughron, S.; Chakrabarti, S.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Cho, S. W.; Choi, S.; Choudhary, B.; Cihangir, S.; Claes, D.; Clutter, J.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M. -C.; Cutts, D.; Das, A.; Davies, G.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Deterre, C.; DeVaughan, K.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dominguez, A.; Dubey, A.; Dudko, L. V.; Duperrin, A.; Dutt, S.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Evans, H.; Evdokimov, V. N.; Feng, L.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Fortner, M.; Fox, H.; Fuess, S.; Garbincius, P. H.; Garcia-Bellido, A.; García-González, J. A.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gershtein, Y.; Ginther, G.; Golovanov, G.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Gris, Ph.; Grivaz, J. -F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Gutierrez, G.; Gutierrez, P.; Haley, J.; Han, L.; Harder, K.; Harel, A.; Hauptman, J. M.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Holzbauer, J. L.; Howley, I.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jayasinghe, A.; Jeong, M. S.; Jesik, R.; Jiang, P.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Joshi, J.; Jung, A. W.; Juste, A.; Kajfasz, E.; Karmanov, D.; Katsanos, I.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kiselevich, I.; Kohli, J. M.; Kozelov, A. V.; Kraus, J.; Kumar, A.; Kupco, A.; Kurča, T.; Kuzmin, V. A.; Lammers, S.; Lebrun, P.; Lee, H. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, H.; Liu, Y.; Lobodenko, A.; Lokajicek, M.; Lopes de Sa, R.; Luna-Garcia, R.; Lyon, A. L.; Maciel, A. K. A.; Madar, R.; Magaña-Villalba, R.; Malik, S.; Malyshev, V. L.; Mansour, J.; Martínez-Ortega, J.; McCarthy, R.; McGivern, C. L.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Meyer, A.; Meyer, J.; Miconi, F.; Mondal, N. K.; Mulhearn, M.; Nagy, E.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nguyen, H. T.; Nunnemann, T.; Orduna, J.; Osman, N.; Osta, J.; Pal, A.; Parashar, N.; Parihar, V.; Park, S. K.; Partridge, R.; Parua, N.; Patwa, A.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Pleier, M. -A.; Podstavkov, V. M.; Popov, A. V.; Prewitt, M.; Price, D.; Prokopenko, N.; Qian, J.; Quadt, A.; Quinn, B.; Ratoff, P. N.; Razumov, I.; Ripp-Baudot, I.; Rizatdinova, F.; Rominsky, M.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Sánchez-Hernández, A.; Sanders, M. P.; Santos, A. S.; Savage, G.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schwanenberger, C.; Schwienhorst, R.; Sekaric, J.; Severini, H.; Shabalina, E.; Shary, V.; Shaw, S.; Shchukin, A. A.; Simak, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Soustruznik, K.; Stark, J.; Stoyanova, D. A.; Strauss, M.; Suter, L.; Svoisky, P.; Titov, M.; Tokmenin, V. V.; Tsai, Y. -T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Verkheev, A. Y.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vilanova, D.; Vokac, P.; Wahl, H. D.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; Williams, M. R. J.; Wilson, G. W.; Wobisch, M.; Wood, D. R.; Wyatt, T. R.; Xie, Y.; Yamada, R.; Yang, S.; Yasuda, T.; Yatsunenko, Y. A.; Ye, W.; Ye, Z.; Yin, H.; Yip, K.; Youn, S. W.; Yu, J. M.; Zennamo, J.; Zhao, T. G.; Zhou, B.; Zhu, J.; Zielinski, M.; Zieminska, D.; Zivkovic, L.

    2014-01-01

    We measure the inclusive single muon charge asymmetry and the like-sign dimuon charge asymmetry in $p \\bar{p}$ collisions using the full data set of 10.4 fb$^{-1}$ collected with the D0 detector at the Fermilab Tevatron. The standard model predictions of the charge asymmetries induced by CP violation are small in magnitude compared to the current experimental precision, so non-zero measurements could indicate new sources of CP violation. The measurements differ from the standard model predictions of CP violation in these asymmetries with a significance of 3.6 standard deviations. These results are interpreted in a framework of $B$ meson mixing within the CKM formalism to measure the relative width difference $\\dgg$ between the mass eigenstates of the $\\Bd$ meson system, and the semileptonic charge asymmetries $\\asld$ and $\\asls$ of $\\Bd$ and $\\Bs$ mesons respectively.

  17. Association between tuberculosis and circulating microRNA hsa-let-7b and hsa-miR-30b: A pilot study in a Chinese population.

    Science.gov (United States)

    Xin, Henan; Yang, Yu; Liu, Jianmin; Li, Xiangwei; Li, Mufei; Feng, Boxuan; Li, Zhen; Zhang, Haoran; Li, Hengjing; Shen, Fei; Guan, Ling; Gao, Lei

    2016-07-01

    Tuberculosis remains one of the world's deadliest communicable diseases. Limitations in the current diagnosis tools have heavily slowed down the step to eliminate TB. The objective of this study was to identify potential circulating miRNA associated with tuberculosis (TB) infection and disease development. Agilent human miRNA microarray was used to estimate the circulating levels of 1887 miRNAs among 34 study participants (10 patients with pulmonary TB, 13 controls with latent TB infection and 11 non-infected healthy controls). The identified miRNAs were subsequently verified by real-time qPCR. Target gene prediction and miRNA-gene network construction were further explored. A total of 119 miRNAs were identified to be in different levels between any two groups of the study population by microarray (Fold Change>2, p < 0.01). 11 most promising miRNAs were then selected for verification by real-time qPCR. The levels of hsa-let-7b-5p and hsa-miR-30b-5p were confirmed to be significantly up-regulated in pulmonary TB patients as compared to both control groups (p < 0.01). Caspase 3 was predicted to be one common target gene for these two miRNAs. None of the selected miRNA was confirmed to be related with the infection status. This pilot study suggested circulating hsa-let-7b and hsa-miR-30b might be associated with TB development by regulating the target genes involved in TLR-NF-kB mediated signal pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. A rapid, ratiometric, enzyme-free, and sensitive single-step miRNA detection using three-way junction based FRET probes

    Science.gov (United States)

    Luo, Qingying; Liu, Lin; Yang, Cai; Yuan, Jing; Feng, Hongtao; Chen, Yan; Zhao, Peng; Yu, Zhiqiang; Jin, Zongwen

    2018-03-01

    MicroRNAs (miRNAs) are single stranded endogenous molecules composed of only 18-24 nucleotides which are critical for gene expression regulating the translation of messenger RNAs. Conventional methods based on enzyme-assisted nucleic acid amplification techniques have many problems, such as easy contamination, high cost, susceptibility to false amplification, and tendency to have sequence mismatches. Here we report a rapid, ratiometric, enzyme-free, sensitive, and highly selective single-step miRNA detection using three-way junction assembled (or self-assembled) FRET probes. The developed strategy can be operated within the linear range from subnanomolar to hundred nanomolar concentrations of miRNAs. In comparison with the traditional approaches, our method showed high sensitivity for the miRNA detection and extreme selectivity for the efficient discrimination of single-base mismatches. The results reveal that the strategy paved a new avenue for the design of novel highly specific probes applicable in diagnostics and potentially in microscopic imaging of miRNAs in real biological environments.

  19. Experimental study of the rearrangements of valence protons and neutrons amongst single-particle orbits during double- <mi>β> decay in <mi>Mo>100

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, S. J.; Sharp, D. K.; McAllister, S. A.; Kay, B. P.; Deibel, C. M.; Faestermann, T.; Hertenberger, R.; Mitchell, A. J.; Schiffer, J. P.; Szwec, S. V.; Thomas, J. S.; Wirth, H. -F.

    2017-11-01

    The rearrangements of protons and neutrons amongst the valence single-particle orbitals during double-beta decay of Mo-100 have been determined by measuring cross sections in (d, p), (p, d), (He-3, a), and (He-3, d) reactions on Mo-98,Mo-100 and Ru-100,Ru-102 targets. The deduced nucleon occupancies reveal significant discrepancies when compared with theoretical calculations; the same calculations have previously been used to determine the nuclear matrix element associated with the decay probability of double-beta decay of the Mo-100 system.

  20. Single-Step Incubation Determination of miRNAs in Cancer Cells Using an Amperometric Biosensor Based on Competitive Hybridization onto Magnetic Beads

    Directory of Open Access Journals (Sweden)

    Eva Vargas

    2018-03-01

    Full Text Available This work reports an amperometric biosensor for the determination of miRNA-21, a relevant oncogene. The methodology involves a competitive DNA-target miRNA hybridization assay performed on the surface of magnetic microbeads (MBs and amperometric transduction at screen-printed carbon electrodes (SPCEs. The target miRNA competes with a synthetic fluorescein isothiocyanate (FITC-modified miRNA with an identical sequence for hybridization with a biotinylated and complementary DNA probe (b-Cp immobilized on the surface of streptavidin-modified MBs (b-Cp-MBs. Upon labeling, the FITC-modified miRNA attached to the MBs with horseradish peroxidase (HRP-conjugated anti-FITC Fab fragments and magnetic capturing of the MBs onto the working electrode surface of SPCEs. The cathodic current measured at −0.20 V (versus the Ag pseudo-reference electrode was demonstrated to be inversely proportional to the concentration of the target miRNA. This convenient biosensing method provided a linear range between 0.7 and 10.0 nM and a limit of detection (LOD of 0.2 nM (5 fmol in 25 μL of sample for the synthetic target miRNA without any amplification step. An acceptable selectivity towards single-base mismatched oligonucleotides, a high storage stability of the b-Cp-MBs, and usefulness for the accurate determination of miRNA-21 in raw total RNA (RNAt extracted from breast cancer cells (MCF-7 were demonstrated.

  1. Declines in moose population density at Isle Royle National Park, MI, USA and accompanied changes in landscape patterns

    Science.gov (United States)

    De Jager, N. R.; Pastor, J.

    2009-01-01

    Ungulate herbivores create patterns of forage availability, plant species composition, and soil fertility as they range across large landscapes and consume large quantities of plant material. Over time, herbivore populations fluctuate, producing great potential for spatio-temporal landscape dynamics. In this study, we extend the spatial and temporal extent of a long-term investigation of the relationship of landscape patterns to moose foraging behavior at Isle Royale National Park, MI. We examined how patterns of browse availability and consumption, plant basal area, and soil fertility changed during a recent decline in the moose population. We used geostatistics to examine changes in the nature of spatial patterns in two valleys over 18 years and across short-range and long-range distance scales. Landscape patterns of available and consumed browse changed from either repeated patches or randomly distributed patches in 1988-1992 to random point distributions by 2007 after a recent record high peak followed by a rapid decline in the moose population. Patterns of available and consumed browse became decoupled during the moose population low, which is in contrast to coupled patterns during the earlier high moose population. Distributions of plant basal area and soil nitrogen availability also switched from repeated patches to randomly distributed patches in one valley and to random point distributions in the other valley. Rapid declines in moose population density may release vegetation and soil fertility from browsing pressure and in turn create random landscape patterns. ?? Springer Science+Business Media B.V. 2009.

  2. Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci

    OpenAIRE

    Nowak, Dorota M.; Gajecka, Marzena

    2015-01-01

    Despite numerous studies, the causes of both development and progression of keratoconus remain elusive. Previous studies of this disorder focused mainly on one or two genetic factors only. However, in the analysis of such complex diseases all potential factors should be taken into consideration. The purpose of this study was a comprehensive analysis of known keratoconus loci to uncover genetic factors involved in this disease causation in the general population, which could be omitted in the ...

  3. GraMi: Generalized Frequent Pattern Mining in a Single Large Graph

    KAUST Repository

    Saeedy, Mohammed El

    2011-11-01

    Mining frequent subgraphs is an important operation on graphs. Most existing work assumes a database of many small graphs, but modern applications, such as social networks, citation graphs or protein-protein interaction in bioinformatics, are modeled as a single large graph. Interesting interactions in such applications may be transitive (e.g., friend of a friend). Existing methods, however, search for frequent isomorphic (i.e., exact match) subgraphs and cannot discover many useful patterns. In this paper the authors propose GRAMI, a framework that generalizes frequent subgraph mining in a large single graph. GRAMI discovers frequent patterns. A pattern is a graph where edges are generalized to distance-constrained paths. Depending on the definition of the distance function, many instantiations of the framework are possible. Both directed and undirected graphs, as well as multiple labels per vertex, are supported. The authors developed an efficient implementation of the framework that models the frequency resolution phase as a constraint satisfaction problem, in order to avoid the costly enumeration of all instances of each pattern in the graph. The authors also implemented CGRAMI, a version that supports structural and semantic constraints; and AGRAMI, an approximate version that supports very large graphs. The experiments on real data demonstrate that the authors framework is up to 3 orders of magnitude faster and discovers more interesting patterns than existing approaches.

  4. MicroRNAs and Drinking: Association between the Pre-miR-27a rs895819 Polymorphism and Alcohol Consumption in a Mediterranean Population

    Directory of Open Access Journals (Sweden)

    Rocío Barragán

    2016-08-01

    Full Text Available Recently, microRNAs (miRNA have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvención con DIeta MEDiterránea (PREDIMED-Valencia participants (n = 1007, including men and women aged 67 ± 7 years and measured their alcohol consumption (total and alcoholic beverages through a validated questionnaire. We found a strong association between the pre-miR-27a polymorphism and total alcohol intake, this being higher in GG subjects (5.2 ± 0.4 in AA, 5.9 ± 0.5 in AG and 9.1 ± 1.8 g/day in GG; padjusted = 0.019. We also found a statistically-significant association of the pre-miR-27a polymorphism with the risk of having a high alcohol intake (>2 drinks/day in men and >1 in women: 5.9% in AA versus 17.5% in GG; padjusted < 0.001. In the sensitivity analysis, this association was homogeneous for sex, obesity and Mediterranean diet adherence. In conclusion, we report for the first time a significant association between a miRNA polymorphism (rs895819 and daily alcohol consumption.

  5. MicroRNAs and Drinking: Association between the Pre-miR-27a rs895819 Polymorphism and Alcohol Consumption in a Mediterranean Population

    Science.gov (United States)

    Barragán, Rocío; Coltell, Oscar; Asensio, Eva M.; Francés, Francesc; Sorlí, José V.; Estruch, Ramon; Salas-Huetos, Albert; Ordovas, Jose M.; Corella, Dolores

    2016-01-01

    Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G) gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvención con DIeta MEDiterránea (PREDIMED)-Valencia participants (n = 1007, including men and women aged 67 ± 7 years) and measured their alcohol consumption (total and alcoholic beverages) through a validated questionnaire. We found a strong association between the pre-miR-27a polymorphism and total alcohol intake, this being higher in GG subjects (5.2 ± 0.4 in AA, 5.9 ± 0.5 in AG and 9.1 ± 1.8 g/day in GG; padjusted = 0.019). We also found a statistically-significant association of the pre-miR-27a polymorphism with the risk of having a high alcohol intake (>2 drinks/day in men and >1 in women): 5.9% in AA versus 17.5% in GG; padjusted < 0.001. In the sensitivity analysis, this association was homogeneous for sex, obesity and Mediterranean diet adherence. In conclusion, we report for the first time a significant association between a miRNA polymorphism (rs895819) and daily alcohol consumption. PMID:27537871

  6. Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with Ossification of the Posterior Longitudinal Ligament of the Cervical Spine.

    Directory of Open Access Journals (Sweden)

    Jae Joon Lim

    Full Text Available Ossification of the posterior longitudinal ligament (OPLL of the spine is considered a multifactorial and polygenic disease. We aimed to investigate the association between four single nucleotide polymorphisms (SNPs of pre-miRNAs [miR-146aC>G (rs2910164, miR-149T>C (rs2292832, miR-196a2T>C (rs11614913, and miR-499A>G (rs3746444] and the risk of cervical OPLL in the Korean population.The genotypic frequencies of these four SNPs were analyzed in 207 OPLL patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP assay.For four SNPs in pre-miRNAs, no significant differences were found between OPLL patients and controls. However, subgroup analysis based on OPLL subgroup (continuous: continuous type plus mixed type, segmental: segmental and localized type showed that miR-499GG genotype was associated with an increased risk of segmental type OPLL (adjusted odds ratio = 4.314 with 95% confidence interval: 1.109-16.78. In addition, some allele combinations (C-T-T-G, G-T-T-A, and G-T-C-G of miR-146a/-149/-196a2/-499 and combined genotypes (miR-149TC/miR-196a2TT were associated with increased OPLL risk, whereas the G-T-T-G and G-C-C-G allele combinations were associated with decreased OPLL risk.The results indicate that GG genotype of miR-499 is associated with significantly higher risks of OPLL in the segmental OPLL group. The miR-146a/-149/-196a2/-499 allele combinations may be a genetic risk factor for cervical OPLL in the Korean population.

  7. Genetic variant of miR-4293 rs12220909 is associated with susceptibility to non-small cell lung cancer in a Chinese Han population.

    Directory of Open Access Journals (Sweden)

    Lixia Fan

    Full Text Available Non-small cell lung cancer is one of the most common cancers and the leading cause of cancer death worldwide. Genetic variants in regulatory regions of some miRNAs might be involved in non-small cell lung cancer susceptibility and survival. rs12220909 (G/C genetic polymorphism in miR-4293 has been shown to be associated with decreased risk of esophageal squamous cell carcinoma. However, the influence of rs12220909 genetic variation on non-small cell lung cancer susceptibility has not been reported. In order to evaluate the potential association between miR-4293 rs12220909 and non-small cell lung cancer risk in a Chinese population, we performed a case-control study among 998 non-small cell lung cancer cases and 1471 controls. The data shows that miR-4293 rs12220909 was significantly associated with decreased susceptibility to non-small cell lung cancer (GC vs.GG: OR = 0.681, 95%CI = 0.555-0.835, P = 2.19E-4; GG vs. GC+CC: OR = 0.687, 95%CI = 0.564-0.837, P = 1.95E-4, which indicates that rs12220909 in miR-4293 may play a significant role in the development of non-small cell lung cancer.

  8. Global Asymptotic Stability for Discrete Single Species Population Models

    Directory of Open Access Journals (Sweden)

    A. Bilgin

    2017-01-01

    Full Text Available We present some basic discrete models in populations dynamics of single species with several age classes. Starting with the basic Beverton-Holt model that describes the change of single species we discuss its basic properties such as a convergence of all solutions to the equilibrium, oscillation of solutions about the equilibrium solutions, Allee’s effect, and Jillson’s effect. We consider the effect of the constant and periodic immigration and emigration on the global properties of Beverton-Holt model. We also consider the effect of the periodic environment on the global properties of Beverton-Holt model.

  9. Inclusive cross sections for pairs of identified light charged hadrons and for single protons in <mi>emi>+<mi>e> at <mi>s>=10.58<mi>GeV>

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, R.; Abdesselam, A.; Adachi, I.; Aihara, H.; Al Said, S.; Asner, D. M.; Aushev, T.; Ayad, R.; Babu, V.; Badhrees, I.; Bakich, A. M.; Barberio, E.; Bhardwaj, V.; Bhuyan, B.; Biswal, J.; Bozek, A.; Bračko, M.; Browder, T. E.; Červenkov, D.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Cho, K.; Chobanova, V.; Choi, Y.; Cinabro, D.; Dalseno, J.; Dash, N.; Dingfelder, J.; Doležal, Z.; Drásal, Z.; Dutta, D.; Eidelman, S.; Farhat, H.; Fast, J. E.; Ferber, T.; Fulsom, B. G.; Gaur, V.; Gabyshev, N.; Garmash, A.; Gillard, R.; Giordano, F.; Goh, Y. M.; Goldenzweig, P.; Golob, B.; Haba, J.; Hara, T.; Hayasaka, K.; Hayashii, H.; He, X. H.; Hou, W. -S.; Hsu, C. -L.; Iijima, T.; Inami, K.; Ishikawa, A.; Itoh, R.; Iwasaki, Y.; Jacobs, W. W.; Jaegle, I.; Joffe, D.; Joo, K. K.; Kang, K. H.; Kato, E.; Katrenko, P.; Kawasaki, T.; Kim, D. Y.; Kim, H. J.; Kim, J. B.; Kim, J. H.; Kim, K. T.; Kim, M. J.; Kim, S. H.; Kim, Y. J.; Kodyš, P.; Korpar, S.; Križan, P.; Krokovny, P.; Kuzmin, A.; Kwon, Y. -J.; Lange, J. S.; Lee, D. H.; Li, L.; Li Gioi, L.; Libby, J.; Liu, Y.; Liventsev, D.; Lukin, P.; Masuda, M.; Matvienko, D.; Miyabayashi, K.; Miyake, H.; Miyata, H.; Mizuk, R.; Mohanty, S.; Moll, A.; Moon, H. K.; Mori, T.; Mussa, R.; Nakano, E.; Nakao, M.; Nanut, T.; Natkaniec, Z.; Nayak, M.; Niiyama, M.; Nisar, N. K.; Nishida, S.; Ogawa, S.; Okuno, S.; Oswald, C.; Pakhlov, P.; Pakhlova, G.; Pal, B.; Park, C. W.; Park, H.; Pedlar, T. K.; Pestotnik, R.; Petrič, M.; Piilonen, L. E.; Ribežl, E.; Ritter, M.; Rostomyan, A.; Ryu, S.; Sahoo, H.; Sakai, K.; Sakai, Y.; Sandilya, S.; Santelj, L.; Sanuki, T.; Savinov, V.; Schneider, O.; Schnell, G.; Schwanda, C.; Seino, Y.; Senyo, K.; Seon, O.; Sevior, M. E.; Shebalin, V.; Shibata, T. -A.; Shiu, J. -G.; Simon, F.; Sohn, Y. -S.; Sokolov, A.; Solovieva, E.; Starič, M.; Sumihama, M.; Sumisawa, K.; Sumiyoshi, T.; Tamponi, U.; Teramoto, Y.; Trusov, V.; Uchida, M.; Uglov, T.; Unno, Y.; Uno, S.; Usov, Y.; Van Hulse, C.; Vanhoefer, P.; Varner, G.; Vorobyev, V.; Vossen, A.; Wagner, M. N.; Wang, C. H.; Wang, M. -Z.; Wang, P.; Watanabe, M.; Watanabe, Y.; Williams, K. M.; Won, E.; Yamaoka, J.; Yashchenko, S.; Yelton, J.; Yusa, Y.; Zhang, Z. P.; Zhilich, V.; Zhulanov, V.

    2015-11-01

    We report the first double differential cross sections of two charged pions and kaons (e+e- ->hhX) in electron-positron annihilation as a function of the fractional energies of the two hadrons for any charge and hadron combination. The dependence of these di-hadron cross sections on the topology (same, opposite-hemisphere or anywhere) is also studied with the help of the event shape variable combinations directly shed light on the contributing fragmentation functions. For example, we find energies where disfavored fragmentation is expected to be suppressed. These di-hadron results are the KEKB asymmetric-energy e+e- collider. Extending the previously published single-pion and single-kaon cross sections, single-proton (e+e- -> pX) cross sections are extracted from a 159 fb^-1 data sub-sample.

  10. Study of <mi>π>0 pair production in single-tag two-photon collisions

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, M.; Uehara, S.; Watanabe, Y.; Nakazawa, H.; Abdesselam, A.; Adachi, I.; Aihara, H.; Al Said, S.; Asner, D. M.; Atmacan, H.; Aulchenko, V.; Aushev, T.; Babu, V.; Badhrees, I.; Bakich, A. M.; Barberio, E.; Behera, P.; Bhuyan, B.; Biswal, J.; Bobrov, A.; Bonvicini, G.; Bozek, A.; Bračko, M.; Browder, T. E.; Červenkov, D.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Chistov, R.; Cho, K.; Chobanova, V.; Choi, S. -K.; Choi, Y.; Cinabro, D.; Dalseno, J.; Danilov, M.; Dash, N.; Dingfelder, J.; Doležal, Z.; Drásal, Z.; Dutta, D.; Eidelman, S.; Epifanov, D.; Farhat, H.; Fast, J. E.; Ferber, T.; Fulsom, B. G.; Gaur, V.; Gabyshev, N.; Garmash, A.; Gillard, R.; Giordano, F.; Glattauer, R.; Goh, Y. M.; Goldenzweig, P.; Golob, B.; Haba, J.; Hayasaka, K.; Hayashii, H.; He, X. H.; Hou, W. -S.; Iijima, T.; Inami, K.; Ishikawa, A.; Itoh, R.; Iwasaki, Y.; Jaegle, I.; Joffe, D.; Joo, K. K.; Julius, T.; Kang, K. H.; Kato, E.; Kawasaki, T.; Kim, D. Y.; Kim, J. B.; Kim, J. H.; Kim, K. T.; Kim, M. J.; Kim, S. H.; Kim, Y. J.; Ko, B. R.; Korpar, S.; Križan, P.; Krokovny, P.; Kumita, T.; Kuzmin, A.; Kwon, Y. -J.; Lange, J. S.; Lee, D. H.; Lee, I. S.; Li, C.; Li, L.; Li, Y.; Libby, J.; Liventsev, D.; Lukin, P.; Matvienko, D.; Miyabayashi, K.; Miyata, H.; Mizuk, R.; Mohanty, G. B.; Mohanty, S.; Moll, A.; Moon, H. K.; Mori, T.; Mussa, R.; Nakano, E.; Nakao, M.; Nanut, T.; Natkaniec, Z.; Nayak, M.; Nisar, N. K.; Nishida, S.; Ogawa, S.; Pakhlov, P.; Pakhlova, G.; Pal, B.; Park, C. W.; Park, H.; Pedlar, T. K.; Pestotnik, R.; Petrič, M.; Piilonen, L. E.; Rauch, J.; Ribežl, E.; Ritter, M.; Rostomyan, A.; Sandilya, S.; Santelj, L.; Sanuki, T.; Sato, Y.; Savinov, V.; Schneider, O.; Schnell, G.; Schwanda, C.; Seino, Y.; Senyo, K.; Seon, O.; Sevior, M. E.; Shebalin, V.; Shen, C. P.; Shibata, T. -A.; Shiu, J. -G.; Shwartz, B.; Simon, F.; Sohn, Y. -S.; Sokolov, A.; Solovieva, E.; Starič, M.; Sumihama, M.; Sumiyoshi, T.; Tamponi, U.; Tanida, K.; Teramoto, Y.; Uglov, T.; Unno, Y.; Uno, S.; Van Hulse, C.; Vanhoefer, P.; Varner, G.; Vinokurova, A.; Vorobyev, V.; Vossen, A.; Wagner, M. N.; Wang, C. H.; Wang, M. -Z.; Wang, P.; Williams, K. M.; Won, E.; Yamaoka, J.; Yamashita, Y.; Yashchenko, S.; Ye, H.; Yusa, Y.; Zhang, C. C.; Zhang, Z. P.; Zhilich, V.; Zhulanov, V.; Zupanc, A.

    2016-02-01

    We report a measurement of the differential cross section of π^0 pair production in single-tag two-photon collisions, y*y->π^0π^0, in e+e- scattering. The cross section is measured for Q^2up to 30 GeV^2 is the negative of the invariant mass squared of the tagged photon

  11. Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

    Science.gov (United States)

    Liu, Xiao-Lin; Pan, Qin; Zhang, Rui-Nan; Shen, Feng; Yan, Shi-Yan; Sun, Chao; Xu, Zheng-Jie; Chen, Yuan-Wen; Fan, Jian-Gao

    2016-01-01

    AIM To assess disease-specific circulating microRNAs (miRNAs) in non-alcoholic steatohepatitis (NASH) patients. METHODS A total of 111 biopsy-proven non-alcoholic fatty liver disease (NAFLD) or chronic hepatitis B (CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of miR-122, -125b, -146b, -16, -21, -192, -27b and -34a. The correlations between serum miRNAs and histological features of NAFLD were determined. The diagnostic value of miRNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI), respectively. RESULTS Circulating miR-122, -16, -192 and -34a showed differential expression levels between NAFLD and CHB patients, and miR-34a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples (P steatosis (R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity (R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum miR-16 levels were associated with fibrosis (R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of miR-34a for NASH (area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but miR-16 showed a limited performance in the diagnosis of significant fibrosis in NASH. CONCLUSION Circulating miR-34a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH. PMID:27956809

  12. Observation of <mi>s> -Channel Production of Single Top Quarks at the Tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, T.; Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Agnew, J. P.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Askew, A.; Atkins, S.; Auerbach, B.; Augsten, K.; Aurisano, A.; Avila, C.; Azfar, F.; Badaud, F.; Badgett, W.; Bae, T.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barbaro-Galtieri, A.; Barberis, E.; Baringer, P.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartlett, J. F.; Bartos, P.; Bassler, U.; Bauce, M.; Bazterra, V.; Bean, A.; Bedeschi, F.; Begalli, M.; Behari, S.; Bellantoni, L.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Bhatti, A.; Bland, K. R.; Blazey, G.; Blessing, S.; Bloom, K.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Bortoletto, D.; Borysova, M.; Boudreau, J.; Boveia, A.; Brandt, A.; Brandt, O.; Brigliadori, L.; Brock, R.; Bromberg, C.; Bross, A.; Brown, D.; Brucken, E.; Bu, X. B.; Budagov, J.; Budd, H. S.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Burkett, K.; Busetto, G.; Bussey, P.; Buszello, C. P.; Butti, P.; Buzatu, A.; Calamba, A.; Camacho-Pérez, E.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Casey, B. C. K.; Castilla-Valdez, H.; Castro, A.; Catastini, P.; Caughron, S.; Cauz, D.; Cavaliere, V.; Cavalli-Sforza, M.; Cerri, A.; Cerrito, L.; Chakrabarti, S.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Cho, S. W.; Choi, S.; Chokheli, D.; Choudhary, B.; Cihangir, S.; Claes, D.; Clark, A.; Clarke, C.; Clutter, J.; Convery, M. E.; Conway, J.; Cooke, M.; Cooper, W. E.; Corbo, M.; Corcoran, M.; Cordelli, M.; Couderc, F.; Cousinou, M. -C.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; Cutts, D.; Das, A.; d’Ascenzo, N.; Datta, M.; Davies, G.; de Barbaro, P.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Demortier, L.; Deninno, M.; Denisov, D.; Denisov, S. P.; D’Errico, M.; Desai, S.; Deterre, C.; DeVaughan, K.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dittmann, J. R.; Dominguez, A.; Donati, S.; D’Onofrio, M.; Dorigo, M.; Driutti, A.; Dubey, A.; Dudko, L. V.; Duperrin, A.; Dutt, S.; Eads, M.; Ebina, K.; Edgar, R.; Edmunds, D.; Elagin, A.; Ellison, J.; Elvira, V. D.; Enari, Y.; Erbacher, R.; Errede, S.; Esham, B.; Evans, H.; Evdokimov, V. N.; Farrington, S.; Feng, L.; Ferbel, T.; Fernández Ramos, J. P.; Fiedler, F.; Field, R.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Flanagan, G.; Forrest, R.; Fortner, M.; Fox, H.; Franklin, M.; Freeman, J. C.; Frisch, H.; Fuess, S.; Funakoshi, Y.; Galloni, C.; Garbincius, P. H.; Garcia-Bellido, A.; García-González, J. A.; Garfinkel, A. F.; Garosi, P.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gerberich, H.; Gerchtein, E.; Gershtein, Y.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Ginther, G.; Giokaris, N.; Giromini, P.; Giurgiu, G.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Golossanov, A.; Golovanov, G.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Grinstein, S.; Gris, Ph.; Grivaz, J. -F.; Grohsjean, A.; Grosso-Pilcher, C.; Group, R. C.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Guimaraes da Costa, J.; Gutierrez, G.; Gutierrez, P.; Hahn, S. R.; Haley, J.; Han, J. Y.; Han, L.; Happacher, F.; Hara, K.; Harder, K.; Hare, M.; Harel, A.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hauptman, J. M.; Hays, C.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinrich, J.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herndon, M.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hocker, A.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Holzbauer, J. L.; Hong, Z.; Hopkins, W.; Hou, S.; Howley, I.; Hubacek, Z.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Introzzi, G.; Iori, M.; Ito, A. S.; Ivanov, A.; Jabeen, S.; Jaffré, M.; James, E.; Jang, D.; Jayasinghe, A.; Jayatilaka, B.; Jeon, E. J.; Jeong, M. S.; Jesik, R.; Jiang, P.; Jindariani, S.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jones, M.; Jonsson, P.; Joo, K. K.; Joshi, J.; Jun, S. Y.; Jung, A. W.; Junk, T. R.; Juste, A.; Kajfasz, E.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Karmanov, D.; Kasmi, A.; Kato, Y.; Katsanos, I.; Kehoe, R.; Kermiche, S.; Ketchum, W.; Keung, J.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. H.; Kim, S. B.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Kiselevich, I.; Knoepfel, K.; Kohli, J. M.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kozelov, A. V.; Kraus, J.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kumar, A.; Kupco, A.; Kurata, M.; Kurča, T.; Kuzmin, V. A.; Laasanen, A. T.; Lammel, S.; Lammers, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lebrun, P.; Lee, H. S.; Lee, H. S.; Lee, J. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Leo, S.; Leone, S.; Lewis, J. D.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Limosani, A.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipeles, E.; Lipton, R.; Lister, A.; Liu, H.; Liu, H.; Liu, Q.; Liu, T.; Liu, Y.; Lobodenko, A.; Lockwitz, S.; Loginov, A.; Lokajicek, M.; Lopes de Sa, R.; Lucchesi, D.; Lucà, A.; Lueck, J.; Lujan, P.; Lukens, P.; Luna-Garcia, R.; Lungu, G.; Lyon, A. L.; Lys, J.; Lysak, R.; Maciel, A. K. A.; Madar, R.; Madrak, R.; Maestro, P.; Magaña-Villalba, R.; Malik, S.; Malik, S.; Malyshev, V. L.; Manca, G.; Manousakis-Katsikakis, A.; Mansour, J.; Marchese, L.; Margaroli, F.; Marino, P.; Martínez-Ortega, J.; Martínez, M.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McCarthy, R.; McGivern, C. L.; McNulty, R.; Mehta, A.; Mehtala, P.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Mesropian, C.; Meyer, A.; Meyer, J.; Miao, T.; Miconi, F.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Mondal, N. K.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Mulhearn, M.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nagy, E.; Nakano, I.; Napier, A.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Nett, J.; Neu, C.; Neustroev, P.; Nguyen, H. T.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Nunnemann, T.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Orduna, J.; Ortolan, L.; Osman, N.; Osta, J.; Pagliarone, C.; Pal, A.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parashar, N.; Parihar, V.; Park, S. K.; Parker, W.; Partridge, R.; Parua, N.; Patwa, A.; Pauletta, G.; Paulini, M.; Paus, C.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Phillips, T. J.; Piacentino, G.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pleier, M. -A.; Podstavkov, V. M.; Pondrom, L.; Popov, A. V.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prewitt, M.; Price, D.; Prokopenko, N.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Qian, J.; Quadt, A.; Quinn, B.; Ranjan, N.; Ratoff, P. N.; Razumov, I.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ripp-Baudot, I.; Ristori, L.; Rizatdinova, F.; Robson, A.; Rodriguez, T.; Rolli, S.; Rominsky, M.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sajot, G.; Sakumoto, W. K.; Sakurai, Y.; Sánchez-Hernández, A.; Sanders, M. P.; Santi, L.; Santos, A. S.; Sato, K.; Savage, G.; Saveliev, V.; Savoy-Navarro, A.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schlabach, P.; Schmidt, E. E.; Schwanenberger, C.; Schwarz, T.; Schwienhorst, R.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Sekaric, J.; Semenov, A.; Severini, H.; Sforza, F.; Shabalina, E.; Shalhout, S. Z.; Shary, V.; Shaw, S.; Shchukin, A. A.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simak, V.; Simonenko, A.; Skubic, P.; Slattery, P.; Sliwa, K.; Smirnov, D.; Smith, J. R.; Snider, F. D.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Song, H.; Sonnenschein, L.; Sorin, V.; Soustruznik, K.; St. Denis, R.; Stancari, M.; Stark, J.; Stentz, D.; Stoyanova, D. A.; Strauss, M.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Suter, L.; Svoisky, P.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Titov, M.; Toback, D.; Tokar, S.; Tokmenin, V. V.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Tsai, Y. -T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Ukegawa, F.; Uozumi, S.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Vázquez, F.; Velev, G.; Vellidis, C.; Verkheev, A. Y.; Vernieri, C.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vidal, M.; Vilanova, D.; Vilar, R.; Vizán, J.; Vogel, M.; Vokac, P.; Volpi, G.; Wagner, P.; Wahl, H. D.; Wallny, R.; Wang, M. H. L. S.; Wang, S. M.; Warchol, J.; Waters, D.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; Wester, W. C.; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Williams, M. R. J.; Wilson, G. W.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wobisch, M.; Wolbers, S.; Wolfe, H.; Wood, D. R.; Wright, T.; Wu, X.; Wu, Z.; Wyatt, T. R.; Xie, Y.; Yamada, R.; Yamamoto, K.; Yamato, D.; Yang, S.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W. -M.; Yasuda, T.; Yatsunenko, Y. A.; Ye, W.; Ye, Z.; Yeh, G. P.; Yi, K.; Yin, H.; Yip, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Youn, S. W.; Yu, G. B.; Yu, I.; Yu, J. M.; Zanetti, A. M.; Zeng, Y.; Zennamo, J.; Zhao, T. G.; Zhou, B.; Zhou, C.; Zhu, J.; Zielinski, M.; Zieminska, D.; Zivkovic, L.; Zucchelli, S.

    2014-06-01

    We report the first observation of single-top-quark production in the s channel through the combination of the CDF and D0 measurements of the cross section in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb-1 per experiment. The measured cross section is $\\sigma_s = 1.29^{+0.26}_{-0.24}$ pb. The probability of observing a statistical fluctuation of the background to a cross section of the observed size or larger is $1.8 \\times 10^{-10}$, corresponding to a significance of 6.3 standard deviations for the presence of an s-channel contribution to the production of single-top quarks.

  13. Tevatron Combination of Single-Top-Quark Cross Sections and Determination of the Magnitude of the Cabibbo-Kobayashi-Maskawa Matrix Element <mi>Vmi><mi>tb>

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, T.; Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Agnew, J. P.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Askew, A.; Atkins, S.; Auerbach, B.; Augsten, K.; Aurisano, A.; Avila, C.; Azfar, F.; Badaud, F.; Badgett, W.; Bae, T.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barbaro-Galtieri, A.; Barberis, E.; Baringer, P.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartlett, J. F.; Bartos, P.; Bassler, U.; Bauce, M.; Bazterra, V.; Bean, A.; Bedeschi, F.; Begalli, M.; Behari, S.; Bellantoni, L.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Bhatti, A.; Bland, K. R.; Blazey, G.; Blessing, S.; Bloom, K.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Bortoletto, D.; Borysova, M.; Boudreau, J.; Boveia, A.; Brandt, A.; Brandt, O.; Brigliadori, L.; Brock, R.; Bromberg, C.; Bross, A.; Brown, D.; Brucken, E.; Bu, X. B.; Budagov, J.; Budd, H. S.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Burkett, K.; Busetto, G.; Bussey, P.; Buszello, C. P.; Butti, P.; Buzatu, A.; Calamba, A.; Camacho-Pérez, E.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Casey, B. C. K.; Castilla-Valdez, H.; Castro, A.; Catastini, P.; Caughron, S.; Cauz, D.; Cavaliere, V.; Cerri, A.; Cerrito, L.; Chakrabarti, S.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Cho, S. W.; Choi, S.; Chokheli, D.; Choudhary, B.; Cihangir, S.; Claes, D.; Clark, A.; Clarke, C.; Clutter, J.; Convery, M. E.; Conway, J.; Cooke, M.; Cooper, W. E.; Corbo, M.; Corcoran, M.; Cordelli, M.; Couderc, F.; Cousinou, M. -C.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; Cutts, D.; Das, A.; d’Ascenzo, N.; Datta, M.; Davies, G.; de Barbaro, P.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Demortier, L.; Deninno, M.; Denisov, D.; Denisov, S. P.; D’Errico, M.; Desai, S.; Deterre, C.; DeVaughan, K.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dittmann, J. R.; Dominguez, A.; Donati, S.; D’Onofrio, M.; Dorigo, M.; Driutti, A.; Dubey, A.; Dudko, L. V.; Duperrin, A.; Dutt, S.; Eads, M.; Ebina, K.; Edgar, R.; Edmunds, D.; Elagin, A.; Ellison, J.; Elvira, V. D.; Enari, Y.; Erbacher, R.; Errede, S.; Esham, B.; Evans, H.; Evdokimov, A.; Evdokimov, V. N.; Farrington, S.; Fauré, A.; Feng, L.; Ferbel, T.; Fernández Ramos, J. P.; Fiedler, F.; Field, R.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Flanagan, G.; Forrest, R.; Fortner, M.; Fox, H.; Franklin, M.; Freeman, J. C.; Frisch, H.; Fuess, S.; Funakoshi, Y.; Galloni, C.; Garbincius, P. H.; Garcia-Bellido, A.; García-González, J. A.; Garfinkel, A. F.; Garosi, P.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gerberich, H.; Gerchtein, E.; Gershtein, Y.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Ginther, G.; Giokaris, N.; Giromini, P.; Glagolev, V.; Glenzinski, D.; Gogota, O.; Gold, M.; Goldin, D.; Golossanov, A.; Golovanov, G.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Gris, Ph.; Grivaz, J. -F.; Grohsjean, A.; Grosso-Pilcher, C.; Group, R. C.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Guimaraes da Costa, J.; Gutierrez, G.; Gutierrez, P.; Hahn, S. R.; Haley, J.; Han, J. Y.; Han, L.; Happacher, F.; Hara, K.; Harder, K.; Hare, M.; Harel, A.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hauptman, J. M.; Hays, C.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinrich, J.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herndon, M.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hocker, A.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Holzbauer, J. L.; Hong, Z.; Hopkins, W.; Hou, S.; Howley, I.; Hubacek, Z.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Introzzi, G.; Iori, M.; Ito, A. S.; Ivanov, A.; Jabeen, S.; Jaffré, M.; James, E.; Jang, D.; Jayasinghe, A.; Jayatilaka, B.; Jeon, E. J.; Jeong, M. S.; Jesik, R.; Jiang, P.; Jindariani, S.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jones, M.; Jonsson, P.; Joo, K. K.; Joshi, J.; Jun, S. Y.; Jung, A. W.; Junk, T. R.; Juste, A.; Kajfasz, E.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Karmanov, D.; Kasmi, A.; Kato, Y.; Katsanos, I.; Kaur, M.; Kehoe, R.; Kermiche, S.; Ketchum, W.; Keung, J.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. H.; Kim, S. B.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Kiselevich, I.; Knoepfel, K.; Kohli, J. M.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kozelov, A. V.; Kraus, J.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kumar, A.; Kupco, A.; Kurata, M.; Kurča, T.; Kuzmin, V. A.; Laasanen, A. T.; Lammel, S.; Lammers, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lebrun, P.; Lee, H. S.; Lee, H. S.; Lee, J. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Leo, S.; Leone, S.; Lewis, J. D.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Limosani, A.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipeles, E.; Lipton, R.; Lister, A.; Liu, H.; Liu, H.; Liu, Q.; Liu, T.; Liu, Y.; Lobodenko, A.; Lockwitz, S.; Loginov, A.; Lokajicek, M.; Lopes de Sa, R.; Lucchesi, D.; Lucà, A.; Lueck, J.; Lujan, P.; Lukens, P.; Luna-Garcia, R.; Lungu, G.; Lyon, A. L.; Lys, J.; Lysak, R.; Maciel, A. K. A.; Madar, R.; Madrak, R.; Maestro, P.; Magaña-Villalba, R.; Malik, S.; Malik, S.; Malyshev, V. L.; Manca, G.; Manousakis-Katsikakis, A.; Mansour, J.; Marchese, L.; Margaroli, F.; Marino, P.; Martínez-Ortega, J.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McCarthy, R.; McGivern, C. L.; McNulty, R.; Mehta, A.; Mehtala, P.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Mesropian, C.; Meyer, A.; Meyer, J.; Miao, T.; Miconi, F.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Mondal, N. K.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Mulhearn, M.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nagy, E.; Nakano, I.; Napier, A.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Nett, J.; Neu, C.; Neustroev, P.; Nguyen, H. T.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Nunnemann, T.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Orduna, J.; Ortolan, L.; Osman, N.; Osta, J.; Pagliarone, C.; Pal, A.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parashar, N.; Parihar, V.; Park, S. K.; Parker, W.; Partridge, R.; Parua, N.; Patwa, A.; Pauletta, G.; Paulini, M.; Paus, C.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Phillips, T. J.; Piacentino, G.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pleier, M. -A.; Podstavkov, V. M.; Pondrom, L.; Popov, A. V.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prewitt, M.; Price, D.; Prokopenko, N.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Qian, J.; Quadt, A.; Quinn, B.; Ratoff, P. N.; Razumov, I.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ripp-Baudot, I.; Ristori, L.; Rizatdinova, F.; Robson, A.; Rodriguez, T.; Rolli, S.; Rominsky, M.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sajot, G.; Sakumoto, W. K.; Sakurai, Y.; Sánchez-Hernández, A.; Sanders, M. P.; Santi, L.; Santos, A. S.; Sato, K.; Savage, G.; Saveliev, V.; Savitskyi, M.; Savoy-Navarro, A.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schlabach, P.; Schmidt, E. E.; Schwanenberger, C.; Schwarz, T.; Schwienhorst, R.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Sekaric, J.; Semenov, A.; Severini, H.; Sforza, F.; Shabalina, E.; Shalhout, S. Z.; Shary, V.; Shaw, S.; Shchukin, A. A.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simak, V.; Simonenko, A.; Skubic, P.; Slattery, P.; Sliwa, K.; Smirnov, D.; Smith, J. R.; Snider, F. D.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Song, H.; Sonnenschein, L.; Sorin, V.; Soustruznik, K.; St. Denis, R.; Stancari, M.; Stark, J.; Stentz, D.; Stoyanova, D. A.; Strauss, M.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Suter, L.; Svoisky, P.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Titov, M.; Toback, D.; Tokar, S.; Tokmenin, V. V.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Tsai, Y. -T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Ukegawa, F.; Uozumi, S.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Vázquez, F.; Velev, G.; Vellidis, C.; Verkheev, A. Y.; Vernieri, C.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vidal, M.; Vilanova, D.; Vilar, R.; Vizán, J.; Vogel, M.; Vokac, P.; Volpi, G.; Wagner, P.; Wahl, H. D.; Wallny, R.; Wang, M. H. L. S.; Wang, S. M.; Warchol, J.; Waters, D.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; Wester, W. C.; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Williams, M. R. J.; Wilson, G. W.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wobisch, M.; Wolbers, S.; Wolfe, H.; Wood, D. R.; Wright, T.; Wu, X.; Wu, Z.; Wyatt, T. R.; Xie, Y.; Yamada, R.; Yamamoto, K.; Yamato, D.; Yang, S.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W. -M.; Yasuda, T.; Yatsunenko, Y. A.; Ye, W.; Ye, Z.; Yeh, G. P.; Yi, K.; Yin, H.; Yip, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Youn, S. W.; Yu, G. B.; Yu, I.; Yu, J. M.; Zanetti, A. M.; Zeng, Y.; Zennamo, J.; Zhao, T. G.; Zhou, B.; Zhou, C.; Zhu, J.; Zielinski, M.; Zieminska, D.; Zivkovic, L.; Zucchelli, S.

    2015-10-01

    Here, we present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb-1 per experiment. The t-channel cross section is measured to be σt=2.25+0.29-0.31 pb. We also present the combinations of the two-dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s+t channel cross section measurement resulting in σs+t=3.30+0.52-0.40 pb , without assuming the standard model value for the ratio σs/σt. Moreover, the resulting value of the magnitude of the top-to-bottom quark coupling is |Vtb|=1.02+0.06-0.05, corresponding to |Vtb|>0.92 at the 95% C.L.

  14. Modeling bacterial population growth from stochastic single-cell dynamics.

    Science.gov (United States)

    Alonso, Antonio A; Molina, Ignacio; Theodoropoulos, Constantinos

    2014-09-01

    A few bacterial cells may be sufficient to produce a food-borne illness outbreak, provided that they are capable of adapting and proliferating on a food matrix. This is why any quantitative health risk assessment policy must incorporate methods to accurately predict the growth of bacterial populations from a small number of pathogens. In this aim, mathematical models have become a powerful tool. Unfortunately, at low cell concentrations, standard deterministic models fail to predict the fate of the population, essentially because the heterogeneity between individuals becomes relevant. In this work, a stochastic differential equation (SDE) model is proposed to describe variability within single-cell growth and division and to simulate population growth from a given initial number of individuals. We provide evidence of the model ability to explain the observed distributions of times to division, including the lag time produced by the adaptation to the environment, by comparing model predictions with experiments from the literature for Escherichia coli, Listeria innocua, and Salmonella enterica. The model is shown to accurately predict experimental growth population dynamics for both small and large microbial populations. The use of stochastic models for the estimation of parameters to successfully fit experimental data is a particularly challenging problem. For instance, if Monte Carlo methods are employed to model the required distributions of times to division, the parameter estimation problem can become numerically intractable. We overcame this limitation by converting the stochastic description to a partial differential equation (backward Kolmogorov) instead, which relates to the distribution of division times. Contrary to previous stochastic formulations based on random parameters, the present model is capable of explaining the variability observed in populations that result from the growth of a small number of initial cells as well as the lack of it compared to

  15. A Comparison and Integration of MiSeq and MinION Platforms for Sequencing Single Source and Mixed Mitochondrial Genomes.

    Directory of Open Access Journals (Sweden)

    Michael R Lindberg

    Full Text Available Single source and multiple donor (mixed samples of human mitochondrial DNA were analyzed and compared using the MinION and the MiSeq platforms. A generalized variant detection strategy was employed to provide a cursory framework for evaluating the reliability and accuracy of mitochondrial sequences produced by the MinION. The feasibility of long-read phasing was investigated to establish its efficacy in quantitatively distinguishing and deconvolving individuals in a mixture. Finally, a proof-of-concept was demonstrated by integrating both platforms in a hybrid assembly that leverages solely mixture data to accurately reconstruct full mitochondrial genomes.

  16. SNP-SNP interactions of three new pri-miRNAs with the target gene PGC and multidimensional analysis of H. pylori in the gastric cancer/atrophic gastritis risk in a Chinese population.

    Science.gov (United States)

    Xu, Qian; Wu, Ye-Feng; Li, Ying; He, Cai-Yun; Sun, Li-Ping; Liu, Jing-Wei; Yuan, Yuan

    2016-04-26

    Gastric cancer (GC) is a multistep complex disease involving multiple genes, and gene-gene interactions have a greater effect than a single gene in determining cancer susceptibility. This study aimed to explore the interaction of the let-7e rs8111742, miR-365b rs121224, and miR-4795 rs1002765 single nucleotide polymorphisms (SNPs) with SNPs of the predicted target gene PGC and Helicobacter pylori status in GC and atrophic gastritis (AG) risk. Three miRNA SNPs and seven PGC SNPs were detected in 2448 cases using the Sequenom MassArray platform. Two pairwise combinations of miRNA and PGC SNPs were associated with increased AG risk (let-7e rs8111742 - PGC rs6458238 and miR-4795 rs1002765 - PGC rs9471643). Singly, miR-365b rs121224 and PGC rs6912200 had no effect individually but in combination they demonstrated an epistatic interaction associated with AG risk. Similarly, let-7e rs8111742 and miR-4795 rs1002765 SNPs interacted with H. pylori infection to increase GC risk (rs8111742: Pinteraction = 0.024; rs1002765: Pinteraction = 0.031, respectively). A three-dimensional interaction analysis found miR-4795 rs1002765, PGC rs9471643, and H. pylori infection positively interacted to increase AG risk (Pinteraction = 0.027). Also, let-7e rs8111742, PGC rs6458238, and H. pylori infection positively interacted to increase GC risk (Pinteraction = 0.036). Furthermore, both of these three-dimensional interactions had a dosage-effect correspondence (Ptrend < 0.001) and were verified by MDR. In conclusion, the miRNAs SNPs (let-7e rs8111742 and miR-4795 rs1002765) might have more superior efficiency when combined with PGC SNPs and/or H. pylori for GC or AG risk than a single SNP on its own.

  17. A miRNA-492 binding-site polymorphism in BSG (basigin) confers risk to psoriasis in central south Chinese population.

    Science.gov (United States)

    Wu, Li-Sha; Li, Fang-Fang; Sun, Liang-Dan; Li, Dai; Su, Juan; Kuang, Ye-Hong; Chen, Gang; Chen, Xiao-Ping; Chen, Xiang

    2011-12-01

    Psoriasis (PS; MIM#177900) is a chronic inflammatory immune-mediated skin disorder. Although the disease is believed to be caused by a combination of genetic, immunologic and environmental factors, its complete etiology has not been fully understood. Here, we focused on the BSG (MIM#109480), a member of the immunoglobulin superfamily expressed ubiquitously in circulating immune cell populations. We observed that the expression level of BSG in PBMCs was elevated in psoriasis patients. To understand the underlying mechanism for this change, we genotyped the rs8259 T>A SNP located in the 3'UTR of the BSG gene from 668 psoriasis patients and 1,143 healthy controls. The rs8259 T allele was associated with significantly decreased psoriasis susceptibility (OR = 0.758, 95% CI 0.638-0.901, p = 0.002). Interestingly, the rs8259 polymorphism was located in a seed region for miR-492 binding. The miR-492 was able to bind to the BSG 3'UTR sequence bearing the rs8259 T allele as assayed by luciferase reporter gene assay. The substitution of T with A abolished miR-492 binding. BSG protein expression in PBMCs from patients carrying the rs8259 AA genotype was significantly higher than in those from patients carrying the rs8259 TT genotype. Our study suggests that miR-492 may physiologically suppress BSG expression and the BSG rs8259 polymorphism is associated with decreased psoriasis susceptibility through affecting miR-492 binding.

  18. Genetic study of two single nucleotide polymorphisms within corresponding microRNAs and susceptibility to tuberculosis in a Chinese Tibetan and Han population.

    Science.gov (United States)

    Li, Dongdong; Li, Dingdong; Wang, Tingting; Song, Xingbo; Qucuo, MeiLang; Yang, Bin; Zhang, Junlong; Wang, Jun; Ying, Binwu; Tao, Chuanmin; Wang, Lanlan

    2011-07-01

    MicroRNAs (miRNA) are thought to play important roles in the pathogenesis of diseases. Single nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics via altering their target selection and/or expression, resulting in functional and/or phenotypic changes. We decided to investigate the genetic association with pulmonary tuberculosis with 2 nucleotide variations within corresponding microRNAs regulating the Toll-like receptor (TLR)-mediating signal pathway. MiRNAs potentially regulating the TLR-mediating signal pathway were predicted via bioinformatics. Finally, 2 SNPs, rs2910164 G>C and rs3746444 T>C within miR-146a and miR-499, were selected as candidates in accordance with some criteria. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism and validated by sequencing to demonstrate their association with susceptibility to pulmonary tuberculosis (PTB) in 337 PTB cases and 738 healthy controls, including 318 Tibetan and 757 Han individuals. Bioinformatics databases were searched to support the association between miRNAs and PTB. There was no association between rs3746444 and PTB risk (p = 0.118) in the Han population, but subjects carrying the C allele exhibited decreased PTB risk (odds ratio [OR] = 0.403 [95% confidence interval (95% CI) 0.278-0.583]). However, there was an association between rs3746444 and PTB in the Tibetan population, and individuals carrying the C allele exhibited increased PTB risk (OR = 1.870 [95% CI 1.218-2.871]). A polymorphism (rs2910164 G>C) indicated an association with PTB risk in both Tibetan (p = 0.031) and Han (p = 0.000) populations. However, the role of the G allele of rs2910164, like the C allele in rs3746444, differed in the Tibetan (OR = 1.509, p tuberculosis with SNPs within the corresponding miRNAs potentially regulates the TLR signal pathway. It is interesting that both the G allele (rs2910164) and the C allele (rs3746444) play different roles in 2 populations

  19. A sirolimus-eluting bioabsorbable polymer-coated stent (MiStent) versus an everolimus-eluting durable polymer stent (Xience) after percutaneous coronary intervention (DESSOLVE III): a randomised, single-blind, multicentre, non-inferiority, phase 3 trial.

    Science.gov (United States)

    de Winter, Robbert J; Katagiri, Yuki; Asano, Taku; Milewski, Krzysztof P; Lurz, Philipp; Buszman, Pawel; Jessurun, Gillian A J; Koch, Karel T; Troquay, Roland P T; Hamer, Bas J B; Ophuis, Ton Oude; Wöhrle, Jochen; Wyderka, Rafał; Cayla, Guillaume; Hofma, Sjoerd H; Levesque, Sébastien; Żurakowski, Aleksander; Fischer, Dieter; Kośmider, Maciej; Goube, Pascal; Arkenbout, E Karin; Noutsias, Michel; Ferrari, Markus W; Onuma, Yoshinobu; Wijns, William; Serruys, Patrick W

    2018-02-03

    MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting stents has not been investigated in a large randomised trial in an all-comer population. We did a randomised, single-blind, multicentre, phase 3 study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland. Eligible participants were any patients aged at least 18 years who underwent percutaneous coronary intervention in a lesion and had a reference vessel diameter of 2·50-3·75 mm. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting bioresorbable polymer stent (MiStent) or an everolimus-eluting durable polymer stent (Xience). Randomisation was done by local investigators via web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint (DOCE)-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between the groups at 12 months after the procedure assessed by intention-to-treat. A margin of 4·0% was defined for non-inferiority of the MiStent group compared with the Xience group. All participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02385279. Between March 20, and Dec 3, 2015, we randomly assigned 1398 patients with 2030 lesions; 703 patients with 1037 lesions were assigned to MiStent, of whom 697 received the index procedure, and 695 patients with 993 lesions were asssigned to Xience, of whom 690 received the index procedure. At 12 months, the primary endpoint had occurred in 40 patients (5·8%) in the sirolimus-eluting stent group and in 45

  20. Genome-wide analysis of single non-templated nucleotides in plant endogenous siRNAs and miRNAs.

    Science.gov (United States)

    Wang, Feng; Johnson, Nathan R; Coruh, Ceyda; Axtell, Michael J

    2016-09-06

    Plant small RNAs are subject to various modifications. Previous reports revealed widespread 3' modifications (truncations and non-templated tailing) of plant miRNAs when the 2'-O-methyltransferase HEN1 is absent. However, non-templated nucleotides in plant heterochromatic siRNAs have not been deeply studied, especially in wild-type plants. We systematically studied non-templated nucleotide patterns in plant small RNAs by analyzing small RNA sequencing libraries from Arabidopsis, tomato, Medicago, rice, maize and Physcomitrella Elevated rates of non-templated nucleotides were observed at the 3' ends of both miRNAs and endogenous siRNAs from wild-type specimens of all species. 'Off-sized' small RNAs, such as 25 and 23 nt siRNAs arising from loci dominated by 24 nt siRNAs, often had very high rates of 3'-non-templated nucleotides. The same pattern was observed in all species that we studied. Further analysis of 24 nt siRNA clusters in Arabidopsis revealed distinct patterns of 3'-non-templated nucleotides of 23 nt siRNAs arising from heterochromatic siRNA loci. This pattern of non-templated 3' nucleotides on 23 nt siRNAs is not affected by loss of known small RNA 3'-end modifying enzymes, and may result from modifications added to longer heterochromatic siRNA precursors. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Altered levels of miR-21, miR-125b-2*, miR-138, miR-155, miR-184, and miR-205 in oral squamous cell carcinoma and association with clinicopathological characteristics.

    Science.gov (United States)

    Manikandan, Mayakannan; Deva Magendhra Rao, Arunagiri K; Rajkumar, Kottayasamy Seenivasagam; Rajaraman, Ramamurthy; Munirajan, Arasambattu K

    2015-11-01

    Previous studies have described the aberrantly expressed microRNAs (miRNAs) in oral squamous cell carcinoma (OSCC), and we reasoned that studying frequently deregulated candidate miRNAs in OSCC of Indian ethnicity could aid in better understanding of the genetic/environmental impact on the expression statuses of these miRNAs. Therefore, we evaluated the differential expression of six selected miRNAs namely hsa-miR-21, hsa-miR-125b2*, hsa-miR-138, hsa-miR-155, hsa-miR-184, and hsa-miR-205 in OSCC specimens of Indian ethnicity. Two-step Reverse transcriptase quantitative PCR using inventoried TaqMan single miRNA assays was employed to study the expression of the selected miRNAs in 42 OSCC tumors and eight adjacent normal specimens. The expression levels of the miRNAs were tested for any association with clinicopathological parameters. miR-21 was significantly elevated while miR-125b-2* was significantly downregulated in tumors compared to controls (P 184 were observed to be predominantly downregulated in the tumor samples. High levels of miR-155 were associated with the habit of chewing tobacco/betel quid. Our results corroborate the previous findings on the overexpression of mir-21 and downregulation of miR-138 in OSCC. As the expression of miR-184 is controversial in tongue/oral cancer, the downregulation may be specific to tumor anatomical localization. On the other hand, to the best of our knowledge, this is the first report to show the association of miR-155 with tobacco chewing and the downregulation of miR-125b-2* in OSCC. Computational predictions suggest that miR-125b-2* may have a role in alternative splicing. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Association Between Functional PSMD10 Rs111638916 Variant Regulated by MiR-505 and Gastric Cancer Risk in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Yong Liu

    2015-09-01

    Full Text Available Background/Aims: Gankyrin is an oncoprotein involved in regulating the cell cycle through protein-protein interactions with cyclin-dependent kinase 4 and p53. However, its association with gastric cancer (GC risk has not yet been determined. In this study, we investigated micro RNA (miRNA-associated single nucleotide polymorphisms (SNPs in the 3′-untranslated region (UTR of the gankyrin gene PSMD10 to clarify the relationship between these SNPs and miRNAs in Chinese patients with GC. Methods: We performed a case-control study including 857 GC patients and 748 cancer-free controls. PSMD10 expression was investigated using genotyping, real-time polymerase chain reaction, cell transfection, and dual luciferase reporter assays. Results: Patients with histories of smoking, alcohol consumption, and cancer were more susceptible to GC than controls. The SNP rs111638916 in the PSMD10 3′-UTR was identified as a risk factor for GC and acted as a tumor promoting factor. SNP rs111638916 was also regulated by miR-505, resulting in up-regulation of gankyrin expression in patients with GA and AA genotypes. Carriers of the GA and AA genotypes also presented with larger tumors and had a higher risk of metastasis. Conclusion: The PSMD10 rs111638916 SNP is highly associated with an increased risk of GC in Chinese patients, and could serve as a novel biomarker for this disease.

  3. Existence of a Strong Correlation of Biomarkers and miRNA in Females with Metabolic Syndrome and Obesity in a Population of West Virginia.

    Science.gov (United States)

    Goguet-Rubio, Perrine; Klug, Rebecca L; Sharma, Dana L; Srikanthan, Krithika; Puri, Nitin; Lakhani, Vishal H; Nichols, Alexandra; O'Hanlon, Kathleen M; Abraham, Nader G; Shapiro, Joseph I; Sodhi, Komal

    2017-01-01

    Objectives: Metabolic syndrome causes complications like cardiovascular disease and type 2 diabetes mellitus (T2DM). As metabolic syndrome develops, altered levels of cytokines and microRNAs (miRNA) are measurable in the circulation. We aimed to construct a panel detecting abnormal levels of cytokines and miRNAs in patients at risk for metabolic syndrome. Methods: Participants included 54 patients from a Family Medicine Clinic at Marshall University School of Medicine, in groups of: Control, Obese, and Metabolic Syndrome (MetS). Results: Serum levels of leptin, adiponectin, leptin: adiponectin ratio, IL-6, six miRNAs (320a, 197-3p, 23-3p, 221-3p, 27a-3p, and 130a-3p), were measured. Among the three groups, leptin, and leptin: adiponectin ratio, and IL-6 levels were highest in MetS, and levels in Obese were greater than Control (p>0.05). Adiponectin levels were lower in Obese compared to Control, but lowest in MetS (p0.05). Conclusion: Our results support the clinical application of biomarkers in diagnosing early stage MetS, which will enable attenuation of disease progression before onset of irreversible complications. Since West Virginians are high-risk for developing MetS, our biomarker panel could reduce the disease burden on our population.

  4. A polymorphism in miR-1262 regulatory region confers the risk of lung cancer in Chinese population.

    Science.gov (United States)

    Xie, Kaipeng; Chen, Mengxi; Zhu, Meng; Wang, Cheng; Qin, Na; Liang, Cheng; Song, Ci; Dai, Juncheng; Jin, Guangfu; Shen, Hongbing; Lin, Dongxin; Ma, Hongxia; Hu, Zhibin

    2017-09-01

    It has been proposed that the majority of disease-associated loci identified by genome-wide association studies (GWAS) are enriched in non-coding regions, such as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage case-control study to systematically evaluate the association of genetic variants in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in 7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation stage: 1,065 cases and 1,290 controls). As a result, we identified that rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the increased risk of lung cancer (additive model in discovery stage: adjusted OR = 1.31, 95%CI = 1.13-1.53, p = 3.846 × 10 -4 in Nanjing GWAS; adjusted OR = 1.20, 95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR = 1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the association between rs12740674 and lung cancer risk reached 6.204 × 10 -6 (adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome Atlas (TCGA) data and functional assays, we observed that the risk T allele of rs12740674 reduced the expression level of miR-1262 in lung tissue through chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell proliferation probably through targeting the expression levels of ULK1 and RAB3D. Our findings confirmed the important role that genetic variants of noncoding sequence play in lung cancer susceptibility and indicated that rs12740674 in miR-1262 may be biologically relevant to lung carcinogenesis. © 2017 UICC.

  5. Single bumps in a 2-population homogenized neuronal network model

    Science.gov (United States)

    Kolodina, Karina; Oleynik, Anna; Wyller, John

    2018-05-01

    We investigate existence and stability of single bumps in a homogenized 2-population neural field model, when the firing rate functions are given by the Heaviside function. The model is derived by means of the two-scale convergence technique of Nguetseng in the case of periodic microvariation in the connectivity functions. The connectivity functions are periodically modulated in both the synaptic footprint and in the spatial scale. The bump solutions are constructed by using a pinning function technique for the case where the solutions are independent of the local variable. In the weakly modulated case the generic picture consists of two bumps (one narrow and one broad bump) for each admissible set of threshold values for firing. In addition, a new threshold value regime for existence of bumps is detected. Beyond the weakly modulated regime the number of bumps depends sensitively on the degree of heterogeneity. For the latter case we present a configuration consisting of three coexisting bumps. The linear stability of the bumps is studied by means of the spectral properties of a Fredholm integral operator, block diagonalization of this operator and the Fourier decomposition method. In the weakly modulated regime, one of the bumps is unstable for all relative inhibition times, while the other one is stable for small and moderate values of this parameter. The latter bump becomes unstable as the relative inhibition time exceeds a certain threshold. In the case of the three coexisting bumps detected in the regime of finite degree of heterogeneity, we have at least one stable bump (and maximum two stable bumps) for small and moderate values of the relative inhibition time.

  6. Search for <mi>s> -Channel Single-Top-Quark Production in Events with Missing Energy Plus Jets in <mi>p><mi>p>¯ Collisions at <mi>s>=1.96<mi>TeV>

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, T.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Auerbach, B.; Aurisano, A.; Azfar, F.; Badgett, W.; Bae, T.; Barbaro-Galtieri, A.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartos, P.; Bauce, M.; Bedeschi, F.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Bhatti, A.; Bland, K. R.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brigliadori, L.; Bromberg, C.; Brucken, E.; Budagov, J.; Budd, H. S.; Burkett, K.; Busetto, G.; Bussey, P.; Butti, P.; Buzatu, A.; Calamba, A.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cavalli-Sforza, M.; Cerri, A.; Cerrito, L.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Chokheli, D.; Clark, A.; Clarke, C.; Convery, M. E.; Conway, J.; Corbo, M.; Cordelli, M.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; d’Ascenzo, N.; Datta, M.; de Barbaro, P.; Demortier, L.; Deninno, M.; D’Errico, M.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Dittmann, J. R.; Donati, S.; D’Onofrio, M.; Dorigo, M.; Driutti, A.; Ebina, K.; Edgar, R.; Elagin, A.; Erbacher, R.; Errede, S.; Esham, B.; Farrington, S.; Fernández Ramos, J. P.; Field, R.; Flanagan, G.; Forrest, R.; Franklin, M.; Freeman, J. C.; Frisch, H.; Funakoshi, Y.; Galloni, C.; Garfinkel, A. F.; Garosi, P.; Gerberich, H.; Gerchtein, E.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Giokaris, N.; Giromini, P.; Giurgiu, G.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grinstein, S.; Grosso-Pilcher, C.; Group, R. C.; Guimaraes da Costa, J.; Hahn, S. R.; Han, J. Y.; Happacher, F.; Hara, K.; Hare, M.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hays, C.; Heinrich, J.; Herndon, M.; Hocker, A.; Hong, Z.; Hopkins, W.; Hou, S.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jang, D.; Jayatilaka, B.; Jeon, E. J.; Jindariani, S.; Jones, M.; Joo, K. K.; Jun, S. Y.; Junk, T. R.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Kasmi, A.; Kato, Y.; Ketchum, W.; Keung, J.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. H.; Kim, S. B.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Knoepfel, K.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kurata, M.; Laasanen, A. T.; Lammel, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lee, H. S.; Lee, J. S.; Leo, S.; Leone, S.; Lewis, J. D.; Limosani, A.; Lipeles, E.; Lister, A.; Liu, H.; Liu, Q.; Liu, T.; Lockwitz, S.; Loginov, A.; Lucchesi, D.; Lucà, A.; Lueck, J.; Lujan, P.; Lukens, P.; Lungu, G.; Lys, J.; Lysak, R.; Madrak, R.; Maestro, P.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Marchese, L.; Margaroli, F.; Marino, P.; Martínez, M.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Mesropian, C.; Miao, T.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nakano, I.; Napier, A.; Nett, J.; Neu, C.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Ortolan, L.; Pagliarone, C.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parker, W.; Pauletta, G.; Paulini, M.; Paus, C.; Phillips, T. J.; Piacentino, G.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pondrom, L.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Ranjan, N.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ristori, L.; Robson, A.; Rodriguez, T.; Rolli, S.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sakumoto, W. K.; Sakurai, Y.; Santi, L.; Sato, K.; Saveliev, V.; Savoy-Navarro, A.; Schlabach, P.; Schmidt, E. E.; Schwarz, T.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Semenov, A.; Sforza, F.; Shalhout, S. Z.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simonenko, A.; Sliwa, K.; Smith, J. R.; Snider, F. D.; Song, H.; Sorin, V.; St. Denis, R.; Stancari, M.; Stentz, D.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Ukegawa, F.; Uozumi, S.; Velev, G.; Vellidis, C.; Vernieri, C.; Vidal, M.; Vilar, R.; Vizán, J.; Vogel, M.; Volpi, G.; Vázquez, F.; Wagner, P.; Wallny, R.; Wang, S. M.; Waters, D.; Wester, W. C.; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wolbers, S.; Wolfe, H.; Wright, T.; Wu, X.; Wu, Z.; Yamamoto, K.; Yamato, D.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W. -M.; Yeh, G. P.; Yi, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G. B.; Yu, I.; Zanetti, A. M.; Zeng, Y.; Zhou, C.; Zucchelli, S.

    2014-06-09

    The first search for single-top-quark production from the exchange of an s -channel virtual W boson using events with an imbalance in the total transverse energy, b -tagged jets, and no identified leptons is presented. Assuming the electroweak production of top quarks of mass 172.5 GeV / c 2 in the s channel, a cross section of 1.1 2 $+ 0.61\\atop{- 0.57}$ ( stat + syst ) pb with a significance of 1.9 standard deviations is measured. This measurement is combined with the result obtained from events with an imbalance in total transverse momentum, b -tagged jets, and exactly one identified lepton, yielding a cross section of 1.3 6$+ 0.37\\atop{- 0.32}$ ( stat + syst ) pb, with a significance of 4.2 standard deviations.

  7. On the apllication of single specie dynamic population model | Iguda ...

    African Journals Online (AJOL)

    The Method of mathematical models of Malthus and Verhults were applied on ten years data collected from Magaram Poultry Farm to determine the nature of population growth, population decay or constant ... Keywords: Birth rate, sustainable population, overcrowding, harvesting, independent t-test and one way Anova.

  8. Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients

    Directory of Open Access Journals (Sweden)

    Qiu Shuwei

    2013-01-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common and aggressive brain tumor with poor clinical outcome. Identification and development of new markers could be beneficial for the diagnosis and prognosis of GBM patients. Deregulation of microRNAs (miRNAs or miRs is involved in GBM. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for GBM patient survival. Methods Expression profiles of miRNAs and genes and the corresponding clinical information of 480 GBM samples from The Cancer Genome Atlas (TCGA dataset were downloaded and interested miRNAs were identified. Patients’ overall survival (OS and progression-free survival (PFS associated with interested miRNAs and miRNA-interactions were performed by Kaplan-Meier survival analysis. The impacts of miRNA expressions and miRNA-interactions on survival were evaluated by Cox proportional hazard regression model. Biological processes and network of putative and validated targets of miRNAs were analyzed by bioinformatics. Results In this study, 6 interested miRNAs were identified. Survival analysis showed that high levels of miR-326/miR-130a and low levels of miR-323/miR-329/miR-155/miR-210 were significantly associated with long OS of GBM patients, and also showed that high miR-326/miR-130a and low miR-155/miR-210 were related with extended PFS. Moreover, miRNA-323 and miRNA-329 were found to be increased in patients with no-recurrence or long time to progression (TTP. More notably, our analysis revealed miRNA-interactions were more specific and accurate to discriminate and predict OS and PFS. This interaction stratified OS and PFS related with different miRNA levels more detailed, and could obtain longer span of mean survival in comparison to that of one single miRNA. Moreover, miR-326, miR-130a, miR-155, miR-210 and 4 miRNA-interactions were confirmed for the first time as independent predictors for survival by Cox regression model

  9. High-throughput next-generation sequencing to genotype six classical HLA loci from 96 donors in a single MiSeq run.

    Science.gov (United States)

    Ehrenberg, P K; Geretz, A; Sindhu, R K; Vayntrub, T; Fernández Viña, M A; Apps, R; Michael, N L; Thomas, R

    2017-11-01

    Next generation sequencing (NGS) methods have been established as an efficient approach for HLA typing because unlike traditional Sanger sequencing, they provide unambiguous results at a reasonable cost. We previously developed a multi-locus index method to genotype four HLA loci (A, B, C, and DRB1) on the Illumina MiSeq platform. We have now expanded this method to include two additional loci, HLA-DPB1 and DQB1. Contiguous full-length amplicons from 5'UTR through 3'UTR regions were generated using one long-range PCR reaction per locus for each of the six loci from 96 individuals of different ethnicities. The six amplicons from each donor were pooled, enzymatically fragmented and given a donor-specific index. This approach enabled sequencing of 576 loci from 96 individuals in a single MiSeq run. Donor-specific sequence reads were demultiplexed, and allele calls were generated from FASTQ files using commercially available software. Comparison to HLA genotypes generated from Sanger sequence-based typing (SBT) identified no discordances among any of the alleles analyzed in this study. Importantly, this method was able to resolve 22 DPB1 and 20 DQB1 alleles that were ambiguous with the SBT method. Furthermore, a novel allele in each of these two loci was identified, with the DQB1*05:01:24 allele having a frequency of greater than five percent. This method was subsequently validated against a blinded panel of 22 samples from the 17th International HLA and Immunogenetics Workshop. The flexibility of the method is further highlighted by successful genotyping of eight loci comprising all classical HLA loci for a subset of the samples. We now present a high-throughput, high-resolution, scalable NGS HLA typing method to accurately and efficiently genotype all classical HLA class I and II loci. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Oriented single-crystal nuclear resonance vibrational spectroscopy of [Fe(TPP)(MI)(NO)]: quantitative assessment of the trans effect of NO.

    Science.gov (United States)

    Lehnert, Nicolai; Sage, J Timothy; Silvernail, Nathan; Scheidt, W Robert; Alp, E Ercan; Sturhahn, Wolfgang; Zhao, Jiyong

    2010-08-02

    This paper presents oriented single-crystal Nuclear Resonance Vibrational Spectroscopy (NRVS) data for the six-coordinate (6C) ferrous heme-nitrosyl model complex [(57)Fe(TPP)(MI)(NO)] (1; TPP(2-) = tetraphenylporphyrin dianion; MI = 1-methylimidazole). The availability of these data enables for the first time the detailed simulation of the complete NRVS data, including the porphyrin-based vibrations, of a 6C ferrous heme-nitrosyl, using our quantum chemistry centered normal coordinate analysis (QCC-NCA). Importantly, the Fe-NO stretch is split by interaction with a porphyrin-based vibration into two features, observed at 437 and 472 cm(-1). The 437 cm(-1) feature is strongly out-of-plane (oop) polarized and shows a (15)N(18)O isotope shift of 8 cm(-1) and is therefore assigned to nu(Fe-NO). The admixture of Fe-N-O bending character is small. Main contributions to the Fe-N-O bend are observed in the 520-580 cm(-1) region, distributed over a number of in-plane (ip) polarized porphyrin-based vibrations. The main component, assigned to delta(ip)(Fe-N-O), is identified with the feature at 563 cm(-1). The Fe-N-O bend also shows strong mixing with the Fe-NO stretching internal coordinate, as evidenced by the oop NRVS intensity in the 520-580 cm(-1) region. Very accurate normal mode descriptions of nu(Fe-NO) and delta(ip)(Fe-N-O) have been obtained in this study. These results contradict previous interpretations of the vibrational spectra of 6C ferrous heme-nitrosyls where the higher energy feature at approximately 550 cm(-1) had usually been associated with nu(Fe-NO). Furthermore, these results provide key insight into NO binding to ferrous heme active sites in globins and other heme proteins, in particular with respect to (a) the effect of hydrogen bonding to the coordinated NO and (b) changes in heme dynamics upon NO coordination. [Fe(TPP)(MI)(NO)] constitutes an excellent model system for ferrous NO adducts of myoglobin (Mb) mutants where the distal histidine (His64

  11. A single nucleotide polymorphism (SNP) assay for population ...

    African Journals Online (AJOL)

    Therefore, we developed the first SNP assay to test stratification between Chinese and Japanese populations living in East Asia. The ancestry ... The SNP assay showed excellent promise as a highly potential application to test population stratification in case-control studies of association in Eastern Asians. Key words: ...

  12. MicroRNAs and drinking: association between the pre-miR-27a rs895819 polymorphism and alcohol consumption in a Mediterranean population

    Science.gov (United States)

    Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consu...

  13. MicroRNAs, macrocontrol : Regulation of miRNA processing

    NARCIS (Netherlands)

    Slezak-Prochazka, Izabella; Durmus, Selvi; Kroesen, Bart-Jan; van den Berg, Anke

    MicroRNAs (miRNAs) are a set of small, non-protein-coding RNAs that regulate gene expression at the post-transcriptional level. Maturation of miRNAs comprises several regulated steps resulting in similar to 22-nucleotide single-stranded mature miRNAs. Regulation of miRNA expression can occur both at

  14. A single miRNA complements transcription factor deficiency through the TGF pathway at time of B-cell lineage determination.

    Science.gov (United States)

    Kotaki, Ryutaro; Kotani, Ai

    2017-01-01

    Cell fate and lineage are primarily regulated at the transcriptional level. However, the transcriptional level alone does not appear to control all aspects of cellular functioning, suggesting the presence of other, as-yet-unknown, mechanisms. miR-126 induced B-cell differentiation in MLL-AF4 acute lymphoblastic leukemia (ALL) without upregulation of TCF3/E2A, EBF1, and PAX5. Early B-cell factor 1 (EBF1) which are critical transcription factor involved in B lymphopoiesis. To challenge the conventional wisdom that cell fate is solely governed by transcription factors, we investigated whether microRNAs (miRNAs) could induce complete B-cell lineage commitment in cells lacking EBF1. miR-126 upregulated B220 in EBF1-deficient hematopoietic progenitor cells (HPCs). Moreover, miRNA-195 (miR-195) induced CD19 expression in EBF1-deficient HPCs, suggesting that these cells were committed to the B-cell lineage. The functional target genes of miR-195 involved in this process belonged to the TGF beta family, a potent inhibitor of B-cell differentiation. These results suggest that some miRNAs could function as alternatives to transcription factors.

  15. Single-Phase Mail Survey Design for Rare Population Subgroups

    Science.gov (United States)

    Brick, J. Michael; Andrews, William R.; Mathiowetz, Nancy A.

    2016-01-01

    Although using random digit dialing (RDD) telephone samples was the preferred method for conducting surveys of households for many years, declining response and coverage rates have led researchers to explore alternative approaches. The use of address-based sampling (ABS) has been examined for sampling the general population and subgroups, most…

  16. Mathematical Modeling in Population Dynamics: The Case of Single ...

    African Journals Online (AJOL)

    kofimereku

    formulated by the logistic growth function, where ε is the intrinsic rate of increase and )0(. ≥. µ represents the effect of intraspecific competition on the reproduction rate. Fisher (1937) first proposed this equation as a model in population genetics to describe the process of spatial spread when mutant individuals with higher ...

  17. on the apllication of single specie dynamic population model 306

    African Journals Online (AJOL)

    pc

    used to compare the predicted values and observed values in order to find out whether there is significant difference between the observed and predicted values using these two models. Keywords: Birth rate, sustainable population, overcrowding, harvesting, independent t-test and ..... 95% confidence interval of the.

  18. Defense of single-factor models of population regulation

    International Nuclear Information System (INIS)

    Tamarin, R.H.

    1978-01-01

    I reject a multifactorial approach to the study of the regulation of animal populations for two reasons. First, a mechanism suggested by Chitty, that has natural selection at its base, has not been adequately tested. Second, the multifactorial model suggested by Lidicker is untestable because of its vagueness. As a middle ground, I suggest a model that has natural selection as its mechanism, but is multifacturial because it allows many parameters to be the selective agents. I particularly emphasize prediction and selective dispersal. Methods to test this model are suggested

  19. miRSeqNovel

    DEFF Research Database (Denmark)

    Qian, Kui; Auvinen, Eeva; Greco, Dario

    2012-01-01

    We present miRSeqNovel, an R based workflow for miRNA sequencing data analysis. miRSeqNovel can process both colorspace (SOLiD) and basespace (Illumina/Solexa) data by different mapping algorithms. It finds differentially expressed miRNAs and gives conservative prediction of novel miRNA candidates...

  20. Mi alergia

    OpenAIRE

    Ortiz Benavides, María del Mar

    2012-01-01

    Debería comenzar  con  lo  ocurrido  en  esta  fecha,  pero  todo empieza de tiempo atrás cuando era pequeña. Soy alérgica al Ácido Acetilsalicílico. No puedo consumir nada que contenga este compuesto que tienen las aspirinas, Alka-Seltzer, Ibuprofeno y distintos productos para el cutis. Mi piel es sensible a cualquier insecto que me pique; por ello reacciona con hinchazón o brote. Cuando era menor se evidenció la alergia al consumir un jarabe. Sentí qu...

  1. Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history.

    Science.gov (United States)

    Zhu, Yuan O; Aw, Pauline P K; de Sessions, Paola Florez; Hong, Shuzhen; See, Lee Xian; Hong, Lewis Z; Wilm, Andreas; Li, Chen Hao; Hue, Stephane; Lim, Seng Gee; Nagarajan, Niranjan; Burkholder, William F; Hibberd, Martin

    2017-10-27

    Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients - once before antiviral treatment and once after viral rebound due to resistance. With single-virion sequencing, we obtained 248-8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently through PacBio SMRT and Illumina Pooled deep sequencing. Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance and host adaptation, allows differentiation between soft or hard selective sweeps, and may be useful in the reconstruction of intra-host viral population demographic history.

  2. Dissection of allelic interactions among Pto-miR257 and its targets and their effects on growth and wood properties in Populus.

    Science.gov (United States)

    Chen, B; Du, Q; Chen, J; Yang, X; Tian, J; Li, B; Zhang, D

    2016-08-01

    MicroRNAs (miRNAs) have important roles in the regulation of genes; however, for trees few studies have explored the potential impact of the interactions between miRNAs and their target genes. Here, we performed transcript profiling and association genetics (single-SNP, haplotype-based and multi-SNP associations) to study the genetic regulatory relationship of Pto-miR257 and its 12 target genes in 435 individuals of a natural population of Populus tomentosa. Expression profiling of Pto-miR257 and its targets showed a negative relationship between their expression levels. Of the 61 single-nucleotide polymorphisms (SNPs) detected in Pto-miR257, 6 in the pre-mature region strongly affected its secondary stability and 1 in the mature region could alter its target spectrum. Among the 1029 SNPs in the targets, 3 were located in target sites that could change the binding affinity of Pto-miR257. Single-SNP association analysis revealed that SNPs in Pto-miR257 and target genes associated with both growth and wood property traits, in agreement with haplotype-based identifications. Multi-SNP association found that 10 targets shared at least one common trait with Pto-miR257, with phenotypic variance from 0.5 to 8.5%, suggesting a possible internal genetic interaction between them. Epistasis analysis showed significant epistatic interactions among Pto-miR257 and its targets. Therefore, our study demonstrated Pto-miR257 and its 12 targets had roles in wood formation and revealed the genetic interaction network between the miRNA and its targets under additive, dominant and epistatic models. Thus, association genetics can be used to decipher the interactions between miRNAs and their target genes and to help understand the genetic architecture of complex traits.

  3. Microbial Populations in Naked Neck Chicken Ceca Raised on Pasture Flock Fed with Commercial Yeast Cell Wall Prebiotics via an Illumina MiSeq Platform.

    Directory of Open Access Journals (Sweden)

    Si Hong Park

    Full Text Available Prebiotics are non-digestible carbohydrate dietary supplements that selectively stimulate the growth of one or more beneficial bacteria in the gastrointestinal tract of the host. These bacteria can inhibit colonization of pathogenic bacteria by producing antimicrobial substances such as short chain fatty acids (SCFAs and competing for niches with pathogens within the gut. Pasture flock chickens are generally raised outdoors with fresh grass, sunlight and air, which represents different environmental growth conditions compared to conventionally raised chickens. The purpose of this study was to evaluate the difference in microbial populations from naked neck chicken ceca fed with commercial prebiotics derived from brewer's yeast cell wall via an Illumina MiSeq platform. A total of 147 day-of-hatch naked neck chickens were distributed into 3 groups consisted of 1 C: control (no prebiotic, 2 T1: Biolex® MB40 with 0.2%, and 3 T2: Leiber® ExCel with 0.2%, consistently supplemented prebiotics during the experimental period. At 8 weeks, a total of 15 birds from each group were randomly selected and ceca removed for DNA extraction. The Illumina Miseq platform based on V4 region of 16S rRNA gene was applied for microbiome analysis. Both treatments exhibited limited impact on the microbial populations at the phylum level, with no significant differences in the OTU number of Bacteroidetes among groups and an increase of Proteobacteria OTUs for the T1 (Biolex® MB40 group. In addition there was a significant increase of genus Faecalibacterium OTU, phylum Firmicutes. According to the development of next generation sequencing (NGS, microbiome analysis based on 16S rRNA gene proved to be informative on the prebiotic impact on poultry gut microbiota in pasture-raised naked neck birds.

  4. Identification of novel miRNAs and miRNA expression profiling in wheat hybrid necrosis.

    Directory of Open Access Journals (Sweden)

    Jianping Zhou

    Full Text Available MicroRNAs (miRNAs play essential roles in a vast array of biological processes, including growth and development, defense against viral infection, and responses to environmental changes in plant. Wheat hybrid necrosis is an interesting genetic phenomenon observed frequency and it is lethal or semi lethal, resulting in gradual death or loss of productivity. However, the molecular basis and mechanisms associated with hybrid necrosis in wheat are still not well understood. Here, we report the population and expression profiles of miRNAs in wheat hybrid necrosis. We identified a total of 57 conserved miRNA families as well as 182 putative novel miRNAs. Expression profiling revealed that expression of 49 known miRNAs and 165 novel miRNAs was changed in hybrid necrosis. And the expression levels of some miRNAs and their predicated targets have been confirmed by qRT-PCR. These results indicate that these miRNAs, especially miR159, miR166, miR167 and miR5072 could be involved in the extensive regulation of gene expression in response to hybrid necrosis.

  5. Identification of novel miRNAs and miRNA expression profiling in wheat hybrid necrosis.

    Science.gov (United States)

    Zhou, Jianping; Cheng, Yan; Yin, Meiqi; Yang, Ennian; Gong, Wenping; Liu, Cheng; Zheng, Xuelian; Deng, Kejun; Ren, Zhenglong; Zhang, Yong

    2015-01-01

    MicroRNAs (miRNAs) play essential roles in a vast array of biological processes, including growth and development, defense against viral infection, and responses to environmental changes in plant. Wheat hybrid necrosis is an interesting genetic phenomenon observed frequency and it is lethal or semi lethal, resulting in gradual death or loss of productivity. However, the molecular basis and mechanisms associated with hybrid necrosis in wheat are still not well understood. Here, we report the population and expression profiles of miRNAs in wheat hybrid necrosis. We identified a total of 57 conserved miRNA families as well as 182 putative novel miRNAs. Expression profiling revealed that expression of 49 known miRNAs and 165 novel miRNAs was changed in hybrid necrosis. And the expression levels of some miRNAs and their predicated targets have been confirmed by qRT-PCR. These results indicate that these miRNAs, especially miR159, miR166, miR167 and miR5072 could be involved in the extensive regulation of gene expression in response to hybrid necrosis.

  6. Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single Human Heart Biopsy.

    Science.gov (United States)

    Monsanto, Megan M; White, Kevin S; Kim, Taeyong; Wang, Bingyan J; Fisher, Kristina; Ilves, Kelli; Khalafalla, Farid G; Casillas, Alexandria; Broughton, Kathleen; Mohsin, Sadia; Dembitsky, Walter P; Sussman, Mark A

    2017-07-07

    The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration. Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy. Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm 3 pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit + cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit - mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit + population is further enriched by selection for a CD133 + endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry. Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients. © 2017 American Heart Association, Inc.

  7. Identification of miR-93 as a suitable miR for normalizing miRNA in plasma of tuberculosis patients.

    Science.gov (United States)

    Barry, Simone E; Chan, Brian; Ellis, Magda; Yang, YuRong; Plit, Marshall L; Guan, Guangyu; Wang, Xiaolin; Britton, Warwick J; Saunders, Bernadette M

    2015-07-01

    Tuberculosis (TB) remains a major public health issue. New tests to aid diagnoses and monitor the response to therapy are urgently required. There is growing interest in the use of microRNA (miRNA) profiles as diagnostic, prognostic or predictive markers in a range of clinical and infectious diseases, including Mycobacterium tuberculosis infection, however, challenges exist to accurately normalise miRNA levels in cohorts. This study examined the appropriateness of 12 miRs and RNU6B to normalise circulating plasma miRNA levels in individuals with active TB from 2 different geographical and ethnic regions. Twelve miRs (let-7, miR-16, miR-22, miR-26, miR-93, miR-103, miR-191, miR-192, miR-221, miR-423, miR-425 and miR-451) and RNU6B were selected based on their reported production by lung cells, expression in blood and previous use as a reference miRNA. Expression levels were analysed in the plasma of newly diagnosed TB patients from Australia and China compared with individuals with latent TB infection and healthy volunteers. Analysis with both geNorm and NormFinder software identified miR-93 as the most suitable reference miR in both cohorts, either when analysed separately or collectively. Interestingly, there were large variations in the expression levels of some miRs, in particular miR-192 and let-7, between the two cohorts, independent of disease status. These data identify miR-93 is a suitable reference miR for normalizing miRNA levels in TB patients, and highlight how environmental, and possibly ethnic, factors influence miRNA expression levels, demonstrating the necessity of assessing the suitability of reference miRs within the study population. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  8. Integrated Spectral Energy Distributions and Absorption Feature Indices of Single Stellar Populations

    OpenAIRE

    Zhang, Fenghui; Han, Zhanwen; Li, Lifang; Hurley, Jarrod R.

    2004-01-01

    Using evolutionary population synthesis, we present integrated spectral energy distributions and absorption-line indices defined by the Lick Observatory image dissector scanner (referred to as Lick/IDS) system, for an extensive set of instantaneous burst single stellar populations (SSPs). The ages of the SSPs are in the range 1-19 Gyr and the metallicities [Fe/H] are in the range -2.3 - 0.2. Our models use the rapid single stellar evolution algorithm of Hurley, Pols and Tout for the stellar e...

  9. Investigation of Pre-miR-423 and Pre-miR-608 Gene Polymorphisms in Patients with Colorectal Cancer

    OpenAIRE

    Topal Önal, Harika; Aras, Nurcan; Arslan, Badel; Türkmenoğlu, Mehmet Özgür; Çolak, Tahsin

    2017-01-01

    It has been thought that the polymorphism of pre-miRNAs acting process and maturation of miRNA effect the pathogenesis of colorectal cancers (CRC). SNPs in pre-miRNA genes only effect on expression and formation of mature mi-RNA but olsa it responsible for clinical findings and development of cancer. İn this study was aimed to investigate in the Turkish population to Mersin sample pre-miR-423 and pre-miR-608 gene polimorphisms in relation with CRC. The study includes the average age is 52,6 o...

  10. Pharmaco-miR

    DEFF Research Database (Denmark)

    Rukov, Jakob Lewin; Wilentzik, Roni; Jaffe, Ishai

    2014-01-01

    MicroRNAs (miRNAs) are short regulatory RNAs that down-regulate gene expression. They are essential for cell homeostasis and active in many disease states. A major discovery is the ability of miRNAs to determine the efficacy of drugs, which has given rise to the field of 'miRNA pharmacogenomics......' through 'Pharmaco-miRs'. miRNAs play a significant role in pharmacogenomics by down-regulating genes that are important for drug function. These interactions can be described as triplet sets consisting of a miRNA, a target gene and a drug associated with the gene. We have developed a web server which...... links miRNA expression and drug function by combining data on miRNA targeting and protein-drug interactions. miRNA targeting information derive from both experimental data and computational predictions, and protein-drug interactions are annotated by the Pharmacogenomics Knowledge base (Pharm...

  11. SNP at miR-483-5p-binding site in the 3'-untranslated region of the BSG gene is associated with susceptibility to esophageal cancer in a Chinese population.

    Science.gov (United States)

    Li, H Y; Liu, Y C; Bai, Y H; Sun, M; Wang, L; Zhang, X B; Cai, B

    2016-06-20

    The aim of this study was to investigate the association between a functional variant of the basigin (BSG) gene, caused by a polymorphism (rs11473) at the miR-483-5p binding site, and the risk of esophageal squamous cell carcinoma (ESCC) in the Chinese population. The rs11473 polymorphism was genotyped in 624 esophageal cancer patients and 636 cancer-free age- and gender-matched controls using polymerase chain reaction restriction and direct sequencing. The functional variants resulting from the BSG rs11473 SNP were investigated using a luciferase activity assay and validated by immunoblotting. We discovered that ESCC patients carrying the rs11473 AA genotype or A allele were at a significantly higher risk of esophageal cancer [odds ratio (OR) = 1.560, 95% confidence interval  (CI) = 1.031-2.358, P = 0.037; OR = 1.231, 95%CI = 1.038-1.459, P = 0.017, respectively] than those carrying the GG genotype and G allele. Moreover, the rs11473 polymorphism modifies the binding of miR-483- 5p to basigin, as well as the basigin protein levels in esophageal cancer patients. Our data suggested that the rs11473 polymorphism at the miR- 483-5p binding site in the 3'-UTR of basigin gene may play a key role in the development of esophageal cancer in a Chinese population.

  12. Paternity in the Addo elephant population, South Africa. Is a single ...

    African Journals Online (AJOL)

    The hypothesis that a single dominant male (GAA) monopolized all matings within the elephant population of South Africa's Addo Elephant National Park between 1982 and 1996 was tested using microsatellite analysis. In addition, behavioural data on male musth periods, female oestrous periods, and observations of ...

  13. Neglect of bandwidth of Odontocetes echo location clicks biases propagation loss and single hydrophone population estimates

    NARCIS (Netherlands)

    Ainslie, M.A.

    2013-01-01

    Passive acoustic monitoring with a single hydrophone has been suggested as a cost-effective method to monitor population density of echolocating marine mammals, by estimating the distance at which the hydrophone is able to intercept the echolocation clicks and distinguish these from the background.

  14. The miRNome of bipolar disorder.

    Science.gov (United States)

    Fries, Gabriel R; Carvalho, Andre F; Quevedo, Joao

    2018-06-01

    Epigenetic mechanisms have been suggested to play a key role in the pathophysiology of bipolar disorder (BD), among which microRNAs (miRNAs) may be of particular significance according to recent studies. We aimed to summarize miRNA studies in BD to identify consistent findings, limitations, and future directions of this emerging field. We performed a comprehensive search on PUBMED and Medline for studies investigating an association between BD and miRNAs. The included studies report miRNA alterations in postmortem brain tissues and in the periphery, cell culture and preclinical findings, genetic associations, and the effects of medications. Several studies report changes in miRNA expression levels in postmortem brain and in the periphery of patients, although most of the results so far have not been replicated and are not concordant between different populations. Genetic studies also suggest that miRNA genes are located within susceptibility loci of BD, and also a putative role of miRNAs in modulating genes previously shown to confer risk of BD. We did not perform a systematic review of the literature, and miRNAs represent only one facet of the plethora of epigenetic mechanisms that might be involved in BD's pathophysiology. miRNA findings in BD significantly vary between studies, but are consistent to suggest a key role for these molecules in BD's pathophysiology and treatment, particularly miR-34a and miR-137. Accordingly, miRNA might represent important biomarkers of illness to be used in the clinical settings, and potentially also for the development of novel therapeutics for BD in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Deconstructing stem cell population heterogeneity: Single-cell analysis and modeling approaches

    Science.gov (United States)

    Wu, Jincheng; Tzanakakis, Emmanuel S.

    2014-01-01

    Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives. PMID:24035899

  16. Hepatitis C virus RNA functionally sequesters miR-122

    DEFF Research Database (Denmark)

    Luna, Joseph M; Scheel, Troels K H; Danino, Tal

    2015-01-01

    Hepatitis C virus (HCV) uniquely requires the liver-specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (AGO) during...... HCV infection showed robust AGO binding on the HCV 5'UTR at known and predicted miR-122 sites. On the human transcriptome, we observed reduced AGO binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 "sponge" effect was relieved and redirected to miR-15...... targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and site number. We describe a quantitative mathematical model of HCV-induced miR-122 sequestration...

  17. Microselection - Affinity Selecting Antibodies against a Single Rare Cell in a Heterogeneous Population

    DEFF Research Database (Denmark)

    Sørensen, Morten Dræby; Agerholm, Inge Errebo; Christensen, Britta

    2009-01-01

    antibodies. Here we have generated a microselection method allowing antibody selection, by phage display, targeting a single cell in a heterogeneous population. One K562 cell (female origin) was positioned on glass-slide among millions of lymphocytes from male donor, identifying the K562 cell by FISH (XX......). Several single cell selections were performed on such individual slides. The phage particles bound to the target cell is protected by a minute disc, while inactivating all remaining phage by UV-irradiation; leaving only the phage bound to the target cell viable. We hereby retrieved up to eight antibodies...

  18. Identification of Diagnostic Mitochondrial DNA Single Nucleotide Polymorphisms Specific to Sumatran Orangutan (Pongo abelii Populations

    Directory of Open Access Journals (Sweden)

    Puji Rianti

    2015-10-01

    Full Text Available The hypervariable region I of mitochondrial DNA has frequently been used to distinguish among populations, in particular in species with strong female philopatry. In such cases, populations are expected to diverge rapidly for hypervariable region I markers because of the smaller effective population size and thus increased genetic drift. This rapid divergence leads to the accumulation of mutations exclusively found in one population, which may serve as diagnostic single nucleotide polymorphisms (SNPs. To date, diagnostic SNPs distinctive to Sumatran orangutan populations have not yet been described. However, given the continuously declining numbers of Sumatran orangutans, this information can be vital for effective conservation measures, especially regarding reintroductions of orangutans in rehabilitation centers. Phylogenetic analyses of 54 samples of Sumatran orangutans from nine sampling sites with good provenance, we found five major clades and a total of 20 haplotypes. We propose a total of 52 diagnostic SNPs that are specific to Sumatran orangutan populations. Data can be used to develop restriction fragment length polymorphism assays to carry out genetic assignments using basic laboratory equipment to assign Sumatran orangutan to their population of origin.

  19. Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors.

    Science.gov (United States)

    Israelow, Benjamin; Mullokandov, Gavriel; Agudo, Judith; Sourisseau, Marion; Bashir, Ali; Maldonado, Andres Y; Dar, Arvin C; Brown, Brian D; Evans, Matthew J

    2014-11-18

    Hepatitis C virus (HCV) replication is dependent on a liver-specific microRNA (miRNA), miR-122. A recent clinical trial reported that transient inhibition of miR-122 reduced viral titres in HCV-infected patients. Here we set out to better understand how miR-122 inhibition influences HCV replication over time. Unexpectedly, we observed the emergence of an HCV variant that is resistant to miR-122 knockdown. Next-generation sequencing revealed that this was due to a single nucleotide change at position 28 (G28A) of the HCV genome, which falls between the two miR-122 seed-binding sites. Naturally occurring HCV isolates encoding G28A are similarly resistant to miR-122 inhibition, indicating that subtle differences in viral sequence, even outside the seed-binding site, greatly influence HCV's miR-122 concentration requirement. In addition, we found that HCV itself reduces miR-122's activity in the cell, possibly through binding and sequestering miR-122. Our study provides insight into the interaction between miR-122 and HCV, including viral adaptation to reduced miR-122 bioavailability, and has implications for the development of anti-miR-122-based HCV drugs.

  20. Inequivalence of single-particle and population lifetimes in a cuprate superconductor

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shuolong [SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., Stanford, CA (United States); Sobota, J. A. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Leuenberger, D. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., Stanford, CA (United States); He, Y. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., Stanford, CA (United States); Hashimoto, M. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Lu, D. H. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Eisaki, H. [National Institute of Advanced Industrial Science and Technology, Ibaraki (Japan); Kirchmann, P. S. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Shen, Z. -X. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., Stanford, CA (United States)

    2015-06-15

    We study optimally doped Bi-2212 (Tc=96 K) using femtosecond time- and angle-resolved photoelectron spectroscopy. Energy-resolved population lifetimes are extracted and compared with single-particle lifetimes measured by equilibrium photoemission. The population lifetimes deviate from the single-particle lifetimes in the low excitation limit by 1–2 orders of magnitude. Fundamental considerations of electron scattering unveil that these two lifetimes are in general distinct, yet for systems with only electron-phonon scattering they should converge in the low-temperature, low-fluence limit. As a result, the qualitative disparity in our data, even in this limit, suggests that scattering channels beyond electron-phonon interactions play a significant role in the electron dynamics of cuprate superconductors.

  1. Using Matrix and Tensor Factorizations for the Single-Trial Analysis of Population Spike Trains

    Science.gov (United States)

    Onken, Arno; Liu, Jian K.; Karunasekara, P. P. Chamanthi R.; Delis, Ioannis; Gollisch, Tim; Panzeri, Stefano

    2016-01-01

    Advances in neuronal recording techniques are leading to ever larger numbers of simultaneously monitored neurons. This poses the important analytical challenge of how to capture compactly all sensory information that neural population codes carry in their spatial dimension (differences in stimulus tuning across neurons at different locations), in their temporal dimension (temporal neural response variations), or in their combination (temporally coordinated neural population firing). Here we investigate the utility of tensor factorizations of population spike trains along space and time. These factorizations decompose a dataset of single-trial population spike trains into spatial firing patterns (combinations of neurons firing together), temporal firing patterns (temporal activation of these groups of neurons) and trial-dependent activation coefficients (strength of recruitment of such neural patterns on each trial). We validated various factorization methods on simulated data and on populations of ganglion cells simultaneously recorded in the salamander retina. We found that single-trial tensor space-by-time decompositions provided low-dimensional data-robust representations of spike trains that capture efficiently both their spatial and temporal information about sensory stimuli. Tensor decompositions with orthogonality constraints were the most efficient in extracting sensory information, whereas non-negative tensor decompositions worked well even on non-independent and overlapping spike patterns, and retrieved informative firing patterns expressed by the same population in response to novel stimuli. Our method showed that populations of retinal ganglion cells carried information in their spike timing on the ten-milliseconds-scale about spatial details of natural images. This information could not be recovered from the spike counts of these cells. First-spike latencies carried the majority of information provided by the whole spike train about fine-scale image

  2. Using Matrix and Tensor Factorizations for the Single-Trial Analysis of Population Spike Trains.

    Directory of Open Access Journals (Sweden)

    Arno Onken

    2016-11-01

    Full Text Available Advances in neuronal recording techniques are leading to ever larger numbers of simultaneously monitored neurons. This poses the important analytical challenge of how to capture compactly all sensory information that neural population codes carry in their spatial dimension (differences in stimulus tuning across neurons at different locations, in their temporal dimension (temporal neural response variations, or in their combination (temporally coordinated neural population firing. Here we investigate the utility of tensor factorizations of population spike trains along space and time. These factorizations decompose a dataset of single-trial population spike trains into spatial firing patterns (combinations of neurons firing together, temporal firing patterns (temporal activation of these groups of neurons and trial-dependent activation coefficients (strength of recruitment of such neural patterns on each trial. We validated various factorization methods on simulated data and on populations of ganglion cells simultaneously recorded in the salamander retina. We found that single-trial tensor space-by-time decompositions provided low-dimensional data-robust representations of spike trains that capture efficiently both their spatial and temporal information about sensory stimuli. Tensor decompositions with orthogonality constraints were the most efficient in extracting sensory information, whereas non-negative tensor decompositions worked well even on non-independent and overlapping spike patterns, and retrieved informative firing patterns expressed by the same population in response to novel stimuli. Our method showed that populations of retinal ganglion cells carried information in their spike timing on the ten-milliseconds-scale about spatial details of natural images. This information could not be recovered from the spike counts of these cells. First-spike latencies carried the majority of information provided by the whole spike train about fine

  3. The reverse effects of random perturbation on discrete systems for single and multiple population models

    International Nuclear Information System (INIS)

    Kang, Li; Tang, Sanyi

    2016-01-01

    Highlights: • The discrete single species and multiple species models with random perturbation are proposed. • The complex dynamics and interesting bifurcation behavior have been investigated. • The reverse effects of random perturbation on discrete systems have been discussed and revealed. • The main results can be applied for pest control and resources management. - Abstract: The natural species are likely to present several interesting and complex phenomena under random perturbations, which have been confirmed by simple mathematical models. The important questions are: how the random perturbations influence the dynamics of the discrete population models with multiple steady states or multiple species interactions? and is there any different effects for single species and multiple species models with random perturbation? To address those interesting questions, we have proposed the discrete single species model with two stable equilibria and the host-parasitoid model with Holling type functional response functions to address how the random perturbation affects the dynamics. The main results indicate that the random perturbation does not change the number of blurred orbits of the single species model with two stable steady states compared with results for the classical Ricker model with same random perturbation, but it can strength the stability. However, extensive numerical investigations depict that the random perturbation does not influence the complexities of the host-parasitoid models compared with the results for the models without perturbation, while it does increase the period of periodic orbits doubly. All those confirm that the random perturbation has a reverse effect on the dynamics of the discrete single and multiple population models, which could be applied in reality including pest control and resources management.

  4. Bet-hedging in bacteriocin producing Escherichia coli populations: the single cell perspective

    Science.gov (United States)

    Bayramoglu, Bihter; Toubiana, David; van Vliet, Simon; Inglis, R. Fredrik; Shnerb, Nadav; Gillor, Osnat

    2017-02-01

    Production of public goods in biological systems is often a collaborative effort that may be detrimental to the producers. It is therefore sustainable only if a small fraction of the population shoulders the cost while the majority reap the benefits. We modelled this scenario using Escherichia coli populations producing colicins, an antibiotic that kills producer cells’ close relatives. Colicin expression is a costly trait, and it has been proposed that only a small fraction of the population actively expresses the antibiotic. Colicinogenic populations were followed at the single-cell level using time-lapse microscopy, and showed two distinct, albeit dynamic, subpopulations: the majority silenced colicin expression, while a small fraction of elongated, slow-growing cells formed colicin-expressing hotspots, placing a significant burden on expressers. Moreover, monitoring lineages of individual colicinogenic cells showed stochastic switching between expressers and non-expressers. Hence, colicin expressers may be engaged in risk-reducing strategies—or bet-hedging—as they balance the cost of colicin production with the need to repel competitors. To test the bet-hedging strategy in colicin-mediated interactions, competitions between colicin-sensitive and producer cells were simulated using a numerical model, demonstrating a finely balanced expression range that is essential to sustaining the colicinogenic population.

  5. The population of single and binary white dwarfs of the Galactic bulge

    Science.gov (United States)

    Torres, S.; García-Berro, E.; Cojocaru, R.; Calamida, A.

    2018-02-01

    Recent Hubble Space Telescope observations have unveiled the white dwarf cooling sequence of the Galactic bulge. Although the degenerate sequence can be well fitted employing the most up-to-date theoretical cooling sequences, observations show a systematic excess of red objects that cannot be explained by the theoretical models of single carbon-oxygen white dwarfs of the appropriate masses. Here we present a population synthesis study of the white dwarf cooling sequence of the Galactic bulge that takes into account the populations of both single white dwarfs and binary systems containing at least one white dwarf. These calculations incorporate state-of-the-art cooling sequences for white dwarfs with hydrogen-rich and hydrogen-deficient atmospheres, for both white dwarfs with carbon-oxygen and helium cores, and also take into account detailed prescriptions of the evolutionary history of binary systems. Our Monte Carlo simulator also incorporates all the known observational biases. This allows us to model with a high degree of realism the white dwarf population of the Galactic bulge. We find that the observed excess of red stars can be partially attributed to white dwarf plus main sequence binaries, and to cataclysmic variables or dwarf novae. Our best fit is obtained with a higher binary fraction and an initial mass function slope steeper than standard values, as well as with the inclusion of differential reddening and blending. Our results also show that the possible contribution of double degenerate systems or young and thick-disk bulge stars is negligible.

  6. The population of single and binary white dwarfs of the Galactic bulge

    Science.gov (United States)

    Torres, S.; García-Berro, E.; Cojocaru, R.; Calamida, A.

    2018-05-01

    Recent Hubble Space Telescope observations have unveiled the white dwarf cooling sequence of the Galactic bulge. Although the degenerate sequence can be well fitted employing the most up-to-date theoretical cooling sequences, observations show a systematic excess of red objects that cannot be explained by the theoretical models of single carbon-oxygen white dwarfs of the appropriate masses. Here, we present a population synthesis study of the white dwarf cooling sequence of the Galactic bulge that takes into account the populations of both single white dwarfs and binary systems containing at least one white dwarf. These calculations incorporate state-of-the-art cooling sequences for white dwarfs with hydrogen-rich and hydrogen-deficient atmospheres, for both white dwarfs with carbon-oxygen and helium cores, and also take into account detailed prescriptions of the evolutionary history of binary systems. Our Monte Carlo simulator also incorporates all the known observational biases. This allows us to model with a high degree of realism the white dwarf population of the Galactic bulge. We find that the observed excess of red stars can be partially attributed to white dwarf plus main sequence binaries, and to cataclysmic variables or dwarf novae. Our best fit is obtained with a higher binary fraction and an initial mass function slope steeper than standard values, as well as with the inclusion of differential reddening and blending. Our results also show that the possible contribution of double degenerate systems or young and thick-discbulge stars is negligible.

  7. Performance of autofocusing schemes for single target and populated scenes behind unknown walls

    Science.gov (United States)

    Ahmad, Fauzia; Amin, Moeness G.

    2007-04-01

    The quality and reliability of through-the-wall radar imagery is governed, among other things, by the knowledge of the wall characteristics. Ambiguity in wall characteristics has a two-fold effect. It smears and blurs the image, and also shifts the imaged target positions. Higher order standardized moments have been shown to be suitable measures of the degree of smearing and blurriness of through-the-wall images. These moments can be used to tune the wall variables to achieve autofocusing. It is noted that the solution to the autofocusing problem is not unique, and there exist several assumed wall characteristics, in addition to the exact, that lead to similar focused images. In this paper, we analyze the dependency of the estimated autofocusing wall parameters on the imaged scene, specifically target density and location, in the presence of single uniform wall. We consider single and multiple target cases with different scene complexity and population. Supporting simulation results are also provided.

  8. Mi frente en alto

    OpenAIRE

    Birmaher Avalos, Guithel

    2012-01-01

    Esta foto que estás viendo, es la de una historia de guerra y despedidas. Es la historia de vida y muerte de mi familia, de mi abuelo y mi sangre. Boris  Birmaher y Raquel Ledensnaider eran humildes campesinos rumanos de un pueblito llamado Besarabia; Polonia y Rusia disputaban su pertenencia. Boris y Raquel tuvieron 7 hijos. El primero, Samuel; el segundo, Luis; la tercera, Lía; el cuarto, Jorge (mi abuelo); el quinto, Saúl; el sexto, Daniel; y la séptima, Gentlen. Vivian en las estepas...

  9. In silico lineage tracing through single cell transcriptomics identifies a neural stem cell population in planarians.

    Science.gov (United States)

    Molinaro, Alyssa M; Pearson, Bret J

    2016-04-27

    The planarian Schmidtea mediterranea is a master regenerator with a large adult stem cell compartment. The lack of transgenic labeling techniques in this animal has hindered the study of lineage progression and has made understanding the mechanisms of tissue regeneration a challenge. However, recent advances in single-cell transcriptomics and analysis methods allow for the discovery of novel cell lineages as differentiation progresses from stem cell to terminally differentiated cell. Here we apply pseudotime analysis and single-cell transcriptomics to identify adult stem cells belonging to specific cellular lineages and identify novel candidate genes for future in vivo lineage studies. We purify 168 single stem and progeny cells from the planarian head, which were subjected to single-cell RNA sequencing (scRNAseq). Pseudotime analysis with Waterfall and gene set enrichment analysis predicts a molecularly distinct neoblast sub-population with neural character (νNeoblasts) as well as a novel alternative lineage. Using the predicted νNeoblast markers, we demonstrate that a novel proliferative stem cell population exists adjacent to the brain. scRNAseq coupled with in silico lineage analysis offers a new approach for studying lineage progression in planarians. The lineages identified here are extracted from a highly heterogeneous dataset with minimal prior knowledge of planarian lineages, demonstrating that lineage purification by transgenic labeling is not a prerequisite for this approach. The identification of the νNeoblast lineage demonstrates the usefulness of the planarian system for computationally predicting cellular lineages in an adult context coupled with in vivo verification.

  10. Single species victory in a two-site, two-species model of population dispersion

    Science.gov (United States)

    Waddell, Jack; Sander, Len; Kessler, David

    2008-03-01

    We study the behavior of two species, differentiated only by their dispersal rates in an environment providing heterogeneous growth rates. Previous deterministic studies have shown that the slower-dispersal species always drives the faster species to extinction, while stochastic studies show that the opposite case can occur given small enough population and spatial heterogeneity. Other models of similar systems demonstrate the existence of an optimum dispersal rate, suggesting that distinguishing the species as faster or slower is insufficient. We here study the interface of these models for a small spatial system and determine the conditions of stability for a single species outcome.

  11. Quantitative single cell analysis of cell population dynamics during submandibular salivary gland development and differentiation

    Science.gov (United States)

    Nelson, Deirdre A.; Manhardt, Charles; Kamath, Vidya; Sui, Yunxia; Santamaria-Pang, Alberto; Can, Ali; Bello, Musodiq; Corwin, Alex; Dinn, Sean R.; Lazare, Michael; Gervais, Elise M.; Sequeira, Sharon J.; Peters, Sarah B.; Ginty, Fiona; Gerdes, Michael J.; Larsen, Melinda

    2013-01-01

    Summary Epithelial organ morphogenesis involves reciprocal interactions between epithelial and mesenchymal cell types to balance progenitor cell retention and expansion with cell differentiation for evolution of tissue architecture. Underlying submandibular salivary gland branching morphogenesis is the regulated proliferation and differentiation of perhaps several progenitor cell populations, which have not been characterized throughout development, and yet are critical for understanding organ development, regeneration, and disease. Here we applied a serial multiplexed fluorescent immunohistochemistry technology to map the progressive refinement of the epithelial and mesenchymal cell populations throughout development from embryonic day 14 through postnatal day 20. Using computational single cell analysis methods, we simultaneously mapped the evolving temporal and spatial location of epithelial cells expressing subsets of differentiation and progenitor markers throughout salivary gland development. We mapped epithelial cell differentiation markers, including aquaporin 5, PSP, SABPA, and mucin 10 (acinar cells); cytokeratin 7 (ductal cells); and smooth muscle α-actin (myoepithelial cells) and epithelial progenitor cell markers, cytokeratin 5 and c-kit. We used pairwise correlation and visual mapping of the cells in multiplexed images to quantify the number of single- and double-positive cells expressing these differentiation and progenitor markers at each developmental stage. We identified smooth muscle α-actin as a putative early myoepithelial progenitor marker that is expressed in cytokeratin 5-negative cells. Additionally, our results reveal dynamic expansion and redistributions of c-kit- and K5-positive progenitor cell populations throughout development and in postnatal glands. The data suggest that there are temporally and spatially discreet progenitor populations that contribute to salivary gland development and homeostasis. PMID:23789091

  12. Comparison of standard PCR/cloning to single genome sequencing for analysis of HIV-1 populations.

    Science.gov (United States)

    Jordan, Michael R; Kearney, Mary; Palmer, Sarah; Shao, Wei; Maldarelli, Frank; Coakley, Eoin P; Chappey, Colombe; Wanke, Christine; Coffin, John M

    2010-09-01

    To compare standard PCR/cloning and single genome sequencing (SGS) in their ability to reflect actual intra-patient polymorphism of HIV-1 populations, a total of 530 HIV-1 pro-pol sequences obtained by both sequencing techniques from a set of 17 ART naïve patient specimens was analyzed. For each specimen, 12 and 15 sequences, on average, were characterized by the two techniques. Using phylogenetic analysis, tests for panmixia and entropy, and Bland-Altman plots, no difference in population structure or genetic diversity was shown in 14 of the 17 subjects. Evidence of sampling bias by the presence of subsets of identical sequences was found by either method. Overall, the study shows that neither method was more biased than the other, and providing that an adequate number of PCR templates is analyzed, and that the bulk sequencing captures the diversity of the viral population, either method is likely to provide a similar measure of population diversity. Copyright 2010 Elsevier B.V. All rights reserved.

  13. miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and irinotecan.

    Directory of Open Access Journals (Sweden)

    Jakob V Schou

    Full Text Available MicroRNAs (miRNAs have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic for overall survival (OS in patients with metastatic colorectal cancer (mCRC treated with cetuximab and irinotecan.From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood using the TaqMan MicroRNA Array v2.0. Mutation status of KRAS, BRAF, and PI3KCA was known.After Bonferroni adjustment, 6 miRNAs: (miR-345, miR-143, miR-34a*, miR-628-5p, miR-886-3p and miR-324-3p, were found associated with short OS. miR-345 was the strongest prognostic miRNA, significant in the full cohort and in the non-KRAS mutant population. miR-345, as a continuous variable in the full cohort, resulted in a hazard ratio (HR of 2.38 per IQR (CI 95%: 1.8-3.1, P-value = 2.86e-07, Bonferroni adjusted, univariable analysis and a HR = 1.75 per IQR (CI 95%: 1.24-2.48, P-Wald = 1.45e-03 in the multivariable analysis adjusted for gender, age, KRAS, PI3KCA and performance status. miR-345 was prognostic in progression-free survival (PFS with a HR = 1.63 per IQR (CI 95%: 1.25-2.114, P-Wald = 2.92e-4 in the multivariable analysis. In addition, high miR-345 expression was associated with lack of response to treatment with cetuximab and irinotecan.We identified miR-345 in whole blood as a potential biomarker for clinical outcome. MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and also in the non-KRAS mutant population.

  14. CYP3A5*3 and *6 single nucleotide polymorphisms in three distinct Asian populations.

    Science.gov (United States)

    Balram, C; Zhou, Qingyu; Cheung, Yin Bun; Lee, Edmund J D

    2003-06-01

    To determine the frequencies of two functional single nucleotide polymorphisms, CYP3A5*3 and CYP3A5*6, in the CYP3A5 gene in three distinct Asian ethnic groups, namely, the Chinese, Malays and Indians. Single nucleotide polymorphism analyses of CYP3A5*1, *3 and *6 were performed in 296 healthy subjects (108 Chinese, 98 Malays and 90 Indians) using the polymerase chain reaction-restriction fragment length polymorphism method. The *1 allele frequency was 25% in Chinese compared with 40% in Malays and Indians ( P=0.001). The *3 allele frequency was also higher in the Chinese population, being 76% versus 60% in the Malays and Indians ( P=0.001). The Malays and Indians also had allele frequencies significantly different from Caucasian, Japanese and African-American populations (each Pliterature. The *6 allele was not detected in any the three Asian ethnic groups analysed. These results seem to suggest that genetic polymorphisms in CYP3A5 in Asians, in particular Malays and Indians but also Chinese although to a lesser extent, may be an important genetic contributor to interindividual as well as interethnic differences in clearance of CYP3A substrates.

  15. Reexamining microRNA site accessibility in Drosophila: a population genomics study.

    Directory of Open Access Journals (Sweden)

    Kevin Chen

    Full Text Available Kertesz et al. (Nature Genetics 2008 described PITA, a miRNA target prediction algorithm based on hybridization energy and site accessibility. In this note, we used a population genomics approach to reexamine their data and found that the PITA algorithm had lower specificity than methods based on evolutionary conservation at comparable levels of sensitivity.We also showed that deeply conserved miRNAs tend to have stronger hybridization energies to their targets than do other miRNAs. Although PITA had higher specificity in predicting targets than a naïve seed-match method, this signal was primarily due to the use of a single cutoff score for all miRNAs and to the observed correlation between conservation and hybridization energy. Overall, our results clarify the accuracy of different miRNA target prediction algorithms in Drosophila and the role of site accessibility in miRNA target prediction.

  16. Pharmacokinetic study of single- and multiple-dosing with metolazone tablets in healthy Chinese population.

    Science.gov (United States)

    Li, Xueqing; Wang, Rutao; Liu, Yang; Liu, Yun; Zheng, Heng; Feng, Yabo; Zhao, Na; Geng, Hongbin; Zhang, Wanzhi; Wen, Aidong

    2017-11-16

    Metolazone is a diuretic, saluretic and antihypertensive chemical compound from the quinazoline category that possesses medicinal features similar to those of other thiazide diuretic drugs. However, the pharmacokinetics of metolazone in the Chinese population has rarely been studied. This study aimed to examine the pharmacokinetic characteristics, safety characteristic, and tolerability of metolazone in healthy Chinese subjects after single and multiple doses taken orally as well as the effects that food and gender have on oral metolazone pharmacokinetic parameters. An open-label, randomized, and single- and multiple-dosing investigation was performed in healthy Chinese subjects. The investigation included 3 study groups: the 0.5 mg, 1 mg and 2 mg dose groups were the single-dose study groups in the first stage. Eligible volunteers were randomly and orally administered a single 0.5 mg, 1 mg, or 2 mg metolazone tablet. The 0.5 mg dose group was also part of the multiple-dose study group, and the 1 mg dose group was the food-effect study group in the second stage. Human plasma samples were gathered pre-dosing and up to 48 h after dosing. The human plasma sample concentration of metolazone was quantified using a validated liquid chromatography tandem mass spectrometry method. Pharmacokinetic data were calculated by a noncompartmental analysis method using WinNonlin version 6.4. Tolerability was evaluated based on adverse events, medical examination, 12-lead ECG, and other clinical laboratory exams. Thirty eligible subjects (15 men and 15 women) were registered in our investigation and completed all of the study stages. The AUC and C max showed dose proportionality after a single dose based on the linear-regression analysis. A comparison of the pharmacokinetic data revealed that the differences between the male and female groups were not statistically significant. The t max of metolazone was increased by approximately 100% in the fed condition. Metolazone was

  17. Single cell genomics indicates horizontal gene transfer and viral infections in a deep subsurface Firmicutes population

    Directory of Open Access Journals (Sweden)

    Jessica eLabonté

    2015-04-01

    Full Text Available A major fraction of Earth's prokaryotic biomass dwells in the deep subsurface, where cellular abundances per volume of sample are lower, metabolism is slower, and generation times are longer than those in surface terrestrial and marine environments. How these conditions impact biotic interactions and evolutionary processes is largely unknown. Here we employed single cell genomics to analyze cell-to-cell genome content variability and signatures of horizontal gene transfer (HGT and viral infections in five cells of Candidatus Desulforudis audaxviator, which were collected from a three km-deep fracture water in the 2.9 Ga-old Witwatersrand Basin of South Africa. Between 0 and 32 % of genes recovered from single cells were not present in the original, metagenomic assembly of Desulforudis, which was obtained from a neighboring subsurface fracture. We found a transposable prophage, a retron, multiple clustered regularly interspaced short palindromic repeats (CRISPRs and restriction-modification systems, and an unusually high frequency of transposases in the analyzed single cell genomes. This indicates that recombination, HGT and viral infections are prevalent evolutionary events in the studied population of microorganisms inhabiting a highly stable deep subsurface environment.

  18. Regulation of Monocyte Functional Heterogeneity by miR-146a and Relb

    Directory of Open Access Journals (Sweden)

    Martin Etzrodt

    2012-04-01

    Full Text Available Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA, miR-146a, which is differentially regulated both in mouse (Ly-6Chi/Ly-6Clo and human (CD14hi/CD14loCD16+ monocyte subsets. The single miRNA controlled the amplitude of the Ly-6Chi monocyte response during inflammatory challenge whereas it did not affect Ly-6Clo cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6Chi monocyte responses while sparing Ly-6Clo monocyte activity.

  19. Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Yamashita, Ryo; Sato, Mitsuo; Kakumu, Tomohiko; Hase, Tetsunari; Yogo, Naoyuki; Maruyama, Eiichi; Sekido, Yoshitaka; Kondo, Masashi; Hasegawa, Yoshinori

    2015-01-01

    Both pro- and anti-oncogenic roles of miR-221 and miR-222 microRNAs are reported in several types of human cancers. A previous study suggested their oncogenic role in invasiveness in lung cancer, albeit only one cell line (H460) was used. To further evaluate involvement of miR-221 and miR-222 in lung cancer, we investigated the effects of miR-221 and miR-222 overexpression on six lung cancer cell lines, including H460, as well as one immortalized normal human bronchial epithelial cell line, HBEC4. miR-221 and miR-222 induced epithelial-to-mesenchymal transition (EMT)-like changes in a minority of HBEC4 cells but, unexpectedly, both the microRNAs rather suppressed their invasiveness. Consistent with the prior report, miR-221 and miR-222 promoted growth in H460; however, miR-221 suppressed growth in four other cell lines with no effects in one, and miR-222 suppressed growth in three cell lines but promoted growth in two. These are the first results to show tumor-suppressive effects of miR-221 and miR-222 in lung cancer cells, and we focused on clarifying the mechanisms. Cell cycle and apoptosis analyses revealed that growth suppression by miR-221 and miR-222 occurred through intra-S-phase arrest and/or apoptosis. Finally, lung cancer cell lines transfected with miR-221 or miR-222 became more sensitive to the S-phase targeting drugs, possibly due to an increased S-phase population. In conclusion, our data are the first to show tumor-suppressive effects of miR-221 and miR-222 on lung cancer, warranting testing their potential as therapeutics for the disease

  20. ESR1 single nucleotide polymorphism rs1062577 (c.*3804T>A) alters the susceptibility of breast cancer risk in Iranian population.

    Science.gov (United States)

    Dehghan, Zahra; Sadeghi, Samira; Tabatabaeian, Hossein; Ghaedi, Kamran; Azadeh, Mansoureh; Fazilati, Mohammad; Bagheri, Fatemeh

    2017-05-05

    Albeit single nucleotide polymorphisms related to ESR1 gene have been studied, only a number of them have been reported to be associated with breast cancer risk. rs1062577 is one of the most recent microRNA-related ESR1 SNPs; however, no study has been conducted to investigate the significance this polymorphism in Iranian population. In this study, we aimed to investigate the frequency and also the association between rs1062577 and breast cancer. rs1062577 position was genotyped by Tetra-primer ARMS-PCR in totally 182 blood specimens obtained from breast cancer patients (n=86), and healthy blood donors (n=96). The distribution of different genotypes was statistically analyzed in terms of the potential association between rs1062577 different alleles, breast cancer risk and clinicopathological criteria of breast cancer patients. The statistical analyses confidently indicated that rs1062577 A allele is associated with the increased breast cancer risk in both univariate and multivariate regression models (Odds Ratio=8.403 and 32.602 respectively). rs1062577 T allele was statistically associated with stage I of breast cancer patients (p-value=0.025). In silico studies implied that rs1062577 A allele can alter the binding capacity of ESR1 mRNA and miRNAs via either breakage or formation of hydrogen bonds. rs1062577 A allele is significantly and dramatically associated with the elevated risk and greater stages of breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Mitochondrial Genome Diversity of Native Americans Supports a Single Early Entry of Founder Populations into America

    Science.gov (United States)

    Silva Jr., Wilson A.; Bonatto, Sandro L.; Holanda, Adriano J.; Ribeiro-dos-Santos, Andrea K.; Paixão, Beatriz M.; Goldman, Gustavo H.; Abe-Sandes, Kiyoko; Rodriguez-Delfin, Luis; Barbosa, Marcela; Paçó-Larson, Maria Luiza; Petzl-Erler, Maria Luiza; Valente, Valeria; Santos, Sidney E. B.; Zago, Marco A.

    2002-01-01

    There is general agreement that the Native American founder populations migrated from Asia into America through Beringia sometime during the Pleistocene, but the hypotheses concerning the ages and the number of these migrations and the size of the ancestral populations are surrounded by controversy. DNA sequence variations of several regions of the genome of Native Americans, especially in the mitochondrial DNA (mtDNA) control region, have been studied as a tool to help answer these questions. However, the small number of nucleotides studied and the nonclocklike rate of mtDNA control-region evolution impose several limitations to these results. Here we provide the sequence analysis of a continuous region of 8.8 kb of the mtDNA outside the D-loop for 40 individuals, 30 of whom are Native Americans whose mtDNA belongs to the four founder haplogroups. Haplogroups A, B, and C form monophyletic clades, but the five haplogroup D sequences have unstable positions and usually do not group together. The high degree of similarity in the nucleotide diversity and time of differentiation (i.e., ∼21,000 years before present) of these four haplogroups support a common origin for these sequences and suggest that the populations who harbor them may also have a common history. Additional evidence supports the idea that this age of differentiation coincides with the process of colonization of the New World and supports the hypothesis of a single and early entry of the ancestral Asian population into the Americas. PMID:12022039

  2. Elective single-embryo transfer: persuasive communication strategies can affect choice in a young British population.

    Science.gov (United States)

    van den Akker, O B A; Purewal, S

    2011-12-01

    This study tested the effectiveness of the framing effect and fear appeals to inform young people about the risks of multiple births and the option of selecting elective single-embryo transfer (eSET). A non-patient student sample (age (mean±SD) 23±5.5 years; n=321) were randomly allocated to one of seven groups: (1) framing effect: (1a) gain and (1b) loss frame; (2) fear appeal: (2a) high, (2b) medium and (2c) low fear; or (3) a control group: (3a) education and (3b) non-education. The primary outcome measure was the Attitudes towards Single Embryo Transfer questionnaire, before exposure to the messages (time 1) and immediately afterwards (time 2). Results revealed participants in the high fear, medium fear and gain condition demonstrated the most positive and significant differences (Ppersuasive communication techniques on a student population to promote immediate and hypothetical eSET preferences is more successful at promoting eSET than merely reporting educational content. Future research should investigate its application in a clinical population. A multiple pregnancy is a health risk to both infant and mother following IVF treatment. The aims of this study were to test the effectiveness of two persuasive communication techniques (the framing effect and fear appeals) to inform young people about the risks of multiple births and the hypothetical option of selecting elective single-embryo transfer (eSET) (i.e., only one embryo is transferred to the uterus using IVF treatment). A total of 321 non-patient student sample (mean age 23) were randomly allocated to read a message from one of seven groups: (1) framing effect: (1a) gain and (1b) loss frame; (2) fear appeal: (2a) high, (2b) medium and (2c) low fear; or (3) a control group: education (3a) and (3b) non-education. Participants completed the Attitudes towards Single Embryo Transfer questionnaire, before exposure to the messages (time 1) and immediately afterwards (time 2). Results revealed that participants

  3. Series solution for continuous population models for single and interacting species by the homotopy analysis method

    Directory of Open Access Journals (Sweden)

    Magdy A. El-Tawil

    2012-07-01

    Full Text Available The homotopy analysis method (HAM is used to find approximate analytical solutions of continuous population models for single and interacting species. The homotopy analysis method contains the auxiliary parameter $hbar,$ which provides us with a simple way to adjust and control the convergence region of series solution. the solutions are compared with the numerical results obtained using NDSolve, an ordinary differential equation solver found in the Mathematica package and a good agreement is found. Also the solutions are compared with the available analytic results obtained by other methods and more accurate and convergent series solution found. The convergence region is also computed which shows the validity of the HAM solution. This method is reliable and manageable.

  4. Lyman alpha evolution at high resolution: evidence for a single population?

    International Nuclear Information System (INIS)

    Giallongo, E.

    1991-01-01

    Recent high-resolution spectroscopic data on the Lyman alpha absorption lines allow a statistical investigation of the cosmological evolution of Ly α clouds from z = 1.8 to 3.8. The maximum likelihood analysis shows that the number density evolution is differential, being progressively slower for stronger lines. There are discrepancies in the derived evolution for lines with equivalent widths W>0.3 A from line samples obtained at high and intermediate resolutions. A possible explanation is given in terms of line blending. A differential evolution of this type seems to imply a unified evolutionary scheme which incorporates Ly α and metal-line systems in a single population. (author)

  5. Stochastic adaptation and fold-change detection: from single-cell to population behavior

    Directory of Open Access Journals (Sweden)

    Leier André

    2011-02-01

    Full Text Available Abstract Background In cell signaling terminology, adaptation refers to a system's capability of returning to its equilibrium upon a transient response. To achieve this, a network has to be both sensitive and precise. Namely, the system must display a significant output response upon stimulation, and later on return to pre-stimulation levels. If the system settles at the exact same equilibrium, adaptation is said to be 'perfect'. Examples of adaptation mechanisms include temperature regulation, calcium regulation and bacterial chemotaxis. Results We present models of the simplest adaptation architecture, a two-state protein system, in a stochastic setting. Furthermore, we consider differences between individual and collective adaptive behavior, and show how our system displays fold-change detection properties. Our analysis and simulations highlight why adaptation needs to be understood in terms of probability, and not in strict numbers of molecules. Most importantly, selection of appropriate parameters in this simple linear setting may yield populations of cells displaying adaptation, while single cells do not. Conclusions Single cell behavior cannot be inferred from population measurements and, sometimes, collective behavior cannot be determined from the individuals. By consequence, adaptation can many times be considered a purely emergent property of the collective system. This is a clear example where biological ergodicity cannot be assumed, just as is also the case when cell replication rates are not homogeneous, or depend on the cell state. Our analysis shows, for the first time, how ergodicity cannot be taken for granted in simple linear examples either. The latter holds even when cells are considered isolated and devoid of replication capabilities (cell-cycle arrested. We also show how a simple linear adaptation scheme displays fold-change detection properties, and how rupture of ergodicity prevails in scenarios where transitions between

  6. MiNube

    OpenAIRE

    Villanueva Hernández, Yarilo David

    2015-01-01

    [ES]MiNube es una solución de almacenamiento de datos online enfocada en la privacidad, seguridad y control del usuario final. A diferencia de otras plataformas de almacenamiento en la nube en el que se depende de agentes externos, MiNube cede el control de los datos al usuario, permitiéndole configurar su propio entorno y definiendo políticas de encriptación en las que el propio usuario es el único agente capaz de acceder a sus datos. MiNube se compone de tres partes: Un servidor web para s...

  7. Tourette's syndrome in a special education population: a pilot study involving a single school district.

    Science.gov (United States)

    Kurlan, R; Whitmore, D; Irvine, C; McDermott, M P; Como, P G

    1994-04-01

    To determine whether children requiring special education represent a high-risk group for identifying Tourette's syndrome (TS), we performed direct examinations for the presence of tics in 35 special education and 35 regular classroom students from a single school district. Of the special education students, nine (26%) had definite or probable tics as compared with only two (6%) of the regular classroom students. About one-third of the students with tics currently meet diagnostic criteria for TS and probably more will do so in the future. About one-half of the subjects with tics have evidence of obsessive-compulsive behavior (OCB) or an attention-deficit hyperactivity disorder (ADHD). For three randomly selected students with definite tics, direct examinations of first-degree relatives revealed the presence of tics in all families. Subjects to the limitations of this pilot study, we conclude that TS and related tic disorders are commonly associated with the need for special education in this single school district. TS might also be an important contributor to school problems in the childhood population at large and may be a highly prevalent condition. In addition, we conclude that childhood tics are associated with OCB and ADHD, are genetically determined, and are part of the TS clinical spectrum.

  8. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    Science.gov (United States)

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

  9. Single nucleotide polymorphism discovery in albacore and Atlantic bluefin tuna provides insights into worldwide population structure.

    Science.gov (United States)

    Albaina, A; Iriondo, M; Velado, I; Laconcha, U; Zarraonaindia, I; Arrizabalaga, H; Pardo, M A; Lutcavage, M; Grant, W S; Estonba, A

    2013-12-01

    The optimal management of the commercially important, but mostly over-exploited, pelagic tunas, albacore (Thunnus alalunga Bonn., 1788) and Atlantic bluefin tuna (BFT; Thunnus thynnus L., 1758), requires a better understanding of population structure than has been provided by previous molecular methods. Despite numerous studies of both species, their population structures remain controversial. This study reports the development of single nucleotide polymorphisms (SNPs) in albacore and BFT and the application of these SNPs to survey genetic variability across the geographic ranges of these tunas. A total of 616 SNPs were discovered in 35 albacore tuna by comparing sequences of 54 nuclear DNA fragments. A panel of 53 SNPs yielded FST values ranging from 0.0 to 0.050 between samples after genotyping 460 albacore collected throughout the distribution of this species. No significant heterogeneity was detected within oceans, but between-ocean comparisons (Atlantic, Pacific and Indian oceans along with Mediterranean Sea) were significant. Additionally, a 17-SNP panel was developed in Atlantic BFT by cross-species amplification in 107 fish. This limited number of SNPs discriminated between samples from the two major spawning areas of Atlantic BFT (FST  = 0.116). The SNP markers developed in this study can be used to genotype large numbers of fish without the need for standardizing alleles among laboratories. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

  10. Single-cell analysis of differences in transcriptomic profiles of oocytes and cumulus cells at GV, MI, MII stages from PCOS patients.

    Science.gov (United States)

    Liu, Qiwei; Li, Yumei; Feng, Yun; Liu, Chaojie; Ma, Jieliang; Li, Yifei; Xiang, Huifen; Ji, Yazhong; Cao, Yunxia; Tong, Xiaowen; Xue, Zhigang

    2016-12-22

    Polycystic ovary syndrome (PCOS) is a common frequent endocrine disorder among women of reproductive age. Although assisted reproductive techniques (ARTs) are used to address subfertility in PCOS women, their effectiveness is not clear. Our aim was to compare transcriptomic profiles of oocytes and cumulus cells (CCs) between women with and without PCOS, and assess the effectiveness of ARTs in treating PCOS patients. We collected oocytes and CCs from 16 patients with and without PCOS patients to categorize them into 6 groups according to oocyte nuclear maturation. Transcriptional gene expression of oocyte and CCs was determined via single-cell RNA sequencing. The ratio of fertilization and cleavage was higher in PCOS patients than in non-PCOS patients undergoing ARTs, and there was no difference in the number of high-quality embryos between the groups. Differentially expressed genes including PPP2R1A, PDGFRA, EGFR, GJA1, PTGS2, TNFAIP6, TGF-β1, CAV1, INHBB et al. were investigated as potential causes of PCOS oocytes and CCs disorder at early stages, but their expression returned to the normal level at the metaphase II (MII) stage via ARTs. In conclusion, ARTs can improve the quality of cumulus-oocyte complex (COC) and increase the ratio of fertilization and cleavage in PCOS women.

  11. A 4-miRNA signature to predict survival in glioblastomas

    DEFF Research Database (Denmark)

    Hermansen, Simon K; Sørensen, Mia D; Hansen, Anker

    2017-01-01

    Glioblastomas are among the most lethal cancers; however, recent advances in survival have increased the need for better prognostic markers. microRNAs (miRNAs) hold great prognostic potential being deregulated in glioblastomas and highly stable in stored tissue specimens. Moreover, miRNAs control...... multiple genes representing an additional level of gene regulation possibly more prognostically powerful than a single gene. The aim of the study was to identify a novel miRNA signature with the ability to separate patients into prognostic subgroups. Samples from 40 glioblastoma patients were included...... that expression patterns of miRNAs; particularly the four miRNAs: hsa-miR-107_st, hsa-miR-548x_st, hsa-miR-3125_st and hsa-miR-331-3p_st could determine short- and long-term survival with a predicted accuracy of 78%. Heatmap dendrograms dichotomized glioblastomas into prognostic subgroups with a significant...

  12. Novel form of miR-29b suppresses bleomycin-induced pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Yuko Yamada

    Full Text Available MicroRNA 29b (miR-29b replacement therapy is effective for suppressing fibrosis in a mouse model. However, to develop clinical applications for miRNA mimics, the side effects of nucleic acid drugs have to be addressed. In this study, we focused on miRNA mimics in order to develop therapies for idiopathic pulmonary fibrosis. We developed a single-stranded RNA, termed "miR-29b Psh-match," that has a unique structure to avoid problems associated with the therapeutic uses of miRNAs. A comparison of miR-29b Psh-match and double-stranded one, termed "miR-29b mimic" indicated that the single-stranded form was significantly effective towards fibrosis according to both in vivo and in vitro experiments. This novel form of miR-29b may become the foundation for developing an effective therapeutic drug for pulmonary fibrosis.

  13. Association ofinterleukin-10gene single nucleotide polymorphisms with rheumatoid arthritis in a Chinese population.

    Science.gov (United States)

    Zhang, Tian-Ping; Lv, Tian-Tian; Xu, Shu-Zhen; Pan, Hai-Feng; Ye, Dong-Qing

    2018-02-27

    Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in the IL-10 gene and RA susceptibility. We genotyped three SNPs (rs1800890, rs3024495, rs3024505) of the IL-10 gene in a Chinese population of 354 RA patients and 367 controls. Genotyping was conducted using TaqMan SNP genotyping assays. Plasma IL-10 levels were measured by ELISA. The A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes. The IL-10 rs1800890 variant might contribute to RA susceptibility in the Chinese population. Replication studies in different ethnic groups are required to further examine the critical role of IL-10 gene variation in the pathogenesis of RA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Common single nucleotide polymorphisms and keratoconus in the Han Chinese population.

    Science.gov (United States)

    Wang, Yani; Jin, Tianbo; Zhang, Xuehui; Wei, Wei; Cui, Yan; Geng, Tingting; Liu, Qianping; Gao, Jing; Liu, Ming; Chen, Chao; Zhang, Changning; Zhu, Xiuping

    2013-09-01

    To investigate whether the tag single nucleotide polymorphisms (tSNPs) in VSX1, COL4A3, COL4A4, IL1A and IL1B genes were associated with keratoconus (KTCN) in the Han Chinese population. Ninety-seven KTCN patients and 101 healthy controls were enrolled in this study. All cases were diagnosed on the basis of clinical examination. Twenty-one tSNPs were selected for association study in five genes. SNP genotyping was performed by Sequenom MassARRAY RS1000. Sequenom Typer 4.0 Software, PLINK, Haploview and SHEsis software platform were used to perform data management and analyses. Three tSNPs in the VSX1 gene were observed to be associated with KTCN risk at a 5% level by χ(2) test (rs56157240 and rs12480307, p = 0.0499, OR: 6.42, 95% CI: 0.77-53.78; rs6050307, p = 1.22 × 10(-7), OR: 0.05, 95% CI: 0.01-0.23). Rs2071376 in the IL1A gene was also associated with KTCN (p = 0.0487, OR: 1.51, 95% CI: 1.00-2.26). Three haplotypes in the VSX1 gene were found to be associated with risk of KTCN (p < 0.05). Our findings confirmed previous reports that polymorphisms of VSX1 and IL1A genes were associated with risk of KTCN in the Chinese population, suggesting an important determinant of KTCN development by VSX1 and IL1A genes.

  15. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

    International Nuclear Information System (INIS)

    Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean; Larsen, Annette K.; Escargueil, Alexandre

    2016-01-01

    We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  16. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzi, Tommaso [Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS, Cachan 94230 Cedex, France & INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Chisholm, Rebecca H. [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052 (Australia); Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean [Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Larsen, Annette K.; Escargueil, Alexandre [Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris (France); INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris (France)

    2016-06-08

    We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  17. Search for <mi>CP> Violation and Measurement of the Branching Fraction in the Decay <mi>D>0<mi>KS>0<mi>KS>0

    Energy Technology Data Exchange (ETDEWEB)

    Dash, N.; Bahinipati, S.; Bhardwaj, V.; Trabelsi, K.; Adachi, I.; Aihara, H.; Al Said, S.; Asner, D. M.; Aulchenko, V.; Aushev, T.; Ayad, R.; Babu, V.; Badhrees, I.; Bakich, A. M.; Bansal, V.; Barberio, E.; Bhuyan, B.; Biswal, J.; Bobrov, A.; Bondar, A.; Bonvicini, G.; Bozek, A.; Bračko, M.; Breibeck, F.; Browder, T. E.; Červenkov, D.; Chang, M. -C.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Cho, K.; Choi, Y.; Cinabro, D.; Di Carlo, S.; Doležal, Z.; Drásal, Z.; Dutta, D.; Eidelman, S.; Epifanov, D.; Farhat, H.; Fast, J. E.; Ferber, T.; Fulsom, B. G.; Gaur, V.; Gabyshev, N.; Garmash, A.; Gillard, R.; Goldenzweig, P.; Haba, J.; Hara, T.; Hayasaka, K.; Hayashii, H.; Hedges, M. T.; Hou, W. -S.; Iijima, T.; Inami, K.; Ishikawa, A.; Itoh, R.; Iwasaki, Y.; Jacobs, W. W.; Jaegle, I.; Jeon, H. B.; Jin, Y.; Joffe, D.; Joo, K. K.; Julius, T.; Kahn, J.; Kaliyar, A. B.; Karyan, G.; Katrenko, P.; Kawasaki, T.; Kiesling, C.; Kim, D. Y.; Kim, H. J.; Kim, J. B.; Kim, K. T.; Kim, M. J.; Kim, S. H.; Kim, Y. J.; Kinoshita, K.; Kodyš, P.; Korpar, S.; Kotchetkov, D.; Križan, P.; Krokovny, P.; Kuhr, T.; Kulasiri, R.; Kumar, R.; Kumita, T.; Kuzmin, A.; Kwon, Y. -J.; Lange, J. S.; Lee, I. S.; Li, C. H.; Li, L.; Li, Y.; Li Gioi, L.; Libby, J.; Liventsev, D.; Lubej, M.; Luo, T.; Masuda, M.; Matvienko, D.; Merola, M.; Miyabayashi, K.; Miyata, H.; Mizuk, R.; Mohanty, G. B.; Mohanty, S.; Moon, H. K.; Mori, T.; Mussa, R.; Nakano, E.; Nakao, M.; Nanut, T.; Nath, K. J.; Natkaniec, Z.; Nayak, M.; Niiyama, M.; Nisar, N. K.; Nishida, S.; Ogawa, S.; Okuno, S.; Ono, H.; Pakhlov, P.; Pakhlova, G.; Pal, B.; Pardi, S.; Park, C. -S.; Park, H.; Paul, S.; Pedlar, T. K.; Pesántez, L.; Pestotnik, R.; Piilonen, L. E.; Prasanth, K.; Ritter, M.; Rostomyan, A.; Sahoo, H.; Sakai, Y.; Sandilya, S.; Santelj, L.; Sanuki, T.; Sato, Y.; Savinov, V.; Schneider, O.; Schnell, G.; Schwanda, C.; Schwartz, A. J.; Seino, Y.; Senyo, K.; Sevior, M. E.; Shebalin, V.; Shen, C. P.; Shibata, T. -A.; Shiu, J. -G.; Shwartz, B.; Simon, F.; Sokolov, A.; Solovieva, E.; Starič, M.; Strube, J. F.; Stypula, J.; Sumisawa, K.; Sumiyoshi, T.; Takizawa, M.; Tamponi, U.; Tanida, K.; Tenchini, F.; Uchida, M.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Usov, Y.; Van Hulse, C.; Varner, G.; Vorobyev, V.; Vossen, A.; Waheed, E.; Wang, C. H.; Wang, M. -Z.; Wang, P.; Watanabe, M.; Watanabe, Y.; Widmann, E.; Williams, K. M.; Won, E.; Yamashita, Y.; Ye, H.; Yelton, J.; Yook, Y.; Yuan, C. Z.; Yusa, Y.; Zhang, Z. P.; Zhilich, V.; Zhukova, V.; Zhulanov, V.; Zupanc, A.

    2017-10-01

    We report a study of the decay <mi>D>0<mi>KS>0<mi>KS>0 using 921 fb-1 of data collected at or near the Υ(4S) and Υ(5S) resonances with the Belle detector at the KEKB asymmetric energy e+e- collider. The measured time-integrated CP asymmetry is ACP(<mi>D>0<mi>KS>0<mi>KS>0) = (-0.02 ± 1.53 ± 0.02 ± 0.17)%, and the branching fraction is B(<mi>D>0<mi>KS>0<mi>KS>0) = (1.321 ± 0.023 ± 0.036 ± 0.044) × 10-4, where the first uncertainty is statistical, the second is systematic, and the third is due to the normalization mode (<mi>D>0<mi>KS>0π0). These results are significantly more precise than previous measurements available for this mode. The ACP measurement is consistent with the standard model expectation.

  18. Mutations in MicroRNA Genes and Their Binding Sites are Infrequently Associated with Human Colorectal Cancer in the Kashmiri Population.

    Science.gov (United States)

    Maqbool, Raihana; Ismail, Rehana; Hussain, Mahboob- Ul-

    2014-01-01

    MicroRNAs are small non-coding RNAs, 19-24 nucleotides in length that bind to the 3'UTR of target mRNAs and thus regulate gene expression post transcriptionally. MiRNAs have been implicated in various biological and pathological processes. The binding of miRNAs to 3'UTR is crucial for regulating the mRNA level and hence protein expression. The complementarity between the miRNA and its target mRNA is critical for the outcome of the miRNA mediated translational regulation. Changes in the nucleotide sequence of either the miRNA or its target binding site can deregulate gene expression and hence lead to the development of various pathological conditions, including tumorigenesis. To determine whether sequence alterations in miRNA genes and their target sites in mRNAs are associated with the colorectal cancers, we screened two miRNA genes-Let-7c, mir-206 and selected miRNA binding regions on KRAS, TP53 and GJA1 3'UTR. This study was carried out on 60 human colorectal cancer tissue samples. Our sequencing results did not reveal any mutation/single-nucleotide polymorphism in either the miRNAs or the miRNA binding sites in any of the tumor samples. This data suggests that mutations/SNPs targeting miRNA genes or their binding sites in 3'-untranslated regions are infrequent events in the development of colorectal cancer in Kashmiri population.

  19. Metabolic diversity and ecological niches of Achromatium populations revealed with single-cell genomic sequencing

    Directory of Open Access Journals (Sweden)

    Muammar eMansor

    2015-08-01

    Full Text Available Large, sulfur-cycling, calcite-precipitating bacteria in the genus Achromatium represent a significant proportion of bacterial communities near sediment-water interfaces throughout the world. Our understanding of their potentially crucial roles in calcium, carbon, sulfur, nitrogen, and iron cycling is limited because they have not been cultured or sequenced using environmental genomics approaches to date. We utilized single-cell genomic sequencing to obtain one incomplete and two nearly complete draft genomes for Achromatium collected at Warm Mineral Springs, FL. Based on 16S rRNA gene sequences, the three cells represent distinct and relatively distant Achromatium populations (91-92% identity. The draft genomes encode key genes involved in sulfur and hydrogen oxidation; oxygen, nitrogen and polysulfide respiration; carbon and nitrogen fixation; organic carbon assimilation and storage; chemotaxis; twitching motility; antibiotic resistance; and membrane transport. Known genes for iron and manganese energy metabolism were not detected. The presence of pyrophosphatase and vacuolar (V-type ATPases, which are generally rare in bacterial genomes, suggests a role for these enzymes in calcium transport, proton pumping, and/or energy generation in the membranes of calcite-containing inclusions.

  20. Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations.

    Directory of Open Access Journals (Sweden)

    Christine E McLaren

    Full Text Available The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs using DNA from white men aged ≥ 25 y and women ≥ 50 y in the Hemochromatosis and Iron Overload Screening (HEIRS Study with serum ferritin (SF ≤ 12 µg/L (cases and controls (SF >100 µg/L in men, SF >50 µg/L in women. We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7 × 10(-6 and replicated in African Americans (p = 0.0012.Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p<4.4 × 10(-5; six SNPs replicated in other ethnicities (p<0.01. SNP rs10904850 in the CUBN gene on 10p13 was associated with serum iron in African Americans (P = 1.0 × 10(-5. These results confirm known associations with iron measures and give unique evidence of their role in different ethnicities, suggesting origins in a common founder.

  1. Clonal diversity and population genetic structure of arbuscular mycorrhizal fungi (Glomus spp.) studied by multilocus genotyping of single spores

    DEFF Research Database (Denmark)

    Holtgrewe-Stukenbrock, Eva; Rosendahl, Søren

    2005-01-01

    A nested multiplex PCR (polymerase chain reaction) approach was used for multilocus genotyping of arbuscular mycorrhizal fungal populations. This method allowed us to amplify multiple loci from Glomus single spores in a single PCR amplification. Variable introns in the two protein coding genes Gm......FOX2 and GmTOR2 were applied as codominant genetic markers together with the LSU rDNA.   Genetic structure of Glomus spp. populations from an organically and a conventionally cultured field were compared by hierarchical sampling of spores from four plots in each field. Multilocus genotypes were...

  2. Single-Cell Behavior and Population Heterogeneity: Solving an Inverse Problem to Compute the Intrinsic Physiological State Functions

    OpenAIRE

    Spetsieris, Konstantinos; Zygourakis, Kyriacos

    2011-01-01

    The dynamics of isogenic cell populations can be described by cell population balance models that account for phenotypic heterogeneity. To utilize the predictive power of these models, however, we must know the rates of single-cell reaction and division and the bivariate partition probability density function. These three intrinsic physiological state (IPS) functions can be obtained by solving an inverse problem that requires knowledge of the phenotypic distributions for the overall cell popu...

  3. Brief communication genotyping of Burkholderia pseudomallei revealed high genetic variability among isolates from a single population group

    OpenAIRE

    Zueter, Abdelrahman Mohammad; Rahman, Zaidah Abdul; Yean, Chan Yean; Harun, Azian

    2015-01-01

    Burkholderia pseudomallei is a soil dwelling Gram-negative bacteria predominates in Southeast Asia zone and the tropical part of Australia. Genetic diversity has been explored among various populations and environments worldwide. To date, little data is available on MLST profiling of clinical B. pseudomallei isolates in peninsular Malaysia. In this brief report, thirteen culture positive B. pseudomallei cases collected from a single population of Terengganu state in the Western Peninsular Mal...

  4. Diagnostic and prognostic value of miR-1 and miR-29b on adverse ventricular remodeling after acute myocardial infarction - The SITAGRAMI-miR analysis.

    Science.gov (United States)

    Grabmaier, U; Clauss, S; Gross, L; Klier, I; Franz, W M; Steinbeck, G; Wakili, R; Theiss, H D; Brenner, C

    2017-10-01

    MicroRNAs (miRs) have shown to exert fibrotic and anti-fibrotic effects in preclinical models of acute myocardial infarction (AMI). The aim of this study was to evaluate miR-1, miR-21, miR-29b and miR-92a as circulating biomarkers for adverse ventricular remodeling (AVR) in post-AMI patients. Plasma levels of miR-1, miR-21, miR-29b and miR-92a were measured in 44 patients of the SITAGRAMI trial population at day 4, day 9 and 6month after AMI and in 18 matched controls (CTL). MiR expression patterns were correlated with magnetic resonance imaging (MRI) parameters for AVR (absolute change (Δ) in infarct volume (IV), left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) between day 4 and 6months after AMI) and a combined cardiovascular endpoint. Expression of miR-1, miR-21 and miR-29b but not miR-92a was increased in AMI vs. CTL cohort showing highest miR levels at d9. However, only miR-1 and miR-29b levels significantly correlated with ΔIV and showed a trend for correlation with ΔLVEF. Only miR-29b levels at day 9 correlated with ΔLVEDV at 6-month follow-up. There was no correlation of miR levels with an adverse outcome. Mir-1 and miR-29b plasma levels post-AMI correlate with IV changes. In addition, miR-29b levels are associated with changes of LVEDV over time. These results provide insights into the role of miRs as diagnostic AVR surrogate markers. Further large scale clinical trials will be needed to evaluate the real prognostic relevance of these miRs with respect to a clinical implication in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Models of synchronized hippocampal bursts in the presence of inhibition. I. Single population events.

    Science.gov (United States)

    Traub, R D; Miles, R; Wong, R K

    1987-10-01

    1. We constructed model networks with 520 or 1,020 cells intended to represent the CA3 region of the hippocampus. Model neurons were simulated in enough detail to reproduce intrinsic bursting and the electrotonic flow of currents along dendritic cables. Neurons exerted either excitatory or inhibitory postsynaptic actions on other cells. The network models were simulated with different levels of excitatory and inhibitory synaptic strengths in order to study epileptic and other interesting collective behaviors in the system. 2. Excitatory synapses between neurons in the network were powerful enough so that burst firing in a presynaptic neuron would evoke bursting in its connected cells. Since orthodromic or antidromic stimulation evokes both a fast and a slow phase of inhibition, two types of inhibitory cells were simulated. The properties of these inhibitory cells were modeled to resemble those of two types of inhibitory cells characterized by dual intracellular recordings in the slice preparation. 3. With fast inhibition totally blocked, a stimulus to a single cell lead to a synchronized population burst. Thus the principles of our epileptic synchronization model, developed earlier, apply even when slow inhibitory postsynaptic potentials (IPSPs) are present, as apparently occurs in the epileptic hippocampal slice. The model performs in this way because bursting can propagate through several generations in the network before slow inhibition builds up enough to block burst propagation. This can occur, however, only if connectivity is sufficiently large. With very low connection densities, slow IPSPs will prevent the development of full synchronization. 4. We performed multiple simulations in which the fast inhibitory conductance strength was kept fixed at various levels while the strength of the excitatory synapses was varied. In each simulation, we stimulated either one or four cells. For each level of inhibition, the peak number of cells bursting depended

  6. MiDAS

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads

    2015-01-01

    communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study...... of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes—knowledge that will be an invaluable resource...

  7. MI-Sim: A MATLAB package for the numerical analysis of microbial ecological interactions.

    Science.gov (United States)

    Wade, Matthew J; Oakley, Jordan; Harbisher, Sophie; Parker, Nicholas G; Dolfing, Jan

    2017-01-01

    Food-webs and other classes of ecological network motifs, are a means of describing feeding relationships between consumers and producers in an ecosystem. They have application across scales where they differ only in the underlying characteristics of the organisms and substrates describing the system. Mathematical modelling, using mechanistic approaches to describe the dynamic behaviour and properties of the system through sets of ordinary differential equations, has been used extensively in ecology. Models allow simulation of the dynamics of the various motifs and their numerical analysis provides a greater understanding of the interplay between the system components and their intrinsic properties. We have developed the MI-Sim software for use with MATLAB to allow a rigorous and rapid numerical analysis of several common ecological motifs. MI-Sim contains a series of the most commonly used motifs such as cooperation, competition and predation. It does not require detailed knowledge of mathematical analytical techniques and is offered as a single graphical user interface containing all input and output options. The tools available in the current version of MI-Sim include model simulation, steady-state existence and stability analysis, and basin of attraction analysis. The software includes seven ecological interaction motifs and seven growth function models. Unlike other system analysis tools, MI-Sim is designed as a simple and user-friendly tool specific to ecological population type models, allowing for rapid assessment of their dynamical and behavioural properties.

  8. Genetics of single-cell protein abundance variation in large yeast populations

    Science.gov (United States)

    Albert, Frank W.; Treusch, Sebastian; Shockley, Arthur H.; Bloom, Joshua S.; Kruglyak, Leonid

    2014-02-01

    Variation among individuals arises in part from differences in DNA sequences, but the genetic basis for variation in most traits, including common diseases, remains only partly understood. Many DNA variants influence phenotypes by altering the expression level of one or several genes. The effects of such variants can be detected as expression quantitative trait loci (eQTL). Traditional eQTL mapping requires large-scale genotype and gene expression data for each individual in the study sample, which limits sample sizes to hundreds of individuals in both humans and model organisms and reduces statistical power. Consequently, many eQTL are probably missed, especially those with smaller effects. Furthermore, most studies use messenger RNA rather than protein abundance as the measure of gene expression. Studies that have used mass-spectrometry proteomics reported unexpected differences between eQTL and protein QTL (pQTL) for the same genes, but these studies have been even more limited in scope. Here we introduce a powerful method for identifying genetic loci that influence protein expression in the yeast Saccharomyces cerevisiae. We measure single-cell protein abundance through the use of green fluorescent protein tags in very large populations of genetically variable cells, and use pooled sequencing to compare allele frequencies across the genome in thousands of individuals with high versus low protein abundance. We applied this method to 160 genes and detected many more loci per gene than previous studies. We also observed closer correspondence between loci that influence protein abundance and loci that influence mRNA abundance of a given gene. Most loci that we detected were clustered in `hotspots' that influence multiple proteins, and some hotspots were found to influence more than half of the proteins that we examined. The variants that underlie these hotspots have profound effects on the gene regulatory network and provide insights into genetic variation in cell

  9. Two Positive Periodic Solutions for a Neutral Delay Model of Single-Species Population Growth with Harvesting

    OpenAIRE

    Fang, Hui

    2012-01-01

    By coincidence degree theory for k-set-contractive mapping, this paper establishes a new criterion for the existence of at least two positive periodic solutions for a neutral delay model of single-species population growth with harvesting. An example is given to illustrate the effectiveness of the result.

  10. Two Positive Periodic Solutions for a Neutral Delay Model of Single-Species Population Growth with Harvesting

    Directory of Open Access Journals (Sweden)

    Hui Fang

    2012-01-01

    Full Text Available By coincidence degree theory for k-set-contractive mapping, this paper establishes a new criterion for the existence of at least two positive periodic solutions for a neutral delay model of single-species population growth with harvesting. An example is given to illustrate the effectiveness of the result.

  11. Early and late preterm delivery rates - a comparison of differing tocolytic policies in a single urban population.

    LENUS (Irish Health Repository)

    Hehir, Mark P

    2012-11-01

    Preterm delivery results in neonatal morbidity and mortality. We set out to estimate the difference in rates of preterm delivery in two institutions, serving a single population, with differing policies regarding use of tocolytic drugs for the prevention of preterm delivery.

  12. Aerosol Optical Properties Derived from the DRAGON-NE Asia Campaign, and Implications for a Single-Channel Algorithm to Retrieve Aerosol Optical Depth in Spring from Meteorological Imager (MI) On-Board the Communication, Ocean, and Meteorological Satellite (COMS)

    Science.gov (United States)

    Kim, M.; Kim, J.; Jeong, U.; Kim, W.; Hong, H.; Holben, B.; Eck, T. F.; Lim, J.; Song, C.; Lee, S.; hide

    2016-01-01

    An aerosol model optimized for northeast Asia is updated with the inversion data from the Distributed Regional Aerosol Gridded Observation Networks (DRAGON)-northeast (NE) Asia campaign which was conducted during spring from March to May 2012. This updated aerosol model was then applied to a single visible channel algorithm to retrieve aerosol optical depth (AOD) from a Meteorological Imager (MI) on-board the geostationary meteorological satellite, Communication, Ocean, and Meteorological Satellite (COMS). This model plays an important role in retrieving accurate AOD from a single visible channel measurement. For the single-channel retrieval, sensitivity tests showed that perturbations by 4 % (0.926 +/- 0.04) in the assumed single scattering albedo (SSA) can result in the retrieval error in AOD by over 20 %. Since the measured reflectance at the top of the atmosphere depends on both AOD and SSA, the overestimation of assumed SSA in the aerosol model leads to an underestimation of AOD. Based on the AErosol RObotic NETwork (AERONET) inversion data sets obtained over East Asia before 2011, seasonally analyzed aerosol optical properties (AOPs) were categorized by SSAs at 675 nm of 0.92 +/- 0.035 for spring (March, April, and May). After the DRAGON-NE Asia campaign in 2012, the SSA during spring showed a slight increase to 0.93 +/- 0.035. In terms of the volume size distribution, the mode radius of coarse particles was increased from 2.08 +/- 0.40 to 2.14 +/- 0.40. While the original aerosol model consists of volume size distribution and refractive indices obtained before 2011, the new model is constructed by using a total data set after the DRAGON-NE Asia campaign. The large volume of data in high spatial resolution from this intensive campaign can be used to improve the representative aerosol model for East Asia. Accordingly, the new AOD data sets retrieved from a single-channel algorithm, which uses a precalculated look-up table (LUT) with the new aerosol model, show

  13. Aerosol optical properties derived from the DRAGON-NE Asia campaign, and implications for a single-channel algorithm to retrieve aerosol optical depth in spring from Meteorological Imager (MI on-board the Communication, Ocean, and Meteorological Satellite (COMS

    Directory of Open Access Journals (Sweden)

    M. Kim

    2016-02-01

    Full Text Available An aerosol model optimized for northeast Asia is updated with the inversion data from the Distributed Regional Aerosol Gridded Observation Networks (DRAGON-northeast (NE Asia campaign which was conducted during spring from March to May 2012. This updated aerosol model was then applied to a single visible channel algorithm to retrieve aerosol optical depth (AOD from a Meteorological Imager (MI on-board the geostationary meteorological satellite, Communication, Ocean, and Meteorological Satellite (COMS. This model plays an important role in retrieving accurate AOD from a single visible channel measurement. For the single-channel retrieval, sensitivity tests showed that perturbations by 4 % (0.926 ± 0.04 in the assumed single scattering albedo (SSA can result in the retrieval error in AOD by over 20 %. Since the measured reflectance at the top of the atmosphere depends on both AOD and SSA, the overestimation of assumed SSA in the aerosol model leads to an underestimation of AOD. Based on the AErosol RObotic NETwork (AERONET inversion data sets obtained over East Asia before 2011, seasonally analyzed aerosol optical properties (AOPs were categorized by SSAs at 675 nm of 0.92 ± 0.035 for spring (March, April, and May. After the DRAGON-NE Asia campaign in 2012, the SSA during spring showed a slight increase to 0.93 ± 0.035. In terms of the volume size distribution, the mode radius of coarse particles was increased from 2.08 ± 0.40 to 2.14 ± 0.40. While the original aerosol model consists of volume size distribution and refractive indices obtained before 2011, the new model is constructed by using a total data set after the DRAGON-NE Asia campaign. The large volume of data in high spatial resolution from this intensive campaign can be used to improve the representative aerosol model for East Asia. Accordingly, the new AOD data sets retrieved from a single-channel algorithm, which uses a precalculated look-up table (LUT with the new aerosol model

  14. A panel of 130 autosomal single-nucleotide polymorphisms for ancestry assignment in five Asian populations and in Caucasians.

    Science.gov (United States)

    Hwa, Hsiao-Lin; Lin, Chih-Peng; Huang, Tsun-Ying; Kuo, Po-Hsiu; Hsieh, Wei-Hsin; Lin, Chun-Yen; Yin, Hsiang-I; Tseng, Li-Hui; Lee, James Chun-I

    2017-06-01

    Ancestry informative single-nucleotide polymorphism (AISNP) panels for differentiating between East and Southeast Asian populations are scarce. This study aimed to identify AISNPs for ancestry assignment of five East and Southeast Asian populations, and Caucasians. We analyzed 145 autosomal SNPs of the 627 DNA samples from individuals of six populations (234 Taiwanese Han, 91 Filipinos, 79 Indonesians, 60 Thais, 71 Vietnamese, and 92 Caucasians) using arrays. The multiple logistic regression model and a multi-tier approach were used for ancestry classification. We observed that 130 AISNPs were effective for classifying the ethnic origins with fair accuracy. Among the 130 AISNPs, 122 were useful for stratification between these five Asian populations and 64 were effective for differentiating between Caucasians and these Asian populations. For differentiation between Caucasians and Asians, an accuracy rate of 100% was achieved in these 627 subjects with 50 optimal AISNPs among the 64 effective SNPs. For classification of the five Asian populations, the accuracy rates of ancestry inference using 20 to 57 SNPs for each of the two Asian populations ranged from 74.1% to 100%. Another 14 degraded DNA samples with incomplete profiling were analyzed, and the ancestry of 12 (85.7%) of those subjects was accurately assigned. We developed a 130-AISNP panel for ethnic origin differentiation between the five East and Southeast Asian populations and Caucasians. This AISNP set may be helpful for individual ancestral assignment of these populations in forensic casework.

  15. Association of the miR-196a2 C>T and miR-499 A>G polymorphisms with hepatitis B virus-related hepatocellular carcinoma risk: an updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhu SL

    2016-04-01

    Full Text Available Shao-Liang Zhu,1,* Jian-Hong Zhong,1,* Wen-Feng Gong,1,* Hang Li,2 Le-Qun Li11Department of Hepatobiliary Surgery, 2Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workBackground: This study meta-analyzed data on the possible association of the miR-196a2 C>T (rs11614913 and miR-499 A>G (rs3746444 polymorphisms with risk of hepatitis B virus (HBV-related hepatocellular carcinoma (HCC.Methods: Databases in PubMed, EMBASE, Web of Science, China BioMedicine, and Google Scholar were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association of the miR-196a2 C>T and miR-499 A>G polymorphisms with HBV-related HCC risk. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated.Results: A total of 13 studies involving 3,964 cases and 5,875 healthy controls were included. Random-effect meta-analysis showed that the T allele and TT genotype of miR-196a2 C>T were associated with significantly lower HBV-related HCC risk (allelic model, OR =0.84, 95% CI =0.71–0.99, P=0.04; homozygous model, OR =0.68, 95% CI =0.47–0.98, P=0.04. In contrast, miR-499 A>G showed no significant association with HBV-related HCC risk in either overall pooled analysis or ethnic subgroup analysis according to any of the four genetic models. Based on analysis of ethnic subgroups, neither miR-196a2 C>T nor miR-499 A>G was significantly associated with risk of HBV-related HCC in Chinese population.Conclusion: The polymorphism miR-196a2 C>T, but not miR-499 A>G, may be associated with decreased HBV-related HCC risk. These conclusions should be verified in large, well-designed studies.Keywords: microRNA, single nucleotide polymorphisms, hepatitis B virus related, meta-analysis, hepatocellular carcinoma

  16. MI Gap Clearing Kicker Magnet Design Review

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Chris; /Fermilab

    2008-10-01

    The kicker system requirements were originally conceived for the NOvA project. NOvA is a neutrino experiment located in Minnesota. To achieve the desired neutrino flux several upgrades are required to the accelerator complex. The Recycler will be used as a proton pre-injector for the Main Injector (MI). As the Recycler is the same size as the MI, it is possible to do a single turn fill ({approx}11 {micro}sec), minimizing the proton injection time in the MI cycle and maximizing the protons on target. The Recycler can then be filled with beam while the MI is ramping to extract beam to the target. To do this requires two new transfer lines. The existing Recycler injection line was designed for 10{pi} pbar beams, not the 20{pi} proton beams we anticipate from the Booster. The existing Recycler extraction line allows for proton injection through the MI, while we want direct injection from the Booster. These two lines will be decommissioned. The new injection line from the MI8 line into the Recycler will start at 848 and end with injection kickers at RR104. The new extraction line in the RR30 straight section will start with a new extraction kicker at RR232 and end with new MI injection kickers at MI308. Finally, to reduce beam loss activation in the enclosure, a new gap clearing kicker will be used to extract uncaptured beam created during the slip stack injection process down the existing dump line. It was suggested that the MI could benefit from this type of system immediately. This led to the early installation of the gap clearing system in the MI, followed by moving the system to Recycler during NOvA. The specifications also changed during this process. Initially the rise and fall time requirements were 38 ns and the field stability was {+-}1%. The 38 ns is based on having a gap of 2 RF buckets between injections. (There are 84 RF buckets that can be filled from the Booster for each injection, but 82 would be filled with beam. MI and Recycler contain 588 RF buckets

  17. Novel Insights into miRNA in Lung and Heart Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Amit Kishore

    2014-01-01

    Full Text Available MicroRNAs (miRNAs are noncoding regulatory sequences that govern posttranscriptional inhibition of genes through binding mainly at regulatory regions. The regulatory mechanism of miRNAs are influenced by complex crosstalk among single nucleotide polymorphisms (SNPs within miRNA seed region and epigenetic modifications. Circulating miRNAs exhibit potential characteristics as stable biomarker. Functionally, miRNAs are involved in basic regulatory mechanisms of cells including inflammation. Thus, miRNA dysregulation, resulting in aberrant expression of a gene, is suggested to play an important role in disease susceptibility. This review focuses on the role of miRNA as diagnostic marker in pathogenesis of lung inflammatory diseases and in cardiac remodelling events during inflammation. From recent reports, In this context, the information about the models in which miRNAs expression were investigated including types of biological samples, as well as on the methods for miRNA validation and prediction/definition of their gene targets are emphasized in the review. Besides disease pathogenesis, promising role of miRNAs in early disease diagnosis and prognostication is also discussed. However, some miRNAs are also indicated with protective role. Thus, identifications and usage of such potential miRNAs as well as disruption of disease susceptible miRNAs using antagonists, antagomirs, are imperative and may provide a novel therapeutic approach towards combating the disease progression.

  18. Single-cell behavior and population heterogeneity: solving an inverse problem to compute the intrinsic physiological state functions.

    Science.gov (United States)

    Spetsieris, Konstantinos; Zygourakis, Kyriacos

    2012-04-15

    The dynamics of isogenic cell populations can be described by cell population balance models that account for phenotypic heterogeneity. To utilize the predictive power of these models, however, we must know the rates of single-cell reaction and division and the bivariate partition probability density function. These three intrinsic physiological state (IPS) functions can be obtained by solving an inverse problem that requires knowledge of the phenotypic distributions for the overall cell population, the dividing cell subpopulation and the newborn cell subpopulation. We present here a robust computational procedure that can accurately estimate the IPS functions for heterogeneous cell populations. A detailed parametric analysis shows how the accuracy of the inverse solution is affected by discretization parameters, the type of non-parametric estimators used, the qualitative characteristics of phenotypic distributions and the unknown partitioning probability density function. The effect of finite sampling and measurement errors on the accuracy of the recovered IPS functions is also assessed. Finally, we apply the procedure to estimate the IPS functions of an E. coli population carrying an IPTG-inducible genetic toggle network. This study completes the development of an integrated experimental and computational framework that can become a powerful tool for quantifying single-cell behavior using measurements from heterogeneous cell populations. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A.

    Science.gov (United States)

    Zhang, Y; Roberts, J; Tortorici, M; Veldman, A; St Ledger, K; Feussner, A; Sidhu, J

    2017-06-01

    Essentials rVIII-SingleChain is a unique recombinant factor VIII (FVIII) molecule. A population pharmacokinetic model was based on FVIII activity of severe hemophilia A patients. The model was used to simulate factor VIII activity-time profiles for various dosing scenarios. The model supports prolonged dosing of rVIII-SingleChain with intervals of up to twice per week. Background Single-chain recombinant coagulation factor VIII (rVIII-SingleChain) is a unique recombinant coagulation factor VIII molecule. Objectives To: (i) characterize the population pharmacokinetics (PK) of rVIII-SingleChain in patients with severe hemophilia A; (ii) identify correlates of variability in rVIII-SingleChain PK; and (iii) simulate various dosing scenarios of rVIII-SingleChain. Patients/Methods A population PK model was developed, based on FVIII activity levels of 130 patients with severe hemophilia A (n = 91 for ≥ 12-65 years; n = 39 for  85% and > 93% of patients were predicted to maintain FVIII activity level above 1 IU dL -1 , at all times with three-times-weekly dosing (given on days 0, 2, and 4.5) at the lowest (20 IU kg -1 ) and highest (50 IU kg -1 ) doses, respectively. For twice weekly dosing (days 0 and 3.5) of 50 IU kg -1 rVIII-SingleChain, 62-80% of patients across all ages were predicted to maintain a FVIII activity level above 1 IU dL -1 at day 7. Conclusions The population PK model adequately characterized rVIII-SingleChain PK, and the model can be utilized to simulate FVIII activity-time profiles for various dosing scenarios. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

  20. Analysis of single hyphal growth and fragmentation in submerged cultures using a population model

    DEFF Research Database (Denmark)

    Krabben, Preben; Nielsen, Søren; Michelsen, Michael Locht

    1997-01-01

    Descriptions of population dynamics in submerged cultures are important when studying the mechanisms of growth and fragmentation of filamentous microorganisms. Population models are traditionally formulated as population balance equations. Population models of filamentous morphology are difficult...... to solve because of random fragmentation, which introduces an integral term into the population balance equations. Balances for the systemic properties, e.g. concentration of hyphal elements, substrate concentration, average total hyphal length, and average number of growing tips, are set up. Based...... on these balances one can solve the inverse problem, i.e. determination of kinetic parameters directly from measurements of the hyphal morphology. Both a Monte Carlo method and a discretization method have been used to calculate the steady-state population distribution. The two methods are compared and the Monte...

  1. Comparison on genomic predictions using three GBLUP methods and two single-step blending methods in the Nordic Holstein population

    Directory of Open Access Journals (Sweden)

    Gao Hongding

    2012-07-01

    Full Text Available Abstract Background A single-step blending approach allows genomic prediction using information of genotyped and non-genotyped animals simultaneously. However, the combined relationship matrix in a single-step method may need to be adjusted because marker-based and pedigree-based relationship matrices may not be on the same scale. The same may apply when a GBLUP model includes both genomic breeding values and residual polygenic effects. The objective of this study was to compare single-step blending methods and GBLUP methods with and without adjustment of the genomic relationship matrix for genomic prediction of 16 traits in the Nordic Holstein population. Methods The data consisted of de-regressed proofs (DRP for 5 214 genotyped and 9 374 non-genotyped bulls. The bulls were divided into a training and a validation population by birth date, October 1, 2001. Five approaches for genomic prediction were used: 1 a simple GBLUP method, 2 a GBLUP method with a polygenic effect, 3 an adjusted GBLUP method with a polygenic effect, 4 a single-step blending method, and 5 an adjusted single-step blending method. In the adjusted GBLUP and single-step methods, the genomic relationship matrix was adjusted for the difference of scale between the genomic and the pedigree relationship matrices. A set of weights on the pedigree relationship matrix (ranging from 0.05 to 0.40 was used to build the combined relationship matrix in the single-step blending method and the GBLUP method with a polygenetic effect. Results Averaged over the 16 traits, reliabilities of genomic breeding values predicted using the GBLUP method with a polygenic effect (relative weight of 0.20 were 0.3% higher than reliabilities from the simple GBLUP method (without a polygenic effect. The adjusted single-step blending and original single-step blending methods (relative weight of 0.20 had average reliabilities that were 2.1% and 1.8% higher than the simple GBLUP method, respectively. In

  2. miRNA-mediated functional changes through co-regulating function related genes.

    Directory of Open Access Journals (Sweden)

    Jie He

    Full Text Available BACKGROUND: MicroRNAs play important roles in various biological processes involving fairly complex mechanism. Analysis of genome-wide miRNA microarray demonstrate that a single miRNA can regulate hundreds of genes, but the regulative extent on most individual genes is surprisingly mild so that it is difficult to understand how a miRNA provokes detectable functional changes with such mild regulation. RESULTS: To explore the internal mechanism of miRNA-mediated regulation, we re-analyzed the data collected from genome-wide miRNA microarray with bioinformatics assay, and found that the transfection of miR-181b and miR-34a in Hela and HCT-116 tumor cells regulated large numbers of genes, among which, the genes related to cell growth and cell death demonstrated high Enrichment scores, suggesting that these miRNAs may be important in cell growth and cell death. MiR-181b induced changes in protein expression of most genes that were seemingly related to enhancing cell growth and decreasing cell death, while miR-34a mediated contrary changes of gene expression. Cell growth assays further confirmed this finding. In further study on miR-20b-mediated osteogenesis in hMSCs, miR-20b was found to enhance osteogenesis by activating BMPs/Runx2 signaling pathway in several stages by co-repressing of PPARγ, Bambi and Crim1. CONCLUSIONS: With its multi-target characteristics, miR-181b, miR-34a and miR-20b provoked detectable functional changes by co-regulating functionally-related gene groups or several genes in the same signaling pathway, and thus mild regulation from individual miRNA targeting genes could have contributed to an additive effect. This might also be one of the modes of miRNA-mediated gene regulation.

  3. Non-invasive single-trial detection of variable population spike responses in human somatosensory evoked potentials.

    Science.gov (United States)

    Waterstraat, Gunnar; Scheuermann, Manuel; Curio, Gabriel

    2016-03-01

    Somatosensory evoked potentials (SEPs) around 600 Hz ('σ-bursts') are correlates of cortical population spikes. Recently, single-trial σ-bursts were detected in human scalp EEG using 29-channel low-noise recordings in an electromagnetically shielded room. To achieve clinical applicability, this study aimed to establish a protocol using only 8 EEG channels in an unshielded environment and to quantify the variability of σ-bursts. Median nerve SEPs were recorded in 10 healthy subjects using a custom-built low-noise EEG amplifier. A detection algorithm for single-trial σ-bursts was trained as combination of spatio-temporal filters and a non-linear classifier. The single-trial responses were probed for the presence of significant increases of amplitude and variability. Single-trial σ-burst detection succeeded with Detection Rates and Positive Predictive Values above 80% in subjects with high SNR. A significant inter-trial variability in the amplitudes of early low-frequency SEPs and σ-bursts could be demonstrated. Single-trial σ-bursts can be detected on scalp-EEG using only 8 EEG channels in an electromagnetically disturbed environment. The combination of dedicated hardware and detection algorithms allows quantifying and describing their variability. The variability of population spikes in the human somatosensory cortex can be traced non-invasively in a clinical setting. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Regulation of turkey myogenic satellite cell migration by MicroRNAs miR-128 and miR-24.

    Science.gov (United States)

    Velleman, S G; Harding, R L

    2017-06-01

    Myogenic satellite cells are an adult stem cell responsible for all post-hatch muscle growth in poultry. As a stem cell population, satellite cells are highly heterogeneous, but the origin of this heterogeneity remains unclear. Heterogeneity is, in part, regulated by gene expression. One method of endogenous gene regulation that may contribute to heterogeneity is microRNAs (miRNAs). Two miRNAs previously shown to regulate poultry myogenic satellite cell proliferation and differentiation, miR-128 and miR-24, were studied to determine if they also affected satellite cell migration. Satellite cell migration is an essential step for both proliferation and differentiation. During proliferation, satellite cells will migrate and align to form new myofibers or donate their nuclei to existing myofibers leading to muscle fiber hypertrophy or regeneration. Transient transfection of miRNA specific mimics to each miRNA reduced migration of satellite cells following a cell culture scratch at 72 h of proliferation when the cultures were 90 to 100% confluent. However, only the migration in cells transfected with miR-24 mimics at 24 and 30 h following the scratch was significantly reduced (P ≤ 0.05) to around 70% of the distance migrated by controls. Alternately, transfection with inhibitors specific to miR-128 or miR-24 significantly (P ≤ 0.05) increased migration between 147 and 252% compared to their controls between 24 and 48 h following the scratch. These data demonstrate that miR-128 and miR-24 play a role in myogenic satellite cell migration, which will impact muscle development and growth. © 2016 Poultry Science Association Inc.

  5. Computational identification of putative miRNAs and their target genes in pathogenic amoeba Naegleria fowleri.

    Science.gov (United States)

    Padmashree, Dyavegowda; Swamy, Narayanaswamy Ramachandra

    2015-01-01

    Naegleria fowleri is a parasitic unicellular free living eukaryotic amoeba. The parasite spreads through contaminated water and causes primary amoebic meningoencephalitis (PAM). Therefore, it is of interest to understand its molecular pathogenesis. Hence, we analyzed the parasite genome for miRNAs (microRNAs) that are non-coding, single stranded RNA molecules. We identified 245 miRNAs using computational methods in N. fowleri, of which five miRNAs are conserved. The predicted miRNA targets were analyzed by using miRanda (software) and further studied the functions by subsequently annotating using AmiGo (a gene ontology web tool).

  6. Complete transfer of populations from a single state to a preselected superposition of states using piecewise adiabatic passage: Experiment

    International Nuclear Information System (INIS)

    Zhdanovich, S.; Shapiro, E. A.; Hepburn, J. W.; Shapiro, M.; Milner, V.

    2009-01-01

    We demonstrate a method of adiabatic population transfer from a single quantum state into a coherent superposition of states. The transfer is executed with femtosecond pulses, spectrally shaped in a simple and intuitive manner, which does not require iterative feedback-controlled loops. In contrast to nonadiabatic methods of excitation, our approach is not sensitive to the exact value of laser intensity. We show that the population transfer is complete, and analyze the possibility of controlling the relative phases and amplitudes of the excited eigenstates. We discuss the limitations of the proposed control methods due to the dynamic level shifts and suggest ways of reducing their influence.

  7. The miRNA Mirage: How Close Are We to Finding a Non-Invasive Diagnostic Biomarker in Endometriosis? A Systematic Review

    Directory of Open Access Journals (Sweden)

    Swati Agrawal

    2018-02-01

    . miR-17-5p/20a, miR-200, miR-199a, miR-143, and miR-145 were explored for their pivotal role in the aetiopathogenesis of endometriosis. Wider implications: It is emerging that miRNAs play a central role in the pathogenesis of endometriosis and have the potential of being promising biomarkers. Circulating miRNAs as a non-invasive diagnostic tool may shorten the delay in the diagnosis of the disease, thus alleviating the suffering of women and reducing the burden on health care systems. However, despite numerous studies on circulating miRNAs in endometriosis, no single miRNA or any panel of them seems to meet the criteria of a diagnostic biomarker. The disagreement between the various studies upholds the demand of larger, well-controlled systematic validation studies with uniformity in the research approaches and involving diverse populations.

  8. The miRNA Mirage: How Close Are We to Finding a Non-Invasive Diagnostic Biomarker in Endometriosis? A Systematic Review

    Science.gov (United States)

    Agrawal, Swati; Tapmeier, Thomas T.; Rahmioglu, Nilufer; Kirtley, Shona; Zondervan, Krina T.; Becker, Christian M.

    2018-01-01

    , miR-200, miR-199a, miR-143, and miR-145 were explored for their pivotal role in the aetiopathogenesis of endometriosis. Wider implications: It is emerging that miRNAs play a central role in the pathogenesis of endometriosis and have the potential of being promising biomarkers. Circulating miRNAs as a non-invasive diagnostic tool may shorten the delay in the diagnosis of the disease, thus alleviating the suffering of women and reducing the burden on health care systems. However, despite numerous studies on circulating miRNAs in endometriosis, no single miRNA or any panel of them seems to meet the criteria of a diagnostic biomarker. The disagreement between the various studies upholds the demand of larger, well-controlled systematic validation studies with uniformity in the research approaches and involving diverse populations. PMID:29463003

  9. Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

    OpenAIRE

    Rose, Trine H?yer; R?shammar, Daniel; Erichsen, Lars; Grundemar, Lars; Ottesen, Johnny T.

    2016-01-01

    Objective The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6?) developed for controlled ovarian stimulation prior to assisted reproductive technologies. Methods Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450?IU in 27 pituitary-suppressed healthy female subjects...

  10. Mitochondrial Genome Diversity of Native Americans Supports a Single Early Entry of Founder Populations into America

    OpenAIRE

    Silva Jr., Wilson A.; Bonatto, Sandro L.; Holanda, Adriano J.; Ribeiro-dos-Santos, Andrea K.; Paixão, Beatriz M.; Goldman, Gustavo H.; Abe-Sandes, Kiyoko; Rodriguez-Delfin, Luis; Barbosa, Marcela; Paçó-Larson, Maria Luiza; Petzl-Erler, Maria Luiza; Valente, Valeria; Santos, Sidney E. B.; Zago, Marco A.

    2002-01-01

    There is general agreement that the Native American founder populations migrated from Asia into America through Beringia sometime during the Pleistocene, but the hypotheses concerning the ages and the number of these migrations and the size of the ancestral populations are surrounded by controversy. DNA sequence variations of several regions of the genome of Native Americans, especially in the mitochondrial DNA (mtDNA) control region, have been studied as a tool to help answer these questions...

  11. Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways.

    Science.gov (United States)

    Wilfred, Bernard R; Wang, Wang-Xia; Nelson, Peter T

    2007-07-01

    MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first discovered in worm larvae, miRNAs play fundamental biological roles-including in humans-well beyond development. MiRNAs participate in the regulation of metabolism (including lipid metabolism) for all animal species studied. A review of the fascinating and fast-growing literature on miRNA regulation of metabolism can be parsed into three main categories: (1) adipocyte biochemistry and cell fate determination; (2) regulation of metabolic biochemistry in invertebrates; and (3) regulation of metabolic biochemistry in mammals. Most research into the 'function' of a given miRNA in metabolic pathways has concentrated on a given miRNA acting upon a particular 'target' mRNA. Whereas in some biological contexts the effects of a given miRNA:mRNA pair may predominate, this might not be the case generally. In order to provide an example of how a single miRNA could regulate multiple 'target' mRNAs or even entire human metabolic pathways, we include a discussion of metabolic pathways that are predicted to be regulated by the miRNA paralogs, miR-103 and miR-107. These miRNAs, which exist in vertebrate genomes within introns of the pantothenate kinase (PANK) genes, are predicted by bioinformatics to affect multiple mRNA targets in pathways that involve cellular Acetyl-CoA and lipid levels. Significantly, PANK enzymes also affect these pathways, so the miRNA and 'host' gene may act synergistically. These predictions require experimental verification. In conclusion, a review of the literature on miRNA regulation of metabolism leads us believe that the future will provide researchers with many additional energizing revelations.

  12. A Chrysodeixis chalcites single-nucleocapsid nucleopolyhedrovirus population from the Canary Islands is genotypically structured to maximize survival.

    Science.gov (United States)

    Bernal, Alexandra; Simón, Oihane; Williams, Trevor; Muñoz, Delia; Caballero, Primitivo

    2013-12-01

    A Chrysodeixis chalcites single-nucleocapsid nucleopolyhedrovirus wild-type isolate from the Canary Islands, Spain, named ChchSNPV-TF1 (ChchTF1-wt), appears to have great potential as the basis for a biological insecticide for control of the pest. An improved understanding of the genotypic structure of this wild-type strain population should facilitate the selection of genotypes for inclusion in a bioinsecticidal product. Eight genetically distinct genotypes were cloned in vitro: ChchTF1-A to ChchTF1-H. Quantitative real-time PCR (qPCR) analysis confirmed that ChchTF1-A accounted for 36% of the genotypes in the wild-type population. In bioassays, ChchTF1-wt occlusion bodies (OBs) were significantly more pathogenic than any of the component single-genotype OBs, indicating that genotype interactions were likely responsible for the pathogenicity phenotype of wild-type OBs. However, the wild-type population was slower killing and produced higher OB yields than any of the single genotypes alone. These results strongly suggested that the ChchTF1-wt population is structured to maximize its transmission efficiency. Experimental OB mixtures and cooccluded genotype mixtures containing the most abundant and the rarest genotypes, at frequencies similar to those at which they were isolated, revealed a mutualistic interaction that restored the pathogenicity of OBs. In OB and cooccluded mixtures containing only the most abundant genotypes, ChchTF1-ABC, OB pathogenicity was even greater than that of wild-type OBs. The ChchTF1-ABC cooccluded mixture killed larvae 33 h faster than the wild-type population and remained genotypically and biologically stable throughout five successive passages in vivo. In conclusion, the ChchTF1-ABC mixture shows great potential as the active ingredient of a bioinsecticide to control C. chalcites in the Canary Islands.

  13. Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD-2.

    Directory of Open Access Journals (Sweden)

    Geon-Woo Kim

    2016-07-01

    Full Text Available The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV. Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt prototype miR-122 is modified at its 3' end by 3'-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3'-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3' end. The HCV core protein specifically inhibited GLD-2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation.

  14. Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD-2.

    Science.gov (United States)

    Kim, Geon-Woo; Lee, Seung-Hoon; Cho, Hee; Kim, Minwoo; Shin, Eui-Cheol; Oh, Jong-Won

    2016-07-01

    The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt) prototype miR-122 is modified at its 3' end by 3'-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3'-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3' end. The HCV core protein specifically inhibited GLD-2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation.

  15. Chromosome 9p21 genetic variants are associated with myocardial infarction but not with ischemic stroke in a Taiwanese population.

    Science.gov (United States)

    Lin, Hsiu-Fen; Tsai, Pei-Chien; Liao, Yi-Chu; Lin, Tsung-Hsien; Tai, Chih-Ta; Juo, Suh-Hang Hank; Lin, Ruey-Tay

    2011-08-01

    Genetic variants on chromosome 9p21 confer a robust risk for coronary artery disease but inconsistent risk for stroke. This study investigated whether such genetic variants exert differential risks on myocardial infarction (MI) and ischemic stroke in a Taiwanese population. The study recruited 425 MI patients, 687 patients with ischemic stroke, and 1377 healthy controls. Four key single nucleotide polymorphisms (SNPs) on chromosome 9p21 were genotyped. Multivariate permutation analyses demonstrated that the risk T allele of rs1333040 and G allele of rs2383207 were associated with MI (P = 0.045 and 0.002, respectively). Subjects with the rs2383207 GG genotype had a 1.85-fold (P = 0.021) risk for MI when compared with the subjects with the AA genotype. Further analysis showed that significant results only exist in the young MI group (stroke (adjusted P ranged from 0.097 to 0.540). Haplotype analysis showed global P values of 0.032 for MI and 0.290 for stroke. Genetic variations in the 9p21 region are associated with MI but not with stroke in a Taiwanese population. Early-onset MI was more likely to carry the risk genotypes of 9p21 SNPs.

  16. Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Röshammar, Daniel; Erichsen, Lars

    2016-01-01

    Objective: The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6) developed for controlled ovarian stimulation prior to assisted...... effects population pharmacokinetic modelling in NONMEM 7.2.0. Results: A one-compartment model with first-order absorption and elimination rates was found to best describe the data. A transit model was introduced to describe a delay in the absorption process. The apparent clearance (CL/F) and apparent...... volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F. Conclusions: The single-dose pharmacokinetics of FE 999049 were adequately described by a population...

  17. Single cell cytometry of protein function in RNAi treated cells and in native populations

    Directory of Open Access Journals (Sweden)

    Hill Andrew

    2008-08-01

    Full Text Available Abstract Background High Content Screening has been shown to improve results of RNAi and other perturbations, however significant intra-sample heterogeneity is common and can complicate some analyses. Single cell cytometry can extract important information from subpopulations within these samples. Such approaches are important for immune cells analyzed by flow cytometry, but have not been broadly available for adherent cells that are critical to the study of solid-tumor cancers and other disease models. Results We have directly quantitated the effect of resolving RNAi treatments at the single cell level in experimental systems for both exogenous and endogenous targets. Analyzing the effect of an siRNA that targets GFP at the single cell level permits a stronger measure of the absolute function of the siRNA by gating to eliminate background levels of GFP intensities. Extending these methods to endogenous proteins, we have shown that well-level results of the knockdown of PTEN results in an increase in phospho-S6 levels, but at the single cell level, the correlation reveals the role of other inputs into the pathway. In a third example, reduction of STAT3 levels by siRNA causes an accumulation of cells in the G1 phase of the cell cycle, but does not induce apoptosis or necrosis when compared to control cells that express the same levels of STAT3. In a final example, the effect of reduced p53 levels on increased adriamycin sensitivity for colon carcinoma cells was demonstrated at the whole-well level using siRNA knockdown and in control and untreated cells at the single cell level. Conclusion We find that single cell analysis methods are generally applicable to a wide range of experiments in adherent cells using technology that is becoming increasingly available to most laboratories. It is well-suited to emerging models of signaling dysfunction, such as oncogene addition and oncogenic shock. Single cell cytometry can demonstrate effects on cell

  18. Not a single but multiple populations of GABAergic neurons control sleep.

    Science.gov (United States)

    Luppi, Pierre-Hervé; Peyron, Christelle; Fort, Patrice

    2017-04-01

    The role of gamma-amino butyric acid (GABA) in sleep induction and maintenance is well accepted since most insomnia treatments target GABAa receptors. However, the population(s) of GABAergic neurons involved in the beneficial effect of GABA on sleep remains to be identified. This is not an easy task since GABAergic neurons are widely distributed in all brain structures. A recently growing number of populations of GABAergic neurons have been involved in sleep control. We first review here possible candidates for inducing non-rapid eye movement (NREM) sleep including the GABAergic neurons of the ventrolateral preoptic area, the parafacial zone in the brainstem, the nucleus accumbens and the cortex. We also discuss the role of several populations of GABAergic neurons in rapid eye movement (REM) sleep control. Indeed, it is well accepted that muscle atonia occurring during REM sleep is due to a GABA/glycinergic hyperpolarization of motoneurons. Recent evidence strongly suggests that these neurons are located in the ventral medullary reticular formation. It has also recently been shown that neurons containing the neuropeptide melanin concentrating hormone and GABA located in the lateral hypothalamic area control REM sleep expression. Finally, a population of REM-off GABAergic neurons located in the ventrolateral periaqueductal gray has been shown to gate REM sleep by inhibiting glutamatergic neurons located in the sublaterodorsal tegmental nucleus. In summary, recent data clearly indicate that multiple populations of GABAergic neurons located throughout the brain from the cortex to the medulla oblongata control NREM and REM sleep. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Impact of Type 2 Myocardial Infarction (MI) on Hospital-Level MI Outcomes: Implications for Quality and Public Reporting.

    Science.gov (United States)

    Arora, Sameer; Strassle, Paula D; Qamar, Arman; Wheeler, Evan N; Levine, Alexandra L; Misenheimer, Jacob A; Cavender, Matthew A; Stouffer, George A; Kaul, Prashant

    2018-03-26

    The International Classification of Diseases (ICD) coding system does not recognize type 2 myocardial infarction (MI) as a separate entity; therefore, patients with type 2 MI continue to be categorized under the general umbrella of non-ST-segment-elevation myocardial infarction (NSTEMI). We aim to evaluate the impact of type 2 MI on hospital-level NSTEMI metrics and discuss the implications for quality and public reporting. We conducted a single-center retrospective analysis of 1318 patients discharged with a diagnosis of NSTEMI between July 2013 and October 2014. The Third Universal Definition was used to define type 1 and type 2 MI. Weighted Kaplan-Meier curves were used to analyze risk of mortality and readmission. Overall, 1039 patients met NSTEMI criteria per the Third Universal Definition; of those, 264 (25.4%) had type 2 MI. Patients with type 2 MI were older, were more likely to have chronic kidney disease, and had lower peak troponin levels. Compared with type 1 MI patients, those with type 2 MI had higher inpatient mortality (17.4% versus 4.7%, P <0.0001) and were more likely to die from noncardiovascular causes (71.7% versus 25.0%, P <0.0001). Despite weighting for patient characteristics and discharge medications, patients with type 2 MI had higher mortality at both 30 days (risk ratio: 3.63; 95% confidence interval, 1.67-7.88) and 1 year (risk ratio: 1.98; 95% confidence interval, 1.44-2.73) after discharge. Type 2 MI was also associated with a lower 30-day cardiovascular-related readmission (risk ratio: 0.49; 95% confidence interval, 0.12-2.06). NSTEMI metrics are significantly affected by type 2 MI patients. Type 2 MI patients have distinct etiologies, are managed differently, and have higher mortality compared with patients with type 1 MI. Moving forward, it may be appropriate to exclude type 2 MI data from NSTEMI quality metrics. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  20. Heterogeneity of Metazoan Cells and Beyond: To Integrative Analysis of Cellular Populations at Single-Cell Level.

    Science.gov (United States)

    Barteneva, Natasha S; Vorobjev, Ivan A

    2018-01-01

    In this paper, we review some of the recent advances in cellular heterogeneity and single-cell analysis methods. In modern research of cellular heterogeneity, there are four major approaches: analysis of pooled samples, single-cell analysis, high-throughput single-cell analysis, and lately integrated analysis of cellular population at a single-cell level. Recently developed high-throughput single-cell genetic analysis methods such as RNA-Seq require purification step and destruction of an analyzed cell often are providing a snapshot of the investigated cell without spatiotemporal context. Correlative analysis of multiparameter morphological, functional, and molecular information is important for differentiation of more uniform groups in the spectrum of different cell types. Simplified distributions (histograms and 2D plots) can underrepresent biologically significant subpopulations. Future directions may include the development of nondestructive methods for dissecting molecular events in intact cells, simultaneous correlative cellular analysis of phenotypic and molecular features by hybrid technologies such as imaging flow cytometry, and further progress in supervised and non-supervised statistical analysis algorithms.

  1. Laser capture microdissection of enriched populations of neurons or single neurons for gene expression analysis after traumatic brain injury.

    Science.gov (United States)

    Boone, Deborah R; Sell, Stacy L; Hellmich, Helen Lee

    2013-04-10

    Long-term cognitive disability after TBI is associated with injury-induced neurodegeneration in the hippocampus-a region in the medial temporal lobe that is critical for learning, memory and executive function. Hence our studies focus on gene expression analysis of specific neuronal populations in distinct subregions of the hippocampus. The technique of laser capture microdissection (LCM), introduced in 1996 by Emmert-Buck, et al., has allowed for significant advances in gene expression analysis of single cells and enriched populations of cells from heterogeneous tissues such as the mammalian brain that contains thousands of functional cell types. We use LCM and a well established rat model of traumatic brain injury (TBI) to investigate the molecular mechanisms that underlie the pathogenesis of TBI. Following fluid-percussion TBI, brains are removed at pre-determined times post-injury, immediately frozen on dry ice, and prepared for sectioning in a cryostat. The rat brains can be embedded in OCT and sectioned immediately, or stored several months at -80 °C before sectioning for laser capture microdissection. Additionally, we use LCM to study the effects of TBI on circadian rhythms. For this, we capture neurons from the suprachiasmatic nuclei that contain the master clock of the mammalian brain. Here, we demonstrate the use of LCM to obtain single identified neurons (injured and degenerating, Fluoro-Jade-positive, or uninjured, Fluoro-Jade-negative) and enriched populations of hippocampal neurons for subsequent gene expression analysis by real time PCR and/or whole-genome microarrays. These LCM-enabled studies have revealed that the selective vulnerability of anatomically distinct regions of the rat hippocampus are reflected in the different gene expression profiles of different populations of neurons obtained by LCM from these distinct regions. The results from our single-cell studies, where we compare the transcriptional profiles of dying and adjacent surviving

  2. Single stellar populations in the near-infrared. I. Preparation of the IRTF spectral stellar library

    NARCIS (Netherlands)

    Meneses-Goytia, S.; Peletier, R. F.; Trager, S. C.; Falcón-Barroso, J.; Koleva, M.; Vazdekis, A.

    2015-01-01

    We present a detailed study of the stars of the NASA InfraRed Telescope Facility (IRTF) spectral library to understand its full extent and reliability for use with stellar population (SP) modeling. The library consist of 210 stars, with a total of 292 spectra, covering the wavelength range of 0.94

  3. Impact of environmental colored noise in single-species population dynamics

    Science.gov (United States)

    Spanio, Tommaso; Hidalgo, Jorge; Muñoz, Miguel A.

    2017-10-01

    Variability on external conditions has important consequences for the dynamics and the organization of biological systems. In many cases, the characteristic timescale of environmental changes as well as their correlations play a fundamental role in the way living systems adapt and respond to it. A proper mathematical approach to understand population dynamics, thus, requires approaches more refined than, e.g., simple white-noise approximations. To shed further light onto this problem, in this paper we propose a unifying framework based on different analytical and numerical tools available to deal with "colored" environmental noise. In particular, we employ a "unified colored noise approximation" to map the original problem into an effective one with white noise, and then we apply a standard path integral approach to gain analytical understanding. For the sake of specificity, we present our approach using as a guideline a variation of the contact process—which can also be seen as a birth-death process of the Malthus-Verhulst class—where the propagation or birth rate varies stochastically in time. Our approach allows us to tackle in a systematic manner some of the relevant questions concerning population dynamics under environmental variability, such as determining the stationary population density, establishing the conditions under which a population may become extinct, and estimating extinction times. We focus on the emerging phase diagram and its possible phase transitions, underlying how these are affected by the presence of environmental noise time-correlations.

  4. Barcoding bias in high-throughput multiplex sequencing of miRNA.

    Science.gov (United States)

    Alon, Shahar; Vigneault, Francois; Eminaga, Seda; Christodoulou, Danos C; Seidman, Jonathan G; Church, George M; Eisenberg, Eli

    2011-09-01

    Second-generation sequencing is gradually becoming the method of choice for miRNA detection and expression profiling. Given the relatively small number of miRNAs and improvements in DNA sequencing technology, studying miRNA expression profiles of multiple samples in a single flow cell lane becomes feasible. Multiplexing strategies require marking each miRNA library with a DNA barcode. Here we report that barcodes introduced through adapter ligation confer significant bias on miRNA expression profiles. This bias is much higher than the expected Poisson noise and masks significant expression differences between miRNA libraries. This bias can be eliminated by adding barcodes during PCR amplification of libraries. The accuracy of miRNA expression measurement in multiplexed experiments becomes a function of sample number.

  5. Social perceptions of single-use plastic consumption of the Balinese population

    OpenAIRE

    Lopez Murcia Martin, Javier

    2015-01-01

    The island of Bali has suffered from an increasing amount of single-use plastics being littered into the environment during the past few years. This research aims to determine the social perceptions of plastic bags and bottles in particular, through consumption habits, the degree of awareness of environmental impacts and the willingness to reduce their consumption. The methodology is based on a survey approach and literature review contrasting the characteristics of plastic bottles and bags, ...

  6. Increased frequency of single base substitutions in a population of transcripts expressed in cancer cells

    Directory of Open Access Journals (Sweden)

    Bianchetti Laurent

    2012-11-01

    Full Text Available Abstract Background Single Base Substitutions (SBS that alter transcripts expressed in cancer originate from somatic mutations. However, recent studies report SBS in transcripts that are not supported by the genomic DNA of tumor cells. Methods We used sequence based whole genome expression profiling, namely Long-SAGE (L-SAGE and Tag-seq (a combination of L-SAGE and deep sequencing, and computational methods to identify transcripts with greater SBS frequencies in cancer. Millions of tags produced by 40 healthy and 47 cancer L-SAGE experiments were compared to 1,959 Reference Tags (RT, i.e. tags matching the human genome exactly once. Similarly, tens of millions of tags produced by 7 healthy and 8 cancer Tag-seq experiments were compared to 8,572 RT. For each transcript, SBS frequencies in healthy and cancer cells were statistically tested for equality. Results In the L-SAGE and Tag-seq experiments, 372 and 4,289 transcripts respectively, showed greater SBS frequencies in cancer. Increased SBS frequencies could not be attributed to known Single Nucleotide Polymorphisms (SNP, catalogued somatic mutations or RNA-editing enzymes. Hypothesizing that Single Tags (ST, i.e. tags sequenced only once, were indicators of SBS, we observed that ST proportions were heterogeneously distributed across Embryonic Stem Cells (ESC, healthy differentiated and cancer cells. ESC had the lowest ST proportions, whereas cancer cells had the greatest. Finally, in a series of experiments carried out on a single patient at 1 healthy and 3 consecutive tumor stages, we could show that SBS frequencies increased during cancer progression. Conclusion If the mechanisms generating the base substitutions could be known, increased SBS frequency in transcripts would be a new useful biomarker of cancer. With the reduction of sequencing cost, sequence based whole genome expression profiling could be used to characterize increased SBS frequency in patient’s tumor and aid diagnostic.

  7. Increased frequency of single base substitutions in a population of transcripts expressed in cancer cells

    International Nuclear Information System (INIS)

    Bianchetti, Laurent; Kieffer, David; Féderkeil, Rémi; Poch, Olivier

    2012-01-01

    Single Base Substitutions (SBS) that alter transcripts expressed in cancer originate from somatic mutations. However, recent studies report SBS in transcripts that are not supported by the genomic DNA of tumor cells. We used sequence based whole genome expression profiling, namely Long-SAGE (L-SAGE) and Tag-seq (a combination of L-SAGE and deep sequencing), and computational methods to identify transcripts with greater SBS frequencies in cancer. Millions of tags produced by 40 healthy and 47 cancer L-SAGE experiments were compared to 1,959 Reference Tags (RT), i.e. tags matching the human genome exactly once. Similarly, tens of millions of tags produced by 7 healthy and 8 cancer Tag-seq experiments were compared to 8,572 RT. For each transcript, SBS frequencies in healthy and cancer cells were statistically tested for equality. In the L-SAGE and Tag-seq experiments, 372 and 4,289 transcripts respectively, showed greater SBS frequencies in cancer. Increased SBS frequencies could not be attributed to known Single Nucleotide Polymorphisms (SNP), catalogued somatic mutations or RNA-editing enzymes. Hypothesizing that Single Tags (ST), i.e. tags sequenced only once, were indicators of SBS, we observed that ST proportions were heterogeneously distributed across Embryonic Stem Cells (ESC), healthy differentiated and cancer cells. ESC had the lowest ST proportions, whereas cancer cells had the greatest. Finally, in a series of experiments carried out on a single patient at 1 healthy and 3 consecutive tumor stages, we could show that SBS frequencies increased during cancer progression. If the mechanisms generating the base substitutions could be known, increased SBS frequency in transcripts would be a new useful biomarker of cancer. With the reduction of sequencing cost, sequence based whole genome expression profiling could be used to characterize increased SBS frequency in patient’s tumor and aid diagnostic

  8. MiDAS

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Kirkegaard, Rasmus Hansen; McIlroy, Bianca

    A deep understanding of the microbial communities and dynamics in wastewater treatment systems is a powerful tool for process optimization and design (Rittmann et al., 2006). With the advent of amplicon sequencing of the 16S rRNA gene, the diversity within the microbial communities can now...... web platform about the microbes in activated sludge and their associated ADs. The MiDAS taxonomy proposes putative names for each genus-level-taxon that can be used as a common vocabulary for all researchers in the field....

  9. Association analysis of two single-nucleotide polymorphisms of the RELN gene with autism in the South African population

    KAUST Repository

    Sharma, Jyoti Rajan

    2013-02-01

    Background: Autism (MIM209850) is a neurodevelopmental disorder characterized by a triad of impairments, namely impairment in social interaction, impaired communication skills, and restrictive and repetitive behavior. A number of family and twin studies have demonstrated that genetic factors play a pivotal role in the etiology of autistic disorder. Various reports of reduced levels of reelin protein in the brain and plasma in autistic patients highlighted the role of the reelin gene (RELN) in autism. There is no such published study on the South African (SA) population. Aims: The aim of the present study was to find the genetic association of intronic rs736707 and exonic rs362691 (single-nucleotide polymorphisms [SNPs] of the RELN gene) with autism in a SA population. Methods: Genomic DNA was isolated from cheek cell swabs from autistic (136) as well as control (208) subjects. The TaqMan ® Real-Time polymerase chain reaction and genotyping assay was utilized to determine the genotypes. Results: A significant association of SNP rs736707, but not for SNP rs362691, with autism in the SA population is observed. Conclusion: There might be a possible role of RELN in autism, especially for SA populations. The present study represents the first report on genetic association studies on the RELN gene in the SA population. © 2013, Mary Ann Liebert, Inc.

  10. Using enhanced green fluorescent protein (EGFP) promoter fusions to study gene regulation at single cell and population levels.

    Science.gov (United States)

    Utratna, Marta; O'Byrne, Conor P

    2014-01-01

    Reporter gene fusions based on the enhanced green fluorescent protein (EGFP) are powerful experimental tools that allow real-time changes in gene expression to be monitored both in single cells and in populations. Here we describe the development of a chromosomally integrated transcriptional reporter fusion in Listeria monocytogenes that allows real-time measurements of gene expression. To construct a single copy of an EGFP-based fluorescent reporter fused to a promoter of interest (Px) in L. monocytogenes, a suicide shuttle vector carrying the Px::egfp gene fusion is first constructed in Escherichia coli (as an intermediate host). Then, the vector is transformed into L. monocytogenes and integrated into its chromosome by homologous recombination within the selected promoter region. Subsequently, analysis of fluorescence exhibited by cells carrying a single copy reporter can be performed under selected experimental conditions by stringent sample preparation, optimized image acquisition, and processing of the digital data with the image analysis freeware ImageJ. Thus, the methodology described here can be adapted to investigate the activity and regulation of any promoter in L. monocytogenes both at the cell and population levels.

  11. Single locus typing of MHC class I and class II B loci in a population of red jungle fowl.

    Science.gov (United States)

    Worley, K; Gillingham, M; Jensen, P; Kennedy, L J; Pizzari, T; Kaufman, J; Richardson, D S

    2008-05-01

    In species with duplicated major histocompatibility complex (MHC) genes, estimates of genetic variation often rely on multilocus measures of diversity. It is possible that such measures might not always detect more detailed patterns of selection at individual loci. Here, we describe a method that allows us to investigate classical MHC diversity in red jungle fowl (Gallus gallus), the wild ancestor of the domestic chicken, using a single locus approach. This is possible due to the well-characterised gene organisation of the 'minimal essential' MHC (BF/BL region) of the domestic chicken, which comprises two differentially expressed duplicated class I (BF) and two class II B (BLB) genes. Using a combination of reference strand-mediated conformation analysis, cloning and sequencing, we identify nine BF and ten BLB alleles in a captive population of jungle fowl. We show that six BF and five BLB alleles are from the more highly expressed locus of each gene, BF2 and BLB2, respectively. An excess of non-synonymous substitutions across the jungle fowl BF/BL region suggests that diversifying selection has acted on this population. Importantly, single locus screening reveals that the strength of selection is greatest on the highly expressed BF2 locus. This is the first time that a population of red jungle fowl has been typed at the MHC region, laying the basis for further research into the underlying processes acting to maintain MHC diversity in this and other species.

  12. Estimates for Genetic Variance Components in Reciprocal Recurrent Selection in Populations Derived from Maize Single-Cross Hybrids

    Directory of Open Access Journals (Sweden)

    Matheus Costa dos Reis

    2014-01-01

    Full Text Available This study was carried out to obtain the estimates of genetic variance and covariance components related to intra- and interpopulation in the original populations (C0 and in the third cycle (C3 of reciprocal recurrent selection (RRS which allows breeders to define the best breeding strategy. For that purpose, the half-sib progenies of intrapopulation (P11 and P22 and interpopulation (P12 and P21 from populations 1 and 2 derived from single-cross hybrids in the 0 and 3 cycles of the reciprocal recurrent selection program were used. The intra- and interpopulation progenies were evaluated in a 10×10 triple lattice design in two separate locations. The data for unhusked ear weight (ear weight without husk and plant height were collected. All genetic variance and covariance components were estimated from the expected mean squares. The breakdown of additive variance into intrapopulation and interpopulation additive deviations (στ2 and the covariance between these and their intrapopulation additive effects (CovAτ found predominance of the dominance effect for unhusked ear weight. Plant height for these components shows that the intrapopulation additive effect explains most of the variation. Estimates for intrapopulation and interpopulation additive genetic variances confirm that populations derived from single-cross hybrids have potential for recurrent selection programs.

  13. Brief communication genotyping of Burkholderia pseudomallei revealed high genetic variability among isolates from a single population group.

    Science.gov (United States)

    Zueter, Abdelrahman Mohammad; Rahman, Zaidah Abdul; Yean, Chan Yean; Harun, Azian

    2015-01-01

    Burkholderia pseudomallei is a soil dwelling Gram-negative bacteria predominates in Southeast Asia zone and the tropical part of Australia. Genetic diversity has been explored among various populations and environments worldwide. To date, little data is available on MLST profiling of clinical B. pseudomallei isolates in peninsular Malaysia. In this brief report, thirteen culture positive B. pseudomallei cases collected from a single population of Terengganu state in the Western Peninsular Malaysia and were confirmed by In-house TTS1-PCR. Isolates were subjected for multi-locus sequence typing (MLST) to explore their genotypic diversity and to investigate for possible clonal clustering of a certain sequence type. Patient's clinical information was examined to investigate for clinical correlation among the different genotypes. In spite of small sample set, MLST results indicated predictive results; considerable genotypic diversity, predominance and novelty among B. pseudomallei collected over a single geographically-located population in Malaysia. Massive genotypic heterogeneity was observed; 8 different sequence types with predominance of sequence type 54 and discovery of two novel sequence types. However, no clear pathogenomic or organ tropism clonal relationships were predicted.

  14. Diversity of knockdown resistance alleles in a single house fly population facilitates adaptation to pyrethroid insecticides.

    Science.gov (United States)

    Kasai, S; Sun, H; Scott, J G

    2017-02-01

    Insecticide use exerts a tremendous selection force on house fly populations, but the frequencies of the initial resistance mutations may not reach high levels if they have a significant fitness cost in the absence of insecticides. However, with the continued use of the same (or similar) insecticides, it is expected that new mutations (conferring equal or greater resistance, but less of a fitness cost) will evolve. Pyrethroid insecticides target the insect voltage sensitive sodium channel (VSSC) and have been widely used for control of house flies at animal production facilities for more than three decades. There are three Vssc mutations known that cause resistance to pyrethroids in house flies: knockdown resistance (kdr, L1014F), kdr-his (L1014H) and super-kdr (M918T + L1014F). Whether or not there are any new mutations in house fly populations has not been examined for decades. We collected house flies from a dairy in Kansas (USA) and selected this population for three generations. We discovered multiple new Vssc alleles, including two that give very high levels of resistance to most pyrethroids. The importance of these findings to understanding the evolution of insecticide resistance, designing appropriate resistance monitoring and management schemes, and the future of pyrethroids for house fly control are discussed. © 2016 The Royal Entomological Society.

  15. Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects

    Directory of Open Access Journals (Sweden)

    Kirsch Lee E

    2009-12-01

    Full Text Available Abstract Background The population pharmacokinetics of artesunate (AS and its active metabolite dihydroartemisinin (DHA were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR or as a monotherapy with or without food. Methods Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability parameter estimates. Results A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka of 3.85 h-1. The population estimates of apparent clearance (CL/F and volume of distribution (V2/F for AS were 1190 L/h with 36.2% inter-individual variability (IIV and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F and central volume of distribution (V3/F were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F and peripheral volume of distribution (V4/F for DHA were 5.74 L/h and 18.5 L, respectively. Intake of high-fat and high-caloric meal prior to the drug administration resulted in 84% reduction in Ka. Body weight impacted CLM/F, such that a unit change in

  16. In-vitro activity of taurolidine on single species and a multispecies population associated with periodontitis.

    Science.gov (United States)

    Zollinger, Lilly; Schnyder, Simone; Nietzsche, Sandor; Sculean, Anton; Eick, Sigrun

    2015-04-01

    The antimicrobial activity of taurolidine was compared with minocycline against microbial species associated with periodontitis (four single strains and a 12-species mixture). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs), killing as well as activities on established and forming single-species biofilms and a 12-species biofilm were determined. The MICs of taurolidine against single species were always 0.31 mg/ml, the MBCs were 0.64 mg/ml. The used mixed microbiota was less sensitive to taurolidine, MIC and the MBC was 2.5 mg/ml. The strains and the mixture were completely killed by 2.5 mg/ml taurolidine, whereas 256 μg/ml minocycline reduced the bacterial counts of the mixture by 5 log10 colony forming units (cfu). Coating the surface with 10 mg/ml taurolidine or 256 μg/ml minocycline prevented completely biofilm formation of Porphyromonas gingivalis ATCC 33277 but not of Aggregatibacter actinomycetemcomitans Y4 and the mixture. On 4.5 d old biofilms, taurolidine acted concentration dependent with a reduction by 5 log10 cfu (P. gingivalis ATCC 33277) and 7 log10 cfu (A. actinomycetemcomitans Y4) when applying 10 mg/ml. Minocycline decreased the cfu counts by 1-2 log10 cfu independent of the used concentration. The reduction of the cfu counts in the 4.5 d old multi-species biofilms was about 3 log10 cfu after application of any minocycline concentration and after using 10 mg/ml taurolidine. Taurolidine is active against species associated with periodontitis, even within biofilms. Nevertheless a complete elimination of complex biofilms by taurolidine seems to be impossible and underlines the importance of a mechanical removal of biofilms prior to application of taurolidine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Quantification of miRNAs by a simple and specific qPCR method

    DEFF Research Database (Denmark)

    Cirera Salicio, Susanna; Busk, Peter K.

    2014-01-01

    RNA expression levels in different systems. In this chapter we describe a PCR method for quantification of miRNAs based on a single reverse transcription reaction for all miRNAs combined with real-time PCR with two miRNA-specific DNA primers. This method quantifies synthetic templates over eight orders...... of magnitude and successfully discriminates miRNAs that differ by one single nucleotide. Due to the usage of DNA primers this method allows higher amplification efficiencies than a similar method based on locked nucleic acid-spiked primers. The high efficiency translates into higher sensitivity and precision...... in miRNA quantification. Furthermore, the method is easy to perform with common laboratory reagents, which allows miRNA quantification at low cost....

  18. Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia

    DEFF Research Database (Denmark)

    Welten, S. M. J.; Bastiaansen, Ajnm; de Jong, R. C. M.

    2014-01-01

    in mice after single femoral artery ligation. Methods and Results: Gene silencing oligonucleotides (GSOs) were used to inhibit 4 14q32 microRNAs, miR-329, miR-487b, miR-494, and miR-495, 1 day before double femoral artery ligation. Blood flow recovery was followed by laser Doppler perfusion imaging. All 4...... GSOs clearly improved blood flow recovery after ischemia. Mice treated with GSO-495 or GSO-329 showed increased perfusion already after 3 days (30% perfusion versus 15% in control), and those treated with GSO-329 showed a full recovery of perfusion after 7 days (versus 60% in control). Increased...... collateral artery diameters (arteriogenesis) were observed in adductor muscles of GSO-treated mice, as well as increased capillary densities (angiogenesis) in the ischemic soleus muscle. In vitro, treatment with GSOs led to increased sprout formation and increased arterial endothelial cell proliferation...

  19. Abiotic stress miRNomes in the Triticeae.

    Science.gov (United States)

    Alptekin, Burcu; Langridge, Peter; Budak, Hikmet

    2017-05-01

    The continued growth in world population necessitates increases in both the quantity and quality of agricultural production. Triticeae members, particularly wheat and barley, make an important contribution to world food reserves by providing rich sources of carbohydrate and protein. These crops are grown over diverse production environments that are characterized by a range of environmental or abiotic stresses. Abiotic stresses such as drought, heat, salinity, or nutrient deficiencies and toxicities cause large yield losses resulting in economic and environmental damage. The negative effects of abiotic stresses have increased at an alarming rate in recent years and are predicted to further deteriorate due to climate change, land degradation, and declining water supply. New technologies have provided an important tool with great potential for improving crop tolerance to the abiotic stresses: microRNAs (miRNAs). miRNAs are small regulators of gene expression that act on many different molecular and biochemical processes such as development, environmental adaptation, and stress tolerance. miRNAs can act at both the transcriptional and post-transcriptional levels, although post-transcriptional regulation is the most common in plants where miRNAs can inhibit the translation of their mRNA targets via complementary binding and cleavage. To date, expression of several miRNA families such as miR156, miR159, and miR398 has been detected as responsive to environmental conditions to regulate stress-associated molecular mechanisms individually and/or together with their various miRNA partners. Manipulation of these miRNAs and their targets may pave the way to improve crop performance under several abiotic stresses. Here, we summarize the current status of our knowledge on abiotic stress-associated miRNAs in members of the Triticeae tribe, specifically in wheat and barley, and the miRNA-based regulatory mechanisms triggered by stress conditions. Exploration of further mi

  20. Single nucleotide polymorphisms unravel hierarchical divergence and signatures of selection among Alaskan sockeye salmon (Oncorhynchus nerka populations

    Directory of Open Access Journals (Sweden)

    Habicht Christopher

    2011-02-01

    Full Text Available Abstract Background Disentangling the roles of geography and ecology driving population divergence and distinguishing adaptive from neutral evolution at the molecular level have been common goals among evolutionary and conservation biologists. Using single nucleotide polymorphism (SNP multilocus genotypes for 31 sockeye salmon (Oncorhynchus nerka populations from the Kvichak River, Alaska, we assessed the relative roles of geography (discrete boundaries or continuous distance and ecology (spawning habitat and timing driving genetic divergence in this species at varying spatial scales within the drainage. We also evaluated two outlier detection methods to characterize candidate SNPs responding to environmental selection, emphasizing which mechanism(s may maintain the genetic variation of outlier loci. Results For the entire drainage, Mantel tests suggested a greater role of geographic distance on population divergence than differences in spawn timing when each variable was correlated with pairwise genetic distances. Clustering and hierarchical analyses of molecular variance indicated that the largest genetic differentiation occurred between populations from distinct lakes or subdrainages. Within one population-rich lake, however, Mantel tests suggested a greater role of spawn timing than geographic distance on population divergence when each variable was correlated with pairwise genetic distances. Variable spawn timing among populations was linked to specific spawning habitats as revealed by principal coordinate analyses. We additionally identified two outlier SNPs located in the major histocompatibility complex (MHC class II that appeared robust to violations of demographic assumptions from an initial pool of eight candidates for selection. Conclusions First, our results suggest that geography and ecology have influenced genetic divergence between Alaskan sockeye salmon populations in a hierarchical manner depending on the spatial scale. Second

  1. Elucidating distinct ion channel populations on the surface of hippocampal neurons via single-particle tracking recurrence analysis

    Science.gov (United States)

    Sikora, Grzegorz; Wyłomańska, Agnieszka; Gajda, Janusz; Solé, Laura; Akin, Elizabeth J.; Tamkun, Michael M.; Krapf, Diego

    2017-12-01

    Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface. We specifically study the dynamics of the K+ channel Kv1.4 and the Na+ channel Nav1.6 on the surface of cultured hippocampal neurons at the single-molecule level. We find that both these molecules are expressed in two different forms with distinct kinetics with regards to surface interactions, emphasizing the complex proteomic landscape of the neuronal surface. Further, the tools presented in this work provide new methods for the analysis of membrane nanodomains, transient confinement, and identification of populations within single-particle trajectories.

  2. Expression profiling of miR-96, miR-584 and miR-422a in colon ...

    African Journals Online (AJOL)

    RESULTS. Expression levels of miR-96, miR-584 and. miR-422a in colon cancer tissues. The expression levels of miR-96, miR-584 and. miR-422a were analyzed in 60 colon cancer patient tissue samples and their adjacent normal mucosal counterparts using quantitative RT-. PCR. Clinical characteristics of the 60 patients.

  3. Syncope unit in the paediatric population: A single-centre experience.

    Science.gov (United States)

    Courtheix, Mathieu; Jalal, Zakaria; Bordachar, Pierre; Iriart, Xavier; Pillois, Xavier; Escobedo, Cécile; Rabot, Catherine; Tribout, Laetitia; Thambo, Jean-Benoit

    2016-03-01

    Syncopes are frequent in the paediatric population. Most are benign, but rare cases are caused by cardiac life-threatening diseases. Syncope units developed in the adult population have demonstrated improvement in evaluation and treatment, with a reduction in hospitalization. We report our experience of paediatric syncope management in a dedicated unit, and analyse the value of different elements in the identification of cardiac causes. This prospective study included 97 consecutive patients (mean age: 12.1±3.3 years) referred between January 2011 and June 2013 to a syncope unit with a paediatric cardiologist, a nurse, a physiotherapist and a psychologist. Patients were classified into diagnostic categories after an initial evaluation that included history, physical examination, electrocardiography, echocardiography and Holter monitoring. The most common diagnosis was neurocardiogenic syncope (n=69, 70.4%). Fifty-two cases (81.3%) had no or less recurrence after specific management that included physiotherapy and psychological support (follow-up: 11.5±5.4 months). Psychogenic pseudosyncopes affected 20 children (20.6%). Two patients had epileptic seizures. There were five cases of cardiac syncope (5.1%): two long QT syndromes and a catecholaminergic polymorphic ventricular tachycardia received beta-blockers; two atrioventricular complete blocks required pacemakers. One case was of indeterminate cause and received an insertable loop recorder after exhaustive investigations. Exercise-induced syncopes were significantly associated with cardiac origins (P=0.003), such as electrocardiographic abnormalities (PSyncope units in the paediatric population may be useful in the diagnostic process, to help identify rare cardiac aetiologies, and could decrease recurrence through specific management. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Strategies for imputation to whole genome sequence using a single or multi-breed reference population in cattle

    DEFF Research Database (Denmark)

    Brøndum, Rasmus Froberg; Guldbrandtsen, Bernt; Sahana, Goutam

    2014-01-01

    autosome 29 using 387,436 bi-allelic variants and 13,612 SNP markers from the bovine HD panel. Results A combined breed reference population led to higher imputation accuracies than did a single breed reference. The highest accuracy of imputation for all three test breeds was achieved when using BEAGLE...... with un-phased reference data (mean genotype correlations of 0.90, 0.89 and 0.87 for Holstein, Jersey and Nordic Red respectively) but IMPUTE2 with un-phased reference data gave similar accuracies for Holsteins and Nordic Red. Pre-phasing the reference data only lead to a minor decrease in the imputation...

  5. Effects of extracellular nucleotides on single cells and populations of human osteoblasts: contribution of cell heterogeneity to relative potencies

    OpenAIRE

    Jane Dixon, C; Bowler, Wayne B; Walsh, Catherine A; Gallagher, James A

    1997-01-01

    Human osteoblasts responded to the application of extracellular nucleotides, acting at P2-receptors, with increases in cytosolic free calcium concentration ([Ca2+]i).In populations of human osteoblasts, adenosine 5′-diphosphate (ADP) evoked a rise in [Ca2+]i with less than 40% of the amplitude of that induced by adenosine 5′-triphosphate (ATP).ATP and uridine 5′-triphosphate (UTP) were applied to single human osteoblasts and induced [Ca2+]i rises of comparable amplitude in every cell tested.H...

  6. miR-146a promotes the initiation and progression of melanoma by activating Notch signaling.

    Science.gov (United States)

    Forloni, Matteo; Dogra, Shaillay Kumar; Dong, Yuying; Conte, Darryl; Ou, Jianhong; Zhu, Lihua Julie; Deng, April; Mahalingam, Meera; Green, Michael R; Wajapeyee, Narendra

    2014-02-18

    Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. In this study, we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma. DOI: http://dx.doi.org/10.7554/eLife.01460.001.

  7. The Bifurcation and Control of a Single-Species Fish Population Logistic Model with the Invasion of Alien Species

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2014-01-01

    Full Text Available The objective of this paper is to study systematically the bifurcation and control of a single-species fish population logistic model with the invasion of alien species based on the theory of singular system and bifurcation. It regards Spartina anglica as an invasive species, which invades the fisheries and aquaculture. Firstly, the stabilities of equilibria in this model are discussed. Moreover, the sufficient conditions for existence of the trans-critical bifurcation and the singularity induced bifurcation are obtained. Secondly, the state feedback controller is designed to eliminate the unexpected singularity induced bifurcation by combining harvested effort with the purification capacity. It obviously inhibits the switch of population and makes the system stable. Finally, the numerical simulation is proposed to show the practical significance of the bifurcation and control from the biological point of view.

  8. Single-nucleotide polymorphism-based population genetic analysis of Mycobacterium tuberculosis strains from 4 geographic sites.

    Science.gov (United States)

    Gutacker, Michaela M; Mathema, Barun; Soini, Hanna; Shashkina, Elena; Kreiswirth, Barry N; Graviss, Edward A; Musser, James M

    2006-01-01

    We studied genetic relationships among 5069 Mycobacterium tuberculosis strains recovered from patients enrolled in 4 population-based studies in the United States and Europe, by analysis of 36 synonymous single-nucleotide polymorphisms (SNPs). All strains were assigned to 1 of 9 major genetic clusters based on sSNP profile. The same 9 genetic clusters were revealed by analysis of 227 nonsynonymous SNPs, 121 intergenic SNPs, and concatenated profiles of 578 SNPs available for a subset of 48 representative strains. IS6110 profiles, spoligotypes, and mycobacterial interspersed repetitive unit patterns were nonrandomly associated with SNP-based phylogenetic lineages, together indicating a strongly clonal population structure. Isolates of the 9 genetic clusters were not distributed with equal frequency in all localities, reflecting geographic subdivision. The SNP-based phylogenetic framework provides new insight into the worldwide evolution of M. tuberculosis and a gateway for investigating genotype-disease phenotype relationships in large samples of strains.

  9. Single Cell Dynamics Causes Pareto-Like Effect in Stimulated T Cell Populations.

    Science.gov (United States)

    Cosette, Jérémie; Moussy, Alice; Onodi, Fanny; Auffret-Cariou, Adrien; Neildez-Nguyen, Thi My Anh; Paldi, Andras; Stockholm, Daniel

    2015-12-09

    Cell fate choice during the process of differentiation may obey to deterministic or stochastic rules. In order to discriminate between these two strategies we used time-lapse microscopy of individual murine CD4 + T cells that allows investigating the dynamics of proliferation and fate commitment. We observed highly heterogeneous division and death rates between individual clones resulting in a Pareto-like dominance of a few clones at the end of the experiment. Commitment to the Treg fate was monitored using the expression of a GFP reporter gene under the control of the endogenous Foxp3 promoter. All possible combinations of proliferation and differentiation were observed and resulted in exclusively GFP-, GFP+ or mixed phenotype clones of very different population sizes. We simulated the process of proliferation and differentiation using a simple mathematical model of stochastic decision-making based on the experimentally observed parameters. The simulations show that a stochastic scenario is fully compatible with the observed Pareto-like imbalance in the final population.

  10. Kinetic Modeling of ABCG2 Transporter Heterogeneity: A Quantitative, Single-Cell Analysis of the Side Population Assay.

    Directory of Open Access Journals (Sweden)

    Adam F Prasanphanich

    2016-11-01

    Full Text Available The side population (SP assay, a technique used in cancer and stem cell research, assesses the activity of ABC transporters on Hoechst staining in the presence and absence of transporter inhibition, identifying SP and non-SP cell (NSP subpopulations by differential staining intensity. The interpretation of the assay is complicated because the transporter-mediated mechanisms fail to account for cell-to-cell variability within a population or adequately control the direct role of transporter activity on staining intensity. We hypothesized that differences in dye kinetics at the single-cell level, such as ABCG2 transporter-mediated efflux and DNA binding, are responsible for the differential cell staining that demarcates SP/NSP identity. We report changes in A549 phenotype during time in culture and with TGFβ treatment that correlate with SP size. Clonal expansion of individually sorted cells re-established both SP and NSPs, indicating that SP membership is dynamic. To assess the validity of a purely kinetics-based interpretation of SP/NSP identity, we developed a computational approach that simulated cell staining within a heterogeneous cell population; this exercise allowed for the direct inference of the role of transporter activity and inhibition on cell staining. Our simulated SP assay yielded appropriate SP responses for kinetic scenarios in which high transporter activity existed in a portion of the cells and little differential staining occurred in the majority of the population. With our approach for single-cell analysis, we observed SP and NSP cells at both ends of a transporter activity continuum, demonstrating that features of transporter activity as well as DNA content are determinants of SP/NSP identity.

  11. Kinetic Modeling of ABCG2 Transporter Heterogeneity: A Quantitative, Single-Cell Analysis of the Side Population Assay

    Science.gov (United States)

    Prasanphanich, Adam F.; White, Douglas E.; Gran, Margaret A.

    2016-01-01

    The side population (SP) assay, a technique used in cancer and stem cell research, assesses the activity of ABC transporters on Hoechst staining in the presence and absence of transporter inhibition, identifying SP and non-SP cell (NSP) subpopulations by differential staining intensity. The interpretation of the assay is complicated because the transporter-mediated mechanisms fail to account for cell-to-cell variability within a population or adequately control the direct role of transporter activity on staining intensity. We hypothesized that differences in dye kinetics at the single-cell level, such as ABCG2 transporter-mediated efflux and DNA binding, are responsible for the differential cell staining that demarcates SP/NSP identity. We report changes in A549 phenotype during time in culture and with TGFβ treatment that correlate with SP size. Clonal expansion of individually sorted cells re-established both SP and NSPs, indicating that SP membership is dynamic. To assess the validity of a purely kinetics-based interpretation of SP/NSP identity, we developed a computational approach that simulated cell staining within a heterogeneous cell population; this exercise allowed for the direct inference of the role of transporter activity and inhibition on cell staining. Our simulated SP assay yielded appropriate SP responses for kinetic scenarios in which high transporter activity existed in a portion of the cells and little differential staining occurred in the majority of the population. With our approach for single-cell analysis, we observed SP and NSP cells at both ends of a transporter activity continuum, demonstrating that features of transporter activity as well as DNA content are determinants of SP/NSP identity. PMID:27851764

  12. Spontaneous Coronary Artery Dissection as a Cause of Acute Myocardial Infarction in Young Female Population: A Single-center Study.

    Science.gov (United States)

    Meng, Pei-Na; Xu, Chen; You, Wei; Wu, Zhi-Ming; Xie, Du-Jiang; Zhang, Hang; Pan, Chang; Ye, Fei

    2017-07-05

    Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic but a rare and extremely dangerous clinical entity, it has a high prevalence in young female population with acute myocardial infarction (AMI). The previous reports were restricted to other countries' population, but rare in China. Hence, this study aimed to focus on the characteristics of SCAD as a cause of young female AMI population in Jiangsu, China. This study enrolled young female AMI patients aged ≤50 years who underwent coronary angiography (CAG) and intracoronary imaging in our center between January 2013 and December 2016. Their clinical presentations, risk factors, and CAG characteristics were analyzed. A total of 60 young female AMI (SCAD in young female AMI population was 35% (21/60), the prevalence of coronary atherosclerostic heart disease was 65% (39/60). In the SCAD group, 43% (9/21) presented with non-ST-elevation myocardial infarction (NSTEMI) and the remainder presenting as STEMI. SCAD usually occurred in a single vessel (20/21, 95%), especially in left anterior descending artery (14/21, 67%). Eighteen patients (18/21, 86%) underwent conservative treatment, whereas the remaining three patients (3/21, 14%) underwent percutaneous coronary intervention. Regarding the angiographic results of SCAD lesions, intramural hematoma was discriminated in 95% (20/21), and Type I imaging was observed in 5% (1/21), Type II was observed in 67% (14/21), and Type III was 29% (6/21). The average stenosis in the group was 76.9% ± 20.6%, and the mean lesion length was 36.6 ± 8.6 mm. SCAD has a high prevalence in young female AMI population in Jiangsu, China. Discriminating the cause of AMI in young female population is very important.

  13. Mitochondrial population genomics supports a single pre-Clovis origin with a coastal route for the peopling of the Americas.

    Science.gov (United States)

    Fagundes, Nelson J R; Kanitz, Ricardo; Eckert, Roberta; Valls, Ana C S; Bogo, Mauricio R; Salzano, Francisco M; Smith, David Glenn; Silva, Wilson A; Zago, Marco A; Ribeiro-dos-Santos, Andrea K; Santos, Sidney E B; Petzl-Erler, Maria Luiza; Bonatto, Sandro L

    2008-03-01

    It is well accepted that the Americas were the last continents reached by modern humans, most likely through Beringia. However, the precise time and mode of the colonization of the New World remain hotly disputed issues. Native American populations exhibit almost exclusively five mitochondrial DNA (mtDNA) haplogroups (A-D and X). Haplogroups A-D are also frequent in Asia, suggesting a northeastern Asian origin of these lineages. However, the differential pattern of distribution and frequency of haplogroup X led some to suggest that it may represent an independent migration to the Americas. Here we show, by using 86 complete mitochondrial genomes, that all Native American haplogroups, including haplogroup X, were part of a single founding population, thereby refuting multiple-migration models. A detailed demographic history of the mtDNA sequences estimated with a Bayesian coalescent method indicates a complex model for the peopling of the Americas, in which the initial differentiation from Asian populations ended with a moderate bottleneck in Beringia during the last glacial maximum (LGM), around approximately 23,000 to approximately 19,000 years ago. Toward the end of the LGM, a strong population expansion started approximately 18,000 and finished approximately 15,000 years ago. These results support a pre-Clovis occupation of the New World, suggesting a rapid settlement of the continent along a Pacific coastal route.

  14. Response of single bacterial cells to stress gives rise to complex history dependence at the population level

    Science.gov (United States)

    Mathis, Roland; Ackermann, Martin

    2016-01-01

    Most bacteria live in ever-changing environments where periods of stress are common. One fundamental question is whether individual bacterial cells have an increased tolerance to stress if they recently have been exposed to lower levels of the same stressor. To address this question, we worked with the bacterium Caulobacter crescentus and asked whether exposure to a moderate concentration of sodium chloride would affect survival during later exposure to a higher concentration. We found that the effects measured at the population level depended in a surprising and complex way on the time interval between the two exposure events: The effect of the first exposure on survival of the second exposure was positive for some time intervals but negative for others. We hypothesized that the complex pattern of history dependence at the population level was a consequence of the responses of individual cells to sodium chloride that we observed: (i) exposure to moderate concentrations of sodium chloride caused delays in cell division and led to cell-cycle synchronization, and (ii) whether a bacterium would survive subsequent exposure to higher concentrations was dependent on the cell-cycle state. Using computational modeling, we demonstrated that indeed the combination of these two effects could explain the complex patterns of history dependence observed at the population level. Our insight into how the behavior of single cells scales up to processes at the population level provides a perspective on how organisms operate in dynamic environments with fluctuating stress exposure. PMID:26960998

  15. Embryonic miRNA profiles of normal and ectopic pregnancies.

    Directory of Open Access Journals (Sweden)

    Francisco Dominguez

    Full Text Available Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs and controlled abortions (voluntary termination of pregnancy; VTOP. Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-196b, hsa-mir-30a, hsa-mir-873, and hsa-mir-337-3p and three upregulated (hsa-mir-1288, hsa-mir-451, and hsa-mir-223 in EP compared to control tissue samples. Hsa-miR-196, hsa-miR-223, and hsa-miR-451 were further validated by real time PCR in a wider population of EP and control samples. We also performed a computational analysis to identify the gene targets and pathways which might be modulated by these three differentially expressed miRNAs. The most significant pathways found were the mucin type O-glycan biosynthesis and the ECM-receptor-interaction pathways. We also checked that the dysregulation of these three miRNAs was able to alter the expression of the gene targets in the embryonic tissues included in these pathways such as GALNT13 and ITGA2 genes. In conclusion, analysis of miRNAs in ectopic and eutopic embryonic tissues shows different expression patterns that could modify pathways which are critical for correct implantation, providing new insights into the understanding of ectopic implantation in humans.

  16. Embryonic miRNA Profiles of Normal and Ectopic Pregnancies

    Science.gov (United States)

    Dominguez, Francisco; Moreno-Moya, Juan Manuel; Lozoya, Teresa; Romero, Ainhoa; Martínez, Sebastian; Monterde, Mercedes; Gurrea, Marta; Ferri, Blanca; Núñez, Maria Jose; Simón, Carlos; Pellicer, Antonio

    2014-01-01

    Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs) and controlled abortions (voluntary termination of pregnancy; VTOP). Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-196b, hsa-mir-30a, hsa-mir-873, and hsa-mir-337-3p) and three upregulated (hsa-mir-1288, hsa-mir-451, and hsa-mir-223) in EP compared to control tissue samples. Hsa-miR-196, hsa-miR-223, and hsa-miR-451 were further validated by real time PCR in a wider population of EP and control samples. We also performed a computational analysis to identify the gene targets and pathways which might be modulated by these three differentially expressed miRNAs. The most significant pathways found were the mucin type O-glycan biosynthesis and the ECM-receptor-interaction pathways. We also checked that the dysregulation of these three miRNAs was able to alter the expression of the gene targets in the embryonic tissues included in these pathways such as GALNT13 and ITGA2 genes. In conclusion, analysis of miRNAs in ectopic and eutopic embryonic tissues shows different expression patterns that could modify pathways which are critical for correct implantation, providing new insights into the understanding of ectopic implantation in humans. PMID:25013942

  17. Reclaiming Sámi languages

    DEFF Research Database (Denmark)

    Rasmussen, Torkel; Nolan, John Shaun

    2011-01-01

    at the local level, they encounter prejudice and neglect from other people, even in their families, and as a result they often experience difficulty in transmitting Sámi to their children. Nevertheless, they also express belief in Sámi and feel a need for this transmission, not only for affective reasons...

  18. In silico miRNA prediction in metazoan genomes: balancing between sensitivity and specificity

    Directory of Open Access Journals (Sweden)

    Fiers Mark WJE

    2009-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs, short ~21-nucleotide RNA molecules, play an important role in post-transcriptional regulation of gene expression. The number of known miRNA hairpins registered in the miRBase database is rapidly increasing, but recent reports suggest that many miRNAs with restricted temporal or tissue-specific expression remain undiscovered. Various strategies for in silico miRNA identification have been proposed to facilitate miRNA discovery. Notably support vector machine (SVM methods have recently gained popularity. However, a drawback of these methods is that they do not provide insight into the biological properties of miRNA sequences. Results We here propose a new strategy for miRNA hairpin prediction in which the likelihood that a genomic hairpin is a true miRNA hairpin is evaluated based on statistical distributions of observed biological variation of properties (descriptors of known miRNA hairpins. These distributions are transformed into a single and continuous outcome classifier called the L score. Using a dataset of known miRNA hairpins from the miRBase database and an exhaustive set of genomic hairpins identified in the genome of Caenorhabditis elegans, a subset of 18 most informative descriptors was selected after detailed analysis of correlation among and discriminative power of individual descriptors. We show that the majority of previously identified miRNA hairpins have high L scores, that the method outperforms miRNA prediction by threshold filtering and that it is more transparent than SVM classifiers. Conclusion The L score is applicable as a prediction classifier with high sensitivity for novel miRNA hairpins. The L-score approach can be used to rank and select interesting miRNA hairpin candidates for downstream experimental analysis when coupled to a genome-wide set of in silico-identified hairpins or to facilitate the analysis of large sets of putative miRNA hairpin loci obtained in deep

  19. Properties of the single Jovian planet population and the pursuit of Solar system analogues

    Science.gov (United States)

    Agnew, Matthew T.; Maddison, Sarah T.; Horner, Jonathan

    2018-04-01

    While the number of exoplanets discovered continues to increase at a rapid rate, we are still to discover any system that truly resembles the Solar system. Existing and near future surveys will likely continue this trend of rapid discovery. To see if these systems are Solar system analogues, we will need to efficiently allocate resources to carry out intensive follow-up observations. We seek to uncover the properties and trends across systems that indicate how much of the habitable zone is stable in each system to provide focus for planet hunters. We study the dynamics of all known single Jovian planetary systems, to assess the dynamical stability of the habitable zone around their host stars. We perform a suite of simulations of all systems where the Jovian planet will interact gravitationally with the habitable zone, and broadly classify these systems. Besides the system's mass ratio (Mpl/Mstar), and the Jovian planet's semi-major axis (apl) and eccentricity (epl), we find that there are no underlying system properties which are observable that indicate the potential for planets to survive within the system's habitable zone. We use Mpl/Mstar, apl and epl to generate a parameter space over which the unstable systems cluster, thus allowing us to predict which systems to exclude from future observational or numerical searches for habitable exoplanets. We also provide a candidate list of 20 systems that have completely stable habitable zones and Jovian planets orbiting beyond the habitable zone as potential first order Solar system analogues.

  20. SNPer: an R library for quantitative variant analysis on single nucleotide polymorphisms among influenza virus populations.

    Directory of Open Access Journals (Sweden)

    Unitsa Sangket

    Full Text Available Influenza virus (IFV can evolve rapidly leading to genetic drifts and shifts resulting in human and animal influenza epidemics and pandemics. The genetic shift that gave rise to the 2009 influenza A/H1N1 pandemic originated from a triple gene reassortment of avian, swine and human IFVs. More minor genetic alterations in genetic drift can lead to influenza drug resistance such as the H274Y mutation associated with oseltamivir resistance. Hence, a rapid tool to detect IFV mutations and the potential emergence of new virulent strains can better prepare us for seasonal influenza outbreaks as well as potential pandemics. Furthermore, identification of specific mutations by closely examining single nucleotide polymorphisms (SNPs in IFV sequences is essential to classify potential genetic markers associated with potentially dangerous IFV phenotypes. In this study, we developed a novel R library called "SNPer" to analyze quantitative variants in SNPs among IFV subpopulations. The computational SNPer program was applied to three different subpopulations of published IFV genomic information. SNPer queried SNPs data and grouped the SNPs into (1 universal SNPs, (2 likely common SNPs, and (3 unique SNPs. SNPer outperformed manual visualization in terms of time and labor. SNPer took only three seconds with no errors in SNP comparison events compared with 40 hours with errors using manual visualization. The SNPer tool can accelerate the capacity to capture new and potentially dangerous IFV strains to mitigate future influenza outbreaks.

  1. Psidium guajava: A Single Plant for Multiple Health Problems of Rural Indian Population.

    Science.gov (United States)

    Daswani, Poonam G; Gholkar, Manasi S; Birdi, Tannaz J

    2017-01-01

    The rural population in India faces a number of health problems and often has to rely on local remedies. Psidium guajava Linn. (guava), a tropical plant which is used as food and medicine can be used by rural communities due to its several medicinal properties. A literature search was undertaken to gauge the rural health scenario in India and compile the available literature on guava so as to reflect its usage in the treatment of multiple health conditions prevalent in rural communities. Towards this, electronic databases such as Pubmed, Science Direct, google scholar were scanned. Information on clinical trials on guava was obtained from Cochrane Central Register of Controlled Trials and Clinicaltrial.gov. The literature survey revealed that guava possesses various medicinal properties which have been reported from across the globe in the form of ethnobotanical/ethnopharmacological surveys, laboratory investigations and clinical trials. Besides documenting the safety of guava, the available literature shows that guava is efficacious against the following conditions which rural communities would encounter. (a) Gastrointestinal infections; (b) Malaria; (c)Respiratory infections; (d) Oral/dental infections; (e) Skin infections; (f) Diabetes; (g) Cardiovascular/hypertension; (h) Cancer; (i) Malnutrition; (j) Women problems; (k) Pain; (l) Fever; (m) Liver problems; (n) Kidney problems. In addition, guava can also be useful for treatment of animals and explored for its commercial applications. In conclusion, popularization of guava, can have multiple applications for rural communities.

  2. The Fitness Effects of Men's Family Investments : A Test of Three Pathways in a Single Population.

    Science.gov (United States)

    Winking, Jeffrey; Koster, Jeremy

    2015-09-01

    Men's investments in parenting and long-term reproductive relationships are a hallmark feature of human reproduction and life history. The uniqueness of such male involvement among catarrhines has driven an extensive debate surrounding the selective pressures that led to and maintain such capacities in men. Three major pathways have been proposed through which men's involvement might confer fitness benefits: enhancing child well-being, increasing couple fertility, and decreasing likelihood of partner desertion. Previous research has explored the impact of father involvement on these factors individually, but here we present novel research that explores all three pathways within the same population, the Mayangna/Miskito horticulturalists of Nicaragua. Furthermore, we expand the traditional dichotomous measure of father presence/absence by using a continuous measure of overall male investment, as well as two continuous measures of its subcomponents: direct care and wealth. We find that men's investments are associated with children's growth and possibly with wife's marital satisfaction; however, they are not associated with couple fertility.

  3. miRNA genes of an invasive vector mosquito, Aedes albopictus.

    Directory of Open Access Journals (Sweden)

    Jinbao Gu

    Full Text Available Aedes albopictus, a vector of Dengue and Chikungunya viruses, is a robust invasive species in both tropical and temperate environments. MicroRNAs (miRNAs regulate gene expression and biological processes including embryonic development, innate immunity and infection. While a number of miRNAs have been discovered in some mosquitoes, no comprehensive effort has been made to characterize them from different developmental stages from a single species. Systematic analysis of miRNAs in Ae. albopictus will improve our understanding of its basic biology and inform novel strategies to prevent virus transmission. Between 10-14 million Illumina sequencing reads per sample were obtained from embryos, larvae, pupae, adult males, sugar-fed and blood-fed adult females. A total of 119 miRNA genes represented by 215 miRNA or miRNA star (miRNA* sequences were identified, 15 of which are novel. Eleven, two, and two of the newly-discovered miRNA genes appear specific to Aedes, Culicinae, and Culicidae, respectively. A number of miRNAs accumulate predominantly in one or two developmental stages and the large number that showed differences in abundance following a blood meal likely are important in blood-induced mosquito biology. Gene Ontology (GO analysis of the targets of all Ae. albopictus miRNAs provides a useful starting point for the study of their functions in mosquitoes. This study is the first systematic analysis of miRNAs based on deep-sequencing of small RNA samples of all developmental stages of a mosquito species. A number of miRNAs are related to specific physiological states, most notably, pre- and post-blood feeding. The distribution of lineage-specific miRNAs is consistent with mosquito phylogeny and the presence of a number of Aedes-specific miRNAs likely reflects the divergence between the Aedes and Culex genera.

  4. dPORE-miRNA: Polymorphic regulation of microRNA genes

    KAUST Repository

    Schmeier, Sebastian

    2011-02-04

    Background: MicroRNAs (miRNAs) are short non-coding RNA molecules that act as post-transcriptional regulators and affect the regulation of protein-coding genes. Mostly transcribed by PolII, miRNA genes are regulated at the transcriptional level similarly to protein-coding genes. In this study we focus on human miRNAs. These miRNAs are involved in a variety of pathways and can affect many diseases. Our interest is on possible deregulation of the transcription initiation of the miRNA encoding genes, which is facilitated by variations in the genomic sequence of transcriptional control regions (promoters). Methodology: Our aim is to provide an online resource to facilitate the investigation of the potential effects of single nucleotide polymorphisms (SNPs) on miRNA gene regulation. We analyzed SNPs overlapped with predicted transcription factor binding sites (TFBSs) in promoters of miRNA genes. We also accounted for the creation of novel TFBSs due to polymorphisms not present in the reference genome. The resulting changes in the original TFBSs and potential creation of new TFBSs were incorporated into the Dragon Database of Polymorphic Regulation of miRNA genes (dPORE-miRNA). Conclusions: The dPORE-miRNA database enables researchers to explore potential effects of SNPs on the regulation of miRNAs. dPORE-miRNA can be interrogated with regards to: a/miRNAs (their targets, or involvement in diseases, or biological pathways), b/SNPs, or c/transcription factors. dPORE-miRNA can be accessed at http://cbrc.kaust.edu.sa/dpore and http://apps.sanbi.ac.za/dpore/. Its use is free for academic and non-profit users. © 2011 Schmeier et al.

  5. The concept of multiple-target anti-miRNA antisense oligonucleotide technology.

    Science.gov (United States)

    Wang, Zhiguo

    2011-01-01

    The multiple-target AMO technology or MT-AMO technology is an innovative strategy, which confers on a single AMO fragment the capability of targeting multiple miRNAs. This modified AMO is single-stranded 2'-O-methyl-modified oligoribonucleotides carrying multiple AMO units, which are engineered into a single unit and are able to simultaneously silence multiple-target miRNAs or multiple miRNA seed families. Studies suggest that the MT-AMO is an improved approach for miRNA target finding and miRNA function validation; it not only enhances the effectiveness of targeting miRNAs but also confers diversity of actions. It has been successfully used to identify target genes and cellular function of several oncogenic miRNAs and of the muscle-specific miRNAs (Lu et al., Nucleic Acids Res 37:e24-e33, 2009). This novel strategy may find its broad application as a useful tool in miRNA research for exploring biological processes involving multiple miRNAs and multiple genes, and the potential as an miRNA therapy for human disease such as cancer and cardiac disorders. This technology was developed by my research laboratory in collaboration with Yang's group (Lu et al., Nucleic Acids Res 37:e24-e33, 2009), and it is similar but distinct from the miRNA Sponge technology developed by Sharp's laboratory in 2007 (Ebert et al., Nat Methods 4:721-726, 2007) and modified by Gentner et al. (Nat Methods 6:63-66, 2009).

  6. Unrelated hematopoietic stem cell transplantation in the pediatric population: single institution experience

    Directory of Open Access Journals (Sweden)

    Daniela Hespanha Marinho

    2015-08-01

    Full Text Available OBJECTIVE: Hematopoietic stem cell transplantation has been successfully used to treat the pediatric population with malignant and non-malignant hematological diseases. This paper reports the results up to 180 days after the procedure of all unrelated hematopoietic stem cell transplantations in pediatric patients that were performed in one institution.METHODS: A retrospective review was performed of all under 18-year-old patients who received unrelated transplantations between 1995 and 2009. Data were analyzed using the log-rank test, Cox stepwise model, Kaplan-Meier method, Fine and Gray model and Fisher's exact test.RESULTS: This study included 118 patients (46.8% who received bone marrow and 134 (53.2% who received umbilical cord blood transplants. Engraftment occurred in 89.47% of the patients that received bone marrow and 65.83% of those that received umbilical cord blood (p-value < 0.001. Both neutrophil and platelet engraftments were faster in the bone marrow group. Acute graft-versus-host disease occurred in 48.6% of the patients without statistically significant differences between the two groups (p-value = 0.653. Chronic graft-versus-host disease occurred in 9.2% of the patients with a higher incidence in the bone marrow group (p-value = 0.007. Relapse occurred in 24% of the 96 patients with malignant disease with 2-year cumulative incidences of 45% in the bone marrow group and 25% in the umbilical cord blood group (p-value = 0.117. Five-year overall survival was 47%, with an average survival time of 1207 days, and no significant differences between the groups (p-value = 0.4666.CONCLUSION: Despite delayed engraftment in the umbilical cord blood group, graft-versus-host disease, relapse and survival were similar in both groups.

  7. Management, treatment and outcomes of acute appendicitis in an elderly population: a single-center experience.

    Science.gov (United States)

    Cohen-Arazi, O; Dabour, K; Bala, M; Haran, A; Almogy, G

    2017-10-01

    Only 5-10% of cases of acute appendicitis (AA) are diagnosed above the age of 60 years. Complicated AA is more common in the elderly, who also have more comorbidities. The goals of this study were to describe our experience with elderly patients and identify predictors of increased morbidity. Patients ≥65 years who were treated for AA between 2006 and 2013 were selected. The control consisted of patients aged 20-45 years, who were randomly selected from a pool of 900 patients. Seventy-four patients ≥65 years, mean age of 74.6 ± 7.4, were included. Time from onset of symptoms to surgery was similar between the groups. CT scan was performed for all patients in the elderly group compared to 55.6% in the younger group (p < 0.001). 77% of the younger patients underwent laparoscopic appendectomy compared to 43.2% of the elderly patients (p < 0.001). Pathological findings of severe appendicitis were significantly more common in the elderly group (39.2 vs. 10.5%, p < 0.001). Sixteen elderly patients (21.6%) developed complications, compared with 4 patients (3.2%) in the younger group (p < 0.001). The length of stay was longer in the elderly group and even longer for patients with complications (p < 0.001). There was no mortality. Cardiac disease was the only independent predictor of peri-operative complications (OR = 4.2). Severe forms of acute appendicitis and post-operative morbidity are higher in the elderly population. Cardiac disease is the only predictor for increased morbidity. Although CT scan was performed universally in the elderly group, it did not appear to increase time from presentation to surgery.

  8. A single population of red globular clusters around the massive compact galaxy NGC 1277

    Science.gov (United States)

    Beasley, Michael A.; Trujillo, Ignacio; Leaman, Ryan; Montes, Mireia

    2018-03-01

    Massive galaxies are thought to form in two phases: an initial collapse of gas and giant burst of central star formation, followed by the later accretion of material that builds up their stellar and dark-matter haloes. The systems of globular clusters within such galaxies are believed to form in a similar manner. The initial central burst forms metal-rich (spectrally red) clusters, whereas more metal-poor (spectrally blue) clusters are brought in by the later accretion of less-massive satellites. This formation process is thought to result in the multimodal optical colour distributions that are seen in the globular cluster systems of massive galaxies. Here we report optical observations of the massive relic-galaxy candidate NGC 1277—a nearby, un-evolved example of a high-redshift ‘red nugget’ galaxy. We find that the optical colour distribution of the cluster system of NGC 1277 is unimodal and entirely red. This finding is in strong contrast to other galaxies of similar and larger stellar mass, the cluster systems of which always exhibit (and are generally dominated by) blue clusters. We argue that the colour distribution of the cluster system of NGC 1277 indicates that the galaxy has undergone little (if any) mass accretion after its initial collapse, and use simulations of possible merger histories to show that the stellar mass due to accretion is probably at most ten per cent of the total stellar mass of the galaxy. These results confirm that NGC 1277 is a genuine relic galaxy and demonstrate that blue clusters constitute an accreted population in present-day massive galaxies.

  9. A single, plastic population of Mycosphaerella pinodes causes ascochyta blight on winter and spring peas (Pisum sativum) in France.

    Science.gov (United States)

    Le May, Christophe; Guibert, Michèle; Leclerc, Aurélie; Andrivon, Didier; Tivoli, Bernard

    2012-12-01

    Plant diseases are caused by pathogen populations continuously subjected to evolutionary forces (genetic flow, selection, and recombination). Ascochyta blight, caused by Mycosphaerella pinodes, is one of the most damaging necrotrophic pathogens of field peas worldwide. In France, both winter and spring peas are cultivated. Although these crops overlap by about 4 months (March to June), primary Ascochyta blight infections are not synchronous on the two crops. This suggests that the disease could be due to two different M. pinodes populations, specialized on either winter or spring pea. To test this hypothesis, 144 pathogen isolates were collected in the field during the winter and spring growing seasons in Rennes (western France), and all the isolates were genotyped using amplified fragment length polymorphism (AFLP) markers. Furthermore, the pathogenicities of 33 isolates randomly chosen within the collection were tested on four pea genotypes (2 winter and 2 spring types) grown under three climatic regimes, simulating winter, late winter, and spring conditions. M. pinodes isolates from winter and spring peas were genetically polymorphic but not differentiated according to the type of cultivars. Isolates from winter pea were more pathogenic than isolates from spring pea on hosts raised under winter conditions, while isolates from spring pea were more pathogenic than those from winter pea on plants raised under spring conditions. These results show that disease developed on winter and spring peas was initiated by a single population of M. pinodes whose pathogenicity is a plastic trait modulated by the physiological status of the host plant.

  10. Genomic variation and population structure detected by single nucleotide polymorphism arrays in Corriedale, Merino and Creole sheep

    Directory of Open Access Journals (Sweden)

    Andrés N Grasso

    2014-06-01

    Full Text Available The aim of this study was to investigate the genetic diversity within and among three breeds of sheep: Corriedale, Merino and Creole. Sheep from the three breeds (Merino n = 110, Corriedale n = 108 and Creole n = 10 were genotyped using the Illumina Ovine SNP50 beadchip®. Genetic diversity was evaluated by comparing the minor allele frequency (MAF among breeds. Population structure and genetic differentiation were assessed using STRUCTURE software, principal component analysis (PCA and fixation index (F ST. Fixed markers (MAF = 0 that were different among breeds were identified as specific breed markers. Using a subset of 18,181 single nucleotide polymorphisms (SNPs, PCA and STUCTURE analysis were able to explain population stratification within breeds. Merino and Corriedale divergent lines showed high levels of polymorphism (89.4% and 86% of polymorphic SNPs, respectively and moderate genetic differentiation (F ST = 0.08 between them. In contrast, Creole had only 69% polymorphic SNPs and showed greater genetic differentiation from the other two breeds (F ST = 0.17 for both breeds. Hence, a subset of molecular markers present in the OvineSNP50 is informative enough for breed assignment and population structure analysis of commercial and Creole breeds.

  11. miRNA Long-Term Response to Early Metabolic Environmental Challenge in Hypothalamic Arcuate Nucleus

    Directory of Open Access Journals (Sweden)

    Charlotte Benoit

    2018-03-01

    Full Text Available Epidemiological reports and studies using rodent models indicate that early exposure to nutrient and/or hormonal challenges can reprogram metabolism at adulthood. Hypothalamic arcuate nucleus (ARC integrates peripheral and central signals to adequately regulate energy homeostasis. microRNAs (miRNAs participate in the control of gene expression of large regulatory networks including many signaling pathways involved in epigenetics regulations. Here, we have characterized and compared the miRNA population of ARC of adult male rats continuously exposed to a balanced metabolic environment to the one of adult male rats exposed to an unbalanced high-fat/high-carbohydrate/moderate-protein metabolic environment during the perinatal period and/or at adulthood that consequently displayed hyperinsulinemia and/or hyperleptinemia. We identified more than 400 miRNA species in ARC of adult male rats. By comparing the miRNA content of six biological replicates in each of the four perinatal/adult environments/rat groups, we identified the 10 miRNAs specified by clusters miR-96/182/183, miR-141/200c, and miR-200a/200b/429 as miRNAs of systematic and uncommonly high variation of expression. This uncommon variation of expression may underlie high individual differences in aging disease susceptibilities. By comparing the miRNA content of the adult ARC between the rat groups, we showed that the miRNA population was not affected by the unbalanced adult environment while, in contrast, the expression of 11 miRNAs was repeatedly impacted by the perinatal unbalanced environment. Our data revealed a miRNA response of adult ARC to early metabolic environmental challenge.

  12. MiRNA expression patterns predict survival in glioblastoma.

    Science.gov (United States)

    Niyazi, Maximilian; Zehentmayr, Franz; Niemöller, Olivier M; Eigenbrod, Sabina; Kretzschmar, Hans; Schulze-Osthoff, Klaus; Tonn, Jörg-Christian; Atkinson, Mike; Mörtl, Simone; Belka, Claus

    2011-11-10

    In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom® Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.

  13. MiRNA expression patterns predict survival in glioblastoma

    Directory of Open Access Journals (Sweden)

    Niyazi Maximilian

    2011-11-01

    Full Text Available Abstract Background In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs from paraffin tissues followed by a bio-mathematical analysis was performed. Methods 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemotherapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom® Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. Results It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days (p = 0.01. The pattern and the prognostic power were both independent of the MGMT status. Conclusions At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.

  14. MiRNA expression patterns predict survival in glioblastoma

    International Nuclear Information System (INIS)

    Niyazi, Maximilian; Belka, Claus; Zehentmayr, Franz; Niemöller, Olivier M; Eigenbrod, Sabina; Kretzschmar, Hans; Osthoff, Klaus-Schulze; Tonn, Jörg-Christian; Atkinson, Mike; Mörtl, Simone

    2011-01-01

    In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip 'Geniom ® Biochip MPEA homo-sapiens' was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required

  15. Identification of miRNAs involved in fruit ripening in Cavendish bananas by deep sequencing.

    Science.gov (United States)

    Bi, Fangcheng; Meng, Xiangchun; Ma, Chao; Yi, Ganjun

    2015-10-13

    MicroRNAs (miRNAs) are a family of non-coding small RNAs that play an important regulatory role in various biological processes. Previous studies have reported that miRNAs are closely related to the ripening process in model plants. However, the miRNAs that are closely involved in the banana fruit ripening process remain unknown. Here, we investigated the miRNA populations from banana fruits in response to ethylene or 1-MCP treatment using a deep sequencing approach and bioinformatics analysis combined with quantitative RT-PCR validation. A total of 125 known miRNAs and 26 novel miRNAs were identified from three libraries. MiRNA profiling of bananas in response to ethylene treatment compared with 1-MCP treatment showed differential expression of 82 miRNAs. Furthermore, the differentially expressed miRNAs were predicted to target a total of 815 target genes. Interestingly, some targets were annotated as transcription factors and other functional proteins closely involved in the development and the ripening process in other plant species. Analysis by qRT-PCR validated the contrasting expression patterns between several miRNAs and their target genes. The miRNAome of the banana fruit in response to ethylene or 1-MCP treatment were identified by high-throughput sequencing. A total of 82 differentially expressed miRNAs were found to be closely associated with the ripening process. The miRNA target genes encode transcription factors and other functional proteins, including SPL, APETALA2, EIN3, E3 ubiquitin ligase, β-galactosidase, and β-glucosidase. These findings provide valuable information for further functional research of the miRNAs involved in banana fruit ripening.

  16. Different risk-increasing drugs in recurrent versus single fallers: are recurrent fallers a distinct population?

    Science.gov (United States)

    Askari, Marjan; Eslami, Saied; Scheffer, Alice C; Medlock, Stephanie; de Rooij, Sophia E; van der Velde, Nathalie; Abu-Hanna, Ameen

    2013-10-01

    classes that showed significant association with recurrent falls. In part, these classes may act as markers of frailty and comorbidity, or they may reflect differences in the risk factors affecting the older, frailer population that tends to sustain recurrent falls. Further investigation is needed to elucidate causes and ways to prevent recurrent falls.

  17. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival.

    LENUS (Irish Health Repository)

    Bray, Isabella

    2009-01-01

    MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145) that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR) and for DNA copy number alterations (array CGH) to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96) and a validation set (n = 49) for data analysis. Thirty-seven miRNAs were significantly over- or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics.

  18. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival.

    Directory of Open Access Journals (Sweden)

    Isabella Bray

    Full Text Available MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145 that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR and for DNA copy number alterations (array CGH to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96 and a validation set (n = 49 for data analysis. Thirty-seven miRNAs were significantly over- or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics.

  19. Search for signatures in miRNAs associated with cancer

    Science.gov (United States)

    Kothandan, Ram; Biswas, Sumit

    2013-01-01

    Since the first discovery in the early 1990's, the predicted and validated population of microRNAs (miRNAs or miRs) has grown significantly. These small (~22 nucleotides long) regulators of gene expression have been implicated and associated with several genes in the cancer pathway as well. Globally, the identification and verification of microRNAs as biomarkers for cancer cell types has been the area of thrust for most miRNA biologists. However, there has been a noticeable vacuum when it comes to identifying a common signature or trademark that could be used to demarcate a miR to be associated with the development or suppression of cancer. To answer these queries, we report an in silico study involving the identification of global signatures in experimentally validated microRNAs which have been associated with cancer. This study has thrown light on the presence of significant common signatures, viz., - sequential and hybridization, which may distinguish a miR to be associated with cancer. Based on our analysis, we suggest the utility of such signatures in the design and development of algorithms for prediction of miRs involved in the cancer pathway. PMID:23861569

  20. Population.

    Science.gov (United States)

    International Planned Parenthood Federation, London (England).

    In an effort to help meet the growing interest and concern about the problems created by the rapid growth of population, The International Planned Parenthood Federation has prepared this booklet with the aim of assisting the study of the history and future trends of population growth and its impact on individual and family welfare, national,…

  1. Patients come from populations and populations contain patients. A two-stage scientific and ethics review: The next adaptation for single institutional review boards.

    Science.gov (United States)

    Knopman, David; Alford, Eli; Tate, Kaitlin; Long, Mark; Khachaturian, Ara S

    2017-08-01

    For nearly 50 years, institutional review boards (IRB) and independent ethics committees have featured local oversight as a core function of research ethics reviews. However growing complexity in Alzheimer's clinical research suggests current approaches to research volunteer safety is hampering development of new therapeutics. As a partial response to this challenge, the NIH has mandated that all NIH-funded multi-site studies will use a single Institutional Review Board. The perspective describes a joint program to provide a single IRB of record (sIRB) for phases of multi-site studies. The approach follows two steps. One, an expert Scientific Review Committee (SRC) of senior researchers in the field will conduct the review principally of scientific merit, significance, feasibility, and the likelihood of meaningful results. The second step will be the IRB's regulatory and ethics review. The IRB will apply appropriate regulatory criteria for approval including minimization of risks to subjects and risks reasonable in relation to anticipated benefits, equitable subject selection, informed consent, protections for vulnerable populations, and application of local context considerations, among others. There is a steady demand for scientific, ethical and regulatory review of planned Alzheimer's studies. As of January 15, 2017, there are nearly 400 open studies, Phase II and III, industry and NIH sponsored trials on disease indications affecting memory, movement and mood in the US. The effort will initially accept protocols for studies of Alzheimer's disease, dementia, and related disorders effecting memory, movement and mood. Future aims will be to provide scientific review and, where applicable, regulatory and ethical review in an international context outside North America with sites possibly in Asia, Europe and Australia. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  2. COMPARISON OF SINGLE NUCLEOTIDE POLYMORPHISMS AND MICROSATELLITES IN NON-INVASIVE GENETIC MONITORING OF A WOLF POPULATION

    DEFF Research Database (Denmark)

    Fabbri, Elena; Caniglia, R.; Mucci, Nadia

    2012-01-01

    Single nucleotide polymorphisms (SNPs) which represent the most widespread source of sequence variation in genomes, are becoming a routine application in several fields such as forensics, ecology and conservation genetics. Their use, requiring short amplifications, may allow a more efficient...... genotyping of degraded DNA. We provide the first application of SNP genotyping in an Italian non-invasive genetic monitoring project of the wolf. We compared three different techniques for genotyping SNPs: pyrosequencing, SNaPshot* and TaqMan* Probe Assay in Real-Time PCR. We successively genotyped nine SNPs....... We evaluated the cost, laboratory effort and reliability of these different markers and discuss the possible future use of VeraCode, SNPlex and Fluidigm EP1 system in wild population monitoring....

  3. Expression profiling of miR-96, miR-584 and miR-422a in colon ...

    African Journals Online (AJOL)

    Purpose: To determine the correlation between miRNAs; miR-96, miR-422a and miR584, and colon cancer, and also to test whether any of these miRNAs can act as non-invasive biomarkers in colon cancer. Methods: The tumor samples and the corresponding normal mucosa used in this study were collected from 60 ...

  4. Post-MI pericarditis (image)

    Science.gov (United States)

    Post-MI pericarditis is inflammation of the pericardium (the sac-like covering of the heart). Any previous injury to the heart muscle can cause pericarditis. Incidences of pericarditis are associated with Dressler's syndrome, ...

  5. Generation of miRNA sponge constructs

    NARCIS (Netherlands)

    Kluiver, Joost; Slezak-Prochazka, Izabella; Smigielska-Czepiel, Katarzyna; Halsema, Nancy; Kroesen, Bart-Jan; van den Berg, Anke

    2012-01-01

    MicroRNA (miRNA) sponges are RNA molecules with repeated miRNA antisense sequences that can sequester miRNAs from their endogenous targets and thus serve as a decoy. Stably expressed miRNA sponges are especially valuable for long-term loss-of-function studies and can be used in vitro and in vivo. We

  6. miR482 regulation of NBS-LRR defense genes during fungal pathogen infection in cotton.

    Directory of Open Access Journals (Sweden)

    Qian-Hao Zhu

    Full Text Available In this study, we characterized the miR482 family in cotton using existing small RNA datasets and the recently released draft genome sequence of Gossypium raimondii, a diploid cotton species whose progenitor is the putative contributor of the Dt (representing the D genome of tetraploid genome of the cultivated tetraploid cotton species G. hirsutum and G. barbadense. Of the three ghr-miR482 members reported in G. hirsutum, ghr-miR482a has no homolog in G. raimondii, ghr-miR482b and ghr-miR482c each has a single homolog in G. raimondii. Gra-miR482d has five homologous loci (gra-miR482d, f-i in G. raimondii and also exists in G. hirsutum (ghr-miR482d. A variant, miR482.2 that is a homolog of miR2118 in other species, is produced from several GHR-MIR482 loci in G. hirsutum. Approximately 12% of the G. raimondii NBS-LRR genes were predicted targets of various members of the gra-miR482 family. Based on the rationale that the regulatory relationship between miR482 and NBS-LRR genes will be conserved in G. raimondii and G. hirsutum, we investigated this relationship using G. hirsutum miR482 and G. raimondii NBS-LRR genes, which are not currently available in G. hirsutum. Ghr-miR482/miR482.2-mediated cleavage was confirmed for three of the four NBS-LRR genes analysed. As in tomato, miR482-mediated cleavage of NBS-LRR genes triggered production of phased secondary small RNAs in cotton. In seedlings of the susceptible cultivar Sicot71 (G. hirsutum infected with the fungal pathogen Verticillium dahliae, the expression levels of ghr-miR482b/miR482b.2, ghr-miR482c and ghr-miR482d.2 were down-regulated, and several NBS-LRR targets of ghr-miR482c and ghr-miR482d were up-regulated. These results imply that, like tomato plants infected with viruses or bacteria, cotton plants are able to induce expression of NBS-LRR defence genes by suppression of the miRNA-mediated gene silencing pathway upon fungal pathogen attack.

  7. Evidence for miRNA-mediated modulation of the host transcriptome in cnidarian-dinoflagellate symbiosis

    KAUST Repository

    Baumgarten, Sebastian

    2017-12-08

    Reef-building corals and other cnidarians living in symbiotic relationships with intracellular, photosynthetic dinoflagellates in the genus Symbiodinium undergo transcriptomic changes during infection with the algae and maintenance of the endosymbiont population. However, the precise regulatory mechanisms modulating the host transcriptome are unknown. Here we report apparent post-transcriptional gene regulation by miRNAs in the sea anemone Aiptasia, a model system for cnidarian-dinoflagellate endosymbiosis. Aiptasia encodes mainly species-specific miRNAs, and there appears to have been recent differentiation within the Aiptasia genome of miRNAs that are commonly conserved among anthozoan cnidarians. Analysis of miRNA expression showed that both conserved and species-specific miRNAs are differentially expressed in response to endosymbiont infection. Using cross-linking immunoprecipitation of Argonaute, the central protein of the miRNA-induced silencing complex, we identified miRNA binding sites on a transcriptome-wide scale and found that the targets of the miRNAs regulated in response to symbiosis include genes previously implicated in biological processes related to Symbiodinium infection. Our study shows that cnidarian miRNAs recognize their mRNA targets via high-complementarity target binding and suggests that miRNA-mediated modulations of genes and pathways are important during the onset and maintenance of cnidarian-dinoflagellate endosymbiosis. This article is protected by copyright. All rights reserved.

  8. Frequency of single nucleotide polymorphisms of some immune response genes in a population sample from São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Léa Campos de Oliveira

    2011-09-01

    Full Text Available Objective: To present the frequency of single nucleotide polymorphismsof a few immune response genes in a population sample from SãoPaulo City (SP, Brazil. Methods: Data on allele frequencies ofknown polymorphisms of innate and acquired immunity genes werepresented, the majority with proven impact on gene function. Datawere gathered from a sample of healthy individuals, non-HLA identicalsiblings of bone marrow transplant recipients from the Hospital dasClínicas da Faculdade de Medicina da Universidade de São Paulo,obtained between 1998 and 2005. The number of samples variedfor each single nucleotide polymorphism analyzed by polymerasechain reaction followed by restriction enzyme cleavage. Results:Allele and genotype distribution of 41 different gene polymorphisms,mostly cytokines, but also including other immune response genes,were presented. Conclusion: We believe that the data presentedhere can be of great value for case-control studies, to define whichpolymorphisms are present in biologically relevant frequencies and toassess targets for therapeutic intervention in polygenic diseases witha component of immune and inflammatory responses.

  9. Genomewide single nucleotide polymorphism discovery in Atlantic salmon (Salmo salar): validation in wild and farmed American and European populations.

    Science.gov (United States)

    Yáñez, J M; Naswa, S; López, M E; Bassini, L; Correa, K; Gilbey, J; Bernatchez, L; Norris, A; Neira, R; Lhorente, J P; Schnable, P S; Newman, S; Mileham, A; Deeb, N; Di Genova, A; Maass, A

    2016-07-01

    A considerable number of single nucleotide polymorphisms (SNPs) are required to elucidate genotype-phenotype associations and determine the molecular basis of important traits. In this work, we carried out de novo SNP discovery accounting for both genome duplication and genetic variation from American and European salmon populations. A total of 9 736 473 nonredundant SNPs were identified across a set of 20 fish by whole-genome sequencing. After applying six bioinformatic filtering steps, 200 K SNPs were selected to develop an Affymetrix Axiom(®) myDesign Custom Array. This array was used to genotype 480 fish representing wild and farmed salmon from Europe, North America and Chile. A total of 159 099 (79.6%) SNPs were validated as high quality based on clustering properties. A total of 151 509 validated SNPs showed a unique position in the genome. When comparing these SNPs against 238 572 markers currently available in two other Atlantic salmon arrays, only 4.6% of the SNP overlapped with the panel developed in this study. This novel high-density SNP panel will be very useful for the dissection of economically and ecologically relevant traits, enhancing breeding programmes through genomic selection as well as supporting genetic studies in both wild and farmed populations of Atlantic salmon using high-resolution genomewide information. © 2016 John Wiley & Sons Ltd.

  10. Accurate single nucleotide variant detection in viral populations by combining probabilistic clustering with a statistical test of strand bias

    Science.gov (United States)

    2013-01-01

    Background Deep sequencing is a powerful tool for assessing viral genetic diversity. Such experiments harness the high coverage afforded by next generation sequencing protocols by treating sequencing reads as a population sample. Distinguishing true single nucleotide variants (SNVs) from sequencing errors remains challenging, however. Current protocols are characterised by high false positive rates, with results requiring time consuming manual checking. Results By statistical modelling, we show that if multiple variant sites are considered at once, SNVs can be called reliably from high coverage viral deep sequencing data at frequencies lower than the error rate of the sequencing technology, and that SNV calling accuracy increases as true sequence diversity within a read length increases. We demonstrate these findings on two control data sets, showing that SNV detection is more reliable on a high diversity human immunodeficiency virus sample as compared to a moderate diversity sample of hepatitis C virus. Finally, we show that in situations where probabilistic clustering retains false positive SNVs (for instance due to insufficient sample diversity or systematic errors), applying a strand bias test based on a beta-binomial model of forward read distribution can improve precision, with negligible cost to true positive recall. Conclusions By combining probabilistic clustering (implemented in the program ShoRAH) with a statistical test of strand bias, SNVs may be called from deeply sequenced viral populations with high accuracy. PMID:23879730

  11. Single nucleotide polymorphisms of ABCB1 (MDR1) gene and distinct haplotype profile in a West Black African population.

    Science.gov (United States)

    Allabi, Aurel C; Horsmans, Yves; Issaoui, Bouchra; Gala, Jean-Luc

    2005-04-01

    The ABCB1 (MDR1) multidrug transporter plays a key role in determining drug bioavailability. Differences in drug response exist among different ethnic groups. However, until now, no haplotype data are available in a Black African population. Exons 2, 7, 10, 11, 12, 14, 17, 21, 26, and the surrounding intronic regions were sequenced using genomic DNA from 111 Beninese subjects to examine 19 intragenic single nucleotide polymorphisms (SNPs). Linkage disequilibrium analysis and haplotypes were generated using the expectation-maximization algorithm. We identified 12 SNPs, 3 of which were novel: IVS9-57delA, IVS9-8T>A, 1662G>C (exon 14). The most common SNP was IVS14+38A>G. At the MRD1 locus, 53 haplotypes were inferred from the SNP data sets. The 4 SNPs, IVS6+139C>T, IVS9-44A>G, 1236C>T, and 3435C>T, showed strong linkage disequilibrium with each other, confirming the block concept. Moreover, our findings suggest that ABCB1 exonic SNPs are less frequently observed in our population than in African-Americans. Our data are compatible with a close evolutionary relationship in Black Africans from Benin.

  12. Integrative analysis of single nucleotide polymorphisms and gene expression efficiently distinguishes samples from closely related ethnic populations

    Directory of Open Access Journals (Sweden)

    Yang Hsin-Chou

    2012-07-01

    Full Text Available Abstract Background Ancestry informative markers (AIMs are a type of genetic marker that is informative for tracing the ancestral ethnicity of individuals. Application of AIMs has gained substantial attention in population genetics, forensic sciences, and medical genetics. Single nucleotide polymorphisms (SNPs, the materials of AIMs, are useful for classifying individuals from distinct continental origins but cannot discriminate individuals with subtle genetic differences from closely related ancestral lineages. Proof-of-principle studies have shown that gene expression (GE also is a heritable human variation that exhibits differential intensity distributions among ethnic groups. GE supplies ethnic information supplemental to SNPs; this motivated us to integrate SNP and GE markers to construct AIM panels with a reduced number of required markers and provide high accuracy in ancestry inference. Few studies in the literature have considered GE in this aspect, and none have integrated SNP and GE markers to aid classification of samples from closely related ethnic populations. Results We integrated a forward variable selection procedure into flexible discriminant analysis to identify key SNP and/or GE markers with the highest cross-validation prediction accuracy. By analyzing genome-wide SNP and/or GE markers in 210 independent samples from four ethnic groups in the HapMap II Project, we found that average testing accuracies for a majority of classification analyses were quite high, except for SNP-only analyses that were performed to discern study samples containing individuals from two close Asian populations. The average testing accuracies ranged from 0.53 to 0.79 for SNP-only analyses and increased to around 0.90 when GE markers were integrated together with SNP markers for the classification of samples from closely related Asian populations. Compared to GE-only analyses, integrative analyses of SNP and GE markers showed comparable testing

  13. Imputation Accuracy from Low to Moderate Density Single Nucleotide Polymorphism Chips in a Thai Multibreed Dairy Cattle Population

    Directory of Open Access Journals (Sweden)

    Danai Jattawa

    2016-04-01

    Full Text Available The objective of this study was to investigate the accuracy of imputation from low density (LDC to moderate density SNP chips (MDC in a Thai Holstein-Other multibreed dairy cattle population. Dairy cattle with complete pedigree information (n = 1,244 from 145 dairy farms were genotyped with GeneSeek GGP20K (n = 570, GGP26K (n = 540 and GGP80K (n = 134 chips. After checking for single nucleotide polymorphism (SNP quality, 17,779 SNP markers in common between the GGP20K, GGP26K, and GGP80K were used to represent MDC. Animals were divided into two groups, a reference group (n = 912 and a test group (n = 332. The SNP markers chosen for the test group were those located in positions corresponding to GeneSeek GGP9K (n = 7,652. The LDC to MDC genotype imputation was carried out using three different software packages, namely Beagle 3.3 (population-based algorithm, FImpute 2.2 (combined family- and population-based algorithms and Findhap 4 (combined family- and population-based algorithms. Imputation accuracies within and across chromosomes were calculated as ratios of correctly imputed SNP markers to overall imputed SNP markers. Imputation accuracy for the three software packages ranged from 76.79% to 93.94%. FImpute had higher imputation accuracy (93.94% than Findhap (84.64% and Beagle (76.79%. Imputation accuracies were similar and consistent across chromosomes for FImpute, but not for Findhap and Beagle. Most chromosomes that showed either high (73% or low (80% imputation accuracies were the same chromosomes that had above and below average linkage disequilibrium (LD; defined here as the correlation between pairs of adjacent SNP within chromosomes less than or equal to 1 Mb apart. Results indicated that FImpute was more suitable than Findhap and Beagle for genotype imputation in this Thai multibreed population. Perhaps additional increments in imputation accuracy could be achieved by increasing the completeness of pedigree information.

  14. Elevated Serum miR-7, miR-9, miR-122, and miR-141 Are Noninvasive Biomarkers of Acute Pancreatitis

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    Pan Lu

    2017-01-01

    Full Text Available Background. It has been reported that several microRNAs (miRNAs, such as miR-141, miR-9, and miR-122, are involved in the regulation of pancreatitis-related proteins or that their levels change in acute pancreatitis (AP animal models. However, the serum levels, as well as the clinical diagnostic and prognostic values, of these miRNAs in AP patients remain unclear. Furthermore, as a pancreas- (islet enriched miRNA, miR-7 was reported to be downregulated in AP patients, which requires further verification. Methods. The levels of miR-7, miR-9, miR-122, and miR-141 were examined and compared using qRT-PCR among 80 severe AP patients, 80 mild AP patients, and 74 healthy controls. Results. The serum levels of these four miRNAs were increased markedly in the AP patients compared with the controls, and these levels decreased significantly after effective therapy. Particularly, the level of miR-7 was higher in severe AP patients than in mild AP patients. ROC curve analysis demonstrated that four miRNAs could be used as potential biomarkers for AP. Moreover, these miRNAs showed strong positive correlations with CRP, which may be associated with inflammation. Conclusions. The serum miR-7, miR-9, miR-122, and miR-141 levels were increased in AP patients. These 4 miRNAs may represent diagnostic and prognostic biomarkers for AP.

  15. Association of single nucleotide polymorphisms in TCF2 with type 2 diabetes susceptibility in a Han Chinese population.

    Directory of Open Access Journals (Sweden)

    Xuelong Zhang

    Full Text Available Hepatocyte nuclear factor 1β (HNF1β, a transcription factor encoded by the transcription factor 2 gene (TCF2, plays a critical role in pancreatic cell formation and glucose homeostasis. It has been suggested that single nucleotide polymorphisms (SNPs of TCF2 are associated with susceptibility to type 2 diabetes (T2D. However, published results are inconsistent and inclusive. To further investigate the role of these common variants, we examined the association of TCF2 polymorphisms with the risk of T2D in a Han population in northeastern China. We genotyped five SNPs in 624 T2D patients and 630 healthy controls by using a SNaPshot method, and evaluated the T2D risk conferred by individual SNPs and haplotypes. In the single-locus analysis, we found that rs752010, rs4430796 and rs7501939 showed allelic differences between T2D patients and healthy controls, with an OR of 1.26 (95% CI 1.08-1.51, P = 0.003, an OR of 1.23 (95% CI 1.06-1.55, P = 0.001 and an OR of 1.28 (95% CI 1.10-1.61, P = 0.001, respectively. Genotype association analysis of each locus also revealed that the homozygous carriers of the at-risk allele had a significant increased T2D risk compared to homozygous carriers of the other allele (OR 1.78, 95% CI 1.20-2.64 for rs752010; OR 1.82, 95% CI 1.24-2.67 for rs4430796; OR 1.95, 95% CI 1.31-2.90 for rs7501939, even after Bonferroni correction for multiple comparisons. Besides, the haplotype-based analysis demonstrated that AGT in block rs752010-rs4430796-rs7501939 was associated with about 30% increase in T2D risk (OR 1.31, 95% CI 1.09-1.57, P = 0.01. Our findings suggested that TCF2 variants may be involved in T2D risk in a Han population of northeastern China. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.

  16. Clinical relevance of microRNA miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145 in colorectal cancer

    International Nuclear Information System (INIS)

    Schee, Kristina; Boye, Kjetil; Abrahamsen, Torveig Weum; Fodstad, Øystein; Flatmark, Kjersti

    2012-01-01

    MicroRNAs (miRNAs) regulate gene expression by binding to mRNA, and can function as oncogenes or tumor suppressors depending on the target. In this study, using qRT-PCR, we examined the expression of six miRNAs (miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145) in tumors from 193 prospectively recruited patients with colorectal cancer, and associations with clinicopathological parameters and patient outcome were analyzed. The miRNAs were chosen based on previous studies for their biomarker potential and suggested biological relevance in colorectal cancer. The miRNA expression was examined by qRT-PCR. Associations between miRNA expression and clinicopathological variables were explored using Mann–Whitney U and Kruskal-Wallis test while survival was estimated using the Kaplan-Meier method and compared using the log-rank test. MiR-101 was hardly expressed in the tumor samples, while for the other miRNAs, variable expression levels and expression ranges were observed, with miR-21 being most abundantly expressed relative to the reference (RNU44). In our study cohort, major clinical significance was demonstrated only for miR-31, as high expression was associated with advanced tumor stage and poor differentiation. No significant associations were found between expression of the investigated miRNAs and metastasis-free or overall survival. Investigating the expression of six miRNAs previously identified as candidate biomarkers in colorectal cancer, few clinically relevant associations were detected in our patient cohort. Our results emphasize the importance of validating potential tumor markers in independent patient cohorts, and indicate that the role of miRNAs as colorectal cancer biomarkers is still undetermined

  17. Two-miRNA classifiers differentiate mutation-negative follicular thyroid carcinomas and follicular thyroid adenomas in fine needle aspirations with high specificity

    DEFF Research Database (Denmark)

    Stokowy, Tomasz; Wojtas, Bartosz; Jarzab, Barbara

    2016-01-01

    , since no single miRNA had satisfactory predictive power, classifiers comprising two differentially expressed miRNAs were designed with the aim to improve the classification. Six two-miRNA classifiers were established and quantitative polymerase chain reaction validated in fine needle aspiration samples...

  18. MSDD: a manually curated database of experimentally supported associations among miRNAs, SNPs and human diseases.

    Science.gov (United States)

    Yue, Ming; Zhou, Dianshuang; Zhi, Hui; Wang, Peng; Zhang, Yan; Gao, Yue; Guo, Maoni; Li, Xin; Wang, Yanxia; Zhang, Yunpeng; Ning, Shangwei; Li, Xia

    2018-01-04

    The MiRNA SNP Disease Database (MSDD, http://www.bio-bigdata.com/msdd/) is a manually curated database that provides comprehensive experimentally supported associations among microRNAs (miRNAs), single nucleotide polymorphisms (SNPs) and human diseases. SNPs in miRNA-related functional regions such as mature miRNAs, promoter regions, pri-miRNAs, pre-miRNAs and target gene 3'-UTRs, collectively called 'miRSNPs', represent a novel category of functional molecules. miRSNPs can lead to miRNA and its target gene dysregulation, and resulting in susceptibility to or onset of human diseases. A curated collection and summary of miRSNP-associated diseases is essential for a thorough understanding of the mechanisms and functions of miRSNPs. Here, we describe MSDD, which currently documents 525 associations among 182 human miRNAs, 197 SNPs, 153 genes and 164 human diseases through a review of more than 2000 published papers. Each association incorporates information on the miRNAs, SNPs, miRNA target genes and disease names, SNP locations and alleles, the miRNA dysfunctional pattern, experimental techniques, a brief functional description, the original reference and additional annotation. MSDD provides a user-friendly interface to conveniently browse, retrieve, download and submit novel data. MSDD will significantly improve our understanding of miRNA dysfunction in disease, and thus, MSDD has the potential to serve as a timely and valuable resource. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. miREE: miRNA recognition elements ensemble

    Directory of Open Access Journals (Sweden)

    Reyes-Herrera Paula H

    2011-11-01

    Full Text Available Abstract Background Computational methods for microRNA target prediction are a fundamental step to understand the miRNA role in gene regulation, a key process in molecular biology. In this paper we present miREE, a novel microRNA target prediction tool. miREE is an ensemble of two parts entailing complementary but integrated roles in the prediction. The Ab-Initio module leverages upon a genetic algorithmic approach to generate a set of candidate sites on the basis of their microRNA-mRNA duplex stability properties. Then, a Support Vector Machine (SVM learning module evaluates the impact of microRNA recognition elements on the target gene. As a result the prediction takes into account information regarding both miRNA-target structural stability and accessibility. Results The proposed method significantly improves the state-of-the-art prediction tools in terms of accuracy with a better balance between specificity and sensitivity, as demonstrated by the experiments conducted on several large datasets across different species. miREE achieves this result by tackling two of the main challenges of current prediction tools: (1 The reduced number of false positives for the Ab-Initio part thanks to the integration of a machine learning module (2 the specificity of the machine learning part, obtained through an innovative technique for rich and representative negative records generation. The validation was conducted on experimental datasets where the miRNA:mRNA interactions had been obtained through (1 direct validation where even the binding site is provided, or through (2 indirect validation, based on gene expression variations obtained from high-throughput experiments where the specific interaction is not validated in detail and consequently the specific binding site is not provided. Conclusions The coupling of two parts: a sensitive Ab-Initio module and a selective machine learning part capable of recognizing the false positives, leads to an improved

  20. CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

    Science.gov (United States)

    Vartanian, Keri B; Mitchell, Hugh D; Stevens, Susan L; Conrad, Valerie K; McDermott, Jason E; Stenzel-Poore, Mary P

    2015-01-01

    Cytosine-phosphate-guanine (CpG) preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms underlying genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate gene expression; however, their role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning before and after stroke using microarray. Importantly, we have data from previous gene microarrays under the same conditions, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. CpG preconditioning did not significantly alter miRNA expression before stroke, indicating that miRNA regulation is not critical for the initiation of preconditioning-induced neuroprotection. However, after stroke, differentially regulated miRNAs between CpG- and saline-treated animals associated with the upregulation of several neuroprotective genes, implicating these miRNAs in genomic reprogramming that increases neuroprotection. Statistical analysis revealed that the miRNA targets were enriched in the gene population regulated in the setting of stroke, implying that miRNAs likely orchestrate this gene expression. These data suggest that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel neuroprotective processes that reduce damage. PMID:25388675

  1. Differing effects of attention in single-units and populations are well predicted by heterogeneous tuning and the normalization model of attention.

    Science.gov (United States)

    Hara, Yuko; Pestilli, Franco; Gardner, Justin L

    2014-01-01

    Single-unit measurements have reported many different effects of attention on contrast-response (e.g., contrast-gain, response-gain, additive-offset dependent on visibility), while functional imaging measurements have more uniformly reported increases in response across all contrasts (additive-offset). The normalization model of attention elegantly predicts the diversity of effects of attention reported in single-units well-tuned to the stimulus, but what predictions does it make for more realistic populations of neurons with heterogeneous tuning? Are predictions in accordance with population-scale measurements? We used functional imaging data from humans to determine a realistic ratio of attention-field to stimulus-drive size (a key parameter for the model) and predicted effects of attention in a population of model neurons with heterogeneous tuning. We found that within the population, neurons well-tuned to the stimulus showed a response-gain effect, while less-well-tuned neurons showed a contrast-gain effect. Averaged across the population, these disparate effects of attention gave rise to additive-offsets in contrast-response, similar to reports in human functional imaging as well as population averages of single-units. Differences in predictions for single-units and populations were observed across a wide range of model parameters (ratios of attention-field to stimulus-drive size and the amount of baseline response modifiable by attention), offering an explanation for disparity in physiological reports. Thus, by accounting for heterogeneity in tuning of realistic neuronal populations, the normalization model of attention can not only predict responses of well-tuned neurons, but also the activity of large populations of neurons. More generally, computational models can unify physiological findings across different scales of measurement, and make links to behavior, but only if factors such as heterogeneous tuning within a population are properly accounted for.

  2. MiSeq: A Next Generation Sequencing Platform for Genomic Analysis.

    Science.gov (United States)

    Ravi, Rupesh Kanchi; Walton, Kendra; Khosroheidari, Mahdieh

    2018-01-01

    MiSeq, Illumina's integrated next generation sequencing instrument, uses reversible-terminator sequencing-by-synthesis technology to provide end-to-end sequencing solutions. The MiSeq instrument is one of the smallest benchtop sequencers that can perform onboard cluster generation, amplification, genomic DNA sequencing, and data analysis, including base calling, alignment and variant calling, in a single run. It performs both single- and paired-end runs with adjustable read lengths from 1 × 36 base pairs to 2 × 300 base pairs. A single run can produce output data of up to 15 Gb in as little as 4 h of runtime and can output up to 25 M single reads and 50 M paired-end reads. Thus, MiSeq provides an ideal platform for rapid turnaround time. MiSeq is also a cost-effective tool for various analyses focused on targeted gene sequencing (amplicon sequencing and target enrichment), metagenomics, and gene expression studies. For these reasons, MiSeq has become one of the most widely used next generation sequencing platforms. Here, we provide a protocol to prepare libraries for sequencing using the MiSeq instrument and basic guidelines for analysis of output data from the MiSeq sequencing run.

  3. Population pharmacokinetics of a single dose of meloxicam after oral and intramuscular administration to captive lesser flamingos (Phoeniconaias minor).

    Science.gov (United States)

    Zordan, Martín A; Papich, Mark G; Pich, Ashley A; Unger, Katy M; Sánchez, Carlos R

    2016-12-01

    OBJECTIVE To determine the pharmacokinetics of a single dose of meloxicam after IM and oral administration to healthy lesser flamingos (Phoeniconaias minor) by use of a population approach. ANIMALS 16 healthy captive lesser flamingos between 1 and 4 years of age. PROCEDURES A single dose of meloxicam (0.5 mg/kg) was administered IM to each bird, and blood samples were collected from birds at 3 (n = 13 birds), 2 (2), or 1 (1) selected point between 0 and 13 hours after administration, with samples collected from birds at each point. After a 15-day washout period, the same dose of meloxicam was administered PO via a red rubber tube and blood samples were collected as described for IM administration. Pharmacokinetic values were determined from plasma concentrations measured by high-performance liquid chromatography. RESULTS Plasma drug concentrations after IM administration of meloxicam reached a mean ± SD maximum value of 6.01 ± 3.38 μg/mL. Mean area under the concentration-versus-time curve was 17.78 ± 2.79 μg•h/mL, and mean elimination half-life was 1.93 ± 0.32 hours. Plasma concentrations after oral administration reached a mean maximum value of 1.79 ± 0.33 μg/mL. Mean area under the curve was 22.16 ± 7.17 μg•h/mL, and mean elimination half-life was 6.05 ± 3.53 hours. CONCLUSIONS AND CLINICAL RELEVANCE In lesser flamingos, oral administration of meloxicam resulted in higher bioavailability and a longer elimination half-life than did IM administration, but the maximum plasma concentration was low and may be insufficient to provide analgesia in flamingos. Conversely, IM administration achieved the desired plasma concentration but would require more frequent administration.

  4. Effects of Single and Fractionated Irradiation on Natural Killer Cell Populations: Radiobiological Characteristics of Viability and Cytotoxicity In Vitro.

    Science.gov (United States)

    Hietanen, Tenho; Pitkänen, Maunu; Kapanen, Mika; Kellokumpu-Lehtinen, Pirkko-Liisa

    2015-10-01

    Natural killer (NK) cells are important in destroying tumor cells. However, they are damaged by radiation therapy. We studied the effects of single and fractionated irradiation on the viability and cytotoxicity of human non-selected NK cells and sub-groups with cluster of differentiation (CD) CD16(+) and CD56(+) in vitro. Only very few studies dealing with the standard radiobiological parameters for characterizing NK cells exist in the literature. NK cell populations were isolated from buffy coats using different methods and irradiated with single doses up to 80 Gy and fractionated doses of 10 or 30 Gy with different numbers of applications and at different intervals. The study end-points were viability using propidium iodide (PI), trypan blue and intracellular adenosine triphosphate (ATP) assays, and cytotoxicity using the (51)Cr-release assay. The standard radiobiological parameters α and β of the linear-quadratic (L-Q) model and the mean inactivation dose D̅ taken as the area under the curve (AUC) were calculated to characterize the radiosensitivity of different NK cell populations. The AUC values of the 51Cr release data in the dose range of 0-40 Gy were as follows: for non-selected NK cells, 23.6-20.9 Gy; for CD16(+) and CD56(+) cells, 14.5-13.2 Gy. The AUC values of ATP, trypan blue and propidium iodide methods equally well described the viability of irradiated NK cells. The α/β ratio for cytotoxicity and viability data in the L-Q model corresponded to the acutely responding tissues. Splitting a 30-Gy dose into two fractions applied at different intervals caused a significant rise in ATP levels and cytotoxicity. Dividing the total dose into four doses applied at fixed intervals also resulted in significant elevations of ATP content and cytotoxicity of NK cells at 10 Gy. According to the L-Q method, irradiated NK cells behaved similarly to acutely responding human tissues with respect to cytotoxicity and viability. The AUC proved very useful for comparing

  5. MiR-214 regulates the function of osteoblast under simulated microgravity by targeting ATF4

    Science.gov (United States)

    Li, Yingxian; Wang, Xiaogang; Li, Qi; Lv, Ke; Wan, Yumin; Li, Yinghui; Bai, Yanqiang

    Background: MicroRNAs (miRNAs) are small fragments of single-stranded RNA containing 18-24 nucleotides, and are generated from endogenous transcripts. MicroRNAs function in post-transcriptional gene silencing by targeting the 3'-untranslated region (UTR) of mRNAs, resulting in translational repression. Growing evidence shows that microRNAs (miRNAs) regu-late various developmental and homeostatic events in vertebrates and invertebrates. Osteoblast differentiation is a key step in proper skeletal development and acquisition of bone mass; How-ever, the physiological role of non-coding small RNAs, especially miRNAs, in osteoblast dif-ferentiation remains elusive. Methods: To study the potential involvement of miRNAs in osteoblast differentiation under stimulated microgravity, we analyzed the expression of 20 bone relative miRNAs using real time PCR platform to find particularly miRNAs whose expression is altered during osteoblast differentiation. TargetScan, miRBase and Miranda were used to predict the target gene of candidate miRNA. To investigate whether ATF4 can be directly targeted by miR-214, we engineered luciferase reporters that have either the wild-type 3'UTRs of these genes, or the mutant UTRs with a 6 base pair (bp) deletion in the target sites. Lastly, to address the in vivo role of miR-214 in bone formation, tail suspension mice model was used to simulate the change of osteoblast function and bone loss. Results: Recent studies have sug-gested that miRNAs might play a role in osteoblast differentiation and bone formation. Here, we identify miR-214 in MC3T3-E1 cells, which is a primary mouse osteoblasts cell line, to promote osteoblast differentiation by repressing Activating Transcription Factor4 (ATF4) ex-pression at the posttranscriptional level. What is more, miR-214 was found to be transcribed in C2C12 cells during bone morphogenetic protein 2-induced (BMP2-induced) osteogenesis, and overexpression of miR-214 attenuated BMP2-induced osteoblastogenesis

  6. A Putative Association of a Single Nucleotide Polymorphism in GPR126 with Aggressive Periodontitis in a Japanese Population.

    Science.gov (United States)

    Kitagaki, Jirouta; Miyauchi, Shizuka; Asano, Yoshihiro; Imai, Atsuko; Kawai, Shinji; Michikami, Ikumi; Yamashita, Motozo; Yamada, Satoru; Kitamura, Masahiro; Murakami, Shinya

    2016-01-01

    Periodontitis is an inflammatory disease causing loss of tooth-supporting periodontal tissue. Disease susceptibility to the rapidly progressive form of periodontitis, aggressive periodontitis (AgP), appears to be influenced by genetic risk factors. To identify these in a Japanese population, we performed whole exome sequencing of 41 unrelated generalized or localized AgP patients. We found that AgP is putatively associated with single nucleotide polymorphism (SNP) rs536714306 in the G-protein coupled receptor 126 gene, GPR126 [c.3086 G>A (p.Arg1029Gln)]. Since GPR126 activates the cAMP/PKA signaling pathway, we performed cAMP ELISA analysis of cAMP concentrations, and found that rs536714306 impaired the signal transactivation of GPR126. Moreover, transfection of human periodontal ligament (HPDL) cells with wild-type or mutant GPR126 containing rs536714306 showed that wild-type GPR126 significantly increased the mRNA expression of bone sialoprotein, osteopontin, and Runx2 genes, while mutant GPR126 had no effect on the expression of these calcification-related genes. The increase in expression of these genes was through the GPR126-induced increase of bone morphogenic protein-2, inhibitor of DNA binding (ID) 2, and ID4 expression. These data indicate that GPR126 might be important in maintaining the homeostasis of periodontal ligament tissues through regulating the cytodifferentiation of HPDL cells. The GPR126 SNP rs536714306 negatively influences this homeostasis, leading to the development of AgP, suggesting that it is a candidate genetic risk factor for AgP in the Japanese population.

  7. Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Kim, Yo Han; Hong, Donghyun; Kim, Seong Su; Bae, Kyun-Seop; Lim, Hyeong-Seok

    2015-08-01

    We performed population pharmacokinetic (PK) analysis of a novel transdermal donepezil patch in healthy subjects who participated in a phase I trial. We also studied the optimal dosage regimen with repeated patch application for achieving a therapeutic range using a PK simulation model. This study used data from a randomized, single-dose escalation phase I clinical trial conducted in Korea. The population PK analysis was performed using NONMEM software, version 7.3. From the final PK model, we simulated repeat patch application results assuming various transdermal absorption rates. Based on the clinical trial data, novel donepezil patches with doses of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), and 175 mg/50 cm(2) were placed on each subject. A linear one-compartment, first-order elimination with sequential zero- and first-order absorption model best described the donepezil plasma concentrations after patch application. Simulated results on the basis of the PK model showed that repeat application of the patches of 87.5 mg/25 cm(2) and 175 mg/50 cm(2) every 72 h would cover the therapeutic range of donepezil and reach steady-state faster with fewer fluctuations in concentration compared to typical oral administrations. A linear one-compartment with sequential zero- and first-order absorption model was effective for describing the PKs of donepezil after application of patch. Based on this analysis, 87.5 mg/25 cm(2) or 175 mg/50 cm(2) patch application every 72 h is expected to achieve the desired plasma concentration of donepezil.

  8. A single haplotype hyposensitive to light and requiring strong vernalization dominates Arabidopsis thaliana populations in Patagonia, Argentina.

    Science.gov (United States)

    Kasulin, Luciana; Rowan, Beth A; León, Rolando J C; Schuenemann, Verena J; Weigel, Detlef; Botto, Javier F

    2017-07-01

    The growing collection of sequenced or genotyped Arabidopsis thaliana accessions includes mostly individuals from the native Eurasian and N. African range and introduced North American populations. Here, we describe the genetic and phenotypic diversity, along with habitats and life history, of A. thaliana plants collected at the southernmost end of its worldwide distribution. Seed samples were harvested from plants growing in four sites within a ~3500-km 2 -area in Patagonia, Argentina, and represent the first germplasm to be collected in South America for this species. Whole-genome resequencing revealed that plants from the four sites and a Patagonia herbarium specimen collected in 1967 formed a single haplogroup (Pat), indicating that the phenotypic variation observed in the field reflected plastic responses to the environment. admixture and principal components analyses suggest that the ancestor of the Pat haplogroup either came from Italy or the Balkan/Caucasus regions of Eurasia. In the laboratory, plants from the Pat haplogroup were hyposensitive to continuous red (Rc) and shade light, with corresponding changes in the expression of phytochrome signalling genes. Pat had higher PIF3 and PIF5 and lower HY5 expression under Rc light; and lower expression of PIL1, ATHB2 and HFR1 under shade compared to Col-0. In addition, Pat plants had a strong vernalization requirement associated with high levels of FLC expression. We conclude that including Pat in studies of natural variation and in comparison with other introduced populations will provide additional information for association studies and allow for a more detailed assessment of the demographic events following colonization. © 2017 John Wiley & Sons Ltd.

  9. The association between two common polymorphisms in MicroRNAs and hepatocellular carcinoma risk in Asian population.

    Directory of Open Access Journals (Sweden)

    Miao Hu

    Full Text Available BACKGROUND: Emerging evidence has shown that microRNAs (miRNAs participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP located in the miRNAs may influence the function of mature miRNAs and then affect the processing of carcinogenesis. It has been suggested that two common SNPs rs2910164 in miR-146a and rs3746444 in miR-499 are associated with susceptibility to hepatocellular carcinoma (HCC. However, published results are inconsistent and inconclusive. To acquire a more precise effect of the association between these polymorphisms and HCC risk, we performed this meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: We have conducted a search of case-control studies on the associations of SNPs rs2910164 and/or rs3746444 with susceptibility to HCC in PubMed, ScienceDirect, Cochrane Central Register of Controlled Trials, and Chinese National Knowledge Infrastructure databases for the period up to Sep 10th, 2012. A total of 6 studies were identified with 2071 cases and 2350 controls for miR-146a rs2910164 polymorphism, 667 cases and 1006 controls for miR-499 rs3746444 polymorphism. It was found that neither allele frequency nor genotype distribution of the two polymorphisms was associated with risk of HCC in all genetic models. Similarly, subgroup analysis in Asian population showed no associations between the two SNPs and the susceptibility to HCC. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that miR-146a rs2910164 and miR-499 rs3746444 polymorphisms may not be associated with the risk of HCC, especially for Asian population. However, well-designed studies with larger sample size and more detailed data are needed to confirm these conclusions.

  10. A Pre-microRNA-149 (miR-149) Genetic Variation Affects miR-149 Maturation and Its Ability to Regulate the Puma Protein in Apoptosis*♦

    Science.gov (United States)

    Ding, Su-Ling; Wang, Jian-Xun; Jiao, Jian-Qin; Tu, Xin; Wang, Qing; Liu, Fang; Li, Qian; Gao, Jie; Zhou, Qun-Yong; Gu, Dong-Feng; Li, Pei-Feng

    2013-01-01

    MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs that function as negative regulators of gene expression. They are transcribed from endogenous DNA and form hairpin structures (termed as pre-miRNAs) that are processed to form mature miRNAs. It remains largely unknown as to the molecular consequences of the natural genetic variation in pre-miRNAs. Here, we report that an A→G polymorphism (rs71428439) is located in Homo sapiens miR-149 stem-loop region. This polymorphism results in a change in the structure of the miR-149 precursor. Our results showed that the genotype distribution of this polymorphism in myocardial infarction cases was significantly different from that in the control subjects. We examined the biological significance of this polymorphism on the production of mature miR-149, and we observed that the G-allelic miR-149 precursor displayed a lower production of mature miR-149 compared with the A-allelic one. Further investigations disclosed that miR-149 could withstand mitochondrial fission and apoptosis through targeting the pro-apoptotic factor p53-up-regulated modulator of apoptosis (Puma). Enforced expression of miR-149 promoted cell survival, whereas knockdown of miR-149 rendered cells to be sensitive to apoptotic stimulation. Intriguingly, the A to G variation led pre-miR-149 to elicit an attenuated effect on the inhibition of mitochondrial fission and apoptosis. Finally, this polymorphism exerts its influence on cardiac function in the mouse model of myocardial infarction. These data suggest that this polymorphism in the miR-149 precursor may result in important phenotypic traits of myocardial infarction. Our findings warrant further investigations on the relationship between miR-149 polymorphism and myocardial infarction. PMID:23873935

  11. Identification of a new target of miR-16, Vacuolar Protein Sorting 4a.

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    Neeta Adhikari

    Full Text Available The rationale was to utilize a bioinformatics approach to identify miRNA binding sites in genes with single nucleotide mutations (SNPs to discover pathways in heart failure (HF.The objective was to focus on the genes containing miRNA binding sites with miRNAs that were significantly altered in end-stage HF and in response to a left ventricular assist device (LVAD.BEDTools v2.14.3 was used to discriminate SNPs within predicted 3'UTR miRNA binding sites. A member of the miR-15/107 family, miR-16, was decreased in the circulation of end-stage HF patients and increased in response to a LVAD (p<0.001. MiR-16 decreased Vacuolar Protein Sorting 4a (VPS4a expression in HEK 293T cells (p<0.01. The SNP rs16958754 was identified in the miR-15/107 family binding site of VPS4a which abolished direct binding of miR-16 to the 3'UTR of VPS4a (p<0.05. VPS4a was increased in the circulation of end-stage HF patients (p<0.001, and led to a decrease in the number of HEK 293T cells in vitro (p<0.001.We provide evidence that miR-16 decreases in the circulation of end-stage HF patients and increases with a LVAD. Modeling studies suggest that miR-16 binds to and decreases expression of VPS4a. Overexpression of VPS4a decreases cell number. Together, these experiments suggest that miR-16 and VPS4a expression are altered in end-stage HF and in response to unloading with a LVAD. This signaling pathway may lead to reduced circulating cell number in HF.

  12. MiR-34a deficiency accelerates medulloblastoma formation in vivo.

    Science.gov (United States)

    Thor, Theresa; Künkele, Annette; Pajtler, Kristian W; Wefers, Annika K; Stephan, Harald; Mestdagh, Pieter; Heukamp, Lukas; Hartmann, Wolfgang; Vandesompele, Jo; Sadowski, Natalie; Becker, Lore; Garrett, Lillian; Hölter, Sabine M; Horsch, Marion; Calzada-Wack, Julia; Klein-Rodewald, Tanja; Racz, Ildiko; Zimmer, Andreas; Beckers, Johannes; Neff, Frauke; Klopstock, Thomas; De Antonellis, Pasqualino; Zollo, Massimo; Wurst, Wolfgang; Fuchs, Helmut; Gailus-Durner, Valérie; Schüller, Ulrich; de Angelis, Martin Hrabě; Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H

    2015-05-15

    Previous studies have evaluated the role of miRNAs in cancer initiation and progression. MiR-34a was found to be downregulated in several tumors, including medulloblastomas. Here we employed targeted transgenesis to analyze the function of miR-34a in vivo. We generated mice with a constitutive deletion of the miR-34a gene. These mice were devoid of mir-34a expression in all analyzed tissues, but were viable and fertile. A comprehensive standardized phenotypic analysis including more than 300 single parameters revealed no apparent phenotype. Analysis of miR-34a expression in human medulloblastomas and medulloblastoma cell lines revealed significantly lower levels than in normal human cerebellum. Re-expression of miR-34a in human medulloblastoma cells reduced cell viability and proliferation, induced apoptosis and downregulated the miR-34a target genes, MYCN and SIRT1. Activation of the Shh pathway by targeting SmoA1 transgene overexpression causes medulloblastoma in mice, which is dependent on the presence and upregulation of Mycn. Analysis of miR-34a in medulloblastomas derived from ND2:SmoA1(tg) mice revealed significant suppression of miR-34a compared to normal cerebellum. Tumor incidence was significantly increased and tumor formation was significantly accelerated in mice transgenic for SmoA1 and lacking miR-34a. Interestingly, Mycn and Sirt1 were strongly expressed in medulloblastomas derived from these mice. We here demonstrate that miR-34a is dispensable for normal development, but that its loss accelerates medulloblastomagenesis. Strategies aiming to re-express miR-34a in tumors could, therefore, represent an efficient therapeutic option. © 2014 UICC.

  13. Response of Listeria monocytogenes to disinfection stress at the single-cell and population levels as monitored by intracellular pH measurements and viable-cell counts

    DEFF Research Database (Denmark)

    Kastbjerg, Vicky Gaedt; Nielsen, Dennis S.; Arneborg, Nils

    2009-01-01

    of the bacterium. In situ analyses of Listeria monocytogenes single cells were performed during exposure to different concentrations of the disinfectant Incimaxx DES to study a possible population subdivision. Bacterial survival was quantified with plate counting and disinfection stress at the single-cell level...... by measuring intracellular pH (pHi) over time by fluorescence ratio imaging microscopy. pHi values were initially 7 to 7.5 and decreased in both attached and planktonic L. monocytogenes cells during exposure to sublethal and lethal concentrations of Incimaxx DES. The response of the bacterial population...... that a population of L. monocytogenes cells, whether planktonic or attached, is homogenous with respect to sensitivity to an acidic disinfectant studied on the single-cell level. Hence a major subpopulation more tolerant to disinfectants, and hence more persistent, does not appear to be present....

  14. QTLs Associated with Agronomic Traits in the Cutler × AC Barrie Spring Wheat Mapping Population Using Single Nucleotide Polymorphic Markers

    Science.gov (United States)

    Perez-Lara, Enid; Semagn, Kassa; Chen, Hua; Iqbal, Muhammad; N’Diaye, Amidou; Kamran, Atif; Navabi, Alireza; Pozniak, Curtis; Spaner, Dean

    2016-01-01

    We recently reported three earliness per se quantitative trait loci (QTL) associated with flowering and maturity in a recombinant inbred lines (RILs) population derived from a cross between the spring wheat (Triticum aestivum L.) cultivars ‘Cutler’ and ‘AC Barrie’ using 488 microsatellite and diversity arrays technology (DArT) markers. Here, we present QTLs associated with flowering time, maturity, plant height, and grain yield using high density single nucleotide polymorphic (SNP) markers in the same population. A mapping population of 158 RILs and the two parents were evaluated at five environments for flowering, maturity, plant height and grain yield under field conditions, at two greenhouse environments for flowering, and genotyped with a subset of 1809 SNPs out of the 90K SNP array and 2 functional markers (Ppd-D1 and Rht-D1). Using composite interval mapping on the combined phenotype data across all environments, we identified a total of 19 QTLs associated with flowering time in greenhouse (5), and field (6) conditions, maturity (5), grain yield (2) and plant height (1). We mapped these QTLs on 8 chromosomes and they individually explained between 6.3 and 37.8% of the phenotypic variation. Four of the 19 QTLs were associated with multiple traits, including a QTL on 2D associated with flowering, maturity and grain yield; two QTLs on 4A and 7A associated with flowering and maturity, and another QTL on 4D associated with maturity and plant height. However, only the QTLs on both 2D and 4D had major effects, and they mapped adjacent to well-known photoperiod response Ppd-D1 and height reducing Rht-D1 genes, respectively. The QTL on 2D reduced flowering and maturity time up to 5 days with a yield penalty of 436 kg ha-1, while the QTL on 4D reduced plant height by 13 cm, but increased maturity by 2 days. The high density SNPs allowed us to map eight moderate effect, two major effect, and nine minor effect QTLs that were not identified in our previous study

  15. The regulatory effect of miRNAs is a heritable genetic trait in humans

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    Geeleher Paul

    2012-08-01

    Full Text Available Abstract Background microRNAs (miRNAs have been shown to regulate the expression of a large number of genes and play key roles in many biological processes. Several previous studies have quantified the inhibitory effect of a miRNA indirectly by considering the expression levels of genes that are predicted to be targeted by the miRNA and this approach has been shown to be robust to the choice of prediction algorithm. Given a gene expression dataset, Cheng et al. defined the regulatory effect score (RE-score of a miRNA as the difference in the gene expression rank of targets of the miRNA compared to non-targeted genes. Results Using microarray data from parent-offspring trios from the International HapMap project, we show that the RE-score of most miRNAs is correlated between parents and offspring and, thus, inter-individual variation in RE-score has a genetic component in humans. Indeed, the mean RE-score across miRNAs is correlated between parents and offspring, suggesting genetic differences in the overall efficiency of the miRNA biogenesis pathway between individuals. To explore the genetics of this quantitative trait further, we carried out a genome-wide association study of the mean RE-score separately in two HapMap populations (CEU and YRI. No genome-wide significant associations were discovered; however, a SNP rs17409624, in an intron of DROSHA, was significantly associated with mean RE-score in the CEU population following permutation-based control for multiple testing based on all SNPs mapped to the canonical miRNA biogenesis pathway; of 244 individual miRNA RE-scores assessed in the CEU, 214 were associated (p p = 0.04 with mean RE-score in the YRI population. Interestingly, the same SNP was associated with 17 (8.5% of all expressed miRNA expression levels in the CEU. We also show here that the expression of the targets of most miRNAs is more highly correlated with global changes in miRNA regulatory effect than with the expression of

  16. Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

    International Nuclear Information System (INIS)

    Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A.; Pustylnyak, Yuliya A.; Pustylnyak, Vladimir O.

    2015-01-01

    MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR decreases

  17. miRge - A Multiplexed Method of Processing Small RNA-Seq Data to Determine MicroRNA Entropy.

    Directory of Open Access Journals (Sweden)

    Alexander S Baras

    Full Text Available Small RNA RNA-seq for microRNAs (miRNAs is a rapidly developing field where opportunities still exist to create better bioinformatics tools to process these large datasets and generate new, useful analyses. We built miRge to be a fast, smart small RNA-seq solution to process samples in a highly multiplexed fashion. miRge employs a Bayesian alignment approach, whereby reads are sequentially aligned against customized mature miRNA, hairpin miRNA, noncoding RNA and mRNA sequence libraries. miRNAs are summarized at the level of raw reads in addition to reads per million (RPM. Reads for all other RNA species (tRNA, rRNA, snoRNA, mRNA are provided, which is useful for identifying potential contaminants and optimizing small RNA purification strategies. miRge was designed to optimally identify miRNA isomiRs and employs an entropy based statistical measurement to identify differential production of isomiRs. This allowed us to identify decreasing entropy in isomiRs as stem cells mature into retinal pigment epithelial cells. Conversely, we show that pancreatic tumor miRNAs have similar entropy to matched normal pancreatic tissues. In a head-to-head comparison with other miRNA analysis tools (miRExpress 2.0, sRNAbench, omiRAs, miRDeep2, Chimira, UEA small RNA Workbench, miRge was faster (4 to 32-fold and was among the top-two methods in maximally aligning miRNAs reads per sample. Moreover, miRge has no inherent limits to its multiplexing. miRge was capable of simultaneously analyzing 100 small RNA-Seq samples in 52 minutes, providing an integrated analysis of miRNA expression across all samples. As miRge was designed for analysis of single as well as multiple samples, miRge is an ideal tool for high and low-throughput users. miRge is freely available at http://atlas.pathology.jhu.edu/baras/miRge.html.

  18. MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b.

    Science.gov (United States)

    Roscigno, Giuseppina; Quintavalle, Cristina; Donnarumma, Elvira; Puoti, Ilaria; Diaz-Lagares, Angel; Iaboni, Margherita; Fiore, Danilo; Russo, Valentina; Todaro, Matilde; Romano, Giulia; Thomas, Renato; Cortino, Giuseppina; Gaggianesi, Miriam; Esteller, Manel; Croce, Carlo M; Condorelli, Gerolama

    2016-01-05

    Cancer stem cells (CSCs) are a small part of the heterogeneous tumor cell population possessing self-renewal and multilineage differentiation potential as well as a great ability to sustain tumorigenesis. The molecular pathways underlying CSC phenotype are not yet well characterized. MicroRNAs (miRs) are small noncoding RNAs that play a powerful role in biological processes. Early studies have linked miRs to the control of self-renewal and differentiation in normal and cancer stem cells. We aimed to study the functional role of miRs in human breast cancer stem cells (BCSCs), also named mammospheres. We found that miR-221 was upregulated in BCSCs compared to their differentiated counterpart. Similarly, mammospheres from T47D cells had an increased level of miR-221 compared to differentiated cells. Transfection of miR-221 in T47D cells increased the number of mammospheres and the expression of stem cell markers. Among miR-221's targets, we identified DNMT3b. Furthermore, in BCSCs we found that DNMT3b repressed the expression of various stemness genes, such as Nanog and Oct 3/4, acting on the methylation of their promoters, partially reverting the effect of miR-221 on stemness. We hypothesize that miR-221 contributes to breast cancer tumorigenicity by regulating stemness, at least in part through the control of DNMT3b expression.

  19. miR-34a expands myeloid-derived suppressor cells via apoptosis inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Anfei, E-mail: huang_anfei@163.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Zhang, Haitao, E-mail: zhanghtjp@126.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215021, Jiangsu Province (China); Chen, Si, E-mail: chensisdyxb@126.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Xia, Fei, E-mail: xiafei87@gmail.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Yang, Yi, E-mail: 602744364@qq.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Dong, Fulu, E-mail: adiok0903@126.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Sun, Di, E-mail: dongfl@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Xiong, Sidong, E-mail: sdxiong@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Zhang, Jinping, E-mail: j_pzhang@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China)

    2014-08-15

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population and show significant expansion under pathological conditions. microRNA plays important roles in many biological processes, whether microRNAs have a function in the expansion of MDSCs is still not very clear. In this study, miR-34a overexpression can induce the expansion of MDSCs in bone marrow chimera and transgenic mice model. The experimental results suggest that miR-34a inhibited the apoptosis of MDSCs but did not affect the proliferation of MDSCs. The distinct mRNA microarray profiles of MDSCs of wild type and miR-34a over-expressing MDSCs combined with the target prediction of miR-34a suggest that miR-34a may target genes such as p2rx7, Tia1, and plekhf1 to inhibit the apoptosis of MDSCs. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis of MDSCs. - Highlights: • Over-expression of miR-34a increases the number of MDSCs. • miR-34a inhibits the apoptosis of MDSCs, but does not affects their proliferation. • miR-34a may inhibit the apoptosis of MDSCs via targeting the p2rx7, Tia1 and plekhf1.

  20. Safety of and tolerance to adenosine infusion for myocardial perfusion single-photon emission computed tomography in a Japanese population.

    Science.gov (United States)

    Hatanaka, Kunihiko; Doi, Masayuki; Hirohata, Satoshi; Kamikawa, Shigeshi; Kaji, Yoko; Katoh, Tsutomu; Kusachi, Shozo; Ninomiya, Yoshifumi; Ohe, Tohru

    2007-06-01

    Adenosine has been available for use in myocardial perfusion single-photon emission computed tomography (SPECT) in Japan since 2005. The purpose of this study was to evaluate the safety of and tolerance to thallium-201 myocardial perfusion SPECT with intravenous adenosine infusion in Japanese patients with suspected coronary artery disease. Two hundred and six consecutive patients who underwent an adenosine infusion (120 mug . kg(-1) . min(-1)) SPECT at Sumitomo Besshi Hospital (Niihama, Japan) were investigated. The effects of adenosine infusion were monitored for each patient. A coronary angiography was performed in 81 patients. Adenosine infusion significantly decreased blood pressure and increased heart rate. Adverse reactions were observed in 161 patients (78.2%). Most reactions were transient, disappearing soon after the termination of adenosine infusion. No serious adverse reactions, such as acute myocardial infarction or death, occurred. Adenosine infusion was terminated in 3 patients (1.5%) because of near syncope or sustained 2:1 atrioventricular block. Electrocardiographic changes occurred in 15 patients (7.3%). Self-assessed scoring after SPECT showed that the patients were very tolerant (74.6% of 177 patients) of adenosine infusion myocardial SPECT. The sensitivity and specificity were 75.0% and 69.7%, respectively. Adenosine infusion myocardial SPECT is safe and well tolerated in the Japanese population, despite the frequent occurrence of minor adverse reactions.

  1. Comparison of single nucleotide polymorphisms and microsatellites in non-invasive genetic monitoring of a wolf population

    Directory of Open Access Journals (Sweden)

    Fabbri Elena

    2012-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs which represent the most widespread source of sequence variation in genomes, are becoming a routine application in several fields such as forensics, ecology and conservation genetics. Their use, requiring short amplifications, may allow a more efficient genotyping of degraded DNA. We provide the first application of SNP genotyping in an Italian non-invasive genetic monitoring project of the wolf. We compared three different techniques for genotyping SNPs: pyrosequencing, SNaPshot® and TaqMan® Probe Assay in Real-Time PCR. We successively genotyped nine SNPs using the TaqMan Probe Assay in 51 Italian wolves, 57 domestic dogs, 15 wolf x dog hybrids and 313 wolf scats collected in the northern Apennines. The obtained results were used to estimate genetic variability and PCR error rates in SNP genotyping protocols compared to standard microsatellite analysis. We evaluated the cost, laboratory effort and reliability of these different markers and discuss the possible future use of VeraCode, SNPlex and Fluidigm EP1 system in wild population monitoring.

  2. A novel high-resolution single locus sequence typing scheme for mixed populations of Propionibacterium acnes in vivo.

    Directory of Open Access Journals (Sweden)

    Christian F P Scholz

    Full Text Available The Gram-positive anaerobic bacterium Propionibacterium acnes is a prevalent member of the normal skin microbiota of human adults. In addition to its suspected role in acne vulgaris it is involved in a variety of opportunistic infections. Multi-locus sequence-typing (MLST schemes identified distinct phylotypes associated with health and disease. Being based on 8 to 9 house-keeping genes these MLST schemes have a high discriminatory power, but their application is time- and cost-intensive. Here we describe a single-locus sequence typing (SLST scheme for P. acnes. The target locus was identified with a genome mining approach that took advantage of the availability of representative genome sequences of all known phylotypes of P. acnes. We applied this SLST on a collection of 188 P. acnes strains and demonstrated a resolution comparable to that of existing MLST schemes. Phylogenetic analysis applied to the SLST locus resulted in clustering patterns identical to a reference tree based on core genome sequences. We further demonstrate that SLST can be applied to detect multiple phylotypes in complex microbial communities by a metagenomic pyrosequencing approach. The described SLST strategy may be applied to any bacterial species with a basically clonal population structure to achieve easy typing and mapping of multiple phylotypes in complex microbiotas. The P. acnes SLST database can be found at http://medbac.dk/slst/pacnes.

  3. Chosen single nucleotide polymorphisms (SNPs) of enamel formation genes and dental caries in a population of Polish children.

    Science.gov (United States)

    Gerreth, Karolina; Zaorska, Katarzyna; Zabel, Maciej; Borysewicz-Lewicka, Maria; Nowicki, Michał

    2017-09-01

    It is increasingly emphasized that the influence of a host's factors in the etiology of dental caries are of most interest, particularly those concerned with genetic aspect. The aim of the study was to analyze the genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in AMELX, AMBN, TUFT1, TFIP11, MMP20 and KLK4 genes and to prove their association with dental caries occurrence in a population of Polish children. The study was performed in 96 children (48 individuals with caries - "cases" and 48 free of this disease - "controls"), aged 20-42 months, chosen out of 262 individuals who had dental examination performed and attended 4 day nurseries located in Poznań (Poland). From both groups oral swab was collected for molecular evaluation. Eleven selected SNPs markers were genotyped by Sanger sequencing. Genotype and allele frequencies were calculated and a standard χ2 analysis was used to test for deviation from Hardy-Weinberg equilibrium. The association of genetic variations with caries susceptibility or resistance was assessed by the Fisher's exact test and p ≤ 0.05 was considered statistically significant. Five markers were significantly associated with caries incidence in children in the study: rs17878486 in AMELX (p caries occurrence in Polish children.

  4. Diverse miRNA spatial expression patterns suggest important roles in homeostasis and regeneration in planarians.

    Science.gov (United States)

    González-Estévez, Cristina; Arseni, Varvara; Thambyrajah, Roshana S; Felix, Daniel A; Aboobaker, A Aziz

    2009-01-01

    miRNAs are an important class of non-protein coding small RNAs whose specific functions in animals are rapidly being elucidated. It is clear that miRNAs can play crucial roles in stem cell maintenance, cell fate determination and differentiation. We use planarians, which possess a large population of pluripotent somatic stem cells, as a powerful model system to study many aspects of stem cell biology and regeneration. In particular we wish to investigate the regulatory role miRNAs may have in planarian stem cell self renewal, proliferation and differentiation. Here, we characterized the differential spatial patterns of expression of miRNAs in whole and regenerating planarians by in situ hybridization to nascent miRNA transcripts. These miRNA expression patterns are the first which have been determined for a Lophotrocozoan animal. We have characterized the expression patterns of 42 miRNAs in adult planarians, constituting a complete range of tissue specific expression patterns. We also followed miRNA expression during planarian regeneration. The majority of planarian miRNAs were expressed either in areas where stem cells (neoblasts) are located and/or in the nervous system. Some miRNAs were definitively expressed in stem cells and dividing cells as confirmed by in situ hybridisation after irradiation. We also found miRNAs to be expressed in germ stem cells of the sexual strain. Together, these data suggest an important role for miRNAs in stem cell regulation and in neural cell differentiation in planarians.

  5. Microelectromechanical System-Based Sensing Arrays for Comparative in Vitro Nanotoxicity Assessment at Single Cell and Small Cell-Population Using Electrochemical Impedance Spectroscopy.

    Science.gov (United States)

    Shah, Pratikkumar; Zhu, Xuena; Zhang, Xueji; He, Jin; Li, Chen-zhong

    2016-03-09

    The traditional in vitro nanotoxicity assessment approaches are conducted on a monolayer of cell culture. However, to study a cell response without interference from the neighbor cells, a single cell study is necessary; especially in cases of neuronal, cancerous, and stem cells, wherein an individual cell's fate is often not explained by the whole cell population. Nonetheless, a single cell does not mimic the actual in vivo environment and lacks important information regarding cell communication with its microenvironment. Both a single cell and a cell population provide important and complementary information about cells' behaviors. In this research, we explored nanotoxicity assessment on a single cell and a small cell population using electrochemical impedance spectroscopy and a microelectromechanical system (MEMS) device. We demonstrated a controlled capture of PC12 cells in different-sized microwells (to capture a different number of cells) using a combined method of surface functionalization and dielectrophoresis. The present approach provides a rapid nanotoxicity response as compared to other conventional approaches. This is the first study, to our knowledge, which demonstrates a comparative response of a single cell and small cell colonies on the same MEMS platform, when exposed to metaloxide nanoparticles. We demonstrated that the microenvironment of a cell is also accountable for cells' behaviors and their responses to nanomaterials. The results of this experimental study open up a new hypothesis to be tested for identifying the role of cell communication in spreading toxicity in a cell population.

  6. miRNA-720 controls stem cell phenotype, proliferation and differentiation of human dental pulp cells.

    Directory of Open Access Journals (Sweden)

    Emilio Satoshi Hara

    Full Text Available Dental pulp cells (DPCs are known to be enriched in stem/progenitor cells but not well characterized yet. Small non-coding microRNAs (miRNAs have been identified to control protein translation, mRNA stability and transcription, and have been reported to play important roles in stem cell biology, related to cell reprogramming, maintenance of stemness and regulation of cell differentiation. In order to characterize dental pulp stem/progenitor cells and its mechanism of differentiation, we herein sorted stem-cell-enriched side population (SP cells from human DPCs and periodontal ligament cells (PDLCs, and performed a locked nucleic acid (LNA-based miRNA array. As a result, miR-720 was highly expressed in the differentiated main population (MP cells compared to that in SP cells. In silico analysis and a reporter assay showed that miR-720 targets the stem cell marker NANOG, indicating that miR-720 could promote differentiation of dental pulp stem/progenitor cells by repressing NANOG. Indeed, gain-and loss-of-function analyses showed that miR-720 controls NANOG transcript and protein levels. Moreover, transfection of miR-720 significantly decreased the number of cells positive for the early stem cell marker SSEA-4. Concomitantly, mRNA levels of DNA methyltransferases (DNMTs, which are known to play crucial factors during stem cell differentiation, were also increased by miR-720 through unknown mechanism. Finally, miR-720 decreased DPC proliferation as determined by immunocytochemical analysis against ki-67, and promoted odontogenic differentiation as demonstrated by alizarin red staining, as well as alkaline phosphatase and osteopontin mRNA levels. Our findings identify miR-720 as a novel miRNA regulating the differentiation of DPCs.

  7. Serum miR-19a predicts resistance to FOLFOX chemotherapy in advanced colorectal cancer cases.

    Science.gov (United States)

    Chen, Qi; Xia, Hong-Wei; Ge, Xiao-Jun; Zhang, Yu-Chen; Tang, Qiu-Lin; Bi, Feng

    2013-01-01

    Colorectal cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advanced colorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predicting resistance in such first-line application. To explore the potential molecular biomarkers predicting the resistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAs in serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNA expression was further validated in an independent population by reverse transcription and quantitative real- time PCR. 62 microRNAs expressing differentially with fold-change >2 were screened out by microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validation in an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated in resistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a to discriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonic antigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquired drug resistance. Our findings confirmed aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.

  8. Bocadillos de Mi Tierra Ltda.

    OpenAIRE

    2011-01-01

    Bocadillos de mi Tierra Ltda. es una empresa del sector alimenticio desarrollada con el fin de transformar los conocimientos en beneficios tales como la elaboración de bocadillo de distintos sabores mostrando nuevos estilos, diseños y presentaciones que ayude a ampliar el mercado a nivel nacional e internacional. La presente tesis da a conocer el plan de negocios de la empresa Bocadillos de mi Tierra Ltda. que tiene como objetivo la producción y comercialización de bocadillos a base de fruta...

  9. Identification of miRNAs and miRNA-mediated regulatory pathways in Carica papaya.

    Science.gov (United States)

    Liang, Gang; Li, Yang; He, Hua; Wang, Fang; Yu, Diqiu

    2013-10-01

    Plant microRNAs (miRNAs) post-transcriptionally regulate target gene expression to modulate growth and development and biotic and abiotic stress responses. By analyzing small RNA deep sequencing data in combination with the genome sequence, we identified 75 conserved miRNAs and 11 novel miRNAs. Their target genes were also predicted. For most conserved miRNAs, the miRNA-target pairs were conserved across plant species. In addition to these conserved miRNA-target pairs, we also identified some papaya-specific miRNA-target regulatory pathways. Both miR168 and miR530 target the Argonaute 1 gene, indicating a second autoregulatory mechanism for miRNA regulation. A non-conserved miRNA was mapped within an intron of Dicer-like 1 (DCL1), suggesting a conserved homeostatic autoregulatory mechanism for DCL1 expression. A 21-nt miRNA triggers secondary siRNA production from its target genes, nucleotide-binding site leucine-rich repeat protein genes. Certain phased-miRNAs were processed from their conserved miRNA precursors, indicating a putative miRNA evolution mechanism. In addition, we identified a Carica papaya-specific miRNA that targets an ethylene receptor gene, implying its function in the ethylene signaling pathway. This work will also advance our understanding of miRNA functions and evolution in plants.

  10. Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression

    Czech Academy of Sciences Publication Activity Database

    Aherne, S.T.; Madden, S.F.; Hughes, D. J.; Pardini, B.; Naccarati, A.; Levý, M.; Vodička, Pavel; Neary, P.; Dowling, P.; Clynes, M.

    2015-01-01

    Roč. 15, apr 30 (2015), s. 2-13 ISSN 1471-2407 R&D Projects: GA ČR GAP304/10/1286 Institutional support: RVO:68378041 Keywords : colorectal cancer * circulating miRNAs * miR-34a * miR-150 * miR-923 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.265, year: 2015

  11. Novel modeling of combinatorial miRNA targeting identifies SNP with potential role in bone density.

    Directory of Open Access Journals (Sweden)

    Claudia Coronnello

    Full Text Available MicroRNAs (miRNAs are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting, a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential

  12. 34A, miRNA-944, miRNA-101 and miRNA-218 in cervical cancer

    African Journals Online (AJOL)

    Expressions and clinic significance of miRNA-143, miRNA- ... cancer tissues. Our research on miRNAs is aimed to provide reference for the early clinical diagnosis of cervical cancer and provide novel therapeutic target for cervical cancer. .... Table 2: Baseline demographics and disease characteristics. Group. Height (cm).

  13. Association analysis of single nucleotide polymorphisms at five loci: comparison between atopic dermatitis and asthma in the Chinese Han population.

    Directory of Open Access Journals (Sweden)

    Hua-Yang Tang

    Full Text Available Atopic diseases, such as atopic dermatitis (AD and asthma, are closely related to clinical phenotypes with hypersensitivity, and often share some similar genetic and pathogenic bases. Our recent GWAS identified three susceptibility gene/loci FLG (rs11204971 and rs3126085, 5q22.1 (rs10067777, rs7701890, rs13360927 and rs13361382 and 20q13.33 (rs6010620 to AD. The effect of these AD associated polymorphisms in asthma is so far unknown. To investigate whether AD relevant genetic variants is identical to asthma and reveal the differences in genetic factors between AD and asthma in Chinese Han population, seven AD associated single nucleotide polymorphisms (SNPs as well as 3 other SNPs (rs7936562 and rs7124842 at 11q13.5 and rs4982958 at 14q11.2 from our previous AD GWAS were genotyped in 463 asthma patients and 985 controls using Sequenom MassArray system. We found rs4982958 at 14q11.2 was significantly associated with asthma (P = 3.04×10(-4, OR = 0.73. We also detected one significant risk haplotype GGGA from the 4 SNPs (rs10067777, rs7701890, rs13360927 and rs13361382 at 5q22.1 in AD cases (P(correction = 3.60×10(-10, OR = 1.26, and the haplotype was suggestive of risk in asthma cases in this study (P = 0.014, P(correction = 0.084, OR = 1.38. These SNPs (rs11204971, rs3126085, rs7936562, rs712484 and rs6010620 at AD susceptibility genes/loci FLG, 11q13.5 and 20q13.33 were not associated with asthma in this study. Our results further comfirmed that 14q11.2 was an important candidate locus for asthma and demonstrated that 5q22.1 might be shared by AD and asthma in Chinese Han population.

  14. miRNA-dysregulation associated with tenderness variation induced by acute stress in Angus cattle

    Directory of Open Access Journals (Sweden)

    Zhao Chunping

    2012-06-01

    Full Text Available Abstract miRNAs are a class of small, single-stranded, non-coding RNAs that perform post-transcriptional repression of target genes by binding to 3’ untranslated regions. Research has found that miRNAs involved in the regulation of many metabolic processes. Here we uncovered that the beef quality of Angus cattle sharply diversified after acute stress. By performing miRNA microarray analysis, 13 miRNAs were significantly differentially expressed in stressed group compared to control group. Using a bioinformatics method, 135 protein-coding genes were predicted as the targets of significant differentially expressed miRNAs. Gene Ontology (GO term and Ingenuity Pathway Analysis (IPA mined that these target genes involved in some important pathways, which may have impact on meat quality and beef tenderness.

  15. Encuentro "Mi marca y yo"

    OpenAIRE

    Universidad de Alicante. Observatorio Comunicación en Cambio

    2013-01-01

    La gestión de la marca personal, especialmente en los entornos digitales, ha cobrado actualmente gran importancia como estrategia de posicionamiento profesional. Te invitamos a que asistas a nuestro encuentro "Mi marca y yo" para reflexionar sobre qué implica contar con una marca personal.

  16. Insertion sequence element single nucleotide polymorphism typing provides insights into the population structure and evolution of Mycobacterium ulcerans across Africa.

    Science.gov (United States)

    Vandelannoote, Koen; Jordaens, Kurt; Bomans, Pieter; Leirs, Herwig; Durnez, Lies; Affolabi, Dissou; Sopoh, Ghislain; Aguiar, Julia; Phanzu, Delphin Mavinga; Kibadi, Kapay; Eyangoh, Sara; Manou, Louis Bayonne; Phillips, Richard Odame; Adjei, Ohene; Ablordey, Anthony; Rigouts, Leen; Portaels, Françoise; Eddyani, Miriam; de Jong, Bouke C

    2014-02-01

    Buruli ulcer is an indolent, slowly progressing necrotizing disease of the skin caused by infection with Mycobacterium ulcerans. In the present study, we applied a redesigned technique to a vast panel of M. ulcerans disease isolates and clinical samples originating from multiple African disease foci in order to (i) gain fundamental insights into the population structure and evolutionary history of the pathogen and (ii) disentangle the phylogeographic relationships within the genetically conserved cluster of African M. ulcerans. Our analyses identified 23 different African insertion sequence element single nucleotide polymorphism (ISE-SNP) types that dominate in different areas where Buruli ulcer is endemic. These ISE-SNP types appear to be the initial stages of clonal diversification from a common, possibly ancestral ISE-SNP type. ISE-SNP types were found unevenly distributed over the greater West African hydrological drainage basins. Our findings suggest that geographical barriers bordering the basins to some extent prevented bacterial gene flow between basins and that this resulted in independent focal transmission clusters associated with the hydrological drainage areas. Different phylogenetic methods yielded two well-supported sister clades within the African ISE-SNP types. The ISE-SNP types from the "pan-African clade" were found to be widespread throughout Africa, while the ISE-SNP types of the "Gabonese/Cameroonian clade" were much rarer and found in a more restricted area, which suggested that the latter clade evolved more recently. Additionally, the Gabonese/Cameroonian clade was found to form a strongly supported monophyletic group with Papua New Guinean ISE-SNP type 8, which is unrelated to other Southeast Asian ISE-SNP types.

  17. Incidence and characteristics of acute referred orofacial pain caused by a posterior single tooth pulpitis in an Iranian population.

    Science.gov (United States)

    Hashemipour, Maryam Alsadat; Borna, Roya

    2014-02-01

    This study was designed to evaluate incidence and characteristics of acute referred orofacial pain caused by a posterior single tooth pulpitis in an Iranian population. In this cross-sectional study, 3,150 patients (1,400 males and 1,750 females) with pain in the orofacial region were evaluated via clinical and radiographic examination to determine their pain source. Patients completed a standardized clinical questionnaire consisting of a numerical rating scale for pain intensity and chose verbal descriptors from short form McGill questionnaire to describe the quality of their pain. Visual analog scale (VAS) was used to score pain intensity. In addition, patients indicated sites to which pain referred by drawing on an illustration of the head and neck. Data were analyzed using chi-square, fisher exact, and Mann-Whitney tests. Two thousand and hundred twenty patients (67/3%) reported pain in sites that diagnostically differed from the pain source. According to statistical analysis, sex (P = 0.02), intensity of pain (0.04), and quality (P = 0.001) of pain influenced its referral nature, while age of patients and kind of stimulus had no considerable effect on pain referral (P > 0.05). The results of the present study show the prevalence of referred pain in the head, face, and neck region is moderately high. Therefore, in patients with orofacial pain, it is essential to carefully examination before carrying out treatment that could be inappropriate. © 2013 The Authors Pain Practice © 2013 World Institute of Pain.

  18. Association of body mass index-related single nucleotide polymorphisms with psychiatric disease and memory performance in a Japanese population.

    Science.gov (United States)

    Ninomiya-Baba, Midori; Matsuo, Junko; Sasayama, Daimei; Hori, Hiroaki; Teraishi, Toshiya; Ota, Miho; Hattori, Kotaro; Noda, Takamasa; Ishida, Ikki; Shibata, Shigenobu; Kunugi, Hiroshi

    2017-10-01

    Obesity is a risk factor for psychiatric diseases. Recently, a number of single nucleotide polymorphisms (SNPs) have been shown to be related to body mass index (BMI). In this study, we investigated the association of BMI-related SNPs with psychiatric diseases and one of their endophenotypes, memory performance, in a Japanese population. The subjects were 1624 patients with one of three psychiatric diseases (799 patients with major depressive disorder, 594 with schizophrenia, and 231 with bipolar disorder) and 1189 healthy controls. Memory performance was assessed using the Wechsler Memory Scale - Revised (WMS-R). Genomic DNA was prepared from venous blood and used to genotype 23 BMI-related SNPs using the TaqMan 5'-exonuclease allelic discrimination assay. We then analysed the relationships between the SNPs and psychiatric disease and various subscales of the WMS-R. Three SNPs (rs11142387, rs12597579, and rs6548238) showed significant differences in the genotype or allele frequency between patients with any psychiatric diseases and controls. Furthermore, six SNPs (rs11142387, rs12597579, rs2815752, rs2074356, rs4776970, and rs2287019) showed significant differences in at least one subscale of the WMS-R depending on the genotypes of the healthy controls. Interestingly, rs11142387 near the Kruppel-like factor 9 (KLF9) was significantly associated with psychiatric disease and poor memory function. We identified three and six BMI-related SNPs associated with psychiatric disease and memory performance, respectively. In particular, carrying the A allele of rs11142387 near KLF9 was found to be associated with psychiatric disease and poor memory performance, which warrants further investigations.

  19. Correlation between single nucleotide polymorphisms of NADPH oxidase p22phox gene and ischemic stroke in Shanghai Han population

    Directory of Open Access Journals (Sweden)

    Wei XU

    2015-09-01

    Full Text Available Objective This paper aims to investigate the distribution of genotypes and alleles of nicotinamide adenine dinucleotide phosphate (NADPH oxidase p22phox -930A/G, 242C/T and -675A/T, so as to evaluate the association between three single-nucleotide polymorphisms (SNPs and risk of atherosclerotic ischemic stroke in permanent resident population of Han nationality living in Shanghai area. Methods The genotypes and allele frequencies of NADPH oxidase p22phox subunit -930A/G, 242C/T and -675A/T were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis in 205 patients with ischemic stroke and 136 healthy controls. Results In patients with ischemic stroke, the results of PCR-RFLP in variant genetic loci were different. For -930A/G, one band appeared at 268 bp of genotype AA; 2 bands appeared at 197 and 71 bp of genotype GG; 3 bands appeared at 268, 197 and 71 bp of genotype AG. For 242C/T, one band appeared at 348 bp of genotype CC; 2 bands appeared at 188 and 160 bp of genotype TT; 3 bands appeared at 348, 188 and 160 bp of genotype CT. For -675A/T, 2 bands appeared at 158 and 54 bp of genotype TT; 3 bands appeared at 212, 158 and 54 bp of genotype AT. The genotypes and allele frequency of all three SNPs of NADPH oxidase p22phox gene had no significant difference between ischemic stroke patients and healthy controls (P > 0.05. Conclusions The genetic polymorphism of NADPH oxidase p22phox gene -930A/G, 242C/T and -675A/T might have no association with ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2015.09.011

  20. Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population

    DEFF Research Database (Denmark)

    Yin, Jiaoyang; Vogel, Ulla Birgitte; Ma, Yegang

    2008-01-01

    To evaluate the joint effect of nine single nucleotide polymorphisms for three DNA repair genes in the region of chromosome 19q13.2-3 on susceptibility of lung cancer in a Chinese population, we conducted a hospital-based case-control study consisting of 247 lung cancer cases and 253 cancer...

  1. Dynamic single-cell analysis of Saccharomyces cerevisiae under process perturbation: Comparison of different methods for monitoring the intensity of population heterogeneity

    DEFF Research Database (Denmark)

    Delvigne, Frank; Baert, Jonathan; Gofflot, Sébastien

    2015-01-01

    BACKGROUND: Single cell biology has attracted a lot of attention in recent years and has led to numerous fundamental results pointing out the heterogeneity of clonal cell populations. In this context, microbial phenotypic heterogeneity under bioprocessing conditions needs to be further investigat...

  2. Circulating microRNA (miRNA Expression Profiling in Plasma of Patients with Gestational Diabetes Mellitus Reveals Upregulation of miRNA miR-330-3p

    Directory of Open Access Journals (Sweden)

    Guido Sebastiani

    2017-12-01

    Full Text Available Gestational diabetes mellitus (GDM is characterized by insulin resistance accompanied by low/absent beta-cell compensatory adaptation to the increased insulin demand. Although the molecular mechanisms and factors acting on beta-cell compensatory response during pregnancy have been partially elucidated and reported, those inducing an impaired beta-cell compensation and function, thus evolving in GDM, have yet to be fully addressed. MicroRNAs (miRNAs are a class of small endogenous non-coding RNAs, which negatively modulate gene expression through their sequence-specific binding to 3′UTR of mRNA target. They have been described as potent modulators of cell survival and proliferation and, furthermore, as orchestrating molecules of beta-cell compensatory response and function in diabetes. Moreover, it has been reported that miRNAs can be actively secreted by cells and found in many biological fluids (e.g., serum/plasma, thus representing both optimal candidate disease biomarkers and mediators of tissues crosstalk(s. Here, we analyzed the expression profiles of circulating miRNAs in plasma samples obtained from n = 21 GDM patients and from n = 10 non-diabetic control pregnant women (24–33 weeks of gestation using TaqMan array microfluidics cards followed by RT-real-time PCR single assay validation. The results highlighted the upregulation of miR-330-3p in plasma of GDM vs non-diabetics. Furthermore, the analysis of miR-330-3p expression levels revealed a bimodally distributed GDM patients group characterized by high or low circulating miR-330 expression and identified as GDM-miR-330high and GDM-miR-330low. Interestingly, GDM-miR-330high subgroup retained lower levels of insulinemia, inversely correlated to miR-330-3p expression levels, and a significant higher rate of primary cesarean sections. Finally, miR-330-3p target genes analysis revealed major modulators of beta-cell proliferation and of insulin secretion, such as the

  3. Prognostic significance of altered miRNA expression in whole blood of OSCC patients.

    Science.gov (United States)

    Ries, Jutta; Baran, Christoph; Wehrhan, Falk; Weber, Manuel; Neukam, Friedrich W; Krautheim-Zenk, Andrea; Nkenke, Emeka

    2017-06-01

    Currently, there is a lack of blood markers for the detection of recurrent oral squamous cell carcinoma (OSCC). The present study aimed to investigate whether the aberrant expression of single microRNAs (miRNAs) in whole blood of patients could serve as a biomarker for persistent or recurrent OSCC. Whole blood of 2 groups of formerly treated OSCC patients was investigated by RT-qPCR for their circulating miRNA profiles. The R-OC group included patients with recurrence of OSCC (n=21) and the NR-OC group included patients without recurrence (n=21). Fold-changes and significance of the differences in miRNA expression levels between the groups were determined. A cut-off point (COP) for the discrimination between the R-OC and NR-OC groups was calculated and the significance between over/under expression of the miRNAs and the recurrence of malignancy was determined. Significant differences in the miRNA expression in whole blood of the R-OC and NR-OC groups were found. The levels of miR-3651 and miR-494 were significantly increased and the level of miR-186 was significantly decreased in whole blood of the R-OC patients (pmiR-3651=0.001, pmiR-494=0.003 and pmiR-186=0.001). By the determination of the COP, increased or decreased expression of the markers was significantly correlated to the recurrence of the disease. Altered expression of miR-494, miR-3651 and miR-186 appears to be associated with the recurrence of OSCC. The present study may form the basis for establishing a blood test as a minimally invasive method for the detection of the recurrence of OSCC.

  4. miRNA-130a regulates C/EBP-ε expression during granulopoiesis

    DEFF Research Database (Denmark)

    Larsen, Maria T; Häger, Mattias; Glenthøj, Andreas

    2014-01-01

    cells. In contrast, C/EBP-ε protein is virtually detectable only in the MC/MM population, indicating that expression in more immature cells could be inhibited by microRNAs (miRNAs). We found that miRNA-130a (miR-130a) regulates C/EBP-ε protein expression in both murine and human granulocytic precursors...... target site for miR-130a restored both C/EBP-ε production, expression of Camp and Lcn2, and resulted in the cells having a more mature phenotype. We conclude that miR-130a is important for the regulation of the timed expression of C/EBP-ε during granulopoiesis.......CCAAT/enhancer binding protein-ε (C/EBP-ε) is considered a master transcription factor regulating terminal neutrophil maturation. It is essential for expression of secondary granule proteins, but it also regulates proliferation, cell cycle, and maturation during granulopoiesis. Cebpe(-/-) mice have...

  5. Genetic effects and reparation of single-stranded DNA breaks in Arabidopsis thaliana populations growing in the vicinity of the Chernobyl Nuclear Power Station

    International Nuclear Information System (INIS)

    Abramov, V.I.; Sergeeva, S.A.; Ptitsyna, S.N.; Semov, A.B.; Shevchenko, V.A.

    1992-01-01

    The genetic effects and efficiency of repair of single-stranded DNA breaks in natural populations of Arabidopsis growing within a thirty-kilometer zone of the Chernobyl Nuclear Power Station were studied. A direct relationship was found between the level of radioactive contamination and the frequency of embryonal lethal mutations in the Arabidopsis populations studied. A decrease in the efficiency of reparation of single-stranded DNA breaks was found in Arabidopsis plants growing in the contaminated sites. The level of efficiency of DNA reparation was dependent on the duration for which the Arabidopsis population had been growing in the contaminated sites and on the degree of radioactive contamination of the sites. 9 refs., 4 tabs

  6. Miltenberger blood group typing by real-time polymerase chain reaction (qPCR) melting curve analysis in Thai population.

    Science.gov (United States)

    Vongsakulyanon, A; Kitpoka, P; Kunakorn, M; Srikhirin, T

    2015-12-01

    To develop reliable and convenient methods for Miltenberger (Mi(a) ) blood group typing. To apply real-time polymerase chain reaction (qPCR) melting curve analysis to Mi(a) blood group typing. The Mi(a) blood group is the collective set of glycophorin hybrids in the MNS blood group system. Mi(a+) blood is common among East Asians and is also found in the Thai population. Incompatible Mi(a) blood transfusions pose the risk of life-threatening haemolysis; therefore, Mi(a) blood group typing is necessary in ethnicities where the Mi(a) blood group is prevalent. One hundred and forty-three blood samples from Thai blood donors were used in the study. The samples included 50 Mi(a+) samples and 93 Mi(a-) samples, which were defined by serology. The samples were typed by Mi(a) typing qPCR, and 50 Mi(a+) samples were sequenced to identify the Mi(a) subtypes. Mi(a) subtyping qPCR was performed to define GP.Mur. Both Mi(a) typing and Mi(a) subtyping were tested on a conventional PCR platform. The results of Mi(a) typing qPCR were all concordant with serology. Sequencing of the 50 Mi(a+) samples revealed 47 GP.Mur samples and 3 GP.Hop or Bun samples. Mi(a) subtyping qPCR was the supplementary test used to further define GP.Mur from other Mi(a) subtypes. Both Mi(a) typing and Mi(a) subtyping performed well using a conventional PCR platform. Mi(a) typing qPCR correctly identified Mi(a) blood groups in a Thai population with the feasibility of Mi(a) subtype discrimination, and Mi(a) subtyping qPCR was able to further define GP.Mur from other Mi(a) subtypes. © 2015 British Blood Transfusion Society.

  7. miRNAs in brain development

    Energy Technology Data Exchange (ETDEWEB)

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan, E-mail: johan.jakobsson@med.lu.se

    2014-02-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function.

  8. miRNAs in brain development

    International Nuclear Information System (INIS)

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan

    2014-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function

  9. miR-424 levels in hair shaft are increased in psoriatic patients.

    Science.gov (United States)

    Tsuru, Yasuo; Jinnin, Masatoshi; Ichihara, Asako; Fujisawa, Akihiko; Moriya, Chikako; Sakai, Keisuke; Fukushima, Satoshi; Ihn, Hironobu

    2014-05-01

    Objective diagnostic markers have not been in clinical use for psoriasis. In this study, we investigated the levels of miR-424 in hair roots and hair shafts in psoriatic patients, and evaluated the possibility that miR-424 can be a biomarker of the disease. A single hair root and five pieces of hair shafts (~5 cm in length) were obtained from the non-lesional occiput of each individual of 26 psoriatic patients. Control hair samples were collected from nine normal subjects. Samples from 10 atopic dermatitis patients were also included as the disease control. miR-424 levels were determined by quantitative real-time polymerase chain reaction. Hair shaft miR-424 levels were significantly upregulated only in patients with psoriasis compared with normal controls and those with atopic dermatitis. By receiver-operator curve analysis of hair shaft miR-424 to distinguish psoriatic patients from normal subjects, the area under the curve was 0.77. However, relative miR-424 levels were not correlated with disease activity markers including disease duration, body surface area and Psoriasis Area and Severity Index. Hair root miR-424 was not useful for evaluating both diagnosis and severity of the disease. Our results indicated hair shaft miR-424 levels may be useful as a diagnostic marker of psoriasis. © 2014 Japanese Dermatological Association.

  10. A pri-miR-218 variant and risk of cervical carcinoma in Chinese women

    Directory of Open Access Journals (Sweden)

    Shi Ting-Yan

    2013-01-01

    Full Text Available Abstract Background MicroRNA (miRNA-related single nucleotide polymorphisms (SNPs may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. Methods In this case–control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. Results We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015. However, this association was not observed for the miR-218 binding site SNP (rs2566 on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. Conclusions The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.

  11. miRNA-mediated auxin signalling repression during Vat-mediated aphid resistance in Cucumis melo.

    Science.gov (United States)

    Sattar, Sampurna; Addo-Quaye, Charles; Thompson, Gary A

    2016-06-01

    Resistance to Aphis gossypii in melon is attributed to the presence of the single dominant R gene virus aphid transmission (Vat), which is biologically expressed as antibiosis, antixenosis and tolerance. However, the mechanism of resistance is poorly understood at the molecular level. Aphid-induced transcriptional changes, including differentially expressed miRNA profiles that correspond to resistance interaction have been reported in melon. The potential regulatory roles of miRNAs in Vat-mediated aphid resistance were further revealed by identifying the specific miRNA degradation targets. A total of 70 miRNA:target pairs, including 28 novel miRNA:target pairs, for the differentially expressed miRNAs were identified: 11 were associated with phytohormone regulation, including six miRNAs that potentially regulate auxin interactions. A model for a redundant regulatory system of miRNA-mediated auxin insensitivity is proposed that incorporates auxin perception, auxin modification and auxin-regulated transcription. Chemically inhibiting the transport inhibitor response-1 (TIR-1) auxin receptor in susceptible melon tissues provides in vivo support for the model of auxin-mediated impacts on A. gossypii resistance. © 2016 John Wiley & Sons Ltd.

  12. MiRNA Biogenesis and Intersecting Pathways

    DEFF Research Database (Denmark)

    Ben Chaabane, Samir

    (DCL1) protein complex. Mature miRNAs are loaded onto and guide an ARGONAUTE1 (AGO1) effector complex, leading to target mRNA silencing. The miRNA pathway is under tight temporal and spatial control and is regulated at multiple levels from transcription and precursor processing through miRNA mode...... questions need to be addressed to establish a valid link, we provide encouraging evidence of the involvement of chromatin remodeling factors FAS1 and FAS2 in miRNA biogenesis. Together, we have expanded our understanding of the intersections between miRNA biogenesis and other pathways....

  13. MiR-192-Mediated Positive Feedback Loop Controls the Robustness of Stress-Induced p53 Oscillations in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Richard Moore

    2015-12-01

    Full Text Available The p53 tumor suppressor protein plays a critical role in cellular stress and cancer prevention. A number of post-transcriptional regulators, termed microRNAs, are closely connected with the p53-mediated cellular networks. While the molecular interactions among p53 and microRNAs have emerged, a systems-level understanding of the regulatory mechanism and the role of microRNAs-forming feedback loops with the p53 core remains elusive. Here we have identified from literature that there exist three classes of microRNA-mediated feedback loops revolving around p53, all with the nature of positive feedback coincidentally. To explore the relationship between the cellular performance of p53 with the microRNA feedback pathways, we developed a mathematical model of the core p53-MDM2 module coupled with three microRNA-mediated positive feedback loops involving miR-192, miR-34a, and miR-29a. Simulations and bifurcation analysis in relationship to extrinsic noise reproduce the oscillatory behavior of p53 under DNA damage in single cells, and notably show that specific microRNA abrogation can disrupt the wild-type cellular phenotype when the ubiquitous cell-to-cell variability is taken into account. To assess these in silico results we conducted microRNA-perturbation experiments in MCF7 breast cancer cells. Time-lapse microscopy of cell-population behavior in response to DNA double-strand breaks, together with image classification of single-cell phenotypes across a population, confirmed that the cellular p53 oscillations are compromised after miR-192 perturbations, matching well with the model predictions. Our study via modeling in combination with quantitative experiments provides new evidence on the role of microRNA-mediated positive feedback loops in conferring robustness to the system performance of stress-induced response of p53.

  14. Compilation of a panel of informative single nucleotide polymorphisms for bovine identification in the Northern Irish cattle population

    Directory of Open Access Journals (Sweden)

    Hartshorne David

    2010-01-01

    Full Text Available Abstract Background Animal identification is pivotal in governmental agricultural policy, enabling the management of subsidy payments, movement of livestock, test scheduling and control of disease. Advances in bovine genomics have made it possible to utilise inherent genetic variability to uniquely identify individual animals by DNA profiling, much as has been achieved with humans over the past 20 years. A DNA profiling test based on bi-allelic single nucleotide polymorphism (SNP markers would offer considerable advantages over current short tandem repeat (STR based industry standard tests, in that it would be easier to analyse and interpret. In this study, a panel of 51 genome-wide SNPs were genotyped across panels of semen DNA from 6 common breeds for the purposes of ascertaining allelic frequency. For SNPs on the same chromosome, the extent of linkage disequilbrium was determined from genotype data by Expectation Maximization (EM algorithm. Minimum probabilities of unique identification were determined for each breed panel. The usefulness of this SNP panel was ascertained by comparison to the current bovine STR Stockmarks II assay. A statistically representative random sampling of bovine animals from across Northern Ireland was assembled for the purposes of determining the population allele frequency for these STR loci and subsequently, the minimal probability of unique identification they conferred in sampled bovine animals from Northern Ireland. Results 6 SNPs exhibiting a minor allele frequency of less than 0.2 in more than 3 of the breed panels were excluded. 2 Further SNPs were found to reside in coding areas of the cattle genome and were excluded from the final panel. The remaining 43 SNPs exhibited genotype frequencies which were in Hardy Weinberg Equilibrium. SNPs on the same chromosome were observed to have no significant linkage disequilibrium/allelic association. Minimal probabilities of uniquely identifying individual animals from

  15. Study of GABAergic extra-synaptic tonic inhibition in single neurons and neural populations by traversing neural scales: application to propofol-induced anaesthesia.

    Science.gov (United States)

    Hutt, Axel; Buhry, Laure

    2014-12-01

    Anaesthetic agents are known to affect extra-synaptic GABAergic receptors, which induce tonic inhibitory currents. Since these receptors are very sensitive to small concentrations of agents, they are supposed to play an important role in the underlying neural mechanism of general anaesthesia. Moreover anaesthetic agents modulate the encephalographic activity (EEG) of subjects and hence show an effect on neural populations. To understand better the tonic inhibition effect in single neurons on neural populations and hence how it affects the EEG, the work considers single neurons and neural populations in a steady-state and studies numerically and analytically the modulation of their firing rate and nonlinear gain with respect to different levels of tonic inhibition. We consider populations of both type-I (Leaky Integrate-and-Fire model) and type-II (Morris-Lecar model) neurons. To bridge the single neuron description to the population description analytically, a recently proposed statistical approach is employed which allows to derive new analytical expressions for the population firing rate for type-I neurons. In addition, the work shows the derivation of a novel transfer function for type-I neurons as considered in neural mass models and studies briefly the interaction of synaptic and extra-synaptic inhibition. We reveal a strong subtractive and divisive effect of tonic inhibition in type-I neurons, i.e. a shift of the firing rate to higher excitation levels accompanied by a change of the nonlinear gain. Tonic inhibition shortens the excitation window of type-II neurons and their populations while maintaining the nonlinear gain. The gained results are interpreted in the context of recent experimental findings under propofol-induced anaesthesia.

  16. Insights on the Functional Interactions between miRNAs and Copy Number Variations in the Aging Brain

    Directory of Open Access Journals (Sweden)

    Stephan ePersengiev

    2013-10-01

    Full Text Available MicroRNAs (miRNAs are regulatory genetic elements that coordinate the expression of thousands of genes and play important roles in brain aging and neurodegeneration. DNA polymorphisms affecting miRNA biogenesis, dosage and gene targeting may represent potentially functional variants. The consequences of single nucleotide polymorphisms (SNPs affecting miRNA function were previously demonstrated by both experimental and computational methods. However, little is known about how copy number variations (CNVs influence miRNA metabolism and regulatory networks. We discuss potential mechanisms of CNVs-mediated effects on miRNA function and regulation that might have consequences for brain aging. We argue that CNVs, which potentially can alter miRNA expression, regulation or target gene recognition, are possible functional variants and should be considered high priority candidates in genotype-phenotype mapping studies of brain-related disorders.

  17. Impact of a Genetic Risk Score on Myocardial Infarction Risk Across Different Ethnic Populations.

    Science.gov (United States)

    Joseph, Philip G; Pare, Guillaume; Asma, Senay; Engert, James C; Yusuf, Salim; Anand, Sonia S

    2016-12-01

    Myocardial infarction (MI) risk varies by ethnicity, although the influence of genetic factors remains unclear. Using a genetic risk score (GRS), we examined the association between 25 coronary artery disease (CAD)-related single nucleotide polymorphisms and MI across 6 ethnic groups. We studied 8556 participants in the INTERHEART case-control study from 6 ethnic groups: Europeans, South Asians, Southeast Asians, Arabs, Latin Americans, and Africans. Associations between the GRS and MI were tested in each group by logistic regression and overall by meta-analysis. Overall, the GRS increased the odds of MI by 1.07 (95% confidence interval [CI], 1.04-1.09) per risk allele in the unadjusted model, with little change (odds ratio, 1.06; 95% CI, 1.04-1.09) after adjusting for demographic and modifiable factors. In Europeans, South Asians, Southeast Asians, and Arabs, the GRS was significantly associated with MI, with minimal heterogeneity observed. In these groups, a score > 23 risk alleles (highest 4 quintiles) was associated with only a 5% difference in population attributable risk (PAR) (36% to 41%) for MI. The GRS was not significant in Latin Americans or Africans. In the overall cohort, modest changes, beyond clinical factors, in PAR (88% to 91%), concordance statistic (0.73 to 0.74), and continuous net reclassification improvement (12%) were observed with the GRS. A CAD GRS is associated with MI across a multiethnic cohort, with significant and consistent effects across 4 distinct ethnicities. However, it only modestly improves MI risk prediction beyond clinical factors. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  18. [Association between single nucleotide polymorphism in Wnt3 and nonsyndromic cleft lip with or without cleft palate in Hui and Han population of Ningxia Autonomous Region].

    Science.gov (United States)

    Xin, Yanhua; Ma, Lijuan; Zhai, Kun; Zhou, Zhongwei; Yang, Xiong; Ma, Jian; Wang, Yirui; Zhu, Jinfang; Jiang, Min; Huang, Yongqing

    2013-08-01

    To investigate the association between rs142167, rs7216231 single nucleotide polymorphism (SNP) in Wnt3 and nonsyndromic cleft lip and palate (NSCL/P) in Hui and Han population of Ningxia Autonomous Region. The study consisted of 371 NSCL/P patients from Ningxia Hui and Han population (Han population 166, Hui population 205), their parents (196 fathers, 224 mothers, 150 trios) and 258 normal controls (Han population 190, Hui population 68). Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) was used to identify rs142167, rs7216231 genotypes of the samples. The data was analyzed by case-control analysis, transmission disequilibrium test (TDT) and family based associated test (FBAT). Case-control study showed that no differences in cleft lip, cleft palate, cleft lip and palate, and the total case group compared with the control group at rs142167 and rs7216231 (P > 0.05) in Hui and Han population and in stratified comparison. TDT test showed that rs142167 and rs7216231's allele had not over-transmitted (P > 0.05) in NSCL/P. FBAT test showed that G-G specific haplotypes showed statistically significant (P Hui and Han population.

  19. MicroRNA profiling in prostate cancer--the diagnostic potential of urinary miR-205 and miR-214.

    Directory of Open Access Journals (Sweden)

    Anvesha Srivastava

    Full Text Available Prostate cancer (PCa is the most common type of cancer in men in the United States, which disproportionately affects African American descents. While metastasis is the most common cause of death among PCa patients, no specific markers have been assigned to severity and ethnic biasness of the disease. MicroRNAs represent a promising new class of biomarkers owing to their inherent stability and resilience. In the present study, we investigated potential miRNAs that can be used as biomarkers and/or therapeutic targets and can provide insight into the severity and ethnic biasness of PCa. PCR array was performed in FFPE PCa tissues (5 Caucasian American and 5 African American and selected differentially expressed miRNAs were validated by qRT-PCR, in 40 (15 CA and 25 AA paired PCa and adjacent normal tissues. Significantly deregulated miRNAs were also analyzed in urine samples to explore their potential as non-invasive biomarker for PCa. Out of 8 miRNAs selected for validation from PCR array data, miR-205 (p<0.0001, mir-214 (p<0.0001, miR-221(p<0.001 and miR-99b (p<0.0001 were significantly downregulated in PCa tissues. ROC curve shows that all four miRNAs successfully discriminated between PCa and adjacent normal tissues. MiR-99b showed significant down regulation (p<0.01 in AA PCa tissues as compared to CA PCa tissues and might be related to the aggressiveness associated with AA population. In urine, miR-205 (p<0.05 and miR-214 (p<0.05 were significantly downregulated in PCa patients and can discriminate PCa patients from healthy individuals with 89% sensitivity and 80% specificity. In conclusion, present study showed that miR-205 and miR-214 are downregulated in PCa and may serve as potential non-invasive molecular biomarker for PCa.

  20. A method for high precision sequencing of near full-length 16S rRNA genes on an Illumina MiSeq

    Directory of Open Access Journals (Sweden)

    Catherine M. Burke

    2016-09-01

    Full Text Available Background The bacterial 16S rRNA gene has historically been used in defining bacterial taxonomy and phylogeny. However, there are currently no high-throughput methods to sequence full-length 16S rRNA genes present in a sample with precision. Results We describe a method for sequencing near full-length 16S rRNA gene amplicons using the high throughput Illumina MiSeq platform and test it using DNA from human skin swab samples. Proof of principle of the approach is demonstrated, with the generation of 1,604 sequences greater than 1,300 nt from a single Nano MiSeq run, with accuracy estimated to be 100-fold higher than standard Illumina reads. The reads were chimera filtered using information from a single molecule dual tagging scheme that boosts the signal available for chimera detection. Conclusions This method could be scaled up to generate many thousands of sequences per MiSeq run and could be applied to other sequencing platforms. This has great potential for populating databases with high quality, near full-length 16S rRNA gene sequences from under-represented taxa and environments and facilitates analyses of microbial communities at higher resolution.

  1. Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder.

    Science.gov (United States)

    Garcia-Martínez, I; Sánchez-Mora, C; Pagerols, M; Richarte, V; Corrales, M; Fadeuilhe, C; Cormand, B; Casas, M; Ramos-Quiroga, J A; Ribasés, M

    2016-08-30

    Attention deficit and hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by impairment to sustain attention and inability to control impulses and activity level. The etiology of ADHD is complex, with an estimated heritability of 70-80%. Under the hypothesis that alterations in the processing or target binding of microRNAs (miRNAs) may result in functional alterations predisposing to ADHD, we explored whether common polymorphisms potentially affecting miRNA-mediated regulation are involved in this psychiatric disorder. We performed a comprehensive association study focused on 134 miRNAs in 754 ADHD subjects and 766 controls and found association between the miR-34b/c locus and ADHD. Subsequently, we provided preliminary evidence for overexpression of the miR-34c-3p mature form in peripheral blood mononuclear cells of ADHD subjects. Next, we tested the effect on gene expression of single-nucleotide polymorphisms within the ADHD-associated region and found that rs4938923 in the promoter of the pri-miR-34b/c tags cis expression quantitative trait loci for both miR-34b and miR-34c and has an impact on the expression levels of 681 transcripts in trans, including genes previously associated with ADHD. This gene set was enriched for miR-34b/c binding sites, functional categories related to the central nervous system, such as axon guidance or neuron differentiation, and serotonin biosynthesis and signaling canonical pathways. Our results provide preliminary evidence for the contribution to ADHD of a functional variant in the pri-miR-34b/c promoter, possibly through dysregulation of the expression of mature forms of miR-34b and miR-34c and some target genes. These data highlight the importance of abnormal miRNA function as a potential epigenetic mechanism contributing to ADHD.

  2. MiRNA profiles of prostate carcinoma detected by multi-platform miRNA screening

    DEFF Research Database (Denmark)

    Wach, Sven; Nolte, Elke; Szczyrba, Jaroslaw

    2012-01-01

    MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. They play a vital role in tumorigenesis. To characterize the diagnostic potential of miRNAs in prostate cancer, a leading cause of cancer mortality, we performed...... screening of miRNA expression profiles. We used commercially available microarrays to establish miRNA expression profiles from a cohort of 20 cancer samples. The expression of selected miRNAs was analyzed by quantitative real-time PCR and the identity of miRNA expressing cells was determined by miRNA...... in situ hybridization. We identified 25 miRNAs that showed a significant differential expression in cancer samples. The comparison with previously published data generated by deep sequencing of cDNA libraries of small RNA molecules revealed a concordance rate of 47% among miRNAs identified with both...

  3. A single-longitudinal-mode Brillouin fiber laser passively stabilized at the pump resonance frequency with a dynamic population inversion grating

    International Nuclear Information System (INIS)

    Spirin, V V; López-Mercado, C A; Kinet, D; Mégret, P; Fotiadi, A A; Zolotovskiy, I O

    2013-01-01

    We demonstrate a single-longitudinal-mode Brillouin ring fiber laser passively stabilized at the resonance frequency with a 1.7 m section that is an unpumped polarization-maintaining erbium-doped fiber. The two coupled all-fiber Fabry–Perot interferometers that comprise the cavity, in combination with the dynamical population inversion gratings self-induced in the active fiber, provide adaptive pump-mode selection and Stokes wave generation at the same time. The laser is shown to emit a single-frequency Stokes wave with a linewidth narrower than 100 Hz. (letter)

  4. Random population model to explain the recombination dynamics in single InAs/GaAs quantum dots under selective optical pumping

    Energy Technology Data Exchange (ETDEWEB)

    Gomis-Bresco, Jordi; Munoz-Matutano, Guillermo; Martinez-Pastor, Juan [Institut de Ciencies dels Materials de la Universitat de Valencia, Universitat de Valencia, Valencia (Spain); Alen, Benito [IMM, Instituto de Microelectronica de Madrid (CNM, CSIC), Isaac Newton 8, 28760 Tres Cantos, Madrid (Spain); Seravalli, Luca; Frigeri, Paola; Trevisi, Giovanna; Franchi, Secondo, E-mail: jrdi.gomis@icn.cat [CNR-IMEM Institute, Parco delle Scienze 37a, I-43100 Parma (Italy)

    2011-02-15

    We model the time-resolved and time-integrated photoluminescence of a single InAs/GaAs quantum dot (QD) using a random population description. We reproduce the joint power dependence of the single QD exciton complexes (neutral exciton, neutral biexciton and charged trions). We use the model to investigate the selective optical pumping phenomenon, a predominance of the negative trion observed when the optical excitation is resonant to a non-intentional impurity level. Our experiments and simulations determine that the negative charge confined in the QD after exciting resonance to the impurity level escapes in 10 ns.

  5. Extinction risk of Zamia inermis (Zamiaceae): a genetic approach for the conservation of its single natural population.

    Science.gov (United States)

    Zamia inermis, a narrowly endemic cycad has been classified under the IUCN Red List as Critically Endangered based on a 75% population decline over last 50 years. There is only one known population occupying an area of less than 10 km2 with 654 individuals with extremely low seed production and recr...

  6. Role of micro RNAs (miRs) involved in hemato lymphoid differentiation and malignancy: identification of novel miRs expressed in b-, t- lymphoid and hematopoietic cells

    International Nuclear Information System (INIS)

    Bronte, V.; Zanovello, P.; Dalla Favera, R.

    2009-01-01

    Total RNA from CD14+ cells (monocytes), CD15+ cells (polymorphonuclear cells), eosinophils, CD8+ T cells, resting and activated CD4+ T cells, two HTLV-1-infected cell lines (C91PL and MT-2), and different thymocyte populations was used as a source of small RNAs for the construction of miR cDNA libraries. In the initial phase of the study, sequences were identified after cloning cDNAs into a plasmid; to expedite this analysis, the cloning step has been replaced by direct 454 sequencing of uncloned cDNAs, carried out by Drs. G. DeBellis and A. Guffanti of the CNR, Istituto di Tecnologie Biomediche (Segrate-Milano). Resulting sequences are subjected to a series of bioinformatics analysis steps designed to identify known miRs (i.e., those catalogued in the Sanger miRBASE) and sequences that represent potential new miRs

  7. Multi-Genetic Marker Approach and Spatio-Temporal Analysis Suggest There Is a Single Panmictic Population of Swordfish Xiphias gladius in the Indian Ocean

    Science.gov (United States)

    Muths, Delphine; Le Couls, Sarah; Evano, Hugues; Grewe, Peter; Bourjea, Jerome

    2013-01-01

    Genetic population structure of swordfish Xiphias gladius was examined based on 2231 individual samples, collected mainly between 2009 and 2010, among three major sampling areas within the Indian Ocean (IO; twelve distinct sites), Atlantic (two sites) and Pacific (one site) Oceans using analysis of nineteen microsatellite loci (n = 2146) and mitochondrial ND2 sequences (n = 2001) data. Sample collection was stratified in time and space in order to investigate the stability of the genetic structure observed with a special focus on the South West Indian Ocean. Significant AMOVA variance was observed for both markers indicating genetic population subdivision was present between oceans. Overall value of F-statistics for ND2 sequences confirmed that Atlantic and Indian Oceans swordfish represent two distinct genetic stocks. Indo-Pacific differentiation was also significant but lower than that observed between Atlantic and Indian Oceans. However, microsatellite F-statistics failed to reveal structure even at the inter-oceanic scale, indicating that resolving power of our microsatellite loci was insufficient for detecting population subdivision. At the scale of the Indian Ocean, results obtained from both markers are consistent with swordfish belonging to a single unique panmictic population. Analyses partitioned by sampling area, season, or sex also failed to identify any clear structure within this ocean. Such large spatial and temporal homogeneity of genetic structure, observed for such a large highly mobile pelagic species, suggests as satisfactory to consider swordfish as a single panmictic population in the Indian Ocean. PMID:23717447

  8. Role of miR-145 in human laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Karatas, Omer Faruk; Yuceturk, Betul; Suer, Ilknur; Yilmaz, Mehmet; Cansiz, Harun; Solak, Mustafa; Ittmann, Michael; Ozen, Mustafa

    2016-02-01

    Laryngeal squamous cell carcinoma (SCC), being an aggressive malignancy, is one of the most commonly diagnosed malignant types of head and neck SCC worldwide. Incidences of laryngeal SCC have been reported to increase recently. In this study, we aimed to explore the biological effects of miR-145 on laryngeal cancer cells. The relative miR-145 level in laryngeal SCC tumor tissues and normal samples was investigated. Then, Hep-2 cells were utilized for functional analysis of miR-145. The proliferation abilities of transfected cells were measured using MTS assay. Scratch assay and single colony migration assay were performed to observe the alterations in migration behavior of transfected cells. Caspase assay and cell cycle analysis were used to investigate the underlying reasons of proliferative inhibition in cells in which miR-145 is overexpressed. Moreover, expression of SOX2 was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis in Hep-2 cells upon miR-145 transfection and its expression was evaluated in tumor and normal tissue sample of the larynx. The miR-145 expression in laryngeal SCC tumor samples has been shown to be downregulated. The miR-145 overexpression caused inhibition of proliferation and migration in Hep-2 cells through induction of apoptosis and cell cycle arrest. The SOX2 level was demonstrated to be overexpressed in tumor samples and its expression was significantly decreased in miR-145 overexpressed Hep-2 cells. We have demonstrated the deregulation of miR-145 and SOX2 in laryngeal SCC. Based on these results, we propose that miR-145, as an important regulator of SOX2, carries crucial roles in laryngeal SCC tumorigenesis. © 2015 Wiley Periodicals, Inc.

  9. Miłosz, wojna i poezja cywilna

    Directory of Open Access Journals (Sweden)

    Irena Grudzińska-Gross

    2012-12-01

    Full Text Available Miłosz, war and civilian poetry The article addresses the reaction of the Polish population during Second World War towards the military resistance to the occupier. The author offers a case study of the life choices of Czesław Miłosz, the poet. Considering them hopeless and counterproductive, Miłosz decided not to participate in military actions. He had no confidence in the Polish government in exile and its military decisions. Instead, the poet concentrated on writing and publishing; he also criticized what he viewed as unjustified sacrifice of life in the Warsaw Uprising of 1944. His attitude was criticized then, and today continues to be a source of attacks against the poet. The article analyses the logic of national solidarity in the times of foreign occupation and the arguments of the poet’s critics. The author of the article comes to the conclusion that Miłosz’s stand was beneficial not only for himself but also for the community as a whole.

  10. Perspectives on Sámi historiography

    Directory of Open Access Journals (Sweden)

    Lars Ivar Hansen

    2017-09-01

    Full Text Available The article focuses on Sámi history and historical methods. The main results and central aspects of Sámi history, in its relational context, are gone through. What effects and consequences — regarding both methodology and narrative styles — these aspects have had, and ought to have, for the processes of doing research on and writing Sámi history? The focus is on the politics of Sámi history and research. The issues, who is “allowed” to write Sámi history and the way Sámi research is demanded to stand in the service of different societal-cultural needs of the Sámi is dealt with. This expectation of applicability concerns Sámi history in general, and the more delimited efforts of presenting situated accounts of Sámi cultural practices, traditions and experience with relations to other folk groups. Finally, methodological considerations and recommendations of Sámi history are presented, in which a number of methodological competences and in-depth usage of numerous source categories are called for.

  11. Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Afsar R. Naqvi

    2018-03-01

    Full Text Available Prevalence of the members of herpesvirus family in oral inflammatory diseases is increasingly acknowledged suggesting their likely role as an etiological factor. However, the underlying mechanisms remain obscure. In our recent miRNA profiling of healthy and diseased human tooth pulps, elevated expression of human herpesvirus encoded viral microRNAs (v-miRs were identified. Based on the fold induction and significance values, we selected three v-miRs namely miR-K12-3-3p [Kaposi sarcoma-associated virus (KSHV], miR-H1 [herpes simplex virus 1 (HSV1], and miR-UL-70-3p [human cytomegalovirus (HCMV] to further examine their impact on host cellular functions. We examined their impact on cellular miRNA profiles of primary human oral keratinocytes (HOK. Our results show differential expression of several host miRNAs in v-miR-transfected HOK. High levels of v-miRs were detected in exosomes derived from v-miR transfected HOK as well as the KSHV-infected cell lines. We show that HOK-derived exosomes release their contents into macrophages (Mφ and alter expression of endogenous miRNAs. Concurrent expression analysis of precursor (pre-miRNA and mature miRNA suggest transcriptional or posttranscriptional impact of v-miRs on the cellular miRNAs. Employing bioinformatics, we predicted several pathways targeted by deregulated cellular miRNAs that include cytoskeletal organization, endocytosis, and cellular signaling. We validated three novel targets of miR-K12-3-3p and miR-H1 that are involved in endocytic and intracellular trafficking pathways. To evaluate the functional consequence of this regulation, we performed phagocytic uptake of labeled bacteria and noticed significant attenuation in miR-H1 and miR-K12-3-3p but not miR-UL70-3p transfected primary human Mφ. Multiple cytokine analysis of E. coli challenged Mφ revealed marked reduction of secreted cytokine levels with important roles in innate and adaptive immune responses suggesting a role of v-miRs in

  12. Secreted protein gene derived-single nucleotide polymorphisms (SP-SNPs) reveal population diversity and differentiation of Puccinia striiformis f. sp. tritici in the United States.

    Science.gov (United States)

    Xia, Chongjing; Wan, Anmin; Wang, Meinan; Jiwan, Derick A; See, Deven R; Chen, Xianming

    2016-05-01

    Single nucleotide polymorphism (SNP) is a powerful molecular marker technique that has been widely used in population genetics and molecular mapping studies for various organisms. However, the technique has not been used for studying Puccinia striiformis f. sp. tritici (Pst), the wheat stripe rust pathogen. In this study, we developed over a hundred secreted protein gene-derived SNP (SP-SNP) markers and used 92 markers to study the population structure of Pst. From 352 isolates collected in the United States, we identified 242 multi-locus genotypes. The SP-SNP genotypes had a moderate, but significant correlation with the virulence phenotype data. Clustering of the multi-locus genotypes was consistent by various analyses, revealing distinct genetic groups. Analysis of molecular variance detected significant differences between the eastern and western US Pst populations. High heterozygosity was found in the US population with significant differences identified among epidemiological regions. Analysis of population differentiation revealed that populations between the eastern and western US were highly differentiated while moderate differentiation was found in populations within the western or eastern US. Isolates from the western US were more diverse than isolates from the eastern US. The information is useful for guiding the disease management in different epidemiological regions. Published by Elsevier Ltd.

  13. Reduction of a single granule drying model: An essential step in preparation of a population balance model with a continuous growth term

    DEFF Research Database (Denmark)

    Mortier, Séverine Thérèse F.C.; Daele, Timothy, Van; Gernaey, Krist V.

    2013-01-01

    for a single granule needs reduction in complexity. The starting point is a detailed model that describes the drying behavior of single pharmaceutical granules. A Global Sensitivity Analysis (GSA) was performed to detect the most sensitive degrees of freedom in the model as these need to be retained...... in the reduced model. Simulations of the complex drying model were, in a next phase, used to develop the reduced model, which describes the decrease of the moisture content in function of the gas temperature. The developed reduced model was then included in a Population Balance Equation (PBE) to describe......The development of a Population Balance Model (PBM) for a pharmaceutical granule drying process requires a continuous growth term; the latter actually represents the drying process as the moisture content is the internal coordinate of the PBM. To establish such a PBM, a complex drying model...

  14. miRConnect:Identifying effector genes of miRNAs and miRNA families in cancer cells

    DEFF Research Database (Denmark)

    Hua, Youjia; Duan, Shiwei; Murmann, Andrea E

    2011-01-01

    have generated custom data sets containing expression information of 54 miRNA families sharing the same seed match. We have developed a novel strategy for correlating miRNAs with individual genes based on a summed Pearson Correlation Coefficient (sPCC) that mimics an in silico titration experiment......micro(mi)RNAs are small non-coding RNAs that negatively regulate expression of most mRNAs. They are powerful regulators of various differentiation stages, and the expression of genes that either negatively or positively correlate with expressed miRNAs is expected to hold information...

  15. Differential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients.

    Science.gov (United States)

    Vrabec, Katarina; Boštjančič, Emanuela; Koritnik, Blaž; Leonardis, Lea; Dolenc Grošelj, Leja; Zidar, Janez; Rogelj, Boris; Glavač, Damjan; Ravnik-Glavač, Metka

    2018-01-01

    Genetic studies have managed to explain many cases of familial amyotrophic lateral sclerosis (ALS) through mutations in several genes. However, the cause of a majority of sporadic cases remains unknown. Recently, epigenetics, especially miRNA studies, show some promising aspects. We aimed to evaluate the differential expression of 10 miRNAs, including miR-9, miR-338, miR-638, miR-663a, miR-124a, miR-143, miR-451a, miR-132, miR-206, and let-7b, for which some connection to ALS was shown previously in ALS culture cells, animal models or patients, and in three miRNA host genes, including C1orf61 (miR-9), AATK (miR-338), and DNM2 (miR-638), in leukocyte samples of 84 patients with sporadic ALS. We observed significant aberrant dysregulation across our patient cohort for miR-124a, miR-206, miR-9, let-7b, and miR-638. Since we did not use neurological controls we cannot rule out that the revealed differences in expression of investigated miRNAs are specific for ALS. Nevertheless, the group of these five miRNAs is worth of additional research in leukocytes of larger cohorts from different populations in order to verify their potential association to ALS disease. We also detected a significant up-regulation of the AAKT gene and down-regulation of the DNM2 gene, and thus, for the first time, we connected these with sporadic ALS cases. These findings open up new research toward miRNAs as diagnostic biomarkers and epigenetic processes involved in ALS. The detected significant deregulation of AAKT and DNM2 in sporadic ALS also represents an interesting finding. The DNM2 gene was previously found to be mutated in Charcot-Marie-Tooth neuropathy-type CMT2M and centronuclear myopathy (CNM). In addition, as recent studies connected AATK and frontotemporal dementia (FTD) and DNM2 and hereditary spastic paraplegia (HSP), these two genes together with our results genetically connect, at least in part, five diseases, including FTD, HSP, Charcot-Marie-Tooth (type CMT2M), CNM, and ALS

  16. Deep sequencing of RNA from three different extracellular vesicle (EV subtypes released from the human LIM1863 colon cancer cell line uncovers distinct miRNA-enrichment signatures.

    Directory of Open Access Journals (Sweden)

    Hong Ji

    Full Text Available Secreted microRNAs (miRNAs enclosed within extracellular vesicles (EVs play a pivotal role in intercellular communication by regulating recipient cell gene expression and affecting target cell function. Here, we report the isolation of three distinct EV subtypes from the human colon carcinoma cell line LIM1863--shed microvesicles (sMVs and two exosome populations (immunoaffinity isolated A33-exosomes and EpCAM-exosomes. Deep sequencing of miRNA libraries prepared from parental LIM1863 cells/derived EV subtype RNA yielded 254 miRNA identifications, of which 63 are selectively enriched in the EVs--miR-19a/b-3p, miR-378a/c/d, and miR-577 and members of the let-7 and miR-8 families being the most prominent. Let-7a-3p*, let-7f-1-3p*, miR-451a, miR-574-5p*, miR-4454 and miR-7641 are common to all EV subtypes, and 6 miRNAs (miR-320a/b/c/d, miR-221-3p, and miR-200c-3p discern LIM1863 exosomes from sMVs; miR-98-5p was selectively represented only in sMVs. Notably, A33-Exos contained the largest number (32 of exclusively-enriched miRNAs; 14 of these miRNAs have not been reported in the context of CRC tissue/biofluid analyses and warrant further examination as potential diagnostic markers of CRC. Surprisingly, miRNA passenger strands (star miRNAs for miR-3613-3p*, -362-3p*, -625-3p*, -6842-3p* were the dominant strand in A33-Exos, the converse to that observed in parental cells. This finding suggests miRNA biogenesis may be interlinked with endosomal/exosomal processing.

  17. Expression, Covariation, and Genetic Regulation of miRNA Biogenesis Genes in Brain Supports their Role in Addiction, Psychiatric Disorders, and Disease

    Directory of Open Access Journals (Sweden)

    Megan Kathleen Mulligan

    2013-07-01

    Full Text Available The role of miRNA and miRNA biogenesis genes in the adult brain is just beginning to be explored. In this study we have performed a comprehensive analysis of the expression, genetic regulation, and co-expression of major components of the miRNA biogenesis pathway using human and mouse data sets and resources available on the GeneNetwork web site (genenetwork.org. We found a wide range of variation in expression in both species for key components of the pathway—Drosha, Pasha, and Dicer. Across species, tissues, and expression platforms all three genes are generally well correlated. No single genetic locus exerts a strong and consistent influence on the expression of these key genes across murine brain regions. However, in mouse striatum, many members of the miRNA pathway are correlated—including Dicer, Drosha, Pasha, Ars2 (Srrt, Eif2c1 (Ago1, Eif2c2 (Ago2, Zcchc11, and Snip1. The expression of these genes may be partly influenced by a locus on Chromosome 9 (105.67 to 106.32 Mb. We explored ~1500 brain phenotypes available for the C57BL/6J x DBA/2J (BXD genetic mouse population in order to identify miRNA biogenesis genes correlated with traits related to addiction and psychiatric disorders. We found a significant association between expression of Dicer and Drosha in several brain regions and the response to many drugs of abuse, including ethanol, cocaine, and methamphetamine. Expression of Dicer, Drosha, and Pasha in most of the brain regions explored is strongly correlated with the expression of key members of the dopamine system. Drosha, Pasha, and Dicer expression is also correlated with the expression of behavioral traits measuring depression and sensorimotor gating, impulsivity, and anxiety, respectively. Our study provides a global survey of the expression and regulation of key miRNA biogenesis genes in brain and provides preliminary support for the involvement of these genes and their product miRNAs in addiction and psychiatric disease

  18. Invasive cyprinid fish in Europe originate from the single introduction of an admixed source population followed by a complex pattern of spread.

    Directory of Open Access Journals (Sweden)

    Andrea Simon

    Full Text Available The Asian cyprinid fish, the topmouth gudgeon (Pseudorasbora parva, was introduced into Europe in the 1960s. A highly invasive freshwater fish, it is currently found in at least 32 countries outside its native range. Here we analyse a 700 base pair fragment of the mitochondrial cytochrome b gene to examine different models of colonisation and spread within the invasive range, and to investigate the factors that may have contributed to their invasion success. Haplotype and nucleotide diversity of the introduced populations from continental Europe was higher than that of the native populations, although two recently introduced populations from the British Isles showed low levels of variability. Based on coalescent theory, all introduced and some native populations showed a relative excess of nucleotide diversity compared to haplotype diversity. This suggests that these populations are not in mutation-drift equilibrium, but rather that the relative inflated level of nucleotide diversity is consistent with recent admixture. This study elucidates the colonisation patterns of P. parva in Europe and provides an evolutionary framework of their invasion. It supports the hypothesis that their European colonisation was initiated by their introduction to a single location or small geographic area with subsequent complex pattern of spread including both long distance and stepping-stone dispersal. Furthermore, it was preceded by, or associated with, the admixture of genetically diverse source populations that may have augmented its invasive-potential.

  19. Single nucleotide polymorphism rs1800872 in the promoter region of the IL10 gene is associated with predisposition to chronic hepatitis C in Russian population.

    Science.gov (United States)

    Barkhash, Andrey V; Kochneva, Galina V; Chub, Elena V; Romaschenko, Aida G

    2018-03-01

    Previously, we studied an association of two IL28B gene single nucleotide polymorphisms (SNPs) and three IL10 gene SNPs with predisposition to tick-borne encephalitis in a Russian population. In this study, a possible involvement of these SNPs in the development of predisposition to chronic hepatitis C (caused by structurally similar, related virus from the Flaviviridae family) was investigated in the same population. Only the IL10 promoter rs1800872 SNP was associated with predisposition to chronic hepatitis C. This SNP seems to be a common genetic marker of predisposition to two diseases caused by hepatitis C and tick-borne encephalitis viruses in Russian population. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  20. Demethylation of miR-9-3 and miR-193a Genes Suppresses Proliferation and Promotes Apoptosis in Non-Small Cell Lung Cancer Cell Lines

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    Jinliang Wang

    2013-12-01

    Full Text Available Background: MicroRNAs miR-9-3 and miR-193a have recently been found to be hypermethylated in a variety of non-small cell lung cancer (NSCLC cells and primary human tumors. The objectives of this study were to investigate the role of demethylation of miR-9-3 and miR-193a genes in regulating proliferation and apoptosis in NSCLCs, and to decipher the potential mechanisms underlying the properties. Methods: MTT and population doubling time by flow cytometry were used to assess cell proliferation. Enzyme-Linked Immunosorbent Assay and caspase-3 activity assay were employed to evaluate apoptosis. Real-time RT-PCR and Western blot were used to quantify gene expression at mRNA and protein levels, respectively. Methylation-specific PCR was utilized to assess methylation status. Results: We found that demethylation agent 5-Aza-2'-deoxycytidine (5-AzaC reduced cell numbers and prolonged population doubling time (PDT, and promoted doxorubicin-induced apoptosis in seven NSCLC cell lines with different methylation statuses on miR-9-3 and miR-193a promoter regions: NCI-H1993/NCI-H1915 (miR-9-3+/miR-193a+, NCI-H1975/NCI-H200 (miR-9-3+/miR-193a-, A427/NCI-H2073 (miR-9-3-/miR-193a+, and NCI-H1703 (miR-9-3-/miR-193a-. Treatment with 5-AzaC concomitantly upregulated expression of miR-9-3 and miR-193a, and downregulated their respective target genes NF-κB and Mcl-1. The effects of 5-AzaC were abolished by concomitant knockdown of miR-9-3 and miR-193a using the complex antisense technique, whereas forced ectopic expression of miR-9-3 and miR-193a mimicked the effects of 5-AzaC. We further observed that the strength of proliferation inhibition and apoptosis promotion elicited by 5-AzaC was in the order of NCI-H1993/NCI-H1915 > A427/NCI-H2073 > NCI-H1975/NCI-H200 > NCI-H1703. Conclusions: Methylation-silencing of miR-9-3 and miR-193a may be an important epigenetic mechanisms favoring NSCLC cell growth and survival for carcinogenesis and cancer progression, and

  1. Single nucleotide polymorphisms of the SLC22A2 gene within the Xhosa population of South Africa.

    Science.gov (United States)

    Jacobs, Clifford; Pearce, Brendon; Du Plessis, Mornè; Hoosain, Nisreen; Benjeddou, Mongi

    2015-12-01

    Human organic cation transporter 2 (hOCT2) is thought to play a critical role in the uptake, pharmacological effects and/or adverse effects of many cationic clinical therapeutics and xenobiotics. Moreover, genetic variations in hOCT2 gene, SLC22A2, are increasingly being recognized as a possible mechanism that can explain individual variation in drug response. To screen for variations in this gene, SLC22A2 was directly sequenced in 96 healthy Xhosa individuals. A total of 27 variations, including three novel ones, were identified in SLC22A2: eight in exons, 15 in introns, and four in the 5'-untranslated region. The minor allele frequencies (MAF) of genetic variants observed in the Xhosa population were compared both to other African and other world populations. Seventeen of the variants observed in the SLC22A2 gene of the Xhosa population were specific to/or occurred at a higher frequency in African populations or populations with a recent connection to the African continent. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  2. Population genetic structure in farm and feral American mink (Neovison vison) inferred from RAD sequencing-generated single nucleotide polymorphisms.

    Science.gov (United States)

    Thirstrup, J P; Ruiz-Gonzalez, A; Pujolar, J M; Larsen, P F; Jensen, J; Randi, E; Zalewski, A; Pertoldi, C

    2015-08-01

    Feral American mink populations (), derived from mink farms, are widespread in Europe. In this study we investigated genetic diversity and genetic differentiation between feral and farm mink using a panel of genetic markers (194 SNP) generated from RAD sequencing data. Sampling included a total of 211 individuals from 14 populations, 4 feral and 10 from farms, the latter including a total of 7 color types (Brown, Black, Mahogany, Sapphire, White, Pearl, and Silver). Our study revealed similar low levels of genetic diversity in both farm and feral mink. Results are consistent with small effective population size as a consequence of line selection in the farms and founder effects of a few escapees from the farms in feral populations. Moderately high genetic differentiation was found between farm and feral animals, suggesting a scenario in which wild populations were founded from farm escapes a few decades ago. Currently, escapes and gene flow are probably limited. Genetic differentiation was higher among farm color types than among farms, consistent with line selection using few individuals to create the lines. Finally, no indications of inbreeding were found in either farm or feral samples, with significant negative values found in most farm samples, showing farms are successful in avoiding inbreeding.

  3. Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Andersen, Morten; Grauslund, Morten; Ravn, Jesper

    2014-01-01

    Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). It is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMPs. Thus, we screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 mi......RNAs in formalin-fixed, paraffin-embedded, preoperative diagnostic biopsy samples, surgically resected MPM specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP), from five patients. miR-126, miR-143, miR-145, and miR-652 were significantly down-regulated (≥twofold......) in resected MPM and/or chemotherapy-naïve diagnostic tumor biopsy samples. The miRNA expression pattern was validated by RT-qPCR in a cohort of 40 independent MPMs. By performing binary logistic regression on the RT-qPCR data for the four miRNAs, the established four-miRNA classifier differentiated MPM from...

  4. The prospective association between obesity and major depression in the general population : does single or recurrent episode matter?

    NARCIS (Netherlands)

    Nigatu, Yeshambel T.; Bultmann, Ute; Reijneveld, Sijmen A.

    2015-01-01

    Background: Obesity and major depressive disorder (MDD) are important public health problems. MDD is a heterogeneous disorder and the direction of its association with obesity remains unclear. Evidence grows that recurrent MDD (MDD-R) differs in etiology and prognosis from single episode MDD

  5. Expression Variations of miRNAs and mRNAs in Rice (Oryza sativa).

    Science.gov (United States)

    Wen, Ming; Xie, Munan; He, Lian; Wang, Yushuai; Shi, Suhua; Tang, Tian

    2016-12-31

    Differences in expression levels are an important source of phenotypic variation within and between populations. MicroRNAs (miRNAs) are key players in post-transcriptional gene regulation that are important for plant development and stress responses. We surveyed expression variation of miRNAs and mRNAs of six accessions from two rice subspecies Oryza sativa L. ssp. indica and Oryza sativa L. ssp. japonica using deep sequencing. While more than half (53.7%) of the mature miRNAs exhibit differential expression between grains and seedlings of rice, only 11.0% show expression differences between subspecies, with an additional 2.2% differentiated for the development-by-subspecies interaction. Expression variation is greater for lowly conserved miRNAs than highly conserved miRNAs, whereas the latter show stronger negative correlation with their targets in expression changes between subspecies. Using a permutation test, we identified 51 miRNA-mRNA pairs that correlate negatively or positively in expression level among cultivated rice. Genes involved in various metabolic processes and stress responses are enriched in the differentially expressed genes between rice indica and japonica subspecies. Our results indicate that stabilizing selection is the major force governing miRNA expression in cultivated rice, albeit positive selection may be responsible for much of the between-subspecies expression divergence. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Characteristics and Outcomes of Open Globe Trauma in the Urban versus Rural Population: A Single Center Retrospective Review.

    Science.gov (United States)

    Fu, Roxana; Kancherla, Swarupa; Eller, Andrew W; Yu, Jenny Y

    2017-07-05

    To examine the characteristics and outcomes of open globe injuries sustained by the urban population compared to the rural population. This is a retrospective chart review of 429 patients presenting to University of Pittsburgh Medical Center (UPMC) Presbyterian Hospital with traumatic open globes from July 2005 to July 2013. Rural patients had a longer time which elapsed from injury to presentation (P = 0.023, average 12.04 hours vs 7.53 hours). There was a higher incidence of patient transfer prior to arrival to UPMC Presbyterian Hospital (P = 0.018), patient follow-up elsewhere (P = 0.049), and patients sustaining intraocular foreign bodies (IOFBs) (P = 0.009). Health care access is a well-known problem in rural areas and using rural-urban commuting area (RUCA) codes can help identify a population for risk factors or potential disparities in care. Rural patients sustained a higher rate of IOFBs; this should heighten the clinicians' suspicion during the evaluation of an open globe in other rural populations.

  7. Analysis of genetic diversity in Brown Swiss, Jersey and Holstein populations using genome-wide single nucleotide polymorphism markers

    Directory of Open Access Journals (Sweden)

    Melka Melkaye G

    2012-03-01

    Full Text Available Abstract Background Studies of genetic diversity are essential in understanding the extent of differentiation between breeds, and in designing successful diversity conservation strategies. The objective of this study was to evaluate the level of genetic diversity within and between North American Brown Swiss (BS, n = 900, Jersey (JE, n = 2,922 and Holstein (HO, n = 3,535 cattle, using genotyped bulls. GENEPOP and FSTAT software were used to evaluate the level of genetic diversity within each breed and between each pair of the three breeds based on genome-wide SNP markers (n = 50,972. Results Hardy-Weinberg equilibrium (HWE exact test within breeds showed a significant deviation from equilibrium within each population (P st indicated that the combination of BS and HO in an ideally amalgamated population had higher genetic diversity than the other pairs of breeds. Conclusion Results suggest that the three bull populations have substantially different gene pools. BS and HO show the largest gene differentiation and jointly the highest total expected gene diversity compared to when JE is considered. If the loss of genetic diversity within breeds worsens in the future, the use of crossbreeding might be an option to recover genetic diversity, especially for the breeds with small population size.

  8. Need for a nomogram of renal sizes in the Indian population- findings from a single centre sonographic study

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    Prakash Muthusami

    2014-01-01

    Full Text Available Background & objectives: Renal size is an important parameter used in the diagnosis and follow up of renal diseases. However, while making decisions, clinicians must be aware of the dependence of these dimensions on the ethnicity of the individual, independent of anthropometric indices. There is no established nomogram for renal sizes in the Indian population. The aim of this study was to assess the applicability of oft-quoted ranges of normal renal sizes in our population. Methods: Renal dimensions including length, width and parenchymal thickness were sonographically measured in 140 individuals with no renal disease. Analysis was done for differences due to age, gender and laterality. The correlation of renal dimensions with anthropometric parameters like weight, height, body mass index (BMI and body surface area (BSA was analyzed. Results: The means of length, width and parenchymal thickness of all 280 kidneys of 140 patients were 9.65 ± 0.63, 4.5 ± 0.42 and 2.04 ± 0.2 cm, respectively. There was a significant difference in parenchymal thickness between the right and left kidneys, while there was no significant right-left difference in length or width. Gender-wise analysis showed significant differences between male and female renal breadths but not length and parenchymal thickness. Age group-wise analysis showed significant decrease in renal length and parenchymal thickness beyond the seventh decade. There was a moderate positive correlation of bilateral renal length with body weight and BSA, and a weak positive correlation with body height and BMI. Interpretation & conclusions: Renal sizes in our population are in contrast to commonly quoted normal values in literature. Conclusions about renal sizes need to be made with reference to nomograms and should not be based upon data from other populations. We also present formulae whereby to derive renal sizes from anthropometric indices in our population.

  9. Bacillus cereus AR156 primes induced systemic resistance by suppressing miR825/825* and activating defense-related genes in Arabidopsis.

    Science.gov (United States)

    Niu, Dongdong; Xia, Jing; Jiang, Chunhao; Qi, Beibei; Ling, Xiaoyu; Lin, Siyuan; Zhang, Weixiong; Guo, Jianhua; Jin, Hailing; Zhao, Hongwei

    2016-04-01

    Small RNAs play an important role in plant immune responses. However, their regulatory function in induced systemic resistance (ISR) is nascent. Bacillus cereus AR156 is a plant growth-promoting rhizobacterium that induces ISR in Arabidopsis against bacterial infection. Here, by comparing small RNA profiles of Pseudomonas syringae pv. tomato (Pst) DC3000-infected Arabidopsis with and without AR156 pretreatment, we identified a group of Arabidopsis microRNAs (miRNAs) that are differentially regulated by AR156 pretreatment. miR825 and miR825* are two miRNA generated from a single miRNA gene. Northern blot analysis indicated that they were significantly downregulated in Pst DC3000-infected plants pretreated with AR156, in contrast to the plants without AR156 pretreatment. miR825 targets two ubiquitin-protein ligases, while miR825* targets toll-interleukin-like receptor (TIR)-nucleotide binding site (NBS) and leucine-rich repeat (LRR) type resistance (R) genes. The expression of these target genes negatively correlated with the expression of miR825 and miR825*. Moreover, transgenic plants showing reduced expression of miR825 and miR825* displayed enhanced resistance to Pst DC3000 infection, whereas transgenic plants overexpressing miR825 and miR825* were more susceptible. Taken together, our data indicates that Bacillus cereus AR156 pretreatment primes ISR to Pst infection by suppressing miR825 and miR825* and activating the defense related genes they targeted. © 2015 Institute of Botany, Chinese Academy of Sciences.

  10. Evolutionary and Expression Analysis of miR-#-5p and miR-#-3p at the miRNAs/isomiRs Levels

    Directory of Open Access Journals (Sweden)

    Li Guo

    2015-01-01

    Full Text Available We mainly discussed miR-#-5p and miR-#-3p under three aspects: (1 primary evolutionary analysis of human miRNAs; (2 evolutionary analysis of miRNAs from different arms across the typical 10 vertebrates; (3 expression pattern analysis of miRNAs at the miRNA/isomiR levels using public small RNA sequencing datasets. We found that no bias can be detected between the numbers of 5p-miRNA and 3p-miRNA, while miRNAs from miR-#-5p and miR-#-3p show variable nucleotide compositions. IsomiR expression profiles from the two arms are always stable, but isomiR expressions in diseased samples are prone to show larger degree of dispersion. miR-#-5p and miR-#-3p have relative independent evolution/expression patterns and datasets of target mRNAs, which might also contribute to the phenomena of arm selection and/or arm switching. Simultaneously, miRNA/isomiR expression profiles may be regulated via arm selection and/or arm switching, and the dynamic miRNAome and isomiRome will adapt to functional and/or evolutionary pressures. A comprehensive analysis and further experimental study at the miRNA/isomiR levels are quite necessary for miRNA study.

  11. Current trends in miRNAs and their relationship with oral squamous cell carcinoma.

    Science.gov (United States)

    Pérez-Sayáns, Mario; Pilar, Gayoso-Diz; Barros-Angueira, Francisco; Suárez-Peñaranda, José Manuel; Fernández, Alexia Conde; Gándara-Rey, José Manuel; García-García, Abel

    2012-07-01

    A micro RNA (miRNA) is a single-stranded endogenous, non-coding RNA, with length ranging between 18 and 24 nucleotides and the ability of regulating the expression of other genes on a post-transcriptional level by means of various processes, degradation or repression of target mRNA. miRNAs play a crucial role in regulating fundamental processes such as cell cycle, differentiation and apoptosis; thus, their deregulation can affect normal cell growth and development, and even participate in carcinogenesis. The goals of this paper are: to outline the formation and functions of miRNAs; to determine their role in oral squamous cell carcinoma; to analyze the different miRNAs described and their roles as oncogenes or tumor suppressor genes, depending on their overexpression or subexpression; to describe the different polymorphisms and epigenetic alterations identified; and to determine their role in multidrug resistance. © 2011 John Wiley & Sons A/S.

  12. Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon).

    Science.gov (United States)

    Scala, Christopher; Marsot, Amélie; Limoges, Marie-Josée; Locatelli, Yann; Simon, Nicolas; Alvarez, Jean-Claude

    2015-03-01

    To assess the population pharmacokinetics of methadone in deer. Prospective non-randomized experimental trial. Twelve healthy adult sika deer (nine males and three females). Deer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg(-1) or 1 mg kg(-1) . Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM). A two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour(-1) ), metabolic clearance (34.6 L hour(-1) ), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour(-1) ), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour(-1) , 121.0 L hour (-1) , 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration. Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  13. You Can't Unscramble an Egg: Population Genetic Structure of Oncorhynchus mykiss in the California Central Valley Inferred from Combined Microsatellite and Single Nucleotide Polymorphism Data

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    Devon E. Pearse

    2015-12-01

    Full Text Available doi: http://dx.doi.org/10.15447/sfews.2015v13iss4art3Steelhead/rainbow trout (Oncorhynchus mykiss are found in all of the major tributaries of the Sacramento and San Joaquin rivers, which flow through California’s Central Valley and enter the ocean through San Francisco Bay and the Golden Gate. This river system is heavily affected by water development, agriculture, and invasive species, and salmon and trout hatchery propagation has been occurring for over 100 years. We collected genotype data for 18 highly variable microsatellite loci and 95 single nucleotide polymorphisms (SNPs from more than 1,900 fish from Central Valley drainages to analyze genetic diversity, population structure, differentiation between populations above and below dams, and the relationship of Central Valley O. mykiss populations to coastal California steelhead. In addition, we evaluate introgression by both hatchery rainbow trout strains, which have primarily native Central Valley ancestry, and imported coastal steelhead stocks. In contrast to patterns typical of coastal steelhead, Central Valley O. mykiss above and below dams within the same tributary were not found to be each others’ closest relatives, and we found no relationship between genetic and geographic distance among below-barrier populations. While introgression by hatchery rainbow trout strains does not appear to be widespread among above-barrier populations, steelhead in the American River and some neighboring tributaries have been introgressed by coastal steelhead. Together, these results demonstrate that the ancestral population genetic structure that existed among Central Valley tributaries has been significantly altered in contemporary populations. Future conservation, restoration, and mitigation efforts should take this into account when working to meet recovery planning goals.

  14. Genomic diversity and affinities in population groups of North West India: an analysis of Alu insertion and a single nucleotide polymorphism.

    Science.gov (United States)

    Saini, J S; Kumar, A; Matharoo, K; Sokhi, J; Badaruddoza; Bhanwer, A J S

    2012-12-15

    The North West region of India is extremely important to understand the peopling of India, as it acted as a corridor to the foreign invaders from Eurasia and Central Asia. A series of these invasions along with multiple migrations led to intermixture of variable populations, strongly contributing to genetic variations. The present investigation was designed to explore the genetic diversities and affinities among the five major ethnic groups from North West India; Brahmin, Jat Sikh, Bania, Rajput and Gujjar. A total of 327 individuals of the abovementioned ethnic groups were analyzed for 4 Alu insertion marker loci (ACE, PV92, APO and D1) and a Single Nucleotide Polymorphism (SNP) rs2234693 in the intronic region of the ESR1 gene. Statistical analysis was performed to interpret the genetic structure and diversity of the population groups. Genotypes for ACE, APO, ESR1 and PV92 loci were found to be in Hardy-Weinberg equilibrium in all the ethnic groups, while significant departures were observed at the D1 locus in every investigated population after Bonferroni's correction. The average heterozygosity for all the loci in these ethnic groups was fairly substantial ranging from 0.3927 ± 0.1877 to 0.4333 ± 0.1416. Inbreeding coefficient indicated an overall 10% decrease in heterozygosity in these North West Indian populations. The gene differentiation among the populations was observed to be of the order of 0.013. Genetic distance estimates revealed that Gujjars were close to Banias and Jat Sikhs were close to Rajputs. Overall the study favored the recent division of the populations of North West India into largely endogamous groups. It was observed that the populations of North West India represent a more or less homogenous genetic entity, owing to their common ancestral history as well as geographical proximity. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Positive Association of Metabolic Syndrome with a Single Nucleotide Polymorphism of Syndecan-3 (rs2282440 in the Taiwanese Population

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    Betty Chia-Chen Chang

    2018-01-01

    Full Text Available Background/Purpose. Metabolic syndrome (MetS poses a major public health burden on the general population worldwide. Syndecan-3 (SDC3, a heparin sulfate proteoglycan, had been found by previous studies to be linked with energy balance and obesity, but its association with MetS is not known. The objective of this study is to investigate whether SDC3 polymorphism (rs2282440 is associated with MetS in the Taiwanese population. Methods. Genotypes of SDC3 polymorphism (rs2282440 were analyzed in 545 Taiwanese adult subjects, of which 154 subjects had MetS. Results. Subjects with SDC3 rs2282440 TT homozygote had higher frequency of MetS than those with CC or CT genotype (p=0.0217. SDC3 rs2282440 TT homozygote had a 1.96-fold risk of being obese and 1.8-fold risk of having MetS (with CC genotype as reference. As for the individual components of MetS, subjects with SDC3 rs2282440 TT homozygote were more likely to have large waist circumference and low high-density lipoprotein cholesterol (OR = 1.75 and OR = 1.84, resp.. Conclusion. SDC3 rs2282440 polymorphism is positively associated with MetS in the Taiwanese population. Further investigation is needed to see if this association is mediated by mere adiposity or SDC3 polymorphism is also linked with other components of MetS such as lipid metabolism.

  16. miR-71b regulation of insulin/IGF-1 signaling during starvation in planarians.

    Science.gov (United States)

    Wu, Y Y; Zhao, J M; Liu, Q; Guo, Q; Liu, Z; Wang, X X; Wang, C Y; Li, R Y; Zhang, Y Z; Zhang, S T

    2015-10-05

    Planarians, which have a large population of stem cells called neoblasts, are molecularly tractable model systems used in the study of regeneration. However, planarians have strong resistance to hunger and have developed growth arrest strategies. For example, they can change their size and undergo growth regression during starvation periods. The results of the current study show that the microRNA, miR-71b, and the insulin/IGF-1 signaling pathway have important functions in the development of starvation-induced planarians. We demonstrate tissue-specific expression of miR-71b using in situ hybridization. By employing real-time polymerase chain reaction, we provide evidence that miR-71b is upregulated in starvation-induced planarians. Furthermore, we validate and verify the target genes of miR-71b.

  17. MTUS1 tumor suppressor and its miRNA regulators in fibroadenoma and breast cancer.

    Science.gov (United States)

    Kara, Murat; Kaplan, Mehmet; Bozgeyik, Ibrahim; Ozcan, Onder; Celik, Ozgur Ilhan; Bozgeyik, Esra; Yumrutas, Onder

    2016-08-10

    Breast cancer is major public health problem predominantly effects female population. Current therapeutic approaches to deal with breast cancer are still lack of effectiveness. Thus, identifying/developing novel strategies to fight against breast cancer is very important. The frequent deletions at 8p21.3-22 chromosomal location nearby D8S254 marker enabled the discovery of a novel tumor suppressor gene, MTUS1. Subsequently, MTUS1 was demonstrated to be less expressed in a variety cancer types including breast cancer. Also, it is obvious that gene expression is widely regulated by miRNAs. Here, we aimed to report differential expression of MTUS1 and its regulatory miRNAs in breast cancer and fibroadenoma tissues. Dynamic analysis of MTUS1 expression levels and its miRNAs regulators were attained by Fluidigm 96×96 Dynamic Array Expression chips and reactions were performed in Fluidigm BioMark™ HD System qPCR. Consequently, MTUS1 mRNA levels were significantly diminished in breast cancer tissues and elevated in fibroadenoma tissues. Also, among MTUS1 targeting miRNAs, miR-183-5p was identified to be overexpressed in breast cancer and down-regulated in fibroadenoma tissues. Also, expression levels of MTUS1 and miR-183-5p were well correlated with clinical parameters. In particular, MTUS1 expression was found to be diminished and miR-183-5p expression was elevated with the advancing stage. In conclusion, as a potential therapeutic target, miR-183-5p can be a chief regulator of MTUS1 and MTUS1-miR-183-5p axis may have significant influence in the pathology of breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Miércoles al cine

    OpenAIRE

    Aguado Franco, Juan Carlos

    2014-01-01

    Se analiza un caso concreto de demanda ante una iniciativa empresarial: los miércoles al cine. Se analiza un caso concreto de demanda ante una iniciativa empresarial: los miércoles al cine. Fundamentos del Análisis Económico

  19. MiRNA Biogenesis and Intersecting Pathways

    DEFF Research Database (Denmark)

    Ben Chaabane, Samir

    of action and turnover. During my PhD period we have shown that the STA1 protein, a factor for pre-mRNA splicing and mRNA stability, is specifically involved in the splicing of pri-miRNAs and in the modulation of DCL1 transcript levels. Also, we established a novel and essential regulatory network in which......MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Plant miRNAs are critical for plant growth, development and stress response, and are processed in Arabidopsis from primary miRNA transcripts (pri-miRNAs) by the endonuclease activity of the DICER-LIKE1...... (DCL1) protein complex. Mature miRNAs are loaded onto and guide an ARGONAUTE1 (AGO1) effector complex, leading to target mRNA silencing. The miRNA pathway is under tight temporal and spatial control and is regulated at multiple levels from transcription and precursor processing through miRNA mode...

  20. The regulatory epicenter of miRNAs

    Indian Academy of Sciences (India)

    miRNAs are small non-coding RNAs with average length of ∼21 bp. miRNA formation seems to be dependent upon multiple factors besides Drosha and Dicer, in a tissue/stage-specific manner, with interplay of several specific binding factors. In the present study, we have investigated transcription factor binding sites in and ...

  1. Taking a multiple intelligences (MI) perspective.

    Science.gov (United States)

    Gardner, Howard

    2017-01-01

    The theory of multiple intelligences (MI) seeks to describe and encompass the range of human cognitive capacities. In challenging the concept of general intelligence, we can apply an MI perspective that may provide a more useful approach to cognitive differences within and across species.

  2. Quantifying kinematic differences between land and water during squats, split squats, and single-leg squats in a healthy population.

    Directory of Open Access Journals (Sweden)

    Anna C Severin

    Full Text Available Aquatic exercises can be used in clinical and sporting disciplines for both rehabilitation and sports training. However, there is limited knowledge on the influence of water immersion on the kinematics of exercises commonly used in rehabilitation and fitness programs. The aim of this study was to use inertial sensors to quantify differences in kinematics and movement variability of bodyweight squats, split squats, and single-leg squats performed on dry land and whilst immersed to the level of the greater trochanter. During two separate testing sessions, 25 active healthy university students (22.3±2.9 yr. performed ten repetitions of each exercise, whilst tri-axial inertial sensors (100 Hz recorded their trunk and lower body kinematics. Repeated-measures statistics tested for differences in segment orientation and speed, movement variability, and waveform patterns between environments, while coefficient of variance was used to assess differences in movement variability. Between-environment differences in segment orientation and speed were portrayed by plotting the mean difference ±95% confidence intervals (CI throughout the tasks. The results showed that the depth of the squat and split squat were unaffected by the changed environment while water immersion allowed for a deeper single leg squat. The different environments had significant effects on the sagittal plane orientations and speeds for all segments. Water immersion increased the degree of movement variability of the segments in all exercises, except for the shank in the frontal plane, which showed more variability on land. Without compromising movement depth, the aquatic environment induces more upright trunk and shank postures during squats and split squats. The aquatic environment allows for increased squat depth during the single-leg squat, and increased shank motions in the frontal plane. Our observations therefore support the use of water-based squat tasks for rehabilitation as

  3. Quantifying kinematic differences between land and water during squats, split squats, and single-leg squats in a healthy population.

    Science.gov (United States)

    Severin, Anna C; Burkett, Brendan J; McKean, Mark R; Wiegand, Aaron N; Sayers, Mark G L

    2017-01-01

    Aquatic exercises can be used in clinical and sporting disciplines for both rehabilitation and sports training. However, there is limited knowledge on the influence of water immersion on the kinematics of exercises commonly used in rehabilitation and fitness programs. The aim of this study was to use inertial sensors to quantify differences in kinematics and movement variability of bodyweight squats, split squats, and single-leg squats performed on dry land and whilst immersed to the level of the greater trochanter. During two separate testing sessions, 25 active healthy university students (22.3±2.9 yr.) performed ten repetitions of each exercise, whilst tri-axial inertial sensors (100 Hz) recorded their trunk and lower body kinematics. Repeated-measures statistics tested for differences in segment orientation and speed, movement variability, and waveform patterns between environments, while coefficient of variance was used to assess differences in movement variability. Between-environment differences in segment orientation and speed were portrayed by plotting the mean difference ±95% confidence intervals (CI) throughout the tasks. The results showed that the depth of the squat and split squat were unaffected by the changed environment while water immersion allowed for a deeper single leg squat. The different environments had significant effects on the sagittal plane orientations and speeds for all segments. Water immersion increased the degree of movement variability of the segments in all exercises, except for the shank in the frontal plane, which showed more variability on land. Without compromising movement depth, the aquatic environment induces more upright trunk and shank postures during squats and split squats. The aquatic environment allows for increased squat depth during the single-leg squat, and increased shank motions in the frontal plane. Our observations therefore support the use of water-based squat tasks for rehabilitation as they appear to

  4. Temporal Variation in Single-Cell Power-Law Rheology Spans the Ensemble Variation of Cell Population.

    Science.gov (United States)

    Cai, PingGen; Takahashi, Ryosuke; Kuribayashi-Shigetomi, Kaori; Subagyo, Agus; Sueoka, Kazuhisa; Maloney, John M; Van Vliet, Krystyn J; Okajima, Takaharu

    2017-08-08

    Changes in the cytoskeletal organization within cells can be characterized by large spatial and temporal variations in rheological properties of the cell (e.g., the complex shear modulus G ∗ ). Although the ensemble variation in G ∗ of single cells has been elucidated, the detailed temporal variation of G ∗ remains unknown. In this study, we investigated how the rheological properties of individual fibroblast cells change under a spatially confined environment in which the cell translational motion is highly restricted and the whole cell shape remains unchanged. The temporal evolution of single-cell rheology was probed at the same measurement location within the cell, using atomic force microscopy-based oscillatory deformation. The measurements reveal that the temporal variation in the power-law rheology of cells is quantitatively consistent with the ensemble variation, indicating that the cell system satisfies an ergodic hypothesis in which the temporal statistics are identical to the ensemble statistics. The autocorrelation of G ∗ implies that the cell mechanical state evolves in the ensemble of possible states with a characteristic timescale. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. Intracellular Drug Uptake-A Comparison of Single Cell Measurements Using ToF-SIMS Imaging and Quantification from Cell Populations with LC/MS/MS.

    Science.gov (United States)

    Newman, Carla F; Havelund, Rasmus; Passarelli, Melissa K; Marshall, Peter S; Francis, Ian; West, Andy; Alexander, Morgan R; Gilmore, Ian S; Dollery, Colin T

    2017-11-21

    ToF-SIMS is a label-free imaging method that has been shown to enable imaging of amiodarone in single rat macrophage (NR8383) cells. In this study, we show that the method extends to three other cell lines relevant to drug discovery: human embryonic kidney (HEK293), cervical cancer (HeLa), and liver cancer (HepG2). There is significant interest in the variation of drug uptake at the single cell level, and we use ToF-SIMS to show that there is great diversity between individual cells and when comparing each of the cell types. These single cell measurements are compared to quantitative measurements of cell-associated amiodarone for the population using LC/MS/MS and cell counting with flow cytometry. NR8383 and HepG2 cells uptake the greatest amount of amiodarone with an average of 2.38 and 2.60 pg per cell, respectively, and HeLa and Hek 293 have a significantly lower amount of amiodarone at 0.43 and 0.36 pg per cell, respectively. The amount of cell-associated drug for the ensemble population measurement (LC/MS/MS) is compared with the ToF-SIMS single cell data: a similar amount of drug was detected per cell for the NR8383, and HepG2 cells at a greater level than that for the HEK293 cells. However, the two techniques did not agree for the HeLa cells, and we postulate potential reasons for this.

  6. A genome-wide miRNA screen revealed miR-603 as a MGMT-regulating miRNA in glioblastomas

    OpenAIRE

    Kushwaha, Deepa; Ramakrishnan, Valya; Ng, Kimberly; Steed, Tyler; Nguyen, Thien; Futalan, Diahnn; Akers, Johnny C.; Sarkaria, Jann; Jiang, Tao; Chowdhury, Dipanjan; Carter, Bob S.; Chen, Clark C.

    2014-01-01

    MGMT expression is a critical determinant for therapeutic resistance to DNA alkylating agents. We previously demonstrated that MGMT expression is post-transcriptionally regulated by miR-181d and other miRNAs. Here, we performed a genome-wide screen to identify MGMT regulating miRNAs. Candidate miRNAs were further tested for inverse correlation with MGMT expression in clinical specimens. We identified 15 candidate miRNAs and characterized the top candidate, miR-603. Transfection of miR-603 sup...

  7. The European and Japanese outbreaks of H5N8 derive from a single source population providing evidence for the dispersal along the long distance bird migratory flyways

    OpenAIRE

    Andrew R. Dalby; Munir Iqbal

    2015-01-01

    The origin of recent parallel outbreaks of the high pathogenicity H5N8 avian flu virus in Europe and in Japan can be traced to a single source population, which has most likely been spread by migratory birds. By using Bayesian coalescent methods to analyze the DNA sequences of the virus to find the times for divergence and combining this sequence data with bird migration data we can show the most likely locations and migratory pathways involved in the origin of the current outbreak. This popu...

  8. miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma.

    Science.gov (United States)

    Castro-Magdonel, Blanca Elena; Orjuela, Manuela; Camacho, Javier; García-Chéquer, Adda Jeanette; Cabrera-Muñoz, Lourdes; Sadowinski-Pine, Stanislaw; Durán-Figueroa, Noé; Orozco-Romero, María de Jesús; Velázquez-Wong, Ana Claudia; Hernández-Ángeles, Adriana; Hernández-Galván, Claudia; Lara-Molina, Citlali; Ponce-Castañeda, M Verónica

    2017-07-01

    miRNAs exert their effect through a negative regulatory mechanism silencing expression upon hybridizing to their target mRNA, and have a prominent position in the control of many cellular processes including carcinogenesis. Previous miRNA studies on retinoblastoma (Rb) have been limited to specific miRNAs reported in other tumors or to medium density arrays. Here we report expression analysis of the whole miRNome on 12 retinoblastoma tumor samples using a high throughput microarray platform including 2578 mature miRNAs. Twelve retinoblastoma tumor samples were analyzed using an Affymetrix platform including 2578 mature miRNAs. We applied RMA analysis to normalize raw data, obtained categorical data from detection call values, and also used signal intensity derived expression data. We used Diana-Tools-microT-CDS to find miRNA targets and ChromDraw to map miRNAs in chromosomes. We discovered a core-cluster of 30 miRNAs that were highly expressed in all the cases and a cluster of 993 miRNAs that were uniformly absent in all cases. Another 1022 miRNA were variably present in the samples reflecting heterogeneity between tumors. We explored mRNA targets, pathways and biological processes affected by some of these miRNAs. We propose that the core-cluster of 30 miRs represent miRNA machinery common to all Rb, and affecting most pathways considered hallmarks of cancer. In this core, we identified miR-3613 as a potential and critical down regulatory hub, because it is highly expressed in all the samples and its potential mRNA targets include at least 36 tumor suppressor genes, including RB1. In the variably expressed miRNA, 36 were differentially expressed between males and females. Some of the potential pathways targeted by these 36 miRNAs were associated with hormonal production. These findings indicate that Rb tumor samples share a common miRNA expression profile regardless of tumor heterogeneity, and shed light on potential novel therapeutic targets such as mir-3613 This

  9. The European and Japanese outbreaks of H5N8 derive from a single source population providing evidence for the dispersal along the long distance bird migratory flyways.

    Science.gov (United States)

    Dalby, Andrew R; Iqbal, Munir

    2015-01-01

    The origin of recent parallel outbreaks of the high pathogenicity H5N8 avian flu virus in Europe and in Japan can be traced to a single source population, which has most likely been spread by migratory birds. By using Bayesian coalescent methods to analyze the DNA sequences of the virus to find the times for divergence and combining this sequence data with bird migration data we can show the most likely locations and migratory pathways involved in the origin of the current outbreak. This population was most likely located in the Siberian summer breeding grounds of long-range migratory birds. These breeding grounds provide a connection between different migratory flyways and explain the current outbreaks in remote locations. By combining genetic methods and epidemiological data we can rapidly identify the sources and the dispersion pathways for novel avian influenza outbreaks.

  10. The European and Japanese outbreaks of H5N8 derive from a single source population providing evidence for the dispersal along the long distance bird migratory flyways

    Directory of Open Access Journals (Sweden)

    Andrew R. Dalby

    2015-04-01

    Full Text Available The origin of recent parallel outbreaks of the high pathogenicity H5N8 avian flu virus in Europe and in Japan can be traced to a single source population, which has most likely been spread by migratory birds. By using Bayesian coalescent methods to analyze the DNA sequences of the virus to find the times for divergence and combining this sequence data with bird migration data we can show the most likely locations and migratory pathways involved in the origin of the current outbreak. This population was most likely located in the Siberian summer breeding grounds of long-range migratory birds. These breeding grounds provide a connection between different migratory flyways and explain the current outbreaks in remote locations. By combining genetic methods and epidemiological data we can rapidly identify the sources and the dispersion pathways for novel avian influenza outbreaks.

  11. Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale

    DEFF Research Database (Denmark)

    Liu, Siyang; Huang, Shujia; Rao, Junhua

    2015-01-01

    present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome......) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism. We...... assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity. Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction...

  12. Mi oíslo

    Directory of Open Access Journals (Sweden)

    Mitja Skubic

    2006-12-01

    Full Text Available Hablando Sancho en su primer encuentro con don Quijote de su mujer Juana Gutiérrez, llamada en seguida Teresa Panza o simplemente Teresa, la nombra mi oíslo y repite lo mismo otras dos veces. Conviene tener presente que de su mujer Sancho habla siempre respetuosamente y con mucho cariño, con excepción de una conversación que llega a ser un litigio, II, 5. Allí, Sancho expresa su idea de cómo y con quién casar a la hija Sanchica y por fin impone su voluntad. Teresa se le opone vigorosamente y esto induce a Sancho, sobreexcitado, a formular una gradación sorprendente: mujer mía; mirad, Teresa; mujer; calla, boba; bestia y mujer de Barrabás; animalia; mentecata e ignorante.

  13. A replication study for association of 53 single nucleotide polymorphisms in ScoliScore test with adolescent idiopathic scoliosis in French-Canadian population.

    Science.gov (United States)

    Tang, Qi Lin; Julien, Cedric; Eveleigh, Robert; Bourque, Guillaume; Franco, Anita; Labelle, Hubert; Grimard, Guy; Parent, Stefan; Ouellet, Jean; Mac-Thiong, Jean-Marc; Gorman, Kristen F; Moreau, Alain

    2015-04-15

    A replication association study that used genomic data generated from French-Canadian case and control cohorts. To determine whether the 53 single nucleotide polymorphisms (SNPs) that were previously associated with spinal deformity progression in an American Caucasian cohort are similarly associated in French-Canadian population. It is widely accepted that genetic factors contribute to adolescent idiopathic scoliosis. The identification of genetic variants associated with the predisposition or progression of curvature could facilitate diagnostic/prognostic tool development. Although 53 SNPs have been associated with spinal curve progression in Caucasian cohorts in the United States, these associations were not replicated in a large Japanese population study, arguing that such a discrepancy could be explained by ethnicity, thus raising the importance of a replication study in an independent Caucasian population of European descent. Genomic data were collected from the French-Canadian population, using the Illumina HumanOmni 2.5M BeadChip. Fifty-two SNPs, tested in ScoliScore or in high linkage disequilibrium with SNPs in the test, were selected to assess their association with scoliosis generally, and with spinal curve progression. One SNP in ScoliScore, rs16909285, could not be evaluated in our Genome-Wide association study. None of the SNPs used in ScoliScore were associated with adolescent idiopathic scoliosis curve progression or curve occurrence in French-Canadian population. We evaluated 52 SNPs in severe patients by comparing risk allele frequencies with those in nonsevere patients and with those in control individuals. There was no significant difference between the severe group and the nonsevere group or between the severe group and the control group. Although the 52 SNPs studied here were previously associated with curve progression in an American population of European descent, we found no association in French-Canadian patients with adolescent

  14. Genome-wide survey of single-nucleotide polymorphisms reveals fine-scale population structure and signs of selection in the threatened Caribbean elkhorn coral, Acropora palmata

    Directory of Open Access Journals (Sweden)

    Meghann K. Devlin-Durante

    2017-11-01

    Full Text Available The advent of next-generation sequencing tools has made it possible to conduct fine-scale surveys of population differentiation and genome-wide scans for signatures of selection in non-model organisms. Such surveys are of particular importance in sharply declining coral species, since knowledge of population boundaries and signs of local adaptation can inform restoration and conservation efforts. Here, we use genome-wide surveys of single-nucleotide polymorphisms in the threatened Caribbean elkhorn coral, Acropora palmata, to reveal fine-scale population structure and infer the major barrier to gene flow that separates the eastern and western Caribbean populations between the Bahamas and Puerto Rico. The exact location of this break had been subject to discussion because two previous studies based on microsatellite data had come to differing conclusions. We investigate this contradiction by analyzing an extended set of 11 microsatellite markers including the five previously employed and discovered that one of the original microsatellite loci is apparently under selection. Exclusion of this locus reconciles the results from the SNP and the microsatellite datasets. Scans for outlier loci in the SNP data detected 13 candidate loci under positive selection, however there was no correlation between available environmental parameters and genetic distance. Together, these results suggest that reef restoration efforts should use local sources and utilize existing functional variation among geographic regions in ex situ crossing experiments to improve stress resistance of this species.

  15. Genome-wide survey of single-nucleotide polymorphisms reveals fine-scale population structure and signs of selection in the threatened Caribbean elkhorn coral, Acropora palmata.

    Science.gov (United States)

    Devlin-Durante, Meghann K; Baums, Iliana B

    2017-01-01

    The advent of next-generation sequencing tools has made it possible to conduct fine-scale surveys of population differentiation and genome-wide scans for signatures of selection in non-model organisms. Such surveys are of particular importance in sharply declining coral species, since knowledge of population boundaries and signs of local adaptation can inform restoration and conservation efforts. Here, we use genome-wide surveys of single-nucleotide polymorphisms in the threatened Caribbean elkhorn coral, Acropora palmata , to reveal fine-scale population structure and infer the major barrier to gene flow that separates the eastern and western Caribbean populations between the Bahamas and Puerto Rico. The exact location of this break had been subject to discussion because two previous studies based on microsatellite data had come to differing conclusions. We investigate this contradiction by analyzing an extended set of 11 microsatellite markers including the five previously employed and discovered that one of the original microsatellite loci is apparently under selection. Exclusion of this locus reconciles the results from the SNP and the microsatellite datasets. Scans for outlier loci in the SNP data detected 13 candidate loci under positive selection, however there was no correlation between available environmental parameters and genetic distance. Together, these results suggest that reef restoration efforts should use local sources and utilize existing functional variation among geographic regions in ex situ crossing experiments to improve stress resistance of this species.

  16. Longitudinal transport coefficients of a magnetized plasma consisting of hydrogen and a single impurity element in arbitrarily populated charge states

    International Nuclear Information System (INIS)

    Claassen, H.A.; Gerhauser, H.; El-Sharif, R.N.

    1991-01-01

    The coefficients determining the transport processes along the magnetic field in a magnetized plasma consisting of electrons, protons/deuterons and impurity ions in various charge states have been calculated on the basis of Grad's 21 moment approximation. Assuming a single impurity element, the determinants appearing in the transport coefficients are evaluated analytically for arbitrary ratios m z /m + between the impurity and hydrogen masses. The general formulae are then simplified for the important case m z /m + ≥ 1 and compared with existing data given by V.M. Zhdanov et al. and Yu.L. Igitkhanov et al. Whereas with minor modifications the proton/deuteron and electron coefficients agree well, there are remarkable differences in the impurity ion transport coefficients, which are discussed. (orig.)

  17. Altering β-cell number through stable alteration of miR-21 and miR-34a expression

    DEFF Research Database (Denmark)

    Backe, Marie Balslev; Novotny, Guy Wayne; Christensen, Dan Ploug

    2014-01-01

    RNAs, miR-21 and miR-34a, may be involved in mediating cytokine-induced β-cell dysfunction. Therefore, manipulation of miR-21 and miR-34a levels may potentially be beneficial to β cells. To study the effect of long-term alterations of miR-21 or miR-34a levels upon net β-cell number, we stably overexpressed...

  18. Construction of miRNA-miRNA networks revealing the complexity of miRNA-mediated mechanisms in trastuzumab treated breast cancer cell lines

    Science.gov (United States)

    Cilek, Emine Ezel; Ozturk, Hakime

    2017-01-01

    Trastuzumab is a monoclonal antibody frequently used to prevent the progression of HER2+ breast cancers, which constitute approximately 20% of invasive breast cancers. microRNAs (miRNAs) are small, non-coding RNA molecules that are known to be involved in gene regulation. With their emerging roles in cancer, they are recently promoted as potential candidates to mediate therapeutic actions by targeting genes associated with drug response. In this study we explored miRNA-mediated regulation of trastuzumab mechanisms by identifying the important miRNAs responsible for the drug response via homogenous network analysis. Our network model enabled us to simplify the complexity of miRNA interactions by connecting them through their common pathways. We outlined the functionally relevant miRNAs by constructing pathway-based miRNA-miRNA networks in SKBR3 and BT474 cells, respectively. Identification of the most targeted genes revealed that trastuzumab responsive miRNAs favourably regulate the repression of targets with longer 3’UTR than average considered to be key elements, while the miRNA-miRNA networks highlighted central miRNAs such as hsa-miR-3976 and hsa-miR-3671 that showed strong interactions with the remaining members of the network. Furthermore, the clusters of the miRNA-miRNA networks showed that trastuzumab response was mostly established through cancer related and metabolic pathways. hsa-miR-216b was found to be the part of the most powerful interactions of metabolic pathways, which was defined in the largest clusters in both cell lines. The network based representation of miRNA-miRNA interactions through their shared pathways provided a better understanding of miRNA-mediated drug response and could be suggested for further characterization of miRNA functions. PMID:28981542

  19. Construction of miRNA-miRNA networks revealing the complexity of miRNA-mediated mechanisms in trastuzumab treated breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Emine Ezel Cilek

    Full Text Available Trastuzumab is a monoclonal antibody frequently used to prevent the progression of HER2+ breast cancers, which constitute approximately 20% of invasive breast cancers. microRNAs (miRNAs are small, non-coding RNA molecules that are known to be involved in gene regulation. With their emerging roles in cancer, they are recently promoted as potential candidates to mediate therapeutic actions by targeting genes associated with drug response. In this study we explored miRNA-mediated regulation of trastuzumab mechanisms by identifying the important miRNAs responsible for the drug response via homogenous network analysis. Our network model enabled us to simplify the complexity of miRNA interactions by connecting them through their common pathways. We outlined the functionally relevant miRNAs by constructing pathway-based miRNA-miRNA networks in SKBR3 and BT474 cells, respectively. Identification of the most targeted genes revealed that trastuzumab responsive miRNAs favourably regulate the repression of targets with longer 3'UTR than average considered to be key elements, while the miRNA-miRNA networks highlighted central miRNAs such as hsa-miR-3976 and hsa-miR-3671 that showed strong interactions with the remaining members of the network. Furthermore, the clusters of the miRNA-miRNA networks showed that trastuzumab response was mostly established through cancer related and metabolic pathways. hsa-miR-216b was found to be the part of the most powerful interactions of metabolic pathways, which was defined in the largest clusters in both cell lines. The network based representation of miRNA-miRNA interactions through their shared pathways provided a better understanding of miRNA-mediated drug response and could be suggested for further characterization of miRNA functions.

  20. miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma

    Science.gov (United States)

    Khalil, Susanna; Fabbri, Enrica; Santangelo, Alessandra; Bezzerri, Valentino; Cantù, Cinzia; Gennaro, Gianfranco Di; Finotti, Alessia; Ghimenton, Claudio; Eccher, Albino; Dechecchi, Maria; Scarpa, Aldo; Hirshman, Brian; Chen, Clark; Ferracin, Manuela; Negrini, Massimo; Gambari, Roberto; Cabrini, Giulio

    2016-01-01

    The levels of expression of O6-methylguanine-DNA methyltransferase (MGMT) are relevant in predicting the response to the alkylating chemotherapy in patients affected by glioblastoma. MGMT promoter methylation and the published MGMT regulating microRNAs (miRNAs) do not completely explain the expression pattern of MGMT in clinical glioblastoma specimens. Here we used a genome-wide microarray-based approach to identify MGMT regulating miRNAs. Our screen unveiled three novel MGMT regulating miRNAs, miR-127-3p, miR-409-3p, and miR-124-3p, in addition to the previously identified miR-181d-5p. Transfection of these three novel miRNAs into the T98G glioblastoma cell line suppressed MGMT mRNA and protein expression. However, their MGMT- suppressive effects are 30–50% relative that seen with miR-181d-5p transfection. In silico analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) revealed that miR-181d-5p is the only miRNA that consistently exhibited inverse correlation with MGMT mRNA expression. However, statistical models incorporating both miR-181d-5p and miR-409-3p expression better predict MGMT expression relative to models involving either miRNA alone. Our results confirmed miR-181d-5p as the key MGMT-regulating miRNA. Other MGMT regulating miRNAs, including the miR-409-3p identified in this report, modify the effect of miR-181d-5p on MGMT expression. MGMT expression is, thus, regulated by cooperative interaction between key MGMT-regulating miRNAs. PMID:27057640

  1. Single and combined effects of microplastics and copper on the population growth of the marine microalgae Tetraselmis chuii

    Science.gov (United States)

    Davarpanah, Elham; Guilhermino, Lúcia

    2015-12-01

    As the accumulation of microplastics continues to rise in the marine environment, more knowledge on their potential toxic effects on marine organisms is needed to assess their risks to environmental and human health. Thus, the goal of the present study was to investigate the effects of fluorescent red polyethylene plastic micro-spheres 1-5 μm diameter (used as microplastic model and hereafter indicated as MP), alone and in mixture with copper, on the population growth of the marine microalgae Tetraselmis chuii. Two null hypotheses were tested: (H01) Exposure to MP concentrations in ppb range does not affect the average specific growth rate of T. chuii; (H02) MP do not interact with the toxicity of copper to T. chuii. In laboratory bioassays, T. chuii cultures were exposed for 96 h to MP concentrations ranging from 0.046 to 1.472 mg/l), concentrations of copper alone ranging from 0.02 to 0.64 mg/l, and the same concentrations of copper in the presence of 0.184 mg/l of MP in test media. No significant effects of MP on T. chuii population growth were found (p > 0.05), leading to the acceptance of H01. Copper alone significantly decreased the population growth of T. chuii with EC10, EC20 and EC50 of 0.009, 0.023 and 0.139 mg/l, respectively. The corresponding values in the presence of MP were 0.012, 0.029 and 0.145 mg/l, respectively. Moreover, the study found no significant differences between the toxicity curves of copper in the presence and absence of MP (p > 0.05), leading to the acceptance of H02. Despite these findings, because microplastics are known to adsorb and accumulate copper, aged pellets more than virgin ones, and the toxicity of smaller particles may be higher, further studies on the combined effects of copper and microplastics on microalgae should be performed, especially under long-term exposures to nano-sized aged microplastics.

  2. Classification of various muscular tissues using miRNA profiling.

    Science.gov (United States)

    Endo, Kosuke; Weng, Huachun; Naito, Yukiko; Sasaoka, Toshikuni; Takahashi, Akio; Fukushima, Yasue; Iwai, Naoharu

    2013-01-01

    MicroRNAs (miRNAs) are endogenous small RNAs of 18-23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we explored whether miRNA expression profiling of various muscle cells may be useful for the diagnosis of various diseases involving muscle necrosis. miRNA expression profiling was assessed by miRNA array and real-time reverse-transcriptase polymerase chain reaction by using a reverse primer of a stem loop structure. Profiling of various muscle cells of mouse, including cardiac muscles, skeletal muscles, and vascular and visceral smooth muscles, indicated that profiling of miR-1, miR-133a, miR-133b, miR-145, miR-206, miR-208a, miR-208b, and miR499 were adequate to discriminate muscle cells. miR-145 was remarkably highly expressed in smooth muscles. miR-208a and miR-499 were highly expressed in cardiomyocytes. miR-133a was highly expressed in fast-twitch skeletal muscles. miR-206 and miR-208b were expressed in the slow-twitch skeletal muscles, and they can likely discriminate fast- and slow-twitch types of skeletal muscle cells. We observed that brown fat adipose cells had an miRNA expression profile very similar to those of skeletal muscle cells in the mouse. Plasma concentrations of miR-133a and miR-145 were extremely useful in diagnosing skeletal muscle necrosis in a mouse model of Duchenne muscular dystrophy and colon smooth muscle necrosis in a rat ischemic colitis model, respectively. In the present study, we investigated the miRNA expression profiles of various muscular tissues. Our results suggest that expression profiling would be useful for the diagnosis of various diseases such as muscular necrosis.

  3. Global approaches to the role of miRNAs in drug-induced changes in gene expression

    Directory of Open Access Journals (Sweden)

    Jodi E Eipper-Mains

    2012-06-01

    Full Text Available Neurons modulate gene expression with subcellular precision through excitation-coupled local protein synthesis, a process that is regulated in part through the involvement of microRNAs (miRNAs, a class of small noncoding RNAs. The biosynthesis of miRNAs is reviewed, with special emphasis on miRNA families, the subcellular localization of specific miRNAs in neurons, and their potential roles in the response to drugs of abuse. For over a decade, DNA microarrays have dominated genome-wide gene expression studies, revealing widespread effects of drug exposure on neuronal gene expression. We review a number of recent studies that explore the emerging role of miRNAs in the biochemical and behavioral responses to cocaine. The more powerful next-generation sequencing technology offers certain advantages and is supplanting microarrays for the analysis of complex transcriptomes. RNA-Seq is unparalleled in its ability to identify and quantify low-abundance transcripts without prior sequence knowledge, facilitating the accurate detection and quantification of miRNAs expressed in total tissue and miRNAs localized to postsynaptic densities (PSDs. We previously identified cocaine-responsive miRNAs, synaptically-enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several bioinformatically predicted target genes. The miR-8 family was found to be highly enriched and cocaine-regulated at the PSD, where its members may modulate expression of cell adhesion molecules. An integrative approach that combines mRNA, miRNA, and protein expression profiling in combination with focused single gene studies and innovative behavioral paradigms should facilitate the development of more effective therapeutic approaches to treat addiction.

  4. Diagnostic value of circulating microRNAs for gastric cancer in Asian populations: a meta-analysis.

    Science.gov (United States)

    Liu, Lihua; Wang, Shan; Cao, Xiutang; Liu, Jianchao

    2014-12-01

    Gastric cancer (GC) accounts for one of the highest mortality worldwide and particularly in East Asia. Many studies have reported on the potential value of microRNAs (miRNAs) detection for diagnosing GC, but their results have proven inconclusive. The present meta-analysis was conducted to assess the diagnostic value of circulating miRNAs for GC diagnosis. A literature search was carried out in databases (PubMed, Embase, Web of Science, The Cochrane Library, and CNKI) and other sources using combinations of keywords relating to GC, miRNAs, and diagnosis. The values of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR) reported in individual studies were pooled using random-effects models. Potential sources of heterogeneity were assessed with subgroup and meta-regression analyses. The summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) were used to assess the diagnosis accuracy of miRNAs. This meta-analysis included 1,279 patients with GC and 954 healthy controls from 20 publications. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.78 (95 % CI: 0.73-0.81), 0.80 (95 % CI: 0.76-0.84), 4.0 (95 % CI: 3.1-6.0), 0.28 (95 % CI: 0.23-0.34), 14 (95 % CI: 10-21), and 0.86 (95 % CI: 0.83-0.89), respectively. Subgroup analyses showed that early stages (I and II) GC were more easily detected than later stages and that multiple miRNAs assays were more accurate than single miRNA assays. Our meta-analysis suggests that miRNAs have a high diagnostic value for GC, especially in its early stages (I and II). In addition, multiple miRNAs assays have a better diagnosis value than single miRNA assays. In conclusion, circulating miRNAs might be used as noninvasive biomarkers for the confirmation of GC detection in Asian populations.

  5. MiR-221 and miR-130a regulate lung airway and vascular development.

    Directory of Open Access Journals (Sweden)

    Sana Mujahid

    Full Text Available Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung.

  6. Influence of the Neonicotinoid Insecticide Thiamethoxam on miRNA Expression in the Honey Bee (Hymenoptera: Apidae).

    Science.gov (United States)

    Shi, Teng-Fei; Wang, Yu-Fei; Liu, Fang; Qi, Lei; Yu, Lin-Sheng

    2017-09-01

    MicroRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs regulating gene expression in eukaryotes. They play important roles in regulating caste differentiation, behavior development, and immune defences in the honey bee, Apis mellifera (Linnaeus) (Hymenoptera: Apidae). In this study, we explored the effect of the neonicotinoid insecticide, thiamethoxam, on miRNA expression in this species using deep small RNA sequencing. The results showed that seven miRNAs were significantly differentially expressed (q-value 1) upon exposure to 10 ppb thiamethoxam over 10 d. Some candidate target genes were related to behavior, immunity, and neural function. Several miRNAs, including ame-miR-124, ame-miR-981, ame-miR-3791, and ame-miR-6038, were selected and further validated using real-time quantitative PCR analysis. The findings expand our understanding of the effects of neonicotinoid insecticides on honey bees at the molecular level. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  7. Phage-mediated counting by the naked eye of miRNA molecules at attomolar concentrations in a Petri dish

    Science.gov (United States)

    Zhou, Xin; Cao, Peng; Zhu, Ye; Lu, Wuguang; Gu, Ning; Mao, Chuanbin

    2015-10-01

    The ability to count biomolecules such as cancer-biomarker miRNAs with the naked eye is seemingly impossible in molecular diagnostics. Here, we show an ultrasensitive naked-eye-counting strategy for quantifying miRNAs by employing T7 phage--a bacteria-specific virus nanoparticle--as a surrogate. The phage is genetically engineered to become fluorescent and capable of binding a miRNA-capturing gold nanoparticle (GNP) in a one-to-one manner. Target miRNAs crosslink the resultant phage-GNP couple and miRNA-capturing magnetic microparticles, forming a sandwich complex containing equimolar phage and miRNA. The phage is then released from the complex and developed into one macroscopic fluorescent plaque in a Petri dish by plating it in a host bacterial medium. Counting the plaques by the naked eye enables the quantification of miRNAs with detection limits of ~3 and ~5 aM for single-target and two-target miRNAs, respectively. This approach offers ultrasensitive and convenient quantification of disease biomarkers by the naked eye.

  8. Phage-mediated counting by the naked eye of miRNA molecules at attomolar concentrations in a Petri dish.

    Science.gov (United States)

    Zhou, Xin; Cao, Peng; Zhu, Ye; Lu, Wuguang; Gu, Ning; Mao, Chuanbin

    2015-10-01

    The ability to count biomolecules such as cancer-biomarker miRNAs with the naked eye is seemingly impossible in molecular diagnostics. Here, we show an ultrasensitive naked-eye-counting strategy for quantifying miRNAs by employing T7 phage-a bacteria-specific virus nanoparticle-as a surrogate. The phage is genetically engineered to become fluorescent and capable of binding a miRNA-capturing gold nanoparticle (GNP) in a one-to-one manner. Target miRNAs crosslink the resultant phage-GNP couple and miRNA-capturing magnetic microparticles, forming a sandwich complex containing equimolar phage and miRNA. The phage is then released from the complex and developed into one macroscopic fluorescent plaque in a Petri dish by plating it in a host bacterial medium. Counting the plaques by the naked eye enables the quantification of miRNAs with detection limits of ∼3 and ∼5 aM for single-target and two-target miRNAs, respectively. This approach offers ultrasensitive and convenient quantification of disease biomarkers by the naked eye.

  9. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    Science.gov (United States)

    Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-01-01

    Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

  10. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Paramasivam Prabu

    Full Text Available Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM. While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT, impaired glucose tolerance (IGT and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

  11. Expression of miR-23a by apoptotic regulators in human cancer: A review.

    Science.gov (United States)

    Roufayel, Rabih; Kadry, Seifedine

    2017-05-04

    MicroRNAs play fundamental roles in mammalian development, differentiation and cellular homeostasis by regulating essential processes such as proliferation, migration, metabolism, migration and cell death. These small non-coding RNAs are also responsible in RNA silencing, and in many developmental and pathological processes. Not surprisingly, miR-23a misexpression contributes to numerous diseases including cancer where certain miRNA genes have been classified as either oncogenes or tumor suppressor genes. Since a single microRNA is capable of targeting a large number of mRNA sequences, de-regulated miRNA expression has the ability to alter various transcripts and activate a wide range of cancer-related pathways. This review article documents reduced levels of mature miR-23a in various tumors, primarily due to epigenetic silencing or alterations in biogenesis pathways. Moreover, inhibition of miR-23a in stressed cells represent a general mechanism for inducing apoptosis and these microRNAs are showed to be regulated by molecular chaperon HSP70. Microarray expression analysis of miRNA overexpression or depletion is now used in the characterization of cancer development pathways and as a biomarker for early cancer detection.

  12. Computational tools for genome-wide miRNA prediction and study

    KAUST Repository

    Malas, T.B.

    2012-11-02

    MicroRNAs (miRNAs) are single-stranded non-coding RNA susually of 22 nucleotidesin length that play an important post-transcriptional regulation role in many organisms. MicroRNAs bind a seed sequence to the 3-untranslated region (UTR) region of the target messenger RNA (mRNA), inducing degradation or inhibition of translation and resulting in a reduction in the protein level. This regulatory mechanism is central to many biological processes and perturbation could lead to diseases such as cancer. Given the biological importance, of miRNAs, there is a great need to identify and study their targets and functions. However, miRNAs are very difficult to clone in the lab and this has hindered the identification of novel miRNAs. Next-generation sequencing coupled with new computational tools has recently evolved to help researchers efficiently identify large numbers of novel miRNAs. In this review, we describe recent miRNA prediction tools and discuss their priorities, advantages and disadvantages. Malas and Ravasi.

  13. Safety and efficacy assessment of carotid artery stenting in a high-risk population in a single-centre registry.

    Science.gov (United States)

    Kosowski, Michał; Zimoch, Wojciech; Gwizdek, Tomasz; Konieczny, Radosław; Kübler, Piotr; Telichowski, Artur; Jankowska, Ewa A; Reczuch, Krzysztof

    2014-01-01

    Ischaemic stroke is the primary cause of long-term disability and the third most common cause of death. Internal carotid artery stenosis is an important risk factor for stroke and transient ischaemic attack (TIA). European Society of Cardiology (ESC) and American Heart Association (AHA) guidelines allow carotid artery stenting (CAS) as an alternative to endarterectomy in centres with low rates of death or stroke. To assess the safety and efficacy of CAS in a single-centre observation. We performed a retrospective analysis of all patients treated with CAS between March 2008 and July 2012. Clinical data and outcomes in both asymptomatic and symptomatic patients were analysed. A total of 214 consecutive patients were included in the registry. Symptomatic patients accounted for 57% of the study group and were more likely to have a history of stroke and/or TIA that occurred more than 6 months before the procedure (50% vs. 8%, p likely to have a history of coronary artery disease (88% vs. 61%, p < 0.001), and the rates of previous acute coronary syndrome and revascularisation were also higher in this group (58% vs. 41% and 71% vs. 52%, respectively, both p < 0.05). The symptomatic group had higher incidence of stroke in periprocedural and 30-day observation (4% vs. 0%, p < 0.05). There was no difference in incidence of adverse events in long-term observation. Carotid artery stenting is a safe and efficacious procedure. Every centre performing CAS should monitor the rate of periprocedural complications.

  14. miRNA Signatures of Insulin Resistance in Obesity.

    Science.gov (United States)

    Jones, Angela; Danielson, Kirsty M; Benton, Miles C; Ziegler, Olivia; Shah, Ravi; Stubbs, Richard S; Das, Saumya; Macartney-Coxson, Donia

    2017-10-01

    Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity. One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated. One hundred six miRNAs were significantly (adjusted P ≤ 0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR-122, miR-192); known roles in obesity but no reported changes in circulating levels (e.g., miR-378a); and no current reported role in, or association with, obesity (e.g., miR-28-5p, miR-374b, miR-32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty-eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let-7b, miR-144-5p, miR-34a, and miR-532-5p in a model predictive of insulin resistance (R 2  = 0.57, P = 7.5 × 10 -8 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity. This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity. © 2017 The Obesity Society.

  15. The Association between Single-Nucleotide Polymorphisms of ORAI1 Gene and Breast Cancer in a Taiwanese Population

    Directory of Open Access Journals (Sweden)

    Wei-Chiao Chang

    2012-01-01

    Full Text Available Background. Breast cancer is the most common malignancy in women. There is increasing evidence suggesting that ORAI1, components of store-operated calcium channel, play a pivotal role in breast cancer progression and metastasis. Methods. A total of 384 female patients with breast cancer were included in this study. We selected five representative tagging ORAI1 SNPs from HapMap database with minimum allele frequency (MAF >10%. Genotyping was performed using TaqMan allelic discrimination assay. Chi-square (χ2 test was used to analyze statistical differences among control and patient groups in genotype and allelic frequencies. Results. Two of the ORAI1 SNPs (rs12320939 and rs12313273 were associated with estrogen receptors positive in breast cancer patients under the recessive model. When the Bonferroni correction was performed, the significance still existed. In addition, rs12320939 also associated with the lymph nodal involvement. Conclusion. We showed that genetic polymorphisms of ORAI1 associated strongly with lymph nodal involvement and estrogen receptors (ERs positive breast cancer patients in a Taiwanese population.

  16. Association between single-nucleotide polymorphism in CISH gene and susceptibility to tuberculosis in Chinese Han population.

    Science.gov (United States)

    Zhao, Lan; Chu, Haiqing; Xu, Xiaogang; Yue, Jun; Li, Huiping; Wang, Minggui

    2014-04-01

    The cytokine-inducible SRC homology 2 domain (CISH) gene is up-regulated by IL-2 in response to infection, and inhibits microbial infection. The objective of the present study was to examine whether genetic variants of CISH (SNPs) are associated with increased susceptibility to tuberculosis (TB) in individuals of Chinese Han ethnicity. We sequenced five previously identified SNPs of CISH in patients with TB or healthy controls. Three of the SNPs, rs148685070 [position -639; C/C], rs414171 [position -292; A/T], and rs6768300 [position -163; C/G]) are located in the promoter region, while the fourth (rs2239751 [position +1320; A/C]) near the translation start site, and the fifth (rs622502 [position +3415; C/G]) in the third intron. The AA genotypes of the SNPs rs2239751 and rs414171 were significantly associated with TB. Multivariate logistic regression analysis demonstrated that subjects with the rs414171 AA genotype were more likely to have TB than those with the AT genotype. By contrast, we did not observe genetic variants of the rs148685070 SNP. In conclusion, two genetic variants in CISH gene appear to increase susceptibility to TB in Chinese Han population.

  17. Etiology of Hypopituitarism in Adult Patients: The Experience of a Single Center Database in the Serbian Population

    Directory of Open Access Journals (Sweden)

    M. Doknić

    2017-01-01

    Full Text Available There are only a few published studies related to the population-based etiology of hypopituitarism. New risks for developing hypopituitarism have been recognized in the last 10 years. Aim. To present data regarding the etiology of hypopituitarism collected in a tertiary center over the last decade. This is a cross-sectional database study. Patients and Methods. We included 512 patients (pts with hypopituitarism, with a mean age of 45.9 ± 1.7 yrs (range: 18–82; male: 57.9%. Results. Nonfunctional pituitary adenomas were presented in 205 pts (40.5%, congenital causes in 74 pts (14.6%, while acromegaly and prolactinomas were presented in 37 (7.2% and 36 (7.0% patients, respectively. Craniopharyngiomas were detected in 30 pts (5.9%, and head trauma due to trauma brain injury-TBI and subarachnoid hemorrhage-SAH in 27 pts (5.4%. Survivors of hemorrhagic fever with renal syndrome (HFRS and those with previous cranial irradiation were presented in the same frequency (18 pts, 3.5% each. Conclusion. The most common causes of hypopituitarism in our database are pituitary adenomas. Increased awareness of the other causes of pituitary dysfunction, such as congenital, head trauma, extrapituitary cranial irradiation, and infections, is the reason for a higher frequency of these etiologies of hypopituitarism in the presented database.

  18. Single nucleotide polymorphisms of NR3C1 gene and recurrent depressive disorder in population of Poland.

    Science.gov (United States)

    Gałecka, Elżbieta; Szemraj, Janusz; Bieńkiewicz, Małgorzata; Majsterek, Ireneusz; Przybyłowska-Sygut, Karolina; Gałecki, Piotr; Lewiński, Andrzej

    2013-02-01

    Depressive disorder is a disease characterized by disturbances in the hypothalamo-pituitary-adrenal axis. Abnormalities include the increased level of glucocorticoids (GC) and changes in sensitivity to these hormones. The changes are related to glucocorticoid receptors gene (NR3C1) variants. The NR3C1 gene is suggested to be a candidate gene affecting depressive disorder risk and management. The aim of this study was to investigate polymorphisms within the NR3C1 gene and their role in the susceptibility to recurrent depressive disorder (rDD). 181 depressive patients and 149 healthy ethnically matched controls were included in the study. Single nucleotide polymorphisms were assessed using polymerase chain reaction/restriction fragment length polymorphism method. Statistical significance between rDD patients and controls was observed for the allele and genotype frequencies at three loci: BclI, N363S, and ER22/23EK. The presence of C allele, CC, and GC genotype of BclI polymorphism, G allele and GA genotype for N363S and ER22/23EK variants respectively were associated with increased rDD risk. Two haplotypes indicated higher susceptibility for rDD, while haplotype GAG played a protective role with OR(dis) 0.29 [95 % confidence interval (CI) = 0.13-0.64]. Data generated from this study support the earlier results that genetic variants of the NR3C1 gene are associated with rDD and suggest further consideration on the possible involvement of these variants in etiology of the disease.

  19. Pattern of glomerular disease in the Saudi population: A single-center, five-year retrospective study

    Directory of Open Access Journals (Sweden)

    Z Nawaz

    2013-01-01

    Full Text Available Glomerular diseases continue to be the leading cause of end-stage renal disease (ESRD globally. Hence, it is important to recognize the pattern of glomerular diseases in different geographical areas in order to understand the patho-biology, incidence and progression of the disorder. Published studies from different centers in Saudi Arabia have reported contradicting results. In this retrospective study, we report our experience at the Armed Forces Hospital, Riyadh, Saudi Arabia. A total of 348 native renal biopsies performed at our center on patients with proteinuria >1 g, hematuria and/or renal impairment during a period of 5 years (between January 2005 and December 2009 were studied by a histopathologist using light microscopy, immunofluorescence and electron microscopy, and were categorized. Results showed that primary glomerular disease accounted for 55.1% of all renal biopsies. The most common histological lesion was focal and segmental glomerulosclerosis (FSGS (27.6%, followed by minimal change disease (MCD (17.7% and membrano-proliferative glomerulonephritis (MPGN (13.0%. Secondary glomerular disease accounted for 37.9% of the glomerular diseases, with lupus nephritis (LN being the most common lesion (54.5%, followed by hypertensive nephrosclerosis (22%, post-infectious glomerulonephritis (7.5%, diabetic nephropathy (DN (6.8% and vasculitides (4.5%. Four percent of all biopsies turned out to be ESRD while biopsy was inadequate in 2.8% of the cases. In conclusion, our study showed that FSGS was the most common primary GN encountered, while LN was the most common secondary GN. We encountered 14 cases of crescentic glomerulonephritis. Also, the prevalence of MPGN, MCD, IgA nephropathy and membranous GN was many folds higher in males when compared with the Western data. We believe that it is mandatory to maintain a Saudi Arabian Renal Biopsy Registry to understand better the pattern of glomerular disease in the Saudi population and to follow

  20. Association between single nucleotide polymorphisms of sterol regulatory element binding protein-2 gene and risk of knee osteoarthritis in a Chinese Han population.

    Science.gov (United States)

    Qiu, Xiao-Ming; Jin, Cheng-Tao; Wang, Wei

    2014-04-01

    To investigate associations between single nucleotide polymorphisms (SNPs) rs2228314 and rs2267443 in the sterol regulatory element binding protein-2 gene (SREBP-2) and knee osteoarthritis (OA) susceptibility in a Chinese Han population. SREBP-2 rs2228314 and rs2267443 polymorphisms were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. A total of 402 patients with knee OA and 410 controls were enrolled in the study. GC and CC genotypes of rs2228314, and variant C, were associated with a significantly increased risk of knee OA. On stratification analysis, the association between the risk of OA and rs2228314 GC heterozygotes compared with GG homozygotes was stronger in females and those aged >65 years. In contrast, the GA and AA genotypes of rs2267443 were not significantly associated with the risk of knee OA, even after further stratification analysis according to age or sex. SREBP-2 rs2228314 G to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.

  1. MiR-378 Plays an Important Role in the Differentiation of Bovine Preadipocytes

    Directory of Open Access Journals (Sweden)

    Si-Yuan Liu

    2015-07-01

    Full Text Available Background: Adipocyte, the main cellular component of white adipose tissue, plays a vital role in energy balance in higher eukaryotes. In recent years, adipocytes have also been identified as a major endocrine organ involved in immunological responses, vascular diseases, and appetite regulation. In farm animals, fat content and categories are closely correlated with meat quality. MicroRNAs (miRNAs, a class of endogenous single-stranded non-coding RNA molecules, participate in the regulation of adipocyte differentiation and adipogenesis through regulating the transcription or translation of target mRNAs. MiR-378 plays an important role in a number of biological processes, including cell growth, cell differentiation, tumor cell survival and angiogenesis. Methods: In the present study, bioinformatics analysis and dual-luciferase reporter assay were used to identify and validate the target genes of miR-378. In vitro cell transfection, quantitative reverse transcription polymerase chain reaction (RT-qPCR, western blot analysis, Oil Red O staining, and triglyceride content measurement were conducted to analyze the effects of miR-378 on bovine preadipocyte differentiation. Results: MiR-378 was induced during adipocyte differentiation. In the differentiated adipocytes overexpressing miR-378, the volume of lipid droplets was enlarged, and the triglyceride content was increased. Moreover, the mRNA expression levels of the adipocyte differentiation marker genes, peroxisome proliferator-activated receptor gamma (PPARγ and sterol regulatory element-binding protein (SREBP, were significantly elevated in the differentiated, mature adipocytes. In contrast, the mRNA expression level of preadipocyte factor 1 (Pref-1 was markedly reduced. E2F transcription factor 2 (E2F2 and Ras-related nuclear (RAN-binding protein 10 (RANBP10 were the two target genes of miR-378. The mRNA expression levels of E2F2 and RANBP10 did not significantly change in bovine preadipocytes

  2. The optimal anatomic site for a single slice to estimate the total volume of visceral adipose tissue by using the quantitative computed tomography (QCT) in Chinese population.

    Science.gov (United States)

    Cheng, X; Zhang, Y; Wang, C; Deng, W; Wang, L; Duanmu, Y; Li, K; Yan, D; Xu, L; Wu, C; Shen, W; Tian, W

    2018-03-20

    To investigate the relationship between the cross-sectional visceral adipose tissue (VAT) areas at different anatomic sites and the total VAT volume in a healthy Chinese population using quantitative computed tomography (QCT), and to identify the optimal anatomic site for a single slice to estimate the total VAT volume. A total of 389 healthy Chinese subjects aged 19-63 years underwent lumbar spine QCT scans. The cross-sectional area of total adipose tissue and VAT were measured using the tissue composition module of the software (QCT Pro, Mindways) at each intervertebral disc level from T 12 /L 1 to L 5 /S 1 , as well as at the umbilical level. The total VAT volume was defined as the fat areas multiplied by the height of vertebral body for all six slices. Statistical analysis was performed to determine the correlation between single-slice VAT areas and the total VAT volume. Moreover, the optimal anatomic site for a single slice to estimate the total VAT volume was identified by multiple regression analysis. The cross-sectional area of VAT and subcutaneous adipose tissue (SAT) measured at each anatomic site was all highly correlated with the total VAT volume and the total SAT volume (r = 0.89-0.98). Additionally, the VAT area measured at the L 2 /L 3 level showed the strongest correlation with the total VAT volume (r = 0.98, P VAT volume. It is feasible to perform measurements of VAT area on a single slice at L 2 /L 3 level for estimating the total VAT volume.

  3. Using miRNA-Analyzer for the Analysis of miRNA Data

    Directory of Open Access Journals (Sweden)

    Pietro Hiram Guzzi

    2016-12-01

    Full Text Available MicroRNAs (miRNAs are small biological molecules that play an important role during the mechanisms of protein formation. Recent findings have demonstrated that they act as both positive and negative regulators of protein formation. Thus, the investigation of miRNAs, i.e., the determination of their level of expression, has developed a huge interest in the scientific community. One of the leading technologies for extracting miRNA data from biological samples is the miRNA Affymetrix platform. It provides the quantification of the level of expression of the miRNA in a sample, thus enabling the accumulation of data and allowing the determination of relationships among miRNA, genes, and diseases. Unfortunately, there is a lack of a comprehensive platform able to provide all the functions needed for the extraction of information from miRNA data. We here present miRNA-Analyzer, a complete software tool providing primary functionalities for miRNA data analysis. The current version of miRNA-Analyzer wraps the Affymetrix QCTool for the preprocessing of binary data files, and then provides feature selection (the filtering by species and by the associated p-value of preprocessed files. Finally, preprocessed and filtered data are analyzed by the Multiple Experiment Viewer (T-MEV and Short Time Series Expression Miner (STEM tools, which are also wrapped into miRNA-Analyzer, thus providing a unique environment for miRNA data analysis. The tool offers a plug-in interface so it is easily extensible by adding other algorithms as plug-ins. Users may download the tool freely for academic use at https://sites.google.com/site/mirnaanalyserproject/d.

  4. Universal MI definition update for cardiovascular disease.

    Science.gov (United States)

    White, Harvey; Thygesen, Kristian; Alpert, Joseph S; Jaffe, Allan

    2014-01-01

    The new third universal definition of myocardial infarction (MI) is based on troponin elevation together with ischemic symptoms, ischemic ECG changes, and imaging evidence. MIs are classified into five types as to whether they are spontaneous, secondary to imbalance between coronary artery blood supply and demand, related to sudden death, or related to revascularization procedures. The definition is based on a rise and/or fall in troponin levels occurring in a clinical setting. There have been modifications over previous definitions with adding intracoronary thrombus as a criterion, adding a new type of MI type 4c, and raising the cutpoint for the diagnosis of MI related to percutaneous coronary intervention to five times the 99(th) percentile upper reference limit and requiring evidence of ischemia or angiographic complications. In clinical practice, trials, and registries, different definitions are used. There is a need for consistency with regard to the definition of MI and the universal definition should be implemented.

  5. Lo que mi abuelo me cuenta

    OpenAIRE

    Benavides Muhamad, Amal; Pontificia Universidad Javeriana, Cali

    2014-01-01

    En el estado de Palestina, ubicado en oriente medio, hace más de 57 años en Kofor malek –un pequeño pueblo– vivía una familia muy numerosa. Era la familia de mi abuelo que estaba conformada por once personas incluyendo a sus padres. Como la describe el, su familia la integraban: “Mi madre, una mujer muy cariñosa, excelente cocinera y muy dedicada a su hogar; la madre típica de ese entonces que casi nunca salía del hogar. Su vida giraba en torno a mi padre y a nosotros, sus hijos. Mi padre un ...

  6. MiTAP for SARS Detection

    National Research Council Canada - National Science Library

    Damianos, Laurie E; Bayer, Samuel; Chisholm, Michael A; Henderson, John; Hirschman, Lynette; Morgan, William; Ubaldino, Marc; Zarrella, Guido; Wilson, V, James M; Polyak, Marat G

    2006-01-01

    The MiTAP prototype for SARS detection uses human language technology for detecting, monitoring, and analyzing potential indicators of infectious disease outbreaks and reasoning for issuing warnings and alerts...

  7. miRNAtools: Advanced Training Using the miRNA Web of Knowledge

    Directory of Open Access Journals (Sweden)

    Ewa Ł. Stępień

    2018-02-01

    Full Text Available Micro-RNAs (miRNAs are small non-coding RNAs that act as negative regulators of the genomic output. Their intrinsic importance within cell biology and human disease is well known. Their mechanism of action based on the base pairing binding to their cognate targets have helped the development not only of many computer applications for the prediction of miRNA target recognition but also of specific applications for functional assessment and analysis. Learning about miRNA function requires practical training in the use of specific computer and web-based applications that are complementary to wet-lab studies. In order to guide the learning process about miRNAs, we have created miRNAtools (http://mirnatools.eu, a web repository of miRNA tools and tutorials. This article compiles tools with which miRNAs and their regulatory action can be analyzed and that function to collect and organize information dispersed on the web. The miRNAtools website contains a collection of tutorials that can be used by students and tutors engaged in advanced training courses. The tutorials engage in analyses of the functions of selected miRNAs, starting with their nomenclature and genomic localization and finishing with their involvement in specific cellular functions.

  8. The NuMI neutrino beam

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, P.; Anderson, K.; Andrews, M.; Andrews, R. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Anghel, I. [Department of Physics and Astronomy, Iowa State University, Ames, IA 50011 (United States); Argonne National Laboratory, Argonne, IL 60439 (United States); Augustine, D. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Aurisano, A. [Department of Physics, University of Cincinnati, Cincinnati, OH 45221 (United States); Avvakumov, S. [Department of Physics, Stanford University, Stanford, CA 94305 (United States); Ayres, D.S. [Argonne National Laboratory, Argonne, IL 60439 (United States); Baller, B. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Barish, B. [Lauritsen Laboratory, California Institute of Technology, Pasadena, CA 91125 (United States); Barr, G. [Subdepartment of Particle Physics, University of Oxford, Oxford OX1 3RH (United Kingdom); Barrett, W.L. [Physics Department, Western Washington University, Bellingham, WA 98225 (United States); Bernstein, R.H.; Biggs, J. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Bishai, M. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Blake, A. [Cavendish Laboratory, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Bocean, V.; Bock, G.J.; Boehnlein, D.J. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); and others

    2016-01-11

    This paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual elements. The most important design details of individual components are described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.

  9. Understanding the formation and evolution of early-type galaxies based on newly developed single-burst stellar population synthesis models in the infrared

    Science.gov (United States)

    Roeck, Benjamin

    2015-12-01

    The detailed study of the different stellar populations which can be observed in galaxies is one of the most promising methods to shed light on the evolutionary histories of galaxies. So far, stellar population analysis has been carried out mainly in the optical wavelength range. The infrared spectral range, on the other hand, has been poorly studied so far, although it provides very important insights, particularly into the cooler stellar populations which are present in galaxies. However, in the last years, space telescopes like the Spitzer Space Telescope or the Wide-field Infrared Survey Explorer and instruments like the spectrograph X-Shooter on the Very Large Telescope have collected more and more photometric and spectroscopic data in this wavelength range. In order to analyze these observations, it is necessary to dispose of reliable and accurate stellar population models in the infrared. Only a small number of stellar population models in the infrared exist in the literature. They are mostly based on theoretical stellar libraries and very often cover only the near-infrared wavelength range at a rather low resolution. Hence, we developed new single-burst stellar population models between 8150 and 50000Å which are exclusively based on 180 spectra from the empirical Infrared Telescope Facility stellar library. We computed our single stellar population models for two different sets of isochrones and various types of initial mass functions of different slopes. Since the stars of the Infrared Telescope Facility library present only a limited coverage of the stellar atmospheric parameter space, our models are of sufficient quality only for ages larger than 1 Gyr and metallicities between [Fe/H] = 0.40 and 0.26. By combining our single stellar population models in the infrared with the extended medium-resolution Isaac Newton Telescope library of empirical spectra in the optical spectral range, we created the first single stellar population models covering the

  10. Estimating the effective number of breeders from single parr samples for conservation monitoring of wild populations of Atlantic salmon Salmo salar.

    Science.gov (United States)

    Bacles, C F E; Bouchard, C; Lange, F; Manicki, A; Tentelier, C; Lepais, O

    2018-03-01

    This study assesses whether the effective number of breeders (N b ) can be estimated using a time and cost-effective protocol using genetic sibship reconstruction from a single sample of young-of-the-year (YOY) for the purposes of Atlantic salmon Salmo salar population monitoring. N b was estimated for 10 consecutive reproductive seasons for S. salar in the River Nivelle, a small population located at the rear-edge of the species distribution area in France, chronically under its conservation limit and subjected to anthropogenic and environmental changes. Subsampling of real and simulated data showed that accurate estimates of N b can be obtained from YOY genotypes, collected at moderate random sampling intensity, achievable using routine juvenile electrofishing protocols. Spatial bias and time elapsed since spawning were found to affect estimates, which must be accounted for in sampling designs. N b estimated in autumn for S. salar in the River Nivelle was low and variable across years from 23 (95% C.I. 14-41) to 75 (53-101) and was not statistically correlated with the estimated number of returning adults, but it was positively correlated with the estimated number of YOY at age 9 months. N b was found to be lower for intermediate levels of redd aggregation, suggesting that the strength of the competition between males to access females affects reproductive success variance depending on redd spatial configuration. Thus, environmental factors such as habitat availability and quality for spawning and YOY development predominate over demographic ones (number of returning adults) in driving long-term population viability for S. salar in the River Nivelle. This study showcases N b as an integrated parameter, encompassing demographic and ecological information about a reproductive event, relevant to the assessment of both short-term effects of management practices and long-term population conservation status. © 2018 The Fisheries Society of the British Isles.

  11. Knock-down of miR-221 and miR-222 in the radiosensitization of breast cancer cells

    International Nuclear Information System (INIS)

    Zhang Chunzhi; Kang Chunsheng; Cao Yongzhen; Pu Peiyu; Lu Zhonghong; Du Yue

    2009-01-01

    Objective: To investigate the radiosensitizing effect of knock-down of miR-221 miR-222 on MCF-7 human breast cancer cells and explore the possible mechanism. Methods: Antisense oligonucleotides of miR-221 and miR-222 (AS-miR-221 and AS-miR-222), mediated by lipofectamine, were transfected to MCF-7 cells to knock down miR-221 and miR-222, Northern blotting was conducted to detect the expression of miR-221 and miR-222 in transfected cells. The cell apoptosis was detected by flow cytometry and Caspase-3 and Caspase-7 activity assay. Clonogenic assay was used to measure the sensitizing enhancement ratio. Target genes of miR-221 and miR-222 relevant to radio-sensitivity were searched using bioinformatics analysis. The targeted protein expression was determined by Western blot analysis. Results: The expression of miR-221 and miR-222 in the AS-miR-221/222 cells determined by Northern blotting was significantly reduced. Compared with the control group, the cell apoptosis and mitotic cell death after the radiation were significantly higher in AS-miR-221/222 cells. The sensitizing enhancement ratio was 1.87. Based on bioinformatics analysis, PTEN was a target gene of miR-221 and miR-222 which could enhance the radiosensitivity of MCF-7 cells. In AS-miR-221/222 cells, the expression of PTEN was up-regulated while pAkt down-regulated. Conclusions: AS-miR-221 and AS-miR-222 may enhance the radiosensitivity of MCF-7 breast cancer cells by up-regulating the expression of PTEN. (authors)

  12. Mmu-miR-615-3p regulates lipoapoptosis by inhibiting C/EBP homologous protein.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Miyamoto

    Full Text Available Lipoapoptosis occurring due to an excess of saturated free fatty acids such as palmitate is a key pathogenic event in the initiation of nonalcoholic fatty liver disease. Palmitate loading of cells activates the endoplasmic reticulum stress response, including induction of the proapoptotic transcription factor C/EBP homologous protein (CHOP. Furthermore, the loss of microRNAs is implicated in regulating apoptosis under conditions of endoplasmic reticulum (ER stress. The aim of this study was to identify specific microRNAs regulating CHOP expression during palmitate-induced ER stress. Five microRNAs were repressed under palmitate-induced endoplasmic reticulum stress conditions in hepatocyte cell lines (miR-92b-3p, miR-328-3p, miR-484, miR-574-5p, and miR-615-3p. We identified miR-615-3p as a candidate microRNA which was repressed by palmitate treatment and regulated CHOP protein expression, by RNA sequencing and in silico analyses, respectively. There is a single miR-615-3p binding site in the 3'untranslated region (UTR of the Chop transcript. We characterized this as a functional binding site using a reporter gene-based assay. Augmentation of miR-615-3p levels, using a precursor molecule, repressed CHOP expression; and under these conditions palmitate- or tunicamycin-induced cell death were significantly reduced. Our results suggest that palmitate-induced apoptosis requires maximal expression of CHOP which is achieved via the downregulation of its repressive microRNA, miR-615-3p. We speculate that enhancement of miR-615-3p levels may be of therapeutic benefit by inhibiting palmitate-induced hepatocyte lipoapoptosis.

  13. Cortical morphogenesis during embryonic development is regulated by miR-34c and miR-204

    DEFF Research Database (Denmark)

    Venø, Morten T; Venø, Susanne T; Rehberg, Kati

    2017-01-01

    The porcine brain closely resembles the human brain in aspects such as development and morphology. Temporal miRNA profiling in the developing embryonic porcine cortex revealed a distinct set of miRNAs, including miR-34c and miR-204, which exhibited a highly specific expression profile across...

  14. Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in sepsis.

    Science.gov (United States)

    Wang, Shanshan; Wang, Jun; Zhang, Zengdi; Miao, Hongjun

    2017-08-01

    Glomerular podocytes are injured in sepsis. We studied, in a sepsis patient, whether microRNAs (miRNAs) play a role in the podocyte injury. Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration barrier function of podocyte was analyzed with albumin influx assay. Nephrin level was analyzed with reverse transcription polymerase chain reaction (RT-PCR) and western blot. MiRNAs were detected using miRNAs PCR Array and in situ hybridization. MiRNA target sites were evaluated with luciferase reporter assays. LPS impaired the filtration barrier function of podocytes. MiR-128 level was decreased and miR-21 level was increased in podocytes in vitro and in the sepsis patient. The decrease in miR-128 was sufficient to induce the loss of nephrin and the impairment of filtration barrier function, while the increase of miR-21 exacerbated the process. Snail and phosphatase and tensin homolog (PTEN) were identified as the targets of miR-128 and miR-21. Decreased miR-128 induced Snail expression, and the increased miR-21 stabilized Snail by regulating the PTEN/Akt/GSK3β pathway. Supplementation of miR-128 and inhibition of miR-21 suppressed Snail expression and prevented the podocyte injury induced by LPS. Our study suggests that decreased miR-128 and increased miR-21 synergistically cause podocyte injury and are the potential therapeutic targets in sepsis.

  15. miR-21, miR-29c, and miR-155 as Biomarker to Develop Minimal Invasive Diagnostic in Hepatocellular Carcinoma Patient

    Directory of Open Access Journals (Sweden)

    P Lestari

    2017-02-01

    Objective: The aim of this study is to investigate the level expression of miR-21, miR-29c, and miR-155 as novel serological biomarkers for hepatocellular carcinoma. Methods: This study is quasi experimental and remain as preliminary study. Collecting for more samples is currently underway. HCC patient blood samples obtained from RSUP dr. Sardjito Yogyakarta based on specific inclusion and exclusion criteria. Blood samples were collected from 8 patients and 8 healthy controls. The collected blood samples were treated as follows: plasma isolation, RNA total isolation, cDNA synthesis, quantification by qRT-PCR, data analysis with Biorad CFX ManagerTM Softwere to determine Cq, followed by the calculation of expression levels using Livax Methods. Result: The result showed that miR-21 and miR-155 were upregulated 1.68 fold and 2.38 fold respectively compared with healthy control, while miR-29c was downregulated 3,45 fold compared with healthy control. Conclusion: Based on the result of preliminary study, it can be concluded that miR-21 act as oncomiR, while miR-29c and miR-155 act as tumor supressor miR in HCC. The three microRNAs can be detected in HCC and can be used as minimal invasive biomarkers to detect HCC. Keywords: HCC, miR-21, miR-29c, miR-155, minimal invasive, biomarker

  16. miRNAs associated with immune response in teleost fish.

    Science.gov (United States)

    Andreassen, Rune; Høyheim, Bjørn

    2017-10-01

    MicroRNAs (miRNAs) have been identified as important post transcriptional regulators of gene expression. In higher vertebrates, a subset of miRNAs has been identified as important regulators of a number of key genes in immune system gene networks, and this paper review recent studies on miRNAs associated with immune response in teleost fish. Challenge studies conducted in several species have identified differently expressed miRNAs associated with viral or bacterial infection. The results from these studies point out several miRNAs that are likely to have evolutionary conserved functions that are related to immune response in teleost fish. Changed expression levels of mature miRNAs from the five miRNA genes miRNA-462, miRNA-731, miRNA-146, miRNA-181 and miRNA-223 are observed following viral as well as bacterial infection in several teleost fish. Furthermore, significant changes in expression of mature miRNAs from the five genes miRNA-21, miRNA-155, miRNA-1388, miRNA-99 and miRNA-100 are observed in multiple studies of virus infected fish while changes in expression of mature miRNA from the three genes miRNA-122, miRNA-192 and miRNA-451 are observed in several studies of fish with bacterial infections. Interestingly, some of these genes are not present in higher vertebrates. The function of the evolutionary conserved miRNAs responding to infection depends on the target gene(s) they regulate. A few target genes have been identified while a large number of target genes have been predicted by in silico analysis. The results suggest that many of the targets are genes from the host's immune response gene networks. We propose a model with expected temporal changes in miRNA expression if they target immune response activators/effector genes or immune response inhibitors, respectively. The best way to understand the function of a miRNA is to identify its target gene(s), but as the amount of genome resources for teleost fish is limited, with less well characterized genomes

  17. Uncovering leaf rust responsive miRNAs in wheat (Triticum aestivum L.) using high-throughput sequencing and prediction of their targets through degradome analysis.

    Science.gov (United States)

    Kumar, Dhananjay; Dutta, Summi; Singh, Dharmendra; Prabhu, Kumble Vinod; Kumar, Manish; Mukhopadhyay, Kunal

    2017-01-01

    Deep sequencing identified 497 conserved and 559 novel miRNAs in wheat, while degradome analysis revealed 701 targets genes. QRT-PCR demonstrated differential expression of miRNAs during stages of leaf rust progression. Bread wheat (Triticum aestivum L.) is an important cereal food crop feeding 30 % of the world population. Major threat to wheat production is the rust epidemics. This study was targeted towards identification and functional characterizations of micro(mi)RNAs and their target genes in wheat in response to leaf rust ingression. High-throughput sequencing was used for transcriptome-wide identification of miRNAs and their expression profiling in retort to leaf rust using mock and pathogen-inoculated resistant and susceptible near-isogenic wheat plants. A total of 1056 mature miRNAs were identified, of which 497 miRNAs were conserved and 559 miRNAs were novel. The pathogen-inoculated resistant plants manifested more miRNAs compared with the pathogen infected susceptible plants. The miRNA counts increased in susceptible isoline due to leaf rust, conversely, the counts decreased in the resistant isoline in response to pathogenesis illustrating precise spatial tuning of miRNAs during compatible and incompatible interaction. Stem-loop quantitative real-time PCR was used to profile 10 highly differentially expressed miRNAs obtained from high-throughput sequencing data. The spatio-temporal profiling validated the differential expression of miRNAs between the isolines as well as in retort to pathogen infection. Degradome analysis provided 701 predicted target genes associated with defense response, signal transduction, development, metabolism, and transcriptional regulation. The obtained results indicate that wheat isolines employ diverse arrays of miRNAs that modulate their target genes during compatible and incompatible interaction. Our findings contribute to increase knowledge on roles of microRNA in wheat-leaf rust interactions and could help in rust

  18. Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

    Directory of Open Access Journals (Sweden)

    Jingjing Liang

    2017-05-01

    Full Text Available Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8 for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4 and multiple-trait analyses identified one novel locus (FRMD3 for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

  19. Cross Platform Standardisation of an Experimental Pipeline for Use in the Identification of Dysregulated Human Circulating MiRNAs.

    Directory of Open Access Journals (Sweden)

    Helena Kelly

    Full Text Available Micro RNAs (miRNAs are a class of highly conserved small non-coding RNAs that play an important part in the post-transcriptional regulation of gene expression. A substantial number of miRNAs have been proposed as biomarkers for diseases. While reverse transcriptase Real-time PCR (RT-qPCR is considered the gold standard for the evaluation and validation of miRNA biomarkers, small RNA sequencing is now routinely being adopted for the identification of dysregulated miRNAs. However, in many cases where putative miRNA biomarkers are identified using small RNA sequencing, they are not substantiated when RT-qPCR is used for validation. To date, there is a lack of consensus regarding optimal methodologies for miRNA detection, quantification and standardisation when different platform technologies are used.In this study we present an experimental pipeline that takes into consideration sample collection, processing, enrichment, and the subsequent comparative analysis of circulating small ribonucleic acids using small RNA sequencing and RT-qPCR.Initially, a panel of miRNAs dysregulated in circulating blood from breast cancer patients compared to healthy women were identified using small RNA sequencing. MiR-320a was identified as the most dysregulated miRNA between the two female cohorts. Total RNA and enriched small RNA populations (<30 bp isolated from peripheral blood from the same female cohort samples were then tested for using a miR-320a RT-qPCR assay. When total RNA was analysed with this miR-320a RT-qPCR assay, a 2.3-fold decrease in expression levels was observed between blood samples from healthy controls and breast cancer patients. However, upon enrichment for the small RNA population and subsequent analysis of miR-320a using RT-qPCR, its dysregulation in breast cancer patients was more pronounced with an 8.89-fold decrease in miR-320a expression. We propose that the experimental pipeline outlined could serve as a robust approach for the

  20. miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR.

    Science.gov (United States)

    Sun, Chuanzheng; Huang, Feizhou; Liu, Xunyang; Xiao, Xuefei; Yang, Mingshi; Hu, Gui; Liu, Huaizheng; Liao, Liangkan

    2015-03-01

    Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health issue with a prevalence of 15-30% in Western populations and 6-25% in Asian populations. Certain studies have revealed the alteration of microRNA (miRNA or miR) profiles in NAFLD and it has been suggested that miR-21 is associated with NAFLD. In the present study, we measured the serum levels of miR-21 in patients with NAFLD and also performed in vitro experiments using a cellular model of NAFLD to further investigate the effects of miR-21 on triglyceride and cholesterol metabolism. Furthermore, a novel target through which miR-21 exerts its effects on NAFLD was identified. The results revealed that the serum levels of miR-21 were lower in patients with NAFLD compared with the healthy controls. In addition, 3-hydroxy-3-methylglutaryl-co-enzyme A reductase (HMGCR) expression was increased in the serum of patients with NAFLD both at the mRNA and protein level. To mimic the NAFLD condition in vitro, HepG2 cells were treated with palmitic acid (PA) and oleic acid (OA). Consistent with the results obtained in the in vivo experiments, the expression levels of miR-21 were decreased and those of HMGCR were increased in the in vitro model of NAFLD. Luciferase reporter assay revealed that HMGCR was a direct target of miR-21 and that miR-21 exerted an effect on both HMGCR transcript degradation and protein translation. Furthermore, the results from the in vitro experiments revealed that miR-21 decreased the levels of triglycerides (TG), free cholesterol (FC) and total cholesterol (TC) in the PA/OA-treated HepG2 cells and that this effect was attenuated by HMGCR overexpression. Taken together, to the best of our knowledge, the present study is the first to report that miR-21 regulates triglyceride and cholesterol metabolism in an in vitro model of NAFLD, and that this effect is achieved by the inhibition of HMGCR expression. We speculate that miR-21 may be a useful biomarker for the diagnosis and

  1. A Single Transcriptome of a Green Toad (Bufo viridis Yields Candidate Genes for Sex Determination and -Differentiation and Non-Anonymous Population Genetic Markers.

    Directory of Open Access Journals (Sweden)

    Jörn F Gerchen

    Full Text Available Large genome size, including immense repetitive and non-coding fractions, still present challenges for capacity, bioinformatics and thus affordability of whole genome sequencing in most amphibians. Here, we test the performance of a single transcriptome to understand whether it can provide a cost-efficient resource for species with large unknown genomes. Using RNA from six different tissues from a single Palearctic green toad (Bufo viridis specimen and Hiseq2000, we obtained 22,5 Mio reads and publish >100,000 unigene sequences. To evaluate efficacy and quality, we first use this data to identify green toad specific candidate genes, known from other vertebrates for their role in sex determination and differentiation. Of a list of 37 genes, the transcriptome yielded 32 (87%, many of which providing the first such data for this non-model anuran species. However, for many of these genes, only fragments could be retrieved. In order to allow also applications to population genetics, we further used the transcriptome for the targeted development of 21 non-anonymous microsatellites and tested them in genetic families and backcrosses. Eleven markers were specifically developed to be located on the B. viridis sex chromosomes; for eight markers we can indeed demonstrate sex-specific transmission in genetic families. Depending on phylogenetic distance, several markers, which are sex-linked in green toads, show high cross-amplification success across the anuran phylogeny, involving nine systematic anuran families. Our data support the view that single transcriptome sequencing (based on multiple tissues provides a reliable genomic resource and cost-efficient method for non-model amphibian species with large genome size and, despite limitations, should be considered as long as genome sequencing remains unaffordable for most species.

  2. The Display of Single-Domain Antibodies on the Surfaces of Connectosomes Enables Gap Junction-Mediated Drug Delivery to Specific Cell Populations.

    Science.gov (United States)

    Gadok, Avinash K; Zhao, Chi; Meriwether, Amanda I; Ferrati, Silvia; Rowley, Tanner G; Zoldan, Janet; Smyth, Hugh D C; Stachowiak, Jeanne C

    2018-01-09

    Gap junctions, transmembrane protein channels that directly connect the cytoplasm of neighboring cells and enable the exchange of molecules between cells, are a promising new frontier for therapeutic delivery. Specifically, cell-derived lipid vesicles that contain functional gap junction channels, termed Connectosomes, have recently been demonstrated to substantially increase the effectiveness of small molecule chemotherapeutics. However, because gap junctions are present in nearly all tissues, Connectosomes have no intrinsic ability to target specific cell types, which potentially limits their therapeutic effectiveness. To address this challenge, here we display targeting ligands consisting of single-domain antibodies on the surfaces of Connectosomes. We demonstrate that these targeted Connectosomes selectively interact with cells that express a model receptor, promoting the selective delivery of the chemotherapeutic doxorubicin to this target cell population. More generally, our approach has the potential to boost cytoplasmic delivery of diverse therapeutic molecules to specific cell populations while protecting off-target cells, a critical step toward realizing the therapeutic potential of gap junctions.

  3. Comparison of the clinical effectiveness of a single and a triple-headed toothbrushes in a population of mentally retarded patients.

    Science.gov (United States)

    Sauvetre, E; Rozow, A; de Meel, H; Richebe, A; Abi-Khalil, M; Demeure, F

    1995-01-01

    Tooth brushing is a very simple and effective method for removing daily dental deposits and for preventing dental and periodontal diseases. However, it can cause considerable manipulative difficulties among some populations, e.g., young children, physically handicapped and mentally retarded patients. In order to test and compare the efficiency of a newly designed toothbrush (Superbrush), we have performed a pilot study on patients staying at the "Reine Fabiola Village No. 1", an institution for patients who are followed for mental retardation at different levels. 30 patients were included in the study, aged between 18 to 40 years. Among these 30, five had to be eliminated for their incapacity to follow the initial training in how to brush their teeth. The comparison was made with a normal single headed tooth brush, in a double blind trial, based on bleeding and plaque indexes, performed on 6 different teeth on day 0, 7 and 21. The results of this study indicate that there is no significant difference between the two types of toothbrushes with respect to the ability of plaque removing and gingivitis prevention, during the period of time of this study. However, the easiness of manipulating this newly designed toothbrush renders it a useful tool for the dental hygiene for this special part of the dental compromised population.

  4. miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells.

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    Kinya Okamoto

    Full Text Available BACKGROUND AND AIMS: Cholangiocarcinoma (CCA is highly resistant to chemotherapy, including gemcitabine (Gem treatment. MicroRNAs (miRNAs are endogenous, non-coding, short RNAs that can regulate multiple genes expression. Some miRNAs play important roles in the chemosensitivity of tumors. Here, we examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. METHODS: Microarray analysis was used to determine the miRNA expression profiles of two CCA cell lines, HuH28 and HuCCT1. To determine the effect of candidate miRNAs on Gem sensitivity, expression of each candidate miRNA was modified via either transfection of a miRNA mimic or transfection of an anti-oligonucleotide. Ontology-based programs were used to identify potential target genes of candidate miRNAs that were confirmed to affect the Gem sensitivity of CCA cells. RESULTS: HuCCT1 cells were more sensitive to Gem than were HuH28 cells, and 18 miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221 restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment. Selective siRNA-mediated downregulation of either of two software-predicted targets, PIK3R1 (target of miR-29b and miR-221 or MMP-2 (target of miR-29b, also conferred Gem sensitivity to HuH28. CONCLUSIONS: miRNA expression profiling was used to identify key miRNAs that regulate Gem sensitivity in CCA cells, and software that predicts miRNA targets was used to identify promising target genes for anti-tumor therapies.

  5. Combination Testing Using a Single MSH5 Variant alongside HLA Haplotypes Improves the Sensitivity of Predicting Coeliac Disease Risk in the Polish Population.

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    Agnieszka Paziewska

    Full Text Available Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis. DNA samples of 336 CD and 264 unrelated healthy controls were used to create DNA pools for a genome wide association study (GWAS. GWAS findings were validated with individual HLA tag single nucleotide polymorphism (SNP typing of 473 patients and 714 healthy controls. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8 were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1 and rs3130484 (HLA-independent; mapped to MSH5. Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%. This study confirmed that improvement of CD risk prediction sensitivity could be achieved by including non-HLA SNPs alongside HLA SNPs in genetic testing.

  6. Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci.

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    Stefano Comazzetto

    2014-10-01

    Full Text Available Male fertility requires the continuous production of high quality motile spermatozoa in abundance. Alterations in all three metrics cause oligoasthenoteratozoospermia, the leading cause of human sub/infertility. Post-mitotic spermatogenesis inclusive of several meiotic stages and spermiogenesis (terminal spermatozoa differentiation are transcriptionally inert, indicating the potential importance for the post-transcriptional microRNA (miRNA gene-silencing pathway therein. We found the expression of miRNA generating enzyme Dicer within spermatogenesis peaks in meiosis with critical functions in spermatogenesis. In an expression screen we identified two miRNA loci of the miR-34 family (miR-34b/c and miR-449 that are specifically and highly expressed in post-mitotic male germ cells. A reduction in several miRNAs inclusive of miR-34b/c in spermatozoa has been causally associated with reduced fertility in humans. We found that deletion of both miR34b/c and miR-449 loci resulted in oligoasthenoteratozoospermia in mice. MiR-34bc/449-deficiency impairs both meiosis and the final stages of spermatozoa maturation. Analysis of miR-34bc-/-;449-/- pachytene spermatocytes revealed a small cohort of genes deregulated that were highly enriched for miR-34 family target genes. Our results identify the miR-34 family as the first functionally important miRNAs for spermatogenesis whose deregulation is causal to oligoasthenoteratozoospermia and infertility.

  7. Early Sámi visual artists - Western fine art meets Sámi culture

    Directory of Open Access Journals (Sweden)

    Tuija Hautala-Hirvioja

    2014-04-01

    Full Text Available Johan Turi (1854–1936, Nils Nilsson Skum (1872–1951 and John Savio (1902–1938 were among the first Sámi visual artists. The production of their art work occurred between the 1910s and the early 1950s. Sámi aesthetics had its basis in folklore, i.e., handicraft or duodji, which did not follow the principle of art for art’s sake but combined beauty and practicality. Art was part of community life. Not until the 1970s was the word daidda, which is Finnish in origin and which means “art”, adopted into the Sámi language. Turi and Skum became famous through their books. They drew and wrote in order to pass the traditional knowledge of their people on to succeeding generations. They also wanted to introduce Sámi life and culture to non-Sámi people. One typical feature of their work is that they depicted Sáminess in a realistic way and sought to strengthen and preserve the Sámi identity through their art. In Turi and Skum’s work, both the documentation of community life and their own personal expression were strongly present and equally important; for this reason their pictures and texts have both practical and aesthetic dimensions. They did not attend school and were self-taught artists. The third pioneer of Sámi visual arts was John Savio, who, unlike the other two, attended secondary school and studied visual arts both independently and under the guidance of a mentor. He expressively combined Western ways of depiction with Sámi subjects. My article examines what made these early Sámi artists change over from Sámi handicraft, duodji, to Western visual arts, how they used Western pictorial conventions in dealing with their Sámi subjects, and the significance of their art for Sámi identity and culture. They lived and worked under cross pressure: the first few decades of the 20th century were characterized by racial theories that denigrated Sámi people, and the period following World War II was marked by demands for

  8. miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells.

    Science.gov (United States)

    Kuhn, Stephanie; Johnson, Stuart L; Furness, David N; Chen, Jing; Ingham, Neil; Hilton, Jennifer M; Steffes, Georg; Lewis, Morag A; Zampini, Valeria; Hackney, Carole M; Masetto, Sergio; Holley, Matthew C; Steel, Karen P; Marcotti, Walter

    2011-02-08

    MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is a sensory organ-specific miRNA expressed in the mammalian cochlea during development. Mutations in miR-96 cause nonsyndromic progressive hearing loss in humans and mice. The mouse mutant diminuendo has a single base change in the seed region of the Mir96 gene leading to widespread changes in the expression of many genes. We have used this mutant to explore the role of miR-96 in the maturation of the auditory organ. We found that the physiological development of mutant sensory hair cells is arrested at around the day of birth, before their biophysical differentiation into inner and outer hair cells. Moreover, maturation of the hair cell stereocilia bundle and remodelling of auditory nerve connections within the cochlea fail to occur in miR-96 mutants. We conclude that miR-96 regulates the progression of the physiological and morphological differentiation of cochlear hair cells and, as such, coordinates one of the most distinctive functional refinements of the mammalian auditory system.

  9. Genome-wide search for miRNA-target interactions in Arabidopsis thaliana with an integrated approach

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    Ding Jiandong

    2012-06-01

    Full Text Available Abstract Background MiRNA are about 22nt long small noncoding RNAs that post transcriptionally regulate gene expression in animals, plants and protozoa. Confident identification of MiRNA-Target Interactions (MTI is vital to understand their function. Currently, several integrated computational programs and databases are available for animal miRNAs, the mechanisms of which are significantly different from plant miRNAs. Methods Here we present an integrated MTI prediction and analysis toolkit (imiRTP for Arabidopsis thaliana. It features two important functions: (i combination of several effective plant miRNA target prediction methods provides a sufficiently large MTI candidate set, and (ii different filters allow for an efficient selection of potential targets. The modularity of imiRTP enables the prediction of high quality targets on genome-wide scale. Moreover, predicted MTIs can be presented in various ways, which allows for browsing through the putative target sites as well as conducting simple and advanced analyses. Results Results show that imiRTP could always find high quality candidates compared with single method by choosing appropriate filter and parameter. And we also reveal that a portion of plant miRNA could bind target genes out of coding region. Based on our results, imiRTP could facilitate the further study of Arabidopsis miRNAs in real use. All materials of imiRTP are freely available under a GNU license at (http://admis.fudan.edu.cn/projects/imiRTP.htm.

  10. Role of Viral miRNAs and Epigenetic Modifications in Epstein-Barr Virus-Associated Gastric Carcinogenesis.

    Science.gov (United States)

    Giudice, Aldo; D'Arena, Giovanni; Crispo, Anna; Tecce, Mario Felice; Nocerino, Flavia; Grimaldi, Maria; Rotondo, Emanuela; D'Ursi, Anna Maria; Scrima, Mario; Galdiero, Massimiliano; Ciliberto, Gennaro; Capunzo, Mario; Franci, Gianluigi; Barbieri, Antonio; Bimonte, Sabrina; Montella, Maurizio

    2016-01-01

    MicroRNAs are short (21-23 nucleotides), noncoding RNAs that typically silence posttranscriptional gene expression through interaction with target messenger RNAs. Currently, miRNAs have been identified in almost all studied multicellular eukaryotes in the plant and animal kingdoms. Additionally, recent studies reported that miRNAs can also be encoded by certain single-cell eukaryotes and by viruses. The vast majority of viral miRNAs are encoded by the herpesviruses family. These DNA viruses including Epstein-Barr virus encode their own miRNAs and/or manipulate the expression of cellular miRNAs to facilitate respective infection cycles. Modulation of the control pathways of miRNAs expression is often involved in the promotion of tumorigenesis through a specific cascade of transduction signals. Notably, latent infection with Epstein-Barr virus is considered liable of causing several types of malignancies, including the majority of gastric carcinoma cases detected worldwide. In this review, we describe the role of the Epstein-Barr virus in gastric carcinogenesis, summarizing the functions of the Epstein-Barr virus-encoded viral proteins and related epigenetic alterations as well as the roles of Epstein-Barr virus-encoded and virally modulated cellular miRNAs.

  11. MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma

    NARCIS (Netherlands)

    Boll, K.; Reiche, K.; Kasack, K.; Morbt, N.; Kretzschmar, A.K.; Tomm, J.M.; Verhaegh, G.W.; Schalken, J.A.; Bergen, M. von; Horn, F.; Hackermuller, J.

    2013-01-01

    With approximately 30 000 deaths annually in the United States, prostate cancer (PCa) is a major oncologic disease. Here we show that the microRNAs miR-130a, miR-203 and miR-205 jointly interfere with the two major oncogenic pathways in prostate carcinoma and are downregulated in cancer tissue.

  12. miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict

    2013-01-01

    AIM: To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS: Colonic mucosal pinch biopsies from the descending part...... of these miRNAs may serve as new potential biomarkers for this chronic disease....

  13. Methylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms

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    Chim Chor Sang

    2011-11-01

    Full Text Available Abstract Background MicroRNA (miR miR-34a, -34b/c, -124-1 and -203 are tumor suppressor miRs implicated in carcinogenesis. Methods We studied DNA methylation of these miRs in Philadelphia-negative (Ph-ve myeloproliferative neoplasms (MPNs. Methylation-specific PCR (MSP, verified by direct sequencing of the methylated MSP products, was performed in cell lines, normal controls and diagnostic marrow samples of patients with MPNs. Results Methylation of these miRs was absent in the normal controls. miR-34b/c were homozygously methylated in HEL cells but heterozygously in MEG-01. In HEL cells, homozygous miR-34b/c methylation was associated with miR silencing, and 5-aza-2'-deoxycytidine treatment led to re-expression of both miR-34b and miR-34c, consistent with that both miRs are under the regulation of the same promoter CpG island. miR-34a was heterozygously methylated in MEG-01 and K-562. miR-203 was completely unmethylated in K-562 and SET-2 but no MSP amplification was found in both HEL and MEG-01, suggestive of miR deletion. In primary samples, four each had miR-34b/c and -203 methylation, in which two had concomitant methylation of miR-34b/c and -203. miR-34a was methylated in one patient and none had methylation of miR-124-1. Seven patients (15.6% had methylation of at least one of the four miRs. miR methylation did not correlate with clinical parameters, disease complications or JAK2 V617F mutation. Conclusion This is the first report of miR hypermethylation in MPNs. miR-203 hypermethylation is not specific to Ph+ve leukemias but also present in Ph-ve MPNs. miR-34b/c methylation was associated with reversible miR silencing. There was no correlation of miR methylation with clinical demographic data or outcome.

  14. MiRNA-based Therapeutics for Lung Cancer.

    Science.gov (United States)

    Wu, Miaowei; Wang, Guosheng; Tian, Wei; Deng, Yongchuan; Xu, Yibing

    2018-02-12

    miRNA, a small non-coding RNA molecule containing about 22 nucleotides, functions in RNA silencing and post-transcriptional regulation of gene expression. With these qualities, miRNAs modulate multiple signaling pathways involved in cancer development, such as cellular proliferation, apoptosis, and migration. The goal of this review is to discuss possible miRNAs-based therapeutic strategies, through defining performance of miRNAs in carcinogenesis, in particular in lung cancer. miRNA, a non-coding RNA, is divided into two main types: tumor suppressor miRNAs and oncogenic miRNAs. In addition, special processed miRNAs can be an assistant therapeutic tool. In order to develope antitumor therapy, miRNAs-based therapeutic strategies are worth of deeper studies. In this process, the stability, effectiveness, and side effects should be considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Computational Identification of Putative miRNAs from

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    Ganesh Sathyamurthy

    2010-01-01

    Full Text Available microRNAs represent a class of noncoding small RNAs of approximately 20–23 nt length, which are evolutionarily conserved and play a vital role in various biological processes by either degrading or repressing mRNA translation. The Felis catus (cat genome sequence has been published, and just revealed the number of miRNAs in the genome–-without mention of any further details on these miRNAs. This paper discusses an in silico comparative approach using all known sequences of vertebrate pre-miRNA as query sequence, and report 405 putative miRNAs from cat genome. We determine the identity values of pre-miRNAs and mature miRNAs besides statistical sequence characteristics. Interestingly, among 405 miRNAs–-90, 53 and 50 showed 100% identity to cattle, human and dog, respectively. Further, we have validated 6 miRNAs, whose identity are <85% with the query sequence and validated them using MiPred algorithm. We also identify 25 miRNA clusters in cat based on their homologs in other vertebrates. Most importantly, based on identities among pre-miRNA, mature miRNA, miRNA families and clusters, we observe that miRNAs from cat are more identical to cattle, than humans. Our results, therefore may add a new dimension to the studies related to the evolution of cat.

  16. MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting miR-361.

    Directory of Open Access Journals (Sweden)

    Kun Wang

    2014-07-01

    Full Text Available Long noncoding RNAs (lncRNAs are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL, affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484 and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression.

  17. Plasma Viral miRNAs Indicate a High Prevalence of Occult Viral Infections

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    Enrique Fuentes-Mattei

    2017-06-01

    Full Text Available Prevalence of Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8 varies greatly in different populations. We hypothesized that the actual prevalence of KSHV/HHV8 infection in humans is underestimated by the currently available serological tests. We analyzed four independent patient cohorts with post-surgical or post-chemotherapy sepsis, chronic lymphocytic leukemia and post-surgical patients with abdominal surgical interventions. Levels of specific KSHV-encoded miRNAs were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR, and KSHV/HHV-8 IgG were measured by immunoassay. We also measured specific miRNAs from Epstein Barr Virus (EBV, a virus closely related to KSHV/HHV-8, and determined the EBV serological status by ELISA for Epstein-Barr nuclear antigen 1 (EBNA-1 IgG. Finally, we identified the viral miRNAs by in situ hybridization (ISH in bone marrow cells. In training/validation settings using independent multi-institutional cohorts of 300 plasma samples, we identified in 78.50% of the samples detectable expression of at least one of the three tested KSHV-miRNAs by RT-qPCR, while only 27.57% of samples were found to be seropositive for KSHV/HHV-8 IgG (P < 0.001. The prevalence of KSHV infection based on miRNAs qPCR is significantly higher than the prevalence determined by seropositivity, and this is more obvious for immuno-depressed patients. Plasma viral miRNAs quantification proved that EBV infection is ubiquitous. Measurement of viral miRNAs by qPCR has the potential to become the “gold” standard method to detect certain viral infections in clinical practice.

  18. Characterization of the Merkel Cell Carcinoma miRNome

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    Matthew S. Ning

    2014-01-01

    Full Text Available MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs, next-generation sequencing (NGS of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis. In situ hybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveal that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1. These data indicate that we have identified a set of MCC-miRs with important implications for MCC research.

  19. Population transcriptomics with single-cell resolution: a new field made possible by microfluidics: a technology for high throughput transcript counting and data-driven definition of cell types.

    Science.gov (United States)

    Plessy, Charles; Desbois, Linda; Fujii, Teruo; Carninci, Piero

    2013-02-01

    Tissues contain complex populations of cells. Like countries, which are comprised of mixed populations of people, tissues are not homogeneous. Gene expression studies that analyze entire populations of cells from tissues as a mixture are blind to this diversity. Thus, critical information is lost when studying samples rich in specialized but diverse cells such as tumors, iPS colonies, or brain tissue. High throughput methods are needed to address, model and understand the constitutive and stochastic differences between individual cells. Here, we describe microfluidics technologies that utilize a combination of molecular biology and miniaturized labs on chips to study gene expression at the single cell level. We discuss how the characterization of the transcriptome of each cell in a sample will open a new field in gene expression analysis, population transcriptomics, that will change the academic and biomedical analysis of complex samples by defining them as quantified populations of single cells. Copyright © 2013 WILEY Periodicals, Inc.

  20. miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells

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    Jui-Hung Weng

    2016-07-01

    Full Text Available Oral squamous cell carcinoma (OSCC is the most common malignancy of head and neck. Although radiotherapy is used for OSCC treatment, the occurrence of radioresistant cancer cells limits its efficiency. MicroRNAs (miRNAs are non-coding RNAs with lengths of 18–25 base pairs and known to be involved in carcinogenesis. We previously demonstrated that by targeting B lymphoma Mo-MLV insertion region 1 homolog (Bmi1, miR-494-3p functions as a putative tumor suppressor miRNA in OSCC. In this study, we further discovered that miR-494-3p could enhance the radiosensitivity of SAS OSCC cells and induce cellular senescence. The overexpression of miR-494-3p in SAS cells increased the population of senescence-associated β-galactosidase positive cells, the expression of p16INK4a and retinoblastoma 1 (RB1, as well as downregulated Bmi1. The knockdown of Bmi1 by lentiviral-mediated delivery of specific short hairpin RNAs (shRNAs also enhanced the radiosensitivity of SAS cells and the activation of the senescence pathway. Furthermore, the inverse correlation between Bmi1 and miR-494-3p expression was observed among OSCC tissues. Results suggest that miR-494-3p could increase the radiosensitivity of OSCC cells through the induction of cellular senescence caused by the downregulation of Bmi1.

  1. Measurement of the <mi>t> -Channel Single Top Quark Production Cross Section in <mi>pp> Collisions at <mi>s>=7<mi>TeV>

    Energy Technology Data Exchange (ETDEWEB)

    Chatrchyan, S. [Yerevan Physics Inst. (YerPhI) (Armenia); Khachatryan, V. [Yerevan Physics Inst. (YerPhI) (Armenia); Sirunyan, A. M. [Yerevan Physics Inst. (YerPhI) (Armenia); Tumasyan, A. [Yerevan Physics Inst. (YerPhI) (Armenia); Adam, W. [Osterreichischen Akademie der Wissenschaften (OAW), Wein, (Austria). Inst. fur Hochenergiephysik (HEPHY); Bergauer, T. [Osterreichischen Akademie der Wissenschaften (OAW), Wein, (Austria). Inst. fur Hochenergiephysik (HEPHY); Dragicevic, M. [Osterreichischen Akademie der Wissenschaften (OAW), Wein, (Austria). Inst. fur Hochenergiephysik (HEPHY)

    2011-08-25

    Electroweak production of the top quark is measured in pp collisions at \\(\\sqrt{s} = 7\\) Tev, using a dataset collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 36 pb-1 inverse picobarns. With an event selection optimized for t-channel production, two complementary analyses are performed. The first one exploits the special angular properties of the signal, together with background estimates from data. The second approach uses a multivariate analysis technique to probe the compatibility with signal topology expected from electroweak top quark production. The combined measurement of the cross section is 83.6 ± 29.8 (stat.+syst.) ± 3.3 (lumi.) pb, consistent with the standard model expectation.

  2. A multiplexed miRNA and transgene expression platform for simultaneous repression and expression of protein coding sequences.

    Science.gov (United States)

    Seyhan, Attila A

    2016-01-01

    Knockdown of single or multiple gene targets by RNA interference (RNAi) is necessary to overcome escape mutants or isoform redundancy. It is also necessary to use multiple RNAi reagents to knockdown multiple targets. It is also desirable to express a transgene or positive regulatory elements and inhibit a target gene in a coordinated fashion. This study reports a flexible multiplexed RNAi and transgene platform using endogenous intronic primary microRNAs (pri-miRNAs) as a scaffold located in the green fluorescent protein (GFP) as a model for any functional transgene. The multiplexed intronic miRNA - GFP transgene platform was designed to co-express multiple small RNAs within the polycistronic cluster from a Pol II promoter at more moderate levels to reduce potential vector toxicity. The native intronic miRNAs are co-transcribed with a precursor GFP mRNA as a single transcript and presumably cleaved out of the precursor-(pre) mRNA by the RNA splicing machinery, spliceosome. The spliced intron with miRNA hairpins will be further processed into mature miRNAs or small interfering RNAs (siRNAs) capable of triggering RNAi effects, while the ligated exons become a mature messenger RNA for the translation of the functional GFP protein. Data show that this approach led to robust RNAi-mediated silencing of multiple Renilla Luciferase (R-Luc)-tagged target genes and coordinated expression of functional GFP from a single transcript in transiently transfected HeLa cells. The results demonstrated that this design facilitates the coordinated expression of all mature miRNAs either as individual miRNAs or as multiple miRNAs and the associated protein. The data suggest that, it is possible to simultaneously deliver multiple negative (miRNA or shRNA) and positive (transgene) regulatory elements. Because many cellular processes require simultaneous repression and activation of downstream pathways, this approach offers a platform technology to achieve that dual manipulation efficiently

  3. Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer

    DEFF Research Database (Denmark)

    Winther, Mette; Alsner, Jan; Tramm, Trine

    2015-01-01

    analyses identified miR-21 as an independent prognostic marker for DSS in EAC [HR 3.52 (95% CI 1.06-11.69)]. High miR-375 was not correlated with improved prognosis in either histology. However, Forest plots demonstrated that both miR-21 and miR-375 were of prognostic impact in ESCC. CONCLUSION...... chemotherapy were analyzed. Expression levels of miR-21 and miR-375 were quantified using Affymetrix GeneChip miRNA 1.0 Array. The Cox proportional hazards model was used to assess the correlation of miR-21 and miR-375 with disease-specific survival (DSS) and overall survival (OS). Forest plots were performed...... to evaluate the prognostic impact of miR-21 and miR-375 in the present study and previously published reports. RESULTS: In ESCC, patients with miR-21 expression levels above median showed a trend towards poorer DSS and OS. When dividing miR-21 expression by tertiles, high levels of miR-21 significantly...

  4. High throughput sequencing of small RNA component of leaves and inflorescence revealed conserved and novel miRNAs as well as phasiRNA loci in chickpea.

    Science.gov (United States)

    Srivastava, Sangeeta; Zheng, Yun; Kudapa, Himabindu; Jagadeeswaran, Guru; Hivrale, Vandana; Varshney, Rajeev K; Sunkar, Ramanjulu

    2015-06-01

    Among legumes, chickpea (Cicer arietinum L.) is the second most important crop after soybean. MicroRNAs (miRNAs) play important roles by regulating target gene expression important for plant development and tolerance to stress conditions. Additionally, recently discovered phased siRNAs (phasiRNAs), a new class of small RNAs, are abundantly produced in legumes. Nevertheless, little is known about these regulatory molecules in chickpea. The small RNA population was sequenced from leaves and flowers of chickpea to identify conserved and novel miRNAs as well as phasiRNAs/phasiRNA loci. Bioinformatics analysis revealed 157 miRNA loci for the 96 highly conserved and known miRNA homologs belonging to 38 miRNA families in chickpea. Furthermore, 20 novel miRNAs belonging to 17 miRNA families were identified. Sequence analysis revealed approximately 60 phasiRNA loci. Potential target genes likely to be regulated by these miRNAs were predicted and some were confirmed by modified 5' RACE assay. Predicted targets are mostly transcription factors that might be important for developmental processes, and others include superoxide dismutases, plantacyanin, laccases and F-box proteins that could participate in stress responses and protein degradation. Overall, this study provides an inventory of miRNA-target gene interactions for chickpea, useful for the comparative analysis of small RNAs among legumes. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  5. miR-371, miR-138, miR-544, miR-145, and miR-214 could modulate Th1/Th2 balance in asthma through the combinatorial regulation of Runx3.

    Science.gov (United States)

    Qiu, Yu-Ying; Zhang, Ying-Wei; Qian, Xiu-Fen; Bian, Tao

    2017-01-01

    Asthma is tightly related to the imbalance of Th1/Th2 cells, and Runx3 plays a pivotal role in the differentiation of T helper cells. The present study aimed to investigate dysregulated microRNAs that may target Runx3 in CD4 + T cells from asthmatic patients and reveal Runx3 function in Th1/Th2 balance regulation. We detected the levels of Th1- and Th2-related cytokines by ELISA and analyzed the differentiation marker gene of T helper cells by qRT-PCR. Results indicated that an imbalance of Th1/Th2 cells was present in our asthmatic subject. Runx3 expression was reduced in the CD4 + T cells from asthmatic patients. Overexpression of Runx3 could restore the Th1/Th2 balance. After performing microRNA microarray assay, we found a series of microRNAs that were considerably altered in the CD4 + T cells from asthmatic patients. Among these upregulated microRNAs, eight microRNAs that may target Runx3 were selected by bioinformatics prediction. Five microRNAs, namely miR-371, miR-138, miR-544, miR-145, and miR-214, were confirmed by qRT-PCR and selected as candidate microRNAs. Luciferase reporter assay showed that these five microRNAs could directly target the 3'-UTR of Runx3. However, only simultaneous inhibition of these five microRNAs could alter the expression of Runx3. Most importantly, only simultaneous inhibition could improve the Th1/Th2 balance. Thus, we suggest that miR-371, miR-138, miR-544, miR-145, and miR-214 can modulate the Th1/Th2 balance in asthma by regulating Runx3 in a comb