WorldWideScience

Sample records for selection reveals candidates

  1. "Contrasting patterns of selection at Pinus pinaster Ait. Drought stress candidate genes as revealed by genetic differentiation analyses".

    Science.gov (United States)

    Eveno, Emmanuelle; Collada, Carmen; Guevara, M Angeles; Léger, Valérie; Soto, Alvaro; Díaz, Luis; Léger, Patrick; González-Martínez, Santiago C; Cervera, M Teresa; Plomion, Christophe; Garnier-Géré, Pauline H

    2008-02-01

    The importance of natural selection for shaping adaptive trait differentiation among natural populations of allogamous tree species has long been recognized. Determining the molecular basis of local adaptation remains largely unresolved, and the respective roles of selection and demography in shaping population structure are actively debated. Using a multilocus scan that aims to detect outliers from simulated neutral expectations, we analyzed patterns of nucleotide diversity and genetic differentiation at 11 polymorphic candidate genes for drought stress tolerance in phenotypically contrasted Pinus pinaster Ait. populations across its geographical range. We compared 3 coalescent-based methods: 2 frequentist-like, including 1 approach specifically developed for biallelic single nucleotide polymorphisms (SNPs) here and 1 Bayesian. Five genes showed outlier patterns that were robust across methods at the haplotype level for 2 of them. Two genes presented higher F(ST) values than expected (PR-AGP4 and erd3), suggesting that they could have been affected by the action of diversifying selection among populations. In contrast, 3 genes presented lower F(ST) values than expected (dhn-1, dhn2, and lp3-1), which could represent signatures of homogenizing selection among populations. A smaller proportion of outliers were detected at the SNP level suggesting the potential functional significance of particular combinations of sites in drought-response candidate genes. The Bayesian method appeared robust to low sample sizes, flexible to assumptions regarding migration rates, and powerful for detecting selection at the haplotype level, but the frequentist-like method adapted to SNPs was more efficient for the identification of outlier SNPs showing low differentiation. Population-specific effects estimated in the Bayesian method also revealed populations with lower immigration rates, which could have led to favorable situations for local adaptation. Outlier patterns are discussed

  2. Diversifying Selection in the Wheat Stem Rust Fungus Acts Predominantly on Pathogen-Associated Gene Families and Reveals Candidate Effectors

    Directory of Open Access Journals (Sweden)

    Jana eSperschneider

    2014-09-01

    Full Text Available Plant pathogens cause severe losses to crop plants and threaten global food production. One striking example is the wheat stem rust fungus, Puccinia graminis f. sp. tritici, which can rapidly evolve new virulent pathotypes in response to resistant host lines. Like several other filamentous fungal and oomycete plant pathogens, its genome features expanded gene families that have been implicated in host-pathogen interactions, possibly encoding effector proteins that interact directly with target host defence proteins. Previous efforts to understand virulence largely relied on the prediction of secreted, small and cysteine-rich proteins as candidate effectors and thus delivered an overwhelming number of candidates. Here, we implement an alternative analysis strategy that uses the signal of adaptive evolution as a line of evidence for effector function, combined with comparative information and expression data. We demonstrate that in planta up-regulated genes that are rapidly evolving are found almost exclusively in pathogen-associated gene families, affirming the impact of host-pathogen co-evolution on genome structure and the adaptive diversification of specialised gene families. In particular, we predict 42 effector candidates that are conserved only across pathogens, induced during infection and rapidly evolving. One of our top candidates has recently been shown to induce genotype-specific hypersensitive cell death in wheat. This shows that comparative genomics incorporating the evolutionary signal of adaptation is powerful for predicting effector candidates for laboratory verification. Our system can be applied to a wide range of pathogens and will give insight into host-pathogen dynamics, ultimately leading to progress in strategies for disease control.

  3. Teacher Candidate Selection and Evaluation.

    Science.gov (United States)

    Collins, Mary Lynn; And Others

    Summaries are presented of three papers presented at a summer workshop on Quality Assurance in Teacher Education conducted by the Association of Teacher Educators. The general topic covered by these presentations was teacher candidate selection and evaluation. Papers focused upon the following questions: (1) What entry level criteria should be…

  4. Genome-wide candidate regions for selective sweeps revealed through massive parallel sequencing of DNA across ten turkey populations

    NARCIS (Netherlands)

    Aslam, M.L.; Bastiaansen, J.W.M.; Megens, H.J.W.C.; Crooijmans, R.P.M.A.; Blomberg, L.; Groenen, M.

    2014-01-01

    Background The domestic turkey (Meleagris gallopavo) is an important agricultural species that is largely used as a meat-type bird. Characterizing genetic variation in populations of domesticated species and associating these variation patterns with the evolution, domestication, and selective

  5. Political Candidate Campaign Advertising: A Selected Review of the Literature.

    Science.gov (United States)

    Hellweg, Susan A.

    This paper provides a selected review of political candidate campaign advertising studies from the political science, mass communication, advertising, and political communication literature. The paper examines the literature in terms of research pertaining to (1) candidate advertising content (commercials for male versus female candidates and for…

  6. Psychometric Personality Differences Between Candidates in Astronaut Selection.

    Science.gov (United States)

    Mittelstädt, Justin M; Pecena, Yvonne; Oubaid, Viktor; Maschke, Peter

    This paper investigates personality traits as potential factors for success in an astronaut selection by comparing personality profiles of unsuccessful and successful astronaut candidates in different phases of the ESA selection procedure. It is further addressed whether personality traits could predict an overall assessment rating at the end of the selection. In 2008/2009, ESA performed an astronaut selection with 902 candidates who were either psychologically recommended for mission training (N = 46) or failed in basic aptitude (N = 710) or Assessment Center and interview testing (N = 146). Candidates completed the Temperament Structure Scales (TSS) and the NEO Personality Inventory Revised (NEO-PI-R). Those candidates who failed in basic aptitude testing showed higher levels of Neuroticism (M = 49.8) than the candidates who passed that phase (M = 45.4 and M = 41.6). Additionally, candidates who failed in basic testing had lower levels of Agreeableness (M = 132.9) than recommended candidates (M = 138.1). TSS scales for Achievement (r = 0.19) and Vitality (r = 0.18) showed a significant correlation with the overall assessment rating given by a panel board after a final interview. Results indicate that a personality profile similar to Helmreich's "Right Stuff" is beneficial in astronaut selection. Influences of test anxiety on performance are discussed. Mittelstädt JM, Pecena Y, Oubaid V, Maschke P. Psychometric personality differences between candidates in astronaut selection. Aerosp Med Hum Perform. 2016; 87(11):933-939.

  7. A Genome-Wide Association Study on the Seedless Phenotype in Banana (Musa spp. Reveals the Potential of a Selected Panel to Detect Candidate Genes in a Vegetatively Propagated Crop.

    Directory of Open Access Journals (Sweden)

    Julie Sardos

    Full Text Available Banana (Musa sp. is a vegetatively propagated, low fertility, potentially hybrid and polyploid crop. These qualities make the breeding and targeted genetic improvement of this crop a difficult and long process. The Genome-Wide Association Study (GWAS approach is becoming widely used in crop plants and has proven efficient to detecting candidate genes for traits of interest, especially in cereals. GWAS has not been applied yet to a vegetatively propagated crop. However, successful GWAS in banana would considerably help unravel the genomic basis of traits of interest and therefore speed up this crop improvement. We present here a dedicated panel of 105 accessions of banana, freely available upon request, and their corresponding GBS data. A set of 5,544 highly reliable markers revealed high levels of admixture in most accessions, except for a subset of 33 individuals from Papua. A GWAS on the seedless phenotype was then successfully applied to the panel. By applying the Mixed Linear Model corrected for both kinship and structure as implemented in TASSEL, we detected 13 candidate genomic regions in which we found a number of genes potentially linked with the seedless phenotype (i.e. parthenocarpy combined with female sterility. An additional GWAS performed on the unstructured Papuan subset composed of 33 accessions confirmed six of these regions as candidate. Out of both sets of analyses, one strong candidate gene for female sterility, a putative orthologous gene to Histidine Kinase CKI1, was identified. The results presented here confirmed the feasibility and potential of GWAS when applied to small sets of banana accessions, at least for traits underpinned by a few loci. As phenotyping in banana is extremely space and time-consuming, this latest finding is of particular importance in the context of banana improvement.

  8. A Genome-Wide Association Study on the Seedless Phenotype in Banana (Musa spp.) Reveals the Potential of a Selected Panel to Detect Candidate Genes in a Vegetatively Propagated Crop.

    Science.gov (United States)

    Sardos, Julie; Rouard, Mathieu; Hueber, Yann; Cenci, Alberto; Hyma, Katie E; van den Houwe, Ines; Hribova, Eva; Courtois, Brigitte; Roux, Nicolas

    2016-01-01

    Banana (Musa sp.) is a vegetatively propagated, low fertility, potentially hybrid and polyploid crop. These qualities make the breeding and targeted genetic improvement of this crop a difficult and long process. The Genome-Wide Association Study (GWAS) approach is becoming widely used in crop plants and has proven efficient to detecting candidate genes for traits of interest, especially in cereals. GWAS has not been applied yet to a vegetatively propagated crop. However, successful GWAS in banana would considerably help unravel the genomic basis of traits of interest and therefore speed up this crop improvement. We present here a dedicated panel of 105 accessions of banana, freely available upon request, and their corresponding GBS data. A set of 5,544 highly reliable markers revealed high levels of admixture in most accessions, except for a subset of 33 individuals from Papua. A GWAS on the seedless phenotype was then successfully applied to the panel. By applying the Mixed Linear Model corrected for both kinship and structure as implemented in TASSEL, we detected 13 candidate genomic regions in which we found a number of genes potentially linked with the seedless phenotype (i.e. parthenocarpy combined with female sterility). An additional GWAS performed on the unstructured Papuan subset composed of 33 accessions confirmed six of these regions as candidate. Out of both sets of analyses, one strong candidate gene for female sterility, a putative orthologous gene to Histidine Kinase CKI1, was identified. The results presented here confirmed the feasibility and potential of GWAS when applied to small sets of banana accessions, at least for traits underpinned by a few loci. As phenotyping in banana is extremely space and time-consuming, this latest finding is of particular importance in the context of banana improvement.

  9. Evaluating candidate reactions to selection practices using organisational justice theory.

    Science.gov (United States)

    Patterson, Fiona; Zibarras, Lara; Carr, Victoria; Irish, Bill; Gregory, Simon

    2011-03-01

    This study aimed to examine candidate reactions to selection practices in postgraduate medical training using organisational justice theory. We carried out three independent cross-sectional studies using samples from three consecutive annual recruitment rounds. Data were gathered from candidates applying for entry into UK general practice (GP) training during 2007, 2008 and 2009. Participants completed an evaluation questionnaire immediately after the short-listing stage and after the selection centre (interview) stage. Participants were doctors applying for GP training in the UK. Main outcome measures were participants' evaluations of the selection methods and perceptions of the overall fairness of each selection stage (short-listing and selection centre). A total of 23,855 evaluation questionnaires were completed (6893 in 2007, 10,497 in 2008 and 6465 in 2009). Absolute levels of perceptions of fairness of all the selection methods at both the short-listing and selection centre stages were consistently high over the 3years. Similarly, all selection methods were considered to be job-related by candidates. However, in general, candidates considered the selection centre stage to be significantly fairer than the short-listing stage. Of all the selection methods, the simulated patient consultation completed at the selection centre stage was rated as the most job-relevant. This is the first study to use a model of organisational justice theory to evaluate candidate reactions during selection into postgraduate specialty training. The high-fidelity selection methods are consistently viewed as more job-relevant and fairer by candidates. This has important implications for the design of recruitment systems for all specialties and, potentially, for medical school admissions. Using this approach, recruiters can systematically compare perceptions of the fairness and job relevance of various selection methods. © Blackwell Publishing Ltd 2011.

  10. Intersectionality, Recruitment and Selection : Ethnic Minority Candidates in Dutch Parties

    NARCIS (Netherlands)

    Mügge, L.M.

    2016-01-01

    This article aims to contribute to explanations why ethnic minority women outnumber ethnic minority men in national parliaments of European immigration countries. Extending the intersectional lens it asks: which ethnic minority candidates are recruited and selected? Drawing on nine elections

  11. An annotated history of container candidate material selection

    International Nuclear Information System (INIS)

    McCright, R.D.

    1988-07-01

    This paper documents events in the Nevada Nuclear Waste Storage Investigations (NNWSI) Project that have influenced the selection of metals and alloys proposed for fabrication of waste package containers for permanent disposal of high-level nuclear waste in a repository at Yucca Mountain, Nevada. The time period from 1981 to 1988 is covered in this annotated history. The history traces the candidate materials that have been considered at different stages of site characterization planning activities. At present, six candidate materials are considered and described in the 1988 Consultation Draft of the NNWSI Site Characterization Plan (SCP). The six materials are grouped into two alloy families, copper-base materials and iron to nickel-base materials with an austenitic structure. The three austenitic candidates resulted from a 1983 survey of a longer list of candidate materials; the other three candidates resulted from a special request from DOE in 1984 to evaluate copper and copper-base alloys. 24 refs., 2 tabs

  12. Reintroducing resurrected species: selecting DeExtinction candidates.

    Science.gov (United States)

    Seddon, Philip J; Moehrenschlager, Axel; Ewen, John

    2014-03-01

    Technological advances have raised the controversial prospect of resurrecting extinct species. Species DeExtinction should involve more than the production of biological orphans to be scrutinized in the laboratory or zoo. If DeExtinction is to realize its stated goals of deep ecological enrichment, then resurrected animals must be translocated (i.e., released within suitable habitat). Therefore, DeExtinction is a conservation translocation issue and the selection of potential DeExtinction candidates must consider the feasibility and risks associated with reintroduction. The International Union for the Conservation of Nature (IUCN) Guidelines on Reintroductions and Other Conservation Translocations provide a framework for DeExtinction candidate selection. We translate these Guidelines into ten questions to be addressed early on in the selection process to eliminate unsuitable reintroduction candidates. We apply these questions to the thylacine, Yangtze River Dolphin, and Xerces blue butterfly. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  14. Evaluation and selection of candidate high-level waste forms

    International Nuclear Information System (INIS)

    1982-03-01

    Seven candidate waste forms being developed under the direction of the Department of Energy's National High-Level Waste (HLW) Technology Program, were evaluated as potential media for the immobilization and geologic disposal of high-level nuclear wastes. The evaluation combined preliminary waste form evaluations conducted at DOE defense waste-sites and independent laboratories, peer review assessments, a product performance evaluation, and a processability analysis. Based on the combined results of these four inputs, two of the seven forms, borosilicate glass and a titanate based ceramic, SYNROC, were selected as the reference and alternative forms for continued development and evaluation in the National HLW Program. Both the glass and ceramic forms are viable candidates for use at each of the DOE defense waste-sites; they are also potential candidates for immobilization of commercial reprocessing wastes. This report describes the waste form screening process, and discusses each of the four major inputs considered in the selection of the two forms

  15. Properties of optically selected BL Lacertae candidates from the SDSS

    Science.gov (United States)

    Kügler, S. D.; Nilsson, K.; Heidt, J.; Esser, J.; Schultz, T.

    2014-09-01

    Context. Deep optical surveys open the avenue for finding large numbers of BL Lac objects that are hard to identify because they lack the unique properties classifying them as such. While radio or X-ray surveys typically reveal dozens of sources, recent compilations based on optical criteria alone have increased the number of BL Lac candidates considerably. However, these compilations are subject to biases and may contain a substantial number of contaminating sources. Aims: In this paper we extend our analysis of 182 optically selected BL Lac object candidates from the SDSS with respect to an earlier study. The main goal is to determine the number of bona fide BL Lac objects in this sample. Methods: We examine their variability characteristics, determine their broad-band radio-UV spectral energy distributions (SEDs), and search for the presence of a host galaxy. In addition we present new optical spectra for 27 targets with improved signal-to-noise ratio with respect to the SDSS spectra. Results: At least 59% of our targets have shown variability between SDSS DR2 and our observations by more than 0.1-0.27 mag depending on the telescope used. A host galaxy was detected in 36% of our targets. The host galaxy type and luminosities are consistent with earlier studies of BL Lac host galaxies. Simple fits to broad-band SEDs for 104 targets of our sample derived synchrotron peak frequencies between 13.5 ≤ log 10(νpeak) ≤ 16 with a peak at log 10 ~ 14.5. Our new optical spectra do not reveal any new redshift for any of our objects. Thus the sample contains a large number of bona fide BL Lac objects and seems to contain a substantial fraction of intermediate-frequency peaked BL Lacs. Based on observations collected with the NTT on La Silla (Chile) operated by the European Southern Observatory under proposal 082.B-0133.Based on observations collected at the Centro Astronómico Hispano Alemán (CAHA), operated jointly by the Max-Planck-Institut für Astronomie and the

  16. Multilocus analysis reveals three candidate genes for Chinese migraine susceptibility.

    Science.gov (United States)

    An, X-K; Fang, J; Yu, Z-Z; Lin, Q; Lu, C-X; Qu, H-L; Ma, Q-L

    2017-08-01

    Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform. The genotypic and allelic distributions of MEF2D rs2274316 and ASTN2 rs6478241 were significantly different between migraine patients and controls. Univariate and multivariate analysis revealed significant associations of polymorphisms in the MEF2D and ASTN2 genes with migraine susceptibility. MEF2D, PRDM16 and ASTN2 were also found to be associated with migraine without aura (MO) and migraine with family history. And, MEF2D and ASTN2 also served as genetic risk factors for the migraine without family history. The generalized multifactor dimensionality reduction analysis identified that MEF2D and HTR2E constituted the two-factor interaction model. Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially MO, among Chinese patients. It appears that there is no association with serotonin receptor related genes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Preliminary Analysis and Selection of Mooring Solution Candidates

    DEFF Research Database (Denmark)

    Thomsen, Jonas Bjerg; Delaney, Martin

    This report covers a preliminary analysis of mooring solutions candidates for four large floating wave energy converters. The work is part of the EUDP project “Mooring Solutions for Large Wave Energy Converters” and is the outcome of "Work Package 3: Preliminary Analysis". The report further...... compose the "Milestone 4: Report on results of preliminary analysis and selection of final candidates. The report is produced by Aalborg University with input from the partner WECs Floating Power Plant, KNSwing, LEANCON and Wave Dragon. Tension Technology International (TTI) has provided a significant...

  18. Exercise Testing Reveals Everyday Physical Challenges of Bariatric Surgery Candidates.

    Science.gov (United States)

    Creel, David B; Schuh, Leslie M; Newton, Robert L; Stote, Joseph J; Cacucci, Brenda M

    2017-12-01

    Few studies have quantified cardiorespiratory fitness among individuals seeking bariatric surgery. Treadmill testing allows researchers to determine exercise capacity through metabolic equivalents. These findings can assist clinicians in understanding patients' capabilities to carry out various activities of daily living. The purpose of this study was to determine exercise tolerance and the variables associated with fitness, among individuals seeking bariatric surgery. Bariatric surgery candidates completed submaximal treadmill testing and provided ratings of perceived exertion. Each participant also completed questionnaires related to history of exercise, mood, and perceived barriers/benefits of exercise. Over half of participants reported that exercise was "hard to very hard" before reaching 70% of heart rate reserve, and one-third of participants reported that exercise was "moderately hard" at less than 3 metabolic equivalents (light activity). Body mass index and age accounted for the majority of the variance in exercise tolerance, but athletic history, employment status, and perceived health benefits also contributed. Perceived benefit scores were higher than barrier scores. Categories commonly used to describe moderate-intensity exercise (3-6 metabolic equivalents) do not coincide with perceptions of intensity among many bariatric surgery candidates, especially those with a body mass index of 50 or more.

  19. Selection of Lactic Acid Bacteria as Probiotic Candidate for Chicken

    Directory of Open Access Journals (Sweden)

    F. Hamida

    2015-08-01

    Full Text Available Lactic acid bacteria (LAB regarded as safe microorganisms; they can naturally live in gastrointestinal tract, so appropriately used as a probiotic for chicken. This study aimed to select six isolates of LAB (E1223, E3, E4, E5, E7, and E8 to obtain the isolates potentially as probiotic candidate for chicken. The six isolates were derived from spontaneous fermented corn obtained from Laboratory of Animal Biotechnology and Biomedical, PPSHB, Bogor Agricultural University, Indonesia. LAB isolates were tested their susceptibility to antibiotics (bambermycin, erythromycin, chloramphenicol, and tetracycline then were examined in vitro for their tolerance to gastrointestinal pH (2, 3, 4, and 7.2 and 0.5% bile salt condition, antimicrobial activity against Salmonella enteritidis and Enterococcus casseliflavus, and ability to adhere to chicken ileal cells. The results showed the isolates E5, E7, and E8 were sensitive to tetracycline and chloramphenicol, they could survive at pH 2, 3, 4, and 7.2, could survive at 0.5% bile salts, produced antimicrobial activity, and able to adhere to ileal cells (9.40±0.00 Log CFU/cm2 of E8 and were significantly (P<0.05 higher than those of control (5.30±0.14 Log CFU/cm2. In conclusion, this study showed that isolate E8 had better potential compared to isolates E5 and E7 in most in vitro assays as a probiotic candidate for chicken. E5, E7, and E8 were closely related with Pediococcus pentosaceus based on 16S rRNA gene.

  20. Selection of radio pulsar candidates using artificial neural networks

    OpenAIRE

    Eatough, R. P.; Molkenthin, N.; Kramer, M.; Noutsos, A.; Keith, M. J.; Stappers, B. W.; Lyne, A. G.

    2010-01-01

    Radio pulsar surveys are producing many more pulsar candidates than can be inspected by human experts in a practical length of time. Here we present a technique to automatically identify credible pulsar candidates from pulsar surveys using an artificial neural network. The technique has been applied to candidates from a recent re-analysis of the Parkes multi-beam pulsar survey resulting in the discovery of a previously unidentified pulsar.

  1. Selecting Soldiers and Civilians into the U.S. Army Officer Candidate School : Developing Empirical Selection Composites

    Science.gov (United States)

    2014-07-01

    ultimately led to the development of the Officer Selection Battery ( OSB ),4 which was administered to incoming OCS candidates in 1975. The Army...officially authorized the use of the OSB for selecting OCS candidates in 1979, where it remained for a number of years. However, no other selection tool...replaced the OSB for screening OCS candidates after it was dropped from use. The current eligibility requirements for both in-service and

  2. Selection of candidate sites for a LLRW disposal facility in Connecticut

    International Nuclear Information System (INIS)

    Gingerich, Ronald E.; Holeman, George R.; Hileman, James A.

    1992-01-01

    the geographic location of the sites. Three candidate sites were selected by the Board after which the location of the sites was revealed to the Board and, simultaneously, to the local elected officials and the public. (author)

  3. Optimization of Candidate Selection Using Naive Bayes: Case Study in Company X

    Science.gov (United States)

    Kadar, JA; Agustono, D.; Napitupulu, D.

    2018-01-01

    This research was conducted as a decision-making system, and an alternative solution to complete the candidate assessment for a particular position. The human resources (HR) section on company X is responsible and initiative in selecting candidates in accordance with the assessment of their superiors. Selection by using the method of filling out the manager’s assessment questionnaire on the candidate’s subordinate. Three (3) managers have been determined to assess the 11 candidates for subordinates. By using questionnaire of quality classification of human resources and formula naive bayes it will get result which finally grouped using criteria scale as final grouping. The HR department has also determined that what is received is that which meets criteria 5. The result is three (3) candidates who can be proposed as candidates for certain positions in company X, and have met all required calculations. Furthermore the candidate will be given to management as an alternative input data in the selection of candidates.

  4. Spitzer Photometry of WISE-Selected Brown Dwarf and Hyper-Lumninous Infrared Galaxy Candidates

    Science.gov (United States)

    Griffith, Roger L.; Kirkpatrick, J. Davy; Eisenhardt, Peter R. M.; Gelino, Christopher R.; Cushing, Michael C.; Benford, Dominic; Blain, Andrew; Bridge, Carrie R.; Cohen, Martin; Cutri, Roc M.; hide

    2012-01-01

    We present Spitzer 3.6 and 4.5 micrometer photometry and positions for a sample of 1510 brown dwarf candidates identified by the Wide-field Infrared Survey Explorer (WISE) all-sky survey. Of these, 166 have been spectroscopically classified as objects with spectral types M(1), L(7), T(146), and Y(12). Sixteen other objects are non-(sub)stellar in nature. The remainder are most likely distant L and T dwarfs lacking spectroscopic verification, other Y dwarf candidates still awaiting follow-up, and assorted other objects whose Spitzer photometry reveals them to be background sources. We present a catalog of Spitzer photometry for all astrophysical sources identified in these fields and use this catalog to identify seven fainter (4.5 m to approximately 17.0 mag) brown dwarf candidates, which are possibly wide-field companions to the original WISE sources. To test this hypothesis, we use a sample of 919 Spitzer observations around WISE-selected high-redshift hyper-luminous infrared galaxy candidates. For this control sample, we find another six brown dwarf candidates, suggesting that the seven companion candidates are not physically associated. In fact, only one of these seven Spitzer brown dwarf candidates has a photometric distance estimate consistent with being a companion to the WISE brown dwarf candidate. Other than this, there is no evidence for any widely separated (greater than 20 AU) ultra-cool binaries. As an adjunct to this paper, we make available a source catalog of 7.33 x 10(exp 5) objects detected in all of these Spitzer follow-up fields for use by the astronomical community. The complete catalog includes the Spitzer 3.6 and 4.5 m photometry, along with positionally matched B and R photometry from USNO-B; J, H, and Ks photometry from Two Micron All-Sky Survey; and W1, W2, W3, and W4 photometry from the WISE all-sky catalog.

  5. Most of the benefits from genomic selection can be realised by genotyping a proportion of selection candidates

    DEFF Research Database (Denmark)

    Henryon, Mark; Berg, Peer; Sørensen, Anders Christian

    2012-01-01

    allocated to male and female candidates at ratios of 100:0, 75:25, 50:50, 25:75, and 0:100. For genotyped candidates, a direct-genomic value (DGV) was sampled with reliabilities 0.10, 0.50, and 0.90. Ten sires and 300 dams with the highest breeding values after genotyping were selected at each generation......We reasoned that there are diminishing marginal returns from genomic selection as the proportion of genotyped selection candidates is increased and breeding values based on a priori information are used to choose the candidates that are genotyped. We tested this premise by stochastic simulation...... of breeding schemes that resembled those used for pigs. We estimated rates of genetic gain and inbreeding realized by genomic selection in breeding schemes where candidates were phenotyped before genotyping and 0-100% of the candidates were genotyped based on predicted breeding values. Genotypings were...

  6. Quotas and intersectionality: ethnicity and gender in candidate selection

    NARCIS (Netherlands)

    Celis, K.; Erzeel, S.; Mügge, L.; Damstra, A.

    2014-01-01

    Gender equality is not fully realised when it is restricted to ethnic majority men and women. This article examines how gender quotas as a form of equality policy affect ethnic minority groups, in particular, the gender balance among ethnic minority candidates for political office. Our analysis

  7. Candidate high-z protoclusters among the Planck compact sources, as revealed by Herschel-SPIRE

    Science.gov (United States)

    Greenslade, J.; Clements, D. L.; Cheng, T.; De Zotti, G.; Scott, D.; Valiante, E.; Eales, S.; Bremer, M. N.; Dannerbauer, H.; Birkinshaw, M.; Farrah, D.; Harrison, D. L.; Michałowski, M. J.; Valtchanov, I.; Oteo, I.; Baes, M.; Cooray, A.; Negrello, M.; Wang, L.; van der Werf, P.; Dunne, L.; Dye, S.

    2018-05-01

    By determining the nature of all the Planck compact sources within 808.4 deg2 of large Herschel surveys, we have identified 27 candidate protoclusters of dusty star-forming galaxies (DSFGs) that are at least 3σ overdense in either 250, 350, or 500 μm sources. We find roughly half of all the Planck compact sources are resolved by Herschel into multiple discrete objects, with the other half remaining unresolved by Herschel. We find a significant difference between versions of the Planck catalogues, with earlier releases hosting a larger fraction of candidate protoclusters and Galactic cirrus than later releases, which we ascribe to a difference in the filters used in the creation of the three catalogues. We find a surface density of DSFG candidate protoclusters of (3.3 ± 0.7) × 10-2 sources deg-2, in good agreement with previous similar studies. We find that a Planck colour selection of S857/S545 1. Our candidate protoclusters are a factor of 5 times brighter at 353 GHz than expected from simulations, even in the most conservative estimates. Further observations are needed to confirm whether these candidate protoclusters are physical clusters, multiple protoclusters along the line of sight, or chance alignments of unassociated sources.

  8. Integrated bioinformatics analysis reveals key candidate genes and pathways in breast cancer.

    Science.gov (United States)

    Wang, Yuzhi; Zhang, Yi; Huang, Qian; Li, Chengwen

    2018-04-19

    Breast cancer (BC) is the leading malignancy in women worldwide, yet relatively little is known about the genes and signaling pathways involved in BC tumorigenesis and progression. The present study aimed to elucidate potential key candidate genes and pathways in BC. Five gene expression profile data sets (GSE22035, GSE3744, GSE5764, GSE21422 and GSE26910) were downloaded from the Gene Expression Omnibus (GEO) database, which included data from 113 tumorous and 38 adjacent non‑tumorous tissue samples. Differentially expressed genes (DEGs) were identified using t‑tests in the limma R package. These DEGs were subsequently investigated by pathway enrichment analysis and a protein‑protein interaction (PPI) network was constructed. The most significant module from the PPI network was selected for pathway enrichment analysis. In total, 227 DEGs were identified, of which 82 were upregulated and 145 were downregulated. Pathway enrichment analysis results revealed that the upregulated DEGs were mainly enriched in 'cell division', the 'proteinaceous extracellular matrix (ECM)', 'ECM structural constituents' and 'ECM‑receptor interaction', whereas downregulated genes were mainly enriched in 'response to drugs', 'extracellular space', 'transcriptional activator activity' and the 'peroxisome proliferator‑activated receptor signaling pathway'. The PPI network contained 174 nodes and 1,257 edges. DNA topoisomerase 2‑a, baculoviral inhibitor of apoptosis repeat‑containing protein 5, cyclin‑dependent kinase 1, G2/mitotic‑specific cyclin‑B1 and kinetochore protein NDC80 homolog were identified as the top 5 hub genes. Furthermore, the genes in the most significant module were predominantly involved in 'mitotic nuclear division', 'mid‑body', 'protein binding' and 'cell cycle'. In conclusion, the DEGs, relative pathways and hub genes identified in the present study may aid in understanding of the molecular mechanisms underlying BC progression and provide

  9. Recruitment and selection of candidates in the Republic of Serbia

    OpenAIRE

    Simić, Ivana; Marinović-Matović, Ivana

    2013-01-01

    After a theoretical discussion about recruitment and selection, the key phases of the human resources management process, this paper analyzes the recruitment and selection practices in the Republic of Serbia. These practices, further, are compared with the recruitment and selection practices in certain European and non-European countries. The basis of the mentioned analyses is the data obtained from CRANET research, published in 2011.

  10. Innovation in values based public health nursing student selection: A qualitative evaluation of candidate and selection panel member perspectives.

    Science.gov (United States)

    McGraw, Caroline; Abbott, Stephen; Brook, Judy

    2018-02-19

    Values based recruitment emerges from the premise that a high degree of value congruence, or the extent to which an individual's values are similar to those of the health organization in which they work, leads to organizational effectiveness. The aim of this evaluation was to explore how candidates and selection panel members experienced and perceived innovative methods of values based public health nursing student selection. The evaluation was framed by a qualitative exploratory design involving semi-structured interviews and a group exercise. Data were thematically analyzed. Eight semi-structured interviews were conducted with selection panel members. Twenty-two successful candidates took part in a group exercise. The use of photo elicitation interviews and situational judgment questions in the context of selection to a university-run public health nursing educational program was explored. While candidates were ambivalent about the use of photo elicitation interviews, with some misunderstanding the task, selection panel members saw the benefits for improving candidate expression and reducing gaming and deception. Situational interview questions were endorsed by candidates and selection panel members due to their fidelity to real-life problems and the ability of panel members to discern value congruence from candidates' responses. Both techniques offered innovative solutions to candidate selection for entry to the public health nursing education program. © 2018 Wiley Periodicals, Inc.

  11. Assessing the candidate in the selection interview: The role of interviewer’s personality

    Directory of Open Access Journals (Sweden)

    Čerović Sofija

    2018-01-01

    Full Text Available The study explores the relative contribution of interviewers’ personality and interviewers’ ratings of candidate’s personality in predicting interviewers’ ratings of candidate’s job suitability and examines the moderating effect of interviewers’ personality on the relationship between ratings of candidate’s personality and job suitability. Results showed that ratings of candidate’s Big Five personality traits were related to ratings of candidate’s job suitability, as well as were interviewers’ Agreeableness and Extraversion. Interviewers’ Openness and Agreeableness had a moderating effect on the relationship between interviewers’ ratings of candidate’s personality traits and ratings of candidate’s job suitability. Results reveal the role that interviewer’s Agreeableness, Extraversion and Openness play in the assessment of candidate in the selection interview.

  12. Automated corresponding point candidate selection for image registration using wavelet transformation neurla network with rotation invariant inputs and context information about neighboring candidates

    Science.gov (United States)

    Okumura, Hiroshi; Suezaki, Masashi; Sueyasu, Hideki; Arai, Kohei

    2003-03-01

    An automated method that can select corresponding point candidates is developed. This method has the following three features: 1) employment of the RIN-net for corresponding point candidate selection; 2) employment of multi resolution analysis with Haar wavelet transformation for improvement of selection accuracy and noise tolerance; 3) employment of context information about corresponding point candidates for screening of selected candidates. Here, the 'RIN-net' means the back-propagation trained feed-forward 3-layer artificial neural network that feeds rotation invariants as input data. In our system, pseudo Zernike moments are employed as the rotation invariants. The RIN-net has N x N pixels field of view (FOV). Some experiments are conducted to evaluate corresponding point candidate selection capability of the proposed method by using various kinds of remotely sensed images. The experimental results show the proposed method achieves fewer training patterns, less training time, and higher selection accuracy than conventional method.

  13. RNA deep sequencing reveals novel candidate genes and polymorphisms in boar testis and liver tissues with divergent androstenone levels.

    Directory of Open Access Journals (Sweden)

    Asep Gunawan

    Full Text Available Boar taint is an unpleasant smell and taste of pork meat derived from some entire male pigs. The main causes of boar taint are the two compounds androstenone (5α-androst-16-en-3-one and skatole (3-methylindole. It is crucial to understand the genetic mechanism of boar taint to select pigs for lower androstenone levels and thus reduce boar taint. The aim of the present study was to investigate transcriptome differences in boar testis and liver tissues with divergent androstenone levels using RNA deep sequencing (RNA-Seq. The total number of reads produced for each testis and liver sample ranged from 13,221,550 to 33,206,723 and 12,755,487 to 46,050,468, respectively. In testis samples 46 genes were differentially regulated whereas 25 genes showed differential expression in the liver. The fold change values ranged from -4.68 to 2.90 in testis samples and -2.86 to 3.89 in liver samples. Differentially regulated genes in high androstenone testis and liver samples were enriched in metabolic processes such as lipid metabolism, small molecule biochemistry and molecular transport. This study provides evidence for transcriptome profile and gene polymorphisms of boars with divergent androstenone level using RNA-Seq technology. Digital gene expression analysis identified candidate genes in flavin monooxygenease family, cytochrome P450 family and hydroxysteroid dehydrogenase family. Moreover, polymorphism and association analysis revealed mutation in IRG6, MX1, IFIT2, CYP7A1, FMO5 and KRT18 genes could be potential candidate markers for androstenone levels in boars. Further studies are required for proving the role of candidate genes to be used in genomic selection against boar taint in pig breeding programs.

  14. Transcriptome and proteome data reveal candidate genes for pollinator attraction in sexually deceptive orchids.

    Science.gov (United States)

    Sedeek, Khalid E M; Qi, Weihong; Schauer, Monica A; Gupta, Alok K; Poveda, Lucy; Xu, Shuqing; Liu, Zhong-Jian; Grossniklaus, Ueli; Schiestl, Florian P; Schlüter, Philipp M

    2013-01-01

    Sexually deceptive orchids of the genus Ophrys mimic the mating signals of their pollinator females to attract males as pollinators. This mode of pollination is highly specific and leads to strong reproductive isolation between species. This study aims to identify candidate genes responsible for pollinator attraction and reproductive isolation between three closely related species, O. exaltata, O. sphegodes and O. garganica. Floral traits such as odour, colour and morphology are necessary for successful pollinator attraction. In particular, different odour hydrocarbon profiles have been linked to differences in specific pollinator attraction among these species. Therefore, the identification of genes involved in these traits is important for understanding the molecular basis of pollinator attraction by sexually deceptive orchids. We have created floral reference transcriptomes and proteomes for these three Ophrys species using a combination of next-generation sequencing (454 and Solexa), Sanger sequencing, and shotgun proteomics (tandem mass spectrometry). In total, 121 917 unique transcripts and 3531 proteins were identified. This represents the first orchid proteome and transcriptome from the orchid subfamily Orchidoideae. Proteome data revealed proteins corresponding to 2644 transcripts and 887 proteins not observed in the transcriptome. Candidate genes for hydrocarbon and anthocyanin biosynthesis were represented by 156 and 61 unique transcripts in 20 and 7 genes classes, respectively. Moreover, transcription factors putatively involved in the regulation of flower odour, colour and morphology were annotated, including Myb, MADS and TCP factors. Our comprehensive data set generated by combining transcriptome and proteome technologies allowed identification of candidate genes for pollinator attraction and reproductive isolation among sexually deceptive orchids. This includes genes for hydrocarbon and anthocyanin biosynthesis and regulation, and the development of

  15. Exomic sequencing of immune-related genes reveals novel candidate variants associated with alopecia universalis.

    Directory of Open Access Journals (Sweden)

    Seungbok Lee

    Full Text Available Alopecia areata (AA is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p<1.92×10(-3. Linkage disequilibrium was observed between some of the most significant SNPs, including rs41559420 of HLA-DRB5 (p<0.001, OR 44.57 and rs28362679 of BTNL2 (p<0.001, OR 30.21. While BTNL2 was reported as a general susceptibility gene of AA previously, HLA-DRB5 has not been implicated in AA. In addition, we found several genetic variants in novel genes (HLA-DMB, TLR1, and PMS2 and discovered an additional locus on HLA-A, a known susceptibility gene of AA. This study provides further evidence for the association of previously reported genes with AA and novel findings such as HLA-DRB5, which might represent a hidden culprit gene for AU.

  16. Selection of Possible Candidate Area for Nuclear Power Plant in Johor, Malaysia

    International Nuclear Information System (INIS)

    Nor Afifah Basri; Ahmad Termizi Ramli

    2012-01-01

    Nuclear power is considered as one of the best option for future energy development in Malaysia. Since Malaysia has no experience in nuclear energy generation, commissioning the first nuclear power plant needs tremendous effort in various aspects. Site selection is one of important step in nuclear power plant commissioning process. This paper proposes candidate sites for nuclear power plant in Mersing, Kota Tinggi, Muar and Batu Pahat district in Johor, Malaysia. The candidate selection process uses the IAEA document and AELB guideline as main reference, supported by site selection procedure by various countries. MapInfo Professional software was used to simulate the selection process for candidate areas for the nuclear power plant. This paper concluded that Tenggaroh and Jemaluang area are the most suitable area for nuclear power plant facilities in Johor, Malaysia. (Author)

  17. Selection of possible candidate area for nuclear energy facility in Johor, Malaysia

    International Nuclear Information System (INIS)

    Nor Afifah Basri; Ahmad Termizi Ramli

    2012-01-01

    Nuclear power is considered as one of the best option for future energy development in Malaysia. Since Malaysia has no experience in nuclear energy generation, commissioning the first nuclear power plant needs tremendous effort in various aspects. Site selection is one of important step in nuclear power plant commissioning process. This paper proposes candidate sites for nuclear power plant in Mersing, Kota Tinggi, Muar and Batu Pahat district in Johor, Malaysia. The candidate selection process uses the IAEA document and AELB guideline as main reference, supported by site selection procedure by various countries. MapInfo Professional software was used to stimulate the selection process for candidate areas for the nuclear power plant. This paper concluded that Tenggaroh and Jemaluang area are the most suitable area for nuclear power plant facilities in Johor, Malaysia. (Author)

  18. Dealing with differences: The impact of perceived diversity outcomes on selection and assessment of minority candidates

    NARCIS (Netherlands)

    Hofhuis, J.; van der Zee, K.I.; Otten, S.

    2016-01-01

    Although many strategies have been employed to specifically recruit and select minority employees, the selection rates for designated minority groups are often lower than those for the majority group. Minority candidates with high cultural maintenance (CM) are particularly vulnerable to cultural

  19. Dealing with differences : the impact of perceived diversity outcomes on selection and assessment of minority candidates

    NARCIS (Netherlands)

    Hofhuis, Joep; van der Zee, Karen I.; Otten, Sabine

    2016-01-01

    Although many strategies have been employed to specifically recruit and select minority employees, the selection rates for designated minority groups are often lower than those for the majority group. Minority candidates with high cultural maintenance (CM) are particularly vulnerable to cultural

  20. Combined Analysis of the Fruit Metabolome and Transcriptome Reveals Candidate Genes Involved in Flavonoid Biosynthesis in Actinidia arguta.

    Science.gov (United States)

    Li, Yukuo; Fang, Jinbao; Qi, Xiujuan; Lin, Miaomiao; Zhong, Yunpeng; Sun, Leiming; Cui, Wen

    2018-05-15

    To assess the interrelation between the change of metabolites and the change of fruit color, we performed a combined metabolome and transcriptome analysis of the flesh in two different Actinidia arguta cultivars: "HB" ("Hongbaoshixing") and "YF" ("Yongfengyihao") at two different fruit developmental stages: 70d (days after full bloom) and 100d (days after full bloom). Metabolite and transcript profiling was obtained by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometer and high-throughput RNA sequencing, respectively. The identification and quantification results of metabolites showed that a total of 28,837 metabolites had been obtained, of which 13,715 were annotated. In comparison of HB100 vs. HB70, 41 metabolites were identified as being flavonoids, 7 of which, with significant difference, were identified as bracteatin, luteolin, dihydromyricetin, cyanidin, pelargonidin, delphinidin and (-)-epigallocatechin. Association analysis between metabolome and transcriptome revealed that there were two metabolic pathways presenting significant differences during fruit development, one of which was flavonoid biosynthesis, in which 14 structural genes were selected to conduct expression analysis, as well as 5 transcription factor genes obtained by transcriptome analysis. RT-qPCR results and cluster analysis revealed that AaF3H , AaLDOX , AaUFGT , AaMYB , AabHLH , and AaHB2 showed the best possibility of being candidate genes. A regulatory network of flavonoid biosynthesis was established to illustrate differentially expressed candidate genes involved in accumulation of metabolites with significant differences, inducing red coloring during fruit development. Such a regulatory network linking genes and flavonoids revealed a system involved in the pigmentation of all-red-fleshed and all-green-fleshed A. arguta , suggesting this conjunct analysis approach is not only useful in understanding the relationship between genotype and phenotype

  1. Genetic mapping reveals a candidate gene (ClFS1) for fruit shape in watermelon (Citrullus lanatus L.).

    Science.gov (United States)

    Dou, Junling; Zhao, Shengjie; Lu, Xuqiang; He, Nan; Zhang, Lei; Ali, Aslam; Kuang, Hanhui; Liu, Wenge

    2018-04-01

    A 159 bp deletion in ClFS1 gene encoding IQD protein is responsible for fruit shape in watermelon. Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is known for its rich diversity in fruit size and shape. Fruit shape has been one of the major objectives of watermelon breeding. However, the candidate genes and the underlying genetic mechanism for such an important trait in watermelon are unknown. In this study, we identified a locus on chromosome 3 of watermelon genome controlling fruit shape. Segregation analysis in F 2 and BC 1 populations derived from a cross between two inbred lines "Duan125" (elongate fruit) and "Zhengzhouzigua" (spherical fruit) suggests that fruit shape of watermelon is controlled by a single locus and elongate fruit (OO) is incompletely dominant to spherical fruit (oo) with the heterozygote (Oo) being oval fruit. GWAS profiles among 315 accessions identified a major locus designated on watermelon chromosome 3, which was confirmed by BSA-seq mapping in the F 2 population. The candidate gene was mapped to a region 46 kb on chromosome 3. There were only four genes present in the corresponding region in the reference genome. Four candidate genes were sequenced in this region, revealing that the CDS of Cla011257 had a 159 bp deletion which resulted in the omission of 53 amino acids in elongate watermelon. An indel marker was derived from the 159 bp deletion to test the F 2 population and 105 watermelon accessions. The results showed that Cla011257 cosegregated with watermelon fruit shape. In addition, the Cla011257 expression was the highest at ovary formation stage. The predicted protein of the Cla011257 gene fitted in IQD protein family which was reported to have association with cell arrays and Ca 2+ -CaM signaling modules. Clear understanding of the genes facilitating the fruit shape along with marker association selection will be an effective way to develop new cultivars.

  2. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage

    2014-01-01

    Residual feed intake (RFI) is a complex trait that is economically important for livestock production; however, the genetic and biological mechanisms regulating RFI are largely unknown in pigs. Therefore, the study aimed to identify single nucleotide polymorphisms (SNPs), candidate genes and biol...... revealed key genes and genetic variants that control feed efficiency that could potentially be useful for genetic selection of more feed efficient pigs....

  3. Gene expression profiling reveals candidate genes related to residual feed intake in duodenum of laying ducks.

    Science.gov (United States)

    Zeng, T; Huang, L; Ren, J; Chen, L; Tian, Y; Huang, Y; Zhang, H; Du, J; Lu, L

    2017-12-01

    Feed represents two-thirds of the total costs of poultry production, especially in developing countries. Improvement in feed efficiency would reduce the amount of feed required for production (growth or laying), the production cost, and the amount of nitrogenous waste. The most commonly used measures for feed efficiency are feed conversion ratio (FCR) and residual feed intake (RFI). As a more suitable indicator assessing feed efficiency, RFI is defined as the difference between observed and expected feed intake based on maintenance and growth or laying. However, the genetic and biological mechanisms regulating RFI are largely unknown. Identifying molecular mechanisms explaining divergence in RFI in laying ducks would lead to the development of early detection methods for the selection of more efficient breeding poultry. The objective of this study was to identify duodenum genes and pathways through transcriptional profiling in 2 extreme RFI phenotypes (HRFI and LRFI) of the duck population. Phenotypic aspects of feed efficiency showed that RFI was strongly positive with FCR and feed intake (FI). Transcriptomic analysis identified 35 differentially expressed genes between LRFI and HRFI ducks. These genes play an important role in metabolism, digestibility, secretion, and innate immunity including (), (), (), β (), and (). These results improve our knowledge of the biological basis underlying RFI, which would be useful for further investigations of key candidate genes for RFI and for the development of biomarkers.

  4. Westerbork Synthesis Radio Telescope HI Imaging of HI-selected Local Group Galaxy Candidates

    Science.gov (United States)

    Adams, Elizabeth A.; Cannon, J. M.; Oosterloo, T.; Giovanelli, R.; Haynes, M. P.

    2014-01-01

    The paucity of low mass galaxies in the Universe is a long-standing problem. We recently presented a set of isolated ultra-compact high velocity clouds (UCHVCs) identified within the dataset of the Arecibo Legacy Fast ALFA (ALFALFA) HI line survey that are consistent with representing low mass gas-bearing dark matter halos within the Local Group (Adams et al. 2013). At distances of ~1 Mpc, the UCHVCs have HI masses of ~10^5 Msun and indicative dynamical masses of ~10^7 Msun. The HI diameters of the UCHVCs range from 4' to 20', or 1 to 6 kpc at a distance of 1 Mpc. We have selected the most compact and isolated UCHVCs with the highest average column densities as representing the best galaxy candidates. Seven of these systems have been observed with WSRT to enable higher spatial resolution 40-60") studies of the HI distribution. The HI morphology revealed by the WSRT data offers clues to the environment of the UCHVCs, and velocity fields allow the underlying mass distribution to be constrained. The Cornell ALFALFA team is supported by NSF AST-1107390 and by the Brinson Foundation. JMC is supported by NSF grant AST-1211683.

  5. Selection of candidate plus phenotypes of Jatropha curcas L. using method of paired comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, D.K. [Silviculture Division, Arid Forest Research Institute, P.O. Krishi Mandi, New Pali Road, Jodhpur 342005, Rajasthan (India)

    2009-03-15

    Jatropha curcas L. (Euphorbiaceae) is an oil bearing species with multiple uses and considerable potential as a biodiesel crop. The present communication deals with the method of selecting plus phenotypes of J. curcas for exploiting genetic variability for further improvement. Candidate plus tree selection is the first and most important stage in any tree improvement programme. The selection of candidate plus plants (CPPs) is based upon various important attributes associated with the species and their relative ranking. Relative preference between various traits and scoring for each trait has been worked out by using the method of paired comparisons for the selection of CPP in J. curcas L. The most important ones are seed and oil yields. (author)

  6. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study

    NARCIS (Netherlands)

    K. ten Haaf (Kevin); J. Jeon (Jihyoun); M.C. Tammemagi (Martin); S.S. Han (Summer); C.Y. Kong (Chung Yin); S.K. Plevritis (Sylvia); E. Feuer (Eric); H.J. de Koning (Harry); E.W. Steyerberg (Ewout W.); R. Meza (Rafael)

    2017-01-01

    textabstractBackground: Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years). Nine previously established risk models were assessed for their ability to identify those most

  7. Deep Learning Questions Can Help Selection of High Ability Candidates for Universities

    Science.gov (United States)

    Mellanby, Jane; Cortina-Borja, Mario; Stein, John

    2009-01-01

    Selection of students for places at universities mainly depends on GCSE grades and predictions of A-level grades, both of which tend to favour applicants from independent schools. We have therefore developed a new type of test that would measure candidates' "deep learning" approach since this assesses the motivation and creative thinking…

  8. Plant operator selection system for evaluating employment candidates' potential for success in electric power plant operations positions

    International Nuclear Information System (INIS)

    Dunnette, M.D.

    1982-01-01

    The Plant Operator Selection System is a battery of tests and questionnaires that can be administered to job candidates in less than three hours. Various components of the battery measure what a job candidate has accomplished in previous educational and work situations, how well a candidate compares with others on a number of important aptitudes or abilities, and whether or not a candidate possesses the kind of personal stability required in power plant operations positions. A job candidate's answers to the tests and questionnaires of the Plant Operator Selection System are scored and converted to an OVERALL POTENTIAL INDEX. Values of the OVERALL POTENTIAL INDEX [OPI] range between 0 and 15. Candidates with high OPI values are much more likely to become effective and successful plant operators than candidates with low OPI values. It is possible to estimate the financial advantages to a company of using the Plant Operator Selection System in evaluating candidates for plant operations jobs

  9. Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks.

    Science.gov (United States)

    Saik, Olga V; Demenkov, Pavel S; Ivanisenko, Timofey V; Bragina, Elena Yu; Freidin, Maxim B; Goncharova, Irina A; Dosenko, Victor E; Zolotareva, Olga I; Hofestaedt, Ralf; Lavrik, Inna N; Rogaev, Evgeny I; Ivanisenko, Vladimir A

    2018-02-13

    Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or ~ 22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension - 713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in

  10. Exploring factors contributing to voluntarily withdrawal by candidates during South African operational forces selection

    CSIR Research Space (South Africa)

    Van Heerden, A

    2016-11-01

    Full Text Available context affecting expectancies for control of reinforcement. Cognitive Therapy and Research, 6(4), 409-427. Eskreis-Winkler, L., Shulman, E. P., Beal, S. A., & Duckworth, A. L. (2014). The grit effect: Predicting retention in the military, the workplace... suitability and PT tests. Approximately 41% of candidates invited to attend the pre-selection preparation phase are lost. The Pre-selection Preparation phase entails medical and physical as well as psychological (personality and cognitive) measurements...

  11. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Ma Menggen

    2010-06-01

    Full Text Available Abstract Background Derived from our lignocellulosic conversion inhibitor-tolerant yeast, we generated an ethanol-tolerant strain Saccharomyces cerevisiae NRRL Y-50316 by enforced evolutionary adaptation. Using a newly developed robust mRNA reference and a master equation unifying gene expression data analyses, we investigated comparative quantitative transcription dynamics of 175 genes selected from previous studies for an ethanol-tolerant yeast and its closely related parental strain. Results A highly fitted master equation was established and applied for quantitative gene expression analyses using pathway-based qRT-PCR array assays. The ethanol-tolerant Y-50316 displayed significantly enriched background of mRNA abundance for at least 35 genes without ethanol challenge compared with its parental strain Y-50049. Under the ethanol challenge, the tolerant Y-50316 responded in consistent expressions over time for numerous genes belonging to groups of heat shock proteins, trehalose metabolism, glycolysis, pentose phosphate pathway, fatty acid metabolism, amino acid biosynthesis, pleiotropic drug resistance gene family and transcription factors. The parental strain showed repressed expressions for many genes and was unable to withstand the ethanol stress and establish a viable culture and fermentation. The distinct expression dynamics between the two strains and their close association with cell growth, viability and ethanol fermentation profiles distinguished the tolerance-response from the stress-response in yeast under the ethanol challenge. At least 82 genes were identified as candidate and key genes for ethanol-tolerance and subsequent fermentation under the stress. Among which, 36 genes were newly recognized by the present study. Most of the ethanol-tolerance candidate genes were found to share protein binding motifs of transcription factors Msn4p/Msn2p, Yap1p, Hsf1p and Pdr1p/Pdr3p. Conclusion Enriched background of transcription abundance

  12. Classic selective sweeps revealed by massive sequencing in cattle.

    Directory of Open Access Journals (Sweden)

    Saber Qanbari

    2014-02-01

    Full Text Available Human driven selection during domestication and subsequent breed formation has likely left detectable signatures within the genome of modern cattle. The elucidation of these signatures of selection is of interest from the perspective of evolutionary biology, and for identifying domestication-related genes that ultimately may help to further genetically improve this economically important animal. To this end, we employed a panel of more than 15 million autosomal SNPs identified from re-sequencing of 43 Fleckvieh animals. We mainly applied two somewhat complementary statistics, the integrated Haplotype Homozygosity Score (iHS reflecting primarily ongoing selection, and the Composite of Likelihood Ratio (CLR having the most power to detect completed selection after fixation of the advantageous allele. We find 106 candidate selection regions, many of which are harboring genes related to phenotypes relevant in domestication, such as coat coloring pattern, neurobehavioral functioning and sensory perception including KIT, MITF, MC1R, NRG4, Erbb4, TMEM132D and TAS2R16, among others. To further investigate the relationship between genes with signatures of selection and genes identified in QTL mapping studies, we use a sample of 3062 animals to perform four genome-wide association analyses using appearance traits, body size and somatic cell count. We show that regions associated with coat coloring significantly (P<0.0001 overlap with the candidate selection regions, suggesting that the selection signals we identify are associated with traits known to be affected by selection during domestication. Results also provide further evidence regarding the complexity of the genetics underlying coat coloring in cattle. This study illustrates the potential of population genetic approaches for identifying genomic regions affecting domestication-related phenotypes and further helps to identify specific regions targeted by selection during speciation, domestication and

  13. Fine Mapping and Transcriptome Analysis Reveal Candidate Genes Associated with Hybrid Lethality in Cabbage (Brassica Oleracea).

    Science.gov (United States)

    Xiao, Zhiliang; Hu, Yang; Zhang, Xiaoli; Xue, Yuqian; Fang, Zhiyuan; Yang, Limei; Zhang, Yangyong; Liu, Yumei; Li, Zhansheng; Liu, Xing; Liu, Zezhou; Lv, Honghao; Zhuang, Mu

    2017-06-05

    Hybrid lethality is a deleterious phenotype that is vital to species evolution. We previously reported hybrid lethality in cabbage ( Brassica oleracea ) and performed preliminary mapping of related genes. In the present study, the fine mapping of hybrid lethal genes revealed that BoHL1 was located on chromosome C1 between BoHLTO124 and BoHLTO130, with an interval of 101 kb. BoHL2 was confirmed to be between insertion-deletion (InDels) markers HL234 and HL235 on C4, with a marker interval of 70 kb. Twenty-eight and nine annotated genes were found within the two intervals of BoHL1 and BoHL2 , respectively. We also applied RNA-Seq to analyze hybrid lethality in cabbage. In the region of BoHL1 , seven differentially expressed genes (DEGs) and five resistance (R)-related genes (two in common, i.e., Bo1g153320 and Bo1g153380 ) were found, whereas in the region of BoHL2 , two DEGs and four R-related genes (two in common, i.e., Bo4g173780 and Bo4g173810 ) were found. Along with studies in which R genes were frequently involved in hybrid lethality in other plants, these interesting R-DEGs may be good candidates associated with hybrid lethality. We also used SNP/InDel analyses and quantitative real-time PCR to confirm the results. This work provides new insight into the mechanisms of hybrid lethality in cabbage.

  14. QTL mapping and transcriptome analysis of cowpea reveals candidate genes for root-knot nematode resistance.

    Science.gov (United States)

    Santos, Jansen Rodrigo Pereira; Ndeve, Arsenio Daniel; Huynh, Bao-Lam; Matthews, William Charles; Roberts, Philip Alan

    2018-01-01

    Cowpea is one of the most important food and forage legumes in drier regions of the tropics and subtropics. However, cowpea yield worldwide is markedly below the known potential due to abiotic and biotic stresses, including parasitism by root-knot nematodes (Meloidogyne spp., RKN). Two resistance genes with dominant effect, Rk and Rk2, have been reported to provide resistance against RKN in cowpea. Despite their description and use in breeding for resistance to RKN and particularly genetic mapping of the Rk locus, the exact genes conferring resistance to RKN remain unknown. In the present work, QTL mapping using recombinant inbred line (RIL) population 524B x IT84S-2049 segregating for a newly mapped locus and analysis of the transcriptome changes in two cowpea near-isogenic lines (NIL) were used to identify candidate genes for Rk and the newly mapped locus. A major QTL, designated QRk-vu9.1, associated with resistance to Meloidogyne javanica reproduction, was detected and mapped on linkage group LG9 at position 13.37 cM using egg production data. Transcriptome analysis on resistant and susceptible NILs 3 and 9 days after inoculation revealed up-regulation of 109 and 98 genes and down-regulation of 110 and 89 genes, respectively, out of 19,922 unique genes mapped to the common bean reference genome. Among the differentially expressed genes, four and nine genes were found within the QRk-vu9.1 and QRk-vu11.1 QTL intervals, respectively. Six of these genes belong to the TIR-NBS-LRR family of resistance genes and three were upregulated at one or more time-points. Quantitative RT-PCR validated gene expression to be positively correlated with RNA-seq expression pattern for eight genes. Future functional analysis of these cowpea genes will enhance our understanding of Rk-mediated resistance and identify the specific gene responsible for the resistance.

  15. Dynamic compression of chondrocyte-agarose constructs reveals new candidate mechanosensitive genes.

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    Carole Bougault

    Full Text Available Articular cartilage is physiologically exposed to repeated loads. The mechanical properties of cartilage are due to its extracellular matrix, and homeostasis is maintained by the sole cell type found in cartilage, the chondrocyte. Although mechanical forces clearly control the functions of articular chondrocytes, the biochemical pathways that mediate cellular responses to mechanical stress have not been fully characterised. The aim of our study was to examine early molecular events triggered by dynamic compression in chondrocytes. We used an experimental system consisting of primary mouse chondrocytes embedded within an agarose hydrogel; embedded cells were pre-cultured for one week and subjected to short-term compression experiments. Using Western blots, we demonstrated that chondrocytes maintain a differentiated phenotype in this model system and reproduce typical chondrocyte-cartilage matrix interactions. We investigated the impact of dynamic compression on the phosphorylation state of signalling molecules and genome-wide gene expression. After 15 min of dynamic compression, we observed transient activation of ERK1/2 and p38 (members of the mitogen-activated protein kinase (MAPK pathways and Smad2/3 (members of the canonical transforming growth factor (TGF-β pathways. A microarray analysis performed on chondrocytes compressed for 30 min revealed that only 20 transcripts were modulated more than 2-fold. A less conservative list of 325 modulated genes included genes related to the MAPK and TGF-β pathways and/or known to be mechanosensitive in other biological contexts. Of these candidate mechanosensitive genes, 85% were down-regulated. Down-regulation may therefore represent a general control mechanism for a rapid response to dynamic compression. Furthermore, modulation of transcripts corresponding to different aspects of cellular physiology was observed, such as non-coding RNAs or primary cilium. This study provides new insight into how

  16. QTL mapping and transcriptome analysis of cowpea reveals candidate genes for root-knot nematode resistance.

    Directory of Open Access Journals (Sweden)

    Jansen Rodrigo Pereira Santos

    Full Text Available Cowpea is one of the most important food and forage legumes in drier regions of the tropics and subtropics. However, cowpea yield worldwide is markedly below the known potential due to abiotic and biotic stresses, including parasitism by root-knot nematodes (Meloidogyne spp., RKN. Two resistance genes with dominant effect, Rk and Rk2, have been reported to provide resistance against RKN in cowpea. Despite their description and use in breeding for resistance to RKN and particularly genetic mapping of the Rk locus, the exact genes conferring resistance to RKN remain unknown. In the present work, QTL mapping using recombinant inbred line (RIL population 524B x IT84S-2049 segregating for a newly mapped locus and analysis of the transcriptome changes in two cowpea near-isogenic lines (NIL were used to identify candidate genes for Rk and the newly mapped locus. A major QTL, designated QRk-vu9.1, associated with resistance to Meloidogyne javanica reproduction, was detected and mapped on linkage group LG9 at position 13.37 cM using egg production data. Transcriptome analysis on resistant and susceptible NILs 3 and 9 days after inoculation revealed up-regulation of 109 and 98 genes and down-regulation of 110 and 89 genes, respectively, out of 19,922 unique genes mapped to the common bean reference genome. Among the differentially expressed genes, four and nine genes were found within the QRk-vu9.1 and QRk-vu11.1 QTL intervals, respectively. Six of these genes belong to the TIR-NBS-LRR family of resistance genes and three were upregulated at one or more time-points. Quantitative RT-PCR validated gene expression to be positively correlated with RNA-seq expression pattern for eight genes. Future functional analysis of these cowpea genes will enhance our understanding of Rk-mediated resistance and identify the specific gene responsible for the resistance.

  17. Selection in the dopamine receptor 2 gene: a candidate SNP study

    Directory of Open Access Journals (Sweden)

    Tobias Göllner

    2015-08-01

    Full Text Available Dopamine is a major neurotransmitter in the human brain and is associated with various diseases. Schizophrenia, for example, is treated by blocking the dopamine receptors type 2. Shaner, Miller & Mintz (2004 stated that schizophrenia was the low fitness variant of a highly variable mental trait. We therefore explore whether the dopamine receptor 2 gene (DRD2 underwent any selection processes. We acquired genotype data of the 1,000 Genomes project (phase I, which contains 1,093 individuals from 14 populations. We included single nucleotide polymorphisms (SNPs with two minor allele frequencies (MAFs in the analysis: MAF over 0.05 and over 0.01. This is equivalent to 151 SNPs (MAF > 0.05 and 246 SNPs (MAF > 0.01 for DRD2. We used two different approaches (an outlier approach and a Bayesian approach to detect loci under selection. The combined results of both approaches yielded nine (MAF > 0.05 and two candidate SNPs (MAF > 0.01, under balancing selection. We also found weak signs for directional selection on DRD2, but in our opinion these were too weak to draw any final conclusions on directional selection in DRD2. All candidates for balancing selection are in the intronic region of the gene and only one (rs12574471 has been mentioned in the literature. Two of our candidate SNPs are located in specific regions of the gene: rs80215768 lies within a promoter flanking region and rs74751335 lies within a transcription factor binding site. We strongly encourage research on our candidate SNPs and their possible effects.

  18. The cld mutation: narrowing the critical chromosomal region and selecting candidate genes.

    Science.gov (United States)

    Péterfy, Miklós; Mao, Hui Z; Doolittle, Mark H

    2006-10-01

    Combined lipase deficiency (cld) is a recessive, lethal mutation specific to the tw73 haplotype on mouse Chromosome 17. While the cld mutation results in lipase proteins that are inactive, aggregated, and retained in the endoplasmic reticulum (ER), it maps separately from the lipase structural genes. We have narrowed the gene critical region by about 50% using the tw18 haplotype for deletion mapping and a recombinant chromosome used originally to map cld with respect to the phenotypic marker tf. The region now extends from 22 to 25.6 Mbp on the wild-type chromosome, currently containing 149 genes and 50 expressed sequence tags (ESTs). To identify the affected gene, we have selected candidates based on their known role in associated biological processes, cellular components, and molecular functions that best fit with the predicted function of the cld gene. A secondary approach was based on differences in mRNA levels between mutant (cld/cld) and unaffected (+/cld) cells. Using both approaches, we have identified seven functional candidates with an ER localization and/or an involvement in protein maturation and folding that could explain the lipase deficiency, and six expression candidates that exhibit large differences in mRNA levels between mutant and unaffected cells. Significantly, two genes were found to be candidates with regard to both function and expression, thus emerging as the strongest candidates for cld. We discuss the implications of our mapping results and our selection of candidates with respect to other genes, deletions, and mutations occurring in the cld critical region.

  19. Continuing professional education and the selection of candidates: the case for a tripartite model.

    Science.gov (United States)

    Ellis, L B

    2000-02-01

    This paper argues the case for a tripartite model involving the manager educator and practitioner in the selection of candidates to programmes of continuing professional education (CPE). Nurse educators are said to play a key link in the education practice chain (Pendleton & Myles 1991), yet with the introduction of a market philosophy for education, the educator appears to have little, if any, influence over the selection of CPE candidates. Empirical studies on the value of an effective system for identifying the educational needs of the individual and the locality are unequivocal in specifying the benefits of a collaborative selection process (Larcombe & Maggs 1991). However, there are few studies that offer a model of collaboration and fewer still on how to operationalize such a model. This paper presents the policy and legislative context of CPE leading to the development of a market philosophy. The tension between educational reforms such as life-long learning and diminishing and finite resources are highlighted. These strategic issues provide the backdrop and rationale for considering the process for identifying CPE needs, and the characteristics of an effective system as suggested in the literature. Finally, this paper outlines recommendations for a partnership between the manager practitioner and educationalist in the selection of CPE candidates.

  20. Transcriptome sequencing of Mycosphaerella fijiensis during association with Musa acuminata reveals candidate pathogenicity genes.

    Science.gov (United States)

    Noar, Roslyn D; Daub, Margaret E

    2016-08-30

    Mycosphaerella fijiensis, causative agent of the black Sigatoka disease of banana, is considered the most economically damaging banana disease. Despite its importance, the genetics of pathogenicity are poorly understood. Previous studies have characterized polyketide pathways with possible roles in pathogenicity. To identify additional candidate pathogenicity genes, we compared the transcriptome of this fungus during the necrotrophic phase of infection with that during saprophytic growth in medium. Transcriptome analysis was conducted, and the functions of differentially expressed genes were predicted by identifying conserved domains, Gene Ontology (GO) annotation and GO enrichment analysis, Carbohydrate-Active EnZymes (CAZy) annotation, and identification of genes encoding effector-like proteins. The analysis showed that genes commonly involved in secondary metabolism have higher expression in infected leaf tissue, including genes encoding cytochrome P450s, short-chain dehydrogenases, and oxidoreductases in the 2-oxoglutarate and Fe(II)-dependent oxygenase superfamily. Other pathogenicity-related genes with higher expression in infected leaf tissue include genes encoding salicylate hydroxylase-like proteins, hydrophobic surface binding proteins, CFEM domain-containing proteins, and genes encoding secreted cysteine-rich proteins characteristic of effectors. More genes encoding amino acid transporters, oligopeptide transporters, peptidases, proteases, proteinases, sugar transporters, and proteins containing Domain of Unknown Function (DUF) 3328 had higher expression in infected leaf tissue, while more genes encoding inhibitors of peptidases and proteinases had higher expression in medium. Sixteen gene clusters with higher expression in leaf tissue were identified including clusters for the synthesis of a non-ribosomal peptide. A cluster encoding a novel fusicoccane was also identified. Two putative dispensable scaffolds were identified with a large proportion of

  1. What can the SEDs of first hydrostatic core candidates reveal about their nature?

    Science.gov (United States)

    Young, Alison K.; Bate, Matthew R.; Mowat, Chris F.; Hatchell, Jennifer; Harries, Tim J.

    2018-02-01

    The first hydrostatic core (FHSC) is the first stable object to form in simulations of star formation. This stage has yet to be observed definitively, although several candidate FHSCs have been reported. We have produced synthetic spectral energy distributions (SEDs) from 3D hydrodynamical simulations of pre-stellar cores undergoing gravitational collapse for a variety of initial conditions. Variations in the initial rotation rate, radius and mass lead to differences in the location of the SED peak and far-infrared flux. Secondly, we attempt to fit the SEDs of five FHSC candidates from the literature and five newly identified FHSC candidates located in the Serpens South molecular cloud with simulated SEDs. The most promising FHSC candidates are fitted by a limited number of model SEDs with consistent properties, which suggests that the SED can be useful for placing constraints on the age and rotation rate of the source. The sources we consider most likely to be in FHSC phase are B1-bN, CB17-MMS, Aqu-MM1 and Serpens South candidate K242. We were unable to fit SerpS-MM22, Per-Bolo 58 and Chamaeleon-MMS1 with reasonable parameters, which indicates that they are likely to be more evolved.

  2. Knowledge Discovery in Biological Databases for Revealing Candidate Genes Linked to Complex Phenotypes.

    Science.gov (United States)

    Hassani-Pak, Keywan; Rawlings, Christopher

    2017-06-13

    Genetics and "omics" studies designed to uncover genotype to phenotype relationships often identify large numbers of potential candidate genes, among which the causal genes are hidden. Scientists generally lack the time and technical expertise to review all relevant information available from the literature, from key model species and from a potentially wide range of related biological databases in a variety of data formats with variable quality and coverage. Computational tools are needed for the integration and evaluation of heterogeneous information in order to prioritise candidate genes and components of interaction networks that, if perturbed through potential interventions, have a positive impact on the biological outcome in the whole organism without producing negative side effects. Here we review several bioinformatics tools and databases that play an important role in biological knowledge discovery and candidate gene prioritization. We conclude with several key challenges that need to be addressed in order to facilitate biological knowledge discovery in the future.

  3. Development, evaluation, and selection of candidate high-level waste forms

    International Nuclear Information System (INIS)

    Bernadzikowski, T.A.; Allender, J.S.; Gordon, D.E.; Gould, T.H. Jr.

    1982-01-01

    The seven candidate waste forms, evaluated as potential media for the immobilization and gelogic disposal of high-level nuclear wastes were borosilicate glass, SYNROC, tailored ceramic, high-silica glass, FUETAP concrete, coated sol-gel particles, and glass marbles in a lead matrix. The evaluation, completed on August 1, 1981, combined preliminary waste form evaluations conducted at Department of Energy (DOE) defense waste-sites and at independent laboratories, peer review assessments, a product performance evaluation, and a processability analysis. Based on the combined results of these four inputs, two of the seven forms, borosilicate glass and a titanate-based ceramic, SYNROC, were selected as the reference and alternative forms, respectively, for continued development and evaluation in the National HLW Program. The borosilicate glass and ceramic forms were further compared during FY-1982 on the basis of risk assessments, cost comparisons, properties comparisons, and conformance with proposed regulatory and repository criteria. Both the glass and ceramic forms are viable candidates for use at DOE defense HLW sites; they are also candidates for immobilization of commercial reprocessing wastes. This paper describes the waste form screening process, discusses each of the four major inputs considered in the selection of the two forms in 1981, and presents a brief summary of the comparisons of the two forms during 1982 and the selection process to determine the final form for SRP defense HLW

  4. Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection.

    Science.gov (United States)

    Court, Colin M; Harlander-Locke, Michael P; Markovic, Daniela; French, Samuel W; Naini, Bita V; Lu, David S; Raman, Steven S; Kaldas, Fady M; Zarrinpar, Ali; Farmer, Douglas G; Finn, Richard S; Sadeghi, Saeed; Tomlinson, James S; Busuttil, Ronald W; Agopian, Vatche G

    2017-09-01

    The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (κ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (r s = 0.24; P Liver Transplantation 23 1123-1132 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  5. A Tendon Cell Specific RNAi Screen Reveals Novel Candidates Essential for Muscle Tendon Interaction.

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    Prabhat Tiwari

    Full Text Available Tendons are fibrous connective tissue which connect muscles to the skeletal elements thus acting as passive transmitters of force during locomotion and provide appropriate body posture. Tendon-derived cues, albeit poorly understood, are necessary for proper muscle guidance and attachment during development. In the present study, we used dorsal longitudinal muscles of Drosophila and their tendon attachment sites to unravel the molecular nature of interactions between muscles and tendons. We performed a genetic screen using RNAi-mediated knockdown in tendon cells to find out molecular players involved in the formation and maintenance of myotendinous junction and found 21 candidates out of 2507 RNAi lines screened. Of these, 19 were novel molecules in context of myotendinous system. Integrin-βPS and Talin, picked as candidates in this screen, are known to play important role in the cell-cell interaction and myotendinous junction formation validating our screen. We have found candidates with enzymatic function, transcription activity, cell adhesion, protein folding and intracellular transport function. Tango1, an ER exit protein involved in collagen secretion was identified as a candidate molecule involved in the formation of myotendinous junction. Tango1 knockdown was found to affect development of muscle attachment sites and formation of myotendinous junction. Tango1 was also found to be involved in secretion of Viking (Collagen type IV and BM-40 from hemocytes and fat cells.

  6. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

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    Rajani Rai

    2015-11-01

    Full Text Available Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR and Classification and Regression Tree Analysis (CRT to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634; FAS (rs2234767; FASL (rs763110; DCC (rs2229080, rs4078288, rs7504990, rs714; PSCA (rs2294008, rs2978974; ADRA2A (rs1801253; ADRB1 (rs1800544; ADRB3 (rs4994; CYP17 (rs2486758 involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634, DCC (rs714, rs2229080, rs4078288 and ADRB3 (rs4994 polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994 to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10 or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10. Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

  7. Differing patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens.

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    Christian M Parobek

    2014-04-01

    Full Text Available Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1 (pvmsp-1 and Plasmodium vivax circumsporozoite protein (pvcsp. Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44 and the complete gene of pvcsp (n = 47 from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods to assess for selection and population structure, we found strong evidence of balancing selection in the 42 kDa region of pvmsp-1, which varied significantly over the length of the gene, consistent with immune-mediated selection. In pvcsp, the highly variable central repeat region also showed patterns consistent with immune selection, which were lacking outside the repeat. The patterns of selection seen in both genes differed from their P. falciparum orthologs. In addition, we found that, similar to merozoite antigens from P. falciparum malaria, genetic diversity of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite antigen, pvcsp, showed strong geographic clustering. These findings suggest that while immune selection may act on both vivax vaccine candidate antigens, the geographic distribution of genetic variability differs greatly between these two genes. The selective forces driving this diversification could lead to antigen escape and vaccine failure. Better understanding the geographic distribution of genetic variability in vaccine candidate antigens will be key to designing and implementing efficacious vaccines.

  8. Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer*

    Science.gov (United States)

    Chen, Chien-Lun; Chung, Ting; Wu, Chih-Ching; Ng, Kwai-Fong; Yu, Jau-Song; Tsai, Cheng-Han; Chang, Yu-Sun; Liang, Ying; Tsui, Ke-Hung; Chen, Yi-Ting

    2015-01-01

    More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins—SLC3A2, STMN1, and TAGLN2—in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant

  9. Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb as a novel candidate gene for emotionality in mice.

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    Ludwig Czibere

    Full Text Available Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait "anxiety". We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB or low (LAB anxiety-related behavior, and also show signs of comorbid depression-like behavior. We identified and confirmed sex-independent differences in the basal expression of 13 candidate genes, using tissue from the entire brain, including coronin 7 (Coro7, cathepsin B (Ctsb, muscleblind-like 1 (Mbnl1, metallothionein 1 (Mt1, solute carrier family 25 member 17 (Slc25a17, tribbles homolog 2 (Trib2, zinc finger protein 672 (Zfp672, syntaxin 3 (Stx3, ATP-binding cassette, sub-family A member 2 (Abca2, ectonucleotide pyrophosphatase/phosphodiesterase 5 (Enpp5, high mobility group nucleosomal binding domain 3 (Hmgn3 and pyruvate dehydrogenase beta (Pdhb. Additionally, we confirmed brain region-specific differences in the expression of synaptotagmin 4 (Syt4.Our identification of about 90 polymorphisms in Ctsb suggested that this gene might play a critical role in shaping our mouse model's behavioral endophenotypes. Indeed, the assessment of anxiety-related and depression-like behaviors of Ctsb knock-out mice revealed an increase in depression-like behavior in females. Altogether, our results suggest that Ctsb has significant effects on emotionality, irrespective of the tested mouse strain, making it a promising target for future pharmacotherapy.

  10. Bariatric surgery: the challenges with candidate selection, individualizing treatment and clinical outcomes

    Science.gov (United States)

    2013-01-01

    Obesity is recognized as a global health crisis. Bariatric surgery offers a treatment that can reduce weight, induce remission of obesity-related diseases, and improve the quality of life. In this article, we outline the different options in bariatric surgery and summarize the recommendations for selecting and assessing potential candidates before proceeding to surgery. We present current data on post-surgical outcomes and evaluate the psychosocial and economic effects of bariatric surgery. Finally, we evaluate the complication rates and present recommendations for post-operative care. PMID:23302153

  11. Candidate Targets for New Anti-Virulence Drugs: Selected Cases of Bacterial Adhesion and Biofilm Formation

    DEFF Research Database (Denmark)

    Klemm, Per; Hancock, Viktoria; Kvist, Malin

    2007-01-01

    is particularly problematic in medical contexts because biofilm-associated bacteria are particularly hard to eradicate. Several promising candidate drugs that target bacterial adhesion and biofilm formation are being developed. Some of these might be valuable weapons for fighting infectious diseases in the future...... formation are highly attractive targets for new drugs. Specific adhesion provides bacteria with target selection and prevents removal by hydrodynamic flow forces. Bacterial adhesion is of paramount importance for bacterial pathogenesis. Adhesion is also the first step in biofilm formation. Biofilm formation...

  12. Transcriptome analysis reveals candidate genes involved in luciferin metabolism in Luciola aquatilis (Coleoptera: Lampyridae

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    Wanwipa Vongsangnak

    2016-10-01

    Full Text Available Bioluminescence, which living organisms such as fireflies emit light, has been studied extensively for over half a century. This intriguing reaction, having its origins in nature where glowing insects can signal things such as attraction or defense, is now widely used in biotechnology with applications of bioluminescence and chemiluminescence. Luciferase, a key enzyme in this reaction, has been well characterized; however, the enzymes involved in the biosynthetic pathway of its substrate, luciferin, remains unsolved at present. To elucidate the luciferin metabolism, we performed a de novo transcriptome analysis using larvae of the firefly species, Luciola aquatilis. Here, a comparative analysis is performed with the model coleopteran insect Tribolium casteneum to elucidate the metabolic pathways in L. aquatilis. Based on a template luciferin biosynthetic pathway, combined with a range of protein and pathway databases, and various prediction tools for functional annotation, the candidate genes, enzymes, and biochemical reactions involved in luciferin metabolism are proposed for L. aquatilis. The candidate gene expression is validated in the adult L. aquatilis using reverse transcription PCR (RT-PCR. This study provides useful information on the bio-production of luciferin in the firefly and will benefit to future applications of the valuable firefly bioluminescence system.

  13. Gene Expression Analysis in Tubule Interstitial Compartments Reveals Candidate Agents for IgA Nephropathy

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    Jinling Wang

    2014-09-01

    Full Text Available Background/Aims: Our aim was to explore the molecular mechanism underlying development of IgA nephropathy and discover candidate agents for IgA nephropathy. Methods: The differentially expressed genes (DEGs between patients with IgA nephropathy and normal controls were identified by the data of GSE35488 downloaded from GEO (Gene Expression Omnibus database. The co-expressed gene pairs among DEGs were screened to construct the gene-gene interaction network. Gene Ontology (GO enrichment analysis was performed to analyze the functions of DEGs. The biologically active small molecules capable of targeting IgA nephropathy were identified using the Connectivity Map (cMap database. Results: A total of 55 genes involved in response to organic substance, transcription factor activity and response to steroid hormone stimulus were identified to be differentially expressed in IgA nephropathy patients compared to healthy individuals. A network with 45 co-expressed gene pairs was constructed. DEGs in the network were significantly enriched in response to organic substance. Additionally, a group of small molecules were identified, such as doxorubicin and thapsigargin. Conclusion: Our work provided a systematic insight in understanding the mechanism of IgA nephropathy. Small molecules such as thapsigargin might be potential candidate agents for the treatment of IgA nephropathy.

  14. Genome association study through nonlinear mixed models revealed new candidate genes for pig growth curves

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    Fabyano Fonseca e Silva

    Full Text Available ABSTRACT: Genome association analyses have been successful in identifying quantitative trait loci (QTLs for pig body weights measured at a single age. However, when considering the whole weight trajectories over time in the context of genome association analyses, it is important to look at the markers that affect growth curve parameters. The easiest way to consider them is via the two-step method, in which the growth curve parameters and marker effects are estimated separately, thereby resulting in a reduction of the statistical power and the precision of estimates. One efficient solution is to adopt nonlinear mixed models (NMM, which enables a joint modeling of the individual growth curves and marker effects. Our aim was to propose a genome association analysis for growth curves in pigs based on NMM as well as to compare it with the traditional two-step method. In addition, we also aimed to identify the nearest candidate genes related to significant SNP (single nucleotide polymorphism markers. The NMM presented a higher number of significant SNPs for adult weight (A and maturity rate (K, and provided a direct way to test SNP significance simultaneously for both the A and K parameters. Furthermore, all significant SNPs from the two-step method were also reported in the NMM analysis. The ontology of the three candidate genes (SH3BGRL2, MAPK14, and MYL9 derived from significant SNPs (simultaneously affecting A and K allows us to make inferences with regards to their contribution to the pig growth process in the population studied.

  15. RNA-Seq analysis reveals candidate genes for ontogenic resistance in Malus-Venturia pathosystem.

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    Michele Gusberti

    Full Text Available Ontogenic scab resistance in apple leaves and fruits is a horizontal resistance against the plant pathogen Venturia inaequalis and is expressed as a decrease in disease symptoms and incidence with the ageing of the leaves. Several studies at the biochemical level tried to unveil the nature of this resistance; however, no conclusive results were reported. We decided therefore to investigate the genetic origin of this phenomenon by performing a full quantitative transcriptome sequencing and comparison of young (susceptible and old (ontogenic resistant leaves, infected or not with the pathogen. Two time points at 72 and 96 hours post-inoculation were chosen for RNA sampling and sequencing. Comparison between the different conditions (young and old leaves, inoculated or not should allow the identification of differentially expressed genes which may represent different induced plant defence reactions leading to ontogenic resistance or may be the cause of a constitutive (uninoculated with the pathogen shift toward resistance in old leaves. Differentially expressed genes were then characterised for their function by homology to A. thaliana and other plant genes, particularly looking for genes involved in pathways already suspected of appertaining to ontogenic resistance in apple or other hosts, or to plant defence mechanisms in general. IN THIS WORK, FIVE CANDIDATE GENES PUTATIVELY INVOLVED IN THE ONTOGENIC RESISTANCE OF APPLE WERE IDENTIFIED: a gene encoding an "enhanced disease susceptibility 1 protein" was found to be down-regulated in both uninoculated and inoculated old leaves at 96 hpi, while the other four genes encoding proteins (metallothionein3-like protein, lipoxygenase, lipid transfer protein, and a peroxidase 3 were found to be constitutively up-regulated in inoculated and uninoculated old leaves. The modulation of the five candidate genes has been validated using the real-time quantitative PCR. Thus, ontogenic resistance may be the result

  16. Selection on plant male function genes identifies candidates for reproductive isolation of yellow monkeyflowers.

    Directory of Open Access Journals (Sweden)

    Jan E Aagaard

    Full Text Available Understanding the genetic basis of reproductive isolation promises insight into speciation and the origins of biological diversity. While progress has been made in identifying genes underlying barriers to reproduction that function after fertilization (post-zygotic isolation, we know much less about earlier acting pre-zygotic barriers. Of particular interest are barriers involved in mating and fertilization that can evolve extremely rapidly under sexual selection, suggesting they may play a prominent role in the initial stages of reproductive isolation. A significant challenge to the field of speciation genetics is developing new approaches for identification of candidate genes underlying these barriers, particularly among non-traditional model systems. We employ powerful proteomic and genomic strategies to study the genetic basis of conspecific pollen precedence, an important component of pre-zygotic reproductive isolation among yellow monkeyflowers (Mimulus spp. resulting from male pollen competition. We use isotopic labeling in combination with shotgun proteomics to identify more than 2,000 male function (pollen tube proteins within maternal reproductive structures (styles of M. guttatus flowers where pollen competition occurs. We then sequence array-captured pollen tube exomes from a large outcrossing population of M. guttatus, and identify those genes with evidence of selective sweeps or balancing selection consistent with their role in pollen competition. We also test for evidence of positive selection on these genes more broadly across yellow monkeyflowers, because a signal of adaptive divergence is a common feature of genes causing reproductive isolation. Together the molecular evolution studies identify 159 pollen tube proteins that are candidate genes for conspecific pollen precedence. Our work demonstrates how powerful proteomic and genomic tools can be readily adapted to non-traditional model systems, allowing for genome-wide screens

  17. Use of the Interview in Resident Candidate Selection: A Review of the Literature.

    Science.gov (United States)

    Stephenson-Famy, Alyssa; Houmard, Brenda S; Oberoi, Sidharth; Manyak, Anton; Chiang, Seine; Kim, Sara

    2015-12-01

    Although the resident candidate interview is costly and time-consuming for both applicants and programs, it is considered critically important for resident selection. Noncognitive attributes, including communication skills and professionalism, can be assessed by the personal interview. We conducted a review of the literature on the residency interview to identify the interview characteristics used for resident selection and to ascertain to what extent the interview yields information that predicts future performance. We searched PubMed and Scopus using the following search terms: residency, internship, interview, selection, and performance. We extracted information on characteristics of the interview process, including type of interview format, measures taken to minimize bias by interviewers, and testing of other clinical/surgical skills. We identified 104 studies that pertained to the resident selection interview, with highly varied interview formats and assessment tools. A positive correlation was demonstrated between a medical school academic record and the interview, especially for unblinded interview formats. A total of 34 studies attempted to correlate interview score with performance in residency, with mixed results. We also identified a number of studies that included personality testing, clinical skills testing, or surgical skills testing. Our review identified a wide variety of approaches to the selection interview and a range of factors that have been studied to assess its effectiveness. More research needs to be done not only to address and ascertain appropriate interview formats that predict positive performance in residency, but also to determine interview factors that can predict both residents' "success" and program attrition.

  18. Improving mass candidate detection in mammograms via feature maxima propagation and local feature selection.

    Science.gov (United States)

    Melendez, Jaime; Sánchez, Clara I; van Ginneken, Bram; Karssemeijer, Nico

    2014-08-01

    Mass candidate detection is a crucial component of multistep computer-aided detection (CAD) systems. It is usually performed by combining several local features by means of a classifier. When these features are processed on a per-image-location basis (e.g., for each pixel), mismatching problems may arise while constructing feature vectors for classification, which is especially true when the behavior expected from the evaluated features is a peaked response due to the presence of a mass. In this study, two of these problems, consisting of maxima misalignment and differences of maxima spread, are identified and two solutions are proposed. The first proposed method, feature maxima propagation, reproduces feature maxima through their neighboring locations. The second method, local feature selection, combines different subsets of features for different feature vectors associated with image locations. Both methods are applied independently and together. The proposed methods are included in a mammogram-based CAD system intended for mass detection in screening. Experiments are carried out with a database of 382 digital cases. Sensitivity is assessed at two sets of operating points. The first one is the interval of 3.5-15 false positives per image (FPs/image), which is typical for mass candidate detection. The second one is 1 FP/image, which allows to estimate the quality of the mass candidate detector's output for use in subsequent steps of the CAD system. The best results are obtained when the proposed methods are applied together. In that case, the mean sensitivity in the interval of 3.5-15 FPs/image significantly increases from 0.926 to 0.958 (p < 0.0002). At the lower rate of 1 FP/image, the mean sensitivity improves from 0.628 to 0.734 (p < 0.0002). Given the improved detection performance, the authors believe that the strategies proposed in this paper can render mass candidate detection approaches based on image location classification more robust to feature

  19. Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk.

    Directory of Open Access Journals (Sweden)

    Daria Salyakina

    Full Text Available Copy number variations (CNVs are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than by single nucleotide polymorphisms (SNPs. In the multifaceted etiology of autism spectrum disorders (ASDs, CNVs appear to contribute significantly to our understanding of the pathogenesis of this complex disease. A unique resource of 42 extended ASD families was genotyped for over 1 million SNPs to detect CNVs that may contribute to ASD susceptibility. Each family has at least one avuncular or cousin pair with ASD. Families were then evaluated for co-segregation of CNVs in ASD patients. We identified a total of five deletions and seven duplications in eleven families that co-segregated with ASD. Two of the CNVs overlap with regions on 7p21.3 and 15q24.1 that have been previously reported in ASD individuals and two additional CNVs on 3p26.3 and 12q24.32 occur near regions associated with schizophrenia. These findings provide further evidence for the involvement of ICA1 and NXPH1 on 7p21.3 in ASD susceptibility and highlight novel ASD candidates, including CHL1, FGFBP3 and POUF41. These studies highlight the power of using extended families for gene discovery in traits with a complex etiology.

  20. Transcriptome Analysis Reveals Candidate Genes involved in Blister Blight defense in Tea (Camellia sinensis (L) Kuntze)

    Science.gov (United States)

    Jayaswall, Kuldip; Mahajan, Pallavi; Singh, Gagandeep; Parmar, Rajni; Seth, Romit; Raina, Aparnashree; Swarnkar, Mohit Kumar; Singh, Anil Kumar; Shankar, Ravi; Sharma, Ram Kumar

    2016-07-01

    To unravel the molecular mechanism of defense against blister blight (BB) disease caused by an obligate biotrophic fungus, Exobasidium vexans, transcriptome of BB interaction with resistance and susceptible tea genotypes was analysed through RNA-seq using Illumina GAIIx at four different stages during ~20-day disease cycle. Approximately 69 million high quality reads were assembled de novo, yielding 37,790 unique transcripts with more than 55% being functionally annotated. Differentially expressed, 149 defense related transcripts/genes, namely defense related enzymes, resistance genes, multidrug resistant transporters, transcription factors, retrotransposons, metacaspases and chaperons were observed in RG, suggesting their role in defending against BB. Being present in the major hub, putative master regulators among these candidates were identified from predetermined protein-protein interaction network of Arabidopsis thaliana. Further, confirmation of abundant expression of well-known RPM1, RPS2 and RPP13 in quantitative Real Time PCR indicates salicylic acid and jasmonic acid, possibly induce synthesis of antimicrobial compounds, required to overcome the virulence of E. vexans. Compendiously, the current study provides a comprehensive gene expression and insights into the molecular mechanism of tea defense against BB to serve as a resource for unravelling the possible regulatory mechanism of immunity against various biotic stresses in tea and other crops.

  1. A genome-wide association study reveals a novel candidate gene for sperm motility in pigs

    NARCIS (Netherlands)

    Diniz, D.B.; Lopes, M.S.; Broekhuijse, M.L.W.J.; Lopes, P.S.; Harlizius, B.; Guimaraes, S.E.F.; Duijvesteijn, N.; Knol, E.F.; Silva, F.F.

    2014-01-01

    Sperm motility is one of the most widely used parameters in order to evaluate boar semen quality. However, this trait can only be measured after puberty. Thus, the use of genomic information appears as an appealing alternative to evaluate and improve selection for boar fertility traits earlier in

  2. Translational database selection and multiplexed sequence capture for up front filtering of reliable breast cancer biomarker candidates.

    Directory of Open Access Journals (Sweden)

    Patrik L Ståhl

    Full Text Available Biomarker identification is of utmost importance for the development of novel diagnostics and therapeutics. Here we make use of a translational database selection strategy, utilizing data from the Human Protein Atlas (HPA on differentially expressed protein patterns in healthy and breast cancer tissues as a means to filter out potential biomarkers for underlying genetic causatives of the disease. DNA was isolated from ten breast cancer biopsies, and the protein coding and flanking non-coding genomic regions corresponding to the selected proteins were extracted in a multiplexed format from the samples using a single DNA sequence capture array. Deep sequencing revealed an even enrichment of the multiplexed samples and a great variation of genetic alterations in the tumors of the sampled individuals. Benefiting from the upstream filtering method, the final set of biomarker candidates could be completely verified through bidirectional Sanger sequencing, revealing a 40 percent false positive rate despite high read coverage. Of the variants encountered in translated regions, nine novel non-synonymous variations were identified and verified, two of which were present in more than one of the ten tumor samples.

  3. Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

    Science.gov (United States)

    Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

    2016-11-01

    Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

  4. Transcriptomic Analysis Reveals Candidate Genes for Female Sterility in Pomegranate Flowers

    Directory of Open Access Journals (Sweden)

    Lina Chen

    2017-08-01

    Full Text Available Pomegranate has two types of flowers on the same plant: functional male flowers (FMF and bisexual flowers (BF. BF are female-fertile flowers that can set fruits. FMF are female-sterile flowers that fail to set fruit and that eventually drop. The putative cause of pomegranate FMF female sterility is abnormal ovule development. However, the key stage at which the FMF pomegranate ovules become abnormal and the mechanism of regulation of pomegranate female sterility remain unknown. Here, we studied ovule development in FMF and BF, using scanning electron microscopy to explore the key stage at which ovule development was terminated and then analyzed genes differentially expressed (differentially expressed genes – DEGs between FMF and BF to investigate the mechanism responsible for pomegranate female sterility. Ovule development in FMF ceased following the formation of the inner integument primordium. The key stage for the termination of FMF ovule development was when the bud vertical diameter was 5.0–13.0 mm. Candidate genes influencing ovule development may be crucial factors in pomegranate female sterility. INNER OUTER (INO/YABBY4 (Gglean016270 and AINTEGUMENTA (ANT homolog genes (Gglean003340 and Gglean011480, which regulate the development of the integument, showed down-regulation in FMF at the key stage of ovule development cessation (ATNSII. Their upstream regulator genes, such as AGAMOUS-like (AG-like (Gglean028014, Gglean026618, and Gglean028632 and SPOROCYTELESS (SPL homolog genes (Gglean005812, also showed differential expression pattern between BF and FMF at this key stage. The differential expression of the ethylene response signal genes, ETR (ethylene-resistant (Gglean022853 and ERF1/2 (ethylene-responsive factor (Gglean022880, between FMF and BF indicated that ethylene signaling may also be an important factor in the development of pomegranate female sterility. The increase in BF observed after spraying with ethephon supported this

  5. Comparative genomics reveals candidate carotenoid pathway regulators of ripening watermelon fruit

    Science.gov (United States)

    2013-01-01

    Background Many fruits, including watermelon, are proficient in carotenoid accumulation during ripening. While most genes encoding steps in the carotenoid biosynthetic pathway have been cloned, few transcriptional regulators of these genes have been defined to date. Here we describe the identification of a set of putative carotenoid-related transcription factors resulting from fresh watermelon carotenoid and transcriptome analysis during fruit development and ripening. Our goal is to both clarify the expression profiles of carotenoid pathway genes and to identify candidate regulators and molecular targets for crop improvement. Results Total carotenoids progressively increased during fruit ripening up to ~55 μg g-1 fw in red-ripe fruits. Trans-lycopene was the carotenoid that contributed most to this increase. Many of the genes related to carotenoid metabolism displayed changing expression levels during fruit ripening generating a metabolic flux toward carotenoid synthesis. Constitutive low expression of lycopene cyclase genes resulted in lycopene accumulation. RNA-seq expression profiling of watermelon fruit development yielded a set of transcription factors whose expression was correlated with ripening and carotenoid accumulation. Nineteen putative transcription factor genes from watermelon and homologous to tomato carotenoid-associated genes were identified. Among these, six were differentially expressed in the flesh of both species during fruit development and ripening. Conclusions Taken together the data suggest that, while the regulation of a common set of metabolic genes likely influences carotenoid synthesis and accumulation in watermelon and tomato fruits during development and ripening, specific and limiting regulators may differ between climacteric and non-climacteric fruits, possibly related to their differential susceptibility to and use of ethylene during ripening. PMID:24219562

  6. Selecting ultra-faint dwarf candidate progenitors in cosmological N-body simulations at high redshifts

    Science.gov (United States)

    Safarzadeh, Mohammadtaher; Ji, Alexander P.; Dooley, Gregory A.; Frebel, Anna; Scannapieco, Evan; Gómez, Facundo A.; O'Shea, Brian W.

    2018-06-01

    The smallest satellites of the Milky Way ceased forming stars during the epoch of reionization and thus provide archaeological access to galaxy formation at z > 6. Numerical studies of these ultrafaint dwarf galaxies (UFDs) require expensive cosmological simulations with high mass resolution that are carried out down to z = 0. However, if we are able to statistically identify UFD host progenitors at high redshifts with relatively high probabilities, we can avoid this high computational cost. To find such candidates, we analyse the merger trees of Milky Way type haloes from the high-resolution Caterpillar suite of dark matter only simulations. Satellite UFD hosts at z = 0 are identified based on four different abundance matching (AM) techniques. All the haloes at high redshifts are traced forward in time in order to compute the probability of surviving as satellite UFDs today. Our results show that selecting potential UFD progenitors based solely on their mass at z = 12 (8) results in a 10 per cent (20 per cent) chance of obtaining a surviving UFD at z = 0 in three of the AM techniques we adopted. We find that the progenitors of surviving satellite UFDs have lower virial ratios (η), and are preferentially located at large distances from the main MW progenitor, while they show no correlation with concentration parameter. Haloes with favorable locations and virial ratios are ≈3 times more likely to survive as satellite UFD candidates at z = 0.

  7. Global blending optimization of laminated composites with discrete material candidate selection and thickness variation

    DEFF Research Database (Denmark)

    Sørensen, Søren N.; Stolpe, Mathias

    2015-01-01

    rate. The capabilities of the method and the effect of active versus inactive manufacturing constraints are demonstrated on several numerical examples of limited size, involving at most 320 binary variables. Most examples are solved to guaranteed global optimality and may constitute benchmark examples...... but is, however, convex in the original mixed binary nested form. Convexity is the foremost important property of optimization problems, and the proposed method can guarantee the global or near-global optimal solution; unlike most topology optimization methods. The material selection is limited...... for popular topology optimization methods and heuristics based on solving sequences of non-convex problems. The results will among others demonstrate that the difficulty of the posed problem is highly dependent upon the composition of the constitutive properties of the material candidates....

  8. Diagnostic imaging to select the candidates to orthotopic transplantation: Experience in a general hospital

    International Nuclear Information System (INIS)

    Pozzato, Carlo; Baldini, Umberto; Gattoni, Filippo; Raiteri, Riccardo; Lazzerini, Francesco; Uslenghi, Carlo Matteo; Mevoli, Alessandra

    1997-01-01

    The authors report the experience of our general hospital in selecting the patients for orthotopic liver transplantation (OLT). The accuracy of duplex Doppler and color flow Doppler for portal and/or mesenteric vein thrombosis was evaluated by correlation with resected livers, computerized tomography and angiographic findings. Pathologic examinations diagnosed HCC in 5/20 transplant recipients: 2 lesions were found in 2 resected specimens (total hepatectomy) and 1 lesion was found in 3 cases. The sensitivity of US, plain and dynamic computerized tomography in identifying HCC patients was 20%; US and computerized tomography specificity rates were 100% and 87%, respectively. CTAP sensitivity was 75% and the sensitivity of Lipiodol computerized tomography and angiography was 100%. Therefore, in our series, US was poorly sensitivity in the detection of liver cancers, which may depend on the small number of patients, lesion size and the radiologists ignoring clinical and laboratory data on purpose. Nevertheless, the patients with a single HCC not exceeding 5 cm in diameter or with no more than 3 tumors, none of them exceeding 3 cm in diameter, are generally considered eligible for transplantation: therefore, our patients chosen for OLT on the basis of US and computerized tomography findings were actually eligible for transplantation in spite of US and computerized tomography false negative results. In conclusion, considering also the long stand-by list for OLT, the first selection of transplant candidates could be performed with US and color flow Doppler, plain and dynamic computerized tomography. The patients who are not ruled out as candidates for OLT on the basis of the findings of these imaging techniques and of clinical and laboratory findings are submitted to no further examination and referred to the transplantation unit. Otherwise, if conventional and color flow Doppler US and conventional computerized tomography are not enough to exclude a patient from OLT, the

  9. Hemodynamic exercise testing. A valuable tool in the selection of cardiac transplantation candidates.

    Science.gov (United States)

    Chomsky, D B; Lang, C C; Rayos, G H; Shyr, Y; Yeoh, T K; Pierson, R N; Davis, S F; Wilson, J R

    1996-12-15

    Peak exercise oxygen consumption (Vo2), a noninvasive index of peak exercise cardiac output (CO), is widely used to select candidates for heart transplantation. However, peak exercise Vo2 can be influenced by noncardiac factors such as deconditioning, motivation, or body composition and may yield misleading prognostic information. Direct measurement of the CO response to exercise may avoid this problem and more accurately predict prognosis. Hemodynamic and ventilatory responses to maximal treadmill exercise were measured in 185 ambulatory patients with chronic heart failure who had been referred for cardiac transplantation (mean left ventricular ejection fraction, 22 +/- 7%; mean peak Vo2, 12.9 +/- 3.0 mL. min-1.kg-1). CO response to exercise was normal in 83 patients and reduced in 102. By univariate analysis, patients with normal CO responses had a better 1-year survival rate (95%) than did those with reduced CO responses (72%) (P 14 mL.min-1.kg-1 (88%) was not different from that of patients with peak Vo2 of 10 mL.min-1.kg-1 (89%) (P < .0001). By Cox regression analysis, exercise CO response was the strongest independent predictor of survival (risk ratio, 4.3), with peak Vo2 dichotomized at 10 mL. min-1.kg-1 (risk ratio, 3.3) as the only other independent predictor. Patients with reduced CO responses and peak Vo2 of < or = 10 mL.min-1.kg-1 had an extremely poor 1-year survival rate (38%). Both CO response to exercise and peak exercise Vo2 provide valuable independent prognostic information in ambulatory patients with heart failure. These variables should be used in combination to select potential heart transplantation candidates.

  10. Trust Based Algorithm for Candidate Node Selection in Hybrid MANET-DTN

    Directory of Open Access Journals (Sweden)

    Jan Papaj

    2014-01-01

    Full Text Available The hybrid MANET - DTN is a mobile network that enables transport of the data between groups of the disconnected mobile nodes. The network provides benefits of the Mobile Ad-Hoc Networks (MANET and Delay Tolerant Network (DTN. The main problem of the MANET occurs if the communication path is broken or disconnected for some short time period. On the other side, DTN allows sending data in the disconnected environment with respect to higher tolerance to delay. Hybrid MANET - DTN provides optimal solution for emergency situation in order to transport information. Moreover, the security is the critical factor because the data are transported by mobile devices. In this paper, we investigate the issue of secure candidate node selection for transportation of the data in a disconnected environment for hybrid MANET- DTN. To achieve the secure selection of the reliable mobile nodes, the trust algorithm is introduced. The algorithm enables select reliable nodes based on collecting routing information. This algorithm is implemented to the simulator OPNET modeler.

  11. Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A.

    Science.gov (United States)

    Cadzow, Murray; Merriman, Tony R; Boocock, James; Dalbeth, Nicola; Stamp, Lisa K; Black, Michael A; Visscher, Peter M; Wilcox, Phillip L

    2016-11-15

    The gene PPARGC1A, in particular the Gly482Ser variant (rs8192678), had been proposed to be subject to natural selection, particularly in recent progenitors of extant Polynesian populations. Reasons include high levels of population differentiation and increased frequencies of the derived type 2 diabetes (T2D) risk 482Ser allele, and association with body mass index (BMI) in a small Tongan population. However, no direct statistical tests for selection have been applied. Using a range of Polynesian populations (Tongan, Māori, Samoan) we re-examined evidence for association between Gly482Ser with T2D and BMI as well as gout. Using also Asian, European, and African 1000 Genome Project samples a range of statistical tests for selection (F ST , integrated haplotype score (iHS), cross population extended haplotype homozygosity (XP-EHH), Tajima's D and Fay and Wu's H) were conducted on the PPARGC1A locus. No statistically significant evidence for association between Gly482Ser and any of BMI, T2D or gout was found. Population differentiation (F ST ) was smallest between Asian and Pacific populations (New Zealand Māori ≤ 0.35, Samoan ≤ 0.20). When compared to European (New Zealand Māori ≤ 0.40, Samoan ≤ 0.25) or African populations (New Zealand Māori ≤ 0.80, Samoan ≤ 0.66) this differentiation was larger. We did not find any strong evidence for departure from neutral evolution at this locus when applying any of the other statistical tests for selection. However, using the same analytical methods, we found evidence for selection in specific populations at previously identified loci, indicating that lack of selection was the most likely explanation for the lack of evidence of selection in PPARGC1A. We conclude that there is no compelling evidence for selection at this locus, and that this gene should not be considered a candidate thrifty gene locus in Pacific populations. High levels of population differentiation at this locus and the

  12. Selection and evaluation of inner material candidates for Spanish high level radioactive waste canisters

    International Nuclear Information System (INIS)

    Puig, Francesc; Dies, Javier; Sevilla, Manuel; Pablo, Joan de; Pueyo, Juan Jose; Miralles, Lourdes; Martinez-Esparza, Aurora

    2007-01-01

    This paper summarizes the work carried out to analyse different alternatives related to the inner material selection of the Spanish high level waste canister for long term storage. The preliminary repository design considers granitic or clay formations, compacted bentonite sealing, corrosion allowing steel canisters and glass bead filling between the fuel assemblies and canister walls. This filling material will have the primary role of avoiding the possibility of a criticality event, which becomes an issue of major importance once the container is finally breached by corrosion and flooded by groundwater. In the first place, a complete set of requirements have been devised as evaluation criteria for candidate materials examination and selection; resulting in a compilation of demands significantly deeper and more exhaustive than any other similar work found in literature, including over 20 requirements and some other general aspects that could involve improvements in repository performance. Secondly, eight materials or material families (cast iron or steel, borosilicate glass, spinel, depleted uranium, dehydrated zeolites, hematite, phosphates and olivine) have been chosen and examined in detail, extracting some relevant conclusions. Either cast iron, borosilicate glass, spinel or depleted uranium are considered to look quite promising for the mentioned purpose. (authors)

  13. Fetal Intervention in Right Outflow Tract Obstructive Disease: Selection of Candidates and Results

    Science.gov (United States)

    Gómez Montes, E.; Herraiz, I.; Mendoza, A.; Galindo, A.

    2012-01-01

    Objectives. To describe the process of selection of candidates for fetal cardiac intervention (FCI) in fetuses diagnosed with pulmonary atresia-critical stenosis with intact ventricular septum (PA/CS-IVS) and report our own experience with FCI for such disease. Methods. We searched our database for cases of PA/CS-IVS prenatally diagnosed in 2003–2012. Data of 38 fetuses were retrieved and analyzed. FCI were offered to 6 patients (2 refused). In the remaining it was not offered due to the presence of either favourable prognostic echocardiographic markers (n = 20) or poor prognostic indicators (n = 12). Results. The outcome of fetuses with PA/CS-IVS was accurately predicted with multiparametric scoring systems. Pulmonary valvuloplasty was technically successful in all 4 fetuses. The growth of the fetal right heart and hemodynamic parameters showed a Gaussian-like behaviour with an improvement in the first weeks and slow worsening as pregnancy advanced, probably indicating a restenosis. Conclusions. The most likely type of circulation after birth may be predicted in the second trimester of pregnancy by means of combining cardiac dimensions and functional parameters. Fetal pulmonary valvuloplasty in midgestation is technically feasible and in well-selected cases may improve right heart growth, fetal hemodynamics, and postnatal outcome. PMID:22928144

  14. The APOSTLE project: Local Group kinematic mass constraints and simulation candidate selection

    Science.gov (United States)

    Fattahi, Azadeh; Navarro, Julio F.; Sawala, Till; Frenk, Carlos S.; Oman, Kyle A.; Crain, Robert A.; Furlong, Michelle; Schaller, Matthieu; Schaye, Joop; Theuns, Tom; Jenkins, Adrian

    2016-03-01

    We use a large sample of isolated dark matter halo pairs drawn from cosmological N-body simulations to identify candidate systems whose kinematics match that of the Local Group (LG) of galaxies. We find, in agreement with the `timing argument' and earlier work, that the separation and approach velocity of the Milky Way (MW) and Andromeda (M31) galaxies favour a total mass for the pair of ˜5 × 1012 M⊙. A mass this large, however, is difficult to reconcile with the small relative tangential velocity of the pair, as well as with the small deceleration from the Hubble flow observed for the most distant LG members. Halo pairs that match these three criteria have average masses a factor of ˜2 times smaller than suggested by the timing argument, but with large dispersion. Guided by these results, we have selected 12 halo pairs with total mass in the range 1.6-3.6 × 1012 M⊙ for the APOSTLE project (A Project Of Simulating The Local Environment), a suite of hydrodynamical resimulations at various numerical resolution levels (reaching up to ˜104 M⊙ per gas particle) that use the subgrid physics developed for the EAGLE project. These simulations reproduce, by construction, the main kinematics of the MW-M31 pair, and produce satellite populations whose overall number, luminosities, and kinematics are in good agreement with observations of the MW and M31 companions. The APOSTLE candidate systems thus provide an excellent testbed to confront directly many of the predictions of the Λ cold dark matter cosmology with observations of our local Universe.

  15. Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

    International Nuclear Information System (INIS)

    Matheis, Katja A.; Com, Emmanuelle; Gautier, Jean-Charles; Guerreiro, Nelson; Brandenburg, Arnd; Gmuender, Hans; Sposny, Alexandra; Hewitt, Philip; Amberg, Alexander; Boernsen, Olaf; Riefke, Bjoern; Hoffmann, Dana; Mally, Angela; Kalkuhl, Arno; Suter, Laura; Dieterle, Frank; Staedtler, Frank

    2011-01-01

    The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinical chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.

  16. Candidate genes revealed by a genome scan for mosquito resistance to a bacterial insecticide: sequence and gene expression variations

    Directory of Open Access Journals (Sweden)

    David Jean-Philippe

    2009-11-01

    Full Text Available Abstract Background Genome scans are becoming an increasingly popular approach to study the genetic basis of adaptation and speciation, but on their own, they are often helpless at identifying the specific gene(s or mutation(s targeted by selection. This shortcoming is hopefully bound to disappear in the near future, thanks to the wealth of new genomic resources that are currently being developed for many species. In this article, we provide a foretaste of this exciting new era by conducting a genome scan in the mosquito Aedes aegypti with the aim to look for candidate genes involved in resistance to Bacillus thuringiensis subsp. israelensis (Bti insecticidal toxins. Results The genome of a Bti-resistant and a Bti-susceptible strains was surveyed using about 500 MITE-based molecular markers, and the loci showing the highest inter-strain genetic differentiation were sequenced and mapped on the Aedes aegypti genome sequence. Several good candidate genes for Bti-resistance were identified in the vicinity of these highly differentiated markers. Two of them, coding for a cadherin and a leucine aminopeptidase, were further examined at the sequence and gene expression levels. In the resistant strain, the cadherin gene displayed patterns of nucleotide polymorphisms consistent with the action of positive selection (e.g. an excess of high compared to intermediate frequency mutations, as well as a significant under-expression compared to the susceptible strain. Conclusion Both sequence and gene expression analyses agree to suggest a role for positive selection in the evolution of this cadherin gene in the resistant strain. However, it is unlikely that resistance to Bti is conferred by this gene alone, and further investigation will be needed to characterize other genes significantly associated with Bti resistance in Ae. aegypti. Beyond these results, this article illustrates how genome scans can build on the body of new genomic information (here, full

  17. Catalog of 3 < z < 5.5 Quasar Candidates Selected among XMM-Newton Sources and Its Spectroscopic Verification

    Energy Technology Data Exchange (ETDEWEB)

    Khorunzhev, Georgii; Sazonov, Sergey; Burenin, Rodion [High Energy Astrophysics, Space Research Institute, Russian Academy of Sciences, Moscow (Russian Federation); Eselevich, Maxim, E-mail: horge@iki.rssi.ru [Laboratory of Infrared Methods in Astrophysics, Institute of Solar-Terrestrial Physics, Russian Academy of Sciences, Irkutsk (Russian Federation)

    2017-11-13

    We have compiled a catalog of 903 quasar candidates (including known quasars) at 3 < z < 5.5 selected among X-ray sources from the XMM-Newton serendipitous survey (3XMM-DR4 catalog). We used photometric SDSS, 2MASS, and WISE data to select the objects. The surface number density of objects in our sample exceeds that in the SDSS spectroscopic quasar sample at the same redshifts by a factor of 1.5. We have performed spectroscopic observations of a subsample of new quasar candidates using a new low- and medium-resolution spectrograph at the 1.6-m AZT-33IK telescope (Mondy, Russia) and demonstrated that the purity of these candidates is about 65%. We have discovered one of the most distant (z = 5.08) X-ray selected quasars.

  18. Catalog of 3 < z < 5.5 Quasar Candidates Selected among XMM-Newton Sources and Its Spectroscopic Verification

    Directory of Open Access Journals (Sweden)

    Georgii Khorunzhev

    2017-11-01

    Full Text Available We have compiled a catalog of 903 quasar candidates (including known quasars at 3 < z < 5.5 selected among X-ray sources from the XMM-Newton serendipitous survey (3XMM-DR4 catalog. We used photometric SDSS, 2MASS, and WISE data to select the objects. The surface number density of objects in our sample exceeds that in the SDSS spectroscopic quasar sample at the same redshifts by a factor of 1.5. We have performed spectroscopic observations of a subsample of new quasar candidates using a new low- and medium-resolution spectrograph at the 1.6-m AZT-33IK telescope (Mondy, Russia and demonstrated that the purity of these candidates is about 65%. We have discovered one of the most distant (z = 5.08 X-ray selected quasars.

  19. A SUCCESSFUL BROADBAND SURVEY FOR GIANT Ly{alpha} NEBULAE. I. SURVEY DESIGN AND CANDIDATE SELECTION

    Energy Technology Data Exchange (ETDEWEB)

    Prescott, Moire K. M. [Department of Physics, Broida Hall, Mail Code 9530, University of California, Santa Barbara, CA 93106 (United States); Dey, Arjun; Jannuzi, Buell T., E-mail: mkpresco@physics.ucsb.edu [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States)

    2012-04-01

    Giant Ly{alpha} nebulae (or Ly{alpha} 'blobs') are likely sites of ongoing massive galaxy formation, but the rarity of these powerful sources has made it difficult to form a coherent picture of their properties, ionization mechanisms, and space density. Systematic narrowband Ly{alpha} nebula surveys are ongoing, but the small redshift range covered and the observational expense limit the comoving volume that can be probed by even the largest of these surveys and pose a significant problem when searching for such rare sources. We have developed a systematic search technique designed to find large Ly{alpha} nebulae at 2 {approx}< z {approx}< 3 within deep broadband imaging and have carried out a survey of the 9.4 deg{sup 2} NOAO Deep Wide-Field Survey Booetes field. With a total survey comoving volume of Almost-Equal-To 10{sup 8} h{sup -3}{sub 70} Mpc{sup 3}, this is the largest volume survey for Ly{alpha} nebulae ever undertaken. In this first paper in the series, we present the details of the survey design and a systematically selected sample of 79 candidates, which includes one previously discovered Ly{alpha} nebula.

  20. A SUCCESSFUL BROADBAND SURVEY FOR GIANT Lyα NEBULAE. I. SURVEY DESIGN AND CANDIDATE SELECTION

    International Nuclear Information System (INIS)

    Prescott, Moire K. M.; Dey, Arjun; Jannuzi, Buell T.

    2012-01-01

    Giant Lyα nebulae (or Lyα 'blobs') are likely sites of ongoing massive galaxy formation, but the rarity of these powerful sources has made it difficult to form a coherent picture of their properties, ionization mechanisms, and space density. Systematic narrowband Lyα nebula surveys are ongoing, but the small redshift range covered and the observational expense limit the comoving volume that can be probed by even the largest of these surveys and pose a significant problem when searching for such rare sources. We have developed a systematic search technique designed to find large Lyα nebulae at 2 ∼ 2 NOAO Deep Wide-Field Survey Boötes field. With a total survey comoving volume of ≈10 8 h –3 70 Mpc 3 , this is the largest volume survey for Lyα nebulae ever undertaken. In this first paper in the series, we present the details of the survey design and a systematically selected sample of 79 candidates, which includes one previously discovered Lyα nebula.

  1. Interest rate transmission mechanism of monetary policy in the selected EMU candidate countries

    Directory of Open Access Journals (Sweden)

    Mirdala Rajmund

    2009-01-01

    Full Text Available The stable macroeconomic environment, as one of the primary objectives of the Visegrad countries in the 1990s, was partially supported by the exchange rate policy. Fixed exchange rate systems within gradually widen bands (Czech Republic, Slovak Republic and crawling peg system (Hungary, Poland were replaced by the managed floating in the Czech Republic (May 1997, Poland (April 2000, Slovak Republic (October 1998 and fixed exchange rate to euro in Hungary (January 2000 with broad band (October 2001. Higher macroeconomic and banking sector stability allowed countries from the Visegrad group to implement the monetary policy strategy based on the interest rate transmission mechanism. Continuous harmonization of the monetary policy framework (with the monetary policy of the ECB and the increasing sensitivity of the economy agents to the interest rates changes allowed the central banks from the Visegrad countries to implement monetary policy strategy based on the key interest rates determination. In the paper we analyze the impact of the central banks' monetary policy in the Visegrad countries on the selected macroeconomic variables in the period 1999-2008 implementing SVAR (structural vector autoregression approach. We expect that higher sensitivity of domestic variables to interest rates shocks can be interpreted as a convergence of monetary policies in candidate countries towards the ECB's monetary policy.

  2. Selection of candidate salad vegetables for controlled ecological life support system

    Science.gov (United States)

    Qin, L.; Guo, S.; Ai, W.; Tang, Y.

    Higher plants, as one of the essential biological components of CELSS, can supply food, oxygen and water for human crews during future long-duration space missions and Lunar/Mars habitats. In order to select suitable leaf vegetable varieties for our CELSS Experimental Facility (CEF), five varieties of lettuce (“Nenlvnaiyou”, “Dasusheng”, “Naichoutai”, “Dongfangkaixuan” and “Siji”), two of spinach (“Daye” and “Quanneng”), one of rape (“Jingyou No. 1”) and one of common sowthistle were grown and compared on the basis of edible biomass, and nutrient content. In addition, two series of experiments were conducted to study single leaf photosynthetic rates and transpiration rates at 30 days after planting, one which used various concentrations of CO2 (500, 1000, 1500 and 2000 μmol mol-1) and another which used various light intensities (100, 300, 500 and 700 μmol m-2 s-1). Results showed that lettuce cvs. “Nenlvnaiyou”, “Siji” and “Dasusheng” produced higher yields of edible biomass; common sowthisle would be a good source of β-carotene for the diet. Based on the collective findings, we selected three varieties of lettuce (“Nenlvnaiyou”, “Dasusheng” and “Siji”) and one of common sowthistle as the candidate crops for further research in our CEF. In addition, elevated CO2 concentration increased the rates of photosynthesis and transpiration, and elevated light intensity increased the rate of photosynthesis for these varieties. These results can be useful for determining optimal conditions for controlling CO2 and water fluxes between the crops and the overall CELSS.

  3. Optimizing risk stratification in heart failure and the selection of candidates for heart transplantation.

    Science.gov (United States)

    Pereira-da-Silva, Tiago; M Soares, Rui; Papoila, Ana Luísa; Pinto, Iola; Feliciano, Joana; Almeida-Morais, Luís; Abreu, Ana; Cruz Ferreira, Rui

    2018-02-01

    Selecting patients for heart transplantation is challenging. We aimed to identify the most important risk predictors in heart failure and an approach to optimize the selection of candidates for heart transplantation. Ambulatory patients followed in our center with symptomatic heart failure and left ventricular ejection fraction ≤40% prospectively underwent a comprehensive baseline assessment including clinical, laboratory, electrocardiographic, echocardiographic, and cardiopulmonary exercise testing parameters. All patients were followed for 60 months. The combined endpoint was cardiac death, urgent heart transplantation or need for mechanical circulatory support, up to 36 months. In the 263 enrolled patients (75% male, age 54±12 years), 54 events occurred. The independent predictors of adverse outcome were ventilatory efficiency (VE/VCO 2 ) slope (HR 1.14, 95% CI 1.11-1.18), creatinine level (HR 2.23, 95% CI 1.14-4.36), and left ventricular ejection fraction (HR 0.96, 95% CI 0.93-0.99). VE/VCO 2 slope was the most accurate risk predictor at any follow-up time analyzed (up to 60 months). The threshold of 39.0 yielded high specificity (97%), discriminated a worse or better prognosis than that reported for post-heart transplantation, and outperformed peak oxygen consumption thresholds of 10.0 or 12.0 ml/kg/min. For low-risk patients (VE/VCO 2 slope <39.0), sodium and creatinine levels and variations in end-tidal carbon dioxide partial pressure on exercise identified those with excellent prognosis. VE/VCO 2 slope was the most accurate parameter for risk stratification in patients with heart failure and reduced ejection fraction. Those with VE/VCO 2 slope ≥39.0 may benefit from heart transplantation. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Drug efficiency: a new concept to guide lead optimization programs towards the selection of better clinical candidates.

    Science.gov (United States)

    Braggio, Simone; Montanari, Dino; Rossi, Tino; Ratti, Emiliangelo

    2010-07-01

    As a result of their wide acceptance and conceptual simplicity, drug-like concepts are having a major influence on the drug discovery process, particularly in the selection of the 'optimal' absorption, distribution, metabolism, excretion and toxicity and physicochemical parameters space. While they have an undisputable value when assessing the potential of lead series or in evaluating inherent risk of a portfolio of drug candidates, they result much less useful in weighing up compounds for the selection of the best potential clinical candidate. We introduce the concept of drug efficiency as a new tool both to guide the drug discovery program teams during the lead optimization phase and to better assess the developability potential of a drug candidate.

  5. Evidence of carbon fixation pathway in a bacterium from candidate phylum SBR1093 revealed with genomic analysis.

    Directory of Open Access Journals (Sweden)

    Zhiping Wang

    Full Text Available Autotrophic CO2 fixation is the most important biotransformation process in the biosphere. Research focusing on the diversity and distribution of relevant autotrophs is significant to our comprehension of the biosphere. In this study, a draft genome of a bacterium from candidate phylum SBR1093 was reconstructed with the metagenome of an industrial activated sludge. Based on comparative genomics, this autotrophy may occur via a newly discovered carbon fixation path, the hydroxypropionate-hydroxybutyrate (HPHB cycle, which was demonstrated in a previous work to be uniquely possessed by some genera from Archaea. This bacterium possesses all of the thirteen enzymes required for the HPHB cycle; these enzymes share 30∼50% identity with those in the autotrophic species of Archaea that undergo the HPHB cycle and 30∼80% identity with the corresponding enzymes of the mixotrophic species within Bradyrhizobiaceae. Thus, this bacterium might have an autotrophic growth mode in certain conditions. A phylogenetic analysis based on the 16S rRNA gene reveals that the phylotypes within candidate phylum SBR1093 are primarily clustered into 5 clades with a shallow branching pattern. This bacterium is clustered with phylotypes from organically contaminated environments, implying a demand for organics in heterotrophic metabolism. Considering the types of regulators, such as FnR, Fur, and ArsR, this bacterium might be a facultative aerobic mixotroph with potential multi-antibiotic and heavy metal resistances. This is the first report on Bacteria that may perform potential carbon fixation via the HPHB cycle, thus may expand our knowledge of the distribution and importance of the HPHB cycle in the biosphere.

  6. Exome sequencing of oral squamous cell carcinoma in users of Arabian snuff reveals novel candidates for driver genes.

    Science.gov (United States)

    Al-Hebshi, Nezar Noor; Li, Shiyong; Nasher, Akram Thabet; El-Setouhy, Maged; Alsanosi, Rashad; Blancato, Jan; Loffredo, Christopher

    2016-07-15

    The study sought to identify genetic aberrations driving oral squamous cell carcinoma (OSCC) development among users of shammah, an Arabian preparation of smokeless tobacco. Twenty archival OSCC samples, 15 of which with a history of shammah exposure, were whole-exome sequenced at an average depth of 127×. Somatic mutations were identified using a novel, matched controls-independent filtration algorithm. CODEX and Exomedepth coupled with a novel, Database of Genomic Variant-based filter were employed to call somatic gene-copy number variations. Significantly mutated genes were identified with Oncodrive FM and the Youn and Simon's method. Candidate driver genes were nominated based on Gene Set Enrichment Analysis. The observed mutational spectrum was similar to that reported by the TCGA project. In addition to confirming known genes of OSCC (TP53, CDKNA2, CASP8, PIK3CA, HRAS, FAT1, TP63, CCND1 and FADD) the analysis identified several candidate novel driver events including mutations of NOTCH3, CSMD3, CRB1, CLTCL1, OSMR and TRPM2, amplification of the proto-oncogenes FOSL1, RELA, TRAF6, MDM2, FRS2 and BAG1, and deletion of the recently described tumor suppressor SMARCC1. Analysis also revealed significantly altered pathways not previously implicated in OSCC including Oncostatin-M signalling pathway, AP-1 and C-MYB transcription networks and endocytosis. There was a trend for higher number of mutations, amplifications and driver events in samples with history of shammah exposure particularly those that tested EBV positive, suggesting an interaction between tobacco exposure and EBV. The work provides further evidence for the genetic heterogeneity of oral cancer and suggests shammah-associated OSCC is characterized by extensive amplification of oncogenes. © 2016 UICC.

  7. Selecting Candidates for Key Leadership Positions in Program Executive Offices Ground Combat Systems and Combat Service and Combat Service Support

    Science.gov (United States)

    2016-10-14

    start or continue a profitable growth pattern and boost morale and motivation, a poor decision may bring the company to the brink of financial...HON Frank Kendall issued a memorandum titled “Key Leadership Positions and Qualification Criteria” (Kendall, 2013). This memorandum provides a...Chief Developmental Tester • Program Lead, Business Financial Manager SELECTING CANDIDATES FOR KEY LEADERSHIP POSITIONS 4

  8. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites.

    Science.gov (United States)

    Amambua-Ngwa, Alfred; Tetteh, Kevin K A; Manske, Magnus; Gomez-Escobar, Natalia; Stewart, Lindsay B; Deerhake, M Elizabeth; Cheeseman, Ian H; Newbold, Christopher I; Holder, Anthony A; Knuepfer, Ellen; Janha, Omar; Jallow, Muminatou; Campino, Susana; Macinnis, Bronwyn; Kwiatkowski, Dominic P; Conway, David J

    2012-01-01

    Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome) had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs) for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3), and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%), indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing selection are now

  9. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites.

    Directory of Open Access Journals (Sweden)

    Alfred Amambua-Ngwa

    Full Text Available Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3, and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%, indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing

  10. RNA-Seq reveals seven promising candidate genes affecting the proportion of thick egg albumen in layer-type chickens.

    Science.gov (United States)

    Wan, Yi; Jin, Sihua; Ma, Chendong; Wang, Zhicheng; Fang, Qi; Jiang, Runshen

    2017-12-22

    Eggs with a much higher proportion of thick albumen are preferred in the layer industry, as they are favoured by consumers. However, the genetic factors affecting the thick egg albumen trait have not been elucidated. Using RNA sequencing, we explored the magnum transcriptome in 9 Rhode Island white layers: four layers with phenotypes of extremely high ratios of thick to thin albumen (high thick albumen, HTA) and five with extremely low ratios (low thick albumen, LTA). A total of 220 genes were differentially expressed, among which 150 genes were up-regulated and 70 were down-regulated in the HTA group compared with the LTA group. Gene Ontology (GO) analysis revealed that the up-regulated genes in HTA were mainly involved in a wide range of regulatory functions. In addition, a large number of these genes were related to glycosphingolipid biosynthesis, focal adhesion, ECM-receptor interactions and cytokine-cytokine receptor interactions. Based on functional analysis, ST3GAL4, FUT4, ITGA2, SDC3, PRLR, CDH4 and GALNT9 were identified as promising candidate genes for thick albumen synthesis and metabolism during egg formation. These results provide new insights into the molecular mechanisms of egg albumen traits and may contribute to future breeding strategies that optimise the proportion of thick egg albumen.

  11. Combined analysis of DNA methylome and transcriptome reveal novel candidate genes with susceptibility to bovine Staphylococcus aureus subclinical mastitis.

    Science.gov (United States)

    Song, Minyan; He, Yanghua; Zhou, Huangkai; Zhang, Yi; Li, Xizhi; Yu, Ying

    2016-07-14

    Subclinical mastitis is a widely spread disease of lactating cows. Its major pathogen is Staphylococcus aureus (S. aureus). In this study, we performed genome-wide integrative analysis of DNA methylation and transcriptional expression to identify candidate genes and pathways relevant to bovine S. aureus subclinical mastitis. The genome-scale DNA methylation profiles of peripheral blood lymphocytes in cows with S. aureus subclinical mastitis (SA group) and healthy controls (CK) were generated by methylated DNA immunoprecipitation combined with microarrays. We identified 1078 differentially methylated genes in SA cows compared with the controls. By integrating DNA methylation and transcriptome data, 58 differentially methylated genes were shared with differently expressed genes, in which 20.7% distinctly hypermethylated genes showed down-regulated expression in SA versus CK, whereas 14.3% dramatically hypomethylated genes showed up-regulated expression. Integrated pathway analysis suggested that these genes were related to inflammation, ErbB signalling pathway and mismatch repair. Further functional analysis revealed that three genes, NRG1, MST1 and NAT9, were strongly correlated with the progression of S. aureus subclinical mastitis and could be used as powerful biomarkers for the improvement of bovine mastitis resistance. Our studies lay the groundwork for epigenetic modification and mechanistic studies on susceptibility of bovine mastitis.

  12. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study.

    Directory of Open Access Journals (Sweden)

    Kevin Ten Haaf

    2017-04-01

    Full Text Available Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years. Nine previously established risk models were assessed for their ability to identify those most likely to develop or die from lung cancer. All models considered age and various aspects of smoking exposure (smoking status, smoking duration, cigarettes per day, pack-years smoked, time since smoking cessation as risk predictors. In addition, some models considered factors such as gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer.Retrospective analyses were performed on 53,452 National Lung Screening Trial (NLST participants (1,925 lung cancer cases and 884 lung cancer deaths and 80,672 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO ever-smoking participants (1,463 lung cancer cases and 915 lung cancer deaths. Six-year lung cancer incidence and mortality risk predictions were assessed for (1 calibration (graphically by comparing the agreement between the predicted and the observed risks, (2 discrimination (area under the receiver operating characteristic curve [AUC] between individuals with and without lung cancer (death, and (3 clinical usefulness (net benefit in decision curve analysis by identifying risk thresholds at which applying risk-based eligibility would improve lung cancer screening efficacy. To further assess performance, risk model sensitivities and specificities in the PLCO were compared to those based on the NLST eligibility criteria. Calibration was satisfactory, but discrimination ranged widely (AUCs from 0.61 to 0.81. The models outperformed the NLST eligibility criteria over a substantial range of risk thresholds in decision curve analysis, with a higher sensitivity for all models and a

  13. GWA Mapping of Anthocyanin Accumulation Reveals Balancing Selection of MYB90 in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Johanna A Bac-Molenaar

    Full Text Available Induction of anthocyanin accumulation by osmotic stress was assessed in 360 accessions of Arabidopsis thaliana. A wide range of natural variation, with phenotypes ranging from green to completely red/purple rosettes, was observed. A genome wide association (GWA mapping approach revealed that sequence diversity in a small 15 kb region on chromosome 1 explained 40% of the variation observed. Sequence and expression analyses of alleles of the candidate gene MYB90 identified a causal polymorphism at amino acid (AA position 210 of this transcription factor of the anthocyanin biosynthesis pathway. This amino acid discriminates the two most frequent alleles of MYB90. Both alleles are present in a substantial part of the population, suggesting balancing selection between these two alleles. Analysis of the geographical origin of the studied accessions suggests that the macro climate is not the driving force behind positive or negative selection for anthocyanin accumulation. An important role for local climatic conditions is, therefore, suggested. This study emphasizes that GWA mapping is a powerful approach to identify alleles that are under balancing selection pressure in nature.

  14. Structure-activity relationship analysis of cytotoxic cyanoguanidines: selection of CHS 828 as candidate drug

    Directory of Open Access Journals (Sweden)

    Gullbo Joachim

    2009-06-01

    Full Text Available Abstract Background N-(6-(4-chlorophenoxyhexyl-N'-cyano-N''-4-pyridyl guanidine (CHS 828 is the first candidate drug from a novel group of anti-tumour agents – the pyridyl cyanoguanidines, shown to be potent compounds interfering with cellular metabolism (inhibition of nicotinamide phosphoribosyl transferase and NF-κB signalling. Substituted cyanoguanidines are also found in anti-hypertensive agents such as the potassium channel opener pinacidil (N-cyano-N'-(4-pyridyl-N''-(1,2,2-trimethylpropylguanidine and histamine-II receptor antagonists (e.g. cimetidine, N-cyano-N'-methyl-N''-[2-[[(5-methylimidazol-4-yl]methyl]thio]ethylguanidine. In animal studies, CHS 828 has shown very promising activity, and phase I and II studies resulted in further development of a with a water soluble prodrug. Findings To study the structural requirements for cyanoguanidine cytotoxicity a set of 19 analogues were synthesized. The cytotoxic effects were then studied in ten cell lines selected for different origins and mechanisms of resistance, using the fluorometric microculture cytotoxicity assay (FMCA. The compounds showed varying cytotoxic activity even though the dose-response curves for some analogues were very shallow. Pinacidil and cimetidine were found to be non-toxic in all ten cell lines. Starting with cyanoguanidine as the crucial core it was shown that 4-pyridyl substitution was more efficient than was 3-pyridyl substitution. The 4-pyridyl cyanoguanidine moiety should be linked by an alkyl chain, optimally a hexyl, heptyl or octyl chain, to a bulky end group. The exact composition of this end group did not seem to be of crucial importance; when the end group was a mono-substituted phenyl ring it was shown that the preferred position was 4-substitution, followed by 3- and, finally, 2-substitution as the least active. Whether the substituent was a chloro, nitro or methoxy substituent seemed to be of minor importance. Finally, the activity patterns in the

  15. A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions

    Science.gov (United States)

    Hostetler, Jessica B.; Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.; Fairhurst, Rick M.; Rayner, Julian C.

    2015-01-01

    Background A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. Methodology/Principal Findings We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further

  16. mRNA expression pattern of selected candidate genes differs in bovine oviductal epithelial cells in vitro compared with the in vivo state and during cell culture passages.

    Science.gov (United States)

    Danesh Mesgaran, Sadjad; Sharbati, Jutta; Einspanier, Ralf; Gabler, Christoph

    2016-08-15

    The mammalian oviduct provides the optimal environment for gamete maturation including sperm capacitation, fertilization, and development of the early embryo. Various cell culture models for primary bovine oviductal epithelial cells (BOEC) were established to reveal such physiological events. The aim of this study was to evaluate 17 candidate mRNA expression patterns in oviductal epithelial cells (1) in transition from in vivo cells to in vitro cells; (2) during three consecutive cell culture passages; (3) affected by the impact of LOW or HIGH glucose content media; and (4) influenced by different phases of the estrous cycle in vivo and in vitro. In addition, the release of a metabolite and proteins from BOEC at two distinct cell culture passage numbers was estimated to monitor the functionality. BOEC from 8 animals were isolated and cultured for three consecutive passages. Total RNA was extracted from in vivo and in vitro samples and subjected to reverse transcription quantitative polymerase chain reaction to reveal mRNA expression of selected candidate genes. The release of prostaglandin E2 (PGE2), oviduct-specific glycoprotein 1 (OVGP1) and interleukin 8 (IL8) by BOEC was measured by EIA or ELISA after 24 h. Almost all candidate genes (prostaglandin synthases, enzymes of cellular metabolism and mucins) mRNA expression pattern differed compared in vivo with in vitro state. In addition, transcription of most candidate genes was influenced by the number of cell culture passages. Different glucose medium content did not affect mRNA expression of most candidate genes. The phase of the estrous cycle altered some candidate mRNA expression in BOEC in vitro at later passages. The release of PGE2 and OVGP1 between passages did not differ. However, BOEC in passage 3 released significantly higher amount of IL8 compared with cells in passage 0. This study supports the hypothesis that candidate mRNA expression in BOEC was influenced by transition from the in vivo situation

  17. Signatures of selection in tilapia revealed by whole genome resequencing.

    Science.gov (United States)

    Xia, Jun Hong; Bai, Zhiyi; Meng, Zining; Zhang, Yong; Wang, Le; Liu, Feng; Jing, Wu; Wan, Zi Yi; Li, Jiale; Lin, Haoran; Yue, Gen Hua

    2015-09-16

    Natural selection and selective breeding for genetic improvement have left detectable signatures within the genome of a species. Identification of selection signatures is important in evolutionary biology and for detecting genes that facilitate to accelerate genetic improvement. However, selection signatures, including artificial selection and natural selection, have only been identified at the whole genome level in several genetically improved fish species. Tilapia is one of the most important genetically improved fish species in the world. Using next-generation sequencing, we sequenced the genomes of 47 tilapia individuals. We identified a total of 1.43 million high-quality SNPs and found that the LD block sizes ranged from 10-100 kb in tilapia. We detected over a hundred putative selective sweep regions in each line of tilapia. Most selection signatures were located in non-coding regions of the tilapia genome. The Wnt signaling, gonadotropin-releasing hormone receptor and integrin signaling pathways were under positive selection in all improved tilapia lines. Our study provides a genome-wide map of genetic variation and selection footprints in tilapia, which could be important for genetic studies and accelerating genetic improvement of tilapia.

  18. Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice

    Directory of Open Access Journals (Sweden)

    Ran Huimin

    2008-08-01

    Full Text Available Abstract Background Prosaposin encodes, in tandem, four small acidic activator proteins (saposins with specificities for glycosphingolipid (GSL hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies. Results Our hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null (PS-/- and a V394L/V394L glucocerebrosidase mutation combined with PS-NA (4L/PS-NA. Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT/enhancer-binding protein delta (CEBPD was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport. Conclusion These results show that: 1 Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2 Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3 CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression.

  19. A CAUTIONARY TALE: MARVELS BROWN DWARF CANDIDATE REVEALS ITSELF TO BE A VERY LONG PERIOD, HIGHLY ECCENTRIC SPECTROSCOPIC STELLAR BINARY

    International Nuclear Information System (INIS)

    Mack, Claude E. III; Stassun, Keivan G.; De Lee, Nathan; Ge, Jian; Fleming, Scott W.; Deshpande, Rohit; Mahadevan, Suvrath; Wisniewski, John P.; Gaudi, B. Scott; Eastman, Jason; Beatty, Thomas G.; Ghezzi, Luan; González Hernández, Jonay I.; Femenía, Bruno; Mata Sánchez, Daniel; Ferreira, Letícia; Porto de Mello, Gustavo; Crepp, Justin R.; Agol, Eric; Bizyaev, Dmitry

    2013-01-01

    We report the discovery of a highly eccentric, double-lined spectroscopic binary star system (TYC 3010-1494-1), comprising two solar-type stars that we had initially identified as a single star with a brown dwarf companion. At the moderate resolving power of the MARVELS spectrograph and the spectrographs used for subsequent radial-velocity (RV) measurements (R ∼ Jup ) to a solar-type primary. At least three properties of this system allow it to masquerade as a single star with a very-low-mass companion: its large eccentricity (e ∼ 0.8), its relatively long period (P ∼ 238 days), and the approximately perpendicular orientation of the semi-major axis with respect to the line of sight (ω ∼ 189°). As a result of these properties, for ∼95% of the orbit the two sets of stellar spectral lines are completely blended, and the RV measurements based on centroiding on the apparently single-lined spectrum is very well fit by an orbit solution indicative of a brown dwarf companion on a more circular orbit (e ∼ 0.3). Only during the ∼5% of the orbit near periastron passage does the true, double-lined nature and large RV amplitude of ∼15 km s –1 reveal itself. The discovery of this binary system is an important lesson for RV surveys searching for substellar companions; at a given resolution and observing cadence, a survey will be susceptible to these kinds of astrophysical false positives for a range of orbital parameters. Finally, for surveys like MARVELS that lack the resolution for a useful line bisector analysis, it is imperative to monitor the peak of the cross-correlation function for suspicious changes in width or shape, so that such false positives can be flagged during the candidate vetting process.

  20. Cotranslational protein folding reveals the selective use of ...

    Indian Academy of Sciences (India)

    to fold properly by decelerating the translation rate at these sites. Thus the cotranslational protein folding is believed to be true for many proteins and is an important selection factor for the selective codon usage to optimize proper gene expres- sion and function (Komar 2009). A web server CS and S has been created by ...

  1. Selection of candidate wells and optimization of conformance treatment design in the Barrancas Field using a 3D conformance simulator

    Energy Technology Data Exchange (ETDEWEB)

    Crosta, Dante; Elitseche, Luis [Repsol YPF (Argentina); Gutierrez, Mauricio; Ansah, Joe; Everett, Don [Halliburton Argentina S.A., Buenos Aires (Argentina)

    2004-07-01

    Minimizing the amount of unwanted water production is an important goal at the Barrancas field. This paper describes a selection process for candidate injection wells that is part of a pilot conformance project aimed at improving vertical injection profiles, reducing water cut in producing wells, and improving ultimate oil recovery from this field. The well selection process is based on a review of limited reservoir information available for this field to determine inter-well communications. The methodology focuses on the best use of available information, such as production and injection history, well intervention files, open hole logs and injectivity surveys. After the candidate wells were selected and potential water injection channels were identified, conformance treatment design and future performance of wells in the selected pilot area were evaluated using a new 3 -D conformance simulator, developed specifically for optimization of the design and placement of unwanted fluid shut-off treatments. Thus, when acceptable history match ing of the pilot area production was obtained, the 3 -D simulator was used to: evaluate the required volume of selected conformance treatment fluid; review expected pressures and rates during placement;. model temperature behavior; evaluate placement techniques, and forecast water cut reduction and incremental oil recovery from the producers in this simulated section of the pilot area. This paper outlines a methodology for selecting candidate wells for conformance treatments. The method involves application of several engineering tools, an integral component of which is a user-friendly conformance simulator. The use of the simulator has minimized data preparation time and allows the running of sensitivity cases quickly to explore different possible scenarios that best represent the reservoir. The proposed methodology provides an efficient means of identifying conformance problems and designing optimized solutions for these individual

  2. Machine learning in infrared object classification - an all-sky selection of YSO candidates

    Science.gov (United States)

    Marton, Gabor; Zahorecz, Sarolta; Toth, L. Viktor; Magnus McGehee, Peregrine; Kun, Maria

    2015-08-01

    Object classification is a fundamental and challenging problem in the era of big data. I will discuss up-to-date methods and their application to classify infrared point sources.We analysed the ALLWISE catalogue, the most recent public source catalogue of the Wide-field Infrared Survey Explorer (WISE) to compile a reliable list of Young Stellar Object (YSO) candidates. We tested and compared classical and up-to-date statistical methods as well, to discriminate source types like extragalactic objects, evolved stars, main sequence stars, objects related to the interstellar medium and YSO candidates by using their mid-IR WISE properties and associated near-IR 2MASS data.In the particular classification problem the Support Vector Machines (SVM), a class of supervised learning algorithm turned out to be the best tool. As a result we classify Class I and II YSOs with >90% accuracy while the fraction of contaminating extragalactic objects remains well below 1%, based on the number of known objects listed in the SIMBAD and VizieR databases. We compare our results to other classification schemes from the literature and show that the SVM outperforms methods that apply linear cuts on the colour-colour and colour-magnitude space. Our homogenous YSO candidate catalog can serve as an excellent pathfinder for future detailed observations of individual objects and a starting point of statistical studies that aim to add pieces to the big picture of star formation theory.

  3. THE TAURUS SPITZER SURVEY: NEW CANDIDATE TAURUS MEMBERS SELECTED USING SENSITIVE MID-INFRARED PHOTOMETRY

    International Nuclear Information System (INIS)

    Rebull, L. M.; Padgett, D. L.; McCabe, C.-E.; Noriega-Crespo, A.; Carey, S. J.; Brooke, T.; Hillenbrand, L. A.; Stapelfeldt, K. R.; Angione, J. R.; Huard, T.; Terebey, S.; Audard, M.; Baldovin-Saavedra, C.; Monin, J.-L.; Menard, F.; Bouvier, J.; Fukagawa, M.; Guedel, M.; Knapp, G. R.; Allen, L. E.

    2010-01-01

    We report on the properties of pre-main-sequence objects in the Taurus molecular clouds as observed in seven mid- and far-infrared bands with the Spitzer Space Telescope. There are 215 previously identified members of the Taurus star-forming region in our ∼44 deg 2 map; these members exhibit a range of Spitzer colors that we take to define young stars still surrounded by circumstellar dust (noting that ∼20% of the bona fide Taurus members exhibit no detectable dust excesses). We looked for new objects in the survey field with similar Spitzer properties, aided by extensive optical, X-ray, and ultraviolet imaging, and found 148 new candidate members of Taurus. We have obtained follow-up spectroscopy for about half the candidate sample, thus far confirming 34 new members, three probable new members, and 10 possible new members, an increase of 15%-20% in Taurus members. Of the objects for which we have spectroscopy, seven are now confirmed extragalactic objects, and one is a background Be star. The remaining 93 candidate objects await additional analysis and/or data to be confirmed or rejected as Taurus members. Most of the new members are Class II M stars and are located along the same cloud filaments as the previously identified Taurus members. Among non-members with Spitzer colors similar to young, dusty stars are evolved Be stars, planetary nebulae, carbon stars, galaxies, and active galactic nuclei.

  4. NEW YOUNG STAR CANDIDATES IN THE TAURUS-AURIGA REGION AS SELECTED FROM THE WIDE-FIELD INFRARED SURVEY EXPLORER

    International Nuclear Information System (INIS)

    Rebull, L. M.; Padgett, D. L.; Noriega-Crespo, A.

    2011-01-01

    The Taurus Molecular Cloud subtends a large solid angle on the sky, in excess of 250 deg 2 . The search for legitimate Taurus members to date has been limited by sky coverage as well as the challenge of distinguishing members from field interlopers. The Wide-field Infrared Survey Explorer has recently observed the entire sky, and we take advantage of the opportunity to search for young stellar object (YSO) candidate Taurus members from a ∼260 deg 2 region designed to encompass previously identified Taurus members. We use near- and mid-infrared colors to select objects with apparent infrared excesses and incorporate other catalogs of ancillary data to present a list of rediscovered Taurus YSOs with infrared excesses (taken to be due to circumstellar disks), a list of rejected YSO candidates (largely galaxies), and a list of 94 surviving candidate new YSO-like Taurus members. There is likely to be contamination lingering in this candidate list, and follow-up spectra are warranted.

  5. QUASI-STELLAR OBJECT SELECTION ALGORITHM USING TIME VARIABILITY AND MACHINE LEARNING: SELECTION OF 1620 QUASI-STELLAR OBJECT CANDIDATES FROM MACHO LARGE MAGELLANIC CLOUD DATABASE

    International Nuclear Information System (INIS)

    Kim, Dae-Won; Protopapas, Pavlos; Alcock, Charles; Trichas, Markos; Byun, Yong-Ik; Khardon, Roni

    2011-01-01

    We present a new quasi-stellar object (QSO) selection algorithm using a Support Vector Machine, a supervised classification method, on a set of extracted time series features including period, amplitude, color, and autocorrelation value. We train a model that separates QSOs from variable stars, non-variable stars, and microlensing events using 58 known QSOs, 1629 variable stars, and 4288 non-variables in the MAssive Compact Halo Object (MACHO) database as a training set. To estimate the efficiency and the accuracy of the model, we perform a cross-validation test using the training set. The test shows that the model correctly identifies ∼80% of known QSOs with a 25% false-positive rate. The majority of the false positives are Be stars. We applied the trained model to the MACHO Large Magellanic Cloud (LMC) data set, which consists of 40 million light curves, and found 1620 QSO candidates. During the selection none of the 33,242 known MACHO variables were misclassified as QSO candidates. In order to estimate the true false-positive rate, we crossmatched the candidates with astronomical catalogs including the Spitzer Surveying the Agents of a Galaxy's Evolution LMC catalog and a few X-ray catalogs. The results further suggest that the majority of the candidates, more than 70%, are QSOs.

  6. Integrated Metabolo-Transcriptomics Reveals Fusarium Head Blight Candidate Resistance Genes in Wheat QTL-Fhb2.

    Directory of Open Access Journals (Sweden)

    Dhananjay Dhokane

    Full Text Available Fusarium head blight (FHB caused by Fusarium graminearum not only causes severe losses in yield, but also reduces quality of wheat grain by accumulating mycotoxins. Breeding for host plant resistance is considered as the best strategy to manage FHB. Resistance in wheat to FHB is quantitative in nature, involving cumulative effects of many genes governing resistance. The poor understanding of genetics and lack of precise phenotyping has hindered the development of FHB resistant cultivars. Though more than 100 QTLs imparting FHB resistance have been reported, none discovered the specific genes localized within the QTL region, nor the underlying mechanisms of resistance.In our study recombinant inbred lines (RILs carrying resistant (R-RIL and susceptible (S-RIL alleles of QTL-Fhb2 were subjected to metabolome and transcriptome profiling to discover the candidate genes. Metabolome profiling detected a higher abundance of metabolites belonging to phenylpropanoid, lignin, glycerophospholipid, flavonoid, fatty acid, and terpenoid biosynthetic pathways in R-RIL than in S-RIL. Transcriptome analysis revealed up-regulation of several receptor kinases, transcription factors, signaling, mycotoxin detoxification and resistance related genes. The dissection of QTL-Fhb2 using flanking marker sequences, integrating metabolomic and transcriptomic datasets, identified 4-Coumarate: CoA ligase (4CL, callose synthase (CS, basic Helix Loop Helix (bHLH041 transcription factor, glutathione S-transferase (GST, ABC transporter-4 (ABC4 and cinnamyl alcohol dehydrogenase (CAD as putative resistance genes localized within the QTL-Fhb2 region.Some of the identified genes within the QTL region are associated with structural resistance through cell wall reinforcement, reducing the spread of pathogen through rachis within a spike and few other genes that detoxify DON, the virulence factor, thus eventually reducing disease severity. In conclusion, we report that the wheat

  7. Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds

    Energy Technology Data Exchange (ETDEWEB)

    Shi, CY; Yang, H; Wei, CL; Yu, O; Zhang, ZZ; Sun, J; Wan, XC

    2011-01-01

    Tea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq) provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes. Using high-throughput Illumina RNA-seq, the transcriptome from poly (A){sup +} RNA of C. sinensis was analyzed at an unprecedented depth (2.59 gigabase pairs). Approximate 34.5 million reads were obtained, trimmed, and assembled into 127,094 unigenes, with an average length of 355 bp and an N50 of 506 bp, which consisted of 788 contig clusters and 126,306 singletons. This number of unigenes was 10-fold higher than existing C. sinensis sequences deposited in GenBank (as of August 2010). Sequence similarity analyses against six public databases (Uniprot, NR and COGs at NCBI, Pfam, InterPro and KEGG) found 55,088 unigenes that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Some of the unigenes were assigned to putative metabolic pathways. Targeted searches using these annotations identified the majority of genes associated with several primary metabolic pathways and natural product pathways that are important to tea quality, such as flavonoid, theanine and caffeine biosynthesis pathways. Novel candidate genes of these secondary pathways were discovered. Comparisons with four previously prepared cDNA libraries revealed that this transcriptome dataset has both a high degree of consistency with previous EST data and an approximate 20 times increase in coverage. Thirteen unigenes related to theanine and flavonoid synthesis were validated. Their expression patterns in different organs of the tea plant were analyzed by RT-PCR and quantitative real

  8. A CAUTIONARY TALE: MARVELS BROWN DWARF CANDIDATE REVEALS ITSELF TO BE A VERY LONG PERIOD, HIGHLY ECCENTRIC SPECTROSCOPIC STELLAR BINARY

    Energy Technology Data Exchange (ETDEWEB)

    Mack, Claude E. III; Stassun, Keivan G.; De Lee, Nathan [Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235 (United States); Ge, Jian; Fleming, Scott W. [Department of Astronomy, University of Florida, 211 Bryant Space Science Center, Gainesville, FL, 32611-2055 (United States); Deshpande, Rohit; Mahadevan, Suvrath [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Wisniewski, John P. [Homer L Dodge Department of Physics and Astronomy, University of Oklahoma, 440 W Brooks St, Norman, OK 73019 (United States); Gaudi, B. Scott; Eastman, Jason; Beatty, Thomas G. [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Ghezzi, Luan [Observatorio Nacional, Rua Gal. Jose Cristino 77, Rio de Janeiro, RJ 20921-400 (Brazil); Gonzalez Hernandez, Jonay I.; Femenia, Bruno; Mata Sanchez, Daniel [Instituto de Astrofisica de Canarias (IAC), E-38205 La Laguna, Tenerife (Spain); Ferreira, Leticia; Porto de Mello, Gustavo [Laboratorio Interinstitucional de e-Astronomia-LIneA, Rua Gal. Jose Cristino 77, Rio de Janeiro, RJ 20921-400 (Brazil); Crepp, Justin R. [Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556 (United States); Agol, Eric [Astronomy Department, University of Washington, Box 351580, Seattle, WA 98195 (United States); Bizyaev, Dmitry, E-mail: claude.e.mack@vanderbilt.edu [Apache Point Observatory, P.O. Box 59, Sunspot, NM 88349-0059 (United States); and others

    2013-05-15

    We report the discovery of a highly eccentric, double-lined spectroscopic binary star system (TYC 3010-1494-1), comprising two solar-type stars that we had initially identified as a single star with a brown dwarf companion. At the moderate resolving power of the MARVELS spectrograph and the spectrographs used for subsequent radial-velocity (RV) measurements (R {approx}< 30, 000), this particular stellar binary mimics a single-lined binary with an RV signal that would be induced by a brown dwarf companion (Msin i {approx} 50 M{sub Jup}) to a solar-type primary. At least three properties of this system allow it to masquerade as a single star with a very-low-mass companion: its large eccentricity (e {approx} 0.8), its relatively long period (P {approx} 238 days), and the approximately perpendicular orientation of the semi-major axis with respect to the line of sight ({omega} {approx} 189 Degree-Sign ). As a result of these properties, for {approx}95% of the orbit the two sets of stellar spectral lines are completely blended, and the RV measurements based on centroiding on the apparently single-lined spectrum is very well fit by an orbit solution indicative of a brown dwarf companion on a more circular orbit (e {approx} 0.3). Only during the {approx}5% of the orbit near periastron passage does the true, double-lined nature and large RV amplitude of {approx}15 km s{sup -1} reveal itself. The discovery of this binary system is an important lesson for RV surveys searching for substellar companions; at a given resolution and observing cadence, a survey will be susceptible to these kinds of astrophysical false positives for a range of orbital parameters. Finally, for surveys like MARVELS that lack the resolution for a useful line bisector analysis, it is imperative to monitor the peak of the cross-correlation function for suspicious changes in width or shape, so that such false positives can be flagged during the candidate vetting process.

  9. Deep sequencing of the Camellia sinensis transcriptome revealed candidate genes for major metabolic pathways of tea-specific compounds

    Directory of Open Access Journals (Sweden)

    Chen Qi

    2011-02-01

    Full Text Available Abstract Background Tea is one of the most popular non-alcoholic beverages worldwide. However, the tea plant, Camellia sinensis, is difficult to culture in vitro, to transform, and has a large genome, rendering little genomic information available. Recent advances in large-scale RNA sequencing (RNA-seq provide a fast, cost-effective, and reliable approach to generate large expression datasets for functional genomic analysis, which is especially suitable for non-model species with un-sequenced genomes. Results Using high-throughput Illumina RNA-seq, the transcriptome from poly (A+ RNA of C. sinensis was analyzed at an unprecedented depth (2.59 gigabase pairs. Approximate 34.5 million reads were obtained, trimmed, and assembled into 127,094 unigenes, with an average length of 355 bp and an N50 of 506 bp, which consisted of 788 contig clusters and 126,306 singletons. This number of unigenes was 10-fold higher than existing C. sinensis sequences deposited in GenBank (as of August 2010. Sequence similarity analyses against six public databases (Uniprot, NR and COGs at NCBI, Pfam, InterPro and KEGG found 55,088 unigenes that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Some of the unigenes were assigned to putative metabolic pathways. Targeted searches using these annotations identified the majority of genes associated with several primary metabolic pathways and natural product pathways that are important to tea quality, such as flavonoid, theanine and caffeine biosynthesis pathways. Novel candidate genes of these secondary pathways were discovered. Comparisons with four previously prepared cDNA libraries revealed that this transcriptome dataset has both a high degree of consistency with previous EST data and an approximate 20 times increase in coverage. Thirteen unigenes related to theanine and flavonoid synthesis were validated. Their expression patterns in different organs of the tea plant were

  10. Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection.

    Science.gov (United States)

    Wang, Yong; Wu, Qiao-Feng; Chen, Chen; Wu, Ling-Yun; Yan, Xian-Zhong; Yu, Shu-Guang; Zhang, Xiang-Sun; Liang, Fan-Rong

    2012-01-01

    Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use. In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment. Specifically, we generate and investigate the high-throughput metabolic profiles of acupuncture treatment at several acupoints in human. To select the subsets of metabolites that best characterize the acupuncture effect for each meridian point, an optimization model is proposed to identify biomarkers from high-dimensional metabolic data from case and control samples. Importantly, we use nearest centroid as the prototype to simultaneously minimize the number of selected features and the leave-one-out cross validation error of classifier. We compared the performance of LPFS to several state-of-the-art methods, such as SVM recursive feature elimination (SVM-RFE) and sparse multinomial logistic regression approach (SMLR). We find that our LPFS method tends to reveal a small set of metabolites with small standard deviation and large shifts, which exactly serves our requirement for good biomarker. Biologically, several metabolite biomarkers for acupuncture treatment are revealed and serve as the candidates for further mechanism investigation. Also biomakers derived from five meridian points, Zusanli (ST36), Liangmen (ST21), Juliao (ST3), Yanglingquan (GB34), and Weizhong (BL40), are compared for their similarity and difference, which provide evidence for the specificity of acupoints. Our result demonstrates that metabolic profiling might be a promising method to

  11. FINDING η CAR ANALOGS IN NEARBY GALAXIES USING SPITZER. I. CANDIDATE SELECTION

    International Nuclear Information System (INIS)

    Khan, Rubab; Stanek, K. Z.; Kochanek, C. S.

    2013-01-01

    The late-stage evolution of the most massive stars such as η Carinae is controlled by the effects of mass loss, which may be dominated by poorly understood eruptive mass ejections. Understanding this population is challenging because no true analogs of η Car have been clearly identified in the Milky Way or other galaxies. We utilize Spitzer IRAC images of seven nearby (∼ 10 5 L ☉ in the IRAC bands (3.6 to 8.0 μm) and are not known to be background sources. Based on our estimates for the expected number of background sources, we expect that follow-up observations will show that most of these candidates are not dust enshrouded massive stars, with an expectation of only 6 ± 6 surviving candidates. Since we would detect true analogs of η Car for roughly 200 years post-eruption, this implies that the rate of eruptions like η Car is less than the core-collapse supernova rate. It is possible, however, that every M > 40 M ☉ star undergoes such eruptions given our initial results. In Paper II we will characterize the candidates through further analysis and follow-up observations, and there is no barrier to increasing the galaxy sample by an order of magnitude. The primary limitation of the present search is that Spitzer's resolution limits us to the shorter wavelength IRAC bands. With the James Webb Space Telescope, such surveys can be carried out at the far more optimal wavelengths of 10-30 μm, allowing identification of η Car analogs for millennia rather than centuries post-eruption.

  12. Results of the ESA study on psychological selection of astronaut candidates for Columbus missions II: Personality assessment

    Science.gov (United States)

    Goeters, Klaus-Martin; Fassbender, Christoph

    A unique composition of personality assessment methods was applied to a group of 97 ESA scientists and engineers. This group is highly comparable to real astronaut candidates with respect to age and education. The list of used tests includes personality questionnaires, problem solving in groups as well as a projective technique. The study goals were: 1. Verification of psychometric qualities and applicability of tests to the target group; 2. Search for culture-fair tests by which multi-national European groups can be examined; 3. Identification of test methods by which the adaptability of the candidates to the psycho-social stress of long-duration space flights can be assessed. Based on the empirical findings, a test battery was defined which can be used in the selection of ESA space personnel.

  13. Biohazard Analysis of Select Biodefense Vaccine Candidates - Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella Tularensis LVS

    International Nuclear Information System (INIS)

    Rao, V.

    2007-01-01

    Biohazard assessment of biodefense vaccine candidates forms the basis for a facility- and activity-specific risk assessment performed to determine the biosafety levels and general safety standards required for biological product development. As a part of our support to the US biodefense vaccine development program, we perform a systematic biohazard assessment of potential vaccine candidates with the primary objective to, (a) Identify and characterize hazard elements associated with the wild type and vaccine strains, (b) Provide biohazard information on the etiologic agent (vaccine candidate) to assess Phase 1 clinical trial facility sites, (c) Provide a baseline to conduct an agent and facility-specific risk assessment at clinical trial facilities interested in performing phase 1 clinical trial, (d) Provide comparative hazard profiles of the vaccine candidates wit MSDS for wild-type to identify and establish appropriate protective biosafety levels, and (e) Support determination of a hazard level to select personal protective equipment as required under the OSHA guidelines. This paper will describe the biohazard analysis of two vaccine candidates, Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella tularensis LVS, a viral and bacterial agent, respectively. As part of the biohazard assessment we preformed a thorough review of published literature on medical pathology, epidemiology, pre-clinical investigational studies, and environmental data on the etiologic agent subtypes and the vaccine candidates. Using standard analytical procedures, the data were then analyzed relative to two intrinsic hazard parameters-health hazard and environmental hazard. Using a weight-of-evidence (WOE) approach, the potential hazards of etiologic agent wild subtypes and vaccine candidates were ranked under three main categories: Public Health Hazard, Environmental Hazard, and Overall Hazard. A WOE scoring system allows for both a determination of the intrinsic hazard of each

  14. Biohazard Analysis of Select Biodefense Vaccine Candidates - Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella Tularensis LVS

    Energy Technology Data Exchange (ETDEWEB)

    Rao, V [National Security Programs, Computer Science Corporation, Alexandria (United States)

    2007-07-01

    Biohazard assessment of biodefense vaccine candidates forms the basis for a facility- and activity-specific risk assessment performed to determine the biosafety levels and general safety standards required for biological product development. As a part of our support to the US biodefense vaccine development program, we perform a systematic biohazard assessment of potential vaccine candidates with the primary objective to, (a) Identify and characterize hazard elements associated with the wild type and vaccine strains, (b) Provide biohazard information on the etiologic agent (vaccine candidate) to assess Phase 1 clinical trial facility sites, (c) Provide a baseline to conduct an agent and facility-specific risk assessment at clinical trial facilities interested in performing phase 1 clinical trial, (d) Provide comparative hazard profiles of the vaccine candidates wit MSDS for wild-type to identify and establish appropriate protective biosafety levels, and (e) Support determination of a hazard level to select personal protective equipment as required under the OSHA guidelines. This paper will describe the biohazard analysis of two vaccine candidates, Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella tularensis LVS, a viral and bacterial agent, respectively. As part of the biohazard assessment we preformed a thorough review of published literature on medical pathology, epidemiology, pre-clinical investigational studies, and environmental data on the etiologic agent subtypes and the vaccine candidates. Using standard analytical procedures, the data were then analyzed relative to two intrinsic hazard parameters-health hazard and environmental hazard. Using a weight-of-evidence (WOE) approach, the potential hazards of etiologic agent wild subtypes and vaccine candidates were ranked under three main categories: Public Health Hazard, Environmental Hazard, and Overall Hazard. A WOE scoring system allows for both a determination of the intrinsic hazard of each

  15. Selective interference reveals dissociation between memory for location and colour.

    Science.gov (United States)

    Vuontela, V; Rämä, P; Raninen, A; Aronen, H J; Carlson, S

    1999-08-02

    The aim was to study whether there is indication of a dissociation in processing of visuospatial and colour information in working memory in humans. Experimental subjects performed visuospatial and colour n-back tasks with and without visuospatial and colour distractive stimuli presented in the middle of the delay period to specifically affect mnemonic processing of task-related information. In the high memory-load condition, the visuospatial, but not the colour, task was selectively disrupted by visuospatial but not colour distractors. When subvocal rehearsal of the memoranda in the colour task was prevented by articulatory suppression; colour task performance was also selectively disrupted by distractors qualitatively similar to the memoranda. The results support the suggestion that visual working memory for location is processed separate from that for colour.

  16. The Job Market for Justice: Screening and selecting candidates for the International Court of Justice

    DEFF Research Database (Denmark)

    Creamer, Cosette; Godzimirska, Zuzanna

    2017-01-01

    Over the past few decades, states have granted greater independence and authority to international courts, yet still retain their ability to control who sits on the bench. This article examines how governments use their power of judicial nomination and appointment in the context of the Internatio......Over the past few decades, states have granted greater independence and authority to international courts, yet still retain their ability to control who sits on the bench. This article examines how governments use their power of judicial nomination and appointment in the context...... of the International Court of Justice (ICJ) and assesses the relative influence of three factors on states’ vote choices for ICJ candidates: the candidates’ probability of (in)sensitivity to political considerations; their qualifications; and the role of inter-state politics. Drawing on a new dataset of candidates...... signaling a probability of insensitivity to political considerations reduce a candidate’s expected vote share. A candidate’s qualifications, on the other hand, do not appear to make a considerable difference in winning more votes. Finally, the amount of support during the nomination stage is highly...

  17. How To Select the Right Candidate for an Internship Program for Japanese Host Companies.

    Science.gov (United States)

    Kumayama, Akihisa

    The method used by the American Graduate School of International Management (AZ) to select participants for internships with Japanese companies is described and some case studies are offered as illustrations. The composition of the selection committee is noted, the interview process is discussed briefly (focusing on elicitation of student…

  18. Selecting Resident Assistants: The Relationship between Candidate Assessment and Job Performance

    Science.gov (United States)

    Berg, Stephen A.; Stoner, James C.

    2016-01-01

    Selecting resident assistants is integral to the success of housing operations on college and university campuses. Recruiting high-performing student staff is a priority in achieving departmental goals. Despite the importance of this process and the amount of time and resources expended during selection, there is scarce research investigating the…

  19. Spectro-temporal modulation masking patterns reveal frequency selectivity.

    Science.gov (United States)

    Oetjen, Arne; Verhey, Jesko L

    2015-02-01

    The present study investigated the possibility that the human auditory system demonstrates frequency selectivity to spectro-temporal amplitude modulations. Threshold modulation depth for detecting sinusoidal spectro-temporal modulations was measured using a generalized masked threshold pattern paradigm with narrowband masker modulations. Four target spectro-temporal modulations were examined, differing in their temporal and spectral modulation frequencies: a temporal modulation of -8, 8, or 16 Hz combined with a spectral modulation of 1 cycle/octave and a temporal modulation of 4 Hz combined with a spectral modulation of 0.5 cycles/octave. The temporal center frequencies of the masker modulation ranged from 0.25 to 4 times the target temporal modulation. The spectral masker-modulation center-frequencies were 0, 0.5, 1, 1.5, and 2 times the target spectral modulation. For all target modulations, the pattern of average thresholds for the eight normal-hearing listeners was consistent with the hypothesis of a spectro-temporal modulation filter. Such a pattern of modulation-frequency sensitivity was predicted on the basis of psychoacoustical data for purely temporal amplitude modulations and purely spectral amplitude modulations. An analysis of separability indicates that, for the present data set, selectivity in the spectro-temporal modulation domain can be described by a combination of a purely spectral and a purely temporal modulation filter function.

  20. Size-selective performance evaluation of candidate aerosol inlets using polydisperse aerosols

    Data.gov (United States)

    U.S. Environmental Protection Agency — Presented are detailed techniques for the generation, collection, and analysis of polydisperse calibration aerosols for wind tunnel evaluation of size-selective...

  1. Stroop tasks reveal abnormal selective attention among psychopathic offenders.

    Science.gov (United States)

    Hiatt, Kristina D; Schmitt, William A; Newman, Joseph P

    2004-01-01

    Selective attention among offenders with psychopathy was investigated using 3 Stroop paradigms: a standard color-word (CW) Stroop, a picture-word (PW) Stroop, and a color-word Stroop in which the word and color were spatially separated (separated CW). Consistent with "overselective" attention, offenders with psychopathy displayed reduced Stroop interference on the separated CW and PW tasks relative to offenders who were not psychopathic. However, offenders with psychopathy displayed normal Stroop interference on the standard CW Stroop. Further, the reduced interference of offenders with psychopathy on the separated CW Stroop was accompanied by normal facilitation. These findings suggest a circumscribed attentional deficit in psychopathy that hinders the use of unattended information that is (a) not integrated with deliberately attended information and (b) not compatible with current goal-directed behavior. ((c) 2004 APA, all rights reserved)

  2. The HDUV Survey: Six Lyman Continuum Emitter Candidates at z ˜ 2 Revealed by HST UV Imaging

    Science.gov (United States)

    Naidu, R. P.; Oesch, P. A.; Reddy, N.; Holden, B.; Steidel, C. C.; Montes, M.; Atek, H.; Bouwens, R. J.; Carollo, C. M.; Cibinel, A.; Illingworth, G. D.; Labbé, I.; Magee, D.; Morselli, L.; Nelson, E. J.; van Dokkum, P. G.; Wilkins, S.

    2017-09-01

    We present six galaxies at z˜ 2 that show evidence of Lyman continuum (LyC) emission based on the newly acquired UV imaging of the Hubble Deep UV legacy survey (HDUV) conducted with the WFC3/UVIS camera on the Hubble Space Telescope (HST). At the redshift of these sources, the HDUV F275W images partially probe the ionizing continuum. By exploiting the HST multiwavelength data available in the HDUV/GOODS fields, models of the UV spectral energy distributions, and detailed Monte Carlo simulations of the intergalactic medium absorption, we estimate the absolute ionizing photon escape fractions of these galaxies to be very high—typically > 60 % (> 13 % for all sources at 90% likelihood). Our findings are in broad agreement with previous studies that found only a small fraction of galaxies with high escape fraction. These six galaxies compose the largest sample yet of LyC leaking candidates at z˜ 2 whose inferred LyC flux has been observed at HST resolution. While three of our six candidates show evidence of hosting an active galactic nucleus, two of these are heavily obscured and their LyC emission appears to originate from star-forming regions rather than the central nucleus. Extensive multiwavelength data in the GOODS fields, especially the near-IR grism spectra from the 3D-HST survey, enable us to study the candidates in detail and tentatively test some recently proposed indirect methods to probe LyC leakage. High-resolution spectroscopic follow-up of our candidates will help constrain such indirect methods, which are our only hope of studying f esc at z˜ 5-9 in the JWST era. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute. STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555.

  3. Genome-wide transcriptome profiling of black poplar (Populus nigra L.) under boron toxicity revealed candidate genes responsible in boron uptake, transport and detoxification.

    Science.gov (United States)

    Yıldırım, Kubilay; Uylaş, Senem

    2016-12-01

    Boron (B) is an essential nutrient for normal growth of plants. Despite its low abundance in soils, it could be highly toxic to plants in especially arid and semi-arid environments. Poplars are known to be tolerant species to B toxicity and accumulation. However, physiological and gene regulation responses of these trees to B toxicity have not been investigated yet. Here, B accumulation and tolerance level of black poplar clones were firstly tested in the current study. Rooted cutting of these clones were treated with elevated B toxicity to select the most B accumulator and tolerant genotype. Then we carried out a microarray based transcriptome experiment on the leaves and roots of this genotype to find out transcriptional networks, genes and molecular mechanisms behind B toxicity tolerance. The results of the study indicated that black poplar is quite suitable for phytoremediation of B pollution. It could resist 15 ppm soil B content and >1500 ppm B accumulation in leaves, which are highly toxic concentrations for almost all agricultural plants. Transcriptomics results of study revealed totally 1625 and 1419 altered probe sets under 15 ppm B toxicity in leaf and root tissues, respectively. The highest induction were recorded for the probes sets annotated to tyrosine aminotransferase, ATP binding cassette transporters, glutathione S transferases and metallochaperone proteins. Strong up regulation of these genes attributed to internal excretion of B into the cell vacuole and existence of B detoxification processes in black poplar. Many other candidate genes functional in signalling, gene regulation, antioxidation, B uptake and transport processes were also identified in this hyper B accumulator plant for the first time with the current study. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. A Selected Reaction Monitoring Mass Spectrometry Protocol for Validation of Proteomic Biomarker Candidates in Studies of Psychiatric Disorders.

    Science.gov (United States)

    Reis-de-Oliveira, Guilherme; Garcia, Sheila; Guest, Paul C; Cassoli, Juliana S; Martins-de-Souza, Daniel

    2017-01-01

    Most biomarker candidates arising from proteomic studies of psychiatric disorders have not progressed for use in clinical studies due to insufficient validation steps. Here we describe a selective reaction monitoring mass spectrometry (SRM-MS) approach that could be used as a follow-up validation tool of proteins identified in blood serum or plasma. This protocol specifically covers the stages of peptide selection and optimization. The increasing application of SRM-MS should enable fast, sensitive, and robust methods with the potential for use in clinical studies involving sampling of serum or plasma. Understanding the molecular mechanisms and identifying potential biomarkers for risk assessment, diagnosis, prognosis, and prediction of drug response goes toward the implementation of translational medicine strategies for improved treatment of patients with psychiatric disorders and other debilitating diseases.

  5. Confirming candidate genes for longevity in Drosophila melanogaster using two different genetic backgrounds and selection methods

    DEFF Research Database (Denmark)

    Wit, Janneke; Frydenberg, Jane; Sarup, Pernille Merete

    2013-01-01

    usually focussed on one sex and on flies originating from one genetic background, and results from different studies often do not overlap. Using D. melanogaster selected for increased longevity we aimed to find robust longevity related genes by examining gene expression in both sexes of flies originating......Elucidating genes that affect life span or that can be used as biomarkers for ageing has received attention in diverse studies in recent years. Using model organisms and various approaches several genes have been linked to the longevity phenotype. For Drosophila melanogaster those studies have...... from different genetic backgrounds. Further, we compared expression changes across three ages, when flies were young, middle aged or old, to examine how candidate gene expression changes with the onset of ageing. We selected 10 genes based on their expression differences in prior microarray studies...

  6. MoDOT pavement preservation research program volume VI, pavement treatment trigger tables/decision trees and treatment candidate selection process.

    Science.gov (United States)

    2015-10-01

    The objective of Task 5 was the development of pavement treatment trigger tables and the treatment candidate selection process. : The input to the trigger tables entails such factors as an overall condition indicator, smoothness, individual distress ...

  7. Star Formation Activity Beyond the Outer Arm. I. WISE -selected Candidate Star-forming Regions

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Natsuko; Yasui, Chikako; Saito, Masao [National Astronomical Observatory of Japan, 2-21-1, Osawa, Mitaka, Tokyo 181-8588 (Japan); Kobayashi, Naoto; Hamano, Satoshi, E-mail: natsuko.izumi@nao.ac.jp [Laboratory of Infrared High-resolution spectroscopy (LIH), Koyama Astronomical Observatory, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-ku, Kyoto 603-8555 (Japan)

    2017-10-01

    The outer Galaxy beyond the Outer Arm provides a good opportunity to study star formation in an environment significantly different from that in the solar neighborhood. However, star-forming regions in the outer Galaxy have never been comprehensively studied or cataloged because of the difficulties in detecting them at such large distances. We studied 33 known young star-forming regions associated with 13 molecular clouds at R {sub G} ≥ 13.5 kpc in the outer Galaxy with data from the Wide-field Infrared Survey Explorer ( WISE ) mid-infrared all-sky survey. From their color distribution, we developed a simple identification criterion of star-forming regions in the outer Galaxy with the WISE color. We applied the criterion to all the WISE sources in the molecular clouds in the outer Galaxy at R {sub G} ≥ 13.5 kpc detected with the Five College Radio Astronomy Observatory (FCRAO) {sup 12}CO survey of the outer Galaxy, of which the survey region is 102.°49 ≤  l  ≤ 141.°54, −3.°03 ≤  b  ≤ 5.°41, and successfully identified 711 new candidate star-forming regions in 240 molecular clouds. The large number of samples enables us to perform the statistical study of star formation properties in the outer Galaxy for the first time. This study is crucial to investigate the fundamental star formation properties, including star formation rate, star formation efficiency, and initial mass function, in a primordial environment such as the early phase of the Galaxy formation.

  8. Development and Validation of Measures for Selecting Soldiers for the Officer Candidate School

    Science.gov (United States)

    2011-08-01

    SJT, there has been a debate about what SJTs actually measure and why they work (cf. Moss & Hunt, 1926; Thorndike , 1936), a debate that continues...meta-analytic review and integration. Psychological Bulletin, 129, 914-945. Thorndike , R. L. (1936). Factor analysis of social and abstract...intelligence. The Journal of Educational Psychology, XXVII, 231—233. Thorndike , R. L. (1949). Personnel selection: Test and measurement techniques. New York

  9. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance

    Directory of Open Access Journals (Sweden)

    Elliott Ferris

    2018-03-01

    Full Text Available The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species.

  10. Fast selection of miRNA candidates based on large-scale pre-computed MFE sets of randomized sequences.

    Science.gov (United States)

    Warris, Sven; Boymans, Sander; Muiser, Iwe; Noback, Michiel; Krijnen, Wim; Nap, Jan-Peter

    2014-01-13

    Small RNAs are important regulators of genome function, yet their prediction in genomes is still a major computational challenge. Statistical analyses of pre-miRNA sequences indicated that their 2D structure tends to have a minimal free energy (MFE) significantly lower than MFE values of equivalently randomized sequences with the same nucleotide composition, in contrast to other classes of non-coding RNA. The computation of many MFEs is, however, too intensive to allow for genome-wide screenings. Using a local grid infrastructure, MFE distributions of random sequences were pre-calculated on a large scale. These distributions follow a normal distribution and can be used to determine the MFE distribution for any given sequence composition by interpolation. It allows on-the-fly calculation of the normal distribution for any candidate sequence composition. The speedup achieved makes genome-wide screening with this characteristic of a pre-miRNA sequence practical. Although this particular property alone will not be able to distinguish miRNAs from other sequences sufficiently discriminative, the MFE-based P-value should be added to the parameters of choice to be included in the selection of potential miRNA candidates for experimental verification.

  11. SPIDERS: selection of spectroscopic targets using AGN candidates detected in all-sky X-ray surveys

    Science.gov (United States)

    Dwelly, T.; Salvato, M.; Merloni, A.; Brusa, M.; Buchner, J.; Anderson, S. F.; Boller, Th.; Brandt, W. N.; Budavári, T.; Clerc, N.; Coffey, D.; Del Moro, A.; Georgakakis, A.; Green, P. J.; Jin, C.; Menzel, M.-L.; Myers, A. D.; Nandra, K.; Nichol, R. C.; Ridl, J.; Schwope, A. D.; Simm, T.

    2017-07-01

    SPIDERS (SPectroscopic IDentification of eROSITA Sources) is a Sloan Digital Sky Survey IV (SDSS-IV) survey running in parallel to the Extended Baryon Oscillation Spectroscopic Survey (eBOSS) cosmology project. SPIDERS will obtain optical spectroscopy for large numbers of X-ray-selected active galactic nuclei (AGN) and galaxy cluster members detected in wide-area eROSITA, XMM-Newton and ROSAT surveys. We describe the methods used to choose spectroscopic targets for two sub-programmes of SPIDERS X-ray selected AGN candidates detected in the ROSAT All Sky and the XMM-Newton Slew surveys. We have exploited a Bayesian cross-matching algorithm, guided by priors based on mid-IR colour-magnitude information from the Wide-field Infrared Survey Explorer survey, to select the most probable optical counterpart to each X-ray detection. We empirically demonstrate the high fidelity of our counterpart selection method using a reference sample of bright well-localized X-ray sources collated from XMM-Newton, Chandra and Swift-XRT serendipitous catalogues, and also by examining blank-sky locations. We describe the down-selection steps which resulted in the final set of SPIDERS-AGN targets put forward for spectroscopy within the eBOSS/TDSS/SPIDERS survey, and present catalogues of these targets. We also present catalogues of ˜12 000 ROSAT and ˜1500 XMM-Newton Slew survey sources that have existing optical spectroscopy from SDSS-DR12, including the results of our visual inspections. On completion of the SPIDERS programme, we expect to have collected homogeneous spectroscopic redshift information over a footprint of ˜7500 deg2 for >85 per cent of the ROSAT and XMM-Newton Slew survey sources having optical counterparts in the magnitude range 17 < r < 22.5, producing a large and highly complete sample of bright X-ray-selected AGN suitable for statistical studies of AGN evolution and clustering.

  12. Sequence analysis of chromosome 1 revealed different selection patterns between Chinese wild mice and laboratory strains.

    Science.gov (United States)

    Xu, Fuyi; Hu, Shixian; Chao, Tianzhu; Wang, Maochun; Li, Kai; Zhou, Yuxun; Xu, Hongyan; Xiao, Junhua

    2017-10-01

    Both natural and artificial selection play a critical role in animals' adaptation to the environment. Detection of the signature of selection in genomic regions can provide insights for understanding the function of specific phenotypes. It is generally assumed that laboratory mice may experience intense artificial selection while wild mice more natural selection. However, the differences of selection signature in the mouse genome and underlying genes between wild and laboratory mice remain unclear. In this study, we used two mouse populations: chromosome 1 (Chr 1) substitution lines (C1SLs) derived from Chinese wild mice and mouse genome project (MGP) sequenced inbred strains and two selection detection statistics: Fst and Tajima's D to identify the signature of selection footprint on Chr 1. For the differentiation between the C1SLs and MGP, 110 candidate selection regions containing 47 protein coding genes were detected. A total of 149 selection regions which encompass 7.215 Mb were identified in the C1SLs by Tajima's D approach. While for the MGP, we identified nearly twice selection regions (243) compared with the C1SLs which accounted for 13.27 Mb Chr 1 sequence. Through functional annotation, we identified several biological processes with significant enrichment including seven genes in the olfactory transduction pathway. In addition, we searched the phenotypes associated with the 47 candidate selection genes identified by Fst. These genes were involved in behavior, growth or body weight, mortality or aging, and immune systems which align well with the phenotypic differences between wild and laboratory mice. Therefore, the findings would be helpful for our understanding of the phenotypic differences between wild and laboratory mice and applications for using this new mouse resource (C1SLs) for further genetics studies.

  13. Safety Considerations in the Selection of Nuclear Power Plant Candidate Sites in Johor State, Malaysia

    International Nuclear Information System (INIS)

    Ramli, A.T.; Basri, N.A.; Abu Hanifah, N.Z.H.

    2014-01-01

    Nuclear power is considered as one of the best options for future energy development in Malaysia. Since Malaysia has no experience in nuclear energy generation / production, commissioning the first nuclear power plant needs tremendous effort in various aspects. The most obvious challenges are to ensure the nation’s safety and to handle security issues that may arise from a nuclear power plant site. This paper aims to propose a site for nuclear power plant in Johor State, Malaysia as well as listing the possible safety challenges in the process. The site selection uses the Malaysian Atomic Energy Licensing Board (AELB) guideline document as the main reference, supported by documents from International Atomic Energy Agency (IAEA) and from various countries. Only five site characteristics are chosen as study parameters – geological features and seismic data, air dispersion analysis using meteorological data, population distribution, safety zones and emergency supports. This paper concluded that site number 2 (CS2) at Tanjung Tenggaroh, Mersing is the most suitable area for nuclear power plant in Johor state. It has the least possible risks, safety and security issues. (author)

  14. Safety Considerations in the Selection of Nuclear Power Plant Candidate Sites in Johor State, Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    Ramli, A. T.; Basri, N. A.; Abu Hanifah, N. Z.H., [Department of Physics, Faculty of Science Universiti Teknologi Malaysia Johor (Malaysia)

    2014-10-15

    Nuclear power is considered as one of the best options for future energy development in Malaysia. Since Malaysia has no experience in nuclear energy generation / production, commissioning the first nuclear power plant needs tremendous effort in various aspects. The most obvious challenges are to ensure the nation’s safety and to handle security issues that may arise from a nuclear power plant site. This paper aims to propose a site for nuclear power plant in Johor State, Malaysia as well as listing the possible safety challenges in the process. The site selection uses the Malaysian Atomic Energy Licensing Board (AELB) guideline document as the main reference, supported by documents from International Atomic Energy Agency (IAEA) and from various countries. Only five site characteristics are chosen as study parameters – geological features and seismic data, air dispersion analysis using meteorological data, population distribution, safety zones and emergency supports. This paper concluded that site number 2 (CS2) at Tanjung Tenggaroh, Mersing is the most suitable area for nuclear power plant in Johor state. It has the least possible risks, safety and security issues. (author)

  15. Application of miniaturized disk bend test technique for selection of optimum composition of candidate materials for fusion reactors

    International Nuclear Information System (INIS)

    Tsepelev, A.B.; Poymenov, I.L.

    1992-01-01

    An analysis of the potential of a miniaturized disk bend test (MDBT) technique for estimation of irradiated steel mechanical properties behaviour indicates promise in selecting candidate materials for nuclear applications. The advantages of the method are most clearly demonstrated when a large series of tests is needed. The tiny specimen size gives an additional advantage from the point of view of radiation material science. As an example of the MDBT potential, preliminary results of electron irradiation effects on Cr-Mn-W austenitic and Cr-W ferrite carbon and nitrogen steels are presented. It is shown that electron irradiation causes changes of the loading MDBT-curve form of the steels that most probably are connected with radiation-induced structure-phase transformations in the steels. (orig.)

  16. Differential SPL gene expression patterns reveal candidate genes underlying flowering time and architectural differences in Mimulus and Arabidopsis.

    Science.gov (United States)

    Jorgensen, Stacy A; Preston, Jill C

    2014-04-01

    Evolutionary transitions in growth habit and flowering time responses to variable environmental signals have occurred multiple times independently across angiosperms and have major impacts on plant fitness. Proteins in the SPL family of transcription factors collectively regulate flowering time genes that have been implicated in interspecific shifts in annuality/perenniality. However, their potential importance in the evolution of angiosperm growth habit has not been extensively investigated. Here we identify orthologs representative of the major SPL gene clades in annual Arabidopsis thaliana and Mimulus guttatus IM767, and perennial A. lyrata and M. guttatus PR, and characterize their expression. Spatio-temporal expression patterns are complex across both diverse tissues of the same taxa and comparable tissues of different taxa, consistent with genic sub- or neo-functionalization. However, our data are consistent with a general role for several SPL genes in the promotion of juvenile to adult phase change and/or flowering time in Mimulus and Arabidopsis. Furthermore, several candidate genes were identified for future study whose differential expression correlates with growth habit and architectural variation in annual versus perennial taxa. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance.

    Science.gov (United States)

    Ferris, Elliott; Abegglen, Lisa M; Schiffman, Joshua D; Gregg, Christopher

    2018-03-06

    The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Genome-wide DNA methylation profiles reveal novel candidate genes associated with meat quality at different age stages in hens.

    Science.gov (United States)

    Zhang, Meng; Yan, Feng-Bin; Li, Fang; Jiang, Ke-Ren; Li, Dong-Hua; Han, Rui-Li; Li, Zhuan-Jan; Jiang, Rui-Rui; Liu, Xiao-Jun; Kang, Xiang-Tao; Sun, Gui-Rong

    2017-04-05

    Poultry meat quality is associated with breed, age, tissue and other factors. Many previous studies have focused on distinct breeds; however, little is known regarding the epigenetic regulatory mechanisms in different age stages, such as DNA methylation. Here, we compared the global DNA methylation profiles between juvenile (20 weeks old) and later laying-period (55 weeks old) hens and identified candidate genes related to the development and meat quality of breast muscle using whole-genome bisulfite sequencing. The results showed that the later laying-period hens, which had a higher intramuscular fat (IMF) deposition capacity and water holding capacity (WHC) and less tenderness, exhibited higher global DNA methylation levels than the juvenile hens. A total of 2,714 differentially methylated regions were identified in the present study, which corresponded to 378 differentially methylated genes, mainly affecting muscle development, lipid metabolism, and the ageing process. Hypermethylation of the promoters of the genes ABCA1, COL6A1 and GSTT1L and the resulting transcriptional down-regulation in the later laying-period hens may be the reason for the significant difference in the meat quality between the juvenile and later laying-period hens. These findings contribute to a better understanding of epigenetic regulation in the skeletal muscle development and meat quality of chicken.

  19. Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep.

    Science.gov (United States)

    Harbison, Susan T; Serrano Negron, Yazmin L; Hansen, Nancy F; Lobell, Amanda S

    2017-12-01

    Why do some individuals need more sleep than others? Forward mutagenesis screens in flies using engineered mutations have established a clear genetic component to sleep duration, revealing mutants that convey very long or short sleep. Whether such extreme long or short sleep could exist in natural populations was unknown. We applied artificial selection for high and low night sleep duration to an outbred population of Drosophila melanogaster for 13 generations. At the end of the selection procedure, night sleep duration diverged by 9.97 hours in the long and short sleeper populations, and 24-hour sleep was reduced to 3.3 hours in the short sleepers. Neither long nor short sleeper lifespan differed appreciably from controls, suggesting little physiological consequences to being an extreme long or short sleeper. Whole genome sequence data from seven generations of selection revealed several hundred thousand changes in allele frequencies at polymorphic loci across the genome. Combining the data from long and short sleeper populations across generations in a logistic regression implicated 126 polymorphisms in 80 candidate genes, and we confirmed three of these genes and a larger genomic region with mutant and chromosomal deficiency tests, respectively. Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways-EGFR, Wnt, Hippo, and MAPK. The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.

  20. Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep.

    Directory of Open Access Journals (Sweden)

    Susan T Harbison

    2017-12-01

    Full Text Available Why do some individuals need more sleep than others? Forward mutagenesis screens in flies using engineered mutations have established a clear genetic component to sleep duration, revealing mutants that convey very long or short sleep. Whether such extreme long or short sleep could exist in natural populations was unknown. We applied artificial selection for high and low night sleep duration to an outbred population of Drosophila melanogaster for 13 generations. At the end of the selection procedure, night sleep duration diverged by 9.97 hours in the long and short sleeper populations, and 24-hour sleep was reduced to 3.3 hours in the short sleepers. Neither long nor short sleeper lifespan differed appreciably from controls, suggesting little physiological consequences to being an extreme long or short sleeper. Whole genome sequence data from seven generations of selection revealed several hundred thousand changes in allele frequencies at polymorphic loci across the genome. Combining the data from long and short sleeper populations across generations in a logistic regression implicated 126 polymorphisms in 80 candidate genes, and we confirmed three of these genes and a larger genomic region with mutant and chromosomal deficiency tests, respectively. Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways-EGFR, Wnt, Hippo, and MAPK. The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.

  1. Red blood cell populations and membrane levels of peroxiredoxin 2 as candidate biomarkers to reveal blood doping.

    Science.gov (United States)

    Marrocco, Cristina; Pallotta, Valeria; D'alessandro, Angelo; Alves, Gilda; Zolla, Lello

    2012-05-01

    Blood doping represents one main trend in doping strategies. Blood doping refers to the practice of boosting the number of red blood cells (RBCs) in the bloodstream in order to enhance athletic performance, by means of blood transfusions, administration of erythropoiesis-stimulating substances, blood substitutes, natural or artificial altitude facilities, and innovative gene therapies. While detection of recombinant EPO and homologous transfusion is already feasible through electrophoretic, mass spectrometry or flow cytometry-based approaches, no method is currently available to tackle doping strategies relying on autologous transfusions. We exploited an in vitro model of autologous transfusion through a 1:10 dilution of concentrated RBCs after 30 days of storage upon appropriate dilution in freshly withdrawn RBCs from the same donor. Western blot towards membrane Prdx2 and Percoll density gradients were exploited to assess their suitability as biomarkers of transfusion. Membrane Prdx2 was visible in day 30 samples albeit not in day 0, while it was still visible in the 1:10 dilution of day 30 in day 0 RBCs. Cell gradients also highlighted changes in the profile of the RBC subpopulations upon dilution of stored RBCs in the fresh ones. From this preliminary in vitro investigation it emerges that Prdx2 and RBC populations might be further tested as candidate biomarkers of blood doping through autologous transfusion, though it is yet to be assessed whether the kinetics in vivo of Prdx2 exposure in the membrane of transfused RBCs will endow a sufficient time-window to allow reliable anti-doping testing.

  2. Selection and Validation of Reference Genes for qRT-PCR Expression Analysis of Candidate Genes Involved in Olfactory Communication in the Butterfly Bicyclus anynana

    OpenAIRE

    Arun, Alok; Bauml?, V?ronique; Amelot, Ga?l; Nieberding, Caroline M.

    2015-01-01

    Real-time quantitative reverse transcription PCR (qRT-PCR) is a technique widely used to quantify the transcriptional expression level of candidate genes. qRT-PCR requires the selection of one or several suitable reference genes, whose expression profiles remain stable across conditions, to normalize the qRT-PCR expression profiles of candidate genes. Although several butterfly species (Lepidoptera) have become important models in molecular evolutionary ecology, so far no study aimed at ident...

  3. A data science approach to candidate gene selection of pain regarded as a process of learning and neural plasticity.

    Science.gov (United States)

    Ultsch, Alfred; Kringel, Dario; Kalso, Eija; Mogil, Jeffrey S; Lötsch, Jörn

    2016-12-01

    The increasing availability of "big data" enables novel research approaches to chronic pain while also requiring novel techniques for data mining and knowledge discovery. We used machine learning to combine the knowledge about n = 535 genes identified empirically as relevant to pain with the knowledge about the functions of thousands of genes. Starting from an accepted description of chronic pain as displaying systemic features described by the terms "learning" and "neuronal plasticity," a functional genomics analysis proposed that among the functions of the 535 "pain genes," the biological processes "learning or memory" (P = 8.6 × 10) and "nervous system development" (P = 2.4 × 10) are statistically significantly overrepresented as compared with the annotations to these processes expected by chance. After establishing that the hypothesized biological processes were among important functional genomics features of pain, a subset of n = 34 pain genes were found to be annotated with both Gene Ontology terms. Published empirical evidence supporting their involvement in chronic pain was identified for almost all these genes, including 1 gene identified in March 2016 as being involved in pain. By contrast, such evidence was virtually absent in a randomly selected set of 34 other human genes. Hence, the present computational functional genomics-based method can be used for candidate gene selection, providing an alternative to established methods.

  4. Transcriptional responses of Italian ryegrass during interaction with Xanthomonas translucens pv. graminis reveal novel candidate genes for bacterial wilt resistance

    DEFF Research Database (Denmark)

    Wichmann, Fabienne; Asp, Torben; Widmer, Franko

    2011-01-01

    Xanthomonas translucens pv. graminis (Xtg) causes bacterial wilt, a severe disease of forage grasses such as Italian ryegrass (Lolium multiflorum Lam.). In order to gain a more detailed understanding of the genetic control of resistance mechanisms and to provide prerequisites for marker assisted...... selection, the partial transcriptomes of two Italian ryegrass genotypes, one resistant and one susceptible to bacterial wilt were compared at four time points after Xtg infection. A cDNA microarray developed from a perennial ryegrass (Lolium perenne) expressed sequence tag set consisting of 9,990 unique...

  5. Do candidate reactions relate to job performance or affect criterion-related validity? A multistudy investigation of relations among reactions, selection test scores, and job performance.

    Science.gov (United States)

    McCarthy, Julie M; Van Iddekinge, Chad H; Lievens, Filip; Kung, Mei-Chuan; Sinar, Evan F; Campion, Michael A

    2013-09-01

    Considerable evidence suggests that how candidates react to selection procedures can affect their test performance and their attitudes toward the hiring organization (e.g., recommending the firm to others). However, very few studies of candidate reactions have examined one of the outcomes organizations care most about: job performance. We attempt to address this gap by developing and testing a conceptual framework that delineates whether and how candidate reactions might influence job performance. We accomplish this objective using data from 4 studies (total N = 6,480), 6 selection procedures (personality tests, job knowledge tests, cognitive ability tests, work samples, situational judgment tests, and a selection inventory), 5 key candidate reactions (anxiety, motivation, belief in tests, self-efficacy, and procedural justice), 2 contexts (industry and education), 3 continents (North America, South America, and Europe), 2 study designs (predictive and concurrent), and 4 occupational areas (medical, sales, customer service, and technological). Consistent with previous research, candidate reactions were related to test scores, and test scores were related to job performance. Further, there was some evidence that reactions affected performance indirectly through their influence on test scores. Finally, in no cases did candidate reactions affect the prediction of job performance by increasing or decreasing the criterion-related validity of test scores. Implications of these findings and avenues for future research are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved

  6. Accuracy of computer-calculated and manual QRS duration assessments: Clinical implications to select candidates for cardiac resynchronization therapy.

    Science.gov (United States)

    De Pooter, Jan; El Haddad, Milad; Stroobandt, Roland; De Buyzere, Marc; Timmermans, Frank

    2017-06-01

    QRS duration (QRSD) plays a key role in the field of cardiac resynchronization therapy (CRT). Computer-calculated QRSD assessments are widely used, however inter-manufacturer differences have not been investigated in CRT candidates. QRSD was assessed in 377 digitally stored ECGs: 139 narrow QRS, 140 LBBB and 98 ventricular paced ECGs. Manual QRSD was measured as global QRSD, using digital calipers, by two independent observers. Computer-calculated QRSD was assessed by Marquette 12SL (GE Healthcare, Waukesha, WI, USA) and SEMA3 (Schiller, Baar, Switzerland). Inter-manufacturer differences of computer-calculated QRSD assessments vary among different QRS morphologies: narrow QRSD: 4 [2-9] ms (median [IQR]), p=0.010; LBBB QRSD: 7 [2-10] ms, p=0.003 and paced QRSD: 13 [6-18] ms, p=0.007. Interobserver differences of manual QRSD assessments measured: narrow QRSD: 4 [2-6] ms, p=non-significant; LBBB QRSD: 6 [3-12] ms, p=0.006; paced QRSD: 8 [4-18] ms, p=0.001. In LBBB ECGs, intraclass correlation coefficients (ICCs) were comparable for inter-manufacturer and interobserver agreement (ICC 0.830 versus 0.837). When assessing paced QRSD, manual measurements showed higher ICC compared to inter-manufacturer agreement (ICC 0.902 versus 0.776). Using guideline cutoffs of 130ms, up to 15% of the LBBB ECGs would be misclassified as <130ms or ≥130ms by at least one method. Using a cutoff of 150ms, this number increases to 33% of ECGs being misclassified. However, by combining LBBB-morphology and QRSD, the number of misclassified ECGs can be decreased by half. Inter-manufacturer differences in computer-calculated QRSD assessments are significant and may compromise adequate selection of individual CRT candidates when using QRSD as sole parameter. Paced QRSD should preferentially be assessed by manual QRSD measurements. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Comparative genomic analysis of Brucella abortus vaccine strain 104M reveals a set of candidate genes associated with its virulence attenuation.

    Science.gov (United States)

    Yu, Dong; Hui, Yiming; Zai, Xiaodong; Xu, Junjie; Liang, Long; Wang, Bingxiang; Yue, Junjie; Li, Shanhu

    2015-01-01

    The Brucella abortus strain 104M, a spontaneously attenuated strain, has been used as a vaccine strain in humans against brucellosis for 6 decades in China. Despite many studies, the molecular mechanisms that cause the attenuation are still unclear. Here, we determined the whole-genome sequence of 104M and conducted a comprehensive comparative analysis against the whole genome sequences of the virulent strain, A13334, and other reference strains. This analysis revealed a highly similar genome structure between 104M and A13334. The further comparative genomic analysis between 104M and A13334 revealed a set of genes missing in 104M. Some of these genes were identified to be directly or indirectly associated with virulence. Similarly, a set of mutations in the virulence-related genes was also identified, which may be related to virulence alteration. This study provides a set of candidate genes associated with virulence attenuation in B.abortus vaccine strain 104M.

  8. Single-cell genomics reveals pyrrolysine-encoding potential in members of uncultivated archaeal candidate division MSBL1

    KAUST Repository

    Guan, Yue; Haroon, Mohamed; Alam, Intikhab; Ferry, James G.; Stingl, Ulrich

    2017-01-01

    Pyrrolysine (Pyl), the 22nd canonical amino acid, is only decoded and synthesized by a limited number of organisms in the domains Archaea and Bacteria. Pyl is encoded by the amber codon UAG, typically a stop codon. To date, all known Pyl-decoding archaea are able to carry out methylotrophic methanogenesis. The functionality of methylamine methyltransferases, an important component of corrinoid-dependent methyltransfer reactions, depends on the presence of Pyl. Here, we present a putative pyl gene cluster obtained from single-cell genomes of the archaeal Mediterranean Sea Brine Lakes group 1 (MSBL1) from the Red Sea. Functional annotation of the MSBL1 single cell amplified genomes (SAGs) also revealed a complete corrinoid-dependent methyl-transfer pathway suggesting that members of MSBL1 may possibly be capable of synthesizing Pyl and metabolizing methylated amines. This article is protected by copyright. All rights reserved.

  9. Single-cell genomics reveals pyrrolysine-encoding potential in members of uncultivated archaeal candidate division MSBL1

    KAUST Repository

    Guan, Yue

    2017-05-11

    Pyrrolysine (Pyl), the 22nd canonical amino acid, is only decoded and synthesized by a limited number of organisms in the domains Archaea and Bacteria. Pyl is encoded by the amber codon UAG, typically a stop codon. To date, all known Pyl-decoding archaea are able to carry out methylotrophic methanogenesis. The functionality of methylamine methyltransferases, an important component of corrinoid-dependent methyltransfer reactions, depends on the presence of Pyl. Here, we present a putative pyl gene cluster obtained from single-cell genomes of the archaeal Mediterranean Sea Brine Lakes group 1 (MSBL1) from the Red Sea. Functional annotation of the MSBL1 single cell amplified genomes (SAGs) also revealed a complete corrinoid-dependent methyl-transfer pathway suggesting that members of MSBL1 may possibly be capable of synthesizing Pyl and metabolizing methylated amines. This article is protected by copyright. All rights reserved.

  10. Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates.

    Science.gov (United States)

    Dieterich, Christine; Puey, Angela; Lin, Sylvia; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C; Ng, Hanna H

    2009-01-01

    Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and sacrificed on day 8. Clinical chemistry and histopathology demonstrated kidney injury at 400 mg/kg only. Hierarchical clustering analysis revealed that kidney gene expression profiles of all mice treated at 400 mg/kg clustered with those of mice administered 200 mg/kg iv. Transcriptional profiling might thus be more sensitive than current clinical markers for detecting kidney damage, though the profiles can differ with the route of administration. Analysis of transcripts whose expression was changed by at least twofold compared with vehicle saline after high iv and ip doses of vancomycin suggested the possibility of oxidative stress and mitochondrial damage in vancomycin-induced toxicity. In addition, our data showed changes in expression of several transcripts from the complement and inflammatory pathways. Such expression changes were confirmed by relative real-time reverse transcription-polymerase chain reaction. Finally, our results further substantiate the use of gene markers of kidney toxicity such as KIM-1/Havcr1, as indicators of renal injury.

  11. Exploring evidence of positive selection reveals genetic basis of meat quality traits in Berkshire pigs through whole genome sequencing.

    Science.gov (United States)

    Jeong, Hyeonsoo; Song, Ki-Duk; Seo, Minseok; Caetano-Anollés, Kelsey; Kim, Jaemin; Kwak, Woori; Oh, Jae-Don; Kim, EuiSoo; Jeong, Dong Kee; Cho, Seoae; Kim, Heebal; Lee, Hak-Kyo

    2015-08-20

    Natural and artificial selection following domestication has led to the existence of more than a hundred pig breeds, as well as incredible variation in phenotypic traits. Berkshire pigs are regarded as having superior meat quality compared to other breeds. As the meat production industry seeks selective breeding approaches to improve profitable traits such as meat quality, information about genetic determinants of these traits is in high demand. However, most of the studies have been performed using trained sensory panel analysis without investigating the underlying genetic factors. Here we investigate the relationship between genomic composition and this phenotypic trait by scanning for signatures of positive selection in whole-genome sequencing data. We generated genomes of 10 Berkshire pigs at a total of 100.6 coverage depth, using the Illumina Hiseq2000 platform. Along with the genomes of 11 Landrace and 13 Yorkshire pigs, we identified genomic variants of 18.9 million SNVs and 3.4 million Indels in the mapped regions. We identified several associated genes related to lipid metabolism, intramuscular fatty acid deposition, and muscle fiber type which attribute to pork quality (TG, FABP1, AKIRIN2, GLP2R, TGFBR3, JPH3, ICAM2, and ERN1) by applying between population statistical tests (XP-EHH and XP-CLR). A statistical enrichment test was also conducted to detect breed specific genetic variation. In addition, de novo short sequence read assembly strategy identified several candidate genes (SLC25A14, IGF1, PI4KA, CACNA1A) as also contributing to lipid metabolism. Results revealed several candidate genes involved in Berkshire meat quality; most of these genes are involved in lipid metabolism and intramuscular fat deposition. These results can provide a basis for future research on the genomic characteristics of Berkshire pigs.

  12. Comparative Transcriptome Analysis Reveal Candidate Genes Potentially Involved in Regulation of Primocane Apex Rooting in Raspberry (Rubus spp.).

    Science.gov (United States)

    Liu, Jianfeng; Ming, Yuetong; Cheng, Yunqing; Zhang, Yuchu; Xing, Jiyang; Sun, Yuqi

    2017-01-01

    Raspberries ( Rubus spp.) exhibit a unique rooting process that is initiated from the stem apex of primocane, conferring an unusual asexual mode of reproduction to this plant. However, the full complement of genes involved in this process has not been identified. To this end, the present study analyzed the transcriptomes of the Rubus primocane and floricane stem apex at three developmental stages by Digital Gene Expression profiling to identify genes that regulate rooting. Sequencing and de novo assembly yielded 26.82 Gb of nucleotides and 59,173 unigenes; 498, 7,346, 4,110, 7,900, 9,397, and 4,776 differently expressed genes were identified in paired comparisons of SAF1 (floricane at developmental stage 1) vs. SAP1 (primocane at developmental stage 1), SAF2 vs. SAP2, SAF3 vs. SAP3, SAP1 vs. SAP2, SAP1 vs. SAP3, and SAP2 vs. SAP3, respectively. SAP1 maintains an extension growth pattern; SAP2 then exhibits growth arrest and vertical (downward) gravitropic deflection; and finally, short roots begin to form on the apex of SAP3. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis of SAP1 vs. SAP2 revealed 12 pathways that were activated in response to shoot growth arrest and root differentiation, including circadian rhythm-plant (ko04712) and plant hormone signal transduction (ko04075). Our results indicate that genes related to circadian rhythm, ethylene and auxin signaling, shoot growth, and root development are potentially involved in the regulation of primocane apex rooting in Rubus . These findings provide a basis for elucidating the molecular mechanisms of primocane apex rooting in this economically valuable crop.

  13. Transcriptome analysis of Polygonum minus reveals candidate genes involved in important secondary metabolic pathways of phenylpropanoids and flavonoids

    Directory of Open Access Journals (Sweden)

    Kok-Keong Loke

    2017-02-01

    Full Text Available Background Polygonum minus is an herbal plant in the Polygonaceae family which is rich in ethnomedicinal plants. The chemical composition and characteristic pungent fragrance of Polygonum minus have been extensively studied due to its culinary and medicinal properties. There are only a few transcriptome sequences available for species from this important family of medicinal plants. The limited genetic information from the public expressed sequences tag (EST library hinders further study on molecular mechanisms underlying secondary metabolite production. Methods In this study, we performed a hybrid assembly of 454 and Illumina sequencing reads from Polygonum minus root and leaf tissues, respectively, to generate a combined transcriptome library as a reference. Results A total of 34.37 million filtered and normalized reads were assembled into 188,735 transcripts with a total length of 136.67 Mbp. We performed a similarity search against all the publicly available genome sequences and found similarity matches for 163,200 (86.5% of Polygonum minus transcripts, largely from Arabidopsis thaliana (58.9%. Transcript abundance in the leaf and root tissues were estimated and validated through RT-qPCR of seven selected transcripts involved in the biosynthesis of phenylpropanoids and flavonoids. All the transcripts were annotated against KEGG pathways to profile transcripts related to the biosynthesis of secondary metabolites. Discussion This comprehensive transcriptome profile will serve as a useful sequence resource for molecular genetics and evolutionary research on secondary metabolite biosynthesis in Polygonaceae family. Transcriptome assembly of Polygonum minus can be accessed at http://prims.researchfrontier.org/index.php/dataset/transcriptome.

  14. Systems Perturbation Analysis of a Large-Scale Signal Transduction Model Reveals Potentially Influential Candidates for Cancer Therapeutics

    Science.gov (United States)

    Puniya, Bhanwar Lal; Allen, Laura; Hochfelder, Colleen; Majumder, Mahbubul; Helikar, Tomáš

    2016-01-01

    Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical components that could be further explored as therapeutic targets. Here, we performed perturbation analysis of a large-scale signal transduction model in extracellular environments that stimulate cell death, growth, motility, and quiescence. Each of the model’s components was perturbed under both loss-of-function and gain-of-function mutations. Using 1,300 simulations under both types of perturbations across various extracellular conditions, we identified the most and least influential components based on the magnitude of their influence on the rest of the system. Based on the premise that the most influential components might serve as better drug targets, we characterized them for biological functions, housekeeping genes, essential genes, and druggable proteins. The most influential components under all environmental conditions were enriched with several biological processes. The inositol pathway was found as most influential under inactivating perturbations, whereas the kinase and small lung cancer pathways were identified as the most influential under activating perturbations. The most influential components were enriched with essential genes and druggable proteins. Moreover, known cancer drug targets were also classified in influential components based on the affected components in the network. Additionally, the systemic perturbation analysis of the model revealed a network motif of most influential components which affect each other. Furthermore, our analysis predicted novel combinations of cancer drug targets with various effects on other most influential components. We found that the combinatorial perturbation consisting of PI3K inactivation and overactivation of IP3R1 can lead to increased activity levels of apoptosis

  15. Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance.

    Science.gov (United States)

    Taye, Mengistie; Lee, Wonseok; Caetano-Anolles, Kelsey; Dessie, Tadelle; Hanotte, Olivier; Mwai, Okeyo Ally; Kemp, Stephen; Cho, Seoae; Oh, Sung Jong; Lee, Hak-Kyo; Kim, Heebal

    2017-12-01

    As African indigenous cattle evolved in a hot tropical climate, they have developed an inherent thermotolerance; survival mechanisms include a light-colored and shiny coat, increased sweating, and cellular and molecular mechanisms to cope with high environmental temperature. Here, we report the positive selection signature of genes in African cattle breeds which contribute for their heat tolerance mechanisms. We compared the genomes of five indigenous African cattle breeds with the genomes of four commercial cattle breeds using cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) statistical methods. We identified 296 (XP-EHH) and 327 (XP-CLR) positively selected genes. Gene ontology analysis resulted in 41 biological process terms and six Kyoto Encyclopedia of Genes and Genomes pathways. Several genes and pathways were found to be involved in oxidative stress response, osmotic stress response, heat shock response, hair and skin properties, sweat gland development and sweating, feed intake and metabolism, and reproduction functions. The genes and pathways identified directly or indirectly contribute to the superior heat tolerance mechanisms in African cattle populations. The result will improve our understanding of the biological mechanisms of heat tolerance in African cattle breeds and opens an avenue for further study. © 2017 Japanese Society of Animal Science.

  16. Characterization of JNJ-42847922, a Selective Orexin-2 Receptor Antagonist, as a Clinical Candidate for the Treatment of Insomnia.

    Science.gov (United States)

    Bonaventure, Pascal; Shelton, Jonathan; Yun, Sujin; Nepomuceno, Diane; Sutton, Steven; Aluisio, Leah; Fraser, Ian; Lord, Brian; Shoblock, James; Welty, Natalie; Chaplan, Sandra R; Aguilar, Zuleima; Halter, Robin; Ndifor, Anthony; Koudriakova, Tatiana; Rizzolio, Michele; Letavic, Michael; Carruthers, Nicholas I; Lovenberg, Timothy; Dugovic, Christine

    2015-09-01

    Dual orexin receptor antagonists have been shown to promote sleep in various species, including humans. Emerging research indicates that selective orexin-2 receptor (OX2R) antagonists may offer specificity and a more adequate sleep profile by preserving normal sleep architecture. Here, we characterized JNJ-42847922 ([5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone), a high-affinity/potent OX2R antagonist. JNJ-42847922 had an approximate 2-log selectivity ratio versus the human orexin-1 receptor. Ex vivo receptor binding studies demonstrated that JNJ-42847922 quickly occupied OX2R binding sites in the rat brain after oral administration and rapidly cleared from the brain. In rats, single oral administration of JNJ-42847922 (3-30 mg/kg) during the light phase dose dependently reduced the latency to non-rapid eye movement (NREM) sleep and prolonged NREM sleep time in the first 2 hours, whereas REM sleep was minimally affected. The reduced sleep onset and increased sleep duration were maintained upon 7-day repeated dosing (30 mg/kg) with JNJ-42847922, then all sleep parameters returned to baseline levels following discontinuation. Although the compound promoted sleep in wild-type mice, it had no effect in OX2R knockout mice, consistent with a specific OX2R-mediated sleep response. JNJ-42847922 did not increase dopamine release in rat nucleus accumbens or produce place preference in mice after subchronic conditioning, indicating that the compound lacks intrinsic motivational properties in contrast to zolpidem. In a single ascending dose study conducted in healthy subjects, JNJ-42847922 increased somnolence and displayed a favorable pharmacokinetic and safety profile for a sedative/hypnotic, thus emerging as a promising candidate for further clinical development for the treatment of insomnia. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Validation of candidate gene markers for marker-assisted selection of potato cultivars with improved tuber quality.

    Science.gov (United States)

    Li, Li; Tacke, Eckhard; Hofferbert, Hans-Reinhardt; Lübeck, Jens; Strahwald, Josef; Draffehn, Astrid M; Walkemeier, Birgit; Gebhardt, Christiane

    2013-04-01

    Tuber yield, starch content, starch yield and chip color are complex traits that are important for industrial uses and food processing of potato. Chip color depends on the quantity of reducing sugars glucose and fructose in the tubers, which are generated by starch degradation. Reducing sugars accumulate when tubers are stored at low temperatures. Early and efficient selection of cultivars with superior yield, starch yield and chip color is hampered by the fact that reliable phenotypic selection requires multiple year and location trials. Application of DNA-based markers early in the breeding cycle, which are diagnostic for superior alleles of genes that control natural variation of tuber quality, will reduce the number of clones to be evaluated in field trials. Association mapping using genes functional in carbohydrate metabolism as markers has discovered alleles of invertases and starch phosphorylases that are associated with tuber quality traits. Here, we report on new DNA variants at loci encoding ADP-glucose pyrophosphorylase and the invertase Pain-1, which are associated with positive or negative effect with chip color, tuber starch content and starch yield. Marker-assisted selection (MAS) and marker validation were performed in tetraploid breeding populations, using various combinations of 11 allele-specific markers associated with tuber quality traits. To facilitate MAS, user-friendly PCR assays were developed for specific candidate gene alleles. In a multi-parental population of advanced breeding clones, genotypes were selected for having different combinations of five positive and the corresponding negative marker alleles. Genotypes combining five positive marker alleles performed on average better than genotypes with four negative alleles and one positive allele. When tested individually, seven of eight markers showed an effect on at least one quality trait. The direction of effect was as expected. Combinations of two to three marker alleles were

  18. Enzymatic shaving of the tegument surface of live schistosomes for proteomic analysis: a rational approach to select vaccine candidates.

    Directory of Open Access Journals (Sweden)

    William Castro-Borges

    2011-03-01

    Full Text Available The membrane-associated and membrane-spanning constituents of the Schistosoma mansoni tegument surface, the parasite's principal interface with the host bloodstream, have recently been characterized using proteomic techniques. Biotinylation of live worms using membrane-impermeant probes revealed that only a small subset of the proteins was accessible to the reagents. Their position within the multilayered architecture of the surface has not been ascertained.An enzymatic shaving approach on live worms has now been used to release the most accessible components, for analysis by MS/MS. Treatment with trypsin, or phosphatidylinositol-specific phospholipase C (PiPLC, only minimally impaired membrane integrity. PiPLC-enriched proteins were distinguished from those released in parasite vomitus or by handling damage, using isobaric tagging. Trypsin released five membrane proteins, Sm200, Sm25 and three annexins, plus host CD44 and the complement factors C3 and C4. Nutrient transporters and ion channels were absent from the trypsin fraction, suggesting a deeper location in the surface complex; surprisingly, two BAR-domain containing proteins were released. Seven parasite and two host proteins were enriched by PiPLC treatment, the vaccine candidate Sm29 being the most prominent along with two orthologues of human CD59, potentially inhibitors of complement fixation. The enzymes carbonic anhydrase and APD-ribosyl cyclase were also enriched, plus Sm200 and alkaline phosphatase. Host GPI-anchored proteins CD48 and CD90, suggest 'surface painting' during worm peregrination in the portal system.Our findings suggest that the membranocalyx secreted over the tegument surface is not the inert barrier previously proposed, some tegument proteins being externally accessible to enzymes and thus potentially located within it. Furthermore, the detection of C3 and C4 indicates that the complement cascade is initiated, while two CD59 orthologues suggest a potential

  19. Genome-wide scans between two honeybee populations reveal putative signatures of human-mediated selection.

    Science.gov (United States)

    Parejo, M; Wragg, D; Henriques, D; Vignal, A; Neuditschko, M

    2017-12-01

    Human-mediated selection has left signatures in the genomes of many domesticated animals, including the European dark honeybee, Apis mellifera mellifera, which has been selected by apiculturists for centuries. Using whole-genome sequence information, we investigated selection signatures in spatially separated honeybee subpopulations (Switzerland, n = 39 and France, n = 17). Three different test statistics were calculated in windows of 2 kb (fixation index, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio) and combined into a recently developed composite selection score. Applying a stringent false discovery rate of 0.01, we identified six significant selective sweeps distributed across five chromosomes covering eight genes. These genes are associated with multiple molecular and biological functions, including regulation of transcription, receptor binding and signal transduction. Of particular interest is a selection signature on chromosome 1, which corresponds to the WNT4 gene, the family of which is conserved across the animal kingdom with a variety of functions. In Drosophila melanogaster, WNT4 alleles have been associated with differential wing, cross vein and abdominal phenotypes. Defining phenotypic characteristics of different Apis mellifera ssp., which are typically used as selection criteria, include colour and wing venation pattern. This signal is therefore likely to be a good candidate for human mediated-selection arising from different applied breeding practices in the two managed populations. © 2017 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

  20. Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

    Directory of Open Access Journals (Sweden)

    Yue Huang

    Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

  1. Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies.

    Science.gov (United States)

    Bezençon, Olivier; Heidmann, Bibia; Siegrist, Romain; Stamm, Simon; Richard, Sylvia; Pozzi, Davide; Corminboeuf, Olivier; Roch, Catherine; Kessler, Melanie; Ertel, Eric A; Reymond, Isabelle; Pfeifer, Thomas; de Kanter, Ruben; Toeroek-Schafroth, Michael; Moccia, Luca G; Mawet, Jacques; Moon, Richard; Rey, Markus; Capeleto, Bruno; Fournier, Elvire

    2017-12-14

    We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as a clinical candidate.

  2. Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.

    Science.gov (United States)

    Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung

    2017-05-08

    Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC 50 ) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and

  3. Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in beta-Catenin-Active Cancers | Office of Cancer Genomics

    Science.gov (United States)

    Genome-scale expression studies and comprehensive loss-of-function genetic screens have focused almost exclusively on the highest confidence candidate genes. Here, we describe a strategy for characterizing the lower confidence candidates identified by such approaches.

  4. SDSS QUASARS IN THE WISE PRELIMINARY DATA RELEASE AND QUASAR CANDIDATE SELECTION WITH OPTICAL/INFRARED COLORS

    International Nuclear Information System (INIS)

    Wu Xuebing; Hao Guoqiang; Jia Zhendong; Zhang Yanxia; Peng Nanbo

    2012-01-01

    We present a catalog of 37,842 quasars in the Sloan Digital Sky Survey (SDSS) Data Release 7, which have counterparts within 6'' in the Wide-field Infrared Survey Explorer (WISE) Preliminary Data Release. The overall WISE detection rate of the SDSS quasars is 86.7%, and it decreases to less than 50.0% when the quasar magnitude is fainter than i = 20.5. We derive the median color-redshift relations based on this SDSS-WISE quasar sample and apply them to estimate the photometric redshifts of the SDSS-WISE quasars. We find that by adding the WISE W1- and W2-band data to the SDSS photometry we can increase the photometric redshift reliability, defined as the percentage of sources with photometric and spectroscopic redshift difference less than 0.2, from 70.3% to 77.2%. We also obtain the samples of WISE-detected normal and late-type stars with SDSS spectroscopy, and present a criterion in the z – W1 versus g – z color-color diagram, z – W1 > 0.66(g – z) + 2.01, to separate quasars from stars. With this criterion we can recover 98.6% of 3089 radio-detected SDSS-WISE quasars with redshifts less than four and overcome the difficulty in selecting quasars with redshifts between 2.2 and 3 from SDSS photometric data alone. We also suggest another criterion involving the WISE color only, W1 – W2 > 0.57, to efficiently separate quasars with redshifts less than 3.2 from stars. In addition, we compile a catalog of 5614 SDSS quasars detected by both WISE and UKIDSS surveys and present their color-redshift relations in the optical and infrared bands. By using the SDSS ugriz, UKIDSS, YJHK, and WISE W1- and W2-band photometric data, we can efficiently select quasar candidates and increase the photometric redshift reliability up to 87.0%. We discuss the implications of our results on the future quasar surveys. An updated SDSS-WISE quasar catalog consisting of 101,853 quasars with the recently released WISE all-sky data is also provided.

  5. CLUB-MARTINI: Selecting Favourable Interactions amongst Available Candidates, a Coarse-Grained Simulation Approach to Scoring Docking Decoys.

    Directory of Open Access Journals (Sweden)

    Qingzhen Hou

    Full Text Available Large-scale identification of native binding orientations is crucial for understanding the role of protein-protein interactions in their biological context. Measuring binding free energy is the method of choice to estimate binding strength and reveal the relevance of particular conformations in which proteins interact. In a recent study, we successfully applied coarse-grained molecular dynamics simulations to measure binding free energy for two protein complexes with similar accuracy to full-atomistic simulation, but 500-fold less time consuming. Here, we investigate the efficacy of this approach as a scoring method to identify stable binding conformations from thousands of docking decoys produced by protein docking programs. To test our method, we first applied it to calculate binding free energies of all protein conformations in a CAPRI (Critical Assessment of PRedicted Interactions benchmark dataset, which included over 19000 protein docking solutions for 15 benchmark targets. Based on the binding free energies, we ranked all docking solutions to select the near-native binding modes under the assumption that the native-solutions have lowest binding free energies. In our top 100 ranked structures, for the 'easy' targets that have many near-native conformations, we obtain a strong enrichment of acceptable or better quality structures; for the 'hard' targets without near-native decoys, our method is still able to retain structures which have native binding contacts. Moreover, in our top 10 selections, CLUB-MARTINI shows a comparable performance when compared with other state-of-the-art docking scoring functions. As a proof of concept, CLUB-MARTINI performs remarkably well for many targets and is able to pinpoint near-native binding modes in the top selections. To the best of our knowledge, this is the first time interaction free energy calculated from MD simulations have been used to rank docking solutions at a large scale.

  6. Candidate biomarker discovery and selection for ‘Granny Smith' superficial scald risk management and diagnosis, poster board

    Science.gov (United States)

    Discovery of candidate biomarkers for superficial scald, a peel disorder that develops during storage of susceptible apple cultivars, is part of a larger project aimed at developing biomarker-based risk-management and diagnostic tools for multiple apple postharvest disorders (http://www.tfrec.wsu.ed...

  7. Machine learning techniques to select Be star candidates. An application in the OGLE-IV Gaia south ecliptic pole field

    Science.gov (United States)

    Pérez-Ortiz, M. F.; García-Varela, A.; Quiroz, A. J.; Sabogal, B. E.; Hernández, J.

    2017-09-01

    Context. Optical and infrared variability surveys produce a large number of high quality light curves. Statistical pattern recognition methods have provided competitive solutions for variable star classification at a relatively low computational cost. In order to perform supervised classification, a set of features is proposed and used to train an automatic classification system. Quantities related to the magnitude density of the light curves and their Fourier coefficients have been chosen as features in previous studies. However, some of these features are not robust to the presence of outliers and the calculation of Fourier coefficients is computationally expensive for large data sets. Aims: We propose and evaluate the performance of a new robust set of features using supervised classifiers in order to look for new Be star candidates in the OGLE-IV Gaia south ecliptic pole field. Methods: We calculated the proposed set of features on six types of variable stars and also on a set of Be star candidates reported in the literature. We evaluated the performance of these features using classification trees and random forests along with the K-nearest neighbours, support vector machines, and gradient boosted trees methods. We tuned the classifiers with a 10-fold cross-validation and grid search. We then validated the performance of the best classifier on a set of OGLE-IV light curves and applied this to find new Be star candidates. Results: The random forest classifier outperformed the others. By using the random forest classifier and colours criteria we found 50 Be star candidates in the direction of the Gaia south ecliptic pole field, four of which have infrared colours that are consistent with Herbig Ae/Be stars. Conclusions: Supervised methods are very useful in order to obtain preliminary samples of variable stars extracted from large databases. As usual, the stars classified as Be stars candidates must be checked for the colours and spectroscopic characteristics

  8. Plot of invariant mass distribution of diphoton candidates after all selections of the inclusive analysis for the combined 7 TeV and 8 TeV data

    CERN Multimedia

    ATLAS, Collaboration

    2013-01-01

    Invariant mass distribution of diphoton candidates after all selections of the inclusive analysis for the combined 7 TeV and 8 TeV data. The result of a fit to the data with the sum of a SM Higgs boson signal (with mH =126.8 GeV and free signal strength) and background is superimposed. The residuals of the data with respect to the fitted background are displayed in the lower panel.

  9. NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene

    International Nuclear Information System (INIS)

    Mattila, Henna; Schindler, Martin; Isotalo, Jarkko; Ikonen, Tarja; Vihinen, Mauno; Oja, Hannu; Tammela, Teuvo LJ; Wahlfors, Tiina; Schleutker, Johanna

    2011-01-01

    Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPCX1 at Xq27-q28, but due to the complex structure of the region, the susceptibility gene has not yet been identified. In this study, nonsense-mediated mRNA decay (NMD) inhibition was used for the discovery of truncating mutations. Six prostate cancer (PC) patients and their healthy brothers were selected from a group of HPCX1-linked families. Expression analyses were done using Agilent 44 K oligoarrays, and selected genes were screened for mutations by direct sequencing. In addition, microRNA expression levels in the lymphoblastic cells were analyzed to trace variants that might alter miRNA expression and explain partly an inherited genetic predisposion to PC. Seventeen genes were selected for resequencing based on the NMD array, but no truncating mutations were found. The most interesting variant was MAGEC1 p.Met1?. An association was seen between the variant and unselected PC (OR = 2.35, 95% CI = 1.10-5.02) and HPC (OR = 3.38, 95% CI = 1.10-10.40). miRNA analysis revealed altogether 29 miRNAs with altered expression between the PC cases and controls. miRNA target analysis revealed that 12 of them also had possible target sites in the MAGEC1 gene. These miRNAs were selected for validation process including four miRNAs located in the X chromosome. The expressions of 14 miRNAs were validated in families that contributed to the significant signal differences in Agilent arrays. Further functional studies are needed to fully understand the possible contribution of these miRNAs and MAGEC1 start codon variant to PC

  10. Genic SNP markers and legume synteny reveal candidate genes underlying QTL for Macrophomina phaseolina resistance and maturity in cowpea [Vigna unguiculata (L Walp.

    Directory of Open Access Journals (Sweden)

    Ehlers Jeffrey D

    2011-01-01

    . Conclusion Effective sources of host resistance were identified in this study. QTL mapping and synteny analysis identified genomic loci harboring resistance factors and revealed candidate genes with potential for further functional genomics analysis.

  11. Aiptasia sp. larvae as a model to reveal mechanisms of symbiont selection in cnidarians

    KAUST Repository

    Wolfowicz, Iliona

    2016-09-01

    Symbiosis, defined as the persistent association between two distinct species, is an evolutionary and ecologically critical phenomenon facilitating survival of both partners in diverse habitats. The biodiversity of coral reef ecosystems depends on a functional symbiosis with photosynthetic dinoflagellates of the highly diverse genus Symbiodinium, which reside in coral host cells and continuously support their nutrition. The mechanisms underlying symbiont selection to establish a stable endosymbiosis in non-symbiotic juvenile corals are unclear. Here we show for the first time that symbiont selection patterns for larvae of two Acropora coral species and the model anemone Aiptasia are similar under controlled conditions. We find that Aiptasia larvae distinguish between compatible and incompatible symbionts during uptake into the gastric cavity and phagocytosis. Using RNA-Seq, we identify a set of candidate genes potentially involved in symbiosis establishment. Together, our data complement existing molecular resources to mechanistically dissect symbiont phagocytosis in cnidarians under controlled conditions, thereby strengthening the role of Aiptasia larvae as a powerful model for cnidarian endosymbiosis establishment.

  12. Aiptasia sp. larvae as a model to reveal mechanisms of symbiont selection in cnidarians

    KAUST Repository

    Wolfowicz, Iliona; Baumgarten, Sebastian; Voss, Philipp A.; Hambleton, Elizabeth A.; Voolstra, Christian R.; Hatta, Masayuki; Guse, Annika

    2016-01-01

    Symbiosis, defined as the persistent association between two distinct species, is an evolutionary and ecologically critical phenomenon facilitating survival of both partners in diverse habitats. The biodiversity of coral reef ecosystems depends on a functional symbiosis with photosynthetic dinoflagellates of the highly diverse genus Symbiodinium, which reside in coral host cells and continuously support their nutrition. The mechanisms underlying symbiont selection to establish a stable endosymbiosis in non-symbiotic juvenile corals are unclear. Here we show for the first time that symbiont selection patterns for larvae of two Acropora coral species and the model anemone Aiptasia are similar under controlled conditions. We find that Aiptasia larvae distinguish between compatible and incompatible symbionts during uptake into the gastric cavity and phagocytosis. Using RNA-Seq, we identify a set of candidate genes potentially involved in symbiosis establishment. Together, our data complement existing molecular resources to mechanistically dissect symbiont phagocytosis in cnidarians under controlled conditions, thereby strengthening the role of Aiptasia larvae as a powerful model for cnidarian endosymbiosis establishment.

  13. Selection of candidate container materials for the conceptual waste package design for a potential high level nuclear waste repository at Yucca Mountain

    Energy Technology Data Exchange (ETDEWEB)

    Van Konynenburg, R.A.; Halsey, W.G.; McCright, R.D.; Clarke, W.L. Jr. [Lawrence Livermore National Lab., CA (United States); Gdowski, G.E. [KMI, Inc., Albuquerque, NM (United States)

    1993-02-01

    Preliminary selection criteria have been developed, peer-reviewed, and applied to a field of 41 candidate materials to choose three alloys for further consideration during the advanced conceptual design phase of waste package development for a potential high level nuclear waste repository at Yucca Mountain, Nevada. These three alloys are titanium grade 12, Alloy C-4, and Alloy 825. These selections are specific to the particular conceptual design outlined in the Site Characterization Plan. Other design concepts that may be considered in the advanced conceptual design phase may favor other materials choices.

  14. The use of uranium exploitation techniques in the selection of a candidate site for Cs-137 radioactive wastes from the Goiania accident

    International Nuclear Information System (INIS)

    Saad, S.

    1997-01-01

    The selection of a candidate site for the disposal of wastes containing Cesium-137 originated by the Goiania accident followed a sequence of studies where specific exploratory techniques in the field of geoscience were applied through geophysical, geochemical, hydrological, hydrogeological and pedological investigations and subsurface drillings. This programme has been aimed at characterizing in detail the selected site, in order to obtain parameters for the conceptual engineering design and also to elaborate the Environmental Impact Report. Among the different options encountered, the site which presented the best characteristics to store those wastes is located about 300 m west of the provisional repository. (author)

  15. Selection of candidate container materials for the conceptual waste package design for a potential high level nuclear waste repository at Yucca Mountain

    International Nuclear Information System (INIS)

    Van Konynenburg, R.A.; Halsey, W.G.; McCright, R.D.; Clarke, W.L. Jr.; Gdowski, G.E.

    1993-02-01

    Preliminary selection criteria have been developed, peer-reviewed, and applied to a field of 41 candidate materials to choose three alloys for further consideration during the advanced conceptual design phase of waste package development for a potential high level nuclear waste repository at Yucca Mountain, Nevada. These three alloys are titanium grade 12, Alloy C-4, and Alloy 825. These selections are specific to the particular conceptual design outlined in the Site Characterization Plan. Other design concepts that may be considered in the advanced conceptual design phase may favor other materials choices

  16. Geographical gradients in selection can reveal genetic constraints for evolutionary responses to ocean acidification.

    Science.gov (United States)

    Gaitán-Espitia, Juan Diego; Marshall, Dustin; Dupont, Sam; Bacigalupe, Leonardo D; Bodrossy, Levente; Hobday, Alistair J

    2017-02-01

    Geographical gradients in selection can shape different genetic architectures in natural populations, reflecting potential genetic constraints for adaptive evolution under climate change. Investigation of natural pH/pCO 2 variation in upwelling regions reveals different spatio-temporal patterns of natural selection, generating genetic and phenotypic clines in populations, and potentially leading to local adaptation, relevant to understanding effects of ocean acidification (OA). Strong directional selection, associated with intense and continuous upwellings, may have depleted genetic variation in populations within these upwelling regions, favouring increased tolerances to low pH but with an associated cost in other traits. In contrast, diversifying or weak directional selection in populations with seasonal upwellings or outside major upwelling regions may have resulted in higher genetic variances and the lack of genetic correlations among traits. Testing this hypothesis in geographical regions with similar environmental conditions to those predicted under climate change will build insights into how selection may act in the future and how populations may respond to stressors such as OA. © 2017 The Author(s).

  17. Social phenotype extended to communities: expanded multilevel social selection analysis reveals fitness consequences of interspecific interactions.

    Science.gov (United States)

    Campobello, Daniela; Hare, James F; Sarà, Maurizio

    2015-04-01

    In social species, fitness consequences are associated with both individual and social phenotypes. Social selection analysis has quantified the contribution of conspecific social traits to individual fitness. There has been no attempt, however, to apply a social selection approach to quantify the fitness implications of heterospecific social phenotypes. Here, we propose a novel social selection based approach integrating the role of all social interactions at the community level. We extended multilevel selection analysis by including a term accounting for the group phenotype of heterospecifics. We analyzed nest activity as a model social trait common to two species, the lesser kestrel (Falco naumanni) and jackdaw (Corvus monedula), nesting in either single- or mixed-species colonies. By recording reproductive outcome as a measure of relative fitness, our results reveal an asymmetric system wherein only jackdaw breeding performance was affected by the activity phenotypes of both conspecific and heterospecific neighbors. Our model incorporating heterospecific social phenotypes is applicable to animal communities where interacting species share a common social trait, thus allowing an assessment of the selection pressure imposed by interspecific interactions in nature. Finally, we discuss the potential role of ecological limitations accounting for random or preferential assortments among interspecific social phenotypes, and the implications of such processes to community evolution. © 2015 The Author(s).

  18. Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Jacob A Tennessen

    Full Text Available New strategies to combat the global scourge of schistosomiasis may be revealed by increased understanding of the mechanisms by which the obligate snail host can resist the schistosome parasite. However, few molecular markers linked to resistance have been identified and characterized in snails.Here we test six independent genetic loci for their influence on resistance to Schistosoma mansoni strain PR1 in the 13-16-R1 strain of the snail Biomphalaria glabrata. We first identify a genomic region, RADres, showing the highest differentiation between susceptible and resistant inbred lines among 1611 informative restriction-site associated DNA (RAD markers, and show that it significantly influences resistance in an independent set of 439 outbred snails. The additive effect of each RADres resistance allele is 2-fold, similar to that of the previously identified resistance gene sod1. The data fit a model in which both loci contribute independently and additively to resistance, such that the odds of infection in homozygotes for the resistance alleles at both loci (13% infected is 16-fold lower than the odds of infection in snails without any resistance alleles (70% infected. Genome-wide linkage disequilibrium is high, with both sod1 and RADres residing on haplotype blocks >2 Mb, and with other markers in each block also showing significant effects on resistance; thus the causal genes within these blocks remain to be demonstrated. Other candidate loci had no effect on resistance, including the Guadeloupe Resistance Complex and three genes (aif, infPhox, and prx1 with immunological roles and expression patterns tied to resistance, which must therefore be trans-regulated.The loci RADres and sod1 both have strong effects on resistance to S. mansoni. Future approaches to control schistosomiasis may benefit from further efforts to characterize and harness this natural genetic variation.

  19. A Novel Mgp-Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region.

    Science.gov (United States)

    Borrás, Teresa; Smith, Matthew H; Buie, LaKisha K

    2015-04-01

    Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice. An Mgp-Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry. As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative. Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.

  20. Genome-wide QTL and bulked transcriptomic analysis reveals new candidate genes for the control of tuber carotenoid content in potato (Solanum tuberosum L.).

    Science.gov (United States)

    Campbell, Raymond; Pont, Simon D A; Morris, Jenny A; McKenzie, Gaynor; Sharma, Sanjeev Kumar; Hedley, Pete E; Ramsay, Gavin; Bryan, Glenn J; Taylor, Mark A

    2014-09-01

    Genome-wide QTL analysis of potato tuber carotenoid content was investigated in populations of Solanum tuberosum Group Phureja that segregate for flesh colour, revealing a novel major QTL on chromosome 9. The carotenoid content of edible plant storage organs is a key nutritional and quality trait. Although the structural genes that encode the biosynthetic enzymes are well characterised, much less is known about the factors that determine overall storage organ content. In this study, genome-wide QTL mapping, in concert with an efficient 'genetical genomics' analysis using bulked samples, has been employed to investigate the genetic architecture of potato tuber carotenoid content. Two diploid populations of Solanum tuberosum Group Phureja were genotyped (AFLP, SSR and DArT markers) and analysed for their tuber carotenoid content over two growing seasons. Common to both populations were QTL that explained relatively small proportions of the variation in constituent carotenoids and a major QTL on chromosome 3 explaining up to 71 % of the variation in carotenoid content. In one of the populations (01H15), a second major carotenoid QTL was identified on chromosome 9, explaining up to 20 % of the phenotypic variation. Whereas the major chromosome 3 QTL was likely to be due to an allele of a gene encoding β-carotene hydroxylase, no known carotenoid biosynthetic genes are located in the vicinity of the chromosome 9 QTL. A unique expression profiling strategy using phenotypically distinct bulks comprised individuals with similar carotenoid content provided further support for the QTL mapping to chromosome 9. This study shows the potential of using the potato genome sequence to link genetic maps to data arising from eQTL approaches to enhance the discovery of candidate genes underlying QTLs.

  1. Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures

    International Nuclear Information System (INIS)

    Oyama, Takuji; Toyota, Kenji; Waku, Tsuyoshi; Hirakawa, Yuko; Nagasawa, Naoko; Kasuga, Jun-ichi; Hashimoto, Yuichi; Miyachi, Hiroyuki; Morikawa, Kosuke

    2009-01-01

    The structures of the ligand-binding domains (LBDs) of human peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARδ) in complexes with a pan agonist, an α/δ dual agonist and a PPARδ-specific agonist were determined. The results explain how each ligand is recognized by the PPAR LBDs at an atomic level. Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family, which is defined as transcriptional factors that are activated by the binding of ligands to their ligand-binding domains (LBDs). Although the three PPAR subtypes display different tissue distribution patterns and distinct pharmacological profiles, they all are essentially related to fatty-acid and glucose metabolism. Since the PPARs share similar three-dimensional structures within the LBDs, synthetic ligands which simultaneously activate two or all of the PPARs could be potent candidates in terms of drugs for the treatment of abnormal metabolic homeostasis. The structures of several PPAR LBDs were determined in complex with synthetic ligands, derivatives of 3-(4-alkoxyphenyl)propanoic acid, which exhibit unique agonistic activities. The PPARα and PPARγ LBDs were complexed with the same pan agonist, TIPP-703, which activates all three PPARs and their crystal structures were determined. The two LBD–ligand complex structures revealed how the pan agonist is adapted to the similar, but significantly different, ligand-binding pockets of the PPARs. The structures of the PPARδ LBD in complex with an α/δ-selective ligand, TIPP-401, and with a related δ-specific ligand, TIPP-204, were also determined. The comparison between the two PPARδ complexes revealed how each ligand exhibits either a ‘dual selective’ or ‘single specific’ binding mode

  2. Selective localization of different types of opiate receptors in hippocampus as revealed by in vitro autoradiography

    International Nuclear Information System (INIS)

    Duka, T.; Wuester, M.; Schubert, P.; Stoiber, R.; Herz, A.

    1981-01-01

    The visualization of opiate binding sites within the hippocampus of the rat has been achieved by means of an in vitro autoradiography. In line with the concept of multiple opiate receptors, different opioid agonists revealed a particular distribution pattern. Whereas the selective delta-receptor agonist [ 3 H]D-Ala 2 , D-Leu 5 -enkephalin specifically labelled binding sites in the CA 2 area, [ 3 H]etorphine grains displayed a uniform dense distribution throughout the pyramidal cell layers from CA 1 to CA 4 . (Auth.)

  3. Corrosion Behavior of Candidate Materials Used for Urea Hydrolysis Equipment in Coal-Fired Selective Catalytic Reduction Units

    Science.gov (United States)

    Lu, Jintao; Yang, Zhen; Zhang, Bo; Huang, Jinyang; Xu, Hongjie

    2018-05-01

    Corrosion tests were performed in the laboratory in order to assess the corrosion resistance of candidate materials used in urea hydrolysis equipment. The materials to be evaluated were exposed at 145 °C for 1000 h. Alloys 316L, 316L Mod., HR3C, Inconel 718, and TC4 were evaluated. Additionally, aluminide and chromate coatings applied to a 316L substrate were examined. After exposure, the mass changes in the test samples were measured by a discontinuous weighing method, and the morphologies, compositions, and phases of the corrosion products were analyzed using scanning electron microscopy, energy-dispersive spectroscopy, and x-ray diffraction. Results indicated that continuous pitting and dissolution corrosion were the main failure modes for 316L stainless steel. 316L Mod. and HR3C alloy showed better corrosion resistance than 316L due to their relatively high Cr contents, but HR3C exhibited a strong tendency toward intergranular corrosion. Inconel 718, TC4, and aluminide and chromate coating samples showed similar corrosion processes: only depositions formed by hydrothermal reactions were observed. Based on these results, a possible corrosion process in the urea hydrolysis environment was discussed for these candidate materials and questions to be clarified were proposed.

  4. Preliminary geological study in kabupaten Pamekasan area to support the selection of candidate site of nuclear desalination plant

    International Nuclear Information System (INIS)

    Ngadenin; Lilik Subiantoro; Kurnia Setiawan Widana

    2014-01-01

    The area around the southern coast Pamekasan is one of the candidates for the alternatives location of nuclear desalination plant site. In 1949 around Sampang Madura ever tectonic earthquake measuring 5 on the Richter scale with its epicenter on land. Tectonic earthquake with epicenter on land is likely related to the presence of active faults on the Madura island. Location prospective nuclear desalination plant site should be away or free of active faults. The study aimed to obtain geological information and find out the characteristics of tectonics including active fault to support site studies of nuclear desalination plant on the island of Madura. The method used is the geological mapping scale, 1 : 50,000. Lithology in the area along the south coast district Pamekasan is alluvium Holocene age and conglomerate units of Pleistocene age. There were no indications of active faults in the region. Candidates site at this location is less attractive in terms of geotechnical foundation as can be ascertained bedrock will be found sufficient in that building construction will require expensive. (author)

  5. Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.

    Science.gov (United States)

    Hook, Paul W; McClymont, Sarah A; Cannon, Gabrielle H; Law, William D; Morton, A Jennifer; Goff, Loyal A; McCallion, Andrew S

    2018-03-01

    Genetic variation modulating risk of sporadic Parkinson disease (PD) has been primarily explored through genome-wide association studies (GWASs). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal time points. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including genes with known PD associations and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1-null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Copyright © 2018 American Society of Human Genetics. All rights reserved.

  6. A Feasibility Assessment of Behavioral-based Interviewing to Improve Candidate Selection for a Pulmonary and Critical Care Medicine Fellowship Program.

    Science.gov (United States)

    Tatem, Geneva; Kokas, Maria; Smith, Cathy L; DiGiovine, Bruno

    2017-04-01

    Traditional interviews for residency and fellowship training programs are an important component in the selection process, but can be of variable value due to a nonstandardized approach. We redesigned the candidate interview process for our large pulmonary and critical care medicine fellowship program in the United States using a behavioral-based interview (BBI) structure. The primary goal of this approach was to standardize the assessment of candidates within noncognitive domains with the goal of selecting those with the best fit for our institution's fellowship program. Eight faculty members attended two BBI workshops. The first workshop identified our program's "best fit" criteria using the framework of the Accreditation Council for Graduate Medical Education's six core competencies and additional behaviors that fit within our programs. BBI questions were then selected from a national database and refined based on the attributes deemed most important by our faculty. In the second workshop, faculty practiced the BBI format in mock interviews with third-year fellows. The interview process was further refined based on feedback from the interviewees, and then applied with fellowship candidates for the 2014 recruitment season. The 1-year pilot of behavioral-based interviewing allowed us to achieve consensus on the traits sought for our incoming fellows and to standardize the interview process for our program using the framework of the Accreditation Council for Graduate Medical Education core competencies. Although the effects of this change on the clinical performance of our fellows have not yet been assessed, this description of our development and implementation processes may be helpful for programs seeking to redesign their applicant interviews.

  7. Plot of the distribution of the four-lepton invariant mass, m4l, for the selected candidates in the data

    CERN Multimedia

    ATLAS, Collaboration

    2013-01-01

    The distribution of the four-lepton invariant mass, m4l, for the selected candidates in the data. The estimated background, as well as the expected SM Higgs boson signal for mH = 124.3 GeV (scaled by the signal strength obtained from fits to the data), are also shown. The single-resonant peak at m4l ∼ 90 GeV includes contribu- tions from s-channel Z/γ∗ and t-channel (Z∗/γ∗)(Z∗/γ∗) production.

  8. Probing of RNA structures in a positive sense RNA virus reveals selection pressures for structural elements

    Science.gov (United States)

    Watters, Kyle E; Choudhary, Krishna; Aviran, Sharon; Perry, Keith L

    2018-01-01

    Abstract In single stranded (+)-sense RNA viruses, RNA structural elements (SEs) play essential roles in the infection process from replication to encapsidation. Using selective 2′-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq) and covariation analysis, we explore the structural features of the third genome segment of cucumber mosaic virus (CMV), RNA3 (2216 nt), both in vitro and in plant cell lysates. Comparing SHAPE-Seq and covariation analysis results revealed multiple SEs in the coat protein open reading frame and 3′ untranslated region. Four of these SEs were mutated and serially passaged in Nicotiana tabacum plants to identify biologically selected changes to the original mutated sequences. After passaging, loop mutants showed partial reversion to their wild-type sequence and SEs that were structurally disrupted by mutations were restored to wild-type-like structures via synonymous mutations in planta. These results support the existence and selection of virus open reading frame SEs in the host organism and provide a framework for further studies on the role of RNA structure in viral infection. Additionally, this work demonstrates the applicability of high-throughput chemical probing in plant cell lysates and presents a new method for calculating SHAPE reactivities from overlapping reverse transcriptase priming sites. PMID:29294088

  9. Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

    Science.gov (United States)

    Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

    2017-09-01

    The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

  10. CLUB-MARTINI : Selecting favourable interactions amongst available candidates, a coarse-grained simulation approach to scoring docking decoys

    NARCIS (Netherlands)

    Hou, Qingzhen; Lensink, Marc F; Heringa, Jaap; Feenstra, K Anton

    2016-01-01

    Large-scale identification of native binding orientations is crucial for understanding the role of protein-protein interactions in their biological context. Measuring binding free energy is the method of choice to estimate binding strength and reveal the relevance of particular conformations in

  11. Genome-Resolved Metagenomic Analysis Reveals Roles for Candidate Phyla and Other Microbial Community Members in Biogeochemical Transformations in Oil Reservoirs

    Directory of Open Access Journals (Sweden)

    Ping Hu

    2016-01-01

    Full Text Available Oil reservoirs are major sites of methane production and carbon turnover, processes with significant impacts on energy resources and global biogeochemical cycles. We applied a cultivation-independent genomic approach to define microbial community membership and predict roles for specific organisms in biogeochemical transformations in Alaska North Slope oil fields. Produced water samples were collected from six locations between 1,128 m (24 to 27°C and 2,743 m (80 to 83°C below the surface. Microbial community complexity decreased with increasing temperature, and the potential to degrade hydrocarbon compounds was most prevalent in the lower-temperature reservoirs. Sulfate availability, rather than sulfate reduction potential, seems to be the limiting factor for sulfide production in some of the reservoirs under investigation. Most microorganisms in the intermediate- and higher-temperature samples were related to previously studied methanogenic and nonmethanogenic archaea and thermophilic bacteria, but one candidate phylum bacterium, a member of the Acetothermia (OP1, was present in Kuparuk sample K3. The greatest numbers of candidate phyla were recovered from the mesothermic reservoir samples SB1 and SB2. We reconstructed a nearly complete genome for an organism from the candidate phylum Parcubacteria (OD1 that was abundant in sample SB1. Consistent with prior findings for members of this lineage, the OD1 genome is small, and metabolic predictions support an obligately anaerobic, fermentation-based lifestyle. At moderate abundance in samples SB1 and SB2 were members of bacteria from other candidate phyla, including Microgenomates (OP11, Atribacteria (OP9, candidate phyla TA06 and WS6, and Marinimicrobia (SAR406. The results presented here elucidate potential roles of organisms in oil reservoir biological processes.

  12. Secretome Characterization and Correlation Analysis Reveal Putative Pathogenicity Mechanisms and Identify Candidate Avirulence Genes in the Wheat Stripe Rust Fungus Puccinia striiformis f. sp. tritici.

    Science.gov (United States)

    Xia, Chongjing; Wang, Meinan; Cornejo, Omar E; Jiwan, Derick A; See, Deven R; Chen, Xianming

    2017-01-01

    Stripe (yellow) rust, caused by Puccinia striiformis f. sp. tritici ( Pst ), is one of the most destructive diseases of wheat worldwide. Planting resistant cultivars is an effective way to control this disease, but race-specific resistance can be overcome quickly due to the rapid evolving Pst population. Studying the pathogenicity mechanisms is critical for understanding how Pst virulence changes and how to develop wheat cultivars with durable resistance to stripe rust. We re-sequenced 7 Pst isolates and included additional 7 previously sequenced isolates to represent balanced virulence/avirulence profiles for several avirulence loci in seretome analyses. We observed an uneven distribution of heterozygosity among the isolates. Secretome comparison of Pst with other rust fungi identified a large portion of species-specific secreted proteins, suggesting that they may have specific roles when interacting with the wheat host. Thirty-two effectors of Pst were identified from its secretome. We identified candidates for Avr genes corresponding to six Yr genes by correlating polymorphisms for effector genes to the virulence/avirulence profiles of the 14 Pst isolates. The putative AvYr76 was present in the avirulent isolates, but absent in the virulent isolates, suggesting that deleting the coding region of the candidate avirulence gene has produced races virulent to resistance gene Yr76 . We conclude that incorporating avirulence/virulence phenotypes into correlation analysis with variations in genomic structure and secretome, particularly presence/absence polymorphisms of effectors, is an efficient way to identify candidate Avr genes in Pst . The candidate effector genes provide a rich resource for further studies to determine the evolutionary history of Pst populations and the co-evolutionary arms race between Pst and wheat. The Avr candidates identified in this study will lead to cloning avirulence genes in Pst , which will enable us to understand molecular mechanisms

  13. Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Anna Koczula

    2017-02-01

    Full Text Available Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq. In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism. In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments.

  14. A COMPREHENSIVE SEARCH FOR STELLAR BOWSHOCK NEBULAE IN THE MILKY WAY: A CATALOG OF 709 MID-INFRARED SELECTED CANDIDATES

    Energy Technology Data Exchange (ETDEWEB)

    Kobulnicky, Henry A.; Chick, William T.; Schurhammer, Danielle P.; Andrews, Julian E.; Munari, Stephan A.; Olivier, Grace M.; Sorber, Rebecca L.; Wernke, Heather N.; Dale, Daniel A. [Dept. of Physics and Astronomy, University of Wyoming, Laramie, WY 82070 (United States); Povich, Matthew S.; Dixon, Don M. [Department of Physics and Astronomy, California State Polytechnic University, 3801 West Temple Avenue, Pomona, CA 91768 (United States)

    2016-12-01

    We identify 709 arc-shaped mid-infrared nebula in 24 μ m Spitzer Space Telescope or 22 μ m Wide Field Infrared Explorer surveys of the Galactic Plane as probable dusty interstellar bowshocks powered by early-type stars. About 20% are visible at 8 μ m or at shorter mid-infrared wavelengths. The vast majority (660) have no previous identification in the literature. These extended infrared sources are strongly concentrated near the Galactic mid-plane, with an angular scale height of ∼0.°6. All host a symmetrically placed star implicated as the source of a stellar wind sweeping up interstellar material. These are candidate “runaway” stars potentially having high velocities in the reference frame of the local medium. Among the 286 objects with measured proper motions, we find an unambiguous excess with velocity vectors aligned with the infrared morphology—kinematic evidence that many of these are “runaway” stars with large peculiar motions responsible for the bowshock signature. We discuss a population of “in situ” bowshocks (∼103 objects) that face giant H ii regions where the relative motions between the star and ISM may be caused by bulk outflows from an overpressured bubble. We also identify ∼58 objects that face 8 μ m bright-rimmed clouds and apparently constitute a sub-class of in situ bowshocks where the stellar wind interacts with a photoevaporative flow (PEF) from an eroding molecular cloud interface (i.e., “PEF bowshocks”). Orientations of the arcuate nebulae exhibit a correlation over small angular scales, indicating that external influences such as H ii regions are responsible for producing some bowshock nebulae. However, the vast majority of the nebulae in this sample appear to be isolated (499 objects) from obvious external influences.

  15. Genome-wide Selective Sweeps in Natural Bacterial Populations Revealed by Time-series Metagenomics

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Leong-Keat; Bendall, Matthew L.; Malfatti, Stephanie; Schwientek, Patrick; Tremblay, Julien; Schackwitz, Wendy; Martin, Joel; Pati, Amrita; Bushnell, Brian; Foster, Brian; Kang, Dongwan; Tringe, Susannah G.; Bertilsson, Stefan; Moran, Mary Ann; Shade, Ashley; Newton, Ryan J.; Stevens, Sarah; McMcahon, Katherine D.; Mamlstrom, Rex R.

    2014-05-12

    Multiple evolutionary models have been proposed to explain the formation of genetically and ecologically distinct bacterial groups. Time-series metagenomics enables direct observation of evolutionary processes in natural populations, and if applied over a sufficiently long time frame, this approach could capture events such as gene-specific or genome-wide selective sweeps. Direct observations of either process could help resolve how distinct groups form in natural microbial assemblages. Here, from a three-year metagenomic study of a freshwater lake, we explore changes in single nucleotide polymorphism (SNP) frequencies and patterns of gene gain and loss in populations of Chlorobiaceae and Methylophilaceae. SNP analyses revealed substantial genetic heterogeneity within these populations, although the degree of heterogeneity varied considerably among closely related, co-occurring Methylophilaceae populations. SNP allele frequencies, as well as the relative abundance of certain genes, changed dramatically over time in each population. Interestingly, SNP diversity was purged at nearly every genome position in one of the Chlorobiaceae populations over the course of three years, while at the same time multiple genes either swept through or were swept from this population. These patterns were consistent with a genome-wide selective sweep, a process predicted by the ecotype model? of diversification, but not previously observed in natural populations.

  16. Genome-wide Selective Sweeps in Natural Bacterial Populations Revealed by Time-series Metagenomics

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Leong-Keat; Bendall, Matthew L.; Malfatti, Stephanie; Schwientek, Patrick; Tremblay, Julien; Schackwitz, Wendy; Martin, Joel; Pati, Amrita; Bushnell, Brian; Foster, Brian; Kang, Dongwan; Tringe, Susannah G.; Bertilsson, Stefan; Moran, Mary Ann; Shade, Ashley; Newton, Ryan J.; Stevens, Sarah; McMahon, Katherine D.; Malmstrom, Rex R.

    2014-06-18

    Multiple evolutionary models have been proposed to explain the formation of genetically and ecologically distinct bacterial groups. Time-series metagenomics enables direct observation of evolutionary processes in natural populations, and if applied over a sufficiently long time frame, this approach could capture events such as gene-specific or genome-wide selective sweeps. Direct observations of either process could help resolve how distinct groups form in natural microbial assemblages. Here, from a three-year metagenomic study of a freshwater lake, we explore changes in single nucleotide polymorphism (SNP) frequencies and patterns of gene gain and loss in populations of Chlorobiaceae and Methylophilaceae. SNP analyses revealed substantial genetic heterogeneity within these populations, although the degree of heterogeneity varied considerably among closely related, co-occurring Methylophilaceae populations. SNP allele frequencies, as well as the relative abundance of certain genes, changed dramatically over time in each population. Interestingly, SNP diversity was purged at nearly every genome position in one of the Chlorobiaceae populations over the course of three years, while at the same time multiple genes either swept through or were swept from this population. These patterns were consistent with a genome-wide selective sweep, a process predicted by the ‘ecotype model’ of diversification, but not previously observed in natural populations.

  17. Genome-Resolved Metagenomic Analysis Reveals Roles for Candidate Phyla and Other Microbial Community Members in Biogeochemical Transformations in Oil Reservoirs.

    Science.gov (United States)

    Hu, Ping; Tom, Lauren; Singh, Andrea; Thomas, Brian C; Baker, Brett J; Piceno, Yvette M; Andersen, Gary L; Banfield, Jillian F

    2016-01-19

    Oil reservoirs are major sites of methane production and carbon turnover, processes with significant impacts on energy resources and global biogeochemical cycles. We applied a cultivation-independent genomic approach to define microbial community membership and predict roles for specific organisms in biogeochemical transformations in Alaska North Slope oil fields. Produced water samples were collected from six locations between 1,128 m (24 to 27°C) and 2,743 m (80 to 83°C) below the surface. Microbial community complexity decreased with increasing temperature, and the potential to degrade hydrocarbon compounds was most prevalent in the lower-temperature reservoirs. Sulfate availability, rather than sulfate reduction potential, seems to be the limiting factor for sulfide production in some of the reservoirs under investigation. Most microorganisms in the intermediate- and higher-temperature samples were related to previously studied methanogenic and nonmethanogenic archaea and thermophilic bacteria, but one candidate phylum bacterium, a member of the Acetothermia (OP1), was present in Kuparuk sample K3. The greatest numbers of candidate phyla were recovered from the mesothermic reservoir samples SB1 and SB2. We reconstructed a nearly complete genome for an organism from the candidate phylum Parcubacteria (OD1) that was abundant in sample SB1. Consistent with prior findings for members of this lineage, the OD1 genome is small, and metabolic predictions support an obligately anaerobic, fermentation-based lifestyle. At moderate abundance in samples SB1 and SB2 were members of bacteria from other candidate phyla, including Microgenomates (OP11), Atribacteria (OP9), candidate phyla TA06 and WS6, and Marinimicrobia (SAR406). The results presented here elucidate potential roles of organisms in oil reservoir biological processes. The activities of microorganisms in oil reservoirs impact petroleum resource quality and the global carbon cycle. We show that bacteria

  18. Interactions among Candidate Genes Selected by Meta-Analyses Resulting in Higher Risk of Ischemic Stroke in a Chinese Population.

    Directory of Open Access Journals (Sweden)

    Man Luo

    Full Text Available Ischemic stroke (IS is a multifactorial disorder caused by both genetic and environmental factors. The combined effects of multiple susceptibility genes might result in a higher risk for IS than a single gene. Therefore, we investigated whether interactions among multiple susceptibility genes were associated with an increased risk of IS by evaluating gene polymorphisms identified in previous meta-analyses, including methylenetetrahydrofolate reductase (MTHFR C677T, beta fibrinogen (FGB, β-FG A455G and T148C, apolipoprotein E (APOE ε2-4, angiotensin-converting enzyme (ACE insertion/deletion (I/D, and endothelial nitric oxide synthase (eNOS G894T. In order to examine these interactions, 712 patients with IS and 774 controls in a Chinese Han population were genotyped using the SNaPshot method, and multifactor dimensionality reduction analysis was used to detect potential interactions among the candidate genes. The results of this study found that ACE I/D and β-FG T148C were significant synergistic contributors to IS. In particular, the ACE DD + β-FG 148CC, ACE DD + β-FG 148CT, and ACE ID + β-FG 148CC genotype combinations resulted in higher risk of IS. After adjusting for potential confounding IS risk factors (age, gender, family history of IS, hypertension history and history of diabetes mellitus using a logistic analysis, a significant correlation between the genotype combinations and IS patients persisted (overall stroke: adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.22-2.02, P < 0.001, large artery atherosclerosis subtype: adjusted OR = 1.50, 95% CI: 1.08-2.07, P = 0.016, small-artery occlusion subtype: adjusted OR = 2.04, 95% CI: 1.43-2.91, P < 0.001. The results of this study indicate that the ACE I/D and β-FG T148C combination may result in significantly higher risk of IS in this Chinese population.

  19. Transcriptomics of the rice blast fungus Magnaporthe oryzae in response to the bacterial antagonist Lysobacter enzymogenes reveals candidate fungal defense response genes.

    Directory of Open Access Journals (Sweden)

    Sandra M Mathioni

    Full Text Available Plants and animals have evolved a first line of defense response to pathogens called innate or basal immunity. While basal defenses in these organisms are well studied, there is almost a complete lack of understanding of such systems in fungal species, and more specifically, how they are able to detect and mount a defense response upon pathogen attack. Hence, the goal of the present study was to understand how fungi respond to biotic stress by assessing the transcriptional profile of the rice blast pathogen, Magnaporthe oryzae, when challenged with the bacterial antagonist Lysobacter enzymogenes. Based on microscopic observations of interactions between M. oryzae and wild-type L. enzymogenes strain C3, we selected early and intermediate stages represented by time-points of 3 and 9 hours post-inoculation, respectively, to evaluate the fungal transcriptome using RNA-seq. For comparative purposes, we also challenged the fungus with L. enzymogenes mutant strain DCA, previously demonstrated to be devoid of antifungal activity. A comparison of transcriptional data from fungal interactions with the wild-type bacterial strain C3 and the mutant strain DCA revealed 463 fungal genes that were down-regulated during attack by C3; of these genes, 100 were also found to be up-regulated during the interaction with DCA. Functional categorization of genes in this suite included those with roles in carbohydrate metabolism, cellular transport and stress response. One gene in this suite belongs to the CFEM-domain class of fungal proteins. Another CFEM class protein called PTH11 has been previously characterized, and we found that a deletion in this gene caused advanced lesion development by C3 compared to its growth on the wild-type fungus. We discuss the characterization of this suite of 100 genes with respect to their role in the fungal defense response.

  20. Selecting Candidates for Liver Transplantation: A Medical Ethics Perspective on the Microallocation of a Scarce and Rationed Resource

    Directory of Open Access Journals (Sweden)

    Eric M Yoshida

    1998-01-01

    Full Text Available Liver transplantation has evolved over the past 35 years from an experimental procedure with high perioperative mortality to an accepted form of treatment with an approximate 85% one-year and 80% three-year patient survival rate. Following the success and acceptance of transplantation in the treatment of end-stage liver disease, there has been a progressive increase in the number of patients seeking a limited supply of donor organs. The ethical focus, on a microallocation level, has therefore changed from that of the 1960s, when the question was whether the procedure should be offered at all, to that of the 1990s and beyond, when the focus is on the proper allocation of a scarce, life-saving resource. The ethical issues concerning fair allocation surrounding liver transplantation are explored, from both the referring physician's perspective and the perspective of the transplant physician. In particular, the contrasting viewpoints of bioethicists Nicholas Rescher and James Childress, with respect to nonmedical and social criteria in the selection of patients for scarce, life-saving therapies, are explored. Lastly, some alternative ethical models for patient selection are reviewed.

  1. Objective assessment of surgical performance and its impact on a national selection programme of candidates for higher surgical training in plastic surgery.

    LENUS (Irish Health Repository)

    Carroll, Sean M

    2012-02-01

    OBJECTIVE: The objective of this study was to develop and validate a transparent, fair and objective assessment programme for the selection of surgical trainees into higher surgical training (HST) in plastic surgery in the Republic of Ireland. METHODS: Thirty-four individuals applied for HST in plastic surgery at the Royal College of Surgeons in Ireland (RCSI) in the academic years 2005-2006 and 2006-2007. Eighteen were short-listed for interview and further assessment. All applicants were required to report on their undergraduate educational performance and their postgraduate professional development. Short-listed applicants completed validated objective assessment simulations of surgical skills, an interview and assessment of their suitability for a career in surgery. RESULTS: When applicants\\' short-listing scores were combined with their interview scores and assessment of their suitability for a career in surgery, individuals who were selected for HST in plastic surgery performed significantly better than those who were not (P<0.002). However, when the assessment of technical skills scores were added the significance level of this difference increased further (P<0.0001) as did the statistical power of the difference to 99.9%, thus increasing the robustness of the selection package. CONCLUSION: The results from this study suggest that the assessment protocol we used to select individuals for HST in plastic surgery reliably and statistically significantly discriminated between the performances of candidates.

  2. Selection and validation of potato candidate genes for maturity corrected resistance to Phytophthora infestans based on differential expression combined with SNP association and linkage mapping

    Directory of Open Access Journals (Sweden)

    Meki Shehabu Muktar

    2015-09-01

    Full Text Available Late blight of potato (Solanum tuberosum L. caused by the oomycete Phytophthora infestans (Mont. de Bary, is one of the most important bottlenecks of potato production worldwide. Cultivars with high levels of durable, race unspecific, quantitative resistance are part of a solution to this problem. However, breeding for quantitative resistance is hampered by the correlation between resistance and late plant maturity, which is an undesirable agricultural attribute. The objectives of our research are (i the identification of genes that condition quantitative resistance to P. infestans not compromised by late plant maturity and (ii the discovery of diagnostic single nucleotide polymorphism (SNP markers to be used as molecular tools to increase efficiency and precision of resistance breeding. Twenty two novel candidate genes were selected based on comparative transcript profiling by SuperSAGE (serial analysis of gene expression in groups of plants with contrasting levels of maturity corrected resistance (MCR. Reproducibility of differential expression was tested by quantitative real time PCR and allele specific pyrosequencing in four new sets of genotype pools with contrasting late blight resistance levels, at three infection time points and in three independent infection experiments. Reproducibility of expression patterns ranged from 28% to 97%. Association mapping in a panel of 184 tetraploid cultivars identified SNPs in five candidate genes that were associated with MCR. These SNPs can be used in marker-assisted resistance breeding. Linkage mapping in two half-sib families (n = 111 identified SNPs in three candidate genes that were linked with MCR. The differentially expressed genes that showed association and/or linkage with MCR putatively function in phytosterol synthesis, fatty acid synthesis, asparagine synthesis, chlorophyll synthesis, cell wall modification and in the response to pathogen elicitors.

  3. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain

    Science.gov (United States)

    Nguyen, AnhThu; Rauch, Tibor A.; Pfeifer, Gerd P.; Hu, Valerie W.

    2010-01-01

    Autism is currently considered a multigene disorder with epigenetic influences. To investigate the contribution of DNA methylation to autism spectrum disorders, we have recently completed large-scale methylation profiling by CpG island microarray analysis of lymphoblastoid cell lines derived from monozygotic twins discordant for diagnosis of autism and their nonautistic siblings. Methylation profiling revealed many candidate genes differentially methylated between discordant MZ twins as well as between both twins and nonautistic siblings. Bioinformatics analysis of the differentially methylated genes demonstrated enrichment for high-level functions including gene transcription, nervous system development, cell death/survival, and other biological processes implicated in autism. The methylation status of 2 of these candidate genes, BCL-2 and retinoic acid-related orphan receptor alpha (RORA), was further confirmed by bisulfite sequencing and methylation-specific PCR, respectively. Immunohistochemical analyses of tissue arrays containing slices of the cerebellum and frontal cortex of autistic and age- and sex-matched control subjects revealed decreased expression of RORA and BCL-2 proteins in the autistic brain. Our data thus confirm the role of epigenetic regulation of gene expression via differential DNA methylation in idiopathic autism, and furthermore link molecular changes in a peripheral cell model with brain pathobiology in autism.—Nguyen, A., Rauch, T. A., Pfeifer, G. P., Hu, V. W. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. PMID:20375269

  4. Quasar Photometric Redshifts and Candidate Selection: A New Algorithm Based on Optical and Mid-infrared Photometric Data

    Science.gov (United States)

    Yang, Qian; Wu, Xue-Bing; Fan, Xiaohui; Jiang, Linhua; McGreer, Ian; Green, Richard; Yang, Jinyi; Schindler, Jan-Torge; Wang, Feige; Zuo, Wenwen; Fu, Yuming

    2017-12-01

    We present a new algorithm to estimate quasar photometric redshifts (photo-zs), by considering the asymmetries in the relative flux distributions of quasars. The relative flux models are built with multivariate Skew-t distributions in the multidimensional space of relative fluxes as a function of redshift and magnitude. For 151,392 quasars in the SDSS, we achieve a photo-z accuracy, defined as the fraction of quasars with the difference between the photo-z z p and the spectroscopic redshift z s , | {{Δ }}z| =| {z}s-{z}p| /(1+{z}s) within 0.1, of 74%. Combining the WISE W1 and W2 infrared data with the SDSS data, the photo-z accuracy is enhanced to 87%. Using the Pan-STARRS1 or DECaLS photometry with WISE W1 and W2 data, the photo-z accuracies are 79% and 72%, respectively. The prior probabilities as a function of magnitude for quasars, stars, and galaxies are calculated, respectively, based on (1) the quasar luminosity function, (2) the Milky Way synthetic simulation with the Besançon model, and (3) the Bayesian Galaxy Photometric Redshift estimation. The relative fluxes of stars are obtained with the Padova isochrones, and the relative fluxes of galaxies are modeled through galaxy templates. We test our classification method to select quasars using the DECaLS g, r, z, and WISE W1 and W2 photometry. The quasar selection completeness is higher than 70% for a wide redshift range 0.5publicly available.

  5. Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments.

    Directory of Open Access Journals (Sweden)

    Paul J Wichgers Schreur

    2016-08-01

    Full Text Available The bunyavirus genome comprises a small (S, medium (M, and large (L RNA segment of negative polarity. Although genome segmentation confers evolutionary advantages by enabling genome reassortment events with related viruses, genome segmentation also complicates genome replication and packaging. Accumulating evidence suggests that genomes of viruses with eight or more genome segments are incorporated into virions by highly selective processes. Remarkably, little is known about the genome packaging process of the tri-segmented bunyaviruses. Here, we evaluated, by single-molecule RNA fluorescence in situ hybridization (FISH, the intracellular spatio-temporal distribution and replication kinetics of the Rift Valley fever virus (RVFV genome and determined the segment composition of mature virions. The results reveal that the RVFV genome segments start to replicate near the site of infection before spreading and replicating throughout the cytoplasm followed by translocation to the virion assembly site at the Golgi network. Despite the average intracellular S, M and L genome segments approached a 1:1:1 ratio, major differences in genome segment ratios were observed among cells. We also observed a significant amount of cells lacking evidence of M-segment replication. Analysis of two-segmented replicons and four-segmented viruses subsequently confirmed the previous notion that Golgi recruitment is mediated by the Gn glycoprotein. The absence of colocalization of the different segments in the cytoplasm and the successful rescue of a tri-segmented variant with a codon shuffled M-segment suggested that inter-segment interactions are unlikely to drive the copackaging of the different segments into a single virion. The latter was confirmed by direct visualization of RNPs inside mature virions which showed that the majority of virions lack one or more genome segments. Altogether, this study suggests that RVFV genome packaging is a non-selective process.

  6. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Directory of Open Access Journals (Sweden)

    Chiao-Ling Lo

    2016-08-01

    Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  7. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Science.gov (United States)

    Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

    2016-08-01

    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  8. Within-host selection of drug resistance in a mouse model reveals dose-dependent selection of atovaquone resistance mutations

    NARCIS (Netherlands)

    Nuralitha, Suci; Murdiyarso, Lydia S.; Siregar, Josephine E.; Syafruddin, Din; Roelands, Jessica; Verhoef, Jan; Hoepelman, Andy I.M.; Marzuki, Sangkot

    2017-01-01

    The evolutionary selection of malaria parasites within an individual host plays a critical role in the emergence of drug resistance. We have compared the selection of atovaquone resistance mutants in mouse models reflecting two different causes of failure of malaria treatment, an inadequate

  9. Selection and validation of reference genes for qRT-PCR expression analysis of candidate genes involved in olfactory communication in the butterfly Bicyclus anynana.

    Directory of Open Access Journals (Sweden)

    Alok Arun

    Full Text Available Real-time quantitative reverse transcription PCR (qRT-PCR is a technique widely used to quantify the transcriptional expression level of candidate genes. qRT-PCR requires the selection of one or several suitable reference genes, whose expression profiles remain stable across conditions, to normalize the qRT-PCR expression profiles of candidate genes. Although several butterfly species (Lepidoptera have become important models in molecular evolutionary ecology, so far no study aimed at identifying reference genes for accurate data normalization for any butterfly is available. The African bush brown butterfly Bicyclus anynana has drawn considerable attention owing to its suitability as a model for evolutionary ecology, and we here provide a maiden extensive study to identify suitable reference gene in this species. We monitored the expression profile of twelve reference genes: eEF-1α, FK506, UBQL40, RpS8, RpS18, HSP, GAPDH, VATPase, ACT3, TBP, eIF2 and G6PD. We tested the stability of their expression profiles in three different tissues (wings, brains, antennae, two developmental stages (pupal and adult and two sexes (male and female, all of which were subjected to two food treatments (food stress and control feeding ad libitum. The expression stability and ranking of twelve reference genes was assessed using two algorithm-based methods, NormFinder and geNorm. Both methods identified RpS8 as the best suitable reference gene for expression data normalization. We also showed that the use of two reference genes is sufficient to effectively normalize the qRT-PCR data under varying tissues and experimental conditions that we used in B. anynana. Finally, we tested the effect of choosing reference genes with different stability on the normalization of the transcript abundance of a candidate gene involved in olfactory communication in B. anynana, the Fatty Acyl Reductase 2, and we confirmed that using an unstable reference gene can drastically alter the

  10. Selection and validation of reference genes for qRT-PCR expression analysis of candidate genes involved in olfactory communication in the butterfly Bicyclus anynana.

    Science.gov (United States)

    Arun, Alok; Baumlé, Véronique; Amelot, Gaël; Nieberding, Caroline M

    2015-01-01

    Real-time quantitative reverse transcription PCR (qRT-PCR) is a technique widely used to quantify the transcriptional expression level of candidate genes. qRT-PCR requires the selection of one or several suitable reference genes, whose expression profiles remain stable across conditions, to normalize the qRT-PCR expression profiles of candidate genes. Although several butterfly species (Lepidoptera) have become important models in molecular evolutionary ecology, so far no study aimed at identifying reference genes for accurate data normalization for any butterfly is available. The African bush brown butterfly Bicyclus anynana has drawn considerable attention owing to its suitability as a model for evolutionary ecology, and we here provide a maiden extensive study to identify suitable reference gene in this species. We monitored the expression profile of twelve reference genes: eEF-1α, FK506, UBQL40, RpS8, RpS18, HSP, GAPDH, VATPase, ACT3, TBP, eIF2 and G6PD. We tested the stability of their expression profiles in three different tissues (wings, brains, antennae), two developmental stages (pupal and adult) and two sexes (male and female), all of which were subjected to two food treatments (food stress and control feeding ad libitum). The expression stability and ranking of twelve reference genes was assessed using two algorithm-based methods, NormFinder and geNorm. Both methods identified RpS8 as the best suitable reference gene for expression data normalization. We also showed that the use of two reference genes is sufficient to effectively normalize the qRT-PCR data under varying tissues and experimental conditions that we used in B. anynana. Finally, we tested the effect of choosing reference genes with different stability on the normalization of the transcript abundance of a candidate gene involved in olfactory communication in B. anynana, the Fatty Acyl Reductase 2, and we confirmed that using an unstable reference gene can drastically alter the expression

  11. Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

    Science.gov (United States)

    Ray, Partha; Rialon-Guevara, Kristy L; Veras, Emanuela; Sullenger, Bruce A; White, Rebekah R

    2012-05-01

    Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

  12. Di- or polysulphide-bound biomarkers in sulphur-rich geomacromolecules as revealed by selective chemolysis

    Science.gov (United States)

    Kohnen, Math E. l.; Sinninghe Damsté, Jaap S.; Kock-van Dalen, A. c.; Jan, W. De Leeuw

    1991-05-01

    Three types of sulphur-rich high-molecular-weight material in the alkylsulphide, the polar, and the asphaltene fractions isolated from the bitumen of an immature bituminous shale from the Vena del Gesso basin (Italy) were desulphurised using Raney Ni and were treated with MeLi/MeI, a chemical degradation method which cleaves selectively and quantitatively di- or polysulphide linkages. The products formed were characterised by gas chromatography-mass spectrometry. Raney Ni desulphurisation revealed that these S-rich macromolecules are in substantial part composed of sulphur-linked biomarkers with linear, branched, isoprenoid, steroid, hopanoid, and carotenoid carbon skeletons. MeLi/Mel treatment provided evidence that a major part of the total amount of macromolecularly bound biomarkers are linked via di- or polysulphide moieties to the macromolecular network. Since the di- or polysulphide linkages are attached at specific positions of the bound biomarkers it is proposed that they are formed by intermolecular incorporation reactions of HS x- into low-molecular-weight functionalised biological lipids during early diagenesis. The different properties (solubility and molecular weight) of the sulphur-rich macromolecules in the alkylsulphide, the resin, and the asphaltene fractions can be explained simply by differences in degree of sulphur cross-linking.

  13. Long-term archives reveal shifting extinction selectivity in China's postglacial mammal fauna

    Science.gov (United States)

    Crees, Jennifer J.; Li, Zhipeng; Bielby, Jon; Yuan, Jing

    2017-01-01

    Ecosystems have been modified by human activities for millennia, and insights about ecology and extinction risk based only on recent data are likely to be both incomplete and biased. We synthesize multiple long-term archives (over 250 archaeological and palaeontological sites dating from the early Holocene to the Ming Dynasty and over 4400 historical records) to reconstruct the spatio-temporal dynamics of Holocene–modern range change across China, a megadiverse country experiencing extensive current-day biodiversity loss, for 34 mammal species over three successive postglacial time intervals. Our combined zooarchaeological, palaeontological, historical and current-day datasets reveal that both phylogenetic and spatial patterns of extinction selectivity have varied through time in China, probably in response both to cumulative anthropogenic impacts (an ‘extinction filter’ associated with vulnerable species and accessible landscapes being affected earlier by human activities) and also to quantitative and qualitative changes in regional pressures. China has experienced few postglacial global species-level mammal extinctions, and most species retain over 50% of their maximum estimated Holocene range despite millennia of increasing regional human pressures, suggesting that the potential still exists for successful species conservation and ecosystem restoration. Data from long-term archives also demonstrate that herbivores have experienced more historical extinctions in China, and carnivores have until recently displayed greater resilience. Accurate assessment of patterns of biodiversity loss and the likely predictive power of current-day correlates of faunal vulnerability and resilience is dependent upon novel perspectives provided by long-term archives. PMID:29167363

  14. Assessment of chimeric mice with humanized livers in new drug development: generation of pharmacokinetics, metabolism and toxicity data for selecting the final candidate compound.

    Science.gov (United States)

    Kamimura, Hidetaka; Ito, Satoshi

    2016-01-01

    1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.

  15. Evaluation and selection of Bacillus species based on enzyme production, antimicrobial activity and biofilm synthesis as direct-fed microbials candidates for poultry

    Directory of Open Access Journals (Sweden)

    Juan D Latorre

    2016-10-01

    Full Text Available Social concern about misuse of antibiotics as growth promoters (AGP and generation of multidrug-resistant bacteria have restricted the dietary inclusion of antibiotics in livestock feed in several countries. Direct-fed microbials (DFM are one of the multiple alternatives commonly evaluated as substitutes of AGP. Sporeformer bacteria from the genus Bacillus have been extensively investigated because of their extraordinary properties to form highly-resistant endospores, production of antimicrobial compounds and synthesize different exogenous enzymes. The purpose of the present study was to evaluate and select Bacillus spp. from environmental and poultry sources as DFM candidates, considering their enzyme production profile, biofilm synthesis capacity and pathogen-inhibition activity. Thirty one Bacillus isolates were screened for in vitro relative enzyme activity of amylase, protease, lipase and phytase using a selective media for each enzyme, with 3/31 strains selected as superior enzyme producers. These three isolates were identified as B. subtilis (1/3, and B. amyloliquefaciens (2/3 based on biochemical tests and 16S rRNA sequence analysis. For evaluation of biofilm synthesis, the generation of an adherent crystal violet-stained ring was determined in polypropylene tubes, resulting in 11/31 strains showing a strong biofilm formation. Moreover, all Bacillus strains were evaluated for growth inhibition activity against Salmonella enterica serovar Enteritidis (26/31, Escherichia coli (28/31 and Clostridioides difficile (29/31. Additionally, in previous in vitro and in vivo studies, these selected Bacillus strains have shown to be resistant to different biochemical conditions of the gastrointestinal tract of poultry. Results of the present study suggest that the selection and consumption of Bacillus-DFM, producing a variable set of enzymes and antimicrobial compounds may contribute to enhanced performance through improving nutrient digestibility

  16. Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2

    DEFF Research Database (Denmark)

    Hawthorne, Felicia; Feng, Sheng; Metlapally, Ravikanth

    2013-01-01

    PURPOSE: Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21-23 by four independent linkage studies. METHODS: We performed a genetic association study...... statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10(-6)); rs7134216, in the 3' untranslated region (UTR) of DEPDC4 (P = 5.4 × 10(-7)); and rs17306116, an intronic SNP within PPFIA2 (P Independently conducted whole genome expression array analyses identified...... protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR). CONCLUSIONS: In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs...

  17. Genome scans on experimentally evolved populations reveal candidate regions for adaptation to plant resistance in the potato cyst nematode Globodera pallida.

    Science.gov (United States)

    Eoche-Bosy, D; Gautier, M; Esquibet, M; Legeai, F; Bretaudeau, A; Bouchez, O; Fournet, S; Grenier, E; Montarry, J

    2017-09-01

    Improving resistance durability involves to be able to predict the adaptation speed of pathogen populations. Identifying the genetic bases of pathogen adaptation to plant resistances is a useful step to better understand and anticipate this phenomenon. Globodera pallida is a major pest of potato crop for which a resistance QTL, GpaV vrn , has been identified in Solanum vernei. However, its durability is threatened as G. pallida populations are able to adapt to the resistance in few generations. The aim of this study was to investigate the genomic regions involved in the resistance breakdown by coupling experimental evolution and high-density genome scan. We performed a whole-genome resequencing of pools of individuals (Pool-Seq) belonging to G. pallida lineages derived from two independent populations having experimentally evolved on susceptible and resistant potato cultivars. About 1.6 million SNPs were used to perform the genome scan using a recent model testing for adaptive differentiation and association to population-specific covariables. We identified 275 outliers and 31 of them, which also showed a significant reduction in diversity in adapted lineages, were investigated for their genic environment. Some candidate genomic regions contained genes putatively encoding effectors and were enriched in SPRYSECs, known in cyst nematodes to be involved in pathogenicity and in (a)virulence. Validated candidate SNPs will provide a useful molecular tool to follow frequencies of virulence alleles in natural G. pallida populations and define efficient strategies of use of potato resistances maximizing their durability. © 2017 John Wiley & Sons Ltd.

  18. Voronoi-based spatial analysis reveals selective interneuron changes in the cortex of FALS mice.

    Science.gov (United States)

    Minciacchi, Diego; Kassa, Roman M; Del Tongo, Claudia; Mariotti, Raffaella; Bentivoglio, Marina

    2009-01-01

    The neurodegenerative disease amyotrophic lateral sclerosis affects lower motoneurons and corticospinal cells. Mice expressing human mutant superoxide dismutase (SOD)1 provide widely investigated models of the familial form of disease, but information on cortical changes in these mice is still limited. We here analyzed the spatial organization of interneurons characterized by parvalbumin immunoreactivity in the motor, somatosensory, and visual cortical areas of SOD1(G93A) mice. Cell number and sociological spatial behavior were assessed by digital charts of cell location in cortical samples, cell counts, and generation of two-dimensional Voronoi diagrams. In end-stage SOD1-mutant mice, an increase of parvalbumin-containing cortical interneurons was found in the motor and somatosensory areas (about 35% and 20%, respectively) with respect to wild-type littermates. Changes in cell spatial distribution, as documented by Voronoi-derived coefficients of variation, indicated increased tendency of parvalbumin cells to aggregate into clusters in the same areas of the SOD1-mutant cortex. Counts and coefficients of variation of parvalbumin cells in the visual cortex gave instead similar results in SOD1-mutant and wild-type mice. Analyses of motor and somatosensory areas in presymptomatic SOD1-mutant mice provided findings very similar to those obtained at end-stage, indicating early changes of interneurons in these cortical areas during the pathology. Altogether the data reveal in the SOD1-mutant mouse cortex an altered architectonic pattern of interneurons, which selectively affects areas involved in motor control. The findings, which can be interpreted as pathogenic factors or early disease-related adaptations, point to changes in the cortical regulation and modulation of the motor circuit during motoneuron disease.

  19. 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.

  20. 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.

  1. Selection and Verification of Candidate Reference Genes for Mature MicroRNA Expression by Quantitative RT-PCR in the Tea Plant (Camellia sinensis

    Directory of Open Access Journals (Sweden)

    Hui Song

    2016-05-01

    Full Text Available Quantitative reverse transcription-polymerase chain reaction (qRT-PCR is a rapid and sensitive method for analyzing microRNA (miRNA expression. However, accurate qRT-PCR results depend on the selection of reliable reference genes as internal positive controls. To date, few studies have identified reliable reference genes for differential expression analysis of miRNAs among tissues, and among experimental conditions in plants. In this study, three miRNAs and four non-coding small RNAs (ncRNA were selected as reference candidates, and the stability of their expression was evaluated among different tissues and under different experimental conditions in the tea plant (Camellia sinensis using the geNorm and NormFinder programs. It was shown that miR159a was the best single reference gene in the bud to the fifth leaf, 5S rRNA was the most suitable gene in different organs, miR6149 was the most stable gene when the leaves were attacked by Ectropis oblique and U4, miR5368n and miR159a were the best genes when the leaves were treated by methyl jasmonate (MeJA, salicylic acid (SA and abscisic acid (ABA, respectively. Our results provide suitable reference genes for future investigations on miRNA functions in tea plants.

  2. A Genome-Wide Association Study for Culm Cellulose Content in Barley Reveals Candidate Genes Co-Expressed with Members of the CELLULOSE SYNTHASE A Gene Family

    Science.gov (United States)

    Houston, Kelly; Burton, Rachel A.; Sznajder, Beata; Rafalski, Antoni J.; Dhugga, Kanwarpal S.; Mather, Diane E.; Taylor, Jillian; Steffenson, Brian J.; Waugh, Robbie; Fincher, Geoffrey B.

    2015-01-01

    Cellulose is a fundamentally important component of cell walls of higher plants. It provides a scaffold that allows the development and growth of the plant to occur in an ordered fashion. Cellulose also provides mechanical strength, which is crucial for both normal development and to enable the plant to withstand both abiotic and biotic stresses. We quantified the cellulose concentration in the culm of 288 two – rowed and 288 six – rowed spring type barley accessions that were part of the USDA funded barley Coordinated Agricultural Project (CAP) program in the USA. When the population structure of these accessions was analysed we identified six distinct populations, four of which we considered to be comprised of a sufficient number of accessions to be suitable for genome-wide association studies (GWAS). These lines had been genotyped with 3072 SNPs so we combined the trait and genetic data to carry out GWAS. The analysis allowed us to identify regions of the genome containing significant associations between molecular markers and cellulose concentration data, including one region cross-validated in multiple populations. To identify candidate genes we assembled the gene content of these regions and used these to query a comprehensive RNA-seq based gene expression atlas. This provided us with gene annotations and associated expression data across multiple tissues, which allowed us to formulate a supported list of candidate genes that regulate cellulose biosynthesis. Several regions identified by our analysis contain genes that are co-expressed with CELLULOSE SYNTHASE A (HvCesA) across a range of tissues and developmental stages. These genes are involved in both primary and secondary cell wall development. In addition, genes that have been previously linked with cellulose synthesis by biochemical methods, such as HvCOBRA, a gene of unknown function, were also associated with cellulose levels in the association panel. Our analyses provide new insights into the

  3. A Genome-Wide mRNA Screen and Functional Analysis Reveal FOXO3 as a Candidate Gene for Chicken Growth

    Science.gov (United States)

    Chen, Biao; Xu, Jiguo; He, Xiaomei; Xu, Haiping; Li, Guihuan; Du, Hongli; Nie, Qinghua; Zhang, Xiquan

    2015-01-01

    Chicken growth performance provides direct economic benefits to the poultry industry. However, the underlying genetic mechanisms are unclear. The objective of this study was to identify candidate genes associated with chicken growth and investigate their potential mechanisms. We used RNA-Seq to study the breast muscle transcriptome in high and low tails of Recessive White Rock (WRRh, WRRl) and Xinghua chickens (XHh, XHl). A total of 60, 23, 153 and 359 differentially expressed genes were detected in WRRh vs. WRRl, XHh vs. XHl, WRRh vs. XHh and WRRl vs. XHl, respectively. GO, KEGG pathway and gene network analyses showed that CEBPB, FBXO32, FOXO3 and MYOD1 played key roles in growth. The functions of FBXO32 and FOXO3 were validated. FBXO32 was predominantly expressed in leg muscle, heart and breast muscle. After decreased FBXO32 expression, growth-related genes such as PDK4, IGF2R and IGF2BP3 were significantly down-regulated (P chickens with normal body weight (P chicken growth. Our observations provide new clues to understand the molecular basis of chicken growth. PMID:26366565

  4. Elaborate cellulosome architecture of Acetivibrio cellulolyticus revealed by selective screening of cohesin–dockerin interactions

    Directory of Open Access Journals (Sweden)

    Yuval Hamberg

    2014-10-01

    Full Text Available Cellulosic waste represents a significant and underutilized carbon source for the biofuel industry. Owing to the recalcitrance of crystalline cellulose to enzymatic degradation, it is necessary to design economical methods of liberating the fermentable sugars required for bioethanol production. One route towards unlocking the potential of cellulosic waste lies in a highly complex class of molecular machines, the cellulosomes. Secreted mainly by anaerobic bacteria, cellulosomes are structurally diverse, cell surface-bound protein assemblies that can contain dozens of catalytic components. The key feature of the cellulosome is its modularity, facilitated by the ultra-high affinity cohesin–dockerin interaction. Due to the enormous number of cohesin and dockerin modules found in a typical cellulolytic organism, a major bottleneck in understanding the biology of cellulosomics is the purification of each cohesin- and dockerin-containing component, prior to analyses of their interaction. As opposed to previous approaches, the present study utilized proteins contained in unpurified whole-cell extracts. This strategy was made possible due to an experimental design that allowed for the relevant proteins to be “purified” via targeted affinity interactions as a function of the binding assay. The approach thus represents a new strategy, appropriate for future medium- to high-throughput screening of whole genomes, to determine the interactions between cohesins and dockerins. We have selected the cellulosome of Acetivibrio cellulolyticus for this work due to its exceptionally complex cellulosome systems and intriguing diversity of its cellulosomal modular components. Containing 41 cohesins and 143 dockerins, A. cellulolyticus has one of the largest number of potential cohesin–dockerin interactions of any organism, and contains unusual and novel cellulosomal features. We have surveyed a representative library of cohesin and dockerin modules spanning the

  5. Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis.

    Directory of Open Access Journals (Sweden)

    Jason Abernathy

    Full Text Available Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical with salmonids on long-term plant protein-based feeds. By incorporating this strain into functional analyses, we set out to determine which genes are critical to plant protein utilization in the absence of gut inflammation. After a 12-week feeding trial with our selected strain and a control trout strain fed either a fishmeal-based diet or an all-plant protein diet, high-throughput RNA sequencing was completed on both liver and muscle tissues. Differential gene expression analyses, weighted correlation network analyses and further functional characterization were performed. A strain-by-diet design revealed differential expression ranging from a few dozen to over one thousand genes among the various comparisons and tissues. Major gene ontology groups identified between comparisons included those encompassing central, intermediary and foreign molecule metabolism, associated biosynthetic pathways as well as immunity. A systems approach indicated that genes involved in purine metabolism were highly perturbed. Systems analysis among the tissues tested further suggests the interplay between selection for growth, dietary utilization and protein tolerance may also have implications for nonspecific immunity. By combining data from differential gene expression and co-expression networks using selected trout, along with ontology and pathway analyses, a set of 63 candidate genes for plant diet tolerance was found. Risk loci in human inflammatory bowel diseases were also found in our datasets, indicating rainbow trout selected for plant-diet tolerance may have added utility as a potential biomedical model.

  6. Identification and association analysis of several hundred single nucleotide polymorphisms within candidate genes for back fat thickness in Italian Large White pigs using a selective genotyping approach.

    Science.gov (United States)

    Fontanesi, L; Galimberti, G; Calò, D G; Fronza, R; Martelli, P L; Scotti, E; Colombo, M; Schiavo, G; Casadio, R; Buttazzoni, L; Russo, V

    2012-08-01

    Combining different approaches (resequencing of portions of 54 obesity candidate genes, literature mining for pig markers associated with fat deposition or related traits in 77 genes, and in silico mining of porcine expressed sequence tags and other sequences available in databases), we identified and analyzed 736 SNP within candidate genes to identify markers associated with back fat thickness (BFT) in Italian Large White sows. Animals were chosen using a selective genotyping approach according to their EBV for BFT (276 with most negative and 279 with most positive EBV) within a population of ≈ 12,000 pigs. Association analysis between the SNP and BFT has been carried out using the MAX test proposed for case-control studies. The designed assays were successful for 656 SNP: 370 were excluded (low call rate or minor allele frequency A polymorphism (P(nominal) G polymorphism (P(nominal) = 8.0E-05). The third top SNP (P(nominal) = 6.2E-04) was the intronic TBC1D1 g.219G>A polymorphic site, in agreement with our previous results obtained in an independent study. The list of significant markers also included SNP in additional genes (ABHD16A, ABHD5, ACP2, ALMS1, APOA2, ATP1A2, CALR, COL14A1, CTSF, DARS, DECR1, ENPP1, ESR1, GH1, GHRL, GNMT, IKBKB, JAK3, MTTP, NFKBIA, NT5E, PLAT, PPARG, PPP2R5D, PRLR, RRAGD, RFC2, SDHD, SERPINF1, UBE2H, VCAM1, and WAT). Functional relationships between genes were obtained using the Ingenuity Pathway Analysis (IPA) Knowledge Base. The top scoring pathway included 19 genes with a P(nominal) < 0.1, 2 of which (IKBKB and NFKBIA) are involved in the hypothalamic IKKβ/NFκB program that could represent a key axis to affect fat deposition traits in pigs. These results represent a starting point to plan marker-assisted selection in Italian Large White nuclei for BFT. Because of similarities between humans and pigs, this study might also provide useful clues to investigate genetic factors affecting human obesity.

  7. Selection of suitable prodrug candidates for in vivo studies via in vitro studies; the correlation of prodrug stability in between cell culture homogenates and human tissue homogenates.

    Science.gov (United States)

    Tsume, Yasuhiro; Amidon, Gordon L

    2012-01-01

    To determine the correlations/discrepancies of drug stabilities between in the homogenates of human culture cells and of human tissues. Amino acid/dipeptide monoester prodrugs of floxuridine were chosen as the model drugs. The stabilities (half-lives) of floxuridine prodrugs in human tissues (pancreas, liver, and small intestine) homogenates were obtained and compared with ones in cell culture homogenates (AcPC-1, Capan-2, and Caco-2 cells) as well as human liver microsomes. The correlations of prodrug stability in human small bowel tissue homogenate vs. Caco-2 cell homogenate, human liver tissue homogenate vs. human liver microsomes, and human pancreatic tissue homogenate vs. pancreatic cell, AsPC-1 and Capan-2, homogenates were examined. The stabilities of floxuridine prodrugs in human small bowel homogenate exhibited the great correlation to ones in Caco-2 cell homogenate (slope = 1.0-1.3, r2 = 0.79-0.98). The stability of those prodrugs in human pancreas tissue homogenate also exhibited the good correlations to ones in AsPC-1 and Capan-2 cells homogenates (slope = 0.5-0.8, r2 = 0.58-0.79). However, the correlations of prodrug stabilities between in human liver tissue homogenates and in human liver microsomes were weaker than others (slope = 1.3-1.9, r2 = 0.07-0.24). The correlations of drug stabilities in cultured cell homogenates and in human tissue homogenates were compared. Those results exhibited wide range of correlations between in cell homogenate and in human tissue homogenate (r2 = 0.07 - 0.98). Those in vitro studies in cell homogenates would be good tools to predict drug stabilities in vivo and to select drug candidates for further developments. In the series of experiments, 5'-O-D-valyl-floxuridine and 5'-O-L-phenylalanyl-L-tyrosyl-floxuridine would be selected as candidates of oral drug targeting delivery for cancer chemotherapy due to their relatively good stabilities compared to other tested prodrugs.

  8. RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders.

    Directory of Open Access Journals (Sweden)

    Mingyan Lin

    Full Text Available Genome-wide expression analysis using next generation sequencing (RNA-Seq provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs, pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ, bipolar disorder (BD and autism spectrum disorders (ASD that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients.

  9. Sex-ratio control erodes sexual selection, revealing evolutionary feedback from adaptive plasticity

    NARCIS (Netherlands)

    Fawcett, Tim W.; Kuijper, Bram; Weissing, Franz J.; Pen, Ido

    2011-01-01

    Female choice is a powerful selective force, driving the elaboration of conspicuous male ornaments. This process of sexual selection has profound implications for many life-history decisions, including sex allocation. For example, females with attractive partners should produce more sons, because

  10. Simultaneous attentional guidance by working-memory and selection history reveals two distinct sources of attention.

    Science.gov (United States)

    Schwark, Jeremy D; Dolgov, Igor; Sandry, Joshua; Volkman, C Brooks

    2013-10-01

    Recent theories of attention have proposed that selection history is a separate, dissociable source of information that influences attention. The current study sought to investigate the simultaneous involvement of selection history and working-memory on attention during visual search. Experiments 1 and 2 used target feature probability to manipulate selection history and found significant effects of both working-memory and selection history, although working-memory dominated selection history when they cued different locations. Experiment 3 eliminated the contribution of voluntary refreshing of working-memory and replicated the main effects, although selection history became dominant. Using the same methodology, but with reduced probability cue validity, both effects were present in Experiment 4 and did not significantly differ in their contribution to attention. Effects of selection history and working-memory never interacted. These results suggest that selection history and working-memory are separate influences on attention and have little impact on each other. Theoretical implications for models of attention are discussed. © 2013.

  11. Neural evidence reveals the rapid effects of reward history on selective attention.

    Science.gov (United States)

    MacLean, Mary H; Giesbrecht, Barry

    2015-05-05

    Selective attention is often framed as being primarily driven by two factors: task-relevance and physical salience. However, factors like selection and reward history, which are neither currently task-relevant nor physically salient, can reliably and persistently influence visual selective attention. The current study investigated the nature of the persistent effects of irrelevant, physically non-salient, reward-associated features. These features affected one of the earliest reliable neural indicators of visual selective attention in humans, the P1 event-related potential, measured one week after the reward associations were learned. However, the effects of reward history were moderated by current task demands. The modulation of visually evoked activity supports the hypothesis that reward history influences the innate salience of reward associated features, such that even when no longer relevant, nor physically salient, these features have a rapid, persistent, and robust effect on early visual selective attention. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Perceptual load manipulation reveals sensitivity of the face-selective N170 to attention.

    Science.gov (United States)

    Mohamed, Tarik N; Neumann, Markus F; Schweinberger, Stefan R

    2009-05-27

    It has been controversial whether the face-sensitive N170 is affected by selective attention. We manipulated attention sensu Lavie's perceptual load theory to short (200 ms) presentations of task-irrelevant unfamiliar faces or houses, while participants identified superimposed target letters 'X' versus 'N'. These targets were strings of either six identical (low load) or six different letters (high load). Under low load, we found a prominent face-selective N170 response. Under high load, however, we not only observed a dramatic reduction of the face N170 but also an unexpected enhancement of the house N170, such that face selectivity was almost completely lost. We conclude that the early stages of face processing indexed by the N170 strongly depend on selective attention.

  13. Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

    OpenAIRE

    Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.

    2016-01-01

    Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nocicep...

  14. Fish habitat selection in a large hydropeaking river: Strong individual and temporal variations revealed by telemetry.

    Science.gov (United States)

    Capra, Hervé; Plichard, Laura; Bergé, Julien; Pella, Hervé; Ovidio, Michaël; McNeil, Eric; Lamouroux, Nicolas

    2017-02-01

    Modeling individual fish habitat selection in highly variable environments such as hydropeaking rivers is required for guiding efficient management decisions. We analyzed fish microhabitat selection in the heterogeneous hydraulic and thermal conditions (modeled in two-dimensions) of a reach of the large hydropeaking Rhône River locally warmed by the cooling system of a nuclear power plant. We used modern fixed acoustic telemetry techniques to survey 18 fish individuals (five barbels, six catfishes, seven chubs) signaling their position every 3s over a three-month period. Fish habitat selection depended on combinations of current microhabitat hydraulics (e.g. velocity, depth), past microhabitat hydraulics (e.g. dewatering risk or maximum velocities during the past 15days) and to a lesser extent substrate and temperature. Mixed-effects habitat selection models indicated that individual effects were often stronger than specific effects. In the Rhône, fish individuals appear to memorize spatial and temporal environmental changes and to adopt a "least constraining" habitat selection. Avoiding fast-flowing midstream habitats, fish generally live along the banks in areas where the dewatering risk is high. When discharge decreases, however, they select higher velocities but avoid both dewatering areas and very fast-flowing midstream habitats. Although consistent with the available knowledge on static fish habitat selection, our quantitative results demonstrate temporal variations in habitat selection, depending on individual behavior and environmental history. Their generality could be further tested using comparative experiments in different environmental configurations. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Allosteric Mutant IDH1 Inhibitors Reveal Mechanisms for IDH1 Mutant and Isoform Selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Xiaoling; Baird, Daniel; Bowen, Kimberly; Capka, Vladimir; Chen, Jinyun; Chenail, Gregg; Cho, YoungShin; Dooley, Julia; Farsidjani, Ali; Fortin, Pascal; Kohls, Darcy; Kulathila, Raviraj; Lin, Fallon; McKay, Daniel; Rodrigues, Lindsey; Sage, David; Touré, B. Barry; van der Plas, Simon; Wright, Kirk; Xu, Ming; Yin, Hong; Levell, Julian; Pagliarini, Raymond A. (Novartis)

    2017-03-01

    Oncogenic IDH1 and IDH2 mutations contribute to cancer via production of R-2-hydroxyglutarate (2-HG). Here, we characterize two structurally distinct mutant- and isoform-selective IDH1 inhibitors that inhibit 2-HG production. Both bind to an allosteric pocket on IDH1, yet shape it differently, highlighting the plasticity of this site. Oncogenic IDH1R132H mutation destabilizes an IDH1 “regulatory segment,” which otherwise restricts compound access to the allosteric pocket. Regulatory segment destabilization in wild-type IDH1 promotes inhibitor binding, suggesting that destabilization is critical for mutant selectivity. We also report crystal structures of oncogenic IDH2 mutant isoforms, highlighting the fact that the analogous segment of IDH2 is not similarly destabilized. This intrinsic stability of IDH2 may contribute to observed inhibitor IDH1 isoform selectivity. Moreover, discrete residues in the IDH1 allosteric pocket that differ from IDH2 may also guide IDH1 isoform selectivity. These data provide a deeper understanding of how IDH1 inhibitors achieve mutant and isoform selectivity.

  16. Analysis of Adaptive Evolution in Lyssavirus Genomes Reveals Pervasive Diversifying Selection during Species Diversification

    Directory of Open Access Journals (Sweden)

    Carolina M. Voloch

    2014-11-01

    Full Text Available Lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. The evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive geographical patterns present throughout the diversification of these viruses. Although numerous studies have examined pattern-related questions concerning Lyssavirus evolution, analyses of the evolutionary processes acting on Lyssavirus diversification are scarce. To clarify the relevance of positive natural selection in Lyssavirus diversification, we conducted a comprehensive scan for episodic diversifying selection across all lineages and codon sites of the five coding regions in lyssavirus genomes. Although the genomes of these viruses are generally conserved, the glycoprotein (G, RNA-dependent RNA polymerase (L and polymerase (P genes were frequently targets of adaptive evolution during the diversification of the genus. Adaptive evolution is particularly manifest in the glycoprotein gene, which was inferred to have experienced the highest density of positively selected codon sites along branches. Substitutions in the L gene were found to be associated with the early diversification of phylogroups. A comparison between the number of positively selected sites inferred along the branches of RABV population branches and Lyssavirus intespecies branches suggested that the occurrence of positive selection was similar on the five coding regions of the genome in both groups.

  17. Analysis of adaptive evolution in Lyssavirus genomes reveals pervasive diversifying selection during species diversification.

    Science.gov (United States)

    Voloch, Carolina M; Capellão, Renata T; Mello, Beatriz; Schrago, Carlos G

    2014-11-19

    Lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. The evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive geographical patterns present throughout the diversification of these viruses. Although numerous studies have examined pattern-related questions concerning Lyssavirus evolution, analyses of the evolutionary processes acting on Lyssavirus diversification are scarce. To clarify the relevance of positive natural selection in Lyssavirus diversification, we conducted a comprehensive scan for episodic diversifying selection across all lineages and codon sites of the five coding regions in lyssavirus genomes. Although the genomes of these viruses are generally conserved, the glycoprotein (G), RNA-dependent RNA polymerase (L) and polymerase (P) genes were frequently targets of adaptive evolution during the diversification of the genus. Adaptive evolution is particularly manifest in the glycoprotein gene, which was inferred to have experienced the highest density of positively selected codon sites along branches. Substitutions in the L gene were found to be associated with the early diversification of phylogroups. A comparison between the number of positively selected sites inferred along the branches of RABV population branches and Lyssavirus intespecies branches suggested that the occurrence of positive selection was similar on the five coding regions of the genome in both groups.

  18. Radiation-Induced Esophagitis In Vivo and In Vitro Reveals That Epidermal Growth Factor Is a Potential Candidate for Therapeutic Intervention Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Su [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jeon, Seong-Uk; Lee, Chan-Ju; Kim, Young-Eun; Bok, Seoyeon; Hong, Beom-Ju; Park, Dong-Young [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Ahn, G-One, E-mail: goneahn@postech.ac.kr [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-07-01

    Purpose: To establish and characterize radiation-induced esophagitis (RIE) in vivo and in vitro. Methods and Materials: Fractionated thoracic irradiation at 0, 8, 12, or 15 Gy was given daily for 5 days to Balb/c or C57Bl/6 mice. Changes in body weight gain and daily food intake were assessed. At the end of the study, we removed the esophagus and examined histology by hematoxylin and eosin staining, immune cell infiltration and apoptosis by fluorescence-activated cell sorting, and gene expression changes by quantitative real-time polymerase chain reaction. Het-1A human esophageal epithelial cells were irradiated at 6 Gy, treated with recombinant human growth factors, and examined for gene expression changes, apoptosis, proliferation, and signal transduction pathways. Results: We observed that irradiation at 12 Gy or 15 Gy per fraction produced significant reduction in body weight and decreased food intake in Balb/c mice but not as much in C57Bl/6 mice. Further analyses of Balb/c mice irradiated at 12 Gy/fraction revealed attenuated epithelium, inflamed mucosa, and increased numbers of infiltrating CD4+ helper T cells and apoptotic cells. Moreover, we found that expression of tissue inhibitor for metalloproteinase-1, plasminogen activator inhibitor-1, granulocyte macrophage-colony stimulating factor, vascular endothelial growth factor, and stromal-derived factor-1 were increased, whereas epidermal growth factor (EGF) was decreased. Irradiated Het-1A cells similarly showed a significant decrease in expression of EGF and connective tissue growth factor (CTGF). Treatment of EGF but not CTGF partially protected Het-1A cells from radiation-induced apoptosis and revealed phosphorylation of EGFR, AKT, and ERK signaling pathways. Conclusions: We established a mouse model of RIE in Balb/c mice with 12 Gy × 5 fractions, which showed reduced body weight gain, food intake, and histopathologic features similar to those of human esophagitis. Decreased EGF expression

  19. Meaning Making: What Reflective Essays Reveal about Biology Students' Conceptions about Natural Selection

    Science.gov (United States)

    Balgopal, Meena M.; Montplaisir, Lisa M.

    2011-01-01

    The process of reflective writing can play a central role in making meaning as learners process new information and connect it to prior knowledge. An examination of the written discourse can therefore be revealing of learners' cognitive understanding and affective (beliefs, feelings, motivation to learn) responses to concepts. Despite reflective…

  20. AFLP genome scanning reveals divergent selection in natural populations of Liriodendron chinense (Magnoliaceae along a latitudinal transect

    Directory of Open Access Journals (Sweden)

    Aihong eYang

    2016-05-01

    Full Text Available Understanding adaptive genetic variation and its relation to environmental factors are important for understanding how plants adapt to climate change and for managing genetic resources. Genome scans for the loci exhibiting either notably high or low levels of population differentiation (outlier loci provide one means of identifying genomic regions possibly associated with convergent or divergent selection. In this study, we combined AFLP genome scan and environmental association analysis to test for signals of natural selection in natural populations of Liriodendron chinense (Chinese Tulip Tree; Magnoliaceae along a latitudinal transect. We genotyped 276 individuals from 11 populations of L. chinense using 987 AFLP markers. Two complementary methods (Dfdist and BayeScan and association analysis between AFLP loci and climate factors were applied to detect outlier loci. Our analyses recovered both neutral and potentially adaptive genetic differentiation among populations of L. chinense. We found moderate genetic diversity within populations and high genetic differentiation among populations with reduced genetic diversity towards the periphery of the species ranges. Nine AFLP marker loci showed evidence of being outliers for population differentiation for both detection methods. Of these, six were strongly associated with at least one climate factor. Temperature, precipitation and radiation were found to be three important factors influencing local adaptation of L. chinense. The outlier AFLP loci are likely not the target of natural selection, but the neighboring genes of these loci might be involved in local adaptation. Hence, these candidates should be validated by further studies.

  1. Genome Sequencing Reveals Loci under Artificial Selection that Underlie Disease Phenotypes in the Laboratory Rat

    NARCIS (Netherlands)

    Atanur, Santosh S.; Diaz, Ana Garcia; Maratou, Klio; Sarkis, Allison; Rotival, Maxime; Game, Laurence; Tschannen, Michael R.; Kaisaki, Pamela J.; Otto, Georg W.; Ma, Man Chun John; Keane, Thomas M.; Hummel, Oliver; Saar, Kathrin; Chen, Wei; Guryev, Victor; Gopalakrishnan, Kathirvel; Garrett, Michael R.; Joe, Bina; Citterio, Lorena; Bianchi, Giuseppe; McBride, Martin; Dominiczak, Anna; Adams, David J.; Serikawa, Tadao; Flicek, Paul; Cuppen, Edwin; Hubner, Norbert; Petretto, Enrico; Gauguier, Dominique; Kwitek, Anne; Jacob, Howard; Aitman, Timothy J.

    2013-01-01

    Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and

  2. Punishment induced behavioural and neurophysiological variability reveals dopamine-dependent selection of kinematic movement parameters

    Science.gov (United States)

    Galea, Joseph M.; Ruge, Diane; Buijink, Arthur; Bestmann, Sven; Rothwell, John C.

    2013-01-01

    Action selection describes the high-level process which selects between competing movements. In animals, behavioural variability is critical for the motor exploration required to select the action which optimizes reward and minimizes cost/punishment, and is guided by dopamine (DA). The aim of this study was to test in humans whether low-level movement parameters are affected by punishment and reward in ways similar to high-level action selection. Moreover, we addressed the proposed dependence of behavioural and neurophysiological variability on DA, and whether this may underpin the exploration of kinematic parameters. Participants performed an out-and-back index finger movement and were instructed that monetary reward and punishment were based on its maximal acceleration (MA). In fact, the feedback was not contingent on the participant’s behaviour but pre-determined. Blocks highly-biased towards punishment were associated with increased MA variability relative to blocks with either reward or without feedback. This increase in behavioural variability was positively correlated with neurophysiological variability, as measured by changes in cortico-spinal excitability with transcranial magnetic stimulation over the primary motor cortex. Following the administration of a DA-antagonist, the variability associated with punishment diminished and the correlation between behavioural and neurophysiological variability no longer existed. Similar changes in variability were not observed when participants executed a pre-determined MA, nor did DA influence resting neurophysiological variability. Thus, under conditions of punishment, DA-dependent processes influence the selection of low-level movement parameters. We propose that the enhanced behavioural variability reflects the exploration of kinematic parameters for less punishing, or conversely more rewarding, outcomes. PMID:23447607

  3. Movement reveals scale dependence in habitat selection of a large ungulate

    Science.gov (United States)

    Northrup, Joseph; Anderson, Charles R.; Hooten, Mevin B.; Wittemyer, George

    2016-01-01

    Ecological processes operate across temporal and spatial scales. Anthropogenic disturbances impact these processes, but examinations of scale dependence in impacts are infrequent. Such examinations can provide important insight to wildlife–human interactions and guide management efforts to reduce impacts. We assessed spatiotemporal scale dependence in habitat selection of mule deer (Odocoileus hemionus) in the Piceance Basin of Colorado, USA, an area of ongoing natural gas development. We employed a newly developed animal movement method to assess habitat selection across scales defined using animal-centric spatiotemporal definitions ranging from the local (defined from five hour movements) to the broad (defined from weekly movements). We extended our analysis to examine variation in scale dependence between night and day and assess functional responses in habitat selection patterns relative to the density of anthropogenic features. Mule deer displayed scale invariance in the direction of their response to energy development features, avoiding well pads and the areas closest to roads at all scales, though with increasing strength of avoidance at coarser scales. Deer displayed scale-dependent responses to most other habitat features, including land cover type and habitat edges. Selection differed between night and day at the finest scales, but homogenized as scale increased. Deer displayed functional responses to development, with deer inhabiting the least developed ranges more strongly avoiding development relative to those with more development in their ranges. Energy development was a primary driver of habitat selection patterns in mule deer, structuring their behaviors across all scales examined. Stronger avoidance at coarser scales suggests that deer behaviorally mediated their interaction with development, but only to a degree. At higher development densities than seen in this area, such mediation may not be possible and thus maintenance of sufficient

  4. JELLYFISH GALAXY CANDIDATES AT LOW REDSHIFT

    Energy Technology Data Exchange (ETDEWEB)

    Poggianti, B. M.; Fasano, G.; Omizzolo, A.; Gullieuszik, M.; Bettoni, D.; Paccagnella, A. [INAF-Astronomical Observatory of Padova (Italy); Moretti, A.; D’Onofrio, M. [Physics and Astronomy Department, University of Padova (Italy); Jaffé, Y. L. [Department of Astronomy, Universidad de Concepción, Concepción (Chile); Vulcani, B. [Kavli Institute for the Physics and Mathematics of the universe (WPI), The University of Tokyo Institutes for Advanced Study (UTIAS), the University of Tokyo, Kashiwa, 277-8582 (Japan); Fritz, J. [Centro de Radioastronomía y Astrofísica, CRyA, UNAM, Michoacán (Mexico); Couch, W. [Australian Astronomical Observatory, North Ryde, NSW 1670 (Australia)

    2016-03-15

    Galaxies that are being stripped of their gas can sometimes be recognized from their optical appearance. Extreme examples of stripped galaxies are the so-called “jellyfish galaxies” that exhibit tentacles of debris material with a characteristic jellyfish morphology. We have conducted the first systematic search for galaxies that are being stripped of their gas at low-z (z = 0.04−0.07) in different environments, selecting galaxies with varying degrees of morphological evidence for stripping. We have visually inspected B- and V-band images and identified 344 candidates in 71 galaxy clusters of the OMEGAWINGS+WINGS sample and 75 candidates in groups and lower mass structures in the PM2GC sample. We present the atlas of stripping candidates and a first analysis of their environment and their basic properties, such as morphologies, star formation rates and galaxy stellar masses. Candidates are found in all clusters and at all clustercentric radii, and their number does not correlate with the cluster velocity dispersion σ or X-ray luminosity L{sub X}. Interestingly, convincing cases of candidates are also found in groups and lower mass halos (10{sup 11}−10{sup 14}M{sub ⊙}), although the physical mechanism at work needs to be securely identified. All the candidates are disky, have stellar masses ranging from log M/M{sub ⊙} < 9 to > 11.5 and the majority of them form stars at a rate that is on average a factor of 2 higher (2.5σ) compared to non-stripped galaxies of similar mass. The few post-starburst and passive candidates have weak stripping evidence. We conclude that disturbed morphologies suggestive of stripping phenomena are ubiquitous in clusters and could be present even in groups and low mass halos. Further studies will reveal the physics of the gas stripping and clarify the mechanisms at work.

  5. Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples.

    Science.gov (United States)

    Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Éric; Dublineau, Isabelle; Aigueperse, Jocelyne; Bohand, Sandra; Martin, Jean-Charles; Souidi, Maâmar

    2016-01-01

    Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake. In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L -1 ; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose-effect pattern and identify additional potential biomarkers in urine samples. Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L -1 ). LC-MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages. The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L -1 . Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score. These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L -1 .

  6. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

    Directory of Open Access Journals (Sweden)

    Zulezwan A. Malik

    2013-12-01

    .54-fold (p = 0.0064 more abundant in HCR than LCR soleus. This discovery was verified using selective reaction monitoring (SRM of the y5 ion (551.21 m/z of the doubly-charged peptide SLGVGFATR (454.19 m/z of residues 23–31 of FABPH. SRM was conducted on technical replicates of each biological sample and exhibited a coefficient of variation of 20%. The abundance of FABPH measured by SRM was 2.84-fold greater (p = 0.0095 in HCR muscle. In addition, SRM of FABPH was performed in vastus lateralis samples of young and elderly humans with different habitual activity levels (collected during a previous study finding FABPH abundance was 2.23-fold greater (p = 0.0396 in endurance-trained individuals regardless of differences in age. In summary, our findings in HCR/LCR rats provide protein-level confirmation for earlier transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

  7. Genome-wide DNA methylation sequencing reveals miR-663a is a novel epimutation candidate in CIMP-high endometrial cancer.

    Science.gov (United States)

    Yanokura, Megumi; Banno, Kouji; Adachi, Masataka; Aoki, Daisuke; Abe, Kuniya

    2017-06-01

    Aberrant DNA methylation is widely observed in many cancers. Concurrent DNA methylation of multiple genes occurs in endometrial cancer and is referred to as the CpG island methylator phenotype (CIMP). However, the features and causes of CIMP-positive endometrial cancer are not well understood. To investigate DNA methylation features characteristic to CIMP-positive endometrial cancer, we first classified samples from 25 patients with endometrial cancer based on the methylation status of three genes, i.e. MLH1, CDH1 (E-cadherin) and APC: CIMP-high (CIMP-H, 2/25, 8.0%), CIMP-low (CIMP-L, 7/25, 28.0%) and CIMP-negative (CIMP(-), 16/25, 64.0%). We then selected two samples each from CIMP-H and CIMP(-) classes, and analyzed DNA methylation status of both normal (peripheral blood cells: PBCs) and cancer tissues by genome-wide, targeted bisulfite sequencing. Genomes of the CIMP-H cancer tissues were significantly hypermethylated compared to those of the CIMP(-). Surprisingly, in normal tissues of the CIMP-H patients, promoter region of the miR-663a locus is hypermethylated relative to CIMP(-) samples. Consistent with this finding, miR-663a expression was lower in the CIMP-H PBCs than in the CIMP(-) PBCs. The same region of the miR663a locus is found to be highly methylated in cancer tissues of both CIMP-H and CIMP(-) cases. This is the first report showing that aberrant DNA methylation of the miR-663a promoter can occur in normal tissue of the cancer patients, suggesting a possible link between this epigenetic abnormality and endometrial cancer. This raises the possibility that the hypermethylation of the miR-663a promoter represents an epimutation associated with the CIMP-H endometrial cancers. Based on these findings, relationship of the aberrant DNA methylation and CIMP-H phenotype is discussed.

  8. Genetic Diversity of Selected Mangifera Species Revealed by Inter Simple Sequence Repeats Markers

    OpenAIRE

    Ariffin, Zulhairil; Md Sah, Muhammad Shafie; Idris, Salma; Hashim, Nuradni

    2015-01-01

    ISSR markers were employed to reveal genetic diversity and genetic relatedness among 28 Mangifera accessions collected from Yan (Kedah), Bukit Gantang (Perak), Sibuti (Sarawak), and Papar (Sabah). A total of 198 markers were generated using nine anchored primers and one nonanchored primer. Genetic variation among the 28 accessions of Mangifera species including wild relatives, landraces, and clonal varieties is high, with an average degree of polymorphism of 98% and mean Shannon index, H0=7.5...

  9. Selective inhibition of plant serine hydrolases by agrochemicals revealed by competitive ABPP.

    Science.gov (United States)

    Kaschani, Farnusch; Nickel, Sabrina; Pandey, Bikram; Cravatt, Benjamin F; Kaiser, Markus; van der Hoorn, Renier A L

    2012-01-15

    Organophosphate and -phosphonates and their thio derivatives are often used in agroindustry as herbicides and insecticides, but their potential off-targets in the plant are poorly investigated. Here, we use competitive activity-based protein profiling (ABPP) of serine hydrolases (SHs) to detect targets of these agrochemicals and other compounds in Arabidopsis thaliana. Using broad-range and specific probes, and by overexpression of various SHs in planta, we are able to confirm eight SH-compound interactions, including selective inhibition of carboxylesterase CXE12, prolyloligopeptidase, methylesterase MES2 and tripeptidyl peptidase TPP2. These observations can be used for the design of novel probes and selective inhibitors and may help to assess physiological effects of agrochemicals on crop plants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. The human auditory brainstem response to running speech reveals a subcortical mechanism for selective attention.

    Science.gov (United States)

    Forte, Antonio Elia; Etard, Octave; Reichenbach, Tobias

    2017-10-10

    Humans excel at selectively listening to a target speaker in background noise such as competing voices. While the encoding of speech in the auditory cortex is modulated by selective attention, it remains debated whether such modulation occurs already in subcortical auditory structures. Investigating the contribution of the human brainstem to attention has, in particular, been hindered by the tiny amplitude of the brainstem response. Its measurement normally requires a large number of repetitions of the same short sound stimuli, which may lead to a loss of attention and to neural adaptation. Here we develop a mathematical method to measure the auditory brainstem response to running speech, an acoustic stimulus that does not repeat and that has a high ecological validity. We employ this method to assess the brainstem's activity when a subject listens to one of two competing speakers, and show that the brainstem response is consistently modulated by attention.

  11. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

    Science.gov (United States)

    Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2013-12-01

    earlier transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

  12. A trait-based approach reveals the feeding selectivity of a small endangered Mediterranean fish

    OpenAIRE

    Rodriguez-Lozano, Pablo; Verkaik, Iraima; Maceda Veiga, Alberto; Monroy, Mario; de Sostoa, Adolf; Rieradevall, Maria; Prat, Narcis

    2016-01-01

    Abstract Functional traits are growing in popularity in modern ecology, but feeding studies remain primarily rooted in a taxonomic?based perspective. However, consumers do not have any reason to select their prey using a taxonomic criterion, and prey assemblages are variable in space and time, which makes taxon?based studies assemblage?specific. To illustrate the benefits of the trait?based approach to assessing food choice, we studied the feeding ecology of the endangered freshwater fish Bar...

  13. Characterization of a recombinant humanized anti-cocaine monoclonal antibody produced from multiple clones for the selection of a master cell bank candidate.

    Science.gov (United States)

    Wetzel, Hanna N; Webster, Rose P; Saeed, Fatima O; Kirley, Terence L; Ball, William J; Norman, Andrew B

    2017-06-03

    We have generated a humanized anti-cocaine monoclonal antibody (mAb), which is at an advanced stage of pre-clinical development. We report here in vitro binding affinity studies, and in vivo pharmacokinetic and efficacy studies of the recombinant mAb. The overall aim was to characterize the recombinant antibody from each of the three highest producing transfected clones and to select one to establish a master cell bank. In mAb pharmacokinetic studies, after injection with h2E2 (120 mg/kg iv) blood was collected from the tail tip of mice over 28 days. Antibody concentrations were quantified using ELISA. The h2E2 concentration as a function of time was fit using a two-compartment pharmacokinetic model. To test in vivo efficacy, mice were injected with h2E2 (120 mg/kg iv), then one hour later injected with an equimolar dose of cocaine. Blood and brain were collected 5 min after cocaine administration. Cocaine concentrations were quantified using LC/MS. The affinity of the antibody for cocaine was determined using a [ 3 H] cocaine binding assay. All three antibodies had long elimination half-lives, 2-5 nM Kd for cocaine, and prevented cocaine's entry into the brain by sequestering it in the plasma. Pharmacokinetic and radioligand binding assays supported designation of the highest producing clone 85 as the master cell bank candidate. Overall, the recombinant h2E2 showed favorable binding properties, pharmacokinetics, and in vivo efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Private selective sweeps identified from next-generation pool-sequencing reveal convergent pathways under selection in two inbred Schistosoma mansoni strains.

    Directory of Open Access Journals (Sweden)

    Julie A J Clément

    Full Text Available BACKGROUND: The trematode flatworms of the genus Schistosoma, the causative agents of schistosomiasis, are among the most prevalent parasites in humans, affecting more than 200 million people worldwide. In this study, we focused on two well-characterized strains of S. mansoni, to explore signatures of selection. Both strains are highly inbred and exhibit differences in life history traits, in particular in their compatibility with the intermediate host Biomphalaria glabrata. METHODOLOGY/PRINCIPAL FINDINGS: We performed high throughput sequencing of DNA from pools of individuals of each strain using Illumina technology and identified single nucleotide polymorphisms (SNP and copy number variations (CNV. In total, 708,898 SNPs were identified and roughly 2,000 CNVs. The SNPs revealed low nucleotide diversity (π = 2 × 10(-4 within each strain and a high differentiation level (Fst = 0.73 between them. Based on a recently developed in-silico approach, we further detected 12 and 19 private (i.e. specific non-overlapping selective sweeps among the 121 and 151 sweeps found in total for each strain. CONCLUSIONS/SIGNIFICANCE: Functional annotation of transcripts lying in the private selective sweeps revealed specific selection for functions related to parasitic interaction (e.g. cell-cell adhesion or redox reactions. Despite high differentiation between strains, we identified evolutionary convergence of genes related to proteolysis, known as a key virulence factor and a potential target of drug and vaccine development. Our data show that pool-sequencing can be used for the detection of selective sweeps in parasite populations and enables one to identify biological functions under selection.

  15. Advanced gas cooled nuclear reactor materials evaluation and development program. Selection of candidate alloys. Vol. 1. Advanced gas cooled reactor systems definition

    International Nuclear Information System (INIS)

    Marvin, M.D.

    1978-01-01

    Candidate alloys for a Very High Temperature Reactor (VHTR) Nuclear Process Heal (NPH) and Direct Cycle Helium Turbine (DCHT) applications in terms of the effect of the primary coolant exposure and thermal exposure were evaluated

  16. The strong selective sweep candidate gene ADRA2C does not explain domestication related changes in the stress response of chickens.

    Directory of Open Access Journals (Sweden)

    Magnus Elfwing

    Full Text Available Analysis of selective sweeps to pinpoint causative genomic regions involved in chicken domestication has revealed a strong selective sweep on chromosome 4 in layer chickens. The autoregulatory α-adrenergic receptor 2C (ADRA2C gene is the closest to the selective sweep and was proposed as an important gene in the domestication of layer chickens. The ADRA2C promoter region was also hypermethylated in comparison to the non-selected ancestor of all domesticated chicken breeds, the Red Junglefowl, further supporting its relevance. In mice the receptor is involved in the fight-or-flight response as it modulates epinephrine release from the adrenals. To investigate the involvement of ADRA2C in chicken domestication, we measured gene expression in the adrenals and radiolabeled receptor ligand in three brain regions comparing the domestic White Leghorn strain with the wild ancestor Red Junglefowl. In adrenals ADRA2C was twofold greater expressed than the related receptor gene ADRA2A, indicating that ADRA2C is the predominant modulator of epinephrine release but no strain differences were measured. In hypothalamus and amygdala, regions associated with the stress response, and in striatum, receptor binding pIC50 values ranged between 8.1-8.4, and the level was not influenced by the genotyped allele. Because chicken strains differ in morphology, physiology and behavior, differences attributed to a single gene may be lost in the noise caused by the heterogeneous genetic background. Therefore an F10 advanced intercross strain between White Leghorn and Red Junglefowl was used to investigate effects of ADRA2C alleles on fear related behaviors and fecundity. We did not find compelling genotype effects in open field, tonic immobility, aerial predator, associative learning or fecundity. Therefore we conclude that ADRA2C is probably not involved in the domestication of the stress response in chicken, and the strong selective sweep is probably caused by selection

  17. Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

    Science.gov (United States)

    Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.; Brierley, Stuart M.; Basbaum, Allan I.; Bosmans, Frank; King, Glenn F.; Julius, David

    2016-01-01

    Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nociception and pain has not been explored. We exploit these probes to demonstrate that Nav1.1-expressing fibers are modality-specific nociceptors: their activation elicits robust pain behaviors without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibers also express Nav1.1 and show enhanced toxin sensitivity in a model of irritable bowel syndrome. Altogether, these findings establish an unexpected role for Nav1.1 in regulating the excitability of sensory nerve fibers that underlie mechanical pain. PMID:27281198

  18. Hydrophilic Phage-Mimicking Membrane Active Antimicrobials Reveal Nanostructure-Dependent Activity and Selectivity.

    Science.gov (United States)

    Jiang, Yunjiang; Zheng, Wan; Kuang, Liangju; Ma, Hairong; Liang, Hongjun

    2017-09-08

    The prevalent wisdom on developing membrane active antimicrobials (MAAs) is to seek a delicate, yet unquantified, cationic-hydrophobic balance. Inspired by phages that use nanostructured protein devices to invade bacteria efficiently and selectively, we study here the antibiotic role of nanostructures by designing spherical and rod-like polymer molecular brushes (PMBs) that mimic the two basic structural motifs of bacteriophages. Three model PMBs with different well-defined geometries consisting of multiple, identical copies of densely packed poly(4-vinyl-N-methylpyridine iodide) branches are synthesized by controlled/"living" polymerization, reminiscent of the viral structural motifs comprised of multiple copies of protein subunits. We show that, while the individual linear-chain polymer branch that makes up the PMBs is hydrophilic and a weak antimicrobial, amphiphilicity is not a required antibiotic trait once nanostructures come into play. The nanostructured PMBs induce an unusual topological transition of bacterial but not mammalian membranes to form pores. The sizes and shapes of the nanostructures further help define the antibiotic activity and selectivity of the PMBs against different families of bacteria. This study highlights the importance of nanostructures in the design of MAAs with high activity, low toxicity, and target specificity.

  19. Genome-Wide Analysis of the World's Sheep Breeds Reveals High Levels of Historic Mixture and Strong Recent Selection

    Science.gov (United States)

    Kijas, James W.; Lenstra, Johannes A.; Hayes, Ben; Boitard, Simon; Porto Neto, Laercio R.; San Cristobal, Magali; Servin, Bertrand; McCulloch, Russell; Whan, Vicki; Gietzen, Kimberly; Paiva, Samuel; Barendse, William; Ciani, Elena; Raadsma, Herman; McEwan, John; Dalrymple, Brian

    2012-01-01

    Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species. PMID:22346734

  20. Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection.

    Directory of Open Access Journals (Sweden)

    James W Kijas

    2012-02-01

    Full Text Available Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species.

  1. SEXUAL SELECTION. Irrationality in mate choice revealed by túngara frogs.

    Science.gov (United States)

    Lea, Amanda M; Ryan, Michael J

    2015-08-28

    Mate choice models derive from traditional microeconomic decision theory and assume that individuals maximize their Darwinian fitness by making economically rational decisions. Rational choices exhibit regularity, whereby the relative strength of preferences between options remains stable when additional options are presented. We tested female frogs with three simulated males who differed in relative call attractiveness and call rate. In binary choice tests, females' preferences favored stimulus caller B over caller A; however, with the addition of an inferior "decoy" C, females reversed their preferences and chose A over B. These results show that the relative valuation of mates is not independent of inferior alternatives in the choice set and therefore cannot be explained with the rational choice models currently used in sexual selection theory. Copyright © 2015, American Association for the Advancement of Science.

  2. Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes.

    Science.gov (United States)

    Van Le, Quan; Isbell, Lynne A; Matsumoto, Jumpei; Nguyen, Minh; Hori, Etsuro; Maior, Rafael S; Tomaz, Carlos; Tran, Anh Hai; Ono, Taketoshi; Nishijo, Hisao

    2013-11-19

    Snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of study, but not, surprisingly, from neuroscience, despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects. Here, we report the existence of neurons in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes. Compared with three other categories of stimuli (monkey faces, monkey hands, and geometrical shapes), snakes elicited the strongest, fastest responses, and the responses were not reduced by low spatial filtering. These findings integrate neuroscience with evolutionary biology, anthropology, psychology, herpetology, and primatology by identifying a neurobiological basis for primates' heightened visual sensitivity to snakes, and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage.

  3. Quantitative measures of sexual selection reveal no evidence for sex-role reversal in a sea spider with prolonged paternal care

    OpenAIRE

    Barreto, Felipe S.; Avise, John C.

    2010-01-01

    Taxa in which males alone invest in postzygotic care of offspring are often considered good models for investigating the proffered relationships between sexual selection and mating systems. In the pycnogonid sea spider Pycnogonum stearnsi, males carry large egg masses on their bodies for several weeks, so this species is a plausible candidate for sex-role reversal (greater intensity of sexual selection on females than on males). Here, we couple a microsatellite-based assessment of the mating ...

  4. Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures.

    Directory of Open Access Journals (Sweden)

    Moon Young Lee

    Full Text Available Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC, which serve as slow-wave electrical pacemakers for gastrointestinal (GI smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies.

  5. Genetic Diversity of Selected Mangifera Species Revealed by Inter Simple Sequence Repeats Markers

    Directory of Open Access Journals (Sweden)

    Zulhairil Ariffin

    2015-01-01

    Full Text Available ISSR markers were employed to reveal genetic diversity and genetic relatedness among 28 Mangifera accessions collected from Yan (Kedah, Bukit Gantang (Perak, Sibuti (Sarawak, and Papar (Sabah. A total of 198 markers were generated using nine anchored primers and one nonanchored primer. Genetic variation among the 28 accessions of Mangifera species including wild relatives, landraces, and clonal varieties is high, with an average degree of polymorphism of 98% and mean Shannon index, H0=7.50. Analysis on 18 Mangifera indica accessions also showed high degree of polymorphism of 99% and mean Shannon index, H0=5.74. Dice index of genetic similarity ranged from 0.0938 to 0.8046 among the Mangifera species. The dendrogram showed that the Mangifera species were grouped into three main divergent clusters. Cluster 1 comprised 14 accessions from Kedah and Perak. Cluster II and cluster III comprised 14 accessions from Sarawak and Sabah. Meanwhile, the Dice index of genetic similarity for 18 accessions of Mangifera indica ranged from 0.2588 to 0.7742. The dendrogram also showed the 18 accessions of Mangifera indica were grouped into three main clusters. Cluster I comprised 10 landraces of Mangifera indica from Kedah. Cluster II comprised 7 landraces of Mangifera indica followed by Chokanan to form Cluster III.

  6. Temporary Nerve Block at Selected Digits Revealed Hand Motor Deficits in Grasping Tasks

    Directory of Open Access Journals (Sweden)

    Aude Carteron

    2016-11-01

    Full Text Available Peripheral sensory feedback plays a crucial role in ensuring correct motor execution throughout hand grasp control. Previous studies utilized local anesthesia to deprive somatosensory feedback in the digits or hand, observations included sensorimotor deficits at both corticospinal and peripheral levels. However, the questions of how the disturbed and intact sensory input integrate and interact with each other to assist the motor program execution, and whether the motor coordination based on motor output variability between affected and non-affected elements (e.g., digits becomes interfered by the local sensory deficiency, have not been answered. The current study aims to investigate the effect of peripheral deafferentation through digital nerve blocks at selective digits on motor performance and motor coordination in grasp control. Our results suggested that the absence of somatosensory information induced motor deficits in hand grasp control, as evidenced by reduced maximal force production ability in both local and non-local digits, impairment of force and moment control during object lift and hold, and attenuated motor synergies in stabilizing task performance variables, namely the tangential force and moment of force. These findings implied that individual sensory input is shared across all the digits and the disturbed signal from local sensory channel(s has a more comprehensive impact on the process of the motor output execution in the sensorimotor integration process. Additionally, a feedback control mechanism with a sensation-based component resides in the formation process for the motor covariation structure.

  7. High Guanidinium Permeability Reveals Dehydration-Dependent Ion Selectivity in the Plasmodial Surface Anion Channel

    Directory of Open Access Journals (Sweden)

    Abdullah A. B. Bokhari

    2014-01-01

    Full Text Available Malaria parasites grow within vertebrate erythrocytes and increase host cell permeability to access nutrients from plasma. This increase is mediated by the plasmodial surface anion channel (PSAC, an unusual ion channel linked to the conserved clag gene family. Although PSAC recognizes and transports a broad range of uncharged and charged solutes, it must efficiently exclude the small Na+ ion to maintain infected cell osmotic stability. Here, we examine possible mechanisms for this remarkable solute selectivity. We identify guanidinium as an organic cation with high permeability into human erythrocytes infected with Plasmodium falciparum, but negligible uptake by uninfected cells. Transport characteristics and pharmacology indicate that this uptake is specifically mediated by PSAC. The rank order of organic and inorganic cation permeabilities suggests cation dehydration as the rate-limiting step in transport through the channel. The high guanidinium permeability of infected cells also allows rapid and stringent synchronization of parasite cultures, as required for molecular and cellular studies of this pathogen. These studies provide important insights into how nutrients and ions are transported via PSAC, an established target for antimalarial drug development.

  8. Object-based attention benefits reveal selective abnormalities of visual integration in autism.

    Science.gov (United States)

    Falter, Christine M; Grant, Kate C Plaisted; Davis, Greg

    2010-06-01

    A pervasive integration deficit could provide a powerful and elegant account of cognitive processing in autism spectrum disorders (ASD). However, in the case of visual Gestalt grouping, typically assessed by tasks that require participants explicitly to introspect on their own grouping perception, clear evidence for such a deficit remains elusive. To resolve this issue, we adopt an index of Gestalt grouping from the object-based attention literature that does not require participants to assess their own grouping perception. Children with ASD and mental- and chronological-age matched typically developing children (TD) performed speeded orientation discriminations of two diagonal lines. The lines were superimposed on circles that were either grouped together or segmented on the basis of color, proximity or these two dimensions in competition. The magnitude of performance benefits evident for grouped circles, relative to ungrouped circles, provided an index of grouping under various conditions. Children with ASD showed comparable grouping by proximity to the TD group, but reduced grouping by similarity. ASD seems characterized by a selective bias away from grouping by similarity combined with typical levels of grouping by proximity, rather than by a pervasive integration deficit.

  9. Comparative vesicle proteomics reveals selective regulation of protein expression in chestnut blight fungus by a hypovirus.

    Science.gov (United States)

    Wang, Jinzi; Wang, Fangzhen; Feng, Youjun; Mi, Ke; Chen, Qi; Shang, Jinjie; Chen, Baoshan

    2013-01-14

    The chestnut blight fungus (Cryphonectria parasitica) and hypovirus constitute a model system to study fungal pathogenesis and mycovirus-host interaction. Knowledge in this field has been gained largely from investigations at gene transcription level so far. Here we report a systematic analysis of the vesicle proteins of the host fungus with/without hypovirus infection. Thirty-three differentially expressed protein spots were identified in the purified vesicle protein samples by two-dimensional electrophoresis and mass spectrometry. Down-regulated proteins were mostly cargo proteins involved in primary metabolism and energy generation and up-regulated proteins were mostly vesicle associated proteins and ABC transporter. A virus-encoded protein p48 was found to have four forms with different molecular mass in vesicles from the virus-infected strain. While a few of the randomly selected differentially expressed proteins were in accordance with their transcription profiles, majority were not in agreement with their mRNA accumulation patterns, suggesting that an extensive post-transcriptional regulation may have occurred in the host fungus upon a hypovirus infection. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Selection for Oil Content During Soybean Domestication Revealed by X-Ray Tomography of Ancient Beans

    Science.gov (United States)

    Zong, Yunbing; Yao, Shengkun; Crawford, Gary W.; Fang, Hui; Lang, Jianfeng; Fan, Jiadong; Sun, Zhibin; Liu, Yang; Zhang, Jianhua; Duan, Xiulan; Zhou, Guangzhao; Xiao, Tiqiao; Luan, Fengshi; Wang, Qing; Chen, Xuexiang; Jiang, Huaidong

    2017-02-01

    When and under what circumstances domestication related traits evolved in soybean (Glycine max) is not well understood. Seed size has been a focus of archaeological attention because increased soybean seed weight/size is a trait that distinguishes most modern soybeans from their ancestors; however, archaeological seed size analysis has had limited success. Modern domesticated soybean has a significantly higher oil content than its wild counterpart so oil content is potentially a source of new insight into soybean domestication. We investigated soybean oil content using X-ray computed tomography (CT; specifically, synchrotron radiation X-ray CT or SRX-CT) of charred, archaeological soybean seeds. CT identified holes in the specimens that are associated with oil content. A high oil content facilitates the development of small holes, whereas a high protein content results in larger holes. The volume of small holes increased slowly from 7,500 to 4,000 cal B.P. We infer that human selection for higher oil content began as early as 7,500 cal B.P. and that high oil content cultivars were well established by 4,000 cal B.P.

  11. Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity.

    Directory of Open Access Journals (Sweden)

    Stephen R Doyle

    2017-07-01

    Full Text Available Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR and sub-optimal responder (SOR parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs, with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic

  12. Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

    Science.gov (United States)

    Nana-Djeunga, Hugues C.; Kengne-Ouafo, Jonas A.; Pion, Sébastien D. S.; Bopda, Jean; Kamgno, Joseph; Wanji, Samuel; Che, Hua; Kuesel, Annette C.; Walker, Martin; Basáñez, Maria-Gloria; Boakye, Daniel A.; Osei-Atweneboana, Mike Y.; Boussinesq, Michel; Prichard, Roger K.; Grant, Warwick N.

    2017-01-01

    Background Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana—exposed to more than a decade of regular ivermectin treatment—have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. Methodology/Principal findings Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR. Conclusions/Significance This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different

  13. Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

    Science.gov (United States)

    Hodson, Charlotte; Purkiss, Andrew; Miles, Jennifer Anne; Walden, Helen

    2014-01-01

    Summary The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ∼40 E2s and ∼600 E3s giving rise to a possible ∼24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL. PMID:24389026

  14. Multilocus patterns of nucleotide diversity and divergence reveal positive selection at candidate genes related to cold hardiness in coastal Douglas Fir (Pseudotsuga menziesii var. menziesii).

    Science.gov (United States)

    A. Eckert; J. Wegrzyn; B. Pande; K. Jermstad; J. Lee; J. Liechty; B. Tearse; K. Krutovsky; D. Neale

    2009-01-01

    Forest trees exhibit remarkable adaptations to their environments. The genetic basis for phenotypic adaptation to climatic gradients has been established through a long history of common garden, provenance, and genecological studies. The identities of genes underlying these traits, however, have remained elusive and thus so have the patterns of adaptive molecular...

  15. THE SPITZER MID-INFRARED ACTIVE GALACTIC NUCLEUS SURVEY. I. OPTICAL AND NEAR-INFRARED SPECTROSCOPY OF OBSCURED CANDIDATES AND NORMAL ACTIVE GALACTIC NUCLEI SELECTED IN THE MID-INFRARED

    Energy Technology Data Exchange (ETDEWEB)

    Lacy, M. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Ridgway, S. E. [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States); Gates, E. L. [UCO/Lick Observatory, P.O. Box 85, Mount Hamilton, CA 95140 (United States); Nielsen, D. M. [Department of Astronomy, University of Wisconsin, 475 N. Charter Street, Madison, WI 53706 (United States); Petric, A. O. [Department of Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Sajina, A. [Department of Physics and Astronomy, Tuffs University, 212 College Avenue, Medford, MA 02155 (United States); Urrutia, T. [Leibniz-Institut für Astrophysik Potsdam, An der Sternwarte 16, D-14482 Potsdam (Germany); Cox Drews, S. [946 Mangrove Avenue 102, Sunnyvale, CA 94086 (United States); Harrison, C. [Department of Astronomy, University of Michigan, Ann Arbor, MI 48109 (United States); Seymour, N. [CSIRO, P.O. Box 76, Epping, NSW 1710 (Australia); Storrie-Lombardi, L. J. [Spitzer Science Center, California Institute of Technology, Pasadena, CA 91125 (United States)

    2013-10-01

    We present the results of a program of optical and near-infrared spectroscopic follow-up of candidate active galactic nuclei (AGNs) selected in the mid-infrared. This survey selects both normal and obscured AGNs closely matched in luminosity across a wide range, from Seyfert galaxies with bolometric luminosities L {sub bol} ∼ 10{sup 10} L {sub ☉} to highly luminous quasars (L {sub bol} ∼ 10{sup 14} L {sub ☉}), all with redshifts ranging from 0 to 4.3. Samples of candidate AGNs were selected with mid-infrared color cuts at several different 24 μm flux density limits to ensure a range of luminosities at a given redshift. The survey consists of 786 candidate AGNs and quasars, of which 672 have spectroscopic redshifts and classifications. Of these, 137 (20%) are type 1 AGNs with blue continua, 294 (44%) are type 2 objects with extinctions A{sub V} ∼> 5 toward their AGNs, 96 (14%) are AGNs with lower extinctions (A{sub V} ∼ 1), and 145 (22%) have redshifts, but no clear signs of AGN activity in their spectra. Of the survey objects 50% have L {sub bol} > 10{sup 12} L {sub ☉}, in the quasar regime. We present composite spectra for type 2 quasars and objects with no signs of AGN activity in their spectra. We also discuss the mid-infrared—emission-line luminosity correlation and present the results of cross correlations with serendipitous X-ray and radio sources. The results show that: (1) obscured objects dominate the overall AGN population, (2) mid-infrared selected AGN candidates exist which lack AGN signatures in their optical spectra but have AGN-like X-ray or radio counterparts, and (3) X-ray and optical classifications of obscured and unobscured AGNs often differ.

  16. Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.

    Science.gov (United States)

    Wu, Daichao; Guo, Ming; Philips, Michael A; Qu, Lingzhi; Jiang, Longying; Li, Jun; Chen, Xiaojuan; Chen, Zhuchu; Chen, Lin; Chen, Yongheng

    2016-01-01

    Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2.35 Å. LY2874455, a type I inhibitor for FGFR4, binds to the ATP-binding pocket of FGFR4 in a DFG-in active conformation with three hydrogen bonds and a number of van der Waals contacts. After alignment of the kinase domain sequence of 4 FGFRs, and superposition of the ATP binding pocket of 4 FGFRs, our structural analyses reveal that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly.

  17. High-resolution imaging of expertise reveals reliable object selectivity in the fusiform face area related to perceptual performance.

    Science.gov (United States)

    McGugin, Rankin Williams; Gatenby, J Christopher; Gore, John C; Gauthier, Isabel

    2012-10-16

    The fusiform face area (FFA) is a region of human cortex that responds selectively to faces, but whether it supports a more general function relevant for perceptual expertise is debated. Although both faces and objects of expertise engage many brain areas, the FFA remains the focus of the strongest modular claims and the clearest predictions about expertise. Functional MRI studies at standard-resolution (SR-fMRI) have found responses in the FFA for nonface objects of expertise, but high-resolution fMRI (HR-fMRI) in the FFA [Grill-Spector K, et al. (2006) Nat Neurosci 9:1177-1185] and neurophysiology in face patches in the monkey brain [Tsao DY, et al. (2006) Science 311:670-674] reveal no reliable selectivity for objects. It is thus possible that FFA responses to objects with SR-fMRI are a result of spatial blurring of responses from nonface-selective areas, potentially driven by attention to objects of expertise. Using HR-fMRI in two experiments, we provide evidence of reliable responses to cars in the FFA that correlate with behavioral car expertise. Effects of expertise in the FFA for nonface objects cannot be attributed to spatial blurring beyond the scale at which modular claims have been made, and within the lateral fusiform gyrus, they are restricted to a small area (200 mm(2) on the right and 50 mm(2) on the left) centered on the peak of face selectivity. Experience with a category may be sufficient to explain the spatially clustered face selectivity observed in this region.

  18. Mechanisms of Acquired Drug Resistance to the HDAC6 Selective Inhibitor Ricolinostat Reveals Rational Drug-Drug Combination with Ibrutinib.

    Science.gov (United States)

    Amengual, Jennifer E; Prabhu, Sathyen A; Lombardo, Maximilian; Zullo, Kelly; Johannet, Paul M; Gonzalez, Yulissa; Scotto, Luigi; Serrano, Xavier Jirau; Wei, Ying; Duong, Jimmy; Nandakumar, Renu; Cremers, Serge; Verma, Akanksha; Elemento, Olivier; O'Connor, Owen A

    2017-06-15

    Purpose: Pan-class I/II histone deacetylase (HDAC) inhibitors are effective treatments for select lymphomas. Isoform-selective HDAC inhibitors are emerging as potentially more targeted agents. ACY-1215 (ricolinostat) is a first-in-class selective HDAC6 inhibitor. To better understand the discrete function of HDAC6 and its role in lymphoma, we developed a lymphoma cell line resistant to ACY-1215. Experimental Design: The diffuse large B-cell lymphoma cell line OCI-Ly10 was exposed to increasing concentrations of ACY-1215 over an extended period of time, leading to the development of a resistant cell line. Gene expression profiling (GEP) was performed to investigate differentially expressed genes. Combination studies of ACY-1215 and ibrutinib were performed in cell lines, primary human lymphoma tissue, and a xenograft mouse model. Results: Systematic incremental increases in drug exposure led to the development of distinct resistant cell lines with IC 50 values 10- to 20-fold greater than that for parental lines. GEP revealed upregulation of MAPK10, HELIOS, HDAC9, and FYN, as well as downregulation of SH3BP5 and LCK. Gene-set enrichment analysis (GSEA) revealed modulation of the BTK pathway. Ibrutinib was found to be synergistic with ACY-1215 in cell lines as well as in 3 primary patient samples of lymphoma. In vivo confirmation of antitumor synergy was demonstrated with a xenograft of DLBCL. Conclusions: The development of this ACY-1215-resistant cell line has provided valuable insights into the mechanistic role of HDAC6 in lymphoma and offered a novel method to identify rational synergistic drug combinations. Translation of these findings to the clinic is underway. Clin Cancer Res; 23(12); 3084-96. ©2016 AACR . ©2016 American Association for Cancer Research.

  19. Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 to a select interaction with the candidate tumor suppressor protein ZO-2

    OpenAIRE

    Glaunsinger, Britt A.; Weiss, Robert S.; Lee, Siu Sylvia; Javier, Ronald

    2001-01-01

    Adenovirus type 9 (Ad9) is distinct among human adenoviruses because it elicits solely mammary tumors in animals and its primary oncogenic determinant is the E4 region-encoded ORF1 (E4-ORF1) protein. We report here that the PDZ domain-containing protein ZO-2, which is a candidate tumor suppressor protein, is a cellular target for tumorigenic Ad9 E4-ORF1 but not for non-tumorigenic wild-type E4-ORF1 proteins encoded by adenovirus types 5 and 12. Complex formation was mediated by the C-terminal...

  20. Genome-wide mapping of infection-induced SINE RNAs reveals a role in selective mRNA export.

    Science.gov (United States)

    Karijolich, John; Zhao, Yang; Alla, Ravi; Glaunsinger, Britt

    2017-06-02

    Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci. Applying SINE-seq to monitor murine B2 SINE expression during a gammaherpesvirus infection revealed transcription from 28 270 SINE loci, with ∼50% of active SINE elements residing within annotated RNA Polymerase II loci. Furthermore, B2 RNA can form intermolecular RNA-RNA interactions with complementary mRNAs, leading to nuclear retention of the targeted mRNA via a mechanism involving p54nrb. These findings illuminate a pathway for the selective regulation of mRNA export during stress via retrotransposon activation. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.

    Directory of Open Access Journals (Sweden)

    Matthias Stein

    Full Text Available Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood.Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics.We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.

  2. The Slow:Fast substitution ratio reveals changing patterns of natural selection in gamma-proteobacterial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Alm, Eric; Shapiro, B. Jesse

    2009-04-15

    Different microbial species are thought to occupy distinct ecological niches, subjecting each species to unique selective constraints, which may leave a recognizable signal in their genomes. Thus, it may be possible to extract insight into the genetic basis of ecological differences among lineages by identifying unusual patterns of substitutions in orthologous gene or protein sequences. We use the ratio of substitutions in slow versus fast-evolving sites (nucleotides in DNA, or amino acids in protein sequence) to quantify deviations from the typical pattern of selective constraint observed across bacterial lineages. We propose that elevated S:F in one branch (an excess of slow-site substitutions) can indicate a functionally-relevant change, due to either positive selection or relaxed evolutionary constraint. In a genome-wide comparative study of gamma-proteobacterial proteins, we find that cell-surface proteins involved with motility and secretion functions often have high S:F ratios, while information-processing genes do not. Change in evolutionary constraints in some species is evidenced by increased S:F ratios within functionally-related sets of genes (e.g., energy production in Pseudomonas fluorescens), while other species apparently evolve mostly by drift (e.g., uniformly elevated S:F across most genes in Buchnera spp.). Overall, S:F reveals several species-specific, protein-level changes with potential functional/ecological importance. As microbial genome projects yield more species-rich gene-trees, the S:F ratio will become an increasingly powerful tool for uncovering functional genetic differences among species.

  3. Autoradiography and density gradient separation of technetium-99m-Exametazime (HMPAO) labelled leucocytes reveals selectivity for eosinophils

    Energy Technology Data Exchange (ETDEWEB)

    Puncher, M.R.B. [Biological Lab., Univ. of Kent, Canterbury (United Kingdom); Blower, P.J. [Nuclear Medicine Dept., Kent and Canterbury Hospital (United Kingdom)

    1994-11-01

    Technetium-99m-Exametazime (HMPAO) is widely used for radiolabelling leucocytes for localization of infection. The subcellular distribution of radionuclide in the labelled cells and the distribution of radioactivity among the leucocyte population are incompletely understood. Frozen section autoradiography was used to determine quantitatively the distribution of {sup 99m}Tc in leucocytes labelled with {sup 99m}Tc-Exametazime. Sections of rapidly frozen suspensions of labelled leucocytes in plasma were autoradiographed on Ilford K2 emulsion and stained with haematoxylin and eosin. Neutrophils, eosinophils and mononuclear cells were separated by Percoll density gradient centrifugation. Cell nuclei were isolated by a rapid cell-breakage and fractionation method. In a typical experiment mean grain densities [grains/100 {mu}m{sup 2} (ESD)] over cells were: eosinophils 31.2 (18.4), neutrophils 3.5 (3.5), mononuclear cells 4.2 (5.1). Mean grain numbers per cell (ESD) were: eosinophils 13 (6.8), neutrophils 1.3 (1.3), mononuclear cells 1.1 (1.3). These findings were confirmed by separation of labelled leucocytes on discontinuous density gradients. In four separation experiments, the mean activity-per-cell ratio for eosinophils to neutrophils was 10.1 (4.8):1, and for eosinophils to mononuclear cells, 14.1 (6.7):1. The subcellular distribution of the label was investigated using image analysis of autoradiographs and cell fractionation. This revealed no selectivity for nuclear or extranuclear compartments. It may be concluded that {sup 99m}Tc-Exametazime has strong selectivity for eosinophils over other leucocytes but no selectivity for nuclear/cytoplasmic compartments. (orig.)

  4. Assessment of subsidence in karst terranes at selected areas in East Tennessee and comparison with a candidate site at Oak Ridge, Tennessee: Phase 2

    International Nuclear Information System (INIS)

    Newton, J.G.; Tanner, J.M.

    1987-09-01

    Work in the respective areas included assessment of conditions related to sinkhole development. Information collected and assessed involved geology, hydrogeology, land use, lineaments and linear trends, identification of karst features and zones, and inventory of historical sinkhole development and type. Karstification of the candidate, Rhea County, and Morristown study areas, in comparison to other karst areas in Tennessee, can be classified informally as youthful, submature, and mature, respectively. Historical sinkhole development in the more karstified areas is attributed to the greater degree of structural deformation by faulting and fracturing, subsequent solutioning of bedrock, thinness of residuum, and degree of development by man. Sinkhole triggering mechanisms identified are progressive solution of bedrock, water-level fluctuations, piping, and loading. 68 refs., 18 figs., 11 tabs

  5. Trial application of the candidate root cause categorization scheme and preliminary assessment of selected data bases for the root causes of component failures program

    International Nuclear Information System (INIS)

    Bruske, S.Z.; Cadwallader, L.C.; Stepina, P.L.

    1985-04-01

    The objective of the Nuclear Regulatory Commission's (NRC) Root Causes of Component Failures Program is to develop and apply a categorization scheme for identifying root causes of failures for components that comprise safety and safety support systems of nuclear power plants. Results from this program will provide valuable input in the areas of probabilistic risk assessment, reliability assurance, and application of risk assessments in the inspection program. This report presents the trial application and assessment of the candidate root cause categorization scheme to three failure data bases: the In-Plant Reliability Data System (IPRDS), the Licensee Event Report (LER) data base, and the Nuclear Plant Reliability Data System (NPRDS). Results of the trial application/assessment show that significant root cause information can be obtained from these failure data bases

  6. Affinity selection of Nipah and Hendra virus-related vaccine candidates from a complex random peptide library displayed on bacteriophage virus-like particles

    Energy Technology Data Exchange (ETDEWEB)

    Peabody, David S.; Chackerian, Bryce; Ashley, Carlee; Carnes, Eric; Negrete, Oscar

    2017-01-24

    The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referred to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.

  7. Structure-activity studies of RFamide peptides reveal subtype-selective activation of neuropeptide FF1 and FF2 receptors.

    Science.gov (United States)

    Findeisen, Maria; Rathmann, Daniel; Beck-Sickinger, Annette G

    2011-06-06

    Selectivity is a major issue in closely related multiligand/multireceptor systems. In this study we investigated the RFamide systems of hNPFF₁R and hNPFF₂R that bind the endogenous peptide hormones NPFF, NPAF, NPVF, and NPSF. By use of a systematic approach, we characterized the role of the C-terminal dipeptide with respect to agonistic properties using synthesized [Xaa 7]NPFF and [Xaa 8]NPFF analogues. We were able to identify only slight differences in potency upon changing the position of Arg 7, as all modifications resulted in identical behavior at the NPFF₁R and NPFF₂R. However, the C-terminal Phe 8 was able to be replaced by Trp or His with only a minor loss in potency at the NPFF₂R relative to the NPFF₁R. Analogues with shorter side chains, such as α-amino-4-guanidino butyric acid ([Agb 7]NPFF) or phenylglycine ([Phg 8]NPFF), decreased efficacy for the NPFF₁ R to 25-31 % of the maximal response, suggesting that these agonist-receptor complexes are more susceptible to structural modifications. In contrast, mutations to the conserved Asp 6.59 residue in the third extracellular loop of both receptors revealed a higher sensitivity toward the hNPFF₂R receptor than toward hNPFF₁R. These data provide new insight into the subtype-specific agonistic activation of the NPFF₁ and NPFF(2) receptors that are necessary for the development of selective agonists. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Drug-induced hypotension SEP test and acetazolamide test using sup 133 Xe SPECT in patients with occlusive carotid disease; Selection of candidates for extracranial-intracranial bypass

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, Satoshi; Kamiyama, Hiroyasu; Abe, Hiroshi; Takigawa, Shugo [Hokkaido Univ., Sapporo (Japan). School of Medicine; Mitsumori, Kenji; Nomura, Mikio; Saitoh, Hisatoshi

    1991-01-01

    The correlation between the drug-induced hypotension somatosensory evoked potential (SEP) test and regional cerebral blood flow changes after acetazolamide administration was studied. Fourteen patients presenting with transient ischemic attack, reversible ischemic neurological deficits, or minor completed stroke were evaluated. All patients had no or only localized low-density areas on computed tomographic scans, and unilateral occlusion or severe stenosis of the internal carotid or middle cerebral artery on cerebral angiograms. The Diamox asymmetry enhancement (DAE) was studied to detect reduced cerebral perfusion reserve in the affected hemispheres. The DAE was 7.9+-5.8% in seven patients positive in the SEP test, significantly higher than -1.5+-2.9% in patients negative in the SEP test. Postoperative SEP tests were negative in all five patients who underwent extracranial-intracranial (EC-IC) bypass surgery, suggesting that the EC-IC bypass improved the cerebral perfusion reserve in the affected hemispheres. The DAE decreased significantly in four of these patients. This study disclosed a significant correlation between the drug-induced hypotension SEP test and DAE. These parameters are considered important for evaluating patients with hemodynamic compromise and/or suitable candidates for EC-IC bypass. (author).

  9. Identification of selective inhibitors of RET and comparison with current clinical candidates through development and validation of a robust screening cascade [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Amanda J. Watson

    2016-05-01

    Full Text Available RET (REarranged during Transfection is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET is a mechanism of oncogenesis in medullary thyroid carcinomas where both germline and sporadic activating somatic mutations are prevalent.   At present, there are no known specific RET inhibitors in clinical development, although many potent inhibitors of RET have been opportunistically identified through selectivity profiling of compounds initially designed to target other tyrosine kinases. Vandetanib and cabozantinib, both multi-kinase inhibitors with RET activity, are approved for use in medullary thyroid carcinoma, but additional pharmacological activities, most notably inhibition of vascular endothelial growth factor - VEGFR2 (KDR, lead to dose-limiting toxicity. The recent identification of RET fusions present in ~1% of lung adenocarcinoma patients has renewed interest in the identification and development of more selective RET inhibitors lacking the toxicities associated with the current treatments.   In an earlier publication [Newton et al, 2016; 1] we reported the discovery of a series of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors. Here we describe the development of the robust screening cascade which allowed the identification and advancement of this chemical series.  Furthermore we have profiled a panel of RET-active clinical compounds both to validate the cascade and to confirm that none display a RET-selective target profile.

  10. Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part II. Selection of an orthogonal set of stationary phases.

    Science.gov (United States)

    Lemasson, Elise; Bertin, Sophie; Hennig, Philippe; Boiteux, Hélène; Lesellier, Eric; West, Caroline

    2015-08-21

    Impurity profiling of organic products that are synthesized as possible drug candidates requires complementary analytical methods to ensure that all impurities are identified. Supercritical fluid chromatography (SFC) is a very useful tool to achieve this objective, as an adequate selection of stationary phases can provide orthogonal separations so as to maximize the chances to see all impurities. In this series of papers, we have developed a method for achiral SFC-MS profiling of drug candidates, based on a selection of 160 analytes issued from Servier Research Laboratories. In the first part of this study, focusing on mobile phase selection, a gradient elution with carbon dioxide and methanol comprising 2% water and 20mM ammonium acetate proved to be the best in terms of chromatographic performance, while also providing good MS response [1]. The objective of this second part was the selection of an orthogonal set of ultra-high performance stationary phases, that was carried out in two steps. Firstly, a reduced set of analytes (20) was used to screen 23 columns. The columns selected were all 1.7-2.5μm fully porous or 2.6-2.7μm superficially porous particles, with a variety of stationary phase chemistries. Derringer desirability functions were used to rank the columns according to retention window, column efficiency evaluated with peak width of selected analytes, and the proportion of analytes successfully eluted with good peak shapes. The columns providing the worst performances were thus eliminated and a shorter selection of columns (11) was obtained. Secondly, based on 160 tested analytes, the 11 columns were ranked again. The retention data obtained on these columns were then compared to define a reduced set of the best columns providing the greatest orthogonality, to maximize the chances to see all impurities within a limited number of runs. Two high-performance columns were thus selected: ACQUITY UPC(2) HSS C18 SB and Nucleoshell HILIC. Copyright © 2015

  11. Citizen Candidates Under Uncertainty

    OpenAIRE

    Eguia, Jon X.

    2005-01-01

    In this paper we make two contributions to the growing literature on "citizen-candidate" models of representative democracy. First, we add uncertainty about the total vote count. We show that in a society with a large electorate, where the outcome of the election is uncertain and where winning candidates receive a large reward from holding office, there will be a two-candidate equilibrium and no equilibria with a single candidate. Second, we introduce a new concept of equilibrium, which we te...

  12. The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection

    Czech Academy of Sciences Publication Activity Database

    Sanchez-Mazas, A.; Černý, V.; Di, D.; Buhler, S.; Podgorná, Eliška; Chevallier, E.; Brunet, L.; Weber, S.; Kervaire, B.; Testi, M.; Andreani, M.; Tiercy, J.-M.; Villard, J.; Nunes, J. M.

    2017-01-01

    Roč. 26, č. 22 (2017), s. 6238-6252 ISSN 0962-1083 R&D Projects: GA ČR GA13-37998S Institutional support: RVO:67985912 Keywords : African populations * geographic patterns * HLA polymorphism and disease associations * human population genetics * malaria protection * pathogen-driven selection Subject RIV: AC - Archeology, Anthropology, Ethnology OBOR OECD: Archaeology Impact factor: 6.086, year: 2016

  13. Selective attention modulates neural substrates of repetition priming and "implicit" visual memory: suppressions and enhancements revealed by FMRI.

    Science.gov (United States)

    Vuilleumier, Patrik; Schwartz, Sophie; Duhoux, Stéphanie; Dolan, Raymond J; Driver, Jon

    2005-08-01

    Attention can enhance processing for relevant information and suppress this for ignored stimuli. However, some residual processing may still arise without attention. Here we presented overlapping outline objects at study, with subjects attending to those in one color but not the other. Attended objects were subsequently recognized on a surprise memory test, whereas there was complete amnesia for ignored items on such direct explicit testing; yet reliable behavioral priming effects were found on indirect testing. Event-related fMRI examined neural responses to previously attended or ignored objects, now shown alone in the same or mirror-reversed orientation as before, intermixed with new items. Repetition-related decreases in fMRI responses for objects previously attended and repeated in the same orientation were found in the right posterior fusiform, lateral occipital, and left inferior frontal cortex. More anterior fusiform regions also showed some repetition decreases for ignored objects, irrespective of orientation. View-specific repetition decreases were found in the striate cortex, particularly for previously attended items. In addition, previously ignored objects produced some fMRI response increases in the bilateral lingual gyri, relative to new objects. Selective attention at exposure can thus produce several distinct long-term effects on processing of stimuli repeated later, with neural response suppression stronger for previously attended objects, and some response enhancement for previously ignored objects, with these effects arising in different brain areas. Although repetition decreases may relate to positive priming phenomena, the repetition increases for ignored objects shown here for the first time might relate to processes that can produce "negative priming" in some behavioral studies. These results reveal quantitative and qualitative differences between neural substrates of long-term repetition effects for attended versus unattended objects.

  14. Genome-Wide Footprints of Pig Domestication and Selection Revealed through Massive Parallel Sequencing of Pooled DNA

    NARCIS (Netherlands)

    Amaral, A.J.; Ferretti, L.; Megens, H.J.W.C.; Crooijmans, R.P.M.A.; Nie, H.; Ramos-Onsins, S.E.; Perez-Enciso, M.; Schook, L.B.; Groenen, M.A.M.

    2011-01-01

    Background Artificial selection has caused rapid evolution in domesticated species. The identification of selection footprints across domesticated genomes can contribute to uncover the genetic basis of phenotypic diversity. Methodology/Main Findings Genome wide footprints of pig domestication and

  15. High overlap of CNVs and selection signatures revealed by varLD analyses of taurine and zebu cattle

    Science.gov (United States)

    Selection Signatures (SS) assessed through analysis of genomic data are being widely studied to discover population specific regions selected via artificial or natural selection. Different methodologies have been proposed for these analyses, each having specific limitations as to the age of the sele...

  16. 76 FR 4896 - Call for Candidates

    Science.gov (United States)

    2011-01-27

    ... designated to establish generally accepted accounting principles for federal government entities. Generally, non-federal Board members are selected from the general financial community, the accounting and... FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Call for Candidates AGENCY: Federal Accounting...

  17. Temporally isolated lineages of Pink salmon reveal unique signatures of selection on distinct pools of standing genetic variation

    DEFF Research Database (Denmark)

    Limborg, Morten; Waples, R.K.; Seeb, J.E.

    2014-01-01

    A species’ genetic diversity bears the marks of evolutionary processes that have occurred throughout its history. However, robust detection of selection in wild populations is difficult and often impeded by lack of replicate tests. Here, we investigate selection in pink salmon (Oncorhynchus gorbu...

  18. Quantitative measures of sexual selection reveal no evidence for sex-role reversal in a sea spider with prolonged paternal care.

    Science.gov (United States)

    Barreto, Felipe S; Avise, John C

    2010-10-07

    Taxa in which males alone invest in postzygotic care of offspring are often considered good models for investigating the proffered relationships between sexual selection and mating systems. In the pycnogonid sea spider Pycnogonum stearnsi, males carry large egg masses on their bodies for several weeks, so this species is a plausible candidate for sex-role reversal (greater intensity of sexual selection on females than on males). Here, we couple a microsatellite-based assessment of the mating system in a natural population with formal quantitative measures of genetic fitness to investigate the direction of sexual selection in P. stearnsi. Both sexes proved to be highly polygamous and showed similar standardized variances in reproductive and mating successes. Moreover, the fertility (number of progeny) of males and females appeared to be equally and highly dependent on mate access, as shown by similar Bateman gradients for the two sexes. The absence of sex-role reversal in this population of P. stearnsi is probably attributable to the fact that males are not limited by brooding space but have evolved an ability to carry large numbers of progeny. Body length was not a good predictor of male mating or reproductive success, so the aim of future studies should be to determine what traits are the targets of sexual selection in this species.

  19. The iSelect 9 K SNP analysis revealed polyploidization induced revolutionary changes and intense human selection causing strong haplotype blocks in wheat.

    Science.gov (United States)

    Hao, Chenyang; Wang, Yuquan; Chao, Shiaoman; Li, Tian; Liu, Hongxia; Wang, Lanfen; Zhang, Xueyong

    2017-01-30

    A Chinese wheat mini core collection was genotyped using the wheat 9 K iSelect SNP array. Total 2420 and 2396 polymorphic SNPs were detected on the A and the B genome chromosomes, which formed 878 haplotype blocks. There were more blocks in the B genome, but the average block size was significantly (P polyploidization of wheat (both tetraploidization and hexaploidization) induced revolutionary changes in both the A and the B genomes, with a greater increase of gene diversity compared to their diploid ancestors. Modern breeding has dramatically increased diversity in the gene coding regions, though obvious blocks were formed on most of the chromosomes in both tetraploid and hexaploid wheats. Tag-SNP markers identified in this study can be used for marker assisted selection using haplotype blocks as a wheat breeding strategy. This strategy can also be employed to facilitate genome selection in other self-pollinating crop species.

  20. Molecular Dynamics Simulations of Orai Reveal How the Third Transmembrane Segment Contributes to Hydration and Ca2+ Selectivity in Calcium Release-Activated Calcium Channels.

    Science.gov (United States)

    Alavizargar, Azadeh; Berti, Claudio; Ejtehadi, Mohammad Reza; Furini, Simone

    2018-04-26

    Calcium release-activated calcium (CRAC) channels open upon depletion of Ca 2+ from the endoplasmic reticulum, and when open, they are permeable to a selective flux of calcium ions. The atomic structure of Orai, the pore domain of CRAC channels, from Drosophila melanogaster has revealed many details about conduction and selectivity in this family of ion channels. However, it is still unclear how residues on the third transmembrane helix can affect the conduction properties of the channel. Here, molecular dynamics and Brownian dynamics simulations were employed to analyze how a conserved glutamate residue on the third transmembrane helix (E262) contributes to selectivity. The comparison between the wild-type and mutated channels revealed a severe impact of the mutation on the hydration pattern of the pore domain and on the dynamics of residues K270, and Brownian dynamics simulations proved that the altered configuration of residues K270 in the mutated channel impairs selectivity to Ca 2+ over Na + . The crevices of water molecules, revealed by molecular dynamics simulations, are perfectly located to contribute to the dynamics of the hydrophobic gate and the basic gate, suggesting a possible role in channel opening and in selectivity function.

  1. Genetic diversity and parentage in farmer selections of cacao from Southern Sulawesi, Indonesia revealed by microsatellite markers

    Science.gov (United States)

    Dinarti, Diny; Susilo, Agung W.; Meinhardt, Lyndel W.; Ji, Kun; Motilal, Lambert A.; Mischke, Sue; Zhang, Dapeng

    2015-01-01

    Indonesia is the third largest cocoa-producing country in the world. Knowledge of genetic diversity and parentage of farmer selections is important for effective selection and rational deployment of superior cacao clones in farmers’ fields. We assessed genetic diversity and parentage of 53 farmer selections of cacao in Sulawesi, Indonesia, using 152 international clones as references. Cluster analysis, based on 15 microsatellite markers, showed that these Sulawesi farmer selections are mainly comprised of hybrids derived from Trinitario and two Upper Amazon Forastero groups. Bayesian assignment and likelihood-based parentage analysis further demonstrated that only a small number of germplasm groups, dominantly Trinitario and Parinari, contributed to these farmer selections, in spite of diverse parental clones having been used in the breeding program and seed gardens in Indonesia since the 1950s. The narrow parentage predicts a less durable host resistance to cacao diseases. Limited access of the farmers to diverse planting materials or the strong preference for large pods and large bean size by local farmers, may have affected the selection outcome. Diverse sources of resistance, harbored in different cacao germplasm groups, need to be effectively incorporated to broaden the on-farm diversity and ensure sustainable cacao production in Sulawesi. PMID:26719747

  2. Genetic diversity and parentage in farmer selections of cacao from Southern Sulawesi, Indonesia revealed by microsatellite markers.

    Science.gov (United States)

    Dinarti, Diny; Susilo, Agung W; Meinhardt, Lyndel W; Ji, Kun; Motilal, Lambert A; Mischke, Sue; Zhang, Dapeng

    2015-12-01

    Indonesia is the third largest cocoa-producing country in the world. Knowledge of genetic diversity and parentage of farmer selections is important for effective selection and rational deployment of superior cacao clones in farmers' fields. We assessed genetic diversity and parentage of 53 farmer selections of cacao in Sulawesi, Indonesia, using 152 international clones as references. Cluster analysis, based on 15 microsatellite markers, showed that these Sulawesi farmer selections are mainly comprised of hybrids derived from Trinitario and two Upper Amazon Forastero groups. Bayesian assignment and likelihood-based parentage analysis further demonstrated that only a small number of germplasm groups, dominantly Trinitario and Parinari, contributed to these farmer selections, in spite of diverse parental clones having been used in the breeding program and seed gardens in Indonesia since the 1950s. The narrow parentage predicts a less durable host resistance to cacao diseases. Limited access of the farmers to diverse planting materials or the strong preference for large pods and large bean size by local farmers, may have affected the selection outcome. Diverse sources of resistance, harbored in different cacao germplasm groups, need to be effectively incorporated to broaden the on-farm diversity and ensure sustainable cacao production in Sulawesi.

  3. Candidate cave entrances on Mars

    Science.gov (United States)

    Cushing, Glen E.

    2012-01-01

    This paper presents newly discovered candidate cave entrances into Martian near-surface lava tubes, volcano-tectonic fracture systems, and pit craters and describes their characteristics and exploration possibilities. These candidates are all collapse features that occur either intermittently along laterally continuous trench-like depressions or in the floors of sheer-walled atypical pit craters. As viewed from orbit, locations of most candidates are visibly consistent with known terrestrial features such as tube-fed lava flows, volcano-tectonic fractures, and pit craters, each of which forms by mechanisms that can produce caves. Although we cannot determine subsurface extents of the Martian features discussed here, some may continue unimpeded for many kilometers if terrestrial examples are indeed analogous. The features presented here were identified in images acquired by the Mars Odyssey's Thermal Emission Imaging System visible-wavelength camera, and by the Mars Reconnaissance Orbiter's Context Camera. Select candidates have since been targeted by the High-Resolution Imaging Science Experiment. Martian caves are promising potential sites for future human habitation and astrobiology investigations; understanding their characteristics is critical for long-term mission planning and for developing the necessary exploration technologies.

  4. Microevolution in time and space: SNP analysis of historical DNA reveals dynamic signatures of selection in Atlantic cod

    DEFF Research Database (Denmark)

    Therkildsen, Nina Overgaard; Hansen, Jakob Hemmer; Als, Thomas Damm

    2013-01-01

    of Atlantic cod (Gadus morhua) studied over an 80-year period. Screening of >1000 gene-associated single-nucleotide polymorphisms (SNPs) identified 77 loci that showed highly elevated levels of differentiation, likely as an effect of directional selection, in either time, space or both. Exploratory analysis......Little is known about how quickly natural populations adapt to changes in their environment and how temporal and spatial variation in selection pressures interact to shape patterns of genetic diversity. We here address these issues with a series of genome scans in four overfished populations...... and spatially varying selection. These findings have important implications for our understanding of local adaptation and evolutionary potential in high gene flow organisms and underscore the need to carefully consider all dimensions of biocomplexity for evolutionarily sustainable management...

  5. Issue-Advocacy versus Candidate Advertising: Effects on Candidate Preferences and Democratic Process.

    Science.gov (United States)

    Pfau, Michael; Holbert, R. Lance; Szabo, Erin Alison; Kaminski, Kelly

    2002-01-01

    Examines the influence of soft-money-sponsored issue-advocacy advertising in U.S. House and Senate campaigns, comparing its effects against candidate-sponsored positive advertising and contrast advertising on viewers' candidate preferences and on their attitude that reflect democratic values. Reveals no main effects for advertising approach on…

  6. Species-scanning mutagenesis of the serotonin transporter reveals residues essential in selective, high-affinity recognition of antidepressants

    DEFF Research Database (Denmark)

    Mortensen, O.V.; Wiborg, O.; Kristensen, A.S.

    2001-01-01

    )tropane, or for 3,4-methylenedioxymethamphetamine (MDMA). Analysis of six hSERT/bSERT chimeras and subsequent species-scanning mutagenesis of each isoform revealed methionine-180, tyrosine-495, and phenylalanine-513 to be responsible for the increase in citalopram and paroxetine potencies at hSERT and methionine...

  7. Opinions of the Geography Teacher Candidates toward Mind Maps

    Science.gov (United States)

    Seyihoglu, Aysegul

    2013-01-01

    The purpose of this study is to reveal the opinions of the teacher candidates about mind mapping technique used in Geography education of undergraduate program. In this study, the qualitative research techniques were used. The study group consists of 55 teacher candidates. The teacher candidates have been asked for their opinions about the process…

  8. Selecting Suitable Candidates for Predictive Maintenance

    NARCIS (Netherlands)

    Tiddens, Wieger Willem; Braaksma, Anne Johannes Jan; Tinga, Tiedo

    2018-01-01

    Predictive maintenance (PdM) or Prognostics and Health Management (PHM) assists in better predicting the future state of physical assets and making timely and better-informed maintenance decisions. Many companies nowadays ambition the implementation of such an advanced maintenance policy. However,

  9. Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues.

    Science.gov (United States)

    Koch, Maximilian F; Harteis, Sabrina; Blank, Iris D; Pestel, Galina; Tietze, Lutz F; Ochsenfeld, Christian; Schneider, Sabine; Sieber, Stephan A

    2015-11-09

    Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial π-stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. MtDNA genomes reveal a relaxation of selective constraints in low-BMI individuals in a Uyghur population.

    Science.gov (United States)

    Zheng, Hong-Xiang; Li, Lei; Jiang, Xiao-Yan; Yan, Shi; Qin, Zhendong; Wang, Xiaofeng; Jin, Li

    2017-10-01

    Considerable attention has been focused on the effect of deleterious mutations caused by the recent relaxation of selective constraints on human health, including the prevalence of obesity, which might represent an adaptive response of energy-conserving metabolism under the conditions of modern society. Mitochondrial DNA (mtDNA) encoding 13 core subunits of oxidative phosphorylation plays an important role in metabolism. Therefore, we hypothesized that a relaxation of selection constraints on mtDNA and an increase in the proportion of deleterious mutations have played a role in obesity prevalence. In this study, we collected and sequenced the mtDNA genomes of 722 Uyghurs, a typical population with a high prevalence of obesity. We identified the variants that occurred in the Uyghur population for each sample and found that the number of nonsynonymous mutations carried by Uyghur individuals declined with elevation of their BMI (P = 0.015). We further calculated the nonsynonymous and synonymous ratio (N/S) of the high-BMI and low-BMI haplogroups, and the results showed that a significantly higher N/S occurred in the whole mtDNA genomes of the low-BMI haplogroups (0.64) than in that of the high-BMI haplogroups (0.35, P = 0.030) and ancestor haplotypes (0.41, P = 0.032); these findings indicated that low-BMI individuals showed a recent relaxation of selective constraints. In addition, we investigated six clinical characteristics and found that fasting plasma glucose might be correlated with the N/S and selective pressures. We hypothesized that a higher proportion of deleterious mutations led to mild mitochondrial dysfunction, which helps to drive glucose consumption and thereby prevents obesity. Our results provide new insights into the relationship between obesity predisposition and mitochondrial genome evolution.

  11. Multimodal Microvascular Imaging Reveals that Selective Inhibition of Class I PI3K Is Sufficient to Induce an Antivascular Response

    Directory of Open Access Journals (Sweden)

    Deepak Sampath

    2013-07-01

    Full Text Available The phosphatidylinositol 3-kinase (PI3K pathway is a central mediator of vascular endothelial growth factor (VEGF-driven angiogenesis. The discovery of small molecule inhibitors that selectively target PI3K or PI3K and mammalian target of rapamycin (mTOR provides an opportunity to pharmacologically determine the contribution of these key signaling nodes in VEGF-A-driven tumor angiogenesis in vivo. This study used an array of microvascular imaging techniques to monitor the antivascular effects of selective class I PI3K, mTOR, or dual PI3K/ mTOR inhibitors in colorectal and prostate cancer xenograft models. Micro-computed tomography (micro-CT angiography, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI, vessel size index (VSI MRI, and DCE ultrasound (DCE-U/S were employed to quantitatively evaluate the vascular (structural and physiological response to these inhibitors. GDC-0980, a dual PI3K/mTOR inhibitor, was found to reduce micro-CT angiography vascular density, while VSI MRI demonstrated a significant reduction in vessel density and an increase in mean vessel size, consistent with a loss of small functional vessels and a substantial antivascular response. DCE-MRI showed that GDC-0980 produces a strong functional response by decreasing the vascular permeability/perfusion-related parameter, Ktrans. Interestingly, comparable antivascular effects were observed for both GDC-980 and GNE-490 (a selective class I PI3K inhibitor. In addition, mTOR-selective inhibitors did not affect vascular density, suggesting that PI3K inhibition is sufficient to generate structural changes, characteristic of a robust antivascular response. This study supports the use of noninvasive microvascular imaging techniques (DCE-MRI, VSI MRI, DCE-U/S as pharmacodynamic assays to quantitatively measure the activity of PI3K and dual PI3K/mTOR inhibitors in vivo.

  12. Artificial selection on relative brain size in the guppy reveals costs and benefits of evolving a larger brain.

    Science.gov (United States)

    Kotrschal, Alexander; Rogell, Björn; Bundsen, Andreas; Svensson, Beatrice; Zajitschek, Susanne; Brännström, Ioana; Immler, Simone; Maklakov, Alexei A; Kolm, Niclas

    2013-01-21

    The large variation in brain size that exists in the animal kingdom has been suggested to have evolved through the balance between selective advantages of greater cognitive ability and the prohibitively high energy demands of a larger brain (the "expensive-tissue hypothesis"). Despite over a century of research on the evolution of brain size, empirical support for the trade-off between cognitive ability and energetic costs is based exclusively on correlative evidence, and the theory remains controversial. Here we provide experimental evidence for costs and benefits of increased brain size. We used artificial selection for large and small brain size relative to body size in a live-bearing fish, the guppy (Poecilia reticulata), and found that relative brain size evolved rapidly in response to divergent selection in both sexes. Large-brained females outperformed small-brained females in a numerical learning assay designed to test cognitive ability. Moreover, large-brained lines, especially males, developed smaller guts, as predicted by the expensive-tissue hypothesis, and produced fewer offspring. We propose that the evolution of brain size is mediated by a functional trade-off between increased cognitive ability and reproductive performance and discuss the implications of these findings for vertebrate brain evolution. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Genome-wide analysis reveals signatures of selection for important traits in domestic sheep from different ecoregions.

    Science.gov (United States)

    Liu, Zhaohua; Ji, Zhibin; Wang, Guizhi; Chao, Tianle; Hou, Lei; Wang, Jianmin

    2016-11-03

    Throughout a long period of adaptation and selection, sheep have thrived in a diverse range of ecological environments. Mongolian sheep is the common ancestor of the Chinese short fat-tailed sheep. Migration to different ecoregions leads to changes in selection pressures and results in microevolution. Mongolian sheep and its subspecies differ in a number of important traits, especially reproductive traits. Genome-wide intraspecific variation is required to dissect the genetic basis of these traits. This research resequenced 3 short fat-tailed sheep breeds with a 43.2-fold coverage of the sheep genome. We report more than 17 million single nucleotide polymorphisms and 2.9 million indels and identify 143 genomic regions with reduced pooled heterozygosity or increased genetic distance to each other breed that represent likely targets for selection during the migration. These regions harbor genes related to developmental processes, cellular processes, multicellular organismal processes, biological regulation, metabolic processes, reproduction, localization, growth and various components of the stress responses. Furthermore, we examined the haplotype diversity of 3 genomic regions involved in reproduction and found significant differences in TSHR and PRL gene regions among 8 sheep breeds. Our results provide useful genomic information for identifying genes or causal mutations associated with important economic traits in sheep and for understanding the genetic basis of adaptation to different ecological environments.

  14. Transcriptome Analysis on Single Small Yellow Follicles Reveals That Wnt4 Is Involved in Chicken Follicle Selection

    Directory of Open Access Journals (Sweden)

    Yiya Wang

    2017-11-01

    Full Text Available Ovarian follicle selection is an important process impacting the laying performance and fecundity of hens, and is regulated by follicle-stimulating hormone (FSH through binding to its receptor [follicle-stimulating hormone receptor (FSHR]. In laying hens, the small yellow follicle (6–8 mm in diameter with the highest expression of FSHR will be recruited into the preovulatory hierarchy during ovarian follicle development. The study of molecular mechanism of chicken follicle selection is helpful for the identification of genes underlying egg-laying traits in chicken and other poultry species. Herein, the transcriptomes of chicken small yellow follicles differing in the mRNA expression of FSHR were compared, and a total of 17,993 genes were identified in 3 pairs of small yellow follicles. The Wnt signaling pathway was significantly enriched in the follicles with the greatest fold change in FSHR expression. In this pathway, the expression level of Wnt4 mRNA was significantly upregulated with a log2(fold change of 2.12. We further investigated the expression, function, and regulation of Wnt4 during chicken follicle selection and found that Wnt4 mRNA reached its peak in small yellow follicles; Wnt4 stimulated the proliferation of follicular granulosa cells (GCs, increased the expression of StAR and CYP11A1 mRNA in prehierarchical and hierarchical follicles, increased the expression of FSHR mRNA, and decreased the expression of anti-Müllerian hormone and OCLN mRNA. Treatment with FSH significantly increased Wnt4 expression in GCs. Moreover, Wnt4 facilitated the effects of FSH on the production of progesterone (P4 and the mRNA expression of steroidogenic enzyme genes in the GCs of hierarchical follicles, but inhibited the effects of FSH in the GCs of prehierarchical follicles. Collectively, these data suggest that Wnt4 plays an important role in chicken follicle selection by stimulating GC proliferation and steroidogenesis. This study provides a

  15. Analysis of triclosan-selected Salmonella enterica mutants of eight serovars revealed increased aminoglycoside susceptibility and reduced growth rates.

    Directory of Open Access Journals (Sweden)

    Ulrike Rensch

    Full Text Available The biocide triclosan (TRC is used in a wide range of household, personal care, veterinary, industrial and medical products to control microbial growth. This extended use raises concerns about a possible association between the application of triclosan and the development of antibiotic resistance. In the present study we determined triclosan mutant prevention concentrations (MPC for Salmonella enterica isolates of eight serovars and investigated selected mutants for their mechanisms mediating decreased susceptibility to triclosan. MPCTRC values were 8-64-fold higher than MIC values and ranged between 1-16 µg/ml. The frequencies at which mutants were selected varied between 1.3 x 10(-10-9.9 x 10(-11. Even if MIC values of mutants decreased by 3-7 dilution steps in the presence of the efflux pump inhibitor Phe-Arg-β-naphtylamide, only minor changes were observed in the expression of genes encoding efflux components or regulators, indicating that neither the major multidrug efflux pump AcrAB-TolC nor AcrEF are up-regulated in triclosan-selected mutants. Nucleotide sequence comparisons confirmed the absence of alterations in the regulatory regions acrRA, soxRS, marORAB, acrSE and ramRA of selected mutants. Single bp and deduced Gly93→Val amino acid exchanges were present in fabI, the target gene of triclosan, starting from a concentration of 1 µg/ml TRC used for MPC determinations. The fabI genes were up to 12.4-fold up-regulated. Complementation experiments confirmed the contribution of Gly93→Val exchanges and fabI overexpression to decreased triclosan susceptibility. MIC values of mutants compared to parent strains were even equal or resulted in a more susceptible phenotype (1-2 dilution steps for the aminoglycoside antibiotics kanamycin and gentamicin as well as for the biocide chlorhexidine. Growth rates of selected mutants were significantly lower and hence, might partly explain the rare occurrence of Salmonella field isolates exhibiting

  16. Whole-genome sequencing of two North American Drosophila melanogaster populations reveals genetic differentiation and positive selection.

    Science.gov (United States)

    Campo, D; Lehmann, K; Fjeldsted, C; Souaiaia, T; Kao, J; Nuzhdin, S V

    2013-10-01

    The prevailing demographic model for Drosophila melanogaster suggests that the colonization of North America occurred very recently from a subset of European flies that rapidly expanded across the continent. This model implies a sudden population growth and range expansion consistent with very low or no population subdivision. As flies adapt to new environments, local adaptation events may be expected. To describe demographic and selective events during North American colonization, we have generated a data set of 35 individual whole-genome sequences from inbred lines of D. melanogaster from a west coast US population (Winters, California, USA) and compared them with a public genome data set from Raleigh (Raleigh, North Carolina, USA). We analysed nuclear and mitochondrial genomes and described levels of variation and divergence within and between these two North American D. melanogaster populations. Both populations exhibit negative values of Tajima's D across the genome, a common signature of demographic expansion. We also detected a low but significant level of genome-wide differentiation between the two populations, as well as multiple allele surfing events, which can be the result of gene drift in local subpopulations on the edge of an expansion wave. In contrast to this genome-wide pattern, we uncovered a 50-kilobase segment in chromosome arm 3L that showed all the hallmarks of a soft selective sweep in both populations. A comparison of allele frequencies within this divergent region among six populations from three continents allowed us to cluster these populations in two differentiated groups, providing evidence for the action of natural selection on a global scale. © 2013 John Wiley & Sons Ltd.

  17. Phylodynamic analysis of clinical and environmental Vibrio cholerae isolates from Haiti reveals diversification driven by positive selection.

    Science.gov (United States)

    Azarian, Taj; Ali, Afsar; Johnson, Judith A; Mohr, David; Prosperi, Mattia; Veras, Nazle M; Jubair, Mohammed; Strickland, Samantha L; Rashid, Mohammad H; Alam, Meer T; Weppelmann, Thomas A; Katz, Lee S; Tarr, Cheryl L; Colwell, Rita R; Morris, J Glenn; Salemi, Marco

    2014-12-23

    Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy. Cholera, a dehydrating diarrheal disease caused by toxigenic strains of the bacterium Vibrio cholerae, emerged in 2010 in Haiti, a country where there were no available records on cholera over the past 100 years. While devastating in terms of morbidity and mortality, the outbreak provided a unique opportunity to study the evolutionary dynamics of V. cholerae and its environmental presence. The present study expands on previous work and provides an in-depth phylodynamic analysis inferred from genome-wide single nucleotide polymorphisms of clinical and environmental strains from dispersed geographic settings in

  18. Landscape genomics and biased FST approaches reveal single nucleotide polymorphisms under selection in goat breeds of North-East Mediterranean

    Directory of Open Access Journals (Sweden)

    Joost Stephane

    2009-02-01

    Full Text Available Abstract Background In this study we compare outlier loci detected using a FST based method with those identified by a recently described method based on spatial analysis (SAM. We tested a panel of single nucleotide polymorphisms (SNPs previously genotyped in individuals of goat breeds of southern areas of the Mediterranean basin (Italy, Greece and Albania. We evaluate how the SAM method performs with SNPs, which are increasingly employed due to their high number, low cost and easy of scoring. Results The combined use of the two outlier detection approaches, never tested before using SNP polymorphisms, resulted in the identification of the same three loci involved in milk and meat quality data by using the two methods, while the FST based method identified 3 more loci as under selection sweep in the breeds examined. Conclusion Data appear congruent by using the two methods for FST values exceeding the 99% confidence limits. The methods of FST and SAM can independently detect signatures of selection and therefore can reduce the probability of finding false positives if employed together. The outlier loci identified in this study could indicate adaptive variation in the analysed species, characterized by a large range of climatic conditions in the rearing areas and by a history of intense trade, that implies plasticity in adapting to new environments.

  19. Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition.

    Directory of Open Access Journals (Sweden)

    Matthew W Parker

    Full Text Available Neuropilin (Nrp receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF family of proangiogenic cytokines and the semaphorin 3 (Sema3 family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A(164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.

  20. Mapping Late Leaf Spot Resistance in Peanut (Arachis hypogaea Using QTL-seq Reveals Markers for Marker-Assisted Selection

    Directory of Open Access Journals (Sweden)

    Josh Clevenger

    2018-02-01

    Full Text Available Late leaf spot (LLS; Cercosporidium personatum is a major fungal disease of cultivated peanut (Arachis hypogaea. A recombinant inbred line population segregating for quantitative field resistance was used to identify quantitative trait loci (QTL using QTL-seq. High rates of false positive SNP calls using established methods in this allotetraploid crop obscured significant QTLs. To resolve this problem, robust parental SNPs were first identified using polyploid-specific SNP identification pipelines, leading to discovery of significant QTLs for LLS resistance. These QTLs were confirmed over 4 years of field data. Selection with markers linked to these QTLs resulted in a significant increase in resistance, showing that these markers can be immediately applied in breeding programs. This study demonstrates that QTL-seq can be used to rapidly identify QTLs controlling highly quantitative traits in polyploid crops with complex genomes. Markers identified can then be deployed in breeding programs, increasing the efficiency of selection using molecular tools.Key Message: Field resistance to late leaf spot is a quantitative trait controlled by many QTLs. Using polyploid-specific methods, QTL-seq is faster and more cost effective than QTL mapping.

  1. Three vibrio-resistance related EST-SSR markers revealed by selective genotyping in the clam Meretrix meretrix.

    Science.gov (United States)

    Nie, Qing; Yue, Xin; Chai, Xueliang; Wang, Hongxia; Liu, Baozhong

    2013-08-01

    The clam Meretrix meretrix is an important commercial bivalve distributed in the coastal areas of South and Southeast Asia. In this study, marker-trait association analyses were performed based on the stock materials of M. meretrix with different vibrio-resistance profile obtained by selective breeding. Forty-eight EST-SSR markers were screened and 27 polymorphic SSRs of them were genotyped in the clam stocks with different resistance to Vibrio parahaemolyticus (11-R and 11-S) and to Vibrio harveyi (09-R and 09-C). Allele frequency distributions of the SSRs among different stocks were compared using Pearson's Chi-square test, and three functional EST-SSR markers (MM959, MM4765 and MM8364) were found to be associated with vibrio-resistance trait. The 140-bp allele of MM959 and 128-bp allele of MM4765 had significantly higher frequencies in resistant groups (11-R and 09-R) than in susceptive/control groups (11-S and 09-C) (P SSR markers were consistent with the three subgroups distinctions. The putative functions of contig959, contig4765 and contig8364 also suggested that the three SSR-involved genes might play important roles in immunity of M. meretrix. All these results supported that EST-SSR markers MM959, MM4765 and MM8364 were associated with vibrio-resistance and would be useful for marker-assisted selection (MAS) in M. meretrix genetic breeding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Functional Connectivity Estimated from Resting-State fMRI Reveals Selective Alterations in Male Adolescents with Pure Conduct Disorder.

    Directory of Open Access Journals (Sweden)

    Feng-Mei Lu

    Full Text Available Conduct disorder (CD is characterized by a persistent pattern of antisocial behavior and aggression in childhood and adolescence. Previous task-based and resting-state functional magnetic resonance imaging (fMRI studies have revealed widespread brain regional abnormalities in adolescents with CD. However, whether the resting-state networks (RSNs are altered in adolescents with CD remains unknown. In this study, resting-state fMRI data were first acquired from eighteen male adolescents with pure CD and eighteen age- and gender-matched typically developing (TD individuals. Independent component analysis (ICA was implemented to extract nine representative RSNs, and the generated RSNs were then compared to show the differences between the CD and TD groups. Interestingly, it was observed from the brain mapping results that compared with the TD group, the CD group manifested decreased functional connectivity in four representative RSNs: the anterior default mode network (left middle frontal gyrus, which is considered to be correlated with impaired social cognition, the somatosensory network (bilateral supplementary motor area and right postcentral gyrus, the lateral visual network (left superior occipital gyrus, and the medial visual network (right fusiform, left lingual gyrus and right calcarine, which are expected to be relevant to the perceptual systems responsible for perceptual dysfunction in male adolescents with CD. Importantly, the novel findings suggested that male adolescents with pure CD were identified to have dysfunctions in both low-level perceptual networks (the somatosensory network and visual network and a high-order cognitive network (the default mode network. Revealing the changes in the functional connectivity of these RSNs enhances our understanding of the neural mechanisms underlying the modulation of emotion and social cognition and the regulation of perception in adolescents with CD.

  3. Inverse European Latitudinal Cline at the timeless Locus of Drosophila melanogaster Reveals Selection on a Clock Gene: Population Genetics of ls-tim.

    Science.gov (United States)

    Zonato, Valeria; Vanin, Stefano; Costa, Rodolfo; Tauber, Eran; Kyriacou, Charalambos P

    2018-02-01

    The spread of adaptive genetic variants in populations is a cornerstone of evolutionary theory but with relatively few biologically well-understood examples. Previous work on the ls-tim variant of timeless, which encodes the light-sensitive circadian regulator in Drosophila melanogaster, suggests that it may have originated in southeastern Italy. Flies characterized by the new allele show photoperiod-related phenotypes likely to be adaptive in seasonal environments. ls-tim may be spreading from its point of origin in Italy by directional selection, but there are alternative explanations for its observed clinal geographical distribution, including balancing selection and demography. From population analyses of ls-tim frequencies collected on the eastern side of the Iberian Peninsula, we show that ls-tim frequencies are inverted compared with those in Italy. This pattern is consistent with a scenario of directional selection rather than latitude-associated balancing selection. Neutrality tests further reveal the signature of directional selection at the ls-tim site, which is reduced a few kb pairs either side of ls-tim. A reanalysis of allele frequencies from a large number of microsatellite loci do not demonstrate any frequent ls-tim-like spatial patterns, so a general demographic effect or population expansion from southeastern Italy cannot readily explain current ls-tim frequencies. Finally, a revised estimate of the age of ls-tim allele using linkage disequilibrium and coalescent-based approaches reveals that it may be only 300 to 3000 years old, perhaps explaining why it has not yet gone to fixation. ls-tim thus provides a rare temporal snapshot of a new allele that has come under selection before it reaches equilibrium.

  4. Structural and biochemical studies of a fluoroacetyl-CoA-specific thioesterase reveal a molecular basis for fluorine selectivity.

    Science.gov (United States)

    Weeks, Amy M; Coyle, Scott M; Jinek, Martin; Doudna, Jennifer A; Chang, Michelle C Y

    2010-11-02

    We have initiated a broad-based program aimed at understanding the molecular basis of fluorine specificity in enzymatic systems, and in this context, we report crystallographic and biochemical studies on a fluoroacetyl-coenzyme A (CoA) specific thioesterase (FlK) from Streptomyces cattleya. Our data establish that FlK is competent to protect its host from fluoroacetate toxicity in vivo and demonstrate a 10(6)-fold discrimination between fluoroacetyl-CoA (k(cat)/K(M) = 5 × 10⁷ M⁻¹ s⁻¹) and acetyl-CoA (k(cat)/K(M) = 30 M⁻¹ s⁻¹) based on a single fluorine substitution that originates from differences in both substrate reactivity and binding. We show that Thr 42, Glu 50, and His 76 are key catalytic residues and identify several factors that influence substrate selectivity. We propose that FlK minimizes interaction with the thioester carbonyl, leading to selection against acetyl-CoA binding that can be recovered in part by new C═O interactions in the T42S and T42C mutants. We hypothesize that the loss of these interactions is compensated by the entropic driving force for fluorinated substrate binding in a hydrophobic binding pocket created by a lid structure, containing Val 23, Leu 26, Phe 33, and Phe 36, that is not found in other structurally characterized members of this superfamily. We further suggest that water plays a critical role in fluorine specificity based on biochemical and structural studies focused on the unique Phe 36 "gate" residue, which functions to exclude water from the active site. Taken together, the findings from these studies offer molecular insights into organofluorine recognition and design of fluorine-specific enzymes.

  5. Alu-miRNA interactions modulate transcript isoform diversity in stress response and reveal signatures of positive selection

    Science.gov (United States)

    Pandey, Rajesh; Bhattacharya, Aniket; Bhardwaj, Vivek; Jha, Vineet; Mandal, Amit K.; Mukerji, Mitali

    2016-09-01

    Primate-specific Alus harbor different regulatory features, including miRNA targets. In this study, we provide evidence for miRNA-mediated modulation of transcript isoform levels during heat-shock response through exaptation of Alu-miRNA sites in mature mRNA. We performed genome-wide expression profiling coupled with functional validation of miRNA target sites within exonized Alus, and analyzed conservation of these targets across primates. We observed that two miRNAs (miR-15a-3p and miR-302d-3p) elevated in stress response, target RAD1, GTSE1, NR2C1, FKBP9 and UBE2I exclusively within Alu. These genes map onto the p53 regulatory network. Ectopic overexpression of miR-15a-3p downregulates GTSE1 and RAD1 at the protein level and enhances cell survival. This Alu-mediated fine-tuning seems to be unique to humans as evident from the absence of orthologous sites in other primate lineages. We further analyzed signatures of selection on Alu-miRNA targets in the genome, using 1000 Genomes Phase-I data. We found that 198 out of 3177 Alu-exonized genes exhibit signatures of selection within Alu-miRNA sites, with 60 of them containing SNPs supported by multiple evidences (global-FST > 0.3, pair-wise-FST > 0.5, Fay-Wu’s H  2.0, high ΔDAF) and implicated in p53 network. We propose that by affecting multiple genes, Alu-miRNA interactions have the potential to facilitate population-level adaptations in response to environmental challenges.

  6. Reconstructed ancestral enzymes reveal that negative selection drove the evolution of substrate specificity in ADP-dependent kinases.

    Science.gov (United States)

    Castro-Fernandez, Víctor; Herrera-Morande, Alejandra; Zamora, Ricardo; Merino, Felipe; Gonzalez-Ordenes, Felipe; Padilla-Salinas, Felipe; Pereira, Humberto M; Brandão-Neto, Jose; Garratt, Richard C; Guixe, Victoria

    2017-09-22

    One central goal in molecular evolution is to pinpoint the mechanisms and evolutionary forces that cause an enzyme to change its substrate specificity; however, these processes remain largely unexplored. Using the glycolytic ADP-dependent kinases of archaea, including the orders Thermococcales , Methanosarcinales , and Methanococcales , as a model and employing an approach involving paleoenzymology, evolutionary statistics, and protein structural analysis, we could track changes in substrate specificity during ADP-dependent kinase evolution along with the structural determinants of these changes. To do so, we studied five key resurrected ancestral enzymes as well as their extant counterparts. We found that a major shift in function from a bifunctional ancestor that could phosphorylate either glucose or fructose 6-phosphate (fructose-6-P) as a substrate to a fructose 6-P-specific enzyme was started by a single amino acid substitution resulting in negative selection with a ground-state mode against glucose and a subsequent 1,600-fold change in specificity of the ancestral protein. This change rendered the residual phosphorylation of glucose a promiscuous and physiologically irrelevant activity, highlighting how promiscuity may be an evolutionary vestige of ancestral enzyme activities, which have been eliminated over time. We also could reconstruct the evolutionary history of substrate utilization by using an evolutionary model of discrete binary characters, indicating that substrate uses can be discretely lost or acquired during enzyme evolution. These findings exemplify how negative selection and subtle enzyme changes can lead to major evolutionary shifts in function, which can subsequently generate important adaptive advantages, for example, in improving glycolytic efficiency in Thermococcales . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus)

    Science.gov (United States)

    Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

    2015-01-01

    An intraspecific genetic map for watermelon was constructed using an F2 population derived from ‘Arka Manik’ × ‘TS34’ and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits. PMID:26700647

  8. Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus).

    Science.gov (United States)

    Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

    2015-01-01

    An intraspecific genetic map for watermelon was constructed using an F2 population derived from 'Arka Manik' × 'TS34' and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits.

  9. Selective Sweep Analysis in the Genomes of the 91-R and 91-C Drosophila melanogaster Strains Reveals Few of the ‘Usual Suspects’ in Dichlorodiphenyltrichloroethane (DDT) Resistance

    Science.gov (United States)

    Steele, Laura D.; Coates, Brad; Valero, M. Carmen; Sun, Weilin; Seong, Keon Mook; Muir, William M.; Clark, John M.; Pittendrigh, Barry R.

    2015-01-01

    Adaptation of insect phenotypes for survival after exposure to xenobiotics can result from selection at multiple loci with additive genetic effects. To the authors’ knowledge, no selective sweep analysis has been performed to identify such loci in highly dichlorodiphenyltrichloroethane (DDT) resistant insects. Here we compared a highly DDT resistant phenotype in the Drosophila melanogaster (Drosophila) 91-R strain to the DDT susceptible 91-C strain, both of common origin. Whole genome re-sequencing data from pools of individuals was generated separately for 91-R and 91-C, and mapped to the reference Drosophila genome assembly (v. 5.72). Thirteen major and three minor effect chromosome intervals with reduced nucleotide diversity (π) were identified only in the 91-R population. Estimates of Tajima's D (D) showed corresponding evidence of directional selection in these same genome regions of 91-R, however, no similar reductions in π or D estimates were detected in 91-C. An overabundance of non-synonymous proteins coding to synonymous changes were identified in putative open reading frames associated with 91-R. Except for NinaC and Cyp4g1, none of the identified genes were the ‘usual suspects’ previously observed to be associated with DDT resistance. Additionally, up-regulated ATP-binding cassette transporters have been previously associated with DDT resistance; however, here we identified a structurally altered MDR49 candidate resistance gene. The remaining fourteen genes have not previously been shown to be associated with DDT resistance. These results suggest hitherto unknown mechanisms of DDT resistance, most of which have been overlooked in previous transcriptional studies, with some genes having orthologs in mammals. PMID:25826265

  10. Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. International Consortium for the Genetics of Autoimmune Thyroid Disease.

    Science.gov (United States)

    Barbesino, G; Tomer, Y; Concepcion, E S; Davies, T F; Greenberg, D A

    1998-09-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) in which multiple genetic factors are suspected to play an important role. Until now, only a few minor risk factors for these diseases have been identified. Susceptibility seems to be stronger in women, pointing toward a possible role for genes related to sex steroid action or mechanisms related to genes on the X-chromosome. We have studied a total of 45 multiplex families, each containing at least 2 members affected with either GD (55 patients) or HT (72 patients), and used linkage analysis to target as candidate susceptibility loci genes involved in estrogen activity, such as the estrogen receptor alpha and beta and the aromatase genes. We then screened the entire X-chromosome using a set of polymorphic microsatellite markers spanning the whole chromosome. We found a region of the X-chromosome (Xq21.33-22) giving positive logarithm of odds (LOD) scores and then reanalyzed this area with dense markers in a multipoint analysis. Our results excluded linkage to the estrogen receptor alpha and aromatase genes when either the patients with GD only, those with HT only, or those with any AITD were considered as affected. Linkage to the estrogen receptor beta could not be totally ruled out, partly due to incomplete mapping information for the gene itself at this time. The X-chromosome data revealed consistently positive LOD scores (maximum of 1.88 for marker DXS8020 and GD patients) when either definition of affectedness was considered. Analysis of the family data using a multipoint analysis with eight closely linked markers generated LOD scores suggestive of linkage to GD in a chromosomal area (Xq21.33-22) extending for about 6 cM and encompassing four markers. The maximum LOD score (2.5) occurred at DXS8020. In conclusion, we ruled out a major role for estrogen receptor alpha and the aromatase genes in the genetic predisposition to AITD. Estrogen receptor beta remains a

  11. Nanomolar oligomerization and selective co-aggregation of α-synuclein pathogenic mutants revealed by single-molecule fluorescence

    Science.gov (United States)

    Sierecki, Emma; Giles, Nichole; Bowden, Quill; Polinkovsky, Mark E.; Steinbeck, Janina; Arrioti, Nicholas; Rahman, Diya; Bhumkar, Akshay; Nicovich, Philip R.; Ross, Ian; Parton, Robert G.; Böcking, Till; Gambin, Yann

    2016-01-01

    Protein aggregation is a hallmark of many neurodegenerative diseases, notably Alzheimer’s and Parkinson’s disease. Parkinson’s disease is characterized by the presence of Lewy bodies, abnormal aggregates mainly composed of α-synuclein. Moreover, cases of familial Parkinson’s disease have been linked to mutations in α-synuclein. In this study, we compared the behavior of wild-type (WT) α-synuclein and five of its pathological mutants (A30P, E46K, H50Q, G51D and A53T). To this end, single-molecule fluorescence detection was coupled to cell-free protein expression to measure precisely the oligomerization of proteins without purification, denaturation or labelling steps. In these conditions, we could detect the formation of oligomeric and pre-fibrillar species at very short time scale and low micromolar concentrations. The pathogenic mutants surprisingly segregated into two classes: one group forming large aggregates and fibrils while the other tending to form mostly oligomers. Strikingly, co-expression experiments reveal that members from the different groups do not generally interact with each other, both at the fibril and monomer levels. Together, this data paints a completely different picture of α-synuclein aggregation, with two possible pathways leading to the development of fibrils. PMID:27892477

  12. Selective activation of SHP2 activity by cisplatin revealed by a novel chemical probe-based assay

    International Nuclear Information System (INIS)

    Kuo, Chun-Chen; Chu, Chi-Yuan; Lin, Jing-Jer; Lo, Lee-Chiang

    2010-01-01

    Src homology-2 (SH2) domain-containing phosphatase 2 (SHP2) is known to participate in several different signaling pathways to mediate cell growth, survival, migration, and differentiation. However, due to the lack of proper analytical tools, it is unclear whether the phosphatase activity of SHP2 is activated in most studies. We have previously developed an activity-based probe LCL2 that formed covalent linkage with catalytically active protein tyrosine phosphatases (PTPs). Here, by combining LCL2 with a SHP2 specific antibody, we established an assay system that enables the direct monitoring of SHP2 activity upon cisplatin treatment of cancer cells. The protocol is advantageous over conventional colorimetric or in-gel PTP assays as it is specific and does not require the use of radioisotope reagents. Using this assay, we found SHP2 activity was selectively activated by cisplatin. Moreover, the activation of SHP2 appeared to be specific for cisplatin as other DNA damage agents failed to activate the activity. Although the role of SHP2 activation by cisplatin treatments is still unclear to us, our results provide the first direct evidence for the activation of SHP2 during cisplatin treatments. More importantly, the concept of using activity-based probe in conjunction with target-specific antibodies could be extended to other enzyme classes.

  13. Site selective substitution Pt for Ti in KTiOPO{sub 4}:Ga crystals revealed by electron paramagnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Grachev, V.; Meyer, M.; Jorgensen, J.; Malovichko, G. [Department of Physics, Montana State University, Bozeman, Montana 59717 (United States); Hunt, A. W. [Idaho Accelerator Center, Idaho State University, Pocatello, Idaho 83209 (United States)

    2014-07-28

    Electron Paramagnetic Resonance at low temperatures has been used to characterize potassium titanyl phosphate (KTiOPO{sub 4}) single crystals grown by different techniques. Irradiation with 20 MeV electrons performed at room temperature and liquid nitrogen temperature caused an appearance of electrons and holes. Platinum impurities act as electron traps in KTiOPO{sub 4} creating Pt{sup 3+} centers. Two different Pt{sup 3+} centers were observed, Pt(A) and Pt(D). The Pt(A) centers are dominant in undoped samples, whereas Pt(D)—in Ga-doped KTP crystals. Superhyperfine structure registered for Pt(D) centers was attributed to interactions of platinum electrons with {sup 39}K and two {sup 31}P nuclei in their surroundings. In both Pt(A) and Pt(D) centers, Pt{sup 3+} ions substitute for Ti{sup 4+} ions, but with a preference to one of two electrically distinct crystallographic positions. The site selective substitution can be controlled by the Ga-doping.

  14. Opportunistically collected data reveal habitat selection by migrating Whooping Cranes in the U.S. Northern Plains

    Science.gov (United States)

    Niemuth, Neil D.; Ryba, Adam J.; Pearse, Aaron T.; Kvas, Susan M.; Brandt, David; Wangler, Brian; Austin, Jane; Carlisle, Martha J.

    2018-01-01

    The Whooping Crane (Grus americana) is a federally endangered species in the United States and Canada that relies on wetland, grassland, and cropland habitat during its long migration between wintering grounds in coastal Texas, USA, and breeding sites in Alberta and Northwest Territories, Canada. We combined opportunistic Whooping Crane sightings with landscape data to identify correlates of Whooping Crane occurrence along the migration corridor in North Dakota and South Dakota, USA. Whooping Cranes selected landscapes characterized by diverse wetland communities and upland foraging opportunities. Model performance substantially improved when variables related to detection were included, emphasizing the importance of accounting for biases associated with detection and reporting of birds in opportunistic datasets. We created a predictive map showing relative probability of occurrence across the study region by applying our model to GIS data layers; validation using independent, unbiased locations from birds equipped with platform transmitting terminals indicated that our final model adequately predicted habitat use by migrant Whooping Cranes. The probability map demonstrated that existing conservation efforts have protected much top-tier Whooping Crane habitat, especially in the portions of North Dakota and South Dakota that lie east of the Missouri River. Our results can support species recovery by informing prioritization for acquisition and restoration of landscapes that provide safe roosting and foraging habitats. Our results can also guide the siting of structures such as wind towers and electrical transmission and distribution lines, which pose a strike and mortality risk to migrating Whooping Cranes.

  15. Elections, Information, and State-Dependent Candidate Quality

    DEFF Research Database (Denmark)

    Jensen, Thomas

    voters are uncertain about the state. Candidates are fully informed and completely office-motivated. With a reasonable restriction on voters' beliefs, an equilibrium where candidates' positions reveal the true state does not exist. Non-revealing equilibria always exist. Some main findings...

  16. Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain.

    Directory of Open Access Journals (Sweden)

    Takeaki Saijo

    Full Text Available A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A receptor, called Wf-516 (structural formula: (2S-1-[4-(3,4-dichlorophenylpiperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-ylbenzo[b]furan-4-yloxy]propan-2-ol monohydrochloride, has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A receptors. In addition, [(35S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

  17. Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain.

    Science.gov (United States)

    Saijo, Takeaki; Maeda, Jun; Okauchi, Takashi; Maeda, Jun-ichi; Morio, Yasunori; Kuwahara, Yasuhiro; Suzuki, Masayuki; Goto, Nobuharu; Fukumura, Toshimitsu; Suhara, Tetsuya; Higuchi, Makoto

    2012-01-01

    A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A)) receptor, called Wf-516 (structural formula: (2S)-1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride), has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET) and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A) receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A) receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A) receptors. In addition, [(35)S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A) receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A) receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

  18. mRNA-seq analysis of the Gossypium arboreum transcriptome reveals tissue selective signaling in response to water stress during seedling stage.

    Directory of Open Access Journals (Sweden)

    Xueyan Zhang

    Full Text Available The cotton diploid species, Gossypium arboreum, shows important properties of stress tolerance and good genetic stability. In this study, through mRNA-seq, we de novo assembled the unigenes of multiple samples with 3h H(2O, NaCl, or PEG treatments in leaf, stem and root tissues and successfully obtained 123,579 transcripts of G. arboreum, 89,128 of which were with hits through BLAST against known cotton ESTs and draft genome of G. raimondii. About 36,961 transcripts (including 1,958 possible transcription factor members were identified with differential expression under water stresses. Principal component analysis of differential expression levels in multiple samples suggested tissue selective signalling responding to water stresses. Venn diagram analysis showed the specificity and intersection of transcripts' response to NaCl and PEG treatments in different tissues. Self-organized mapping and hierarchical cluster analysis of the data also revealed strong tissue selectivity of transcripts under salt and osmotic stresses. In addition, the enriched gene ontology (GO terms for the selected tissue groups were differed, including some unique enriched GO terms such as photosynthesis and tetrapyrrole binding only in leaf tissues, while the stem-specific genes showed unique GO terms related to plant-type cell wall biogenesis, and root-specific genes showed unique GO terms such as monooxygenase activity. Furthermore, there were multiple hormone cross-talks in response to osmotic and salt stress. In summary, our multidimensional mRNA sequencing revealed tissue selective signalling and hormone crosstalk in response to salt and osmotic stresses in G. arboreum. To our knowledge, this is the first such report of spatial resolution of transcriptome analysis in G. arboreum. Our study will potentially advance understanding of possible transcriptional networks associated with water stress in cotton and other crop species.

  19. Dark matter candidates

    International Nuclear Information System (INIS)

    Turner, M.S.

    1989-01-01

    One of the simplest, yet most profound, questions we can ask about the Universe is, how much stuff is in it, and further what is that stuff composed of? Needless to say, the answer to this question has very important implications for the evolution of the Universe, determining both the ultimate fate and the course of structure formation. Remarkably, at this late date in the history of the Universe we still do not have a definitive answer to this simplest of questions---although we have some very intriguing clues. It is known with certainty that most of the material in the Universe is dark, and we have the strong suspicion that the dominant component of material in the Cosmos is not baryons, but rather is exotic relic elementary particles left over from the earliest, very hot epoch of the Universe. If true, the Dark Matter question is a most fundamental one facing both particle physics and cosmology. The leading particle dark matter candidates are: the axion, the neutralino, and a light neutrino species. All three candidates are accessible to experimental tests, and experiments are now in progress. In addition, there are several dark horse, long shot, candidates, including the superheavy magnetic monopole and soliton stars. 13 refs

  20. Optical observations of southern planetary nebula candidates

    NARCIS (Netherlands)

    VandeSteene, GC; Sahu, KC; Pottasch, [No Value

    1996-01-01

    We present H alpha+[NII] images and low resolution spectra of 16 IRAS-selected, southern planetary nebula candidates previously detected in the radio continuum. The H alpha+[NII] images are presented as finding charts. Contour plots are shown for the resolved planetary nebulae. From these images

  1. Synthesis of ent-BE-43547A1 reveals a potent hypoxia-selective anticancer agent and uncovers the biosynthetic origin of the APD-CLD natural products

    Science.gov (United States)

    Villadsen, Nikolaj L.; Jacobsen, Kristian M.; Keiding, Ulrik B.; Weibel, Esben T.; Christiansen, Bjørn; Vosegaard, Thomas; Bjerring, Morten; Jensen, Frank; Johannsen, Mogens; Tørring, Thomas; Poulsen, Thomas B.

    2017-03-01

    Tumour hypoxia is speculated to be a key driver of therapeutic resistance and metastatic dissemination. Consequently, the discovery of new potent agents that selectively target the hypoxic cell population may reveal new and untapped antitumour mechanisms. Here we demonstrate that the BE-43547 subclass of the APD-CLD (amidopentadienoate-containing cyclolipodepsipeptides) natural products possesses highly hypoxia-selective growth-inhibitory activity against pancreatic cancer cells. To enable this discovery, we have developed the first synthesis of the BE-43547-macrocyclic scaffold in 16 steps (longest linear sequence), which also allowed access to the full panel of relative stereoisomers and ultimately to the assignment of stereochemical configuration. Discrepancies between the spectroscopic signatures of the synthetic compounds with that originally reported for the BE-43547 members stimulated us to re-isolate the natural product from a BE-43547-producing microorganism during which we elucidated the biosynthetic gene clusters for the BE-43547 family as well as for all other known APD-CLDs. Our studies underline the exciting possibilities for the further development of the anticancer activities of these natural products.

  2. Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors

    Science.gov (United States)

    Giner, Xavier C; Cotnoir-White, David; Mader, Sylvie; Lévesque, Daniel

    2017-01-01

    Retinoid X receptors (RXR) play a role as master regulators due to their capacity to form heterodimers with other nuclear receptors. Accordingly, retinoid signaling is involved in multiple biological processes, including development, cell differentiation, metabolism and cell death. However, the role and functions of RXR in different heterodimer complexes remain unsolved, mainly because most RXR drugs (called rexinoids) are not selective to specific heterodimer complexes. This also strongly limits the use of rexinoids for specific therapeutic approaches. In order to better characterize rexinoids at specific nuclear receptor complexes, we have developed and optimized luciferase protein complementation-based Bioluminescence Resonance Energy Transfer (BRET) assays, which can directly measure recruitment of a co-activator motif fused to yellow fluorescent protein (YFP) by specific nuclear receptor dimers. To validate the assays, we compared rexinoid modulation of co-activator recruitment by RXR homodimer, and heterodimers Nur77/RXR and Nurr1/RXR. Results reveal that some rexinoids display selective co-activator recruitment activities with homo- or hetero-dimer complexes. In particular, SR11237 (BMS649) has increased potency for recruitment of co-activator motif and transcriptional activity with the Nur77/RXR heterodimer compared to other complexes. This technology should prove useful to identify new compounds with specificity for individual dimeric species formed by nuclear receptors. PMID:26148973

  3. Optimized candidal biofilm microtiter assay

    NARCIS (Netherlands)

    Krom, Bastiaan P.; Cohen, Jesse B.; Feser, Gail E. McElhaney; Cihlar, Ronald L.

    Microtiter based candidal biofilm formation is commonly being used. Here we describe the analysis of factors influencing the development of candidal biofilms such as the coating with serum, growth medium and pH. The data reported here show that optimal candidal biofilm formation is obtained when

  4. Metaphors of Social Studies Teacher Candidates on Democracy

    Science.gov (United States)

    Tural, Aysegül

    2018-01-01

    Democracy is a form of government in which principle of equality is based, human rights and freedoms are protected. In this research, it is aimed to reveal democracy perceptions of social science teacher candidates through metaphors. Towards this aim, 105 social science teacher candidates are consulted about their democracy opinions. Study is a…

  5. Elementary School Teacher Candidates' Perceptions of Good Problems

    Science.gov (United States)

    Lee, Ji-Eun; Kim, Kyoung-Tae

    2005-01-01

    This study describes a classroom action research activity regarding a group of elementary school teacher candidates' perceptions of good mathematics problems. A questionnaire containing 20 problems was given, and the candidates were asked to rate the quality of each problem on a 5-point scale. The results revealed that the majority of the teacher…

  6. MAT@USC Candidates and Latino English Language Learners

    Science.gov (United States)

    Lomeli, Cynthia Leticia

    2012-01-01

    The purpose of this study was to further understand the perceptions of MAT@USC teacher candidates and how their perceptions and previous experiences affect the educational experiences of Latino English language learners. Three questions were developed to guide this study: (1) What are the perceptions of MAT@USC candidates in selected courses…

  7. Candidate Political Philosophy: Revelations in the 1960 and 1976 Debates.

    Science.gov (United States)

    Meadow, Robert G.; Jackson-Beeck, Marilyn

    Since voters rarely have access to a candidate's unexpurgated statements, they rely on political advertising, film footage, and media interpretations. Thus, their expectations of candidates generally reflect selective reporting and self-aggrandizement. A framework for researching the degree of understanding reached between politicians and the…

  8. Holmes versus Traditional Teacher Candidates: Labor Market Receptivity.

    Science.gov (United States)

    Young, I. Phillip; And Others

    1997-01-01

    "Typical" paper credentials were used to create 12 hypothetical teacher candidates. Credential contents were varied to reflect all combinations of college preparatory institutions (Holmes vs. traditional), education degree types, and chronological ages. Randomly selected high school principals then evaluated candidates. Holmes-prepared…

  9. Candidate gene studies and the quest for the entrepreneurial gene

    NARCIS (Netherlands)

    M.J.H.M. van der Loos (Matthijs); Ph.D. Koellinger (Philipp); P.J.F. Groenen (Patrick); C.A. Rietveld (Niels); F. Rivadeneira Ramirez (Fernando); F.J.A. van Rooij (Frank); A.G. Uitterlinden (André); A. Hofman (Albert); A.R. Thurik (Roy)

    2011-01-01

    textabstractCandidate gene studies of human behavior are gaining interest in economics and entrepreneurship research. Performing and interpreting these studies is not straightforward because the selection of candidates influences the interpretation of the results. As an example, Nicolaou et al.

  10. Phenotype selection reveals coevolution of muscle glycogen and protein and PTEN as a gate keeper for the accretion of muscle mass in adult female mice.

    Directory of Open Access Journals (Sweden)

    Mandy Sawitzky

    Full Text Available We have investigated molecular mechanisms for muscle mass accretion in a non-inbred mouse model (DU6P mice characterized by extreme muscle mass. This extreme muscle mass was developed during 138 generations of phenotype selection for high protein content. Due to the repeated trait selection a complex setting of different mechanisms was expected to be enriched during the selection experiment. In muscle from 29-week female DU6P mice we have identified robust increases of protein kinase B activation (AKT, Ser-473, up to 2-fold if compared to 11- and 54-week DU6P mice or controls. While a number of accepted effectors of AKT activation, including IGF-I, IGF-II, insulin/IGF-receptor, myostatin or integrin-linked kinase (ILK, were not correlated with this increase, phosphatase and tensin homologue deleted on chromosome 10 (PTEN was down-regulated in 29-week female DU6P mice. In addition, higher levels of PTEN phosphorylation were found identifying a second mechanism of PTEN inhibition. Inhibition of PTEN and activation of AKT correlated with specific activation of p70S6 kinase and ribosomal protein S6, reduced phosphorylation of eukaryotic initiation factor 2α (eIF2α and higher rates of protein synthesis in 29-week female DU6P mice. On the other hand, AKT activation also translated into specific inactivation of glycogen synthase kinase 3ß (GSK3ß and an increase of muscular glycogen. In muscles from 29-week female DU6P mice a significant increase of protein/DNA was identified, which was not due to a reduction of protein breakdown or to specific increases of translation initiation. Instead our data support the conclusion that a higher rate of protein translation is contributing to the higher muscle mass in mid-aged female DU6P mice. Our results further reveal coevolution of high protein and high glycogen content during the selection experiment and identify PTEN as gate keeper for muscle mass in mid-aged female DU6P mice.

  11. Whole-genome resequencing reveals candidate mutations for pig prolificacy.

    Science.gov (United States)

    Li, Wen-Ting; Zhang, Meng-Meng; Li, Qi-Gang; Tang, Hui; Zhang, Li-Fan; Wang, Ke-Jun; Zhu, Mu-Zhen; Lu, Yun-Feng; Bao, Hai-Gang; Zhang, Yuan-Ming; Li, Qiu-Yan; Wu, Ke-Liang; Wu, Chang-Xin

    2017-12-20

    Changes in pig fertility have occurred as a result of domestication, but are not understood at the level of genetic variation. To identify variations potentially responsible for prolificacy, we sequenced the genomes of the highly prolific Taihu pig breed and four control breeds. Genes involved in embryogenesis and morphogenesis were targeted in the Taihu pig, consistent with the morphological differences observed between the Taihu pig and others during pregnancy. Additionally, excessive functional non-coding mutations have been specifically fixed or nearly fixed in the Taihu pig. We focused attention on an oestrogen response element (ERE) within the first intron of the bone morphogenetic protein receptor type-1B gene ( BMPR1B ) that overlaps with a known quantitative trait locus (QTL) for pig fecundity. Using 242 pigs from 30 different breeds, we confirmed that the genotype of the ERE was nearly fixed in the Taihu pig. ERE function was assessed by luciferase assays, examination of histological sections, chromatin immunoprecipitation, quantitative polymerase chain reactions, and western blots. The results suggest that the ERE may control pig prolificacy via the cis-regulation of BMPR1B expression. This study provides new insight into changes in reproductive performance and highlights the role of non-coding mutations in generating phenotypic diversity between breeds. © 2017 The Author(s).

  12. Looking into flowering time in almond (Prunus dulcis (Mill) D. A. Webb): the candidate gene approach.

    Science.gov (United States)

    Silva, C; Garcia-Mas, J; Sánchez, A M; Arús, P; Oliveira, M M

    2005-03-01

    Blooming time is one of the most important agronomic traits in almond. Biochemical and molecular events underlying flowering regulation must be understood before methods to stimulate late flowering can be developed. Attempts to elucidate the genetic control of this process have led to the identification of a major gene (Lb) and quantitative trait loci (QTLs) linked to observed phenotypic differences, but although this gene and these QTLs have been placed on the Prunus reference genetic map, their sequences and specific functions remain unknown. The aim of our investigation was to associate these loci with known genes using a candidate gene approach. Two almond cDNAs and eight Prunus expressed sequence tags were selected as candidate genes (CGs) since their sequences were highly identical to those of flowering regulatory genes characterized in other species. The CGs were amplified from both parental lines of the mapping population using specific primers. Sequence comparison revealed DNA polymorphisms between the parental lines, mainly of the single nucleotide type. Polymorphisms were used to develop co-dominant cleaved amplified polymorphic sequence markers or length polymorphisms based on insertion/deletion events for mapping the candidate genes on the Prunus reference map. Ten candidate genes were assigned to six linkage groups in the Prunus genome. The positions of two of these were compatible with the regions where two QTLs for blooming time were detected. One additional candidate was localized close to the position of the Evergrowing gene, which determines a non-deciduous behaviour in peach.

  13. BEEF CATTLE MUSCULARITY CANDIDATE GENES

    Directory of Open Access Journals (Sweden)

    Irida Novianti

    2010-04-01

    Full Text Available Muscularity is a potential indicator for the selection of more productive cattle. Mapping quantitative trait loci (QTL for traits related to muscularity is useful to identify the genomic regions where the genes affecting muscularity reside. QTL analysis from a Limousin-Jersey double backcross herd was conducted using QTL Express software with cohort and breed as the fixed effects. Nine QTL suggested to have an association with muscularity were identified on cattle chromosomes BTA 1, 2, 3, 4, 5, 8, 12, 14 and 17. The myostatin gene is located at the centromeric end of chromosome 2 and not surprisingly, the Limousin myostatin F94L variant accounted for the QTL on BTA2. However, when the myostatin F94L genotype was included as an additional fixed effect, the QTL on BTA17 was also no longer significant. This result suggests that there may be gene(s that have epistatic effects with myostatin located on cattle chromosome 17. Based on the position of the QTL in base pairs, all the genes that reside in the region were determined using the Ensembl data base (www.ensembl.org. There were two potential candidate genes residing within these QTL regions were selected. They were Smad nuclear interacting protein 1 (SNIP1 and similar to follistatin-like 5 (FSTL5. (JIIPB 2010 Vol 20 No 1: 1-10

  14. Single-step selection of drug resistant Acinetobacter baylyi ADP1 mutants reveals a functional redundancy in the recruitment of multidrug efflux systems.

    Directory of Open Access Journals (Sweden)

    Anthony J Brzoska

    Full Text Available Members of the genus Acinetobacter have been the focus recent attention due to both their clinical significance and application to molecular biology. The soil commensal bacterium Acinetobacter baylyi ADP1 has been proposed as a model system for molecular and genetic studies, whereas in a clinical environment, Acinetobacter spp. are of increasing importance due to their propensity to cause serious and intractable systemic infections. Clinically, a major factor in the success of Acinetobacter spp. as opportunistic pathogens can be attributed to their ability to rapidly evolve resistance to common antimicrobial compounds. Whole genome sequencing of clinical and environmental Acinetobacter spp. isolates has revealed the presence of numerous multidrug transporters within the core and accessory genomes, suggesting that efflux is an important host defense response in this genus. In this work, we used the drug-susceptible organism A. baylyi ADP1 as a model for studies into the evolution of efflux mediated resistance in genus Acinetobacter, due to the high level of conservation of efflux determinants across four diverse Acinetobacter strains, including clinical isolates. A single exposure of therapeutic concentrations of chloramphenicol to populations of A. baylyi ADP1 cells produced five individual colonies displaying multidrug resistance. The major facilitator superfamily pump craA was upregulated in one mutant strain, whereas the resistance nodulation division pump adeJ was upregulated in the remaining four. Within the adeJ upregulated population, two different levels of adeJ mRNA transcription were observed, suggesting at least three separate mutations were selected after single-step exposure to chloramphenicol. In the craA upregulated strain, a T to G substitution 12 nt upstream of the craA translation initiation codon was observed. Subsequent mRNA stability analyses using this strain revealed that the half-life of mutant craA mRNA was significantly

  15. Multi-species sequence comparison reveals dynamic evolution of the elastin gene that has involved purifying selection and lineage-specific insertions/deletions

    Directory of Open Access Journals (Sweden)

    Green Eric D

    2004-05-01

    Full Text Available Abstract Background The elastin gene (ELN is implicated as a factor in both supravalvular aortic stenosis (SVAS and Williams Beuren Syndrome (WBS, two diseases involving pronounced complications in mental or physical development. Although the complete spectrum of functional roles of the processed gene product remains to be established, these roles are inferred to be analogous in human and mouse. This view is supported by genomic sequence comparison, in which there are no large-scale differences in the ~1.8 Mb sequence block encompassing the common region deleted in WBS, with the exception of an overall reversed physical orientation between human and mouse. Results Conserved synteny around ELN does not translate to a high level of conservation in the gene itself. In fact, ELN orthologs in mammals show more sequence divergence than expected for a gene with a critical role in development. The pattern of divergence is non-conventional due to an unusually high ratio of gaps to substitutions. Specifically, multi-sequence alignments of eight mammalian sequences reveal numerous non-aligning regions caused by species-specific insertions and deletions, in spite of the fact that the vast majority of aligning sites appear to be conserved and undergoing purifying selection. Conclusions The pattern of lineage-specific, in-frame insertions/deletions in the coding exons of ELN orthologous genes is unusual and has led to unique features of the gene in each lineage. These differences may indicate that the gene has a slightly different functional mechanism in mammalian lineages, or that the corresponding regions are functionally inert. Identified regions that undergo purifying selection reflect a functional importance associated with evolutionary pressure to retain those features.

  16. Molecular organization and phylogenetic analysis of 5S rDNA in crustaceans of the genus Pollicipes reveal birth-and-death evolution and strong purifying selection.

    Science.gov (United States)

    Perina, Alejandra; Seoane, David; González-Tizón, Ana M; Rodríguez-Fariña, Fernanda; Martínez-Lage, Andrés

    2011-10-17

    The 5S ribosomal DNA (5S rDNA) is organized in tandem arrays with repeat units that consist of a transcribing region (5S) and a variable nontranscribed spacer (NTS), in higher eukaryotes. Until recently the 5S rDNA was thought to be subject to concerted evolution, however, in several taxa, sequence divergence levels between the 5S and the NTS were found higher than expected under this model. So, many studies have shown that birth-and-death processes and selection can drive the evolution of 5S rDNA. In analyses of 5S rDNA evolution is found several 5S rDNA types in the genome, with low levels of nucleotide variation in the 5S and a spacer region highly divergent. Molecular organization and nucleotide sequence of the 5S ribosomal DNA multigene family (5S rDNA) were investigated in three Pollicipes species in an evolutionary context. The nucleotide sequence variation revealed that several 5S rDNA variants occur in Pollicipes genomes. They are clustered in up to seven different types based on differences in their nontranscribed spacers (NTS). Five different units of 5S rDNA were characterized in P. pollicipes and two different units in P. elegans and P. polymerus. Analysis of these sequences showed that identical types were shared among species and that two pseudogenes were present. We predicted the secondary structure and characterized the upstream and downstream conserved elements. Phylogenetic analysis showed an among-species clustering pattern of 5S rDNA types. These results suggest that the evolution of Pollicipes 5S rDNA is driven by birth-and-death processes with strong purifying selection.

  17. Revealing mechanisms of selective, concentration-dependent potentials of 4-hydroxy-2-nonenal to induce apoptosis in cancer cells through inactivation of membrane-associated catalase.

    Science.gov (United States)

    Bauer, Georg; Zarkovic, Neven

    2015-04-01

    Tumor cells generate extracellular superoxide anions and are protected against superoxide anion-mediated intercellular apoptosis-inducing signaling by the expression of membrane-associated catalase. 4-Hydroxy-2-nonenal (4-HNE), a versatile second messenger generated during lipid peroxidation, has been shown to induce apoptosis selectively in malignant cells. The findings described in this paper reveal the strong, concentration-dependent potential of 4-HNE to specifically inactivate extracellular catalase of tumor cells both indirectly and directly and to consequently trigger apoptosis in malignant cells through superoxide anion-mediated intercellular apoptosis-inducing signaling. Namely, 4-HNE caused apoptosis selectively in NOX1-expressing tumor cells through inactivation of their membrane-associated catalase, thus reactivating subsequent intercellular signaling through the NO/peroxynitrite and HOCl pathways, followed by the mitochondrial pathway of apoptosis. Concentrations of 4-HNE of 1.2 µM and higher directly inactivated membrane-associated catalase of tumor cells, whereas at lower concentrations, 4-HNE triggered a complex amplificatory pathway based on initial singlet oxygen formation through H2O2 and peroxynitrite interaction. Singlet-oxygen-dependent activation of the FAS receptor and caspase-8 increased superoxide anion generation by NOX1 and amplification of singlet oxygen generation, which allowed singlet-oxygen-dependent inactivation of catalase. 4-HNE and singlet oxygen cooperate in complex autoamplificatory loops during this process. The finding of these novel anticancer pathways may be useful for understanding the role of 4-HNE in the control of malignant cells and for the optimization of ROS-dependent therapeutic approaches including antioxidant treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. What Do Teacher Candidates Think about the Teaching Education? The Example of Social Studies Teacher Candidates

    Science.gov (United States)

    Tonga, Deniz

    2016-01-01

    In this research, it is aimed to reveal the opinions and observations of social studies teacher candidate about the courses they have taken during their 4-year university education. The focus group interview was used as the data collecting tool, and the content analyses were performed on the data obtained. The criterion sampling approach was used…

  19. A Dense Brown Trout (Salmo trutta) Linkage Map Reveals Recent Chromosomal Rearrangements in the Salmo Genus and the Impact of Selection on Linked Neutral Diversity

    Science.gov (United States)

    Leitwein, Maeva; Guinand, Bruno; Pouzadoux, Juliette; Desmarais, Erick; Berrebi, Patrick; Gagnaire, Pierre-Alexandre

    2017-01-01

    High-density linkage maps are valuable tools for conservation and eco-evolutionary issues. In salmonids, a complex rediploidization process consecutive to an ancient whole genome duplication event makes linkage maps of prime importance for investigating the evolutionary history of chromosome rearrangements. Here, we developed a high-density consensus linkage map for the brown trout (Salmo trutta), a socioeconomically important species heavily impacted by human activities. A total of 3977 ddRAD markers were mapped and ordered in 40 linkage groups using sex- and lineage-averaged recombination distances obtained from two family crosses. Performing map comparison between S. trutta and its sister species, S. salar, revealed extensive chromosomal rearrangements. Strikingly, all of the fusion and fission events that occurred after the S. salar/S. trutta speciation happened in the Atlantic salmon branch, whereas the brown trout remained closer to the ancestral chromosome structure. Using the strongly conserved synteny within chromosome arms, we aligned the brown trout linkage map to the Atlantic salmon genome sequence to estimate the local recombination rate in S. trutta at 3721 loci. A significant positive correlation between recombination rate and within-population nucleotide diversity (π) was found, indicating that selection constrains variation at linked neutral sites in brown trout. This new high-density linkage map provides a useful genomic resource for future aquaculture, conservation, and eco-evolutionary studies in brown trout. PMID:28235829

  20. A Dense Brown Trout (Salmo trutta Linkage Map Reveals Recent Chromosomal Rearrangements in the Salmo Genus and the Impact of Selection on Linked Neutral Diversity

    Directory of Open Access Journals (Sweden)

    Maeva Leitwein

    2017-04-01

    Full Text Available High-density linkage maps are valuable tools for conservation and eco-evolutionary issues. In salmonids, a complex rediploidization process consecutive to an ancient whole genome duplication event makes linkage maps of prime importance for investigating the evolutionary history of chromosome rearrangements. Here, we developed a high-density consensus linkage map for the brown trout (Salmo trutta, a socioeconomically important species heavily impacted by human activities. A total of 3977 ddRAD markers were mapped and ordered in 40 linkage groups using sex- and lineage-averaged recombination distances obtained from two family crosses. Performing map comparison between S. trutta and its sister species, S. salar, revealed extensive chromosomal rearrangements. Strikingly, all of the fusion and fission events that occurred after the S. salar/S. trutta speciation happened in the Atlantic salmon branch, whereas the brown trout remained closer to the ancestral chromosome structure. Using the strongly conserved synteny within chromosome arms, we aligned the brown trout linkage map to the Atlantic salmon genome sequence to estimate the local recombination rate in S. trutta at 3721 loci. A significant positive correlation between recombination rate and within-population nucleotide diversity (π was found, indicating that selection constrains variation at linked neutral sites in brown trout. This new high-density linkage map provides a useful genomic resource for future aquaculture, conservation, and eco-evolutionary studies in brown trout.

  1. A Genome-Wide Association Study on the Seedless Phenotype in Banana (Musa spp.) Reveals the Potential of a Selected Panel to Detect Candidate Genes in a Vegetatively Propagated Crop

    Czech Academy of Sciences Publication Activity Database

    Sardos, J.; Rouard, M.; Hueber, Y.; Cenci, A.; Hyma, K.I.; Van den Houwe, I.; Hřibová, Eva; Courtois, B.; Roux, N.

    2016-01-01

    Roč. 11, č. 5 (2016), e0154448 E-ISSN 1932-6203 Institutional support: RVO:61389030 Keywords : FEMALE GAMETOPHYTE DEVELOPMENT * ARABIDOPSIS HISTIDINE KINASE * MULTILOCUS GENOTYPE DATA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

  2. Various Approaches for Targeting Quasar Candidates

    Science.gov (United States)

    Zhang, Y.; Zhao, Y.

    2015-09-01

    With the establishment and development of space-based and ground-based observational facilities, the improvement of scientific output of high-cost facilities is still a hot issue for astronomers. The discovery of new and rare quasars attracts much attention. Different methods to select quasar candidates are in bloom. Among them, some are based on color cuts, some are from multiwavelength data, some rely on variability of quasars, some are based on data mining, and some depend on ensemble methods.

  3. Counts of low-Redshift SDSS quasar candidates

    International Nuclear Information System (INIS)

    Zeljko Ivezic

    2004-01-01

    We analyze the counts of low-redshift quasar candidates selected using nine-epoch SDSS imaging data. The co-added catalogs are more than 1 mag deeper than single-epoch SDSS data, and allow the selection of low-redshift quasar candidates using UV-excess and also variability techniques. The counts of selected candidates are robustly determined down to g = 21.5. This is about 2 magnitudes deeper than the position of a change in the slope of the counts reported by Boyle (and others) (1990, 2000) for a sample selected by UV-excess, and questioned by Hawkins and Veron (1995), who utilized a variability-selected sample. Using SDSS data, we confirm a change in the slope of the counts for both UV-excess and variability selected samples, providing strong support for the Boyle (and others) results

  4. A MITE-based genotyping method to reveal hundreds of DNA polymorphisms in an animal genome after a few generations of artificial selection

    Directory of Open Access Journals (Sweden)

    Tetreau Guillaume

    2008-10-01

    Full Text Available Abstract Background For most organisms, developing hundreds of genetic markers spanning the whole genome still requires excessive if not unrealistic efforts. In this context, there is an obvious need for methodologies allowing the low-cost, fast and high-throughput genotyping of virtually any species, such as the Diversity Arrays Technology (DArT. One of the crucial steps of the DArT technique is the genome complexity reduction, which allows obtaining a genomic representation characteristic of the studied DNA sample and necessary for subsequent genotyping. In this article, using the mosquito Aedes aegypti as a study model, we describe a new genome complexity reduction method taking advantage of the abundance of miniature inverted repeat transposable elements (MITEs in the genome of this species. Results Ae. aegypti genomic representations were produced following a two-step procedure: (1 restriction digestion of the genomic DNA and simultaneous ligation of a specific adaptor to compatible ends, and (2 amplification of restriction fragments containing a particular MITE element called Pony using two primers, one annealing to the adaptor sequence and one annealing to a conserved sequence motif of the Pony element. Using this protocol, we constructed a library comprising more than 6,000 DArT clones, of which at least 5.70% were highly reliable polymorphic markers for two closely related mosquito strains separated by only a few generations of artificial selection. Within this dataset, linkage disequilibrium was low, and marker redundancy was evaluated at 2.86% only. Most of the detected genetic variability was observed between the two studied mosquito strains, but individuals of the same strain could still be clearly distinguished. Conclusion The new complexity reduction method was particularly efficient to reveal genetic polymorphisms in Ae. egypti. Overall, our results testify of the flexibility of the DArT genotyping technique and open new

  5. Molecular evolution of candidate genes for crop-related traits in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Mandel, Jennifer R; McAssey, Edward V; Nambeesan, Savithri; Garcia-Navarro, Elena; Burke, John M

    2014-01-01

    Evolutionary analyses aimed at detecting the molecular signature of selection during crop domestication and/or improvement can be used to identify genes or genomic regions of likely agronomic importance. Here, we describe the DNA sequence-based characterization of a pool of candidate genes for crop-related traits in sunflower. These genes, which were identified based on homology to genes of known effect in other study systems, were initially sequenced from a panel of improved lines. All genes that exhibited a paucity of sequence diversity, consistent with the possible effects of selection during the evolution of cultivated sunflower, were then sequenced from a panel of wild sunflower accessions an outgroup. These data enabled formal tests for the effects of selection in shaping sequence diversity at these loci. When selection was detected, we further sequenced these genes from a panel of primitive landraces, thereby allowing us to investigate the likely timing of selection (i.e., domestication vs. improvement). We ultimately identified seven genes that exhibited the signature of positive selection during either domestication or improvement. Genetic mapping of a subset of these genes revealed co-localization between candidates for genes involved in the determination of flowering time, seed germination, plant growth/development, and branching and QTL that were previously identified for these traits in cultivated × wild sunflower mapping populations.

  6. Shifts in the evolutionary rate and intensity of purifying selection between two Brassica genomes revealed by analyses of orthologous transposons and relics of a whole genome triplication.

    Science.gov (United States)

    Zhao, Meixia; Du, Jianchang; Lin, Feng; Tong, Chaobo; Yu, Jingyin; Huang, Shunmou; Wang, Xiaowu; Liu, Shengyi; Ma, Jianxin

    2013-10-01

    Recent sequencing of the Brassica rapa and Brassica oleracea genomes revealed extremely contrasting genomic features such as the abundance and distribution of transposable elements between the two genomes. However, whether and how these structural differentiations may have influenced the evolutionary rates of the two genomes since their split from a common ancestor are unknown. Here, we investigated and compared the rates of nucleotide substitution between two long terminal repeats (LTRs) of individual orthologous LTR-retrotransposons, the rates of synonymous and non-synonymous substitution among triplicated genes retained in both genomes from a shared whole genome triplication event, and the rates of genetic recombination estimated/deduced by the comparison of physical and genetic distances along chromosomes and ratios of solo LTRs to intact elements. Overall, LTR sequences and genic sequences showed more rapid nucleotide substitution in B. rapa than in B. oleracea. Synonymous substitution of triplicated genes retained from a shared whole genome triplication was detected at higher rates in B. rapa than in B. oleracea. Interestingly, non-synonymous substitution was observed at lower rates in the former than in the latter, indicating shifted densities of purifying selection between the two genomes. In addition to evolutionary asymmetry, orthologous genes differentially regulated and/or disrupted by transposable elements between the two genomes were also characterized. Our analyses suggest that local genomic and epigenomic features, such as recombination rates and chromatin dynamics reshaped by independent proliferation of transposable elements and elimination between the two genomes, are perhaps partially the causes and partially the outcomes of the observed inter-specific asymmetric evolution. © 2013 Purdue University The Plant Journal © 2013 John Wiley & Sons Ltd.

  7. High-resolution GPS tracking reveals habitat selection and the potential for long-distance seed dispersal by Madagascan flying foxes Pteropus rufus

    Directory of Open Access Journals (Sweden)

    Ryszard Oleksy

    2015-01-01

    Full Text Available Long-distance seed dispersal can be important for the regeneration of forested habitats, especially in regions where deforestation has been severe. Old World fruit bats (Pteropodidae have considerable potential for long-distance seed dispersal. We studied the movement patterns and feeding behaviour of the endemic Madagascan flying fox Pteropus rufus, in Berenty Reserve, southeast Madagascar. Between July and September 2012 (the dry season nine males and six females were tagged with customised GPS loggers which recorded fixes every 2.5 min between 18.00 and 06.00 h. The combined home range of all of the tagged bats during 86 nights exceeded 58,000 ha. Females had larger home ranges and core foraging areas and foraged over longer distances (average 28.1 km; median 26.7 km than males (average 15.4 km; median 9.5 km. Because the study was conducted during the gestation period, the increased energy requirements of females may explain their greater mean foraging area. Compositional analysis revealed that bats show strong preferences for overgrown sisal (Agave sisalana plantations (a mix of shrub, trees and sisal plants and remnant riverside forest patches. Sisal nectar and pollen were abundant food sources during the tracking period and this probably contributed to the selective use of overgrown sisal plantations. The bats also ate large quantities of figs (Ficus grevei during the study, and dispersed seeds of this important pioneer species. The bats flew at an average speed of 9.13 m/s, perhaps to optimise gliding performance. The study confirms that P. rufus has the potential to be a long-distance seed disperser, and is able to fly over a large area, often crossing cleared parts of its habitat. It potentially plays an important role in the regeneration of threatened forest habitats in this biodiversity hotspot.

  8. Voices of Teacher Candidates of Color on White Race Evasion: "I Worried about My Safety!"

    Science.gov (United States)

    Amos, Yukari Takimoto

    2016-01-01

    This qualitative study investigated the negative impacts minority teacher candidates receive from white teacher candidates in a required multicultural education class. The findings reveal that four teacher candidates of color had difficulty positioning themselves among the overwhelming silencing power of whiteness in the class. The white students…

  9. Warm Debris Disk Candidates from WISE

    Science.gov (United States)

    Padgett, Deborah; Stapelfeldt, Karl; Liu, Wilson; Leisawitz, David

    2011-01-01

    The Wide Field Infrared Survey Explorer (WISE) has just completed a sensitive all-sky survey in photometric bands at 3.4, 4.6, 12, and 22 microns. We report on a preliminary investigation of main sequence Hipparcos and Tycho catalog stars with 22 micron emission in excess of photospheric levels. This warm excess emission traces material in the circumstellar region likely to host terrestrial planets and is preferentially found in young systems with ages warm debris disk candidates are detected among FGK stars and 150 A stars within 120 pc. We are in the process of obtaining spectra to determine spectral types and activity level of these stars and are using HST, Herschel and Keck to characterize the dust, multiplicity, and substellar companions of these systems. In this contribution, we will discuss source selection methods and individual examples from among the WISE debris disk candidates.

  10. Temporal Alterations in the Secretome of the Selective Ligninolytic Fungus Ceriporipsis subvermispora during growth on Aspen Wood Reveal this Organism's Strategy for Degrading Lighnocellulose

    Science.gov (United States)

    Chiaki Hori; Jill Gaskell; Kiyohiko Igarashi; Phil Kersten; Michael Mozuch; Masahiro Samejima; Dan Cullen

    2014-01-01

    The white-rot basidiomycetes efficiently degrade all wood cell wall polymers. Generally, these fungi simultaneously degrade cellulose and lignin, but certain organisms, such as Ceriporiopsis subvermispora, selectively remove lignin in advance of cellulose degradation. However, relatively little is known about themechanismof selective ligninolysis. To...

  11. The Hidden Curriculum: Candidate Diversity in Educational Leadership Preparation

    Science.gov (United States)

    Karanxha, Zorka; Agosto, Vonzell; Bellara, Aarti P.

    2014-01-01

    The authors describe a process of self-assessment attuned to equity and justice in the policies and practices that affect student diversity, namely, those associated with the selection of candidates. The disproportionate rate of rejection for applicants from underrepresented groups and the unsystematic process of applicant selection operated as…

  12. Bigger Is Fitter? Quantitative Genetic Decomposition of Selection Reveals an Adaptive Evolutionary Decline of Body Mass in a Wild Rodent Population.

    Directory of Open Access Journals (Sweden)

    Timothée Bonnet

    2017-01-01

    Full Text Available In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called "stasis paradox" highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic environmental change. While the causes underlying the stasis paradox are hotly debated, comprehensive attempts aiming at a resolution are lacking. Here, we apply a quantitative genetic framework to individual-based long-term data for a wild rodent population and show that despite a positive association between body mass and fitness, there has been a genetic change towards lower body mass. The latter represents an adaptive response to viability selection favouring juveniles growing up to become relatively small adults, i.e., with a low potential adult mass, which presumably complete their development earlier. This selection is particularly strong towards the end of the snow-free season, and it has intensified in recent years, coinciding which a change in snowfall patterns. Importantly, neither the negative evolutionary change, nor the selective pressures that drive it, are apparent on the phenotypic level, where they are masked by phenotypic plasticity and a non causal (i.e., non genetic positive association between body mass and fitness, respectively. Estimating selection at the genetic level enabled us to uncover adaptive evolution in action and to identify the corresponding phenotypic selective pressure. We thereby demonstrate that natural populations can show a rapid and adaptive evolutionary response to a novel selective pressure, and that explicitly (quantitative genetic models are able to provide us with an understanding of the causes and consequences of

  13. Bigger Is Fitter? Quantitative Genetic Decomposition of Selection Reveals an Adaptive Evolutionary Decline of Body Mass in a Wild Rodent Population

    Science.gov (United States)

    Wandeler, Peter; Camenisch, Glauco

    2017-01-01

    In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called “stasis paradox” highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic environmental change. While the causes underlying the stasis paradox are hotly debated, comprehensive attempts aiming at a resolution are lacking. Here, we apply a quantitative genetic framework to individual-based long-term data for a wild rodent population and show that despite a positive association between body mass and fitness, there has been a genetic change towards lower body mass. The latter represents an adaptive response to viability selection favouring juveniles growing up to become relatively small adults, i.e., with a low potential adult mass, which presumably complete their development earlier. This selection is particularly strong towards the end of the snow-free season, and it has intensified in recent years, coinciding which a change in snowfall patterns. Importantly, neither the negative evolutionary change, nor the selective pressures that drive it, are apparent on the phenotypic level, where they are masked by phenotypic plasticity and a non causal (i.e., non genetic) positive association between body mass and fitness, respectively. Estimating selection at the genetic level enabled us to uncover adaptive evolution in action and to identify the corresponding phenotypic selective pressure. We thereby demonstrate that natural populations can show a rapid and adaptive evolutionary response to a novel selective pressure, and that explicitly (quantitative) genetic models are able to provide us with an understanding of the causes and consequences of selection that is

  14. Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Stephenson Diane T

    2011-05-01

    doublecortin, PSA-NCAM and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus, and a marked reduction in the number of 5-bromo-2'-deoxyuridine (BrdU positive progenitors. Furthermore, a significant and profound reduction in BDNF mRNA was seen in the BTBR dentate gyrus. No significant differences were seen in the expression of AchE, mossy fiber synapses or immunoreactivities of microtubule-associated protein MAP2, parvalbumin and glutamate decarboxylase GAD65 or GAD67 isoforms. Conclusions We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced neurogenesis in the adult hippocampus. Of all markers examined, the most distinctive changes were seen in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and DCX. Our results are consistent with aberrant development of the nervous system in BTBR mice, and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders.

  15. Impact of ER520, a candidate of selective estrogen receptor modulators, on in vitro cell growth, migration, invasion, angiogenesis and in vivo tumor xenograft of human breast cancer cells.

    Science.gov (United States)

    Wang, Lijun; Wang, Ying; Du, Huaqing; Jiang, Yao; Tang, Zhichao; Liu, Hongyi; Xiang, Hua; Xiao, Hong

    2015-12-01

    ER520, a derivative of indenoisoquinoline, is a patented compound. This study was designed to screen its biological properties and to evaluate its antineoplastic and antiangiogenic effect. Western blot was employed to monitor the ERα and ERβ protein expression in human breast cancer MCF-7 cells and endometrial carcinoma Ishikawa cells. MTT assay was employed to determine cell proliferation. Cell adhesion, scratch and Transwell assay were utilized to estimate the ability of cellular adhesion, migration and invasion. ELISA kit was applied to detect the VEGF products in culture medium. In addition, the inhibitory effect of ER520 on the vessel-like construction of HUVEC cells and the angiogenesis of chicken embryos was investigated. The efficiency of ER520 on tumor growth in nude mice was also assessed. ER520 inhibited the expression of ERα in MCF-7 and Ishikawa cells, while it increased ERβ protein level. ER520 also suppressed the proliferation of MCF-7 and Ishikawa cells. Due to its remarkably negative role in cell adhesion, migration and invasion, ER520 showed a potential ability of inhibiting tumor metastasis. Meanwhile, ER520 reduced the VEGF secretion of MCF-7 and Ishikawa cells, prevented the formation of VEGF-stimulated tubular structure and the cell migration of HUVEC cells, and inhibited the angiogenesis of chicken chorioallantoic membrane. Animal experiment also demonstrated that ER520 could frustrate the in vivo tumor growth and the inhibitory ratio was 48.5 % compared with control group. Our findings indicate that ER520 possesses the competence to be a candidate against breast cancer and angiogenesis.

  16. Geoscience Training for NASA Astronaut Candidates

    Science.gov (United States)

    Young, K. E.; Evans, C. A.; Bleacher, J. E.; Graff, T. G.; Zeigler, R.

    2017-01-01

    After being selected to the astronaut office, crewmembers go through an initial two year training flow, astronaut candidacy, where they learn the basic skills necessary for spaceflight. While the bulk of astronaut candidate training currently centers on the multiple subjects required for ISS operations (EVA skills, Russian language, ISS systems, etc.), training also includes geoscience training designed to train crewmembers in Earth observations, teach astronauts about other planetary systems, and provide field training designed to investigate field operations and boost team skills. This training goes back to Apollo training and has evolved to support ISS operations and future exploration missions.

  17. Lap Shear Testing of Candidate Radiator Panel Adhesives

    Science.gov (United States)

    Ellis, David; Briggs, Maxwell; McGowan, Randy

    2013-01-01

    During testing of a subscale radiator section used to develop manufacturing techniques for a full-scale radiator panel, the adhesive bonds between the titanium heat pipes and the aluminum face sheets failed during installation and operation. Analysis revealed that the thermal expansion mismatch between the two metals resulted in relatively large shear stresses being developed even when operating the radiator at moderate temperatures. Lap shear testing of the adhesive used in the original joints demonstrated that the two-part epoxy adhesive fell far short of the strength required. A literature review resulted in several candidate adhesives being selected for lap shear joint testing at room temperature and 398 K, the nominal radiator operating temperature. The results showed that two-part epoxies cured at room and elevated temperatures generally did not perform well. Epoxy film adhesives cured at elevated temperatures, on the other hand, did very well with most being sufficiently strong to cause yielding in the titanium sheet used for the joints. The use of an epoxy primer generally improved the strength of the joint. Based upon these results, a new adhesive was selected for the second subscale radiator section.

  18. Pupil Dilation and EEG Alpha Frequency Band Power Reveal Load on Executive Functions for Link-Selection Processes during Text Reading.

    Directory of Open Access Journals (Sweden)

    Christian Scharinger

    Full Text Available Executive working memory functions play a central role in reading comprehension. In the present research we were interested in additional load imposed on executive functions by link-selection processes during computer-based reading. For obtaining process measures, we used a methodology of concurrent electroencephalographic (EEG and eye-tracking data recording that allowed us to compare epochs of pure text reading with epochs of hyperlink-like selection processes in an online reading situation. Furthermore, this methodology allowed us to directly compare the two physiological load-measures EEG alpha frequency band power and pupil dilation. We observed increased load on executive functions during hyperlink-like selection processes on both measures in terms of decreased alpha frequency band power and increased pupil dilation. Surprisingly however, the two measures did not correlate. Two additional experiments were conducted that excluded potential perceptual, motor, or structural confounds. In sum, EEG alpha frequency band power and pupil dilation both turned out to be sensitive measures for increased load during hyperlink-like selection processes in online text reading.

  19. Selective sweep analysis in the genomes of the 91-R and 91-C Drosophila melanogaster strains reveals few of the ‘usual suspects’ in Dichlorodiphenyltrichloroethane (DDT) resistance

    Science.gov (United States)

    Adaptation of insect phenotypes for survival after exposure to xenobiotics can result from selection at multiple loci with additive genetic effects. A high level dichlorodiphenyltrichloroethane (DDT) resistance phenotype in the Drosophila melanogaster strain 91-R has resulted due to continuous labo...

  20. Signatures of selection in the Iberian honey bee (Apis mellifera iberiensis) revealed by a genome scan analysis of single nucleotide polymorphisms.

    Science.gov (United States)

    Chávez-Galarza, Julio; Henriques, Dora; Johnston, J Spencer; Azevedo, João C; Patton, John C; Muñoz, Irene; De la Rúa, Pilar; Pinto, M Alice

    2013-12-01

    Understanding the genetic mechanisms of adaptive population divergence is one of the most fundamental endeavours in evolutionary biology and is becoming increasingly important as it will allow predictions about how organisms will respond to global environmental crisis. This is particularly important for the honey bee, a species of unquestionable ecological and economical importance that has been exposed to increasing human-mediated selection pressures. Here, we conducted a single nucleotide polymorphism (SNP)-based genome scan in honey bees collected across an environmental gradient in Iberia and used four FST -based outlier tests to identify genomic regions exhibiting signatures of selection. Additionally, we analysed associations between genetic and environmental data for the identification of factors that might be correlated or act as selective pressures. With these approaches, 4.4% (17 of 383) of outlier loci were cross-validated by four FST -based methods, and 8.9% (34 of 383) were cross-validated by at least three methods. Of the 34 outliers, 15 were found to be strongly associated with one or more environmental variables. Further support for selection, provided by functional genomic information, was particularly compelling for SNP outliers mapped to different genes putatively involved in the same function such as vision, xenobiotic detoxification and innate immune response. This study enabled a more rigorous consideration of selection as the underlying cause of diversity patterns in Iberian honey bees, representing an important first step towards the identification of polymorphisms implicated in local adaptation and possibly in response to recent human-mediated environmental changes. © 2013 John Wiley & Sons Ltd.

  1. Contrasting Patterns of Genomic Diversity Reveal Accelerated Genetic Drift but Reduced Directional Selection on X-Chromosome in Wild and Domestic Sheep Species.

    Science.gov (United States)

    Chen, Ze-Hui; Zhang, Min; Lv, Feng-Hua; Ren, Xue; Li, Wen-Rong; Liu, Ming-Jun; Nam, Kiwoong; Bruford, Michael W; Li, Meng-Hua

    2018-04-01

    Analyses of genomic diversity along the X chromosome and of its correlation with autosomal diversity can facilitate understanding of evolutionary forces in shaping sex-linked genomic architecture. Strong selective sweeps and accelerated genetic drift on the X-chromosome have been inferred in primates and other model species, but no such insight has yet been gained in domestic animals compared with their wild relatives. Here, we analyzed X-chromosome variability in a large ovine data set, including a BeadChip array for 943 ewes from the world's sheep populations and 110 whole genomes of wild and domestic sheep. Analyzing whole-genome sequences, we observed a substantially reduced X-to-autosome diversity ratio (∼0.6) compared with the value expected under a neutral model (0.75). In particular, one large X-linked segment (43.05-79.25 Mb) was found to show extremely low diversity, most likely due to a high density of coding genes, featuring highly conserved regions. In general, we observed higher nucleotide diversity on the autosomes, but a flat diversity gradient in X-linked segments, as a function of increasing distance from the nearest genes, leading to a decreased X: autosome (X/A) diversity ratio and contrasting to the positive correlation detected in primates and other model animals. Our evidence suggests that accelerated genetic drift but reduced directional selection on X chromosome, as well as sex-biased demographic events, explain low X-chromosome diversity in sheep species. The distinct patterns of X-linked and X/A diversity we observed between Middle Eastern and non-Middle Eastern sheep populations can be explained by multiple migrations, selection, and admixture during the domestic sheep's recent postdomestication demographic expansion, coupled with natural selection for adaptation to new environments. In addition, we identify important novel genes involved in abnormal behavioral phenotypes, metabolism, and immunity, under selection on the sheep X-chromosome.

  2. Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures

    Directory of Open Access Journals (Sweden)

    Hayes Michael L

    2012-05-01

    Full Text Available Abstract Background Pentatricopeptide repeat (PPR proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82 and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. Results All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3’ UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. Conclusion PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative

  3. Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures.

    Science.gov (United States)

    Hayes, Michael L; Giang, Karolyn; Mulligan, R Michael

    2012-05-14

    Pentatricopeptide repeat (PPR) proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82) and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3' UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative selection even in the absence of an editing site target

  4. Oriented regions grouping based candidate proposal for infrared pedestrian detection

    Science.gov (United States)

    Wang, Jiangtao; Zhang, Jingai; Li, Huaijiang

    2018-04-01

    Effectively and accurately locating the positions of pedestrian candidates in image is a key task for the infrared pedestrian detection system. In this work, a novel similarity measuring metric is designed. Based on the selective search scheme, the developed similarity measuring metric is utilized to yield the possible locations for pedestrian candidate. Besides this, corresponding diversification strategies are also provided according to the characteristics of the infrared thermal imaging system. Experimental results indicate that the presented scheme can achieve more efficient outputs than the traditional selective search methodology for the infrared pedestrian detection task.

  5. A preliminary systems assessment of the Starlite Demo candidates

    International Nuclear Information System (INIS)

    Bathke, C.G.

    1995-01-01

    The Starlite project has evaluated the following five tokamaks as candidates for the US Demo Power Plant: (1) steady state, first stability regime; (2) pulsed, first stability regime; (3) steady state, second stability regime; (4) steady state, reversed shear; and (5) steady state, low aspect ratio. Systems analysis of these candidates has played an important role in the selection of a reversed-shear tokamak for further conceptual design as a US Demo Power Plant. The cost-based systems analysis that led to the selection of a reversed-shear tokamak is described herein

  6. Comparative Analyses of Physics Candidates Scores in West African and National Examinations Councils

    Science.gov (United States)

    Utibe, Uduak James; Agah, John Joseph

    2015-01-01

    The study is a comparative analysis of physics candidates' scores in West African and National Examinations Councils. It also investigates influence of gender. Results of 480 candidates were randomly selected form three randomly selected Senior Science Colleges using the WASSCE and NECOSSCE computer printout sent to the schools, transformed using…

  7. Signatures of natural selection among lineages and habitats in Oncorhynchus mykiss

    DEFF Research Database (Denmark)

    Limborg, Morten; Blankenship, S.; Young, S.

    2012-01-01

    lineage. Overall patterns of variation affirmed clear distinctions between lineages and in most instances, isolation by distance within them. Evidence for divergent selection at eight candidate loci included significant landscape correlations, particularly with temperature. High diversity of two...... nonsynonymous mutations within the peptide-binding region of the major histocompatibility complex (MHC) class II (DAB) gene provided signatures of balancing selection. Weak signals for potential selection between sympatric resident and anadromous populations were revealed from genome scans and allele frequency...

  8. Synthesis and biological evaluation of bivalent cannabinoid receptor ligands based on hCB₂R selective benzimidazoles reveal unexpected intrinsic properties.

    Science.gov (United States)

    Nimczick, Martin; Pemp, Daniela; Darras, Fouad H; Chen, Xinyu; Heilmann, Jörg; Decker, Michael

    2014-08-01

    The design of bivalent ligands targeting G protein-coupled receptors (GPCRs) often leads to the development of new, highly selective and potent compounds. To date, no bivalent ligands for the human cannabinoid receptor type 2 (hCB₂R) of the endocannabinoid system (ECS) are described. Therefore, two sets of homobivalent ligands containing as parent structure the hCB2R selective agonist 13a and coupled at different attachment positions were synthesized. Changes of the parent structure at these positions have a crucial effect on the potency and efficacy of the ligands. However, we discovered that bivalency has an influence on the effect at both cannabinoid receptors. Moreover, we found out that the spacer length and the attachment position altered the efficacy of the bivalent ligands at the receptors by turning agonists into antagonists and inverse agonists. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Selectivity of neuronal [3H]GABA accumulation in the visual cortex as revealed by Golgi staining of the labeled neurons

    International Nuclear Information System (INIS)

    Somogyi, P.; Freund, T.F.; Kisvarday, Z.F.; Halasz, N.

    1981-01-01

    [ 3 H]GABA was injected into the visual cortex of rats in vivo. The labeled amino acid was demonstrated by autoradiography using semithin sections of Golgi material. Selective accumulation was seen in the perikarya of Golgi-stained, gold-toned, aspinous stellate neurons. Spine-laden pyramidal-like cells did not show labeling. This method gives direct information about the dendritic arborization of a neuron, and its putative transmitter, and allows the identification of its synaptic connections. (Auth.)

  10. Selectivity of primary events in the radiation chemistry of organic solids and polymers as revealed by model studies of ionized molecules

    International Nuclear Information System (INIS)

    Feldman, V.

    2006-01-01

    Selectivity of the primary chemical events induced by ionizing radiation in molecular systems is the key issue of basic radiation chemistry, which is crucially important for controlling the radiation sensitivity of various-type organic and polymeric materials and designing new effective approaches to the radiation modification. In the past decade we have demonstrated that many features of selective localization of the radiation-induced effects in molecular solids can be understood on the basis of model studies of the primary ionized molecules in rigid low-temperature matrices. This talk will outline the key results of these studies and possible implications for radiation chemistry of vatious systems. In particular, the following aspects will be considered: (1) Spectroscopic characteristics of ustable ionized molecules in low-temperature matrices and their correlations with the site-selective reactivity. (2) Experimental modeling of the effect of excess energy on the properties of primary ionized molecules in condensed phases. (3) Intramolecular long-range effects with particular impact on the properties of ionized bifunctional molecules of X-(CH 2 ) n -X and X-(CH 2 ) n -Y types. (4) Modeling of intermolecular long-range positive hole transfer between molecular traps with close ionization energy and manifestations of 'fine tuning' effects resulting from conformation variations and intermolecular interactions. Several illustrative examples of correlation between the properties of primary ionized molecules and selectivity of the radiation-chemical transformations in organic solids and macromolecules will be presented. Finally, the problem of prediction of the radiation-chemical behaviour of complex organic systems on the basis of limited spectroscopic information and quantum-chemical data obtained for model systems will be addressed. This work was supported by the Russian Foundation for Basic Research (Project No. 06-03-33104) and the Russian Academy of Sciences

  11. Bigger Is Fitter? Quantitative Genetic Decomposition of Selection Reveals an Adaptive Evolutionary Decline of Body Mass in a Wild Rodent Population.

    OpenAIRE

    Timothée Bonnet; Peter Wandeler; Glauco Camenisch; Erik Postma

    2017-01-01

    In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions: Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called ‘stasis paradox’ highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic enviro...

  12. Separation properties of the MIL-125(Ti) Metal-Organic Framework in high-performance liquid chromatography revealing cis/trans selectivity.

    Science.gov (United States)

    Van der Perre, Stijn; Liekens, Anuschka; Bueken, Bart; De Vos, Dirk E; Baron, Gino V; Denayer, Joeri F M

    2016-10-21

    Monodisperse MIL-125(Ti) Metal-Organic Framework crystals were synthesized and studied as stationary phase in high performance liquid chromatography (HPLC). Different pure compounds and model mixtures (including stereoisomer mixtures) were injected from which chromatographic parameters, including selectivities and resolution factors, were determined to evaluate the adsorption properties and separation performance of MIL-125(Ti) in liquid phase. The MIL-125(Ti) framework displayed a trans selectivity for cis/trans difunctionalized cyclohexane molecules with high selectivity and resolution for 1,3-dimethylcyclohexane and 4-ethylcyclohexanol. The slurry-packed column was further characterized via van Deemter analysis. Fitting of the van Deemter equation through the experimental points allowed to define the contributions of the different processes to plate height with a significant proportion of the A-term, reflecting the importance of a good crystal packing. Although high in comparison to commercial HPLC stationary phases, a very good plate height of around 50μm was found. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Global gene expression in larval zebrafish (Danio rerio) exposed to selective serotonin reuptake inhibitors (fluoxetine and sertraline) reveals unique expression profiles and potential biomarkers of exposure

    International Nuclear Information System (INIS)

    Park, June-Woo; Heah, Tze Ping; Gouffon, Julia S.; Henry, Theodore B.; Sayler, Gary S.

    2012-01-01

    Larval zebrafish (Danio rerio) were exposed (96 h) to selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and changes in transcriptomes analyzed by Affymetrix GeneChip ® Zebrafish Array were evaluated to enhance understanding of biochemical pathways and differences between these SSRIs. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 μg/L and 131 at 250 μg/L; and after sertraline exposure was 33 at 25 μg/L and 52 at 250 μg/L. Same five genes were differentially regulated in both SSRIs indicating shared molecular pathways. Among these, the gene coding for FK506 binding protein 5, annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated at the gene expression level that regulation of stress response and cholinesterase activities were influenced by these SSRIs, and suggested that changes in transcription of these genes could be used as biomarkers of SSRI exposure. - Highlights: ► Exposure of zebrafish to selective serotonin reuptake inhibitors (SSRIs). ► Fluoxetine and sertraline generate different global gene expression profiles. ► Genes linked to stress response and acetylcholine esterase affected by both SSRIs. - Global gene expression profiles in zebrafish exposed to selective serotonin reuptake inhibitors.

  14. Narcissism Guides Mate Selection: Humans Mate Assortatively, as Revealed by Facial Resemblance, following an Algorithm of “Self Seeking Like”

    Directory of Open Access Journals (Sweden)

    Liliana Alvarez

    2004-01-01

    Full Text Available Theoretical studies suggest that mating and pair formation is not likely to be random. Computer simulations suggested that sex among genetically complex organisms requires mate choice strategies for its evolutionary maintenance, to reduce excessive genetic variance produced by out-crossing. One strategy achieving this aim efficiently in computer simulations is assortative mating modeled as “self seeking like”. Another one is selection of “good genes”. Assortative mating increases the probability of finding a genetically similar mate, without fomenting inbreeding, achieving assortative mating without hindering the working of other mate selection strategies which aim to maximize the search for “good genes”, optimizing the working of sex in evolutionary terms. Here we present indirect evidence that in a significant proportion of human reproductive couples, the partners show much higher facial resemblances than can be expected by random pair formation, or as the outcome of “matching for attractiveness” or the outcome of competition for the most attractive partner accessible, as had been previously assumed. The data presented is compatible with the hypothesis derived from computer simulations, that human mate selection strategies achieve various aims: “self seeking like” (including matching for attractiveness and mating with the best available genes.

  15. Candidate Prediction Models and Methods

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Madsen, Henrik

    2005-01-01

    This document lists candidate prediction models for Work Package 3 (WP3) of the PSO-project called ``Intelligent wind power prediction systems'' (FU4101). The main focus is on the models transforming numerical weather predictions into predictions of power production. The document also outlines...... the possibilities w.r.t. different numerical weather predictions actually available to the project....

  16. On security arguments of the second round SHA-3 candidates

    DEFF Research Database (Denmark)

    Andreeva, Elena; Bogdanov, Andrey; Mennink, Bart

    2012-01-01

    of which got accepted to the first round. 14 candidates were left in the second round, out of which five candidates have been recently chosen for the final round. An important criterion in the selection process is the SHA-3 hash function security. We identify two important classes of security arguments...... for the new designs: (1) the possible reductions of the hash function security to the security of its underlying building blocks and (2) arguments against differential attack on building blocks. In this paper, we compare the state of the art provable security reductions for the second round candidates...... and review arguments and bounds against classes of differential attacks.We discuss all the SHA-3 candidates at a high functional level, analyze, and summarize the security reduction results and bounds against differential attacks. Additionally, we generalize the well-known proof of collision resistance...

  17. Quantum mechanical/molecular mechanical calculated reactivity networks reveal how cytochrome P450cam and Its T252A mutant select their oxidation pathways.

    Science.gov (United States)

    Wang, Binju; Li, Chunsen; Dubey, Kshatresh Dutta; Shaik, Sason

    2015-06-17

    Quantum mechanical/molecular mechanical calculations address the longstanding-question of a "second oxidant" in P450 enzymes wherein the proton-shuttle, which leads to formation of the "primary-oxidant" Compound I (Cpd I), was severed by mutating the crucial residue (in P450cam: Threonine-252-to-Alanine, hence T252A). Investigating the oxidant candidates Cpd I, ferric hydroperoxide, and ferric hydrogen peroxide (Fe(III)(O2H2)), and their reactions, generates reactivity networks which enable us to rule out a "second oxidant" and at the same time identify an additional coupling pathway that is responsible for the epoxidation of 5-methylenylcamphor by the T252A mutant. In this "second-coupling pathway", the reaction starts with the Fe(III)(O2H2) intermediate, which transforms to Cpd I via a O-O homolysis/H-abstraction mechanism. The persistence of Fe(III)(O2H2) and its oxidative reactivity are shown to be determined by interplay of substrate and protein. The substrate 5-methylenylcamphor prevents H2O2 release, while the protein controls the Fe(III)(O2H2) conversion to Cpd I by nailing-through hydrogen-bonding interactions-the conformation of the HO(•) radical produced during O-O homolysis. This conformation prevents HO(•) attack on the porphyrin's meso position, as in heme oxygenase, and prefers H-abstraction from Fe(IV)OH thereby generating H2O + Cpd I. Cpd I then performs substrate oxidations. Camphor cannot prevent H2O2 release and hence the T252A mutant does not oxidize camphor. This "second pathway" transpires also during H2O2 shunting of the cycle of wild-type P450cam, where the additional hydrogen-bonding with Thr252 prevents H2O2 release, and contributes to a successful Cpd I formation. The present results lead to a revised catalytic cycle of Cytochrome P450cam.

  18. Identification of estrogen receptor dimer selective ligands reveals growth-inhibitory effects on cells that co-express ERα and ERβ.

    Directory of Open Access Journals (Sweden)

    Emily Powell

    Full Text Available Estrogens play essential roles in the progression of mammary and prostatic diseases. The transcriptional effects of estrogens are transduced by two estrogen receptors, ERα and ERβ, which elicit opposing roles in regulating proliferation: ERα is proliferative while ERβ is anti-proliferative. Exogenous expression of ERβ in ERα-positive cancer cell lines inhibits cell proliferation in response to estrogen and reduces xenografted tumor growth in vivo, suggesting that ERβ might oppose ERα's proliferative effects via formation of ERα/β heterodimers. Despite biochemical and cellular evidence of ERα/β heterodimer formation in cells co-expressing both receptors, the biological roles of the ERα/β heterodimer remain to be elucidated. Here we report the identification of two phytoestrogens that selectively activate ERα/β heterodimers at specific concentrations using a cell-based, two-step high throughput small molecule screen for ER transcriptional activity and ER dimer selectivity. Using ERα/β heterodimer-selective ligands at defined concentrations, we demonstrate that ERα/β heterodimers are growth inhibitory in breast and prostate cells which co-express the two ER isoforms. Furthermore, using Automated Quantitative Analysis (AQUA to examine nuclear expression of ERα and ERβ in human breast tissue microarrays, we demonstrate that ERα and ERβ are co-expressed in the same cells in breast tumors. The co-expression of ERα and ERβ in the same cells supports the possibility of ERα/β heterodimer formation at physio- and pathological conditions, further suggesting that targeting ERα/β heterodimers might be a novel therapeutic approach to the treatment of cancers which co-express ERα and ERβ.

  19. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

    DEFF Research Database (Denmark)

    Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik

    2010-01-01

    the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

  20. Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement

    KAUST Repository

    Jiang, Hanlun

    2015-07-16

    Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Our model is based on the results of a combination of Markov State Models (MSMs), large-scale protein-RNA docking, and molecular dynamics (MD) simulations. Using MSMs, we identify an open state of apo human Ago-2 in fast equilibrium with partially open and closed states. Conformations in this open state are distinguished by their largely exposed binding grooves that can geometrically accommodate miRNA as indicated in our protein-RNA docking studies. miRNA may then selectively bind to these open conformations. Upon the initial binding, the complex may perform further structural re-arrangement as shown in our MD simulations and eventually reach the stable binary complex structure. Our results provide novel insights in Ago-miRNA recognition mechanisms and our methodology holds great potential to be widely applied in the studies of other important molecular recognition systems.

  1. Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release

    Science.gov (United States)

    Estacion, Mark; Turner, Jamie; Mis, Malgorzata A.; Wilbrey, Anna; Payne, Elizabeth C.; Gutteridge, Alex; Cox, Peter J.; Doyle, Rachel; Printzenhoff, David; Lin, Zhixin; Marron, Brian E.; West, Christopher; Swain, Nigel A.; Storer, R. Ian; Stupple, Paul A.; Castle, Neil A.; Hounshell, James A.; Rivara, Mirko; Randall, Andrew; Dib-Hajj, Sulayman D.; Krafte, Douglas; Waxman, Stephen G.; Patel, Manoj K.; Butt, Richard P.; Stevens, Edward B.

    2016-01-01

    Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7) is a key molecular determinant of pain sensation. However, defining the Nav1.7 contribution to nociceptive signalling has been hampered by a lack of selective inhibitors. Here we report two potent and selective arylsulfonamide Nav1.7 inhibitors; PF-05198007 and PF-05089771, which we have used to directly interrogate Nav1.7’s role in nociceptor physiology. We report that Nav1.7 is the predominant functional TTX-sensitive Nav in mouse and human nociceptors and contributes to the initiation and the upstroke phase of the nociceptor action potential. Moreover, we confirm a role for Nav1.7 in influencing synaptic transmission in the dorsal horn of the spinal cord as well as peripheral neuropeptide release in the skin. These findings demonstrate multiple contributions of Nav1.7 to nociceptor signalling and shed new light on the relative functional contribution of this channel to peripheral and central noxious signal transmission. PMID:27050761

  2. Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement

    KAUST Repository

    Jiang, Hanlun; Sheong, Fu Kit; Zhu, Lizhe; Gao, Xin; Bernauer, Julie; Huang, Xuhui

    2015-01-01

    Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Our model is based on the results of a combination of Markov State Models (MSMs), large-scale protein-RNA docking, and molecular dynamics (MD) simulations. Using MSMs, we identify an open state of apo human Ago-2 in fast equilibrium with partially open and closed states. Conformations in this open state are distinguished by their largely exposed binding grooves that can geometrically accommodate miRNA as indicated in our protein-RNA docking studies. miRNA may then selectively bind to these open conformations. Upon the initial binding, the complex may perform further structural re-arrangement as shown in our MD simulations and eventually reach the stable binary complex structure. Our results provide novel insights in Ago-miRNA recognition mechanisms and our methodology holds great potential to be widely applied in the studies of other important molecular recognition systems.

  3. Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release.

    Directory of Open Access Journals (Sweden)

    Aristos J Alexandrou

    Full Text Available Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7 is a key molecular determinant of pain sensation. However, defining the Nav1.7 contribution to nociceptive signalling has been hampered by a lack of selective inhibitors. Here we report two potent and selective arylsulfonamide Nav1.7 inhibitors; PF-05198007 and PF-05089771, which we have used to directly interrogate Nav1.7's role in nociceptor physiology. We report that Nav1.7 is the predominant functional TTX-sensitive Nav in mouse and human nociceptors and contributes to the initiation and the upstroke phase of the nociceptor action potential. Moreover, we confirm a role for Nav1.7 in influencing synaptic transmission in the dorsal horn of the spinal cord as well as peripheral neuropeptide release in the skin. These findings demonstrate multiple contributions of Nav1.7 to nociceptor signalling and shed new light on the relative functional contribution of this channel to peripheral and central noxious signal transmission.

  4. Transferability of microsatellite markers located in candidate genes for wood properties between Eucalyptus species

    Directory of Open Access Journals (Sweden)

    Cintia V. Acuña

    2014-12-01

    Full Text Available Aim of study:  To analyze the feasibility of extrapolating conclusions on wood quality genetic control between different Eucalyptus species, particularly from species with better genomic information, to those less characterized. For this purpose, the first step is to analyze the conservation and cross-transferability of microsatellites markers (SSRs located in candidate genes.Area of study: Eucalyptus species implanted in Argentina coming from different Australian origins.Materials and methods: Twelve validated and polymorphic SSRs in candidate genes (SSR-CGs for wood quality in E. globulus were selected for cross species amplification in six species: E. grandis, E. saligna, E. dunnii, E. viminalis, E. camaldulensis and E. tereticornis.Main results: High cross-species transferability (92% to 100% was found for the 12 polymorphic SSRs detected in E. globulus. These markers revealed allelic diversity in nine important candidate genes: cinnamoyl CoA reductase (CCR, cellulose synthase 3 (CesA3, the transcription factor LIM1, homocysteine S-methyltransferase (HMT, shikimate kinase (SK, xyloglucan endotransglycosylase 2 (XTH2, glutathione S-transferase (GST, glutamate decarboxylase (GAD and peroxidase (PER.Research highlights: The markers described are potentially suitable for comparative QTL mapping, molecular marker assisted breeding (MAB and for population genetic studies across different species within the subgenus Symphyomyrtus.Keywords: validation; cross-transferability; SSR; functional markers; eucalypts; Symphyomyrtus.

  5. Candidate container materials for Yucca Mountain waste package designs

    International Nuclear Information System (INIS)

    McCright, R.D.; Halsey, W.G.; Gdowski, G.E.; Clarke, W.L.

    1991-09-01

    Materials considered as candidates for fabricating nuclear waste containers are reviewed in the context of the Conceptual Design phase of a potential repository located at Yucca Mountain. A selection criteria has been written for evaluation of candidate materials for the next phase -- Advanced Conceptual Design. The selection criteria is based on the conceptual design of a thin-walled container fabricated from a single metal or alloy; the criteria consider the performance requirements on the container and the service environment in which the containers will be emplaced. A long list of candidate materials is evaluated against the criteria, and a short list of materials is proposed for advanced characterization in the next design phase

  6. Incorporating in situ habitat patchiness in site selection models reveals that site fidelity is not always a consequence of animal choice.

    Science.gov (United States)

    Martinez, Aline S; Queiroz, Eduardo V; Bryson, Mitch; Byrne, Maria; Coleman, Ross A

    2017-07-01

    Understanding site fidelity is important in animal ecology, but evidence is lacking that this behaviour is due to an animal choosing a specific location. To discern site selection behaviour, it is necessary to consider the spatial distribution of habitats that animals can occupy within a landscape. Tracking animals and defining clear habitat boundaries, however, is often difficult. We use in situ habitat distribution data and animal movement simulations to investigate behavioural choice in site fidelity patterns. We resolved the difficulty of gathering data by working with intertidal rock pool systems, which are of manageable size and where boundaries are easy to define. Movements of the intertidal starfish Parvulastra exigua were quantified to test the hypotheses that (1) this species displays fidelity to a particular rock pool and that (2) rock pool fidelity is due to site selection behaviour. Observed patterns of individuals (n = 10 starfish) returning to a previously occupied rock pool (n = 5 pools per location) were tested against an expected null distribution generated through simulations of random movements within their natural patchy environment. Starfish exhibited site selection behaviour at only one location even though site fidelity was high (av. 7·4 starfish out of 10 found in test pools) in two of the three locations. The random chance of a starfish returning to a pool increased 67% for each metre further a rock pool was from the original pool, and 120% for each square metre increase in surface area of an original pool. The decision of returning to an original rock pool was influenced by food availability. When microalgal cover was >60%, there was a c. 50% chance of animals staying faithful to that pool. Our results show the importance to consider spatial distribution of habitats in understanding patterns of animal movement associated with animal choices and site fidelity. Returning to a particular place does not necessarily mean that an animal

  7. Assessment of Educational Neuromyths among Teachers and Teacher Candidates

    Science.gov (United States)

    Canbulat, Tuncay; Kiriktas, Halit

    2017-01-01

    The aim of study is to determine the neuromyth level of teachers and pre-teachers and reveal if there is significant difference in terms of some variables (gender, class, etc.). Research was designed in survey model. The research sample was formed with 241 teachers and 511 teacher candidates. In the collection of data, "Educational neuromyths…

  8. Evaluation of Candidate Teachers Related to the Weblog Writing Process

    Science.gov (United States)

    Çelik, Tugba; Demirgünes, Sercan

    2016-01-01

    Weblogs offer a new writing and reading environment. Most people in the education process may improve their writing skills and achieve new perspectives related to writing via weblogs. In this study the changes that weblog writing process created in undergraduates'/candidate teachers' minds regarding writing are revealed. The weblog writing process…

  9. Transiently expressed pattern during myogenesis and candidate ...

    Indian Academy of Sciences (India)

    The results revealed a high homology between Tmem8C in goose and other animals (indicated by sequence ..... an indicator of selective pressure acting on a protein-coding gene. ... boxes were also found in positions 83–88 and 144–149 in our .... The luciferase activity responses for siRNA .... Blood 115, 1416–1424.

  10. Receptor-Targeted Nipah Virus Glycoproteins Improve Cell-Type Selective Gene Delivery and Reveal a Preference for Membrane-Proximal Cell Attachment.

    Directory of Open Access Journals (Sweden)

    Ruben R Bender

    2016-06-01

    Full Text Available Receptor-targeted lentiviral vectors (LVs can be an effective tool for selective transfer of genes into distinct cell types of choice. Moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. Here we show that LVs pseudotyped with receptor-targeted Nipah virus (NiV glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell membrane (less than 100 Å distance. Then, they were flexible in receptor usage as demonstrated by successful targeting of EpCAM, CD20, and CD8, and as selective as LVs pseudotyped with receptor-targeted measles virus (MV glycoproteins, the current standard for cell-type specific gene delivery. Remarkably, NiV-LVs could be produced at up to two orders of magnitude higher titers compared to their MV-based counterparts and were at least 10,000-fold less effectively neutralized than MV glycoprotein pseudotyped LVs by pooled human intravenous immunoglobulin. An important finding for NiV-LVs targeted to Her2/neu was an about 100-fold higher gene transfer activity when particles were targeted to membrane-proximal regions as compared to particles binding to a more membrane-distal epitope. Likewise, the low gene transfer activity mediated by NiV-LV particles bound to the membrane distal domains of CD117 or the glutamate receptor subunit 4 (GluA4 was substantially enhanced by reducing receptor size to below 100 Å. Overall, the data suggest that the NiV glycoproteins are optimally suited for cell-type specific gene delivery with LVs and, in addition, for the first time define which parts of a cell surface protein should be targeted to achieve optimal gene transfer rates with receptor-targeted LVs.

  11. Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients.

    Science.gov (United States)

    Llewellyn, Martin S; Messenger, Louisa A; Luquetti, Alejandro O; Garcia, Lineth; Torrico, Faustino; Tavares, Suelene B N; Cheaib, Bachar; Derome, Nicolas; Delepine, Marc; Baulard, Céline; Deleuze, Jean-Francois; Sauer, Sascha; Miles, Michael A

    2015-04-01

    Chagas disease results from infection with the diploid protozoan parasite Trypanosoma cruzi. T. cruzi is highly genetically diverse, and multiclonal infections in individual hosts are common, but little studied. In this study, we explore T. cruzi infection multiclonality in the context of age, sex and clinical profile among a cohort of chronic patients, as well as paired congenital cases from Cochabamba, Bolivia and Goias, Brazil using amplicon deep sequencing technology. A 450bp fragment of the trypomastigote TcGP63I surface protease gene was amplified and sequenced across 70 chronic and 22 congenital cases on the Illumina MiSeq platform. In addition, a second, mitochondrial target--ND5--was sequenced across the same cohort of cases. Several million reads were generated, and sequencing read depths were normalized within patient cohorts (Goias chronic, n = 43, Goias congenital n = 2, Bolivia chronic, n = 27; Bolivia congenital, n = 20), Among chronic cases, analyses of variance indicated no clear correlation between intra-host sequence diversity and age, sex or symptoms, while principal coordinate analyses showed no clustering by symptoms between patients. Between congenital pairs, we found evidence for the transmission of multiple sequence types from mother to infant, as well as widespread instances of novel genotypes in infants. Finally, non-synonymous to synonymous (dn:ds) nucleotide substitution ratios among sequences of TcGP63Ia and TcGP63Ib subfamilies within each cohort provided powerful evidence of strong diversifying selection at this locus. Our results shed light on the diversity of parasite DTUs within each patient, as well as the extent to which parasite strains pass between mother and foetus in congenital cases. Although we were unable to find any evidence that parasite diversity accumulates with age in our study cohorts, putative diversifying selection within members of the TcGP63I gene family suggests a link between genetic diversity within this gene

  12. Analysis of HLA class II haplotypes in the Cayapa indians of ecuador: A novel DRBI allele reveals evidence for convergent evolution and balancing selection at position 86

    Energy Technology Data Exchange (ETDEWEB)

    Titus-Trachtenberg, E.A.; Erlich, H. (Roche Molecular Systems, Alameda, CA (United States)); Rickards, O.; De Stefano, G.F. (Universita di Roma, Rome (Italy))

    1994-07-01

    PCR amplification, oligonucleotide probe typing, and sequencing were used to analyze the HLA class II loci (DRB1, DQA1, DAB1, and DPB1) of an isolated South Amerindian tribe. Here the authors report HLA class II variation, including the identification of a new DRB1 allele, several novel DR/DQ haplotypes, and an unusual distribution of DPB1 alleles, among the Cayapa Indians (N=100) of Ecuador. A general reduction of HLA class II allelic variation in the Cayapa is consistent with a population bottleneck during the colonization of the Americas. The new Cayapa DRB1 allele, DRB1[sup *]08042, which arose by a G[yields]T point mutation in the parental DRB1[sup *]0802, contains a novel Val codon (GTT) at position 86. The generation of DRB1[sup *]08042 (Val-86) from DRB1[sup *]0802 (Gly-86) in the Cayapa, by a different mechanism than the (GT[yields]TG) change in the creation of DRB1[sub *]08041 (Val-86) from DRB1[sup *]0802 in Africa, implicates selection in the convergent evolution of position 86 DR[beta] variants. The DRB1[sup *]08042 allele has not been found in >1,800 Amerindian haplotypes and thus presumably arose after the Cayapa separated from other South American Amerindians. Selection pressure for increased haplotype diversity can be inferred in the generation and maintenance of three new DRB1[sup *]08042 haplotypes and several novel DR/DQ haplotypes in this population. The DPB1 allelic distribution in the Cayapa is also extraordinary, with two alleles, DPB1[sup *]1401, a very rare allele in North American Amerindian populations, and DPB1[sup *]0402, the most common Amerindian DPB1 allele, constituting 89% of the Cayapa DPB1. These data are consistent with the postulated rapid rate of evolution as noted for the class I HLA-B locus of other South American Indians. 34 refs., 2 figs., 2 tabs.

  13. Adenoviral vectors for highly selective gene expression in central serotonergic neurons reveal quantal characteristics of serotonin release in the rat brain

    Directory of Open Access Journals (Sweden)

    Teschemacher Anja G

    2009-03-01

    Full Text Available Abstract Background 5-hydroxytryptamine (5 HT, serotonin is one of the key neuromodulators in mammalian brain, but many fundamental properties of serotonergic neurones and 5 HT release remain unknown. The objective of this study was to generate an adenoviral vector system for selective targeting of serotonergic neurones and apply it to study quantal characteristics of 5 HT release in the rat brain. Results We have generated adenoviral vectors which incorporate a 3.6 kb fragment of the rat tryptophan hydroxylase-2 (TPH-2 gene which selectively (97% co-localisation with TPH-2 target raphe serotonergic neurones. In order to enhance the level of expression a two-step transcriptional amplification strategy was employed. This allowed direct visualization of serotonergic neurones by EGFP fluorescence. Using these vectors we have performed initial characterization of EGFP-expressing serotonergic neurones in rat organotypic brain slice cultures. Fluorescent serotonergic neurones were identified and studied using patch clamp and confocal Ca2+ imaging and had features consistent with those previously reported using post-hoc identification approaches. Fine processes of serotonergic neurones could also be visualized in un-fixed tissue and morphometric analysis suggested two putative types of axonal varicosities. We used micro-amperometry to analyse the quantal characteristics of 5 HT release and found that central 5 HT exocytosis occurs predominantly in quanta of ~28000 molecules from varicosities and ~34000 molecules from cell bodies. In addition, in somata, we observed a minority of large release events discharging on average ~800000 molecules. Conclusion For the first time quantal release of 5 HT from somato-dendritic compartments and axonal varicosities in mammalian brain has been demonstrated directly and characterised. Release from somato-dendritic and axonal compartments might have different physiological functions. Novel vectors generated in this

  14. Candidate genes in panic disorder

    DEFF Research Database (Denmark)

    Howe, A. S.; Buttenschön, Henriette N; Bani-Fatemi, A.

    2016-01-01

    The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered...... association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed......-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed...

  15. Elemental abundances of solar sibling candidates

    International Nuclear Information System (INIS)

    Ramírez, I.; Lambert, D. L.; Endl, M.; Cochran, W. D.; MacQueen, P. J.; Bajkova, A. T.; Bobylev, V. V.; Roederer, I. U.; Wittenmyer, R. A.

    2014-01-01

    Dynamical information along with survey data on metallicity and in some cases age have been used recently by some authors to search for candidates of stars that were born in the cluster where the Sun formed. We have acquired high-resolution, high signal-to-noise ratio spectra for 30 of these objects to determine, using detailed elemental abundance analysis, if they could be true solar siblings. Only two of the candidates are found to have solar chemical composition. Updated modeling of the stars' past orbits in a realistic Galactic potential reveals that one of them, HD 162826, satisfies both chemical and dynamical conditions for being a sibling of the Sun. Measurements of rare-element abundances for this star further confirm its solar composition, with the only possible exception of Sm. Analysis of long-term high-precision radial velocity data rules out the presence of hot Jupiters and confirms that this star is not in a binary system. We find that chemical tagging does not necessarily benefit from studying as many elements as possible but instead from identifying and carefully measuring the abundances of those elements that show large star-to-star scatter at a given metallicity. Future searches employing data products from ongoing massive astrometric and spectroscopic surveys can be optimized by acknowledging this fact.

  16. [Identification of candidate genes and expression profiles, as doping biomarkers].

    Science.gov (United States)

    Paparini, A; Impagnatiello, F; Pistilli, A; Rinaldi, M; Gianfranceschi, G; Signori, E; Stabile, A M; Fazio, V; Rende, M; Romano Spica, V

    2007-01-01

    Administration of prohibited substances to enhance athletic performance represents an emerging medical, social, ethical and legal issue. Traditional controls are based on direct detection of substances or their catabolites. However out-of-competition doping may not be easily revealed by standard analytical methods. Alternative indirect control strategies are based on the evaluation of mid- and long-term effects of doping in tissues. Drug-induced long-lasting changes of gene expression may be taken as effective indicators of doping exposure. To validate this approach, we used real-time PCR to monitor the expression pattern of selected genes in human haematopoietic cells exposed to nandrolone, insulin-like growth factor I (IGF-I) or growth hormone (GH). Some candidate genes were found significantly and consistently modulated by treatments. Nandrolone up-regulated AR, ESR2 and PGR in K562 cells, and SRD5A1, PPARA and JAK2 in Jurkat cells; IGF-I up-regulated EPOR and PGR in HL60 cells, and SRD5A1 in Jurkat; GH up-regulated SRD5A1 and GHR in K562. GATA1 expression was down-regulated in IGF-1-treated HL60, ESR2 was down-regulated in nandrolone-treated Jurkat, and AR and PGR were down-regulated in GH-treated Jurkat. This pilot study shows the potential of molecular biology-based strategies in anti-doping controls.

  17. Conflict and Consensus in Teacher Candidates' Discussion of Ethnic Autobiography.

    Science.gov (United States)

    Florio-Ruane, Susan; deTar, Julie

    A Future Teachers' Autobiography Club discussion group/research project invited six elementary teacher candidates to read, write about, and discuss ethnic autobiography in order to foster and investigate the potential of peer discussion in teacher learning. Using a selected list of six autobiographies, the researcher hosted monthly dinner…

  18. THE 3 MU-M SPECTRA OF CANDIDATE CARBON STARS

    NARCIS (Netherlands)

    GROENEWEGEN, MAT; DEJONG, T; GEBALLE, TR

    We have searched for the 3.1 mum absorption feature, a well-known characteristic of optical carbon stars, in a sample of sixteen candidate carbon stars, most of which have very red colors and some of which have no optical counterparts. The sample was selected on the basis of similarity of LRS

  19. Candidate R&D Thrusts for the Software Technology Initiative.

    Science.gov (United States)

    1981-05-01

    Seen as the Result, Not the Cause of Per- formance Problems." Data Management vol. 19, no. 4 (April, 1981), p. 22. McLaughlin, R. A.. "That Old Bugaboo ...magnitude of the synergistic effect. The decision on what set of candidates to select resembles an investment portfolio decision, but has interdependencies

  20. Disease-linked mutations in factor H reveal pivotal role of cofactor activity in self-surface-selective regulation of complement activation.

    Science.gov (United States)

    Kerr, Heather; Wong, Edwin; Makou, Elisavet; Yang, Yi; Marchbank, Kevin; Kavanagh, David; Richards, Anna; Herbert, Andrew P; Barlow, Paul N

    2017-08-11

    Spontaneous activation enables the complement system to respond very rapidly to diverse threats. This activation is efficiently suppressed by complement factor H (CFH) on self-surfaces but not on foreign surfaces. The surface selectivity of CFH, a soluble protein containing 20 complement-control protein modules (CCPs 1-20), may be compromised by disease-linked mutations. However, which of the several functions of CFH drives this self-surface selectivity remains unknown. To address this, we expressed human CFH mutants in Pichia pastoris We found that recombinant I62-CFH (protective against age-related macular degeneration) and V62-CFH functioned equivalently, matching or outperforming plasma-derived CFH, whereas R53H-CFH, linked to atypical hemolytic uremic syndrome (aHUS), was defective in C3bBb decay-accelerating activity (DAA) and factor I cofactor activity (CA). The aHUS-linked CCP 19 mutant D1119G-CFH had virtually no CA on (self-like) sheep erythrocytes ( E S ) but retained DAA. The aHUS-linked CCP 20 mutant S1191L/V1197A-CFH (LA-CFH) had dramatically reduced CA on E S but was less compromised in DAA. D1119G-CFH and LA-CFH both performed poorly at preventing complement-mediated hemolysis of E S PspCN, a CFH-binding Streptococcus pneumoniae protein domain, binds CFH tightly and increases accessibility of CCPs 19 and 20. PspCN did not improve the DAA of any CFH variant on E S Conversely, PspCN boosted the CA, on E S , of I62-CFH, R53H-CFH, and LA-CFH and also enhanced hemolysis protection by I62-CFH and LA-CFH. We conclude that CCPs 19 and 20 are critical for efficient CA on self-surfaces but less important for DAA. Exposing CCPs 19 and 20 with PspCN and thus enhancing CA on self-surfaces may reverse deficiencies of some CFH variants. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. An Evolutionary/Biochemical Connection Between Promoter- and Primer-Dependent Polymerases Revealed by Selective Evolution of Ligands by Exponential Enrichment (SELEX).

    Science.gov (United States)

    Fenstermacher, Katherine J; Achuthan, Vasudevan; Schneider, Thomas D; DeStefano, Jeffrey J

    2018-01-16

    DNA polymerases (DNAPs) recognize 3' recessed termini on duplex DNA and carry out nucleotide catalysis. Unlike promoter-specific RNA polymerases (RNAPs), no sequence specificity is required for binding or initiation of catalysis. Despite this, previous results indicate that viral reverse transcriptases bind much more tightly to DNA primers that mimic the polypurine tract. In the current report, primer sequences that bind with high affinity to Taq and Klenow polymerases were identified using a modified Selective Evolution of Ligands by Exponential Enrichment (SELEX) approach. Two Taq -specific primers that bound ∼10 (Taq1) and over 100 (Taq2) times more stably than controls to Taq were identified. Taq1 contained 8 nucleotides (5' -CACTAAAG-3') that matched the phage T3 RNAP "core" promoter. Both primers dramatically outcompeted primers with similar binding thermodynamics in PCR reactions. Similarly, exonuclease minus Klenow polymerase also selected a high affinity primer that contained a related core promoter sequence from phage T7 RNAP (5' -ACTATAG-3'). For both Taq and Klenow, even small modifications to the sequence resulted in large losses in binding affinity suggesting that binding was highly sequence-specific. The results are discussed in the context of possible effects on multi-primer (multiplex) PCR assays, molecular information theory, and the evolution of RNAPs and DNAPs. Importance This work further demonstrates that primer-dependent DNA polymerases can have strong sequence biases leading to dramatically tighter binding to specific sequences. These may be related to biological function, or be a consequences of the structural architecture of the enzyme. New sequence specificity for Taq and Klenow polymerases were uncovered and among them were sequences that contained the core promoter elements from T3 and T7 phage RNA polymerase promoters. This suggests the intriguing possibility that phage RNA polymerases exploited intrinsic binding affinities of

  2. The Role of Bioacoustic Signals in Koala Sexual Selection: Insights from Seasonal Patterns of Associations Revealed with GPS-Proximity Units.

    Directory of Open Access Journals (Sweden)

    William Ellis

    Full Text Available Despite being a charismatic and well-known species, the social system of the koala (Phascolarctos cinereus--the only extant member of the family Phascolarctidae is poorly known and much of the koala's sociality and mating behaviors remain un-quantified. We evaluated these using proximity logging-GPS enabled tracking collars on wild koalas and discuss their implications for the mating system of this species. The frequency and duration of male-female encounters increased during the breeding season, with male-male encounters quite uncommon, suggesting little direct mating competition. By comparison, female-female interactions were very common across both seasons. Body mass of males was not correlated with their interactions with females during the breeding season, although male size is associated with a variety of acoustic parameters indicating individuality. We hypothesise that vocal advertising reduces the likelihood of male-male encounters in the breeding season while increasing the rate of male-female encounters. We suggest that male mating-season bellows function to reduce physical confrontations with other males allowing them to space themselves apart, while, at the same time, attracting females. We conclude that indirect male-male competition, female mate choice, and possibly female competition, mediate sexual selection in koalas.

  3. The Role of Bioacoustic Signals in Koala Sexual Selection: Insights from Seasonal Patterns of Associations Revealed with GPS-Proximity Units

    Science.gov (United States)

    Whipple, Bill; Barth, Ben; Johnston, Stephen; Seddon, Jenny; Melzer, Alistair; Higgins, Damien

    2015-01-01

    Despite being a charismatic and well-known species, the social system of the koala (Phascolarctos cinereus—the only extant member of the family Phascolarctidae) is poorly known and much of the koala’s sociality and mating behaviors remain un-quantified. We evaluated these using proximity logging-GPS enabled tracking collars on wild koalas and discuss their implications for the mating system of this species. The frequency and duration of male-female encounters increased during the breeding season, with male-male encounters quite uncommon, suggesting little direct mating competition. By comparison, female-female interactions were very common across both seasons. Body mass of males was not correlated with their interactions with females during the breeding season, although male size is associated with a variety of acoustic parameters indicating individuality. We hypothesise that vocal advertising reduces the likelihood of male-male encounters in the breeding season while increasing the rate of male-female encounters. We suggest that male mating-season bellows function to reduce physical confrontations with other males allowing them to space themselves apart, while, at the same time, attracting females. We conclude that indirect male-male competition, female mate choice, and possibly female competition, mediate sexual selection in koalas. PMID:26154295

  4. Enzymatic synthesis of RNAs capped with nucleotide analogues reveals the molecular basis for substrate selectivity of RNA capping enzyme: impacts on RNA metabolism.

    Directory of Open Access Journals (Sweden)

    Moheshwarnath Issur

    Full Text Available RNA cap binding proteins have evolved to specifically bind to the N7-methyl guanosine cap structure found at the 5' ends of eukaryotic mRNAs. The specificity of RNA capping enzymes towards GTP for the synthesis of this structure is therefore crucial for mRNA metabolism. The fact that ribavirin triphosphate was described as a substrate of a viral RNA capping enzyme, raised the possibility that RNAs capped with nucleotide analogues could be generated in cellulo. Owing to the fact that this prospect potentially has wide pharmacological implications, we decided to investigate whether the active site of the model Paramecium bursaria Chlorella virus-1 RNA capping enzyme was flexible enough to accommodate various purine analogues. Using this approach, we identified several key structural determinants at each step of the RNA capping reaction and generated RNAs harboring various different cap analogues. Moreover, we monitored the binding affinity of these novel capped RNAs to the eIF4E protein and evaluated their translational properties in cellulo. Overall, this study establishes a molecular rationale for the specific selection of GTP over other NTPs by RNA capping enzyme It also demonstrates that RNAs can be enzymatically capped with certain purine nucleotide analogs, and it also describes the impacts of modified RNA caps on specific steps involved in mRNA metabolism. For instance, our results indicate that the N7-methyl group of the classical N7-methyl guanosine cap is not always indispensable for binding to eIF4E and subsequently for translation when compensatory modifications are present on the capped residue. Overall, these findings have important implications for our understanding of the molecular determinants involved in both RNA capping and RNA metabolism.

  5. Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels.

    Science.gov (United States)

    Moran, Yehu; Kahn, Roy; Cohen, Lior; Gur, Maya; Karbat, Izhar; Gordon, Dalia; Gurevitz, Michael

    2007-08-15

    Av3 is a short peptide toxin from the sea anemone Anemonia viridis shown to be active on crustaceans and inactive on mammals. It inhibits inactivation of Na(v)s (voltage-gated Na+ channels) like the structurally dissimilar scorpion alpha-toxins and type I sea anemone toxins that bind to receptor site-3. To examine the potency and mode of interaction of Av3 with insect Na(v)s, we established a system for its expression, mutagenized it throughout, and analysed it in toxicity, binding and electrophysiological assays. The recombinant Av3 was found to be highly toxic to blowfly larvae (ED50=2.65+/-0.46 pmol/100 mg), to compete well with the site-3 toxin LqhalphaIT (from the scorpion Leiurus quinquestriatus) on binding to cockroach neuronal membranes (K(i)=21.4+/-7.1 nM), and to inhibit the inactivation of Drosophila melanogaster channel, DmNa(v)1, but not that of mammalian Na(v)s expressed in Xenopus oocytes. Moreover, like other site-3 toxins, the activity of Av3 was synergically enhanced by ligands of receptor site-4 (e.g. scorpion beta-toxins). The bioactive surface of Av3 was found to consist mainly of aromatic residues and did not resemble any of the bioactive surfaces of other site-3 toxins. These analyses have portrayed a toxin that might interact with receptor site-3 in a different fashion compared with other ligands of this site. This assumption was corroborated by a D1701R mutation in DmNa(v)1, which has been shown to abolish the activity of all other site-3 ligands, except Av3. All in all, the present study provides further evidence for the heterogeneity of receptor site-3, and raises Av3 as a unique model for design of selective anti-insect compounds.

  6. Thiopurine treatment in patients with Crohn's disease leads to a selective reduction of an effector cytotoxic gene expression signature revealed by whole-genome expression profiling.

    Science.gov (United States)

    Bouma, G; Baggen, J M; van Bodegraven, A A; Mulder, C J J; Kraal, G; Zwiers, A; Horrevoets, A J; van der Pouw Kraan, C T M

    2013-07-01

    Crohn's disease (CD) is characterized by chronic inflammation of the gastrointestinal tract, as a result of aberrant activation of the innate immune system through TLR stimulation by bacterial products. The conventional immunosuppressive thiopurine derivatives (azathioprine and mercaptopurine) are used to treat CD. The effects of thiopurines on circulating immune cells and TLR responsiveness are unknown. To obtain a global view of affected gene expression of the immune system in CD patients and the treatment effect of thiopurine derivatives, we performed genome-wide transcriptome analysis on whole blood samples from 20 CD patients in remission, of which 10 patients received thiopurine treatment, compared to 16 healthy controls, before and after TLR4 stimulation with LPS. Several immune abnormalities were observed, including increased baseline interferon activity, while baseline expression of ribosomal genes was reduced. After LPS stimulation, CD patients showed reduced cytokine and chemokine expression. None of these effects were related to treatment. Strikingly, only one highly correlated set of 69 genes was affected by treatment, not influenced by LPS stimulation and consisted of genes reminiscent of effector cytotoxic NK cells. The most reduced cytotoxicity-related gene in CD was the cell surface marker CD160. Concordantly, we could demonstrate an in vivo reduction of circulating CD160(+)CD3(-)CD8(-) cells in CD patients after treatment with thiopurine derivatives in an independent cohort. In conclusion, using genome-wide profiling, we identified a disturbed immune activation status in peripheral blood cells from CD patients and a clear treatment effect of thiopurine derivatives selectively affecting effector cytotoxic CD160-positive cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Live imaging-based model selection reveals periodic regulation of the stochastic G1/S phase transition in vertebrate axial development.

    Directory of Open Access Journals (Sweden)

    Mayu Sugiyama

    2014-12-01

    Full Text Available In multicellular organism development, a stochastic cellular response is observed, even when a population of cells is exposed to the same environmental conditions. Retrieving the spatiotemporal regulatory mode hidden in the heterogeneous cellular behavior is a challenging task. The G1/S transition observed in cell cycle progression is a highly stochastic process. By taking advantage of a fluorescence cell cycle indicator, Fucci technology, we aimed to unveil a hidden regulatory mode of cell cycle progression in developing zebrafish. Fluorescence live imaging of Cecyil, a zebrafish line genetically expressing Fucci, demonstrated that newly formed notochordal cells from the posterior tip of the embryonic mesoderm exhibited the red (G1 fluorescence signal in the developing notochord. Prior to their initial vacuolation, these cells showed a fluorescence color switch from red to green, indicating G1/S transitions. This G1/S transition did not occur in a synchronous manner, but rather exhibited a stochastic process, since a mixed population of red and green cells was always inserted between newly formed red (G1 notochordal cells and vacuolating green cells. We termed this mixed population of notochordal cells, the G1/S transition window. We first performed quantitative analyses of live imaging data and a numerical estimation of the probability of the G1/S transition, which demonstrated the existence of a posteriorly traveling regulatory wave of the G1/S transition window. To obtain a better understanding of this regulatory mode, we constructed a mathematical model and performed a model selection by comparing the results obtained from the models with those from the experimental data. Our analyses demonstrated that the stochastic G1/S transition window in the notochord travels posteriorly in a periodic fashion, with doubled the periodicity of the neighboring paraxial mesoderm segmentation. This approach may have implications for the characterization of

  8. Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

    Science.gov (United States)

    Nijssen, Jik; Frost‐Nylen, Johanna

    2015-01-01

    Neuromuscular junctions are primary pathological targets in the lethal motor neuron diseases spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Synaptic pathology and denervation of target muscle fibers has been reported prior to the appearance of clinical symptoms in mouse models of both diseases, suggesting that neuromuscular junctions are highly vulnerable from the very early stages, and are a key target for therapeutic intervention. Here we examined neuromuscular pathology longitudinally in three clinically relevant muscle groups in mouse models of ALS and SMA in order to assess their relative vulnerabilities. We show for the first time that neuromuscular junctions of the extraocular muscles (responsible for the control of eye movement) were resistant to degeneration in endstage SMA mice, as well as in late symptomatic ALS mice. Tongue muscle neuromuscular junctions were also spared in both animal models. Conversely, neuromuscular junctions of the lumbrical muscles of the hind‐paw were vulnerable in both SMA and ALS, with a loss of neuronal innervation and shrinkage of motor endplates in both diseases. Thus, the pattern of selective vulnerability was conserved across these two models of motor neuron disease. However, the first evidence of neuromuscular pathology occurred at different timepoints of disease progression, with much earlier evidence of presynaptic involvement in ALS, progressing to changes on the postsynaptic side. Conversely, in SMA changes appeared concomitantly at the neuromuscular junction, suggesting that mechanisms of neuromuscular disruption are distinct in these diseases. J. Comp. Neurol. 524:1424–1442, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26502195

  9. Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Agniswamy, Johnson; Louis, John M.; Roche, Julien; Harrison, Robert W.; Weber, Irene T. (GSU); (NIH); (Iowa State)

    2016-12-16

    We report structural analysis of HIV protease variant PRS17 which was rationally selected by machine learning to represent wide classes of highly drug-resistant variants. Crystal structures were solved of PRS17 in the inhibitor-free form and in complex with antiviral inhibitor, darunavir. Despite its 17 mutations, PRS17 has only one mutation (V82S) in the inhibitor/substrate binding cavity, yet exhibits high resistance to all clinical inhibitors. PRS17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with darunavir resistance, but has 10,000-fold weaker binding affinity relative to the wild type PR. Comparable binding affinity of 8000-fold weaker than PR is seen for drug resistant mutant PR20, which bears 3 mutations associated with major resistance to darunavir (I47V, I54L and I84V). Inhibitor-free PRS17 shows an open flap conformation with a curled tip correlating with G48V flap mutation. NMR studies on inactive PRS17 D25N unambiguously confirm that the flaps adopt mainly an open conformation in solution very similar to that in the inhibitor-free crystal structure. In PRS17, the hinge loop cluster of mutations, E35D, M36I and S37D, contributes to the altered flap dynamics by a mechanism similar to that of PR20. An additional K20R mutation anchors an altered conformation of the hinge loop. Flap mutations M46L and G48V in PRS17/DRV complex alter the Phe53 conformation by steric hindrance between the side chains. Unlike the L10F mutation in PR20, L10I in PRS17 does not break the inter-subunit ion pair or diminish the dimer stability, consistent with a very low dimer dissociation constant comparable to that of wild type PR. Distal mutations A71V, L90M and I93L propagate alterations to the catalytic site of PRS17. PRS17 exhibits a molecular mechanism whereby mutations act synergistically to alter the flap dynamics resulting in significantly weaker binding yet maintaining active site contacts with darunavir.

  10. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

    Directory of Open Access Journals (Sweden)

    Nicholas M Morton

    Full Text Available Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L strain.To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney was performed. Known obesity quantitative trait loci (QTL information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity.A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.

  11. Alternative dark matter candidates. Axions

    International Nuclear Information System (INIS)

    Ringwald, Andreas

    2017-01-01

    The axion is arguably one of the best motivated candidates for dark matter. For a decay constant >or similar 10 9 GeV, axions are dominantly produced non-thermally in the early universe and hence are ''cold'', their velocity dispersion being small enough to fit to large scale structure. Moreover, such a large decay constant ensures the stability at cosmological time scales and its behaviour as a collisionless fluid at cosmological length scales. Here, we review the state of the art of axion dark matter predictions and of experimental efforts to search for axion dark matter in laboratory experiments.

  12. Alternative dark matter candidates. Axions

    Energy Technology Data Exchange (ETDEWEB)

    Ringwald, Andreas

    2017-01-15

    The axion is arguably one of the best motivated candidates for dark matter. For a decay constant >or similar 10{sup 9} GeV, axions are dominantly produced non-thermally in the early universe and hence are ''cold'', their velocity dispersion being small enough to fit to large scale structure. Moreover, such a large decay constant ensures the stability at cosmological time scales and its behaviour as a collisionless fluid at cosmological length scales. Here, we review the state of the art of axion dark matter predictions and of experimental efforts to search for axion dark matter in laboratory experiments.

  13. Factors Influencing Candidates' Performance in English Language and Mathematics at West African Senior School Certificate Examination

    Science.gov (United States)

    Alade, O. M.; Kuku, O. O.; Osoba, A.

    2017-01-01

    The study investigated influence of some factors on the performance of selected West African Senior School Certificate Examination (WASSCE) candidates. It also examined the relationship between these factors and candidates' performance. Factors investigated include socio-economic background of the candidates (SEB), study hours (SH), attitude…

  14. Selecting and Hiring Psychologically Fit Probation Officers: A Focused Examination of the PEPQ / PSR Plus

    Directory of Open Access Journals (Sweden)

    Don Scott Herrmann

    2014-06-01

    Full Text Available Selecting and hiring the most psychologically fit probation officers is of utmost importance to the judiciary, court administration and the public good.  This study examined the predictive validity of the PsychEval Personality Questionnaire / Protective Service Report Plus (PEPQ / PSR Plus in its ability to predict job performance in a combined cohort of preemployment and incumbent probation officer candidates.  Analyses revealed a statistically significant ability to predict performance problems, demonstrating that the PEPQ / PRS Plus is a valid and clinically useful psychological screening tool for the assessment and selection of probation officer candidates.

  15. Selecting candidate predictor variables for the modelling of post ...

    African Journals Online (AJOL)

    Objectives: The objective of this project was to determine the variables most likely to be associated with post- .... (as defined subjectively by the research team) in global .... ed on their lack of knowledge of wealth scoring tools. ... HIV serology.

  16. A review of selected candidate endophenotypes for depression.

    Science.gov (United States)

    Goldstein, Brandon L; Klein, Daniel N

    2014-07-01

    Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. 11 CFR 100.154 - Candidate debates.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.154 Section 100.154 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Expenditures § 100.154 Candidate debates. Funds used to defray costs incurred in staging candidate debates in...

  18. 11 CFR 100.92 - Candidate debates.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.92 Section 100.92 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Contributions § 100.92 Candidate debates. Funds provided to defray costs incurred in staging candidate debates...

  19. Factors underlying the psychological and behavioral characteristics of Office of Strategic Services candidates: the assessment of men data revisited.

    Science.gov (United States)

    Lenzenweger, Mark F

    2015-01-01

    During World War II, the Office of Strategic Services (OSS), the forerunner of the Central Intelligence Agency, sought the assistance of clinical psychologists and psychiatrists to establish an assessment program for evaluating candidates for the OSS. The assessment team developed a novel and rigorous program to evaluate OSS candidates. It is described in Assessment of Men: Selection of Personnel for the Office of Strategic Services (OSS Assessment Staff, 1948). This study examines the sole remaining multivariate data matrix that includes all final ratings for a group of candidates (n = 133) assessed near the end of the assessment program. It applies the modern statistical methods of both exploratory and confirmatory factor analysis to this rich and highly unique data set. An exploratory factor analysis solution suggested 3 factors underlie the OSS assessment staff ratings. Confirmatory factor analysis results of multiple plausible substantive models reveal that a 3-factor model provides the best fit to these data. The 3 factors are emotional/interpersonal factors (social relations, emotional stability, security), intelligence processing (effective IQ, propaganda skills, observing and reporting), and agency/surgency (motivation, energy and initiative, leadership, physical ability). These factors are discussed in terms of their potential utility for personnel selection within the intelligence community.

  20. Revealing roads

    DEFF Research Database (Denmark)

    Pinder, David

    2018-01-01

    against the motorway’s grain. Based on moving with selected walkers who conduct ‘deliberately slow travelling’, and tracing the narratives of time-based civic art projects, the chapter explores the spectral dimensions of motorways in the UK. The chapter ends by positioning their streams of traffic as much...

  1. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  2. Perceived Social Support and Assertiveness as a Predictor of Candidates Psychological Counselors' Psychological Well-Being

    Science.gov (United States)

    Ates, Bünyamin

    2016-01-01

    In this research, to what extent the variables of perceived social support (family, friends and special people) and assertiveness predicted the psychological well-being levels of candidate psychological counselors. The research group of this study included totally randomly selected 308 candidate psychological counselors including 174 females…

  3. 14 CFR 1214.1104 - Evaluation and ranking of highly qualified candidates.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Evaluation and ranking of highly qualified candidates. 1214.1104 Section 1214.1104 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION... ranking of highly qualified candidates. (a) A selection board consisting of discipline experts, and such...

  4. [Obesity studies in candidate genes].

    Science.gov (United States)

    Ochoa, María del Carmen; Martí, Amelia; Martínez, J Alfredo

    2004-04-17

    There are more than 430 chromosomic regions with gene variants involved in body weight regulation and obesity development. Polymorphisms in genes related to energy expenditure--uncoupling proteins (UCPs), related to adipogenesis and insulin resistance--hormone-sensitive lipase (HLS), peroxisome proliferator-activated receptor gamma (PPAR gamma), beta adrenergic receptors (ADRB2,3), and alfa tumor necrosis factor (TNF-alpha), and related to food intake--ghrelin (GHRL)--appear to be associated with obesity phenotypes. Obesity risk depends on two factors: a) genetic variants in candidate genes, and b) biographical exposure to environmental risk factors. It is necessary to perform new studies, with appropriate control groups and designs, in order to reach relevant conclusions with regard to gene/environmental (diet, lifestyle) interactions.

  5. Candidate gene approach for parasite resistance in sheep--variation in immune pathway genes and association with fecal egg count.

    Directory of Open Access Journals (Sweden)

    Kathiravan Periasamy

    Full Text Available Sheep chromosome 3 (Oar3 has the largest number of QTLs reported to be significantly associated with resistance to gastro-intestinal nematodes. This study aimed to identify single nucleotide polymorphisms (SNPs within candidate genes located in sheep chromosome 3 as well as genes involved in major immune pathways. A total of 41 SNPs were identified across 38 candidate genes in a panel of unrelated sheep and genotyped in 713 animals belonging to 22 breeds across Asia, Europe and South America. The variations and evolution of immune pathway genes were assessed in sheep populations across these macro-environmental regions that significantly differ in the diversity and load of pathogens. The mean minor allele frequency (MAF did not vary between Asian and European sheep reflecting the absence of ascertainment bias. Phylogenetic analysis revealed two major clusters with most of South Asian, South East Asian and South West Asian breeds clustering together while European and South American sheep breeds clustered together distinctly. Analysis of molecular variance revealed strong phylogeographic structure at loci located in immune pathway genes, unlike microsatellite and genome wide SNP markers. To understand the influence of natural selection processes, SNP loci located in chromosome 3 were utilized to reconstruct haplotypes, the diversity of which showed significant deviations from selective neutrality. Reduced Median network of reconstructed haplotypes showed balancing selection in force at these loci. Preliminary association of SNP genotypes with phenotypes recorded 42 days post challenge revealed significant differences (P<0.05 in fecal egg count, body weight change and packed cell volume at two, four and six SNP loci respectively. In conclusion, the present study reports strong phylogeographic structure and balancing selection operating at SNP loci located within immune pathway genes. Further, SNP loci identified in the study were found to have

  6. Old and Unemployable? How Age-Based Stereotypes Affect Willingness to Hire Job Candidates.

    Science.gov (United States)

    Abrams, Dominic; Swift, Hannah J; Drury, Lisbeth

    2016-03-01

    Across the world, people are required, or want, to work until an increasingly old age. But how might prospective employers view job applicants who have skills and qualities that they associate with older adults? This article draws on social role theory, age stereotypes and research on hiring biases, and reports three studies using age-diverse North American participants. These studies reveal that: (1) positive older age stereotype characteristics are viewed less favorably as criteria for job hire, (2) even when the job role is low-status, a younger stereotype profile tends to be preferred, and (3) an older stereotype profile is only considered hirable when the role is explicitly cast as subordinate to that of a candidate with a younger age profile. Implications for age-positive selection procedures and ways to reduce the impact of implicit age biases are discussed.

  7. Old and Unemployable? How Age‐Based Stereotypes Affect Willingness to Hire Job Candidates

    Science.gov (United States)

    Swift, Hannah J.; Drury, Lisbeth

    2016-01-01

    Across the world, people are required, or want, to work until an increasingly old age. But how might prospective employers view job applicants who have skills and qualities that they associate with older adults? This article draws on social role theory, age stereotypes and research on hiring biases, and reports three studies using age‐diverse North American participants. These studies reveal that: (1) positive older age stereotype characteristics are viewed less favorably as criteria for job hire, (2) even when the job role is low‐status, a younger stereotype profile tends to be preferred, and (3) an older stereotype profile is only considered hirable when the role is explicitly cast as subordinate to that of a candidate with a younger age profile. Implications for age‐positive selection procedures and ways to reduce the impact of implicit age biases are discussed. PMID:27635102

  8. A Lyman Break Galaxy Candidate at z ~ 9

    Science.gov (United States)

    Henry, Alaina L.; Malkan, Matthew A.; Colbert, James W.; Siana, Brian; Teplitz, Harry I.; McCarthy, Patrick

    2008-06-01

    We report the discovery of a z ~ 9 Lyman break galaxy candidate, selected from the NICMOS Parallel Imaging Survey as a J-dropout with J110 - H160 = 1.7. Spitzer/IRAC photometry reveals that the galaxy has a blue H160 - 3.6 μm color and a spectral break between 3.6 and 4.5 μm. We interpret this break as the Balmer break and derive a best-fit photometric redshift of z ~ 9. We use Monte Carlo simulations to test the significance of this photometric redshift, and we show that there is a 96% probability of z >= 7. We estimate that the lower limit to the comoving number density of such galaxies at z ~ 9 is phi > 3.8 × 10-6 Mpc-3. If the high redshift of this galaxy is confirmed, this will indicate that the luminous end of the rest-frame UV luminosity function has not evolved substantially from z ~ 9 to z ~ 3. Still, some small degeneracy remains between this z ~ 9 model and models at z ~ 2-3 deep optical imaging (reaching IAB ~ 29) can rule out the lower z models. This work is based in part on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory (JPL), California Institute of Technology, under a contract with NASA. Support for this work was provided by NASA through an award issued by JPL/Caltech. This work is also based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with proposals 9484, 9865, 10226, and 10899.

  9. Revealing Rembrandt