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Sample records for previously identified candidate

  1. Identifying Patients Who May Be Candidates for a Clinical Trial of Salvage Accelerated Partial Breast Irradiation after Previous Whole Breast Irradiation

    Directory of Open Access Journals (Sweden)

    Linna Li

    2012-01-01

    Full Text Available Background and Objectives. Accelerated partial breast irradiation (APBI has been proposed as an alternative to salvage mastectomy for patients with ipsilateral breast tumor recurrence (IBTR after prior breast conservation. We studied factors that are associated with a more favorable local recurrence profile that could make certain patients eligible for APBI. Methods. Between 1980 and 2005, 157 Stage 0–II breast cancer patients had an IBTR treated by mastectomy. Clinical and pathological features were analyzed to identify factors associated with favorable IBTR defined as unifocal DCIS or T1 ≤ 2 cm, without skin involvement, and >2 year interval from initial treatment. Results. Median followup was 140 months and time to recurrence was 73 months. Clinical stage distribution at recurrence was DCIS in 32 pts (20%, T1 in 90 pts (57%, T2 in 14 pts (9%, T3 in 4 pts (3%, and T4 in 9 pts (6%. IBTR was classified as favorable in 71%. Clinical stage of IBTR predicted for pathologic stage –95% of patients with clinical T1 IBTR had pathologic T1 disease at salvage mastectomy . Conclusions. Clinical stage at presentation strongly correlated with pathologic stage at mastectomy. More than 70% of recurrences were favorable and may be appropriate candidates for salvage APBI trials.

  2. ENU Mutagenesis in Mice Identifies Candidate Genes For Hypogonadism

    Science.gov (United States)

    Weiss, Jeffrey; Hurley, Lisa A.; Harris, Rebecca M.; Finlayson, Courtney; Tong, Minghan; Fisher, Lisa A.; Moran, Jennifer L.; Beier, David R.; Mason, Christopher; Jameson, J. Larry

    2012-01-01

    Genome-wide mutagenesis was performed in mice to identify candidate genes for male infertility, for which the predominant causes remain idiopathic. Mice were mutagenized using N-ethyl-N-nitrosourea (ENU), bred, and screened for phenotypes associated with the male urogenital system. Fifteen heritable lines were isolated and chromosomal loci were assigned using low density genome-wide SNP arrays. Ten of the fifteen lines were pursued further using higher resolution SNP analysis to narrow the candidate gene regions. Exon sequencing of candidate genes identified mutations in mice with cystic kidneys (Bicc1), cryptorchidism (Rxfp2), restricted germ cell deficiency (Plk4), and severe germ cell deficiency (Prdm9). In two other lines with severe hypogonadism candidate sequencing failed to identify mutations, suggesting defects in genes with previously undocumented roles in gonadal function. These genomic intervals were sequenced in their entirety and a candidate mutation was identified in SnrpE in one of the two lines. The line harboring the SnrpE variant retains substantial spermatogenesis despite small testis size, an unusual phenotype. In addition to the reproductive defects, heritable phenotypes were observed in mice with ataxia (Myo5a), tremors (Pmp22), growth retardation (unknown gene), and hydrocephalus (unknown gene). These results demonstrate that the ENU screen is an effective tool for identifying potential causes of male infertility. PMID:22258617

  3. Integrating subpathway analysis to identify candidate agents for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Wang J

    2016-03-01

    Full Text Available Jiye Wang,1 Mi Li,2 Yun Wang,3 Xiaoping Liu4 1The Criminal Science and Technology Department, Zhejiang Police College, Hangzhou, Zhejiang Province, 2Department of Nursing, Shandong College of Traditional Chinese Medicine College, Yantai, Shandong Province, 3Office Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, Shanxi Province, 4Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Shanghai, People’s Republic of China Abstract: Hepatocellular carcinoma (HCC is the second most common cause of cancer-associated death worldwide, characterized by a high invasiveness and resistance to normal anticancer treatments. The need to develop new therapeutic agents for HCC is urgent. Here, we developed a bioinformatics method to identify potential novel drugs for HCC by integrating HCC-related and drug-affected subpathways. By using the RNA-seq data from the TCGA (The Cancer Genome Atlas database, we first identified 1,763 differentially expressed genes between HCC and normal samples. Next, we identified 104 significant HCC-related subpathways. We also identified the subpathways associated with small molecular drugs in the CMap database. Finally, by integrating HCC-related and drug-affected subpathways, we identified 40 novel small molecular drugs capable of targeting these HCC-involved subpathways. In addition to previously reported agents (ie, calmidazolium, our method also identified potentially novel agents for targeting HCC. We experimentally verified that one of these novel agents, prenylamine, induced HCC cell apoptosis using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, an acridine orange/ethidium bromide stain, and electron microscopy. In addition, we found that prenylamine not only affected several classic apoptosis-related proteins, including Bax, Bcl-2, and cytochrome c, but also increased caspase-3 activity. These candidate small molecular drugs

  4. A statistical approach to identify candidate cues for nestmate recognition

    Directory of Open Access Journals (Sweden)

    Jelle Stijn van Zweden

    2014-11-01

    Full Text Available The ability of social insects to discriminate nestmates from non-nestmates is mainly achieved through chemical communication. To ultimately understand this recognition and its decision rules, identification of the recognition cues is essential. Although recognition cues are most likely cuticular hydrocarbons, identifying the exact cues for specific species has remained a daunting task, partly due to the sheer number of odor compounds. Perhaps unsurprisingly, one of the few species where the recognition cues have been identified, Formica exsecta, has only around ten major hydrocarbons on its cuticle. In this study we use previous results of this species to search for nestmate recognition cues in two other species of ants, Camponotus aethiops and Monomorium pharaonis. Employing chemical distances and observed aggression between colonies, we first ask which type of data normalization, centroid, and distance calculation is most diagnostic to discriminate between nestmate recognition cues and other compounds. We find that using a global centroid instead of a colony centroid significantly improves the analysis. One reason may be that this new approach, unlike previous ones, provides a biologically meaningful way to quantify the chemical distances between nestmates, allowing for within-colony variation in recognition cues. Next, we ask which subset of hydrocarbons most likely represents the cues that the ants use for nestmate recognition, which shows less clear results for C. aethiops and M. pharaonis than for F. exsecta, possibly due to less than ideal datasets. Nonetheless, some compound sets performed better than others, showing that this approach can be used to identify candidate compounds to be tested in bio-assays, and eventually crack the sophisticated code that governs nestmate recognition.

  5. 'Omics' approaches in tomato aimed at identifying candidate genes ...

    African Journals Online (AJOL)

    adriana

    2013-12-04

    Dec 4, 2013 ... that provides a virtual workbench for researchers working ... lab, we undertook two different 'omics' approaches to in- .... In our laboratory, an association mapping approach by candidate gene has been undertaken with the aim of identifying among 96 different genotypes new alleles in genes that could.

  6. Novel approaches to identify protective malaria vaccine candidates

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    Wan Ni eChia

    2014-11-01

    Full Text Available Efforts to develop vaccines against malaria have been the focus of substantial research activities for decades. Several categories of candidate vaccines are currently being developed for protection against malaria, based on antigens corresponding to the pre-erythrocytic, blood-stage or sexual stages of the parasite. Long lasting sterile protection from Plasmodium falciparum sporozoite challenge has been observed in human following vaccination with whole parasite formulations, clearly demonstrating that a protective immune response targeting predominantly the pre-erythrocytic stages can develop against malaria. However, most of vaccine candidates currently being investigated, which are mostly subunits vaccines, have not been able to induce substantial (>50% protection thus far. This is due to the fact that the antigens responsible for protection against the different parasite stages are still yet to be known and relevant correlates of protection have remained elusive. For a vaccine to be developed in a timely manner, novel approaches are required. In this article, we review the novel approaches that have been developed to identify the antigens for the development of an effective malaria vaccine.

  7. Identifying candidate driver genes by integrative ovarian cancer genomics data

    Science.gov (United States)

    Lu, Xinguo; Lu, Jibo

    2017-08-01

    Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

  8. Testing of Candidate Icons to Identify Acetaminophen-Containing Medicines.

    Science.gov (United States)

    Shiffman, Saul; Cotton, Helene; Jessurun, Christina; Sembower, Mark A; Pype, Steve; Phillips, Jerry

    2016-01-27

    Adding icons on labels of acetaminophen-containing medicines could help users identify the active ingredient and avoid concomitant use of multiple medicines containing acetaminophen. We evaluated five icons for communication effectiveness. Adults ( n = 300) were randomized to view a prescription container label or over-the-counter labels with either one or two icons. Participants saw two icon candidates, and reported their interpretation; experts judged whether these reflected critical confusions that might cause harm. Participants rated how effectively each icon communicated key messages. Icons based on abbreviations of "acetaminophen" ("Ac", "Ace", "Acm") were rated less confusing and more effective in communicating the active ingredient than icons based on "APAP" or an abstract symbol. Icons did not result in critical confusion when seen on a readable medicine label. Icon implementation on prescription labels was more effective at communicating the warning against concomitant use than implementation on over-the-counter (OTC) labels. Adding an icon to a second location on OTC labels did not consistently enhance this communication, but reduced rated effectiveness of acetaminophen ingredient communication among participants with limited health literacy. The abbreviation-based icons seem most suitable for labeling acetaminophen-containing medications to enable users to identify acetaminophen-containing products.

  9. Testing of Candidate Icons to Identify Acetaminophen-Containing Medicines

    Directory of Open Access Journals (Sweden)

    Saul Shiffman

    2016-01-01

    Full Text Available Adding icons on labels of acetaminophen-containing medicines could help users identify the active ingredient and avoid concomitant use of multiple medicines containing acetaminophen. We evaluated five icons for communication effectiveness. Adults (n = 300 were randomized to view a prescription container label or over-the-counter labels with either one or two icons. Participants saw two icon candidates, and reported their interpretation; experts judged whether these reflected critical confusions that might cause harm. Participants rated how effectively each icon communicated key messages. Icons based on abbreviations of “acetaminophen” (“Ac”, “Ace”, “Acm” were rated less confusing and more effective in communicating the active ingredient than icons based on “APAP” or an abstract symbol. Icons did not result in critical confusion when seen on a readable medicine label. Icon implementation on prescription labels was more effective at communicating the warning against concomitant use than implementation on over-the-counter (OTC labels. Adding an icon to a second location on OTC labels did not consistently enhance this communication, but reduced rated effectiveness of acetaminophen ingredient communication among participants with limited health literacy. The abbreviation-based icons seem most suitable for labeling acetaminophen-containing medications to enable users to identify acetaminophen-containing products.

  10. Identifying Candidate Reprogramming Genes in Mouse Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Gao, Fang; Li, Jingyu; Zhang, Heng; Yang, Xu; An, Tiezhu

    2017-08-01

    Factor-based induced reprogramming approaches have tremendous potential for human regenerative medicine, but the efficiencies of these approaches are still low. In this study, we analyzed the global transcriptional profiles of mouse induced pluripotent stem cells (miPSCs) and mouse embryonic stem cells (mESCs) from seven different labs and present here the first successful clustering according to cell type, not by lab of origin. We identified 2131 different expression genes (DEs) as candidate pluripotency-associated genes by comparing mESCs/miPSCs with somatic cells and 720 DEs between miPSCs and mESCs. Interestingly, there was a significant overlap between the two DE sets. Therefore, we defined the overlap DEs as "consensus DEs" including 313 miPSC-specific genes expressed at a higher level in miPSCs versus mESCs and 184 mESC-specific genes in total and reasoned that these may contribute to the differences in pluripotency between mESCs and miPSCs. A classification of "consensus DEs" according to their different expression levels between somatic cells and mESCs/miPSCs shows that 86% of the miPSC-specific genes are more highly expressed in somatic cells, while 73% of mESC-specific genes are highly expressed in mESCs/miPSCs, indicating that the miPSCs have not efficiently silenced the expression pattern of the somatic cells from which they are derived and failed to completely induce the genes with high expression levels in mESCs. We further revealed a strong correlation between oocyte-enriched factors and insufficiently induced mESC-specific genes and identified 11 hub genes via network analysis. In light of these findings, we postulated that these key hub genes might not only drive somatic cell nuclear transfer (SCNT) reprogramming but also augment the efficiency and quality of miPSC reprogramming.

  11. A statistical approach to identify candidate cues for nestmate recognition

    DEFF Research Database (Denmark)

    van Zweden, Jelle; Pontieri, Luigi; Pedersen, Jes Søe

    2014-01-01

    The ability of social insects to discriminate nestmates (NMs) from non-nestmates(nNMs) is mainly achieved through chemical communication. To ultimately understandthis recognition and its decision rules, identification of the recognition cues is essential.Although recognition cues are most likely...... cuticular hydrocarbons (CHCs), identifying theexact cues for specific species has remained a daunting task, partly due to the sheernumber of odor compounds. Perhaps unsurprisingly, one of the few species wherethe recognition cues have been identified, Formica exsecta, has only around ten majorhydrocarbons...... on its cuticle. In this study we use previous results of this species to searchfor nestmate recognition cues (NMR cues) in two other species of ants, Camponotusaethiops, and Monomorium pharaonis. Employing chemical distances and observedaggression between colonies, we first ask which type of data...

  12. Microsatellite Scan Identifies New Candidate Genes for Susceptibility to Alcoholic Chronic Pancreatitis in Japanese Patients

    Directory of Open Access Journals (Sweden)

    Kei Kitahara

    2008-01-01

    Full Text Available Alcohol abuse is one of the most common risk factor for chronic pancreatitis, but the underlying pathophysiological mechanisms remain unclear. The aim of this study was to identify genes that contribute to susceptibility or resistance for alcoholic chronic pancreatitis by screening the whole genome. Sixty-five patients with alcoholic chronic pancreatitis (63 men and 2 women, mean age 55.2 years and 99 healthy Japanese controls were enrolled in this study. This was an association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. This search revealed 10 candidate susceptibility regions and 5 candidate resistant regions throughout the genome. No specific microsatellite markers were detected in association with previously reported susceptibility genes for chronic pancreatitis, such as PRSS1, PRSS2, CTRC, SPINK1, CFTR, ALDH2, and CYP2E1. Among the statistically significant markers, D15S1007 on chromosome 15q14 showed strong evidence for disease susceptibility (70.8% vs. 35.1%, Pc = 0.0001. Within 500 kb of D15S1007, several genes were candidate genes for susceptibility, including FMN1, DKFZP686C2281, LOC440268, RYR3, and AVEN, This study identified 10 candidate susceptibility and 5 candidate resistant regions that may contain genes involved in ACP pathogenesis.

  13. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  14. CVExplorer: identifying candidate developers by mining and exploring their open source contributions.

    CSIR Research Space (South Africa)

    Greene, GJ

    2016-09-01

    Full Text Available demonstrate the usefulness of CVExplorer by using it to recommend candidates for open positions in two companies. Keywords Identifying candidate developers, Developer skills identication, Mining software repositories ...

  15. Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder.

    Science.gov (United States)

    Zhang, Tianxiao; Hou, Liping; Chen, David T; McMahon, Francis J; Wang, Jen-Chyong; Rice, John P

    2018-03-01

    Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Identifying positive selection candidate loci for high-altitude adaptation in Andean populations.

    Science.gov (United States)

    Bigham, Abigail W; Mao, Xianyun; Mei, Rui; Brutsaert, Tom; Wilson, Megan J; Julian, Colleen Glyde; Parra, Esteban J; Akey, Joshua M; Moore, Lorna G; Shriver, Mark D

    2009-12-01

    High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano. We analysed dense microarray genotype data using four test statistics that detect departures from neutrality. Using a candidate gene, single nucleotide polymorphism-based approach, we identified genes exhibiting preliminary evidence of recent genetic adaptation in this population. These included genes that are part of the hypoxia-inducible transcription factor ( HIF ) pathway, a biochemical pathway involved in oxygen homeostasis, as well as three other genomic regions previously not known to be associated with high-altitude phenotypes. In addition to identifying selection-nominated candidate genes, we also tested whether the HIF pathway shows evidence of natural selection. Our results indicate that the genes of this biochemical pathway as a group show no evidence of having evolved in response to hypoxia in Andeans. Results from particular HIF -targeted genes, however, suggest that genes in this pathway could play a role in Andean adaptation to high altitude, even if the pathway as a whole does not show higher relative rates of evolution. These data suggest a genetic role in high-altitude adaptation and provide a basis for genotype/phenotype association studies that are necessary to confirm the role of putative natural selection candidate genes and gene regions in adaptation to altitude.

  17. Targeted pathologic evaluation of bone marrow donors identifies previously undiagnosed marrow abnormalities.

    Science.gov (United States)

    Tilson, Matthew P; Jones, Richard J; Sexauer, Amy; Griffin, C A; Morsberger, Laura A; Batista, Denise A S; Small, Donald; Burns, Kathleen H; Gocke, Christopher D; Vuica-Ross, Milena; Borowitz, Michael J; Duffield, Amy S

    2013-08-01

    Potential bone marrow donors are screened to ensure the safety of both the donor and recipient. At our institution, potential donors with abnormal peripheral blood cell counts, a personal history of malignancy, or age >60 years are evaluated to ensure that they are viable candidates for donation. Evaluation of the marrow includes morphologic, flow cytometric, and cytogenetic studies. A total of 122 potential donors were screened between the years of 2001 and 2011, encompassing approximately 10% of all donors. Of the screened potential donors, the mean age was 59 years and there were 59 men and 63 women. The donors were screened because of age >60 years (n = 33), anemia (n = 22), cytopenias other than anemia (n = 27), elevated peripheral blood counts without a concurrent cytopenia (n = 20), elevated peripheral blood counts with a concurrent cytopenia (n = 10), history of malignancy (n = 4), abnormal peripheral blood differential (n = 3), prior graft failure (n = 1), history of treatment with chemotherapy (n = 1), and body habitus (n = 1). Marrow abnormalities were detected in 9% (11 of 122) of donors. These donors were screened because of anemia (5 of 22, 23%), age >60 years (2 of 33, 6%), history of malignancy (2 of 4, 50%), elevated peripheral blood counts (1 of 20, 5%), and body habitus (1 of 1, 100%). Abnormalities included plasma cell dyscrasia (n = 3), abnormal marrow cellularity (n = 3), clonal cytogenetic abnormalities (n = 2), low-grade myelodysplastic syndrome (1), a mutated JAK2 V617F allele (n = 1), and monoclonal B cell lymphocytosis (n = 1). Our experience indicates that extended screening of potential donors identifies a significant number of donors with previously undiagnosed marrow abnormalities. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    International Nuclear Information System (INIS)

    Abulí, Anna; Morillas, Juan D; Rigau, Joaquim; Latorre, Mercedes; Fernández-Bañares, Fernando; Peña, Elena; Riestra, Sabino; Payá, Artemio; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Fernández-Rozadilla, Ceres; Carvajal-Carmona, Luis; Villanueva, Cristina M; Moreno, Victor; Piqué, Josep M; Carracedo, Angel; Castells, Antoni; Andreu, Montserrat; Ruiz-Ponte, Clara; Castellví-Bel, Sergi; Alonso-Espinaco, Virginia; Muñoz, Jenifer; Gonzalo, Victoria; Bessa, Xavier; González, Dolors; Clofent, Joan; Cubiella, Joaquin

    2011-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1

  19. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    Directory of Open Access Journals (Sweden)

    Moreno Victor

    2011-08-01

    Full Text Available Abstract Background Colorectal cancer (CRC is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive, rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive, rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant, and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive. In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1

  20. Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism.

    Science.gov (United States)

    Wei, Ai-Hua; Zang, Dong-Jie; Zhang, Zhe; Liu, Xuan-Zhu; He, Xin; Yang, Lin; Wang, Yi; Zhou, Zhi-Yong; Zhang, Ming-Rong; Dai, Lan-Lan; Yang, Xiu-Min; Li, Wei

    2013-07-01

    Oculocutaneous albinism (OCA) is a heterogeneous and autosomal recessive disorder with hypopigmentation in the eye, hair, and skin color. Four genes, TYR, OCA2, TYRP1, and SLC45A2, have been identified as causative genes for nonsyndromic OCA1-4, respectively. The genetic identity of OCA5 locus on 4q24 is unknown. Additional unknown OCA genes may exist as at least 5% of OCA patients have not been characterized during mutational screening in several populations. We used exome sequencing with a family-based recessive mutation model to determine that SLC24A5 is a previously unreported candidate gene for nonsyndromic OCA, which we designate as OCA6. Two deleterious mutations in this patient, c.591G>A and c.1361insT, were identified. We found apparent increase of immature melanosomes and less mature melanosomes in the patient's skin melanocytes. However, no defects in the platelet dense granules were observed, excluding typical Hermansky-Pudlak syndrome (HPS), a well-known syndromic OCA. Moreover, the SLC24A5 protein was reduced in steady-state levels in mouse HPS mutants with deficiencies in BLOC-1 and BLOC-2. Our results suggest that SLC24A5 is a previously unreported nonsyndromic OCA candidate gene and that the SLC24A5 transporter is transported into mature melanosomes by HPS protein complexes.

  1. Transcriptomic analysis using olive varieties and breeding progenies identify candidate genes involved in plant architecture

    Directory of Open Access Journals (Sweden)

    Juan José eGonzález Plaza

    2016-03-01

    Full Text Available Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2,252 differentially expressed genes associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  2. Transcriptomic Analysis Using Olive Varieties and Breeding Progenies Identifies Candidate Genes Involved in Plant Architecture.

    Science.gov (United States)

    González-Plaza, Juan J; Ortiz-Martín, Inmaculada; Muñoz-Mérida, Antonio; García-López, Carmen; Sánchez-Sevilla, José F; Luque, Francisco; Trelles, Oswaldo; Bejarano, Eduardo R; De La Rosa, Raúl; Valpuesta, Victoriano; Beuzón, Carmen R

    2016-01-01

    Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2252 differentially expressed genes (DEGs) associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  3. M-giant star candidates identified in LAMOST DR 1

    International Nuclear Information System (INIS)

    Zhong, Jing; Li, Jing; Chen, Li; Hou, Jin-Liang; Lépine, Sébastien; Yang, Ming; Li, Guang-Wei; Zhang, Yong; Hou, Yong-Hui

    2015-01-01

    We perform a discrimination procedure with the spectral index diagram of TiO5 and CaH2+CaH3 to separate M giants from M dwarfs. Using the M giant spectra identified from LAMOST DR1 with high signal-to-noise ratio, we have successfully assembled a set of M giant templates, which show more reliable spectral features. Combining with the M dwarf/subdwarf templates in Zhong et al., we present an extended library of M-type templates which includes not only M dwarfs with a well-defined temperature and metallicity grid but also M giants with subtypes from M0 to M6. Then, the template-fitting algorithm is used to automatically identify and classify M giant stars from LAMOST DR1. The resulting catalog of M giant stars is cross-matched with 2MASS JHK s and WISE W1/W2 infrared photometry. In addition, we calculated the heliocentric radial velocity of all M giant stars by using the cross-correlation method with the template spectrum in a zero-velocity rest frame. Using the relationship between the absolute infrared magnitude M J and our classified spectroscopic subtype, we derived the spectroscopic distance of M giants with uncertainties of about 40%. A catalog of 8639 M giants is provided. As an additional result of this analysis, we also present a catalog of 101 690 M dwarfs/subdwarfs which are processed by our classification pipeline. (paper)

  4. Identifying Candidate Chemical-Disease Linkages (Environmental and Epigenetic Determinants of IBD)

    Science.gov (United States)

    Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This h...

  5. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Odir A. Dellagostin

    2017-01-01

    Full Text Available Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis.

  6. Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.

    Science.gov (United States)

    Laffin, Jennifer J S; Raca, Gordana; Jackson, Craig A; Strand, Edythe A; Jakielski, Kathy J; Shriberg, Lawrence D

    2012-11-01

    The goal of this study was to identify new candidate genes and genomic copy-number variations associated with a rare, severe, and persistent speech disorder termed childhood apraxia of speech. Childhood apraxia of speech is the speech disorder segregating with a mutation in FOXP2 in a multigenerational London pedigree widely studied for its role in the development of speech-language in humans. A total of 24 participants who were suspected to have childhood apraxia of speech were assessed using a comprehensive protocol that samples speech in challenging contexts. All participants met clinical-research criteria for childhood apraxia of speech. Array comparative genomic hybridization analyses were completed using a customized 385K Nimblegen array (Roche Nimblegen, Madison, WI) with increased coverage of genes and regions previously associated with childhood apraxia of speech. A total of 16 copy-number variations with potential consequences for speech-language development were detected in 12 or half of the 24 participants. The copy-number variations occurred on 10 chromosomes, 3 of which had two to four candidate regions. Several participants were identified with copy-number variations in two to three regions. In addition, one participant had a heterozygous FOXP2 mutation and a copy-number variation on chromosome 2, and one participant had a 16p11.2 microdeletion and copy-number variations on chromosomes 13 and 14. Findings support the likelihood of heterogeneous genomic pathways associated with childhood apraxia of speech.

  7. Genetic Architecture and Candidate Genes Identified for Follicle Number in Chicken.

    Science.gov (United States)

    Shen, Manman; Sun, Hongyan; Qu, Liang; Ma, Meng; Dou, Taocun; Lu, Jian; Guo, Jun; Hu, Yuping; Wang, Xingguo; Li, Yongfeng; Wang, Kehua; Yang, Ning

    2017-11-27

    Follicular development has a major impact on reproductive performance. Most previous researchers focused on molecular mechanisms of follicular development. The genetic architecture underlying the number of follicle, however, has yet not to be thoroughly defined in chicken. Here we report a genome-wide association study for the genetic architecture determining the numbers of follicles in a large F 2 resource population. The results showed heritability were low to moderate (0.05-0.28) for number of pre-ovulatory follicles (POF), small yellow follicles (SYF) and atresia follicles (AF). The highly significant SNPs associated with SYF were mainly located on GGA17 and GGA28. Only four significant SNPs were identified for POF on GGA1. The variance partitioned across chromosomes and chromosome lengths had a linear relationship for SYF (R 2  = 0.58). The enriched genes created by the closest correspondent significant SNPs were found to be involved in biological pathways related to cell proliferation, cell cycle and cell survival. Two promising candidate genes, AMH and RGS3, were suggested to be prognostic biomarkers for SYF. In conclusion, this study offers the first evidence of genetic variance and positional candidate genes which influence the number of SYF in chicken. These identified informative SNPs may facilitate selection for an improved reproductive performance of laying hens.

  8. A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy

    DEFF Research Database (Denmark)

    Bruhn, Sören; Fang, Yu; Barrenäs, Fredrik

    2014-01-01

    The identification of diagnostic markers and therapeutic candidate genes in common diseases is complicated by the involvement of thousands of genes. We hypothesized that genes co-regulated with a key gene in allergy, IL13, would form a module that could help to identify candidate genes. We identi...

  9. Extended tracts of homozygosity identify novel candidate genes associated with late onset Alzheimer’s Disease

    Science.gov (United States)

    Nalls, M. A.; Guerreiro, R. J.; Simon-Sanchez, J.; Bras, J. T.; Traynor, B. J.; Gibbs, J. R.; Launer, L.; Hardy, J.; Singleton, A. B.

    2010-01-01

    Large tracts of extended homozygosity are more prevalent in outbred populations than previously thought. With the advent of high-density genotyping platforms, regions of extended homozygosity can be accurately located allowing for the identification of rare recessive risk variants contributing to disease. We compared measures of extended homozygosity (greater than 1 megabase in length) in a population of 837 late onset Alzheimer’s disease (LOAD) cases and 550 controls. In our analyses, we identify one homozygous region on chromosome 8 that is significantly associated with LOAD after adjusting for multiple testing. This region contains seven genes from which the most biologically plausible candidates are STAR, EIF4EBP1 and ADRB3. We also compared the total numbers of homozygous runs and the total length of these runs between cases and controls, showing a suggestive difference in these measures (p-values 0.052-0.062). This research suggests a recessive component to the etiology of LOAD. PMID:19271249

  10. Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

    Science.gov (United States)

    Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

    2017-11-01

    Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

  11. Semantic interrogation of a multi knowledge domain ontological model of tendinopathy identifies four strong candidate risk genes.

    Science.gov (United States)

    Saunders, Colleen J; Jalali Sefid Dashti, Mahjoubeh; Gamieldien, Junaid

    2016-01-25

    Tendinopathy is a multifactorial syndrome characterised by tendon pain and thickening, and impaired performance during activity. Candidate gene association studies have identified genetic factors that contribute to intrinsic risk of developing tendinopathy upon exposure to extrinsic factors. Bioinformatics approaches that data-mine existing knowledge for biological relationships may assist with the identification of candidate genes. The aim of this study was to data-mine functional annotation of human genes and identify candidate genes by ontology-seeded queries capturing the features of tendinopathy. Our BioOntological Relationship Graph database (BORG) integrates multiple sources of genomic and biomedical knowledge into an on-disk semantic network where human genes and their orthologs in mouse and rat are central concepts mapped to ontology terms. The BORG was used to screen all human genes for potential links to tendinopathy. Following further prioritisation, four strong candidate genes (COL11A2, ELN, ITGB3, LOX) were identified. These genes are differentially expressed in tendinopathy, functionally linked to features of tendinopathy and previously implicated in other connective tissue diseases. In conclusion, cross-domain semantic integration of multiple sources of biomedical knowledge, and interrogation of phenotypes and gene functions associated with disease, may significantly increase the probability of identifying strong and unobvious candidate genes in genetic association studies.

  12. Analysis of Over 10,000 Cases Finds No Association between Previously-Reported Candidate Polymorphisms and Ovarian Cancer Outcome

    Science.gov (United States)

    White, Kristin L.; Vierkant, Robert A.; Fogarty, Zachary C.; Charbonneau, Bridget; Block, Matthew S.; Pharoah, Paul D.P.; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel W.; Pearce, C. Leigh; Schildkraut, Joellen M.; Menon, Usha; Kjaer, Susanne Kruger; Levine, Douglas A.; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S.; Karlan, Beth Y.; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V.; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B.; Fasching, Peter A.; Campbell, Ian; Goodman, Marc T.; Pejovic, Tanja; Bean, Yukie; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W.; Ekici, Arif B.; Paul, James; Brown, Robert; Flanagan, James; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K.; Lundvall, Lene; Olson, Sara H.; Orlow, Irene; Paddock, Lisa E.; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K.; Ziolkowska-Seta, Izabela; Brinton, Louise; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Ziogas, Argyrios; Lubiński, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H.; Pike, Malcolm C.; Van Den Berg, David; Terry, Kathryn L.; Vitonis, Allison F.; Doherty, Jennifer A.; Johnatty, Sharon; deFazio, Anna; Song, Honglin; Tyrer, Jonathan; Sellers, Thomas A.; Phelan, Catherine M.; Kalli, Kimberly R.; Cunningham, Julie M.; Fridley, Brooke L.; Goode, Ellen L.

    2013-01-01

    Background Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNPs) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000 observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. PMID:23513043

  13. Analysis of over 10,000 Cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome.

    Science.gov (United States)

    White, Kristin L; Vierkant, Robert A; Fogarty, Zachary C; Charbonneau, Bridget; Block, Matthew S; Pharoah, Paul D P; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel W; Pearce, Celeste Leigh; Schildkraut, Joellen M; Menon, Usha; Kjaer, Susanne Kruger; Levine, Douglas A; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S; Karlan, Beth Y; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B; Fasching, Peter A; Campbell, Ian; Goodman, Marc T; Pejovic, Tanja; Bean, Yukie; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Paul, James; Brown, Robert; Flanagan, James M; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K; Lundvall, Lene; Olson, Sara H; Orlow, Irene; Paddock, Lisa E; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Ziolkowska-Seta, Izabela; Brinton, Louise; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H; Ziogas, Argyrios; Lubinski, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H; Pike, Malcolm C; Van Denberg, David; Terry, Kathryn L; Vitonis, Allison F; Doherty, Jennifer A; Johnatty, Sharon E; Defazio, Anna; Song, Honglin; Tyrer, Jonathan; Sellers, Thomas A; Phelan, Catherine M; Kalli, Kimberly R; Cunningham, Julie M; Fridley, Brooke L; Goode, Ellen L

    2013-05-01

    Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.

  14. BANYAN. II. Very low mass and substellar candidate members to nearby, young kinematic groups with previously known signs of youth

    International Nuclear Information System (INIS)

    Gagné, Jonathan; Lafrenière, David; Doyon, René; Malo, Lison; Artigau, Étienne

    2014-01-01

    We present Bayesian Analysis for Nearby Young AssociatioNs II (BANYAN II), a modified Bayesian analysis for assessing the membership of later-than-M5 objects to any of several Nearby Young Associations (NYAs). In addition to using kinematic information (from sky position and proper motion), this analysis exploits 2MASS-WISE color-magnitude diagrams in which old and young objects follow distinct sequences. As an improvement over our earlier work, the spatial and kinematic distributions for each association are now modeled as ellipsoids whose axes need not be aligned with the Galactic coordinate axes, and we use prior probabilities matching the expected populations of the NYAs considered versus field stars. We present an extensive contamination analysis to characterize the performance of our new method. We find that Bayesian probabilities are generally representative of contamination rates, except when a parallax measurement is considered. In this case contamination rates become significantly smaller and hence Bayesian probabilities for NYA memberships are pessimistic. We apply this new algorithm to a sample of 158 objects from the literature that are either known to display spectroscopic signs of youth or have unusually red near-infrared colors for their spectral type. Based on our analysis, we identify 25 objects as new highly probable candidates to NYAs, including a new M7.5 bona fide member to Tucana-Horologium, making it the latest-type member. In addition, we reveal that a known L2γ dwarf is co-moving with a bright M5 dwarf, and we show for the first time that two of the currently known ultra red L dwarfs are strong candidates to the AB Doradus moving group. Several objects identified here as highly probable members to NYAs could be free-floating planetary-mass objects if their membership is confirmed.

  15. BANYAN. II. Very low mass and substellar candidate members to nearby, young kinematic groups with previously known signs of youth

    Energy Technology Data Exchange (ETDEWEB)

    Gagné, Jonathan; Lafrenière, David; Doyon, René; Malo, Lison; Artigau, Étienne [Département de Physique and Observatoire du Mont-Mégantic, Université de Montréal, C.P. 6128 Succ. Centre-ville, Montréal, Qc H3C 3J7 (Canada)

    2014-03-10

    We present Bayesian Analysis for Nearby Young AssociatioNs II (BANYAN II), a modified Bayesian analysis for assessing the membership of later-than-M5 objects to any of several Nearby Young Associations (NYAs). In addition to using kinematic information (from sky position and proper motion), this analysis exploits 2MASS-WISE color-magnitude diagrams in which old and young objects follow distinct sequences. As an improvement over our earlier work, the spatial and kinematic distributions for each association are now modeled as ellipsoids whose axes need not be aligned with the Galactic coordinate axes, and we use prior probabilities matching the expected populations of the NYAs considered versus field stars. We present an extensive contamination analysis to characterize the performance of our new method. We find that Bayesian probabilities are generally representative of contamination rates, except when a parallax measurement is considered. In this case contamination rates become significantly smaller and hence Bayesian probabilities for NYA memberships are pessimistic. We apply this new algorithm to a sample of 158 objects from the literature that are either known to display spectroscopic signs of youth or have unusually red near-infrared colors for their spectral type. Based on our analysis, we identify 25 objects as new highly probable candidates to NYAs, including a new M7.5 bona fide member to Tucana-Horologium, making it the latest-type member. In addition, we reveal that a known L2γ dwarf is co-moving with a bright M5 dwarf, and we show for the first time that two of the currently known ultra red L dwarfs are strong candidates to the AB Doradus moving group. Several objects identified here as highly probable members to NYAs could be free-floating planetary-mass objects if their membership is confirmed.

  16. Change in knee flexor torque after fatiguing exercise identifies previous hamstring injury in football players.

    Science.gov (United States)

    Lord, C; Ma'ayah, F; Blazevich, A J

    2018-03-01

    Muscular fatigue and interlimb strength asymmetry are factors known to influence hamstring injury risk; however, limb-specific exacerbation of knee flexor (hamstrings) torque production after fatiguing exercise has previously been ignored. To investigate changes in muscular force production before and after sport-specific (repeated-sprint) and non-specific (knee extension-flexion) fatiguing exercise, and explore the sensitivity and specificity of isokinetic endurance (ie, muscle-specific) and single-leg vertical jump (ie, whole limb) tests to identify previous hamstring injury. Twenty Western Australia State League footballers with previous unilateral hamstring injury and 20 players without participated. Peak concentric knee extensor and flexor (180°∙s -1 ) torques were assessed throughout an isokinetic endurance test, which was then repeated alongside a single-leg vertical jump test before and after maximal repeated-sprint exercise. Greater reductions in isokinetic knee flexor torque (-16%) and the concentric hamstring:quadriceps peak torque ratio (-15%) were observed after repeated-sprint running only in the injured (kicking) leg and only in the previously injured subjects. Changes in (1) peak knee flexor torque after repeated-sprint exercise, and (2) the decline in knee flexor torque during the isokinetic endurance test measured after repeated-sprint exercise, correctly identified the injured legs (N = 20) within the cohort (N = 80) with 100% specificity and sensitivity. Decreases in peak knee flexor torque and the knee flexor torque during an isokinetic endurance test after repeated-sprint exercise identified previous hamstring injury with 100% accuracy. Changes in knee flexor torque, but not SLVJ, should be tested to determine its prospective ability to predict hamstring injury in competitive football players. © 2017 The Authors. Scandinavian Journal of Medicine & Science In Sports Published by John Wiley & Sons Ltd.

  17. Using the BITOLA system to identify candidate genes for Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Amela Karić

    2011-08-01

    Full Text Available Complexity of multifactorial diseases as Parkinson’s disease (PD often complicate identifying causal genetic factors by traditional approaches such as positional cloning and candidate gene analyses. PD is etiologically and genetically complex disease and second most common neurodegenerative disorder after Alzheimer’s disease. The most cases of PD are idiopathic and small growing subset of individuals have single gene defect as the cause. The main goal of this research was to identify the potential candidate genes for idiopathic PD by using biomedical discovery support system (BITOLA. For detecting the potential candidate genes for PD was used opened system of bioinformatics tool BITOLA. Data of chromosome location, tissue specific expression of potential candidate genes and their potential association with PD were obtained from Medline, Locus Link, Gene Cards and OMIM. By using BITOLA system is identified 17 genes as potential candidate genes for PD. The role of three genes (MAPT, PARK2, UCHL1 in PD were confirmed earlier. Discovering the novel candidate genes for multifactiorial diseases by using specially mentioned bioinformatics tool BITOLA could offer the new opportunity for researching genetics base of PD without using tissue samples of patients.

  18. Genomic analysis identifies candidate pathogenic variants in 9 of 18 patients with unexplained West syndrome.

    Science.gov (United States)

    Hino-Fukuyo, Naomi; Kikuchi, Atsuo; Arai-Ichinoi, Natsuko; Niihori, Tetsuya; Sato, Ryo; Suzuki, Tasuku; Kudo, Hiroki; Sato, Yuko; Nakayama, Tojo; Kakisaka, Yosuke; Kubota, Yuki; Kobayashi, Tomoko; Funayama, Ryo; Nakayama, Keiko; Uematsu, Mitsugu; Aoki, Yoko; Haginoya, Kazuhiro; Kure, Shigeo

    2015-06-01

    West syndrome, which is narrowly defined as infantile spasms that occur in clusters and hypsarrhythmia on EEG, is the most common early-onset epileptic encephalopathy (EOEE). Patients with West syndrome may have clear etiologies, including perinatal events, infections, gross chromosomal abnormalities, or cases followed by other EOEEs. However, the genetic etiology of most cases of West syndrome remains unexplained. DNA from 18 patients with unexplained West syndrome was subjected to microarray-based comparative genomic hybridization (array CGH), followed by trio-based whole-exome sequencing in 14 unsolved families. We identified candidate pathogenic variants in 50% of the patients (n = 9/18). The array CGH revealed candidate pathogenic copy number variations in four cases (22%, 4/18), including an Xq28 duplication, a 16p11.2 deletion, a 16p13.1 deletion and a 19p13.2 deletion disrupting CACNA1A. Whole-exome sequencing identified candidate mutations in known epilepsy genes in five cases (36%, 5/14). Three candidate de novo mutations were identified in three cases, with two mutations occurring in two new candidate genes (NR2F1 and CACNA2D1) (21%, 3/14). Hemizygous candidate mutations in ALG13 and BRWD3 were identified in the other two cases (14%, 2/14). Evaluating a panel of 67 known EOEE genes failed to identify significant mutations. Despite the heterogeneity of unexplained West syndrome, the combination of array CGH and whole-exome sequencing is an effective means of evaluating the genetic background in unexplained West syndrome. We provide additional evidence for NR2F1 as a causative gene and for CACNA2D1 and BRWD3 as candidate genes for West syndrome.

  19. A transcription map of the 6p22.3 reading disability locus identifying candidate genes.

    Science.gov (United States)

    Londin, Eric R; Meng, Haiying; Gruen, Jeffrey R

    2003-06-30

    Reading disability (RD) is a common syndrome with a large genetic component. Chromosome 6 has been identified in several linkage studies as playing a significant role. A more recent study identified a peak of transmission disequilibrium to marker JA04 (G72384) on chromosome 6p22.3, suggesting that a gene is located near this marker. In silico cloning was used to identify possible candidate genes located near the JA04 marker. The 2 million base pairs of sequence surrounding JA04 was downloaded and searched against the dbEST database to identify ESTs. In total, 623 ESTs from 80 different tissues were identified and assembled into 153 putative coding regions from 19 genes and 2 pseudogenes encoded near JA04. The identified genes were tested for their tissue specific expression by RT-PCR. In total, five possible candidate genes for RD and other diseases mapping to this region were identified.

  20. A transcription map of the 6p22.3 reading disability locus identifying candidate genes

    Directory of Open Access Journals (Sweden)

    Gruen Jeffrey R

    2003-06-01

    Full Text Available Abstract Background Reading disability (RD is a common syndrome with a large genetic component. Chromosome 6 has been identified in several linkage studies as playing a significant role. A more recent study identified a peak of transmission disequilibrium to marker JA04 (G72384 on chromosome 6p22.3, suggesting that a gene is located near this marker. Results In silico cloning was used to identify possible candidate genes located near the JA04 marker. The 2 million base pairs of sequence surrounding JA04 was downloaded and searched against the dbEST database to identify ESTs. In total, 623 ESTs from 80 different tissues were identified and assembled into 153 putative coding regions from 19 genes and 2 pseudogenes encoded near JA04. The identified genes were tested for their tissue specific expression by RT-PCR. Conclusions In total, five possible candidate genes for RD and other diseases mapping to this region were identified.

  1. Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility.

    Science.gov (United States)

    Bruse, Shannon; Moreau, Michael; Bromberg, Yana; Jang, Jun-Ho; Wang, Nan; Ha, Hongseok; Picchi, Maria; Lin, Yong; Langley, Raymond J; Qualls, Clifford; Klensney-Tait, Julia; Zabner, Joseph; Leng, Shuguang; Mao, Jenny; Belinsky, Steven A; Xing, Jinchuan; Nyunoya, Toru

    2016-01-07

    Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15-20 % smokers manifest COPD, suggesting a role for genetic predisposition. Although genome-wide association studies have identified common genetic variants that are associated with susceptibility to COPD, effect sizes of the identified variants are modest, as is the total heritability accounted for by these variants. In this study, an extreme phenotype exome sequencing study was combined with in vitro modeling to identify COPD candidate genes. We performed whole exome sequencing of 62 highly susceptible smokers and 30 exceptionally resistant smokers to identify rare variants that may contribute to disease risk or resistance to COPD. This was a cross-sectional case-control study without therapeutic intervention or longitudinal follow-up information. We identified candidate genes based on rare variant analyses and evaluated exonic variants to pinpoint individual genes whose function was computationally established to be significantly different between susceptible and resistant smokers. Top scoring candidate genes from these analyses were further filtered by requiring that each gene be expressed in human bronchial epithelial cells (HBECs). A total of 81 candidate genes were thus selected for in vitro functional testing in cigarette smoke extract (CSE)-exposed HBECs. Using small interfering RNA (siRNA)-mediated gene silencing experiments, we showed that silencing of several candidate genes augmented CSE-induced cytotoxicity in vitro. Our integrative analysis through both genetic and functional approaches identified two candidate genes (TACC2 and MYO1E) that augment cigarette smoke (CS)-induced cytotoxicity and, potentially, COPD susceptibility.

  2. Thyroid disease awareness is associated with high rates of identifying subjects with previously undiagnosed thyroid dysfunction.

    Science.gov (United States)

    Canaris, Gay J; Tape, Thomas G; Wigton, Robert S

    2013-04-16

    Conventional screening for hypothyroidism is controversial. Although hypothyroidism is underdiagnosed, many organizations do not recommend screening, citing low disease prevalence in unselected populations. We studied attendees at a thyroid health fair, hypothesizing that certain patient characteristics would enhance the yield of testing. We carried out an observational study of participants at a Michigan health fair that focused on thyroid disease. We collected patient-reported symptoms and demographics by questionnaire, and correlated these with the TSH values obtained through the health fair. 794 of 858 health fair attendees participated. Most were women, and over 40% reported a family history of thyroid disease. We identified 97 (12.2%) participants with previously unknown thyroid dysfunction. No symptom or combination of symptoms discriminated between hypothyroid and euthyroid individuals. Hypothyroid and euthyroid participants in the health fair reported each symptom with a similar prevalence (p > 0.01), a prevalence which was very high. In fact, when compared with a previously published case-control study that reported symptoms, the euthyroid health fair participants reported a higher symptom prevalence (range 3.9% to 66.3%, mean 31.5%), than the euthyroid individuals from the case-control study (range 2% to 54%, mean 17.4%). A high proportion of previously undiagnosed thyroid disease was identified at this health fair. We initially hypothesized symptoms would distinguish between thyroid function states. However, this was not the case in this health fair screening population. The prevalence of reported symptoms was similar and high in both euthyroid and hypothyroid participants. Because attendees were self-selected, it is possible that this health fair that focused on thyroid disease attracted participants specifically concerned about thyroid health. Despite the lack of symptom discrimination, the much higher prevalence of hypothyroidism in this study

  3. Streptococcus oralis previously identified as uncommon 'Streptococcus sanguis' in Behçet's disease.

    Science.gov (United States)

    Narikawa, S; Suzuki, Y; Takahashi, M; Furukawa, A; Sakane, T; Mizushima, Y

    1995-08-01

    The relation between the biochemical and serological properties of 'Streptococcus sanguis' was studied to characterize the strains isolated from dental plaque of patients with Behçet's disease and controls. Seven reference and 100 clinical strains preserved by the Behçet's Disease Research Committee of Japan were identified using established criteria and differentiated with antisera against Strep. oralis ATCC 10557, Strep. sanguis ATCC 10556 and 'Strep. sanguis' ST7, compatible with the criteria. Uncommon serovars (serotypes) KTH-1 (= ATCC 49298), KTH-2 (= ATCC 49296), KTH-3 (= ATCC KTH-4 (= ATCC 49297) and B220 (serovar KTH-1) with both IgA1 protease and neuraminidase (sialidase) were identified as Strep. oralis, whereas common serovars ST3 with IgA1 protease alone and ST7 without both enzymes were identified as Strep. sanguis and Strep. gordonii, respectively. Isolates previously ranked as uncommon serovars were identified as Strep. oralis, whereas the rest ranked as common serovars were identified as the same species as those of the grouping strains. A soft-agar technique was available for species identification except for Strep. oralis serovar KTH-1 reacting with the antiserum against Strep. gordonii ST7. The frequency of isolation of Strep. oralis was higher in Behçet's disease (52%) than in controls (38%), but no difference was observed between the properties of the two groups of isolates. Strep. oralis virulence factors may be involved in breach the mucosal barrier in patients with specific reactivity to these antigens and inducing Behçet's disease.

  4. Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection

    Directory of Open Access Journals (Sweden)

    Wenzel Andreas

    2008-02-01

    Full Text Available Abstract Background Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1α in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration. To address the molecular mechanisms of the protection, we analyzed the transcriptome of the hypoxic retina using microarrays and real-time PCR. Results Hypoxic exposure induced a marked alteration in the retinal transcriptome with significantly different expression levels of 431 genes immediately after hypoxic exposure. The normal expression profile was restored within 16 hours of reoxygenation. Among the differentially regulated genes, several candidates for neuroprotection were identified like metallothionein-1 and -2, the HIF-1 target gene adrenomedullin and the gene encoding the antioxidative and cytoprotective enzyme paraoxonase 1 which was previously not known to be a hypoxia responsive gene in the retina. The strongly upregulated cyclin dependent kinase inhibitor p21 was excluded from being essential for neuroprotection. Conclusion Our data suggest that neuroprotection after hypoxic preconditioning is the result of the differential expression of a multitude of genes which may act in concert to protect visual cells against a toxic insult.

  5. Positional RNA-Seq identifies candidate genes for phenotypic engineering of sexual traits.

    Science.gov (United States)

    Arbore, Roberto; Sekii, Kiyono; Beisel, Christian; Ladurner, Peter; Berezikov, Eugene; Schärer, Lukas

    2015-01-01

    RNA interference (RNAi) of trait-specific genes permits the manipulation of specific phenotypic traits ("phenotypic engineering") and thus represents a powerful tool to test trait function in evolutionary studies. The identification of suitable candidate genes, however, often relies on existing functional gene annotation, which is usually limited in emerging model organisms, especially when they are only distantly related to traditional genetic model organisms. A case in point is the free-living flatworm Macrostomum lignano (Lophotrochozoa: Platyhelminthes: Rhabditophora), an increasingly powerful model organism for evolutionary studies of sex in simultaneous hermaphrodites. To overcome the limitation of sparse functional annotation, we have performed a positional RNA-Seq analysis on different body fragments in order to identify organ-specific candidate transcripts. We then performed gene expression (in situ hybridization) and gene function (RNAi) analyses on 23 candidate transcripts, both to evaluate the predictive potential of this approach and to obtain preliminary functional characterizations of these candidate genes. We identified over 4000 transcripts that could be expected to show specific expression in different reproductive organs (including testis, ovary and the male and female genital systems). The predictive potential of the method could then be verified by confirming organ-specific expression for several candidate transcripts, some of which yielded interesting trait-specific knock-down phenotypes that can now be followed up in future phenotypic engineering studies. Our positional RNA-Seq analysis represents a highly useful resource for the identification of candidate transcripts for functional and phenotypic engineering studies in M. lignano, and it has already been used successfully in several studies. Moreover, this approach can overcome some inherent limitations of homology-based candidate selection and thus should be applicable to a broad range of

  6. Functional complementation studies identify candidate genes and common genetic variants associated with ovarian cancer survival

    DEFF Research Database (Denmark)

    Quaye, Lydia; Dafou, Dimitra; Ramus, Susan J

    2009-01-01

    Common germline genetic variation and/or somatic alterations in tumours may be associated with survival in women diagnosed with ovarian cancer. The successful identification of genetic associations relies on a suitable strategy for identifying and testing candidate genes. We used microcell-mediat...

  7. Analyses of the xylem sap proteomes identified candidate Fusarium virguliforme proteinacious toxins.

    Directory of Open Access Journals (Sweden)

    Nilwala S Abeysekara

    Full Text Available Sudden death syndrome (SDS caused by the ascomycete fungus, Fusarium virguliforme, exhibits root necrosis and leaf scorch or foliar SDS. The pathogen has never been identified from the above ground diseased foliar tissues. Foliar SDS is believed to be caused by host selective toxins, including FvTox1, secreted by the fungus. This study investigated if the xylem sap of F. virguliforme-infected soybean plants contains secreted F. virguliforme-proteins, some of which could cause foliar SDS development.Xylem sap samples were collected from five biological replications of F. virguliforme-infected and uninfected soybean plants under controlled conditions. We identified five F. virguliforme proteins from the xylem sap of the F. virguliforme-infected soybean plants by conducting LC-ESI-MS/MS analysis. These five proteins were also present in the excreted proteome of the pathogen in culture filtrates. One of these proteins showed high sequence identity to cerato-platanin, a phytotoxin produced by Ceratocystis fimbriata f. sp. platani to cause canker stain disease in the plane tree. Of over 500 soybean proteins identified in this study, 112 were present in at least 80% of the sap samples collected from F. virguliforme-infected and -uninfected control plants. We have identified four soybean defense proteins from the xylem sap of F. virguliforme-infected soybean plants. The data have been deposited to the ProteomeXchange with identifier PXD000873.This study confirms that a few F. virguliforme proteins travel through the xylem, some of which could be involved in foliar SDS development. We have identified five candidate proteinaceous toxins, one of which showed high similarity to a previously characterized phytotoxin. We have also shown the presence of four soybean defense proteins in the xylem sap of F. virguliforme-infected soybean plants. This study laid the foundation for studying the molecular basis of foliar SDS development in soybean and possible

  8. BAYESIAN ANALYSIS TO IDENTIFY NEW STAR CANDIDATES IN NEARBY YOUNG STELLAR KINEMATIC GROUPS

    International Nuclear Information System (INIS)

    Malo, Lison; Doyon, René; Lafrenière, David; Artigau, Étienne; Gagné, Jonathan; Baron, Frédérique; Riedel, Adric

    2013-01-01

    We present a new method based on a Bayesian analysis to identify new members of nearby young kinematic groups. The analysis minimally takes into account the position, proper motion, magnitude, and color of a star, but other observables can be readily added (e.g., radial velocity, distance). We use this method to find new young low-mass stars in the β Pictoris and AB Doradus moving groups and in the TW Hydrae, Tucana-Horologium, Columba, Carina, and Argus associations. Starting from a sample of 758 mid-K to mid-M (K5V-M5V) stars showing youth indicators such as Hα and X-ray emission, our analysis yields 214 new highly probable low-mass members of the kinematic groups analyzed. One is in TW Hydrae, 37 in β Pictoris, 17 in Tucana-Horologium, 20 in Columba, 6 in Carina, 50 in Argus, 32 in AB Doradus, and the remaining 51 candidates are likely young but have an ambiguous membership to more than one association. The false alarm rate for new candidates is estimated to be 5% for β Pictoris and TW Hydrae, 10% for Tucana-Horologium, Columba, Carina, and Argus, and 14% for AB Doradus. Our analysis confirms the membership of 58 stars proposed in the literature. Firm membership confirmation of our new candidates will require measurement of their radial velocity (predicted by our analysis), parallax, and lithium 6708 Å equivalent width. We have initiated these follow-up observations for a number of candidates, and we have identified two stars (2MASSJ01112542+1526214, 2MASSJ05241914-1601153) as very strong candidate members of the β Pictoris moving group and one strong candidate member (2MASSJ05332558-5117131) of the Tucana-Horologium association; these three stars have radial velocity measurements confirming their membership and lithium detections consistent with young age.

  9. Reproductive compatibility between mite populations previously identified as Euseius concordis (Acari: Phytoseiidae).

    Science.gov (United States)

    Noronha, Aloyséia Cristina da Silva; de Moraes, Gilberto José

    2004-01-01

    The objective of the present research is to study the reproductive compatibility between populations of predatory mites previously identified as Euseius concordis (Chant) based on morphological characteristics. Colonies of these mite populations were established in the lab with specimens collected from different localities and host plants. Reproductive compatibility was evaluated through crosses and backcrosses within and between populations and the subsequent observation of females' oviposition, over a period of 10 days. The levels of oviposition obtained in the crosses between individuals from the same population were higher than those obtained in the crosses between individuals from different populations. Results indicate the occurrence of post-mating reproductive incompatibility between the mite population from Petrolina and the other populations studied. Crosses and backcrosses between populations involving female mites from Petrolina did not produce offspring, although endospermatophores were present inside the spermathecas of those females. Oviposition was reduced, and only sons were obtained, in crosses between populations with males from Petrolina. Crosses of females from Pontes e Lacerda and males from Jaguariúna and vice versa produced only male progeny. Our results established that the populations originating from Arroio do Meio, Pontes e Lacerda, Jaguarúna and Viçosa, are reproductively compatible. However, the latter populations and the population from Petrolina are genetically isolated. Based on these results we suggest that more cytological and genetic studies are needed to establish if this reproductive isolation represents a species barrier.

  10. An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity

    Directory of Open Access Journals (Sweden)

    Volker Noack

    2017-08-01

    included in the library as well as six antioxidants exhibited evidence of toxicity in the absence of gentamicin. The results demonstrate the wide variability in the ability of antioxidants to protect HCs from high-dose gentamicin damage, and identify promising candidate leads for further study as potential drug targets.Highlights• A medium-throughput assay based on micro-explants of the organ of Corti was developed to screen mammalian cochlear hair cells for protection from damage by ototoxins.• Eighty one antioxidants and 3 pro-oxidants were evaluated for hair cell protection from high-dose gentamicin.• Thirteen antioxidants were significantly protective, while 6 proved to be damaging.• The use of a common assay permitted an evaluation of the relative capacity of different antioxidants for the protection of hair cells.

  11. Using a Candidate Gene-Based Genetic Linkage Map to Identify QTL for Winter Survival in Perennial Ryegrass.

    Directory of Open Access Journals (Sweden)

    Cristiana Paina

    Full Text Available Important agronomical traits in perennial ryegrass (Lolium perenne breeding programs such as winter survival and heading date, are quantitative traits that are generally controlled by multiple loci. Individually, these loci have relatively small effects. The aim of this study was to develop a candidate gene based Illumina GoldenGate 1,536-plex assay, containing single nucleotide polymorphism markers designed from transcripts involved in response to cold acclimation, vernalization, and induction of flowering. The assay was used to genotype a mapping population that we have also phenotyped for winter survival to complement the heading date trait previously mapped in this population. A positive correlation was observed between strong vernalization requirement and winter survival, and some QTL for winter survival and heading date overlapped on the genetic map. Candidate genes were located in clusters along the genetic map, some of which co-localized with QTL for winter survival and heading date. These clusters of candidate genes may be used in candidate gene based association studies to identify alleles associated with winter survival and heading date.

  12. 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.

  13. An Approach to Identify and Characterize a Subunit Candidate Shigella Vaccine Antigen.

    Science.gov (United States)

    Pore, Debasis; Chakrabarti, Manoj K

    2016-01-01

    Shigellosis remains a serious issue throughout the developing countries, particularly in children under the age of 5. Numerous strategies have been tested to develop vaccines targeting shigellosis; unfortunately despite several years of extensive research, no safe, effective, and inexpensive vaccine against shigellosis is available so far. Here, we illustrate in detail an approach to identify and establish immunogenic outer membrane proteins from Shigella flexneri 2a as subunit vaccine candidates.

  14. Candidate Gene Sequence Analyses toward Identifying Rsv3-Type Resistance to Soybean Mosaic Virus

    Directory of Open Access Journals (Sweden)

    N. R. Redekar

    2016-07-01

    Full Text Available is one of three genetic loci conferring strain-specific resistance to (SMV. The locus has been mapped to a 154-kb region on chromosome 14, containing a cluster of five nucleotide-binding leucine-rich repeat (NB-LRR resistance genes. High sequence similarity between the candidate genes challenges fine mapping of the locus. Among the five, Glyma14g38533 showed the highest transcript abundance in 1 to 3 h of SMV-G7 inoculation. Comparative sequence analyses were conducted with the five candidate NB-LRR genes from susceptible (-type soybean [ (L. Merr.] cultivar Williams 82, resistant (-type cultivar Hwangkeum, and resistant lines L29 and RRR. Sequence comparisons revealed that Glyma14g38533 had far more polymorphisms than the other candidate genes. Interestingly, Glyma14g38533 gene from -type lines exhibited 150 single-nucleotide polymorphism (SNP and six insertion–deletion (InDel markers relative to -type line, Furthermore, the polymorphisms identified in three -type lines were highly conserved. Several polymorphisms were validated in 18 -type resistant and six -type susceptible lines and were found associated with their disease response. The majority of the polymorphisms were located in LRR domain encoding region, which is involved in pathogen recognition via protein–protein interactions. These findings associating Glyma14g38533 with -type resistance to SMV suggest it is the most likely candidate gene for .

  15. A functional genomics approach identifies candidate effectors from the aphid species Myzus persicae (green peach aphid.

    Directory of Open Access Journals (Sweden)

    Jorunn I B Bos

    2010-11-01

    Full Text Available Aphids are amongst the most devastating sap-feeding insects of plants. Like most plant parasites, aphids require intimate associations with their host plants to gain access to nutrients. Aphid feeding induces responses such as clogging of phloem sieve elements and callose formation, which are suppressed by unknown molecules, probably proteins, in aphid saliva. Therefore, it is likely that aphids, like plant pathogens, deliver proteins (effectors inside their hosts to modulate host cell processes, suppress plant defenses, and promote infestation. We exploited publicly available aphid salivary gland expressed sequence tags (ESTs to apply a functional genomics approach for identification of candidate effectors from Myzus persicae (green peach aphid, based on common features of plant pathogen effectors. A total of 48 effector candidates were identified, cloned, and subjected to transient overexpression in Nicotiana benthamiana to assay for elicitation of a phenotype, suppression of the Pathogen-Associated Molecular Pattern (PAMP-mediated oxidative burst, and effects on aphid reproductive performance. We identified one candidate effector, Mp10, which specifically induced chlorosis and local cell death in N. benthamiana and conferred avirulence to recombinant Potato virus X (PVX expressing Mp10, PVX-Mp10, in N. tabacum, indicating that this protein may trigger plant defenses. The ubiquitin-ligase associated protein SGT1 was required for the Mp10-mediated chlorosis response in N. benthamiana. Mp10 also suppressed the oxidative burst induced by flg22, but not by chitin. Aphid fecundity assays revealed that in planta overexpression of Mp10 and Mp42 reduced aphid fecundity, whereas another effector candidate, MpC002, enhanced aphid fecundity. Thus, these results suggest that, although Mp10 suppresses flg22-triggered immunity, it triggers a defense response, resulting in an overall decrease in aphid performance in the fecundity assays. Overall, we

  16. 76 FR 59488 - Addition to the Identifying Information for an Individual Previously Designated Pursuant to...

    Science.gov (United States)

    2011-09-26

    ... information for the following individual who was previously designated pursuant to the Order: GRAJALES PUENTES...; Cedula No. 52455790 (Colombia) (individual) [SDNT] The listing now appears as follows: GRAJALES PUENTES...

  17. Genome-wide association study identifies candidate genes for starch content regulation in maize kernels

    Directory of Open Access Journals (Sweden)

    Na Liu

    2016-07-01

    Full Text Available Kernel starch content is an important trait in maize (Zea mays L. as it accounts for 65% to 75% of the dry kernel weight and positively correlates with seed yield. A number of starch synthesis-related genes have been identified in maize in recent years. However, many loci underlying variation in starch content among maize inbred lines still remain to be identified. The current study is a genome-wide association study that used a set of 263 maize inbred lines. In this panel, the average kernel starch content was 66.99%, ranging from 60.60% to 71.58% over the three study years. These inbred lines were genotyped with the SNP50 BeadChip maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population structure was controlled by a mixed linear model (MLM as implemented in the software package TASSEL. After the statistical analyses, four SNPs were identified as significantly associated with starch content (P ≤ 0.0001, among which one each are located on chromosomes 1 and 5 and two are on chromosome 2. Furthermore, 77 candidate genes associated with starch synthesis were found within the 100-kb intervals containing these four QTLs, and four highly associated genes were within 20-kb intervals of the associated SNPs. Among the four genes, Glucose-1-phosphate adenylyltransferase (APS1; Gene ID GRMZM2G163437 is known as an important regulator of kernel starch content. The identified SNPs, QTLs, and candidate genes may not only be readily used for germplasm improvement by marker-assisted selection in breeding, but can also elucidate the genetic basis of starch content. Further studies on these identified candidate genes may help determine the molecular mechanisms regulating kernel starch content in maize and other important cereal crops.

  18. Using an epiphytic moss to identify previously unknown sources of atmospheric cadmium pollution

    Science.gov (United States)

    Geoffrey H. Donovan; Sarah E. Jovan; Demetrios Gatziolis; Igor Burstyn; Yvonne L. Michael; Michael C. Amacher; Vicente J. Monleon

    2016-01-01

    Urban networks of air-quality monitors are often too widely spaced to identify sources of air pollutants, especially if they do not disperse far from emission sources. The objectives of this study were to test the use of moss bio-indicators to develop a fine-scale map of atmospherically-derived cadmium and to identify the sources of cadmium in a complex urban setting....

  19. Auto-Vetting Transiting Planet Candidates Identified by the Kepler Pipeline

    Science.gov (United States)

    Jenkins, Jon M.; McCauliff, Sean; Burke, Christopher; Seader, Shawn; Twicken, Joseph; Klaus, Todd; Sanderfer, Dwight; Srivastava, Ashok; Haas, Michael R.

    2014-04-01

    The Kepler Mission simultaneously measures the brightness of more than 150,000 stars every 29.4 minutes primarily for the purpose of transit photometry. Over the course of its 3.5-year primary mission Kepler has observed over 190,000 distinct stars, announcing 2,321 planet candidates, 2,165 eclipsing binaries, and 105 confirmed planets. As Kepler moves into its 4-year extended mission, the total number of transit-like features identified in the light curves has increased to as many as ~18,000. This number of signals has become intractable for human beings to inspect by eye in a thorough and timely fashion. To mitigate this problem we are developing machine learning approaches to perform the task of reviewing the diagnostics for each transit signal candidate to establish a preliminary list of planetary candidates ranked from most credible to least credible. Our preliminary results indicate that random forests can classify potential transiting planet signatures with an accuracy of more than 98.6% as measured by the area under a receiver-operating curve.

  20. Detection of previously undiagnosed cases of COPD in a high-risk population identified in general practice

    DEFF Research Database (Denmark)

    Løkke, Anders; Ulrik, Charlotte Suppli; Dahl, Ronald

    2012-01-01

    Background and Aim: Under-diagnosis of COPD is a widespread problem. This study aimed to identify previously undiagnosed cases of COPD in a high-risk population identified through general practice. Methods: Participating GPs (n = 241) recruited subjects with no previous diagnosis of lung disease,...

  1. Analysis of over 10,000 Cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome

    DEFF Research Database (Denmark)

    White, Kristin L; Vierkant, Robert A; Fogarty, Zachary C

    2013-01-01

    Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis...

  2. From The Cover: Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation

    Science.gov (United States)

    Nollen, Ellen A. A.; Garcia, Susana M.; van Haaften, Gijs; Kim, Soojin; Chavez, Alejandro; Morimoto, Richard I.; Plasterk, Ronald H. A.

    2004-04-01

    Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation. protein misfolding | neurodegenerative diseases

  3. Identifying candidate sites for crop biofortification in Latin America: case studies in Colombia, Nicaragua and Bolivia.

    Science.gov (United States)

    Zapata-Caldas, Emmanuel; Hyman, Glenn; Pachón, Helena; Monserrate, Fredy Alexander; Varela, Liliana Vesga

    2009-05-19

    Agricultural science can address a population's vitamin, amino acid and mineral malnutrition through biofortification - agronomy, plant breeding and biotechnology to develop crops with high nutrient contents. Biofortified crop varieties should be grown in areas with populations at risk of nutrient deficiency and in areas where the same crop is already grown and consumed. Information on the population at risk of nutrient deficiency is rarely available for sub-national administrative units, such as provinces, districts, and municipalities. Nor is this type of information commonly analyzed with data on agricultural production. This project developed a method to identify populations at risk of nutrient deficiency in zones with high crop production, places where biofortification interventions could be targeted. Nutrient deficiency risk data were combined with crop production and socioeconomic data to assess the suitability of establishing an intervention. Our analysis developed maps of candidate sites for biofortification interventions for nine countries in Latin America and the Caribbean. Results for Colombia, Nicaragua, and Bolivia are presented in this paper. Interventions in northern Colombia appear promising for all crops, while sites for bean biofortification are widely scattered throughout the country. The most promising sites in Nicaragua are found in the center-north region. Candidate sites for biofortification in Bolivia are found in the central part of the country, in the Andes Mountains. The availability and resolution of data limits the analysis. Some areas show opportunities for biofortification of several crops, taking advantage of their spatial coincidence. Results from this analysis should be confirmed by experts or through field visits. This study demonstrates a method for identifying candidate sites for biofortification interventions. The method evaluates populations at risk of nutrient deficiencies for sub-national administrative regions, and

  4. Intensive sampling identifies previously unknown chemotypes, population divergence and biosynthetic connections among terpenoids in Eucalyptus tricarpa.

    Science.gov (United States)

    Andrew, Rose L; Keszei, Andras; Foley, William J

    2013-10-01

    Australian members of the Myrtaceae produce large quantities of ecologically and economically important terpenes and display abundant diversity in both yield and composition of their oils. In a survey of the concentrations of leaf terpenes in Eucalyptus tricarpa (L.A.S. Johnson) L.A.S. Johnson & K.D. Hill, which were previously known from few samples, exceptional variability was found in composition. The aim was to characterize the patterns of variation and covariation among terpene components in this species and to use this information to enhance our understanding of their biosynthesis. There were marked discontinuities in the distributions of numerous compounds, including the overall proportions of mono- and sesquiterpenes, leading us to delineate three distinct chemotypes. Overall, positive covariation predominated, but negative covariation suggested competitive interactions involved in monoterpene synthesis. Two groups of covarying monoterpenes were found, each of which was positively correlated with a group of sesquiterpenes and negatively correlated with the alternate sesquiterpene group. These results imply substantial cross-talk between mono- and sesquiterpene biosynthesis pathways. However, only those compounds hypothesized to share final carbocation intermediates or post-processing steps were strongly positively correlated within chemotypes. This suggests that the broader patterns of covariation among groups of compounds may result from co-regulation of multiple biosynthetic genes, controlling the complex terpene profiles of the chemotypes of Eucalyptus. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Using an epiphytic moss to identify previously unknown sources of atmospheric cadmium pollution

    Energy Technology Data Exchange (ETDEWEB)

    Donovan, Geoffrey H., E-mail: gdonovan@fs.fed.us [USDA Forest Service, PNW Research Station, 620 SW Main, Suite 400, Portland, OR 97205 (United States); Jovan, Sarah E., E-mail: sjovan@fs.fed.us [USDA Forest Service, PNW Research Station, 620 SW Main, Suite 400, Portland, OR 97205 (United States); Gatziolis, Demetrios, E-mail: dgatziolis@fs.fed.us [USDA Forest Service, PNW Research Station, 620 SW Main, Suite 400, Portland, OR 97205 (United States); Burstyn, Igor, E-mail: igor.burstyn@drexel.edu [Dornsife School of Public Health, Drexel University, Nesbitt Hall, 3215 Market St, Philadelphia, PA 19104 (United States); Michael, Yvonne L., E-mail: ylm23@drexel.edu [Dornsife School of Public Health, Drexel University, Nesbitt Hall, 3215 Market St, Philadelphia, PA 19104 (United States); Amacher, Michael C., E-mail: mcamacher1@outlook.com [USDA Forest Service, Logan Forest Sciences Laboratory, 860 North 1200 East, Logan, UT 84321 (United States); Monleon, Vicente J., E-mail: vjmonleon@fs.fed.us [USDA Forest Service, PNW Research Station, 3200 SW Jefferson Way, Corvallis, OR 97331 (United States)

    2016-07-15

    Urban networks of air-quality monitors are often too widely spaced to identify sources of air pollutants, especially if they do not disperse far from emission sources. The objectives of this study were to test the use of moss bio-indicators to develop a fine-scale map of atmospherically-derived cadmium and to identify the sources of cadmium in a complex urban setting. We collected 346 samples of the moss Orthotrichum lyellii from deciduous trees in December, 2013 using a modified randomized grid-based sampling strategy across Portland, Oregon. We estimated a spatial linear model of moss cadmium levels and predicted cadmium on a 50 m grid across the city. Cadmium levels in moss were positively correlated with proximity to two stained-glass manufacturers, proximity to the Oregon–Washington border, and percent industrial land in a 500 m buffer, and negatively correlated with percent residential land in a 500 m buffer. The maps showed very high concentrations of cadmium around the two stained-glass manufacturers, neither of which were known to environmental regulators as cadmium emitters. In addition, in response to our findings, the Oregon Department of Environmental Quality placed an instrumental monitor 120 m from the larger stained-glass manufacturer in October, 2015. The monthly average atmospheric cadmium concentration was 29.4 ng/m{sup 3}, which is 49 times higher than Oregon's benchmark of 0.6 ng/m{sup 3}, and high enough to pose a health risk from even short-term exposure. Both stained-glass manufacturers voluntarily stopped using cadmium after the monitoring results were made public, and the monthly average cadmium levels precipitously dropped to 1.1 ng/m{sup 3} for stained-glass manufacturer #1 and 0.67 ng/m{sup 3} for stained-glass manufacturer #2. - Highlights: • Bio-indicators are a valid method for measuring atmospheric pollutants • We used moss to map atmospheric cadmium in Portland, Oregon • Using a spatial linear model, we identified two

  6. A sub-pathway based method to identify candidate agents for Ankylosing Spondylitis.

    Science.gov (United States)

    Chen, Kai; Zhao, Yingchuan; Chen, Yu; Wang, Chuanfeng; Chen, Ziqiang; Bai, Yushu; Zhu, Xiaodong; Li, Ming

    2012-10-22

    The need for new therapeutics for Ankylosing Spondylitis (AS) is highlighted by the general lack of efficacy for most agents currently available for this disease. Many recent studies have detailed molecular pathways in AS, and several molecule-targeting agents are undergoing evaluation. We aimed to explore the mechanism of AS and identify biologically active small molecules capable of targeting the sub-pathways which were disregulated in the development of AS. By using the GSE25101 microarray data accessible from the Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between AS samples and healthy controls, followed by the sub-pathway enrichment analysis of the DEGs. In addition, we propose the use of an approach based on targeting sub-pathways to identify potential agents for AS. A total of 3,280 genes were identified as being significantly different between patients and controls with p-values pathway and some immune-associated pathways may be involved in the development of AS. Besides, our bioinformatics analysis revealed a total of 15 small molecules which may play a role in perturbing the development of AS. Our study proposes the use of an approach based on targeting sub-pathways to identify potential agents for AS. Candidate agents identified by our approach may provide the groundwork for a combination therapy approach for AS.

  7. A Sub-Pathway Based Method to Identify Candidate Agents for Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Ming Li

    2012-10-01

    Full Text Available The need for new therapeutics for Ankylosing Spondylitis (AS is highlighted by the general lack of efficacy for most agents currently available for this disease. Many recent studies have detailed molecular pathways in AS, and several molecule-targeting agents are undergoing evaluation. We aimed to explore the mechanism of AS and identify biologically active small molecules capable of targeting the sub-pathways which were disregulated in the development of AS. By using the GSE25101 microarray data accessible from the Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs between AS samples and healthy controls, followed by the sub-pathway enrichment analysis of the DEGs. In addition, we propose the use of an approach based on targeting sub-pathways to identify potential agents for AS. A total of 3,280 genes were identified as being significantly different between patients and controls with p-values < 0.1. Our study showed that neurotrophic signaling pathway and some immune-associated pathways may be involved in the development of AS. Besides, our bioinformatics analysis revealed a total of 15 small molecules which may play a role in perturbing the development of AS. Our study proposes the use of an approach based on targeting sub-pathways to identify potential agents for AS. Candidate agents identified by our approach may provide the groundwork for a combination therapy approach for AS.

  8. Comparative genomics identifies candidate genes for infectious salmon anemia (ISA) resistance in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Li, Jieying; Boroevich, Keith A; Koop, Ben F; Davidson, William S

    2011-04-01

    Infectious salmon anemia (ISA) has been described as the hoof and mouth disease of salmon farming. ISA is caused by a lethal and highly communicable virus, which can have a major impact on salmon aquaculture, as demonstrated by an outbreak in Chile in 2007. A quantitative trait locus (QTL) for ISA resistance has been mapped to three microsatellite markers on linkage group (LG) 8 (Chr 15) on the Atlantic salmon genetic map. We identified bacterial artificial chromosome (BAC) clones and three fingerprint contigs from the Atlantic salmon physical map that contains these markers. We made use of the extensive BAC end sequence database to extend these contigs by chromosome walking and identified additional two markers in this region. The BAC end sequences were used to search for conserved synteny between this segment of LG8 and the fish genomes that have been sequenced. An examination of the genes in the syntenic segments of the tetraodon and medaka genomes identified candidates for association with ISA resistance in Atlantic salmon based on differential expression profiles from ISA challenges or on the putative biological functions of the proteins they encode. One gene in particular, HIV-EP2/MBP-2, caught our attention as it may influence the expression of several genes that have been implicated in the response to infection by infectious salmon anemia virus (ISAV). Therefore, we suggest that HIV-EP2/MBP-2 is a very strong candidate for the gene associated with the ISAV resistance QTL in Atlantic salmon and is worthy of further study.

  9. Identifying the Relationship of Teacher Candidates' Humor Styles with Anxiety and Self-Compassion Levels

    Science.gov (United States)

    Aydin, Aydan

    2015-01-01

    Problem Statement: Teacher candidates who will soon be responsible for educating the future generations should possess certain characteristics. Specific teacher candidates should have specific characteristics taken into consideration: pre-school and primary teacher candidates should be seen as role models by younger students; psychological…

  10. Genetic similarity between cancers and comorbid Mendelian diseases identifies candidate driver genes.

    Science.gov (United States)

    Melamed, Rachel D; Emmett, Kevin J; Madubata, Chioma; Rzhetsky, Andrey; Rabadan, Raul

    2015-04-30

    Despite large-scale cancer genomics studies, key somatic mutations driving cancer, and their functional roles, remain elusive. Here, we propose that analysis of comorbidities of Mendelian diseases with cancers provides a novel, systematic way to discover new cancer genes. If germline genetic variation in Mendelian loci predisposes bearers to common cancers, the same loci may harbour cancer-associated somatic variation. Compilations of clinical records spanning over 100 million patients provide an unprecedented opportunity to assess clinical associations between Mendelian diseases and cancers. We systematically compare these comorbidities against recurrent somatic mutations from more than 5,000 patients across many cancers. Using multiple measures of genetic similarity, we show that a Mendelian disease and comorbid cancer indeed have genetic alterations of significant functional similarity. This result provides a basis to identify candidate drivers in cancers including melanoma and glioblastoma. Some Mendelian diseases demonstrate 'pan-cancer' comorbidity and shared genetics across cancers.

  11. Sequence-Based Introgression Mapping Identifies Candidate White Mold Tolerance Genes in Common Bean

    Directory of Open Access Journals (Sweden)

    Sujan Mamidi

    2016-07-01

    Full Text Available White mold, caused by the necrotrophic fungus (Lib. de Bary, is a major disease of common bean ( L.. WM7.1 and WM8.3 are two quantitative trait loci (QTL with major effects on tolerance to the pathogen. Advanced backcross populations segregating individually for either of the two QTL, and a recombinant inbred (RI population segregating for both QTL were used to fine map and confirm the genetic location of the QTL. The QTL intervals were physically mapped using the reference common bean genome sequence, and the physical intervals for each QTL were further confirmed by sequence-based introgression mapping. Using whole-genome sequence data from susceptible and tolerant DNA pools, introgressed regions were identified as those with significantly higher numbers of single-nucleotide polymorphisms (SNPs relative to the whole genome. By combining the QTL and SNP data, WM7.1 was located to a 660-kb region that contained 41 gene models on the proximal end of chromosome Pv07, while the WM8.3 introgression was narrowed to a 1.36-Mb region containing 70 gene models. The most polymorphic candidate gene in the WM7.1 region encodes a BEACH-domain protein associated with apoptosis. Within the WM8.3 interval, a receptor-like protein with the potential to recognize pathogen effectors was the most polymorphic gene. The use of gene and sequence-based mapping identified two candidate genes whose putative functions are consistent with the current model of pathogenicity.

  12. Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

    Science.gov (United States)

    Choi, Woonyoung; Park, Yun-Yong; Kim, KyoungHyun; Kim, Sang-Bae; Lee, Ju-Seog; Mills, Gordon B.; Cho, Jae Yong

    2011-01-01

    Background Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. Methodology/Principal Findings Using microarray technology, we generated a gene expression profile of human gastric cancer–specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. Conclusions/Significance We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment. PMID:21931799

  13. Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.

    Directory of Open Access Journals (Sweden)

    Sofie Claerhout

    Full Text Available Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future.Using microarray technology, we generated a gene expression profile of human gastric cancer-specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.

  14. Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk.

    Directory of Open Access Journals (Sweden)

    Montserrat García-Closas

    2007-02-01

    Full Text Available Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5' UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 x 10(-5. To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5' UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651 were associated with increased risk for bladder cancer: odds ratio (95% confidence interval: 2.52 (1.06-5.97, 2.74 (1.26-5.98, and 3.02 (1.36-6.63, respectively; and a polymorphism in intron 2 (rs3024994 was associated with reduced risk: 0.65 (0.46-0.91. Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5' UTR (global p = 0.02 and 0.009, respectively. These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5' UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk.

  15. Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

    Directory of Open Access Journals (Sweden)

    Karacali Bilge

    2007-10-01

    Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

  16. Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE

    Science.gov (United States)

    Nava, C; Lamari, F; Héron, D; Mignot, C; Rastetter, A; Keren, B; Cohen, D; Faudet, A; Bouteiller, D; Gilleron, M; Jacquette, A; Whalen, S; Afenjar, A; Périsse, D; Laurent, C; Dupuits, C; Gautier, C; Gérard, M; Huguet, G; Caillet, S; Leheup, B; Leboyer, M; Gillberg, C; Delorme, R; Bourgeron, T; Brice, A; Depienne, C

    2012-01-01

    The striking excess of affected males in autism spectrum disorders (ASD) suggests that genes located on chromosome X contribute to the etiology of these disorders. To identify new X-linked genes associated with ASD, we analyzed the entire chromosome X exome by next-generation sequencing in 12 unrelated families with two affected males. Thirty-six possibly deleterious variants in 33 candidate genes were found, including PHF8 and HUWE1, previously implicated in intellectual disability (ID). A nonsense mutation in TMLHE, which encodes the ɛ-N-trimethyllysine hydroxylase catalyzing the first step of carnitine biosynthesis, was identified in two brothers with autism and ID. By screening the TMLHE coding sequence in 501 male patients with ASD, we identified two additional missense substitutions not found in controls and not reported in databases. Functional analyses confirmed that the mutations were associated with a loss-of-function and led to an increase in trimethyllysine, the precursor of carnitine biosynthesis, in the plasma of patients. This study supports the hypothesis that rare variants on the X chromosome are involved in the etiology of ASD and contribute to the sex-ratio disequilibrium. PMID:23092983

  17. Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life

    Directory of Open Access Journals (Sweden)

    Reusch Thorsten BH

    2011-01-01

    Full Text Available Abstract Background Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L. Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. Results In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. Conclusions These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

  18. Genome-Wide Association Study with Sequence Variants Identifies Candidate Genes for Mastitis Resistance in Dairy Cattle

    DEFF Research Database (Denmark)

    Sahana, Goutam; Guldbrandtsen, Bernt; Bendixen, Christian

    component in a linear mixed model. A total of 90 bulls’ whole genomes were sequenced with a coverage > 10X. Sequence reads were aligned to the cattle reference genome and polymorphisms in candidate regions were identified when one or more samples differed from the reference sequence. The polymorphisms...... Factor Receptor Alpha (LIFR) emerged as a strong candidate gene for mastitis resistance. The LIFR gene is involved in acute phase response and is expressed in saliva and mammary gland....

  19. Proteomics strategy for identifying candidate bioactive proteins in complex mixtures: application to the platelet releasate.

    LENUS (Irish Health Repository)

    O'Connor, Roisin

    2010-01-01

    Proteomic approaches have proven powerful at identifying large numbers of proteins, but there are fewer reports of functional characterization of proteins in biological tissues. Here, we describe an experimental approach that fractionates proteins released from human platelets, linking bioassay activity to identity. We used consecutive orthogonal separation platforms to ensure sensitive detection: (a) ion-exchange of intact proteins, (b) SDS-PAGE separation of ion-exchange fractions and (c) HPLC separation of tryptic digests coupled to electrospray tandem mass spectrometry. Migration of THP-1 monocytes in response to complete or fractionated platelet releasate was assessed and located to just one of the forty-nine ion-exchange fractions. Over 300 proteins were identified in the releasate, with a wide range of annotated biophysical and biochemical properties, in particular platelet activation, adhesion, and wound healing. The presence of PEDF and involucrin, two proteins not previously reported in platelet releasate, was confirmed by western blotting. Proteins identified within the fraction with monocyte promigratory activity and not in other inactive fractions included vimentin, PEDF, and TIMP-1. We conclude that this analytical platform is effective for the characterization of complex bioactive samples.

  20. A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity

    Directory of Open Access Journals (Sweden)

    Ana C. D’Alessio

    2015-11-01

    Full Text Available Hundreds of transcription factors (TFs are expressed in each cell type, but cell identity can be induced through the activity of just a small number of core TFs. Systematic identification of these core TFs for a wide variety of cell types is currently lacking and would establish a foundation for understanding the transcriptional control of cell identity in development, disease, and cell-based therapy. Here, we describe a computational approach that generates an atlas of candidate core TFs for a broad spectrum of human cells. The potential impact of the atlas was demonstrated via cellular reprogramming efforts where candidate core TFs proved capable of converting human fibroblasts to retinal pigment epithelial-like cells. These results suggest that candidate core TFs from the atlas will prove a useful starting point for studying transcriptional control of cell identity and reprogramming in many human cell types.

  1. 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

  2. Survival of patients identified as candidates for intestinal transplantation: a 3-year prospective follow-up

    DEFF Research Database (Denmark)

    Pironi, L.; Forbes, A.; Joly, F.

    2008-01-01

    ). Survival in the 10 patients receiving a first isolated small bowel transplant was 89% (95% CI, 70%-100%), compared with 85% (95% CI, 74%-96%) in the candidates with parenteral nutrition failure not receiving transplants because of central venous catheter complications, or 70% (95% CI, 53%-88%) in those...

  3. Positional RNA-Seq identifies candidate genes for phenotypic engineering of sexual traits

    NARCIS (Netherlands)

    Arbore, Roberto; Sekii, Kiyono; Beisel, Christian; Ladurner, Peter; Berezikov, Eugene; Schaerer, Lukas

    2015-01-01

    Introduction: RNA interference (RNAi) of trait-specific genes permits the manipulation of specific phenotypic traits ("phenotypic engineering") and thus represents a powerful tool to test trait function in evolutionary studies. The identification of suitable candidate genes, however, often relies on

  4. Gene expression profiling and candidate gene resequencing identifies pathways and mutations important for malignant transformation caused by leukemogenic fusion genes.

    Science.gov (United States)

    Novak, Rachel L; Harper, David P; Caudell, David; Slape, Christopher; Beachy, Sarah H; Aplan, Peter D

    2012-12-01

    NUP98-HOXD13 (NHD13) and CALM-AF10 (CA10) are oncogenic fusion proteins produced by recurrent chromosomal translocations in patients with acute myeloid leukemia (AML). Transgenic mice that express these fusions develop AML with a long latency and incomplete penetrance, suggesting that collaborating genetic events are required for leukemic transformation. We employed genetic techniques to identify both preleukemic abnormalities in healthy transgenic mice as well as collaborating events leading to leukemic transformation. Candidate gene resequencing revealed that 6 of 27 (22%) CA10 AMLs spontaneously acquired a Ras pathway mutation and 8 of 27 (30%) acquired an Flt3 mutation. Two CA10 AMLs acquired an Flt3 internal-tandem duplication, demonstrating that these mutations can be acquired in murine as well as human AML. Gene expression profiles revealed a marked upregulation of Hox genes, particularly Hoxa5, Hoxa9, and Hoxa10 in both NHD13 and CA10 mice. Furthermore, mir196b, which is embedded within the Hoxa locus, was overexpressed in both CA10 and NHD13 samples. In contrast, the Hox cofactors Meis1 and Pbx3 were differentially expressed; Meis1 was increased in CA10 AMLs but not NHD13 AMLs, whereas Pbx3 was consistently increased in NHD13 but not CA10 AMLs. Silencing of Pbx3 in NHD13 cells led to decreased proliferation, increased apoptosis, and decreased colony formation in vitro, suggesting a previously unexpected role for Pbx3 in leukemic transformation. Published by Elsevier Inc.

  5. Activation of two forms of locomotion by a previously identified trigger interneuron for swimming in the medicinal leech.

    Science.gov (United States)

    Brodfuehrer, Peter D; McCormick, Kathryn; Tapyrik, Lauren; Albano, Alfonso M; Graybeal, Carolyn

    2008-03-01

    Higher-order projection interneurons that function in more than one behavior have been identified in a number of preparations. In this study, we document that stimulation of cell Tr1, a previously identified trigger interneuron for swimming in the medicinal leech, can also elicit the motor program for crawling in isolated nerve cords. We also show that motor choice is independent of the firing frequency of Tr1 and amount of spiking activity recorded extracellularly at three locations along the ventral nerve cord prior to Tr1 stimulation. On the other hand, during Tr1 stimulation there is a significant difference in the amount of activity elicited in the ventral nerve cord that correlates with the motor program activated. On average, Tr1 stimulation trials that lead to crawling elicit greater amounts of activity than in trials that lead to swimming.

  6. Coalitional game theory as a promising approach to identify candidate autism genes.

    Science.gov (United States)

    Gupta, Anika; Sun, Min Woo; Paskov, Kelley Marie; Stockham, Nate Tyler; Jung, Jae-Yoon; Wall, Dennis Paul

    2018-01-01

    Despite mounting evidence for the strong role of genetics in the phenotypic manifestation of Autism Spectrum Disorder (ASD), the specific genes responsible for the variable forms of ASD remain undefined. ASD may be best explained by a combinatorial genetic model with varying epistatic interactions across many small effect mutations. Coalitional or cooperative game theory is a technique that studies the combined effects of groups of players, known as coalitions, seeking to identify players who tend to improve the performance--the relationship to a specific disease phenotype--of any coalition they join. This method has been previously shown to boost biologically informative signal in gene expression data but to-date has not been applied to the search for cooperative mutations among putative ASD genes. We describe our approach to highlight genes relevant to ASD using coalitional game theory on alteration data of 1,965 fully sequenced genomes from 756 multiplex families. Alterations were encoded into binary matrices for ASD (case) and unaffected (control) samples, indicating likely gene-disrupting, inherited mutations in altered genes. To determine individual gene contributions given an ASD phenotype, a "player" metric, referred to as the Shapley value, was calculated for each gene in the case and control cohorts. Sixty seven genes were found to have significantly elevated player scores and likely represent significant contributors to the genetic coordination underlying ASD. Using network and cross-study analysis, we found that these genes are involved in biological pathways known to be affected in the autism cases and that a subset directly interact with several genes known to have strong associations to autism. These findings suggest that coalitional game theory can be applied to large-scale genomic data to identify hidden yet influential players in complex polygenic disorders such as autism.

  7. Can suitable candidates for levodopa/carbidopa intestinal gel therapy be identified using current evidence?

    Directory of Open Access Journals (Sweden)

    Maria José Catalán

    2017-09-01

    In recent years, strong evidence has supported the use of LCIG in treating motor fluctuations associated with APD, and several clinical studies provide emerging evidence for additional benefits of LCIG treatment in certain patients. This article provides an overview of the published literature on the benefits, limitations, and drawbacks of LCIG in relation to PD symptoms, the psychosocial impact of the disease, and the quality of life of patients, with the aim of determining candidates for whom treatment with LCIG would be beneficial. According to current evidence, patients with APD (defined as inability to achieve optimal control of the disease with conventional oral treatment, a relatively well-preserved cognitive-behavioral status, and good family/caregiver would count as suitable candidates for LCIG treatment. Contraindications in the opinion of the authors are severe dementia and active psychosis.

  8. Criteria for identifying and evaluating candidate sites for open-field trials of genetically engineered mosquitoes.

    Science.gov (United States)

    Brown, David M; Alphey, Luke S; McKemey, Andrew; Beech, Camilla; James, Anthony A

    2014-04-01

    Recent laboratory successes in the development of genetically engineered mosquitoes for controlling pathogen transmission have fostered the need for standardized procedures for advancing the technical achievements to practical tools. It is incumbent in many cases for the same scientists doing the in-laboratory discovery research to also take on the initial challenges of developing the pathway that will move the technologies to the field. One of these challenges is having a set of criteria for selecting collaborators and sites for efficacy and safety field trials that combine rigorous science with good ethical and legal practices. Specific site-selection criteria were developed in four categories-Scientific, Regulatory, Community Engagement, and Resources-in anticipation of open-field releases of a transgenic mosquito strain designed to suppress populations of the dengue vector mosquito, Aedes aegypti. The criteria are derived from previous published material, discussions, and personal experiences with the expectation of providing guidance to laboratory scientists for addressing the conceptual and operational considerations for identifying partner researchers and countries with whom to collaborate. These criteria are not intended to be prescriptive nor can they be applied to every circumstance where genetic approaches are proposed for deployment. However, we encourage those involved in the discovery phase of research to consider each criterion during project planning activities, and where appropriate, incorporate them into a "go/no-go" decision-making process for further development and testing of the technologies.

  9. A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes for cellulite.

    Science.gov (United States)

    Emanuele, E; Bertona, M; Geroldi, D

    2010-08-01

    Cellulite is a common complex cosmetic problem for many post-adolescent women characterised by relief alterations of the skin surface, which give the skin an orange-peel appearance. Although genetic factors have been suggested to play a role in the development of cellulite, the genetic background of this condition remains unclear. We therefore conducted a multi-locus genetic study examining the potential associations of candidate gene variants in oestrogen receptors, endothelial function/adipose tissue hypoxia, lipid metabolism, extracellular matrix homeostasis, inflammation and adipose tissue biology, with the risk of cellulite. Using a case-control study of 200 lean women with cellulite and 200 age- and BMI-matched controls (grade 0 according to Nurnberger-Muller scale), we examined the association of cellulite with 25 polymorphisms in 15 candidate genes. Two of the 25 polymorphisms were significantly associated with cellulite at the P cellulite were 1.19 (95% CI: 1.10-1.51; P cellulite, may provide novel information on the pathophysiology of this common cosmetic problem, and offer a topic for research for novel beautification interventions.

  10. Comparative analysis of human reproductive proteomes identifies candidate proteins of sperm maturation.

    Science.gov (United States)

    Fu-Jun, Liu; Xiao-Fang, Shen

    2012-12-01

    Male reproductive proteomes provide basis for studying gene products and its involvement or regulation in sperm physiology. Here, a comparative study between these proteomes was performed to find potential proteins and functions associated with human sperm maturation. Seven reproductive proteomes associated with human sperm physiology were integrated. Gene ontology analysis were performed using DAVID and Panther tools to determine enriched functions. Total of 270 proteins overlapped between epididymal, prostatic milieu and sperm proteome were thought to be candidate proteins involved in sperm maturation, and they showed enriched functions of proteasomal protein catabolic process and protein folding. 34 epididymal milieu proteins and 274 prostatic milieu proteins were contributed to the composition of seminal fluids proteome. Literatures have confirmed the involvements in sperm maturation of many of these proteins The spatial expressions of 24 epididymal milieu proteins involved in chaperone and antioxidant activity were authenticated by real-time RT-PCR. These proteins may serve as candidate molecules for future studies of sperm maturation and male infertility.

  11. Survival of patients identified as candidates for intestinal transplantation: a 3-year prospective follow-up

    DEFF Research Database (Denmark)

    Pironi, L.; Forbes, A.; Joly, F.

    2008-01-01

    with parenteral nutrition-related liver failure (P = .364). CONCLUSIONS: The results confirm home parenteral nutrition as the primary therapeutic option for intestinal failure and support the appropriateness and potential life-saving role of timely intestinal transplantation for patients with parenteral nutrition......BACKGROUND & AIMS: The US Medicare indications for intestinal transplantation are based on failure of home parenteral nutrition. The American Society of Transplantation also includes patients at high risk of death from their primary disease or with high morbidity intestinal failure. A 3-year...... prospective study evaluated the appropriateness of these indications. METHODS: Survival on home parenteral nutrition or after transplantation was analyzed in 153 (97 adult, 56 pediatric) candidates for transplantation and 320 (262 adult, 58 pediatric) noncandidates, enrolled through a European multicenter...

  12. Next generation sequencing identifies abnormal Y chromosome and candidate causal variants in premature ovarian failure patients.

    Science.gov (United States)

    Lee, Yujung; Kim, Changshin; Park, YoungJoon; Pyun, Jung-A; Kwack, KyuBum

    2016-12-01

    Premature ovarian failure (POF) is characterized by heterogeneous genetic causes such as chromosomal abnormalities and variants in causal genes. Recently, development of techniques made next generation sequencing (NGS) possible to detect genome wide variants including chromosomal abnormalities. Among 37 Korean POF patients, XY karyotype with distal part deletions of Y chromosome, Yp11.32-31 and Yp12 end part, was observed in two patients through NGS. Six deleterious variants in POF genes were also detected which might explain the pathogenesis of POF with abnormalities in the sex chromosomes. Additionally, the two POF patients had no mutation in SRY but three non-synonymous variants were detected in genes regarding sex reversal. These findings suggest candidate causes of POF and sex reversal and show the propriety of NGS to approach the heterogeneous pathogenesis of POF. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Transposon mutagenesis identifies candidate genes that cooperate with loss of Transforming Growth Factor-beta signaling in mouse intestinal neoplasms

    Science.gov (United States)

    Morris, Shelli M.; Davison, Jerry; Carter, Kelly T.; O’Leary, Rachele M.; Trobridge, Patty; Knoblaugh, Sue E.; Myeroff, Lois L.; Markowitz, Sanford D.; Brett, Benjamin T.; Scheetz, Todd E.; Dupuy, Adam J.; Starr, Timothy K.; Grady, William M.

    2017-01-01

    Colorectal cancer (CRC) results from the accumulation of gene mutations and epigenetic alterations in colon epithelial cells, which promotes CRC formation through deregulating signaling pathways. One of the most commonly deregulated signaling pathways in CRC is the transforming growth factor β (TGF-β) pathway. Importantly, the effects of TGF-β signaling inactivation in CRC are modified by concurrent mutations in the tumor cell, and these concurrent mutations determine the ultimate biological effects of impaired TGF-β signaling in the tumor. However, many of the mutations that cooperate with the deregulated TGF-β signaling pathway in CRC remain unknown. Therefore, we sought to identify candidate driver genes that promote the formation of CRC in the setting of TGF-β signaling inactivation. We performed a forward genetic screen in mice carrying conditionally inactivated alleles of the TGF-β receptor, type II (Tgfbr2) using Sleeping Beauty (SB) transposon mediated mutagenesis. We used TAPDANCE and Gene-centric statistical methods to identify common insertion sites (CIS) and, thus, candidate tumor suppressor genes and oncogenes within the tumor genome. CIS analysis of multiple neoplasms from these mice identified many candidate Tgfbr2 cooperating genes and the Wnt/β-catenin, Hippo and MAPK pathways as the most commonly affected pathways. Importantly, the majority of candidate genes were also found to be mutated in human CRC. The SB transposon system provides an unbiased method to identify Tgfbr2 cooperating genes in mouse CRC that are functionally relevant and that may provide further insight into the pathogenesis of human CRC. PMID:27790711

  14. Association between previously identified loci affecting telomere length and coronary heart disease (CHD in Han Chinese population

    Directory of Open Access Journals (Sweden)

    Ding H

    2014-05-01

    Full Text Available Hui Ding,1 Fen Yan,1 Lin-Lin Zhou,2 Xiu-Hai Ji,3 Xin-Nan Gu,1 Zhi-Wei Tang,1 Ru-Hua Chen11Department of Pulmonary Medicine, The Affiliated Yixing People's Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, 2Department of Cardiology, Affiliated Cixi Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, 3Department of Oncology, Affiliated Taicang Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu Province, People's Republic of ChinaPurpose: To replicate previously confirmed telomere-length loci in a Chinese Han population with coronary heart disease (CHD, and investigate these loci and the possibility of and age at onset of CHD.Patients and methods: 1514 CHD patients and 2470 normal controls were recruited. Medical data including age, sex, body mass index, lipid profiles, history of hypertension, type 2 diabetes mellitus, and dyslipidemia were collected from all the participants. Seven previously identified single-nucleotide polymorphisms (SNPs related to leucocyte telomere length were genotyped, including rs10936599 in TERC, rs2736100 in TERT, rs7675998 in NAF1, rs9420907 in OBFC1, rs8105767 in ZNF208, rs755017 in RTEL1, and rs11125529 in ACYP2.Results: No significant difference in genotype frequencies from the Hardy–Weinberg equilibrium test was noted for all tested SNPs both in the CHD patients and the normal controls. No polymorphism was observed for rs9420907, and AA genotype was noted in both the CHD patients and the controls. Neither the genotype nor the allele frequencies of rs2736100, rs8105767, rs11125529, and rs2967374 were significantly different between the CHD patients and the normal controls. For rs10936599 and rs755017, statistical difference was found for the allele frequency but not genotype. Distributions of genotype and allele were significantly different between the two groups for rs7675998. The odds ratio for carriers of CHD was 2.127 (95% confidence interval: 1.909–2.370 for the A allele of rs

  15. An OMERACT Initiative Toward Consensus to Identify and Characterize Candidate Contextual Factors

    DEFF Research Database (Denmark)

    Finger, Monika E; Boonen, Annelies; Woodworth, Thasia G

    2017-01-01

    preliminary projects on how to identify and analyze CF. CONCLUSION: New methods are urgently needed to assist researchers to identify and characterize CF that significantly influence the interpretation of results in clinical trials. The CFMG defined first steps to develop further guidance....

  16. 2-methyl butyramide, a previously identified urine biomarker for Ascaris lumbricoides, is not present in infected Indonesian individuals.

    Science.gov (United States)

    Lagatie, Ole; Njumbe Ediage, Emmanuel; Pikkemaat, Jeroen A; Djuardi, Yenny; Stuyver, Lieven J

    2017-12-29

    ᅟ: Previous reports suggest that the 2-methyl butyramide and 2-methyl valeramide metabolites of Ascaris lumbricoides in urine of infected individuals could be considered as urinary biomarkers for active infection. We have developed an LC-MS method with a detection limit of 10 ng/mL using synthetic chemicals as reference material. Urine samples (n = 21) of infected individuals were analyzed for the presence of these metabolites, but they were not detected in any of the samples. Furthermore, the recorded 1 H-NMR spectrum for reference 2-methyl butyramide did not match with the spectrum that was described for the Ascaris metabolite. Based on these two observations, we concluded that the urinary biomarkers that were detected for A. lumbricoides infection are not 2-methyl butyramide nor 2-methylvaleramide. New discovery efforts will be required to identify the structure of these metabolite biomarkers in urine of infected individuals. Urine samples used in this study were collected as part of a clinical trial with trial number ISRCTN75636394 (12 November 2013).

  17. A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

    International Nuclear Information System (INIS)

    Mirabello, Lisa; Grotmol, Tom; Douglass, Chester; Hayes, Richard B; Hoover, Robert N; Savage, Sharon A; Yu, Kai; Berndt, Sonja I; Burdett, Laurie; Wang, Zhaoming; Chowdhury, Salma; Teshome, Kedest; Uzoka, Arinze; Hutchinson, Amy

    2011-01-01

    Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways. We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI). Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene FANCM (ORs 1.9-2.0, P = 0.003-0.004) and 2 SNPs downstream of the growth hormone gene GH1 (OR 1.6, P = 0.002; OR 0.5, P = 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: MDM2, MPG, FGF2, FGFR3, GNRH2, and IGF1. Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings

  18. 3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances.

    Science.gov (United States)

    Iourov, Ivan Y; Vorsanova, Svetlana G; Voinova, Victoria Y; Yurov, Yuri B

    2015-01-01

    In contrast to other autism spectrum disorders, chromosome abnormalities are rare in Asperger syndrome (AS) or high-functioning autism. Consequently, AS was occasionally subjected to classical positional cloning. Here, we report on a case of AS associated with a deletion of the short arm of chromosome 3. Further in silico analysis has identified a candidate gene for AS and has suggested a therapeutic strategy for manifestations of the chromosome rearrangement. Using array comparative genomic hybridization, an interstitial deletion of 3p22.1p21.31 (~2.5 Mb in size) in a child with Asperger's syndrome, seborrheic dermatitis and chronic pancreatitis was detected. Original bioinformatic approach to the prioritization of candidate genes/processes identified CCK (cholecystokinin) as a candidate gene for AS. In addition to processes associated with deleted genes, bioinformatic analysis of CCK gene interactome indicated that zinc deficiency might be a pathogenic mechanism in this case. This suggestion was supported by plasma zinc concentration measurements. The increase of zinc intake produced a rise in zinc plasma concentration and the improvement in the patient's condition. Our study supported previous linkage findings and had suggested a new candidate gene in AS. Moreover, bioinformatic analysis identified the pathogenic mechanism, which was used to propose a therapeutic strategy for manifestations of the deletion. The relative success of this strategy allows speculating that therapeutic or dietary normalization of metabolic processes altered by a chromosome imbalance or genomic copy number variations may be a way for treating at least a small proportion of cases of these presumably incurable genetic conditions.

  19. Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

    DEFF Research Database (Denmark)

    Druley, Todd E; Wang, Lihua; Lin, Shiow J

    2016-01-01

    : We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually...... from six pedigrees. OBFC1 (chromosome 10) is involved in telomere maintenance, and falls within a linkage peak recently reported from an analysis of telomere length in LLFS families. Two different algorithms for single gene associations identified three genes with an enrichment of variation...

  20. Candidate gene linkage approach to identify DNA variants that predispose to preterm birth

    DEFF Research Database (Denmark)

    Bream, Elise N A; Leppellere, Cara R; Cooper, Margaret E

    2013-01-01

    used. Premature infants and mothers of premature infants were defined as affected cases in independent analyses.Results:Analyses with the infant as the case identified two genes with evidence of linkage: CRHR1 (P = 0.0012) and CYP2E1 (P = 0.0011). Analyses with the mother as the case identified four...... through the infant and/or the mother in the etiology of PTB....

  1. Association of single nucleotide polymorphisms in candidate genes previously related to genetic variation in fertility with phenotypic measurements of reproductive function in Holstein cows.

    Science.gov (United States)

    Ortega, M Sofia; Denicol, Anna C; Cole, John B; Null, Daniel J; Taylor, Jeremy F; Schnabel, Robert D; Hansen, Peter J

    2017-05-01

    Many genetic markers related to health or production traits are not evaluated in populations independent of the discovery population or related to phenotype. Here we evaluated 68 single nucleotide polymorphisms (SNP) in candidate genes previously associated with genetic merit for fertility and production traits for association with phenotypic measurements of fertility in a population of Holstein cows that was selected based on predicted transmitting ability (PTA) for daughter pregnancy rate (DPR; high, ≥1, n = 989; low, ≤ -1.0, n = 1,285). Cows with a high PTA for DPR had higher pregnancy rate at first service, fewer services per conception, and fewer days open than cows with a low PTA for DPR. Of the 68 SNP, 11 were associated with pregnancy rate at first service, 16 with services per conception, and 19 with days open. Single nucleotide polymorphisms in 12 genes (BDH2, BSP3, CAST, CD2, CD14, FUT1, FYB, GCNT3, HSD17B7, IBSP, OCLN, and PCCB) had significant associations with 2 fertility traits, and SNP in 4 genes (CSPP1, FCER1G, PMM2, and TBC1D24) had significant associations with each of the 3 traits. Results from this experiment were compared with results from 2 earlier studies in which the SNP were associated with genetic estimates of fertility. One study involved the same animals as used here, and the other study was of an independent population of bulls. A total of 13 SNP associated with 1 or more phenotypic estimates of fertility were directionally associated with genetic estimates of fertility in the same cow population. Moreover, 14 SNP associated with reproductive phenotype were directionally associated with genetic estimates of fertility in the bull population. Nine SNP (located in BCAS, BSP3, CAST, FUT1, HSD17B7, OCLN, PCCB, PMM2, and TBC1D24) had a directional association with fertility in all 3 studies. Examination of the function of the genes with SNP associated with reproduction in more than one study indicates the importance of steroid hormones

  2. Transcriptomic analysis in a Drosophila model identifies previously implicated and novel pathways in the therapeutic mechanism in neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Priyanka eSingh

    2011-03-01

    Full Text Available We have taken advantage of a newly described Drosophila model to gain insights into the potential mechanism of antiepileptic drugs (AEDs, a group of drugs that are widely used in the treatment of several neurological and psychiatric conditions besides epilepsy. In the recently described Drosophila model that is inspired by pentylenetetrazole (PTZ induced kindling epileptogenesis in rodents, chronic PTZ treatment for seven days causes a decreased climbing speed and an altered CNS transcriptome, with the latter mimicking gene expression alterations reported in epileptogenesis. In the model, an increased climbing speed is further observed seven days after withdrawal from chronic PTZ. We used this post-PTZ withdrawal regime to identify potential AED mechanism. In this regime, treatment with each of the five AEDs tested, namely, ethosuximide (ETH, gabapentin (GBP, vigabatrin (VGB, sodium valproate (NaVP and levetiracetam (LEV, resulted in rescuing of the altered climbing behavior. The AEDs also normalized PTZ withdrawal induced transcriptomic perturbation in fly heads; whereas AED untreated flies showed a large number of up- and down-regulated genes which were enriched in several processes including gene expression and cell communication, the AED treated flies showed differential expression of only a small number of genes that did not enrich gene expression and cell communication processes. Gene expression and cell communication related upregulated genes in AED untreated flies overrepresented several pathways - spliceosome, RNA degradation, and ribosome in the former category, and inositol phosphate metabolism, phosphatidylinositol signaling, endocytosis and hedgehog signaling in the latter. Transcriptome remodeling effect of AEDs was overall confirmed by microarray clustering that clearly separated the profiles of AED treated and untreated flies. Besides being consistent with previously implicated pathways, our results provide evidence for a role of

  3. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Science.gov (United States)

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G P S

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  4. Leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.

    Science.gov (United States)

    Lakshmi, Bhavana Sethu; Wang, Ruobing; Madhubala, Rentala

    2014-06-24

    Leishmaniasis is a neglected tropical disease caused by Leishmania species. It is a major health concern affecting 88 countries and threatening 350 million people globally. Unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. The emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. The genome sequence of Leishmania, provides access to novel genes that hold potential as chemotherapeutic targets or vaccine candidates. In this study, we selected 19 antigenic genes from about 8000 common Leishmania genes based on the Leishmania major and Leishmania infantum genome information available in the pathogen databases. Potential vaccine candidates thus identified were screened using an in vitro high throughput immunological platform developed in the laboratory. Four candidate genes coding for tuzin, flagellar glycoprotein-like protein (FGP), phospholipase A1-like protein (PLA1) and potassium voltage-gated channel protein (K VOLT) showed a predominant protective Th1 response over disease exacerbating Th2. We report the immunogenic properties and protective efficacy of one of the four antigens, tuzin, as a DNA vaccine against Leishmania donovani challenge. Our results show that administration of tuzin DNA protected BALB/c mice against L. donovani challenge and that protective immunity was associated with higher levels of IFN-γ and IL-12 production in comparison to IL-4 and IL-10. Our study presents a simple approach to rapidly identify potential vaccine candidates using the exhaustive information stored in the genome and an in vitro high-throughput immunological platform. Copyright © 2014. Published by Elsevier Ltd.

  5. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Directory of Open Access Journals (Sweden)

    Sapna Pahil

    Full Text Available Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I, a putative heat shock protein (EL PGI II, Spa32 (EL PGI III, IcsB (EL PGI IV and a hypothetical protein (EL PGI V. These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  6. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    KAUST Repository

    Pahil, Sapna

    2017-08-02

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  7. A Sub-Pathway Based Method to Identify Candidate Agents for Ankylosing Spondylitis

    OpenAIRE

    Chen, Kai; Zhao, Yingchuan; Chen, Yu; Wang, Chuanfeng; Chen, Ziqiang; Bai, Yushu; Zhu, Xiaodong; Li, Ming

    2012-01-01

    The need for new therapeutics for Ankylosing Spondylitis (AS) is highlighted by the general lack of efficacy for most agents currently available for this disease. Many recent studies have detailed molecular pathways in AS, and several molecule-targeting agents are undergoing evaluation. We aimed to explore the mechanism of AS and identify biologically active small molecules capable of targeting the sub-pathways which were disregulated in the development of AS. By using the GSE25101 microarray...

  8. Amplicon-based metagenomics identified candidate organisms in soils that caused yield decline in strawberry

    OpenAIRE

    Xiangming Xu; Thomas Passey; Feng Wei; Robert Saville; Richard J. Harrison

    2015-01-01

    A phenomenon of yield decline due to weak plant growth in strawberry was recently observed in non-chemo-fumigated soils, which was not associated with the soil fungal pathogen Verticillium dahliae, the main target of fumigation. Amplicon-based metagenomics was used to profile soil microbiota in order to identify microbial organisms that may have caused the yield decline. A total of 36 soil samples were obtained in 2013 and 2014 from four sites for metagenomic studies; two of the four sites ha...

  9. Accurately identifying patients who are excellent candidates or unsuitable for a medication: a novel approach

    Directory of Open Access Journals (Sweden)

    South C

    2017-12-01

    Full Text Available Charles South,1–3 A John Rush,4,* Thomas J Carmody,1–3 Manish K Jha,1,2 Madhukar H Trivedi1,2,*1Center for Depression Research and Clinical Care, 2Department of Psychiatry, 3Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Department of Psychiatry and Behavioral Sciences, Duke-National University of Singapore, Singapore; Duke Medical School, Durham, NC, USA*These authors contributed equally to this work Objective: The objective of the study was to determine whether a unique analytic approach – as a proof of concept – could identify individual depressed outpatients (using 30 baseline clinical and demographic variables who are very likely (75% certain to not benefit (NB or to remit (R, accepting that without sufficient certainty, no prediction (NP would be made.Methods: Patients from the Combining Medications to Enhance Depression Outcomes trial treated with escitalopram (S-CIT + placebo (n=212 or S-CIT + bupropion-SR (n=206 were analyzed separately to assess replicability. For each treatment, the elastic net was used to identify subsets of predictive baseline measures for R and NB, separately. Two different equations that estimate the likelihood of remission and no benefit were developed for each patient. The ratio of these two numbers characterized likely outcomes for each patient.Results: The two treatment cells had comparable rates of remission (40% and no benefit (22%. In S-CIT + bupropion-SR, 11 were predicted NB of which 82% were correct; 26 were predicted R – 85% correct (169 had NP. For S-CIT + placebo, 13 were predicted NB – 69% correct; 44 were predicted R – 75% correct (155 were NP. Overall, 94/418 (22% patients were identified with a meaningful degree of certainty (69%–85% correct. Different variable sets with some overlap were predictive of remission and no benefit within and across treatments, despite comparable outcomes.Conclusion: In two separate analyses with two

  10. Candidate Essential Genes in Burkholderia cenocepacia J2315 Identified by Genome-Wide TraDIS

    KAUST Repository

    Wong, Yee-Chin

    2016-08-22

    Burkholderia cenocepacia infection often leads to fatal cepacia syndrome in cystic fibrosis patients. However, antibiotic therapy rarely results in complete eradication of the pathogen due to its intrinsic resistance to many clinically available antibiotics. Recent attention has turned to the identification of essential genes as the proteins encoded by these genes may serve as potential targets for development of novel antimicrobials. In this study, we utilized TraDIS (Transposon Directed Insertion-site Sequencing) as a genome-wide screening tool to facilitate the identification of B. cenocepacia genes essential for its growth and viability. A transposon mutant pool consisting of approximately 500,000 mutants was successfully constructed, with more than 400,000 unique transposon insertion sites identified by computational analysis of TraDIS datasets. The saturated library allowed for the identification of 383 genes that were predicted to be essential in B. cenocepacia. We extended the application of TraDIS to identify conditionally essential genes required for in vitro growth and revealed an additional repertoire of 439 genes to be crucial for B. cenocepacia growth under nutrient-depleted conditions. The library of B. cenocepacia mutants can subsequently be subjected to various biologically related conditions to facilitate the discovery of genes involved in niche adaptation as well as pathogenicity and virulence.

  11. Clustering nuclear receptors in liver regeneration identifies candidate modulators of hepatocyte proliferation and hepatocarcinoma.

    Directory of Open Access Journals (Sweden)

    Michele Vacca

    Full Text Available Liver regeneration (LR is a valuable model for studying mechanisms modulating hepatocyte proliferation. Nuclear receptors (NRs are key players in the control of cellular functions, being ideal modulators of hepatic proliferation and carcinogenesis.We used a previously validated RT-qPCR platform to profile modifications in the expression of all 49 members of the NR superfamily in mouse liver during LR. Twenty-nine NR transcripts were significantly modified in their expression during LR, including fatty acid (peroxisome proliferator-activated receptors, PPARs and oxysterol (liver X receptors, Lxrs sensors, circadian masters RevErbα and RevErbβ, glucocorticoid receptor (Gr and constitutive androxane receptor (Car. In order to detect the NRs that better characterize proliferative status vs. proliferating liver, we used the novel Random Forest (RF analysis to selected a trio of down-regulated NRs (thyroid receptor alpha, Trα; farsenoid X receptor beta, Fxrβ; Pparδ as best discriminators of the proliferating status. To validate our approach, we further studied PPARδ role in modulating hepatic proliferation. We first confirmed the suppression of PPARδ both in LR and human hepatocellular carcinoma at protein level, and then demonstrated that PPARδ agonist GW501516 reduces the proliferative potential of hepatoma cells.Our data suggest that NR transcriptome is modulated in proliferating liver and is a source of biomarkers and bona fide pharmacological targets for the management of liver disease affecting hepatocyte proliferation.

  12. Genome-wide association study identified genetic variations and candidate genes for plant architecture component traits in Chinese upland cotton.

    Science.gov (United States)

    Su, Junji; Li, Libei; Zhang, Chi; Wang, Caixiang; Gu, Lijiao; Wang, Hantao; Wei, Hengling; Liu, Qibao; Huang, Long; Yu, Shuxun

    2018-03-01

    Thirty significant associations between 22 SNPs and five plant architecture component traits in Chinese upland cotton were identified via GWAS. Four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits. A candidate gene, Gh_D03G0922, might be responsible for plant height in upland cotton. A compact plant architecture is increasingly required for mechanized harvesting processes in China. Therefore, cotton plant architecture is an important trait, and its components, such as plant height, fruit branch length and fruit branch angle, affect the suitability of a cultivar for mechanized harvesting. To determine the genetic basis of cotton plant architecture, a genome-wide association study (GWAS) was performed using a panel composed of 355 accessions and 93,250 single nucleotide polymorphisms (SNPs) identified using the specific-locus amplified fragment sequencing method. Thirty significant associations between 22 SNPs and five plant architecture component traits were identified via GWAS. Most importantly, four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits, and these SNPs were harbored in one linkage disequilibrium block. Furthermore, 21 candidate genes for plant architecture were predicted in a 0.95-Mb region including the four peak SNPs. One of these genes (Gh_D03G0922) was near the significant SNP D03_31584163 (8.40 kb), and its Arabidopsis homologs contain MADS-box domains that might be involved in plant growth and development. qRT-PCR showed that the expression of Gh_D03G0922 was upregulated in the apical buds and young leaves of the short and compact cotton varieties, and virus-induced gene silencing (VIGS) proved that the silenced plants exhibited increased PH. These results indicate that Gh_D03G0922 is likely the candidate gene for PH in cotton. The genetic variations and candidate genes identified in this study lay a foundation

  13. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis.

    Science.gov (United States)

    Vincent, Isabel M; Daly, Rónán; Courtioux, Bertrand; Cattanach, Amy M; Biéler, Sylvain; Ndung'u, Joseph M; Bisser, Sylvie; Barrett, Michael P

    2016-12-01

    Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan) showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of "sleeping sickness". Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity) and stage of disease (92% sensitivity and 81% specificity). A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages) versus control.

  14. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Isabel M Vincent

    2016-12-01

    Full Text Available Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF. Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of "sleeping sickness". Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity and stage of disease (92% sensitivity and 81% specificity. A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages versus control.

  15. Amplicon-based metagenomics identified candidate organisms in soils that caused yield decline in strawberry.

    Science.gov (United States)

    Xu, Xiangming; Passey, Thomas; Wei, Feng; Saville, Robert; Harrison, Richard J

    2015-01-01

    A phenomenon of yield decline due to weak plant growth in strawberry was recently observed in non-chemo-fumigated soils, which was not associated with the soil fungal pathogen Verticillium dahliae, the main target of fumigation. Amplicon-based metagenomics was used to profile soil microbiota in order to identify microbial organisms that may have caused the yield decline. A total of 36 soil samples were obtained in 2013 and 2014 from four sites for metagenomic studies; two of the four sites had a yield-decline problem, the other two did not. More than 2000 fungal or bacterial operational taxonomy units (OTUs) were found in these samples. Relative abundance of individual OTUs was statistically compared for differences between samples from sites with or without yield decline. A total of 721 individual comparisons were statistically significant - involving 366 unique bacterial and 44 unique fungal OTUs. Based on further selection criteria, we focused on 34 bacterial and 17 fungal OTUs and found that yield decline resulted probably from one or more of the following four factors: (1) low abundance of Bacillus and Pseudomonas populations, which are well known for their ability of supressing pathogen development and/or promoting plant growth; (2) lack of the nematophagous fungus (Paecilomyces species); (3) a high level of two non-specific fungal root rot pathogens; and (4) wet soil conditions. This study demonstrated the usefulness of an amplicon-based metagenomics approach to profile soil microbiota and to detect differential abundance in microbes.

  16. Genetic Subtraction Profiling Identifies Candidate miRNAs Involved in Rice Female Gametophyte Abortion

    Directory of Open Access Journals (Sweden)

    Liyu Yang

    2017-07-01

    Full Text Available The female gametophyte is an important participant in the sexual reproduction of plants. The molecular mechanism of its development has received much attention in recent years. As important regulators of gene expression, miRNAs have been certified to play a significant role in many biological processes of plants, including sexual reproduction. In this study, to investigate the potential regulatory effects of miRNAs on rice female gametophyte abortion, we used the high-throughput sequencing method to compare the miRNA transcriptome in ovules of a high frequency female-sterile line (fsv1 and a rice wild-type line (Gui 99 during ovule development. As a result, 522 known miRNAs and 295 novel miRNAs were expressed in the developing ovule of rice, while 100 known miRNAs were significantly differentially expressed between these two rice lines during ovule development. Combining with gene expression information, a total of 627 coherent target genes of these differential expressed known miRNAs between fsv1 and Gui 99 were identified. The functional analyses of these coherent target genes revealed that the coherent target genes of differential expressed known miRNAs between the two rice lines are involved in many biological pathways, such as protein degradation, auxin signal transduction, and transcription factor regulation. These results provide us with important clues to investigate the regulatory roles of miRNAs in rice female gametophyte abortion.

  17. Comparative Transcriptome Analysis Identifies Candidate Genes Related to Skin Color Differentiation in Red Tilapia.

    Science.gov (United States)

    Zhu, Wenbin; Wang, Lanmei; Dong, Zaijie; Chen, Xingting; Song, Feibiao; Liu, Nian; Yang, Hui; Fu, Jianjun

    2016-08-11

    Red tilapia is becoming more popular for aquaculture production in China in recent years. However, the pigmentation differentiation in genetic breeding is the main problem limiting its development of commercial red tilapia culture and the genetic basis of skin color variation is still unknown. In this study, we conducted Illumina sequencing of transcriptome on three color variety red tilapia. A total of 224,895,758 reads were generated, resulting in 160,762 assembled contigs that were used as reference contigs. The contigs of red tilapia transcriptome had hits in the range of 53.4% to 86.7% of the unique proteins of zebrafish, fugu, medaka, three-spined stickleback and tilapia. And 44,723 contigs containing 77,423 simple sequence repeats (SSRs) were identified, with 16,646 contigs containing more than one SSR. Three skin transcriptomes were compared pairwise and the results revealed that there were 148 common significantly differentially expressed unigenes and several key genes related to pigment synthesis, i.e. tyr, tyrp1, silv, sox10, slc24a5, cbs and slc7a11, were included. The results will facilitate understanding the molecular mechanisms of skin pigmentation differentiation in red tilapia and accelerate the molecular selection of the specific strain with consistent skin colors.

  18. Assessing the potential of candidate DNA barcodes for identifying non-flowering seed plants.

    Science.gov (United States)

    Pang, X; Luo, H; Sun, C

    2012-09-01

    In plants, matK and rbcL have been selected as core barcodes by the Consortium for the Barcode of Life (CBOL) Plant Working Group (PWG), and ITS/ITS2 and psbA-trnH were suggested as supplementary loci. Yet, research on DNA barcoding of non-flowering seed plants has been less extensive, and the evaluation of DNA barcodes in this division has been limited thus far. Here, we evaluated seven markers (psbA-trnH, matK, rbcL, rpoB, rpoC1, ITS and ITS2) from non-flowering seed plants. The usefulness of each region was assessed using four criteria: the success rate of PCR amplification, the differential intra- and inter-specific divergences, the DNA barcoding gap and the ability to discriminate species. Among the seven loci tested, ITS2 produced the best results in the barcoding of non-flowering seed plants. In addition, we compared the abilities of the five most-recommended markers (psbA-trnH, matK, rbcL, ITS and ITS2) to identify additional species using a large database of gymnosperms from GenBank. ITS2 remained effective for species identification in a wide range of non-flowering seed plants: for the 1531 samples from 608 species of 80 diverse genera, ITS2 correctly authenticated 66% of them at the species level. In conclusion, the ITS2 region can serve as a useful barcode to discriminate non-flowering seed plants, and this study will contribute valuable information for the barcoding of plant species. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

  19. RNA-seq analysis of Paris polyphylla var. yunnanensis roots identified candidate genes for saponin synthesis

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2016-06-01

    Full Text Available Paris polyphylla Smith var. yunnanensis (Franch. Hand.-Mazz. is a rhizomatous, herbaceous, perennial plant that has been used for more than a thousand years in traditional Chinese medicine. It is facing extinction due to overharvesting. Steroids are the major therapeutic components in Paris roots, the commercial value of which increases with age. To date, no genomic data on the species have been available. In this study, transcriptome analysis of an 8-year-old root and a 4-year-old root provided insight into the metabolic pathways that generate the steroids. Using Illumina sequencing technology, we generated a high-quality sequence and demonstrated de novo assembly and annotation of genes in the absence of prior genome information. Approximately 87,577 unique sequences, with an average length of 614 bases, were obtained from the root cells. Using bioinformatics methods, we annotated approximately 65.51% of the unique sequences by conducting a similarity search with known genes in the National Center for Biotechnology Information's non-redundant database. The unique transcripts were functionally classified using the Gene Ontology hierarchy and the Kyoto Encyclopedia of Genes and Genomes database. Of 3082 genes that were identified as significantly differentially expressed between roots of different ages, 1518 (49.25% were upregulated and 1564 (50.75% were downregulated in the older root. Metabolic pathway analysis predicted that 25 unigenes were responsible for the biosynthesis of the saponins steroids. These data represent a valuable resource for future genomic studies on this endangered species and will be valuable for efforts to genetically engineer P. polyphylla and facilitate saponin-rich plant development.

  20. Shotgun Proteomics Identifies Serum Fibronectin as a Candidate Diagnostic Biomarker for Inclusion in Future Multiplex Tests for Ectopic Pregnancy

    Science.gov (United States)

    Brown, Jeremy K.; Lauer, Katarina B.; Ironmonger, Emily L.; Inglis, Neil F.; Bourne, Tom H.; Critchley, Hilary O. D.; Horne, Andrew W.

    2013-01-01

    Ectopic pregnancy (EP) is difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a ‘pregnancy of unknown location’ (PUL), and diagnosis and exclusion of EP is challenging due to a lack of reliable biomarkers. The objective of this study was to identify novel diagnostic biomarkers for EP. Shotgun proteomics, incorporating combinatorial-ligand library pre-fractionation, was used to interrogate pooled sera (n = 40) from women undergoing surgery for EP, termination of viable intrauterine pregnancy and management of non-viable intrauterine pregnancy. Western blot was used to validate results in individual sera. ELISAs were developed to interrogate sera from women with PUL (n = 120). Sera were collected at time of first symptomatic presentation and categorized according to pregnancy outcome. The main outcome measures were differences between groups and area under the receiver operating curve (ROC). Proteomics identified six biomarker candidates. Western blot detected significant differences in levels of two of these candidates. ELISA of sera from second cohort revealed that these differences were only significant for one of these candidates, fibronectin. ROC analysis of ability of fibronectin to discriminate EP from other pregnancy outcomes suggested that fibronectin has diagnostic potential (ROC 0.6439; 95% CI 0.5090 to 0.7788; P>0.05), becoming significant when ‘ambiguous’ medically managed PUL excluded from analysis (ROC 0.6538; 95% CI 0.5158 to 0.7918; P<0.05). Fibronectin may make a useful adjunct to future multiplex EP diagnostic tests. PMID:23826180

  1. A double-screening method to identify reliable candidate non-synonymous SNPs from chicken EST data.

    Science.gov (United States)

    Kim, H; Schmidt, C J; Decker, K S; Emara, M G

    2003-08-01

    Discovery of non-synonymous single nucleotide polymorphisms (nsSNP), which cause amino acid substitutions, is important because they are more likely to alter protein function than synonymous SNPs (sSNP) or those SNPs that do not result in amino acid changes. By changing the coding sequences, nsSNP may play a role in heritable differences between individual organisms. In the chicken and many other vertebrates, the main obstacle for identifying nsSNP is that there is insufficient protein and mRNA sequence information for self-species referencing and thus, determination of the correct reading frame for expressed sequence tags (ESTs) is difficult. Therefore, in order to estimate the correct reading frame at nsSNP in chicken ESTs, a double-screening approach was designed using self- or cross-species protein referencing, in addition to the ESTScan coding region estimation programme. Starting with 23 427 chicken ESTs, 1210 potential SNPs were discovered using a phred/phrap/polyphred/consed pipeline process and among these, 108 candidate nsSNP were identified with the double screening method. A searchable SNP database (chicksnps) for the candidate chicken SNPs, including both nsSNPs and sSNPs is available at http://chicksnps.afs.udel.edu. The chicken SNP data described in this paper have been submitted to the data base SNP under National Center for Biotechnology Information assay ID ss4387050-ss4388259.

  2. Anxiety after completion of treatment for early-stage breast cancer: a systematic review to identify candidate predictors and evaluate multivariable model development.

    Science.gov (United States)

    Harris, Jenny; Cornelius, Victoria; Ream, Emma; Cheevers, Katy; Armes, Jo

    2017-07-01

    The purpose of this review was to identify potential candidate predictors of anxiety in women with early-stage breast cancer (BC) after adjuvant treatments and evaluate methodological development of existing multivariable models to inform the future development of a predictive risk stratification model (PRSM). Databases (MEDLINE, Web of Science, CINAHL, CENTRAL and PsycINFO) were searched from inception to November 2015. Eligible studies were prospective, recruited women with stage 0-3 BC, used a validated anxiety outcome ≥3 months post-treatment completion and used multivariable prediction models. Internationally accepted quality standards were used to assess predictive risk of bias and strength of evidence. Seven studies were identified: five were observational cohorts and two secondary analyses of RCTs. Variability of measurement and selective reporting precluded meta-analysis. Twenty-one candidate predictors were identified in total. Younger age and previous mental health problems were identified as risk factors in ≥3 studies. Clinical variables (e.g. treatment, tumour grade) were not identified as predictors in any studies. No studies adhered to all quality standards. Pre-existing vulnerability to mental health problems and younger age increased the risk of anxiety after completion of treatment for BC survivors, but there was no evidence that chemotherapy was a predictor. Multiple predictors were identified but many lacked reproducibility or were not measured across studies, and inadequate reporting did not allow full evaluation of the multivariable models. The use of quality standards in the development of PRSM within supportive cancer care would improve model quality and performance, thereby allowing professionals to better target support for patients.

  3. The genome sequence of the most widely cultivated cacao type and its use to identify candidate genes regulating pod color

    Science.gov (United States)

    2013-01-01

    Background Theobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders. Results We describe the sequencing and assembly of the genome of Theobroma cacao L. cultivar Matina 1-6. The genome of the Matina 1-6 cultivar is 445 Mbp, which is significantly larger than a sequenced Criollo cultivar, and more typical of other cultivars. The chromosome-scale assembly, version 1.1, contains 711 scaffolds covering 346.0 Mbp, with a contig N50 of 84.4 kbp, a scaffold N50 of 34.4 Mbp, and an evidence-based gene set of 29,408 loci. Version 1.1 has 10x the scaffold N50 and 4x the contig N50 as Criollo, and includes 111 Mb more anchored sequence. The version 1.1 assembly has 4.4% gap sequence, while Criollo has 10.9%. Through a combination of haplotype, association mapping and gene expression analyses, we leverage this robust reference genome to identify a promising candidate gene responsible for pod color variation. We demonstrate that green/red pod color in cacao is likely regulated by the R2R3 MYB transcription factor TcMYB113, homologs of which determine pigmentation in Rosaceae, Solanaceae, and Brassicaceae. One SNP within the target site for a highly conserved trans-acting siRNA in dicots, found within TcMYB113, seems to affect transcript levels of this gene and therefore pod color variation. Conclusions We report a high-quality sequence and annotation of Theobroma cacao L. and demonstrate its utility in identifying candidate genes regulating traits. PMID:23731509

  4. The genome sequence of the most widely cultivated cacao type and its use to identify candidate genes regulating pod color.

    Science.gov (United States)

    Motamayor, Juan C; Mockaitis, Keithanne; Schmutz, Jeremy; Haiminen, Niina; Livingstone, Donald; Cornejo, Omar; Findley, Seth D; Zheng, Ping; Utro, Filippo; Royaert, Stefan; Saski, Christopher; Jenkins, Jerry; Podicheti, Ram; Zhao, Meixia; Scheffler, Brian E; Stack, Joseph C; Feltus, Frank A; Mustiga, Guiliana M; Amores, Freddy; Phillips, Wilbert; Marelli, Jean Philippe; May, Gregory D; Shapiro, Howard; Ma, Jianxin; Bustamante, Carlos D; Schnell, Raymond J; Main, Dorrie; Gilbert, Don; Parida, Laxmi; Kuhn, David N

    2013-06-03

    Theobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders. We describe the sequencing and assembly of the genome of Theobroma cacao L. cultivar Matina 1-6. The genome of the Matina 1-6 cultivar is 445 Mbp, which is significantly larger than a sequenced Criollo cultivar, and more typical of other cultivars. The chromosome-scale assembly, version 1.1, contains 711 scaffolds covering 346.0 Mbp, with a contig N50 of 84.4 kbp, a scaffold N50 of 34.4 Mbp, and an evidence-based gene set of 29,408 loci. Version 1.1 has 10x the scaffold N50 and 4x the contig N50 as Criollo, and includes 111 Mb more anchored sequence. The version 1.1 assembly has 4.4% gap sequence, while Criollo has 10.9%. Through a combination of haplotype, association mapping and gene expression analyses, we leverage this robust reference genome to identify a promising candidate gene responsible for pod color variation. We demonstrate that green/red pod color in cacao is likely regulated by the R2R3 MYB transcription factor TcMYB113, homologs of which determine pigmentation in Rosaceae, Solanaceae, and Brassicaceae. One SNP within the target site for a highly conserved trans-acting siRNA in dicots, found within TcMYB113, seems to affect transcript levels of this gene and therefore pod color variation. We report a high-quality sequence and annotation of Theobroma cacao L. and demonstrate its utility in identifying candidate genes regulating traits.

  5. Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome.

    Science.gov (United States)

    Quaynor, Samuel D; Bosley, Maggie E; Duckworth, Christina G; Porter, Kelsey R; Kim, Soo-Hyun; Kim, Hyung-Goo; Chorich, Lynn P; Sullivan, Megan E; Choi, Jeong-Hyeon; Cameron, Richard S; Layman, Lawrence C

    2016-12-05

    The genetic basis is unknown for ∼60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 18 new candidate genes including: AMN1, CCKBR, CRY1, CXCR4, FGF13, GAP43, GLI3, JAG1, NOS1, MASTL, NOTCH1, NRP2, PALM2, PDE3A, PLEKHA5, RD3, and TRAPPC9, and TSPAN11. Digenic and trigenic variants were found in 8/48 (16.7%) and 1/48 (2.1%) patients, respectively. NGS with confirmation by Sanger sequencing resulted in the identification of new causative FGFR1 gene mutations and suggested 18 new candidate genes in nHH/KS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Genome-wide association study to identify candidate loci and genes for Mn toxicity tolerance in rice.

    Directory of Open Access Journals (Sweden)

    Asis Shrestha

    Full Text Available Manganese (Mn is an essential micro-nutrient for plants, but flooded rice fields can accumulate high levels of Mn2+ leading to Mn toxicity. Here, we present a genome-wide association study (GWAS to identify candidate loci conferring Mn toxicity tolerance in rice (Oryza sativa L.. A diversity panel of 288 genotypes was grown in hydroponic solutions in a greenhouse under optimal and toxic Mn concentrations. We applied a Mn toxicity treatment (5 ppm Mn2+, 3 weeks at twelve days after transplanting. Mn toxicity caused moderate damage in rice in terms of biomass loss and symptom formation despite extremely high shoot Mn concentrations ranging from 2.4 to 17.4 mg g-1. The tropical japonica subpopulation was more sensitive to Mn toxicity than other subpopulations. Leaf damage symptoms were significantly correlated with Mn uptake into shoots. Association mapping was conducted for seven traits using 416741 single nucleotide polymorphism (SNP markers using a mixed linear model, and detected six significant associations for the traits shoot manganese concentration and relative shoot length. Candidate regions contained genes coding for a heavy metal transporter, peroxidase precursor and Mn2+ ion binding proteins. The significant marker SNP-2.22465867 caused an amino acid change in a gene (LOC_Os02g37170 with unknown function. This study demonstrated significant natural variation in rice for Mn toxicity tolerance and the possibility of using GWAS to unravel genetic factors responsible for such complex traits.

  7. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy.

    NARCIS (Netherlands)

    Otto, E.A.; Hurd, T.W.; Airik, R.; Chaki, M.; Zhou, W.; Stoetzel, C.; Patil, S.B.; Levy, S.; Ghosh, A.K.; Murga-Zamalloa, C.A.; Reeuwijk, J. van; Letteboer, S.J.F.; Sang, L.; Giles, R.H.; Liu, Q.; Coene, K.L.M.; Estrada-Cuzcano, A.; Collin, R.W.J.; McLaughlin, H.M.; Held, S.; Kasanuki, J.M.; Ramaswami, G.; Conte, J.; Lopez, I.; Washburn, J.; Macdonald, J.; Hu, J.; Yamashita, Y.; Maher, E.R.; Guay-Woodford, L.M.; Neumann, H.P.; Obermuller, N.; Koenekoop, R.K.; Bergmann, C.; Bei, X.; Lewis, R.A.; Katsanis, N.; Lopes, V.; Williams, D.S.; Lyons, R.H.; Dang, C.V.; Brito, D.A.; Dias, M.B.; Zhang, X.; Cavalcoli, J.D.; Nurnberg, G.; Nurnberg, P.; Pierce, E.A.; Jackson, P.K.; Antignac, C.; Saunier, S.; Roepman, R.; Dollfus, H.; Khanna, H.; Hildebrandt, F.

    2010-01-01

    Nephronophthisis-related ciliopathies (NPHP-RC) are recessive disorders that feature dysplasia or degeneration occurring preferentially in the kidney, retina and cerebellum. Here we combined homozygosity mapping with candidate gene analysis by performing 'ciliopathy candidate exome capture' followed

  8. Haplotype-based genome-wide association study identifies loci and candidate genes for milk yield in Holsteins.

    Directory of Open Access Journals (Sweden)

    Zhenliang Chen

    Full Text Available Since milk yield is a highly important economic trait in dairy cattle, the genome-wide association study (GWAS is vital to explain the genetic architecture underlying milk yield and to perform marker-assisted selection (MAS. In this study, we adopted a haplotype-based empirical Bayesian GWAS to identify the loci and candidate genes for milk yield. A total of 1 092 Holstein cows were sequenced by using the genotyping by genome reducing and sequencing (GGRS method. After filtering, 164 312 high-confidence SNPs and 13 476 haplotype blocks were identified to use for GWAS. The results indicated that 17 blocks were significantly associated with milk yield. We further identified the nearest gene of each haplotype block and annotated the genes with milk-associated quantitative trait locus (QTL intervals and ingenuity pathway analysis (IPA networks. Our analysis showed that four genes, DLGAP1, AP2B1, ITPR2 and THBS4, have relationships with milk yield, while another three, ARHGEF4, TDRD1 and KIF19, were inferred to have potential relationships. Additionally, a network derived from the IPA containing one inferred (ARHGEF4 and all four confirmed genes likely regulates milk yield. Our findings add to the understanding of identifying the causal genes underlying milk production traits and could guide follow up studies for further confirmation of the associated genes, pathways and biological networks.

  9. Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

    Science.gov (United States)

    Zubair, Niha; Luis Ambite, Jose; Bush, William S.; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H.; Absher, Devin; Assimes, Themistocles L.; Bielinski, Suzette J.; Bottinger, Erwin P.; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W.; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A.; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J.; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H.; Martin, Lisa W.; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P.; Robinson, Jennifer; Rotter, Jerome I.; Ryckman, Kelli K.; Schreiner, Pamela J.; Stahl, Eli; Tao, Ran; Tsai, Michael Y.; Waite, Lindsay L.; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C.; Loos, Ruth J.F.; Rich, Stephen S.; Fornage, Myriam; North, Kari E.; Kooperberg, Charles; Carty, Cara L.

    2016-01-01

    Abstract Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. PMID:28426890

  10. Identifying New Candidate Genes and Chemicals Related to Prostate Cancer Using a Hybrid Network and Shortest Path Approach.

    Science.gov (United States)

    Yuan, Fei; Zhou, You; Wang, Meng; Yang, Jing; Wu, Kai; Lu, Changhong; Kong, Xiangyin; Cai, Yu-Dong

    2015-01-01

    Prostate cancer is a type of cancer that occurs in the male prostate, a gland in the male reproductive system. Because prostate cancer cells may spread to other parts of the body and can influence human reproduction, understanding the mechanisms underlying this disease is critical for designing effective treatments. The identification of as many genes and chemicals related to prostate cancer as possible will enhance our understanding of this disease. In this study, we proposed a computational method to identify new candidate genes and chemicals based on currently known genes and chemicals related to prostate cancer by applying a shortest path approach in a hybrid network. The hybrid network was constructed according to information concerning chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions. Many of the obtained genes and chemicals are associated with prostate cancer.

  11. Examination of Previously Published Data to Identify Patterns in the Social Representation of 'Hearing Aids' Across Countries.

    Science.gov (United States)

    Manchaiah, Vinaya; Ratinaud, Pierre; Tympas, Aristotle; Danermark, Berth; Germundsson, Per

    2018-04-01

    Societal factors seem to exercise a strong influence on hearing aid uptake, use, and satisfaction. In particular, knowledge, perception, and attitude of people will have bearing towards their and others health behavior and decisions. The current study aimed at understanding the perception of hearing aids by adults belonging to the general population in different countries. The study employed a crosssectional design. A sample of 404 adults from India, Iran, Portugal, and the United Kingdom were recruited by relying on a convenience sampling. Previously published data was re-analyzed but it was applied for different approach. Free association task was used to collect the data. They were asked to provide up to five words or phrases that come to mind when thinking about "hearing aids." The data was initially analyzed based on qualitative content analysis. This was followed by quantitative cluster analysis and chi square analysis. The content analysis suggested 39 main categories of responses related to hearing aids. The cluster analysis resulted in five main clusters, namely: 1) positive attitude, 2) external factors, 3) hearing aid use and satisfaction, 4) etiology, and 5) benefits and limitations of technology. A few demographic factors (i.e., education, occupation type, country) showed association with different clusters, although country of origin seemed to be associated with most clusters. The study provides us with unique insights into the perception of hearing aids by the general public, and additionally, the way demographic variables may influence these perceptions.

  12. Editor's Highlight: Candidate Risk Factors and Mechanisms for Tolvaptan-Induced Liver Injury Are Identified Using a Collaborative Cross Approach.

    Science.gov (United States)

    Mosedale, Merrie; Kim, Yunjung; Brock, William J; Roth, Sharin E; Wiltshire, Tim; Eaddy, J Scott; Keele, Gregory R; Corty, Robert W; Xie, Yuying; Valdar, William; Watkins, Paul B

    2017-04-01

    Clinical trials of tolvaptan showed it to be a promising candidate for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential for idiosyncratic drug-induced liver injury (DILI) in this patient population. To identify risk factors and mechanisms underlying tolvaptan DILI, 8 mice in each of 45 strains of the genetically diverse Collaborative Cross (CC) mouse population were treated with a single oral dose of either tolvaptan or vehicle. Significant elevations in plasma alanine aminotransferase (ALT) were observed in tolvaptan-treated animals in 3 of the 45 strains. Genetic mapping coupled with transcriptomic analysis in the liver was used to identify several candidate susceptibility genes including epoxide hydrolase 2, interferon regulatory factor 3, and mitochondrial fission factor. Gene pathway analysis revealed that oxidative stress and immune response pathways were activated in response to tolvaptan treatment across all strains, but genes involved in regulation of bile acid homeostasis were most associated with tolvaptan-induced elevations in ALT. Secretory leukocyte peptidase inhibitor (Slpi) mRNA was also induced in the susceptible strains and was associated with increased plasma levels of Slpi protein, suggesting a potential serum marker for DILI susceptibility. In summary, tolvaptan induced signs of oxidative stress, mitochondrial dysfunction, and innate immune response in all strains, but variation in bile acid homeostasis was most associated with susceptibility to the liver response. This CC study has indicated potential mechanisms underlying tolvaptan DILI and biomarkers of susceptibility that may be useful in managing the risk of DILI in ADPKD patients. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk

    DEFF Research Database (Denmark)

    Blackburn, Anneke C; Hill, Linda Z; Roberts, Amy L

    2007-01-01

    Low-penetrance breast cancer susceptibility alleles seem to play a significant role in breast cancer risk but are difficult to identify in human cohorts. A genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and C57BL/6, which differ in their susceptibility to mammary...... tumors, identified a modifier of mammary tumor susceptibility in an approximately 25-Mb interval on mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from 70.7 to 61.1 weeks and increased risk...... twofold (P = 0.002). Dmbt1 (deleted in malignant brain tumors 1) was identified as a candidate modifier gene within the SuprMam1 interval because it was differentially expressed in mammary tissues from BALB/c-Trp53(+/-) and C57BL/6-Trp53(+/-) mice. Dmbt1 mRNA and protein was reduced in mammary glands...

  14. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    Directory of Open Access Journals (Sweden)

    Gonzalez-Neira Anna

    2007-08-01

    Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

  15. Mapping by sequencing in cotton (Gossypium hirsutum) line MD52ne identified candidate genes for fiber strength and its related quality attributes.

    Science.gov (United States)

    Islam, Md S; Zeng, Linghe; Thyssen, Gregory N; Delhom, Christopher D; Kim, Hee Jin; Li, Ping; Fang, David D

    2016-06-01

    Three QTL regions controlling three fiber quality traits were validated and further fine-mapped with 27 new single nucleotide polymorphism (SNP) markers. Transcriptome analysis suggests that receptor-like kinases found within the validated QTLs are potential candidate genes responsible for superior fiber strength in cotton line MD52ne. Fiber strength, length, maturity and fineness determine the market value of cotton fibers and the quality of spun yarn. Cotton fiber strength has been recognized as a critical quality attribute in the modern textile industry. Fine mapping along with quantitative trait loci (QTL) validation and candidate gene prediction can uncover the genetic and molecular basis of fiber quality traits. Four previously-identified QTLs (qFBS-c3, qSFI-c14, qUHML-c14 and qUHML-c24) related to fiber bundle strength, short fiber index and fiber length, respectively, were validated using an F3 population that originated from a cross of MD90ne × MD52ne. A group of 27 new SNP markers generated from mapping-by-sequencing (MBS) were placed in QTL regions to improve and validate earlier maps. Our refined QTL regions spanned 4.4, 1.8 and 3.7 Mb of physical distance in the Gossypium raimondii reference genome. We performed RNA sequencing (RNA-seq) of 15 and 20 days post-anthesis fiber cells from MD52ne and MD90ne and aligned reads to the G. raimondii genome. The QTL regions contained 21 significantly differentially expressed genes (DEGs) between the two near-isogenic parental lines. SNPs that result in non-synonymous substitutions to amino acid sequences of annotated genes were identified within these DEGs, and mapped. Taken together, transcriptome and amino acid mutation analysis indicate that receptor-like kinase pathway genes are likely candidates for superior fiber strength and length in MD52ne. MBS along with RNA-seq demonstrated a powerful strategy to elucidate candidate genes for the QTLs that control complex traits in a complex genome like tetraploid

  16. Time-course microarray analysis for identifying candidate genes involved in obesity-associated pathological changes in the mouse colon.

    Science.gov (United States)

    Bae, Yun Jung; Kim, Sung-Eun; Hong, Seong Yeon; Park, Taesun; Lee, Sang Gyu; Choi, Myung-Sook; Sung, Mi-Kyung

    2016-01-01

    Obesity is known to increase the risk of colorectal cancer. However, mechanisms underlying the pathogenesis of obesity-induced colorectal cancer are not completely understood. The purposes of this study were to identify differentially expressed genes in the colon of mice with diet-induced obesity and to select candidate genes as early markers of obesity-associated abnormal cell growth in the colon. C57BL/6N mice were fed normal diet (11% fat energy) or high-fat diet (40% fat energy) and were euthanized at different time points. Genome-wide expression profiles of the colon were determined at 2, 4, 8, and 12 weeks. Cluster analysis was performed using expression data of genes showing log 2 fold change of ≥1 or ≤-1 (twofold change), based on time-dependent expression patterns, followed by virtual network analysis. High-fat diet-fed mice showed significant increase in body weight and total visceral fat weight over 12 weeks. Time-course microarray analysis showed that 50, 47, 36, and 411 genes were differentially expressed at 2, 4, 8, and 12 weeks, respectively. Ten cluster profiles representing distinguishable patterns of genes differentially expressed over time were determined. Cluster 4, which consisted of genes showing the most significant alterations in expression in response to high-fat diet over 12 weeks, included Apoa4 (apolipoprotein A-IV), Ppap2b (phosphatidic acid phosphatase type 2B), Cel (carboxyl ester lipase), and Clps (colipase, pancreatic), which interacted strongly with surrounding genes associated with colorectal cancer or obesity. Our data indicate that Apoa4 , Ppap2b , Cel , and Clps are candidate early marker genes associated with obesity-related pathological changes in the colon. Genome-wide analyses performed in the present study provide new insights on selecting novel genes that may be associated with the development of diseases of the colon.

  17. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signalling

    Directory of Open Access Journals (Sweden)

    Mehanathan eMuthamilarasan

    2015-10-01

    Full Text Available Transcription factors (TFs are major players in stress signalling and constitute an integral part of signalling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4 model plants, Setaria italica (SiWRKY and S. viridis (SvWRKY, respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins that were computationally analysed for their physicochemical properties. Sequence alignment and phylogenetic analysis classified these proteins into three major groups, namely I, II and III with majority of WRKY proteins belonging to group II (53 SiWRKY and 23 SvWRKY, followed by group III (39 SiWRKY and 11 SvWRKY and group I (10 SiWRKY and 6 SvWRKY. Group II proteins were further classified into 5 subgroups (IIa to IIe based on their phylogeny. Domain analysis showed the presence of WRKY motif and zinc finger-like structures in these proteins along with additional domains in a few proteins. All SiWRKY genes were physically mapped on the S. italica genome and their duplication analysis revealed that 10 and 8 gene pairs underwent tandem and segmental duplications, respectively. Comparative mapping of SiWRKY and SvWRKY genes in related C4 panicoid genomes demonstrated the orthologous relationships between these genomes. In silico expression analysis of SiWRKY and SvWRKY genes showed their differential expression patterns in different tissues and stress conditions. Expression profiling of candidate SiWRKY genes in response to stress (dehydration and salinity and hormone treatments (abscisic acid, salicylic acid and methyl jasmonate suggested the putative involvement of SiWRKY066 and SiWRKY082 in stress and hormone signalling. These genes could be potential candidates for further characterization to delineate their functional roles in abiotic stress signalling.

  18. Get Tough, Get Toxic, or Get a Bodyguard: Identifying Candidate Traits Conferring Belowground Resistance to Herbivores in Grasses.

    Science.gov (United States)

    Moore, Ben D; Johnson, Scott N

    2016-01-01

    Grasses (Poaceae) are the fifth-largest plant family by species and their uses for crops, forage, fiber, and fuel make them the most economically important. In grasslands, which broadly-defined cover 40% of the Earth's terrestrial surface outside of Greenland and Antarctica, 40-60% of net primary productivity and 70-98% of invertebrate biomass occurs belowground, providing extensive scope for interactions between roots and rhizosphere invertebrates. Grasses invest 50-70% of fixed carbon into root construction, which suggests roots are high value tissues that should be defended from herbivores, but we know relatively little about such defenses. In this article, we identify candidate grass root defenses, including physical (tough) and chemical (toxic) resistance traits, together with indirect defenses involving recruitment of root herbivores' natural enemies. We draw on relevant literature to establish whether these defenses are present in grasses, and specifically in grass roots, and which herbivores of grasses are affected by these defenses. Physical defenses could include structural macro-molecules such as lignin, cellulose, suberin, and callose in addition to silica and calcium oxalate. Root hairs and rhizosheaths, a structural adaptation unique to grasses, might also play defensive roles. To date, only lignin and silica have been shown to negatively affect root herbivores. In terms of chemical resistance traits, nitrate, oxalic acid, terpenoids, alkaloids, amino acids, cyanogenic glycosides, benzoxazinoids, phenolics, and proteinase inhibitors have the potential to negatively affect grass root herbivores. Several good examples demonstrate the existence of indirect defenses in grass roots, including maize, which can recruit entomopathogenic nematodes (EPNs) via emission of (E)-β-caryophyllene, and similar defenses are likely to be common. In producing this review, we aimed to equip researchers with candidate root defenses for further research.

  19. Analysis of gene expression in the nervous system identifies key genes and novel candidates for health and disease.

    Science.gov (United States)

    Carpanini, Sarah M; Wishart, Thomas M; Gillingwater, Thomas H; Manson, Jean C; Summers, Kim M

    2017-04-01

    The incidence of neurodegenerative diseases in the developed world has risen over the last century, concomitant with an increase in average human lifespan. A major challenge is therefore to identify genes that control neuronal health and viability with a view to enhancing neuronal health during ageing and reducing the burden of neurodegeneration. Analysis of gene expression data has recently been used to infer gene functions for a range of tissues from co-expression networks. We have now applied this approach to transcriptomic datasets from the mammalian nervous system available in the public domain. We have defined the genes critical for influencing neuronal health and disease in different neurological cell types and brain regions. The functional contribution of genes in each co-expression cluster was validated using human disease and knockout mouse phenotypes, pathways and gene ontology term annotation. Additionally a number of poorly annotated genes were implicated by this approach in nervous system function. Exploiting gene expression data available in the public domain allowed us to validate key nervous system genes and, importantly, to identify additional genes with minimal functional annotation but with the same expression pattern. These genes are thus novel candidates for a role in neurological health and disease and could now be further investigated to confirm their function and regulation during ageing and neurodegeneration.

  20. Environmental Association Analyses Identify Candidates for Abiotic Stress Tolerance in Glycine soja, the Wild Progenitor of Cultivated Soybeans.

    Science.gov (United States)

    Anderson, Justin E; Kono, Thomas J Y; Stupar, Robert M; Kantar, Michael B; Morrell, Peter L

    2016-04-07

    Natural populations across a species range demonstrate population structure owing to neutral processes such as localized origins of mutations and migration limitations. Selection also acts on a subset of loci, contributing to local adaptation. An understanding of the genetic basis of adaptation to local environmental conditions is a fundamental goal in basic biological research. When applied to crop wild relatives, this same research provides the opportunity to identify adaptive genetic variation that may be used to breed for crops better adapted to novel or changing environments. The present study explores an ex situ conservation collection, the USDA germplasm collection, genotyped at 32,416 SNPs to identify population structure and test for associations with bioclimatic and biophysical variables in Glycine soja, the wild progenitor of Glycine max (soybean). Candidate loci were detected that putatively contribute to adaptation to abiotic stresses. The identification of potentially adaptive variants in this ex situ collection may permit a more targeted use of germplasm collections. Copyright © 2016 Anderson et al.

  1. Genome-wide DNA methylation analysis identifies MEGF10 as a novel epigenetically repressed candidate tumor suppressor gene in neuroblastoma.

    Science.gov (United States)

    Charlet, Jessica; Tomari, Ayumi; Dallosso, Anthony R; Szemes, Marianna; Kaselova, Martina; Curry, Thomas J; Almutairi, Bader; Etchevers, Heather C; McConville, Carmel; Malik, Karim T A; Brown, Keith W

    2017-04-01

    Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome-wide mutation analyses, many primary neuroblastomas do not contain recognizable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took the novel approach of comparing neuroblastomas to neural crest precursor cells, using genome-wide DNA methylation analysis. We identified 93 genes that were significantly differentially methylated of which 26 (28%) were hypermethylated and 67 (72%) were hypomethylated. Concentrating on hypermethylated genes to identify candidate tumor suppressor loci, we found the cell engulfment and adhesion factor gene MEGF10 to be epigenetically repressed by DNA hypermethylation or by H3K27/K9 methylation in neuroblastoma cell lines. MEGF10 showed significantly down-regulated expression in neuroblastoma tumor samples; furthermore patients with the lowest-expressing tumors had reduced relapse-free survival. Our functional studies showed that knock-down of MEGF10 expression in neuroblastoma cell lines promoted cell growth, consistent with MEGF10 acting as a clinically relevant, epigenetically deregulated neuroblastoma tumor suppressor gene. © 2016 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc. © 2016 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc.

  2. Genome‐wide DNA methylation analysis identifies MEGF10 as a novel epigenetically repressed candidate tumor suppressor gene in neuroblastoma

    Science.gov (United States)

    Charlet, Jessica; Tomari, Ayumi; Dallosso, Anthony R.; Szemes, Marianna; Kaselova, Martina; Curry, Thomas J.; Almutairi, Bader; Etchevers, Heather C.; McConville, Carmel; Malik, Karim T. A.

    2016-01-01

    Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome‐wide mutation analyses, many primary neuroblastomas do not contain recognizable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took the novel approach of comparing neuroblastomas to neural crest precursor cells, using genome‐wide DNA methylation analysis. We identified 93 genes that were significantly differentially methylated of which 26 (28%) were hypermethylated and 67 (72%) were hypomethylated. Concentrating on hypermethylated genes to identify candidate tumor suppressor loci, we found the cell engulfment and adhesion factor gene MEGF10 to be epigenetically repressed by DNA hypermethylation or by H3K27/K9 methylation in neuroblastoma cell lines. MEGF10 showed significantly down‐regulated expression in neuroblastoma tumor samples; furthermore patients with the lowest‐expressing tumors had reduced relapse‐free survival. Our functional studies showed that knock‐down of MEGF10 expression in neuroblastoma cell lines promoted cell growth, consistent with MEGF10 acting as a clinically relevant, epigenetically deregulated neuroblastoma tumor suppressor gene. © 2016 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc. PMID:27862318

  3. Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L.) Using SLAF-seq

    Science.gov (United States)

    Xie, Dongwei; Dai, Zhigang; Yang, Zemao; Sun, Jian; Zhao, Debao; Yang, Xue; Zhang, Liguo; Tang, Qing; Su, Jianguang

    2018-01-01

    Flax (Linum usitatissimum L.) is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq) was employed to perform a genome-wide association study (GWAS) for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP) loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM) and a mixed linear model (MLM) as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits. PMID:29375606

  4. The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome

    Directory of Open Access Journals (Sweden)

    Molly B. Sheridan

    2015-01-01

    Full Text Available Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome. DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism. DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions of DCAF17 in the proband revealed homozygosity for a previously described founder mutation (c.436delC. Targeted DCAF17 sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified.

  5. A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes

    Directory of Open Access Journals (Sweden)

    Slifer Susan

    2011-07-01

    Full Text Available Abstract Background Left ventricular mass (LVM is an important risk factor for cardiovascular disease. Previously we found evidence for linkage to chromosome 12p11 in Dominican families, with a significant increase in a subset of families with high average waist circumference (WC. In the present study, we use association analysis to further study the genetic effect on LVM. Methods Association analysis with LVM was done in the one LOD critical region of the linkage peak in an independent sample of 897 Caribbean Hispanics. Genotype data were available on 7085 SNPs from 23 to 53 MB on chromosome 12p11. Adjustment was made for vascular risk factors and population substructure using an additive genetic model. Subset analysis by WC was performed to test for a difference in genetic effects between the high and low WC subsets. Results In the overall analysis, the most significant association was found to rs10743465, downstream of the SOX5 gene (p = 1.27E-05. Also, 19 additional SNPs had nominal p TMTC1. Twelve additional SNPs in or near 6 genes had p Conclusions The current study supports previously identified evidence by linkage for a genetic effect on LVM on chromosome 12p11 using association analysis in population-based Caribbean Hispanic cohort. SOX5 may play an important role in the regulation of LVM. An interaction of TMTC1 with abdominal obesity may contribute to phenotypic variation of LVM.

  6. Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.

    Science.gov (United States)

    Bae, Ha Ae; Mills, Richard A D; Lindsay, Richard G; Phillips, Tony; Coster, Douglas J; Mitchell, Paul; Wang, Jie Jin; Craig, Jamie E; Burdon, Kathryn P

    2013-07-30

    Keratoconus is a common complex corneal ectasia that can lead to severe visual impairment. Although a genetic component is well recognized, the genetic risk factors for keratoconus are yet to be fully elucidated. A recent genome-wide association study (GWAS) by Li et al. identified 15 potentially associated single nucleotide polymorphisms (SNPs). Here, we aimed to replicate these associations, and conduct a meta-analysis of the current and previous studies. We genotyped the 15 reported associated SNPs in 524 Australian Caucasian cases with keratoconus and 2761 controls. Association analysis was conducted in PLINK. A meta-analysis of this study with the adjusted P values of the previously published GWAS was conducted using the method of Fisher to combine P values. Our Australian cohort showed association (P keratoconus, with P = 9.26 × 10(-9) passing the genome-wide significance level. Although the mechanism of disease association is yet to be determined, SNP rs4954218 is associated consistently with keratoconus and likely tags a functional variant that contributes to disease susceptibility.

  7. Transcriptomic characterization of two major Fusarium resistance quantitative trait loci (QTLs), Fhb1 and Qfhs.ifa-5A, identifies novel candidate genes

    Science.gov (United States)

    Schweiger, Wolfgang; Steiner, Barbara; Ametz, Christian; Siegwart, Gerald; Wiesenberger, Gerlinde; Berthiller, Franz; Lemmens, Marc; Jia, Haiyan; Adam, Gerhard; Muehlbauer, Gary J; Kreil, David P; Buerstmayr, Hermann

    2013-01-01

    Fusarium head blight, caused by Fusarium graminearum, is a devastating disease of wheat. We developed near-isogenic lines (NILs) differing in the two strongest known F. graminearum resistance quantitative trait loci (QTLs), Qfhs.ndsu-3BS (also known as resistance gene Fhb1) and Qfhs.ifa-5A, which are located on the short arm of chromosome 3B and on chromosome 5A, respectively. These NILs showing different levels of resistance were used to identify transcripts that are changed significantly in a QTL-specific manner in response to the pathogen and between mock-inoculated samples. After inoculation with F. graminearum spores, 16 transcripts showed a significantly different response for Fhb1 and 352 for Qfhs.ifa-5A. Notably, we identified a lipid transfer protein which is constitutively at least 50-fold more abundant in plants carrying the resistant allele of Qfhs.ifa-5A. In addition to this candidate gene associated with Qfhs.ifa-5A, we identified a uridine diphosphate (UDP)-glycosyltransferase gene, designated TaUGT12887, exhibiting a positive difference in response to the pathogen in lines harbouring both QTLs relative to lines carrying only the Qfhs.ifa-5A resistance allele, suggesting Fhb1 dependence of this transcript. Yet, this dependence was observed only in the NIL with already higher basal resistance. The complete cDNA of TaUGT12887 was reconstituted from available wheat genomic sequences, and a synthetic recoded gene was expressed in a toxin-sensitive strain of Saccharomyces cerevisiae. This gene conferred deoxynivalenol resistance, albeit much weaker than that observed with the previously characterized barley HvUGT13248. PMID:23738863

  8. Next-generation sequencing to identify candidate genes and develop diagnostic markers for a novel Phytophthora resistance gene, RpsHC18, in soybean.

    Science.gov (United States)

    Zhong, Chao; Sun, Suli; Li, Yinping; Duan, Canxing; Zhu, Zhendong

    2018-03-01

    A novel Phytophthora sojae resistance gene RpsHC18 was identified and finely mapped on soybean chromosome 3. Two NBS-LRR candidate genes were identified and two diagnostic markers of RpsHC18 were developed. Phytophthora root rot caused by Phytophthora sojae is a destructive disease of soybean. The most effective disease-control strategy is to deploy resistant cultivars carrying Phytophthora-resistant Rps genes. The soybean cultivar Huachun 18 has a broad and distinct resistance spectrum to 12 P. sojae isolates. Quantitative trait loci sequencing (QTL-seq), based on the whole-genome resequencing (WGRS) of two extreme resistant and susceptible phenotype bulks from an F 2:3 population, was performed, and one 767-kb genomic region with ΔSNP-index ≥ 0.9 on chromosome 3 was identified as the RpsHC18 candidate region in Huachun 18. The candidate region was reduced to a 146-kb region by fine mapping. Nonsynonymous SNP and haplotype analyses were carried out in the 146-kb region among ten soybean genotypes using WGRS. Four specific nonsynonymous SNPs were identified in two nucleotide-binding sites-leucine-rich repeat (NBS-LRR) genes, RpsHC18-NBL1 and RpsHC18-NBL2, which were considered to be the candidate genes. Finally, one specific SNP marker in each candidate gene was successfully developed using a tetra-primer ARMS-PCR assay, and the two markers were verified to be specific for RpsHC18 and to effectively distinguish other known Rps genes. In this study, we applied an integrated genomic-based strategy combining WGRS with traditional genetic mapping to identify RpsHC18 candidate genes and develop diagnostic markers. These results suggest that next-generation sequencing is a precise, rapid and cost-effective way to identify candidate genes and develop diagnostic markers, and it can accelerate Rps gene cloning and marker-assisted selection for breeding of P. sojae-resistant soybean cultivars.

  9. Candidate gene analysis of tooth agenesis identifies novel mutations in six genes and suggests significant role for WNT and EDA signaling and allele combinations.

    Directory of Open Access Journals (Sweden)

    Sirpa Arte

    Full Text Available Failure to develop complete dentition, tooth agenesis, is a common developmental anomaly manifested most often as isolated but also as associated with many developmental syndromes. It typically affects third molars or one or few other permanent teeth but severe agenesis is also relatively prevalent. Here we report mutational analyses of seven candidate genes in a cohort of 127 probands with non-syndromic tooth agenesis. 82 lacked more than five permanent teeth excluding third molars, called as oligodontia. We identified 28 mutations, 17 of which were novel. Together with our previous reports, we have identified two mutations in MSX1, AXIN2 and EDARADD, five in PAX9, four in EDA and EDAR, and nine in WNT10A. They were observed in 58 probands (44%, with a mean number of missing teeth of 11.7 (range 4 to 34. Almost all of these probands had severe agenesis. Only few of the probands but several relatives with heterozygous genotypes of WNT10A or EDAR conformed to the common type of non-syndromic tooth agenesis, incisor-premolar hypodontia. Mutations in MSX1 and PAX9 affected predominantly posterior teeth, whereas both deciduous and permanent incisors were especially sensitive to mutations in EDA and EDAR. Many mutations in EDAR, EDARADD and WNT10A were present in several families. Biallelic or heterozygous genotypes of WNT10A were observed in 32 and hemizygous or heterozygous genotypes of EDA, EDAR or EDARADD in 22 probands. An EDARADD variant were in seven probands present together with variants in EDAR or WNT10A, suggesting combined phenotypic effects of alleles in distinct genes.

  10. Candidate Gene Analysis of Tooth Agenesis Identifies Novel Mutations in Six Genes and Suggests Significant Role for WNT and EDA Signaling and Allele Combinations

    Science.gov (United States)

    Arte, Sirpa; Parmanen, Satu; Pirinen, Sinikka; Alaluusua, Satu; Nieminen, Pekka

    2013-01-01

    Failure to develop complete dentition, tooth agenesis, is a common developmental anomaly manifested most often as isolated but also as associated with many developmental syndromes. It typically affects third molars or one or few other permanent teeth but severe agenesis is also relatively prevalent. Here we report mutational analyses of seven candidate genes in a cohort of 127 probands with non-syndromic tooth agenesis. 82 lacked more than five permanent teeth excluding third molars, called as oligodontia. We identified 28 mutations, 17 of which were novel. Together with our previous reports, we have identified two mutations in MSX1, AXIN2 and EDARADD, five in PAX9, four in EDA and EDAR, and nine in WNT10A. They were observed in 58 probands (44%), with a mean number of missing teeth of 11.7 (range 4 to 34). Almost all of these probands had severe agenesis. Only few of the probands but several relatives with heterozygous genotypes of WNT10A or EDAR conformed to the common type of non-syndromic tooth agenesis, incisor-premolar hypodontia. Mutations in MSX1 and PAX9 affected predominantly posterior teeth, whereas both deciduous and permanent incisors were especially sensitive to mutations in EDA and EDAR. Many mutations in EDAR, EDARADD and WNT10A were present in several families. Biallelic or heterozygous genotypes of WNT10A were observed in 32 and hemizygous or heterozygous genotypes of EDA, EDAR or EDARADD in 22 probands. An EDARADD variant were in seven probands present together with variants in EDAR or WNT10A, suggesting combined phenotypic effects of alleles in distinct genes. PMID:23991204

  11. Transcriptomic Analysis Identifies Candidate Genes Related to Intramuscular Fat Deposition and Fatty Acid Composition in the Breast Muscle of Squabs (Columba

    Directory of Open Access Journals (Sweden)

    Manhong Ye

    2016-07-01

    Full Text Available Despite the fact that squab is consumed throughout the world because of its high nutritional value and appreciated sensory attributes, aspects related to its characterization, and in particular genetic issues, have rarely been studied. In this study, meat traits in terms of pH, water-holding capacity, intramuscular fat content, and fatty acid profile of the breast muscle of squabs from two meat pigeon breeds were determined. Breed-specific differences were detected in fat-related traits of intramuscular fat content and fatty acid composition. RNA-Sequencing was applied to compare the transcriptomes of muscle and liver tissues between squabs of two breeds to identify candidate genes associated with the differences in the capacity of fat deposition. A total of 27 differentially expressed genes assigned to pathways of lipid metabolism were identified, of which, six genes belonged to the peroxisome proliferator-activated receptor signaling pathway along with four other genes. Our results confirmed in part previous reports in livestock and provided also a number of genes which had not been related to fat deposition so far. These genes can serve as a basis for further investigations to screen markers closely associated with intramuscular fat content and fatty acid composition in squabs. The data from this study were deposited in the National Center for Biotechnology Information (NCBI’s Sequence Read Archive under the accession numbers SRX1680021 and SRX1680022. This is the first transcriptome analysis of the muscle and liver tissue in Columba using next generation sequencing technology. Data provided here are of potential value to dissect functional genes influencing fat deposition in squabs.

  12. Comparative transcriptome analysis of stylar canal cells identifies novel candidate genes implicated in the self-incompatibility response of Citrus clementina

    Directory of Open Access Journals (Sweden)

    Caruso Marco

    2012-02-01

    Full Text Available Abstract Background Reproductive biology in citrus is still poorly understood. Although in recent years several efforts have been made to study pollen-pistil interaction and self-incompatibility, little information is available about the molecular mechanisms regulating these processes. Here we report the identification of candidate genes involved in pollen-pistil interaction and self-incompatibility in clementine (Citrus clementina Hort. ex Tan.. These genes have been identified comparing the transcriptomes of laser-microdissected stylar canal cells (SCC isolated from two genotypes differing for self-incompatibility response ('Comune', a self-incompatible cultivar and 'Monreal', a self- compatible mutation of 'Comune'. Results The transcriptome profiling of SCC indicated that the differential regulation of few specific, mostly uncharacterized transcripts is associated with the breakdown of self-incompatibility in 'Monreal'. Among them, a novel F-box gene showed a drastic up-regulation both in laser microdissected stylar canal cells and in self-pollinated whole styles with stigmas of 'Comune' in concomitance with the arrest of pollen tube growth. Moreover, we identify a non-characterized gene family as closely associated to the self-incompatibility genetic program activated in 'Comune'. Three different aspartic-acid rich (Asp-rich protein genes, located in tandem in the clementine genome, were over-represented in the transcriptome of 'Comune'. These genes are tightly linked to a DELLA gene, previously found to be up-regulated in the self-incompatible genotype during pollen-pistil interaction. Conclusion The highly specific transcriptome survey of the stylar canal cells identified novel genes which have not been previously associated with self-pollen rejection in citrus and in other plant species. Bioinformatic and transcriptional analyses suggested that the mutation leading to self-compatibility in 'Monreal' affected the expression of non

  13. A Bayesian Framework for Generalized Linear Mixed Modeling Identifies New Candidate Loci for Late-Onset Alzheimer's Disease.

    Science.gov (United States)

    Wang, Xulong; Philip, Vivek M; Ananda, Guruprasad; White, Charles C; Malhotra, Ankit; Michalski, Paul J; Karuturi, Krishna R Murthy; Chintalapudi, Sumana R; Acklin, Casey; Sasner, Michael; Bennett, David A; De Jager, Philip L; Howell, Gareth R; Carter, Gregory W

    2018-03-05

    Recent technical and methodological advances have greatly enhanced genome-wide association studies (GWAS). The advent of low-cost whole-genome sequencing facilitates high-resolution variant identification, and the development of linear mixed models (LMM) allows improved identification of putatively causal variants. While essential for correcting false positive associations due to sample relatedness and population stratification, LMMs have commonly been restricted to quantitative variables. However, phenotypic traits in association studies are often categorical, coded as binary case-control or ordered variables describing disease stages. To address these issues, we have devised a method for genomic association studies that implements a generalized linear mixed model (GLMM) in a Bayesian framework, called Bayes-GLMM Bayes-GLMM has four major features: (1) support of categorical, binary and quantitative variables; (2) cohesive integration of previous GWAS results for related traits; (3) correction for sample relatedness by mixed modeling; and (4) model estimation by both Markov chain Monte Carlo (MCMC) sampling and maximal likelihood estimation. We applied Bayes-GLMM to the whole-genome sequencing cohort of the Alzheimer's Disease Sequencing Project (ADSP). This study contains 570 individuals from 111 families, each with Alzheimer's disease diagnosed at one of four confidence levels. With Bayes-GLMM we identified four variants in three loci significantly associated with Alzheimer's disease. Two variants, rs140233081 and rs149372995 lie between PRKAR1B and PDGFA The coded proteins are localized to the glial-vascular unit, and PDGFA transcript levels are associated with AD-related neuropathology. In summary, this work provides implementation of a flexible, generalized mixed model approach in a Bayesian framework for association studies. Copyright © 2018, Genetics.

  14. Genome-wide association analysis identifies new candidate risk loci for familial intracranial aneurysm in the French-Canadian population.

    Science.gov (United States)

    Zhou, Sirui; Gan-Or, Ziv; Ambalavanan, Amirthagowri; Lai, Dongbing; Xie, Pingxing; Bourassa, Cynthia V; Strong, Stephanie; Ross, Jay P; Dionne-Laporte, Alexandre; Spiegelman, Dan; Dupré, Nicolas; Foroud, Tatiana M; Xiong, Lan; Dion, Patrick A; Rouleau, Guy A

    2018-03-12

    Intracranial Aneurysm (IA) is a common disease with a worldwide prevalence of 1-3%. In the French-Canadian (FC) population, where there is an important founder effect, the incidence of IA is higher and is frequently seen in families. In this study, we genotyped a cohort of 257 mostly familial FC IA patients and 1,992 FC controls using the Illumina NeuroX SNP-chip. The most strongly associated loci were tested in 34 Inuit IA families and in 32 FC IA patients and 106 FC controls that had been exome sequenced (WES). After imputation, one locus at 3p14.2 (FHIT, rs1554600, p = 4.66 × 10 -9 ) reached a genome-wide significant level of association and a subsequent validation in Nunavik Inuit cohort further confirmed the significance of the FHIT variant association (rs780365, FBAT-O, p = 0.002839). Additionally, among the other promising loci (p < 5 × 10 -6 ), the one at 3q13.2 (rs78125721, p = 4.77 × 10 -7 ), which encompasses CCDC80, also showed an increased mutation burden in the WES data (CCDC80, SKAT-O, p = 0.0005). In this study, we identified two new potential IA loci in the FC population: FHIT, which is significantly associated with hypertensive IA, and CCDC80, which has potential genetic and functional relevance to IA pathogenesis, providing evidence on the additional risk loci for familial IA. We also replicated the previous IA GWAS risk locus 18q11.2, and suggested a potential locus at 8p23.1 that warrants further study.

  15. Using microarrays to identify positional candidate genes for QTL: the case study of ACTH response in pigs

    DEFF Research Database (Denmark)

    Jouffe, Vincent; Rowe, Suzanne; Liaubet, Laurence

    2009-01-01

    of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH) Microarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide...... this with information on published QTL. The starting point is a set of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH) Results: Different approaches to localize the differentially expressed (DE) genes to the pig genome...

  16. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    Science.gov (United States)

    Vigorito, Elena; Kuchenbaecker, Karoline B.; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A.; Andrulis, Irene L.; Arun, Banu K.; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Chan, Salina B.; Claes, Kathleen B. M.; Cohn, David E.; Cook, Jackie; Daly, Mary B.; Damiola, Francesca; Davidson, Rosemarie; de Pauw, Antoine; Delnatte, Capucine; Diez, Orland; Domchek, Susan M.; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F.; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D. Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D.; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A.; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K.; Goldgar, David E.; Hake, Christopher R.; Hansen, Thomas V. O.; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B. L.; Houdayer, Claude; Hulick, Peter J.; Imyanitov, Evgeny N.; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M.; Vijai, Joseph; Karlan, Beth Y.; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L.; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R.; Montagna, Marco; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I.; Ong, Kai-ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C.; Rookus, Matti A.; Ross, Eric A.; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F.; Slavin, Thomas P.; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I.; Tea, Muy-Kheng; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J.; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N.; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J.; Greene, Mark H.; Couch, Fergus J.; Offit, Kenneth; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. PMID:27463617

  17. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

    Directory of Open Access Journals (Sweden)

    Elena Vigorito

    Full Text Available Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases BRCA1 and 8,211 (631 ovarian cancer cases BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16. These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6. The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

  18. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

    Science.gov (United States)

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A; Andrulis, Irene L; Arun, Banu K; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A; Campbell, Ian; Chan, Salina B; Claes, Kathleen B M; Cohn, David E; Cook, Jackie; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; Pauw, Antoine de; Delnatte, Capucine; Diez, Orland; Domchek, Susan M; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K; Goldgar, David E; Hake, Christopher R; Hansen, Thomas V O; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B L; Houdayer, Claude; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Vijai, Joseph; Karlan, Beth Y; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R; Montagna, Marco; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C; Rookus, Matti A; Ross, Eric A; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F; Slavin, Thomas P; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I; Tea, Muy-Kheng; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J; Greene, Mark H; Couch, Fergus J; Offit, Kenneth; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

  19. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    DEFF Research Database (Denmark)

    Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra

    2014-01-01

    exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key...... negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.......Human bone marrow (BM) contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs), which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show...

  20. Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission

    DEFF Research Database (Denmark)

    Alenius, Malin; Hammarlund-Udenaes, Margareta; Honoré, Per Gustaf Hartvig

    2009-01-01

    ; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. METHOD: A naturalistic......, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment...... history (PT), was used to group the patients according to treatment response. CANSEPT was evaluated by comparison of expected and observed results. RESULTS: In the patient population (n = 123), the patients in functional remission, as defined by CANSEPT, had higher quality of life, fewer hospitalizations...

  1. Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Barbara Gasse

    2017-06-01

    Full Text Available Amelogenesis imperfecta (AI designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20 produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues, pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

  2. Grouping Parturients by Parity, Previous-Cesarean, and Mode of Delivery (P-C-MoD Classification) Better Identifies Groups at Risk for Postpartum Hemorrhage.

    Science.gov (United States)

    Reichman, Orna; Gal, Micahel; Sela, Hen Y; Khayyat, Izzat; Emanuel, Michael; Samueloff, Arnon

    2016-10-01

    Objective We aimed to create a clinical classification to better identify parturients at risk for postpartum hemorrhage (PPH). Method A retrospective cohort, including all women who delivered at a single tertiary care medical center, between 2006 and 2014. Parturients were grouped by parity and history of cesarean delivery (CD): primiparas, multipara, and multipara with previous CD. Each were further subgrouped by mode of delivery (spontaneous vaginal delivery [SVD], operative vaginal delivery [OVD], emergency or elective CD). In all, 12 subgroups, based on parity, previous cesarean, and mode of delivery, formed the P-C-MoD classification. PPH was defined as a decrease of ≥3 gram% hemoglobin from admission and/or transfusion of blood products. Univariate analysis followed by multivariate analysis was performed to assess risk for PPH, controlling for confounders. Results The crude rate of PPH among 126,693 parturients was 7%. The prevalence differed significantly among independent risk factors: primiparity, 14%; multiparity, 4%; OVD, 22%; and CD, 15%. The P-C-MoD classification, segregated better between parturients at risk for PPH. The prevalence of PPH was highest for primiparous undergoing OVD (27%) compared with multiparous with SVD (3%), odds ratio [OR] = 12.8 (95% confidence interval [CI],11.9-13.9). These finding were consistent in the multivariate analysis OR = 13.1 (95% CI,12.1-14.3). Conclusion Employing the P-C-MoD classification more readily identifies parturients at risk for PPH and is superior to estimations based on single risk factors. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Molecular analysis of desmoid tumors with a high-density single-nucleotide polymorphism array identifies new molecular candidate lesions.

    Science.gov (United States)

    Erben, Philipp; Nowak, Daniel; Sauer, Christian; Ströbel, Philipp; Hofmann, Wolf-Karsten; Hofheinz, Ralf-Dieter; Hohenberger, Peter; Kasper, Bernd

    2012-01-01

    Desmoid tumors are neoplastic proliferations of connective tissues. The mutation status of the gene coding for catenin (cadherin-associated protein) beta 1 (CTNNB1) and trisomy 8 on the chromosomal level have been described to have prognostic relevance. In order to elucidate new molecular mechanisms underlying these tumors, we carried out a molecular analysis with a genome-wide human high-density single-nucleotide polymorphism (SNP) array, in 9 patients. Single samples showed numerical aberrations on chromosomes (Chrs) 20 and 6 with either trisomy 20 or monosomy 6. No trisomy 8 could be detected. Recurrent heterozygous deletions were found in Chr 5q (including the APC gene locus, n = 3) and Chr 8p23 (n = 4, containing coding regions for the potential tumor suppressor gene CSMD1). This novel deletion in 8p23 showed an association with local recurrence. In addition, structural chromosomal changes (gain of Chrs 8 and 20) were found in a minority of cases. The genomic alteration affecting the candidate gene CSMD1 could be important in the development of desmoid tumors.

  4. HIV gene expression from intact proviruses positioned in bacterial artificial chromosomes at integration sites previously identified in latently infected T cells

    International Nuclear Information System (INIS)

    Eipers, Peter G.; Salazar-Gonzalez, Jesus F.; Morrow, Casey D.

    2011-01-01

    HIV integration predominantly occurs in introns of transcriptionally active genes. To study the impact of the integration site on HIV gene expression, a complete HIV-1 provirus (with GFP as a fusion with Nef) was inserted into bacterial artificial chromosomes (BACs) at three sites previously identified in latent T cells of patients: topoisomerase II (Top2A), DNA methyltransferase 1 (DNMT1), or basic leucine transcription factor 2 (BACH2). Transfection of BAC-HIV into 293 T cells resulted in a fourfold difference in production of infectious HIV-1. Cell lines were established that contained BAC-Top2A, BAC-DNMT1, or BAC-BACH2, but only BAC-DNMT1 spontaneously produced virus, albeit at a low level. Stimulation with TNF-α resulted in virus production from four of five BAC-Top2A and all BAC-DNMT1 cell lines, but not from the BAC-BACH2 lines. The results of these studies highlight differences between integration sites identified in latent T cells to support virus production and reactivation from latency.

  5. Genome-wide transcriptome study in wheat identified candidate genes related to processing quality, majority of them showing interaction (quality x development) and having temporal and spatial distributions

    Science.gov (United States)

    2014-01-01

    Background The cultivated bread wheat (Triticum aestivum L.) possesses unique flour quality, which can be processed into many end-use food products such as bread, pasta, chapatti (unleavened flat bread), biscuit, etc. The present wheat varieties require improvement in processing quality to meet the increasing demand of better quality food products. However, processing quality is very complex and controlled by many genes, which have not been completely explored. To identify the candidate genes whose expressions changed due to variation in processing quality and interaction (quality x development), genome-wide transcriptome studies were performed in two sets of diverse Indian wheat varieties differing for chapatti quality. It is also important to understand the temporal and spatial distributions of their expressions for designing tissue and growth specific functional genomics experiments. Results Gene-specific two-way ANOVA analysis of expression of about 55 K transcripts in two diverse sets of Indian wheat varieties for chapatti quality at three seed developmental stages identified 236 differentially expressed probe sets (10-fold). Out of 236, 110 probe sets were identified for chapatti quality. Many processing quality related key genes such as glutenin and gliadins, puroindolines, grain softness protein, alpha and beta amylases, proteases, were identified, and many other candidate genes related to cellular and molecular functions were also identified. The ANOVA analysis revealed that the expression of 56 of 110 probe sets was involved in interaction (quality x development). Majority of the probe sets showed differential expression at early stage of seed development i.e. temporal expression. Meta-analysis revealed that the majority of the genes expressed in one or a few growth stages indicating spatial distribution of their expressions. The differential expressions of a few candidate genes such as pre-alpha/beta-gliadin and gamma gliadin were validated by RT

  6. Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk

    DEFF Research Database (Denmark)

    Blackburn, Anneke C; Hill, Linda Z; Roberts, Amy L

    2007-01-01

    Low-penetrance breast cancer susceptibility alleles seem to play a significant role in breast cancer risk but are difficult to identify in human cohorts. A genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and C57BL/6, which differ in their susceptibility to mammary...... tumors, identified a modifier of mammary tumor susceptibility in an approximately 25-Mb interval on mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from 70.7 to 61.1 weeks and increased risk...

  7. Optimal definition of biochemical recurrence after radical prostatectomy depends on pathologic risk factors: identifying candidates for early salvage therapy.

    Science.gov (United States)

    Mir, Maria C; Li, Jianbo; Klink, Joseph C; Kattan, Michael W; Klein, Eric A; Stephenson, Andrew J

    2014-08-01

    The use of prostate-specific antigen (PSA) thresholds (definitions for patients treated with radical prostatectomy may be useful in the identification of candidates for early salvage therapy with improved outcome; however, the practice risks overtreatment, as the risk of subsequent PSA progression may be low. To analyze 14 BCR definitions for their association with subsequent PSA and treatment progression among subgroups of patients at varying risk of prostate cancer-specific mortality. The subsequent risk of PSA and treatment progression after BCR based on 14 BCR definitions (six standard definitions and eight definitions requiring one or more successive PSA rises ≤0.1 ng/ml) was analyzed according to various clinicopathologic risk criteria among 2348 patients with a detectable PSA ≥0.03 ng/ml at least 6 wk after radical prostatectomy. Radical prostatectomy. Probability of subsequent PSA progression after BCR, defined as a PSA rise >0.1 ng/ml above BCR PSA, initiation of secondary treatment, or clinical progression. Using standard BCR definitions, the risk of PSA progression was >70%, regardless of clinicopathologic features. A single PSA ≤0.1 ng/ml was associated with PSA progression in only 30-55% of patients but ranged from 18-25% to 73-88% for patients without and with adverse pathologic features, respectively. Based on discrimination and calibration analysis, the optimal BCR definition for patients with 5-yr progression-free probability of 90% was a single PSA ≥0.05 ng/ml, two or more rising PSAs ≥0.05 ng/ml, PSA ≥0.2 ng/ml and rising, and PSA ≥0.4 ng/ml and rising. BCR definitions below currently accepted PSA thresholds appear to be valid for selecting patients with adverse clinicopathologic risk factors for secondary therapy. This information may be useful in selecting for early salvage radiotherapy to improve clinical outcome. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  8. Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Ludvigsen, Maja; Bendix, Knud

    2016-01-01

    . Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. A tissue microarray, containing diagnostic HIV-lymphoma tissue samples (N = 40), was used to investigate immunohistochemical expression of markers in tumoural lesions. RESULTS: Fourteen differentially expressed...... protein spots were detected. Using principal components analysis, spots containing immunoglobulin J chain, apolipoprotein A-I, procollagen C-endopeptidase enhancer-1 and complement C4-A were associated with lymphoma development (P ... with subsequent lymphoma compared with patients without subsequent lymphoma. In the tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). CONCLUSION: We identified several differentially expressed protein spots present already...

  9. Mapping and Identifying a Candidate Gene (Bnmfs for Female-Male Sterility through Whole-Genome Resequencing and RNA-Seq in Rapeseed (Brassica napus L.

    Directory of Open Access Journals (Sweden)

    Changcai Teng

    2017-12-01

    Full Text Available In oilseed crops, carpel and stamen development play vital roles in pollination and rapeseed yield, but the genetic mechanisms underlying carpel and stamen development remain unclear. Herein, a male- and female-sterile mutant was obtained in offspring of a (Brassica napus cv. Qingyou 14 × (Qingyou 14 × B. rapa landrace Dahuang cross. Subsequently, F2–F9 populations were generated through selfing of the heterozygote plants among the progeny of each generation. The male- and female-sterility exhibited stable inheritance in successive generations and was controlled by a recessive gene. The mutant kept the same chromosome number (2n = 38 as B. napus parent but showed abnormal meiosis for male and female. One candidate gene for the sterility was identified by simple sequence repeat (SSR and insertion deletion length polymorphism (InDel markers in F7–F9 plants, and whole-genome resequencing with F8 pools and RNA sequencing with F9 pools. Whole-genome resequencing found three candidate intervals (35.40–35.68, 35.74–35.75, and 45.34–46.45 Mb on chromosome C3 in B. napus and candidate region for Bnmfs was narrowed to approximately 1.11-Mb (45.34–46.45 M by combining SSR and InDel marker analyses with whole-genome resequencing. From transcriptome profiling in 0–2 mm buds, all of the genes in the candidate interval were detected, and only two genes with significant differences (BnaC03g56670D and BnaC03g56870D were revealed. BnaC03g56870D was a candidate gene that shared homology with the CYP86C4 gene of Arabidopsis thaliana. Quantitative reverse transcription (qRT-PCR analysis showed that Bnmfs primarily functioned in flower buds. Thus, sequencing and expression analyses provided evidence that BnaC03g56870D was the candidate gene for male and female sterility in the B. napus mutant.

  10. Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission.

    Science.gov (United States)

    Alenius, Malin; Hammarlund-Udenaes, Margareta; Hartvig, Per; Sundquist, Staffan; Lindström, Leif

    2009-01-01

    Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. A naturalistic, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment history (PT), was used to group the patients according to treatment response. CANSEPT was evaluated by comparison of expected and observed results. In the patient population (n = 123), the patients in functional remission, as defined by CANSEPT, had higher quality of life, fewer hospitalizations, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic or in research.

  11. RNA-Seq analysis and annotation of a draft blueberry genome assembly identifies candidate genes involved in fruit ripening, biosynthesis of bioactive compounds, and stage-specific alternative splicing.

    Science.gov (United States)

    Gupta, Vikas; Estrada, April D; Blakley, Ivory; Reid, Rob; Patel, Ketan; Meyer, Mason D; Andersen, Stig Uggerhøj; Brown, Allan F; Lila, Mary Ann; Loraine, Ann E

    2015-01-01

    Blueberries are a rich source of antioxidants and other beneficial compounds that can protect against disease. Identifying genes involved in synthesis of bioactive compounds could enable the breeding of berry varieties with enhanced health benefits. Toward this end, we annotated a previously sequenced draft blueberry genome assembly using RNA-Seq data from five stages of berry fruit development and ripening. Genome-guided assembly of RNA-Seq read alignments combined with output from ab initio gene finders produced around 60,000 gene models, of which more than half were similar to proteins from other species, typically the grape Vitis vinifera. Comparison of gene models to the PlantCyc database of metabolic pathway enzymes identified candidate genes involved in synthesis of bioactive compounds, including bixin, an apocarotenoid with potential disease-fighting properties, and defense-related cyanogenic glycosides, which are toxic. Cyanogenic glycoside (CG) biosynthetic enzymes were highly expressed in green fruit, and a candidate CG detoxification enzyme was up-regulated during fruit ripening. Candidate genes for ethylene, anthocyanin, and 400 other biosynthetic pathways were also identified. Homology-based annotation using Blast2GO and InterPro assigned Gene Ontology terms to around 15,000 genes. RNA-Seq expression profiling showed that blueberry growth, maturation, and ripening involve dynamic gene expression changes, including coordinated up- and down-regulation of metabolic pathway enzymes and transcriptional regulators. Analysis of RNA-seq alignments identified developmentally regulated alternative splicing, promoter use, and 3' end formation. We report genome sequence, gene models, functional annotations, and RNA-Seq expression data that provide an important new resource enabling high throughput studies in blueberry.

  12. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    DEFF Research Database (Denmark)

    Vigorito, E.; Kuchenbaecker, Karoline B; Beesley, J

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2...... mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively...... of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest...

  13. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    Full Text Available BACKGROUND: Roux-en-Y gastric bypass (RYGB surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. METHODOLOGY AND PRINCIPAL FINDINGS: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7. Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172 of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05, including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9 and obese/diabetic (n = 5 groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2, nervonic (C24:1 acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI and estimates for insulin resistance (HOMA-IR. Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55. CONCLUSIONS: Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.

  14. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

    DEFF Research Database (Denmark)

    Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

    2017-01-01

    We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D a...

  15. Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development-Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus.

    Directory of Open Access Journals (Sweden)

    Katarina Truvé

    2016-05-01

    Full Text Available Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs, occurring with similar frequencies in both species. Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesis. Several brachycephalic breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, but others, including Pug and Pekingese, are not at higher risk. To identify glioma-associated genetic susceptibility factors, an across-breed genome-wide association study (GWAS was performed on 39 dog glioma cases and 141 controls from 25 dog breeds, identifying a genome-wide significant locus on canine chromosome (CFA 26 (p = 2.8 x 10-8. Targeted re-sequencing of the 3.4 Mb candidate region was performed, followed by genotyping of the 56 SNVs that best fit the association pattern between the re-sequenced cases and controls. We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR. CAMKK2 showed reduced expression in both canine and human brain tumors, and a non-synonymous variant in P2RX7, previously demonstrated to have a 50% decrease in receptor function, was also associated with disease. Thus, one or more of these genes appear to affect glioma susceptibility.

  16. Comprehensive meta-analysis, co-expression, and miRNA nested network analysis identifies gene candidates in citrus against Huanglongbing disease.

    Science.gov (United States)

    Rawat, Nidhi; Kiran, Sandhya P; Du, Dongliang; Gmitter, Fred G; Deng, Zhanao

    2015-07-28

    Huanglongbing (HLB), the most devastating disease of citrus, is associated with infection by Candidatus Liberibacter asiaticus (CaLas) and is vectored by the Asian citrus psyllid (ACP). Recently, the molecular basis of citrus-HLB interactions has been examined using transcriptome analyses, and these analyses have identified many probe sets and pathways modulated by CaLas infection among different citrus cultivars. However, lack of consistency among reported findings indicates that an integrative approach is needed. This study was designed to identify the candidate probe sets in citrus-HLB interactions using meta-analysis and gene co-expression network modelling. Twenty-two publically available transcriptome studies on citrus-HLB interactions, comprising 18 susceptible (S) datasets and four resistant (R) datasets, were investigated using Limma and RankProd methods of meta-analysis. A combined list of 7,412 differentially expressed probe sets was generated using a Teradata in-house Structured Query Language (SQL) script. We identified the 65 most common probe sets modulated in HLB disease among different tissues from the S and R datasets. Gene ontology analysis of these probe sets suggested that carbohydrate metabolism, nutrient transport, and biotic stress were the core pathways that were modulated in citrus by CaLas infection and HLB development. We also identified R-specific probe sets, which encoded leucine-rich repeat proteins, chitinase, constitutive disease resistance (CDR), miraculins, and lectins. Weighted gene co-expression network analysis (WGCNA) was conducted on 3,499 probe sets, and 21 modules with major hub probe sets were identified. Further, a miRNA nested network was created to examine gene regulation of the 3,499 target probe sets. Results suggest that csi-miR167 and csi-miR396 could affect ion transporters and defence response pathways, respectively. Most of the potential candidate hub probe sets were co-expressed with gibberellin pathway (GA

  17. Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer.

    Directory of Open Access Journals (Sweden)

    Pablo Palma

    Full Text Available Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders. Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11 and non-responders (n = 16 to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029 gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with

  18. Tensor decomposition-based unsupervised feature extraction identifies candidate genes that induce post-traumatic stress disorder-mediated heart diseases.

    Science.gov (United States)

    Taguchi, Y-H

    2017-12-21

    Although post-traumatic stress disorder (PTSD) is primarily a mental disorder, it can cause additional symptoms that do not seem to be directly related to the central nervous system, which PTSD is assumed to directly affect. PTSD-mediated heart diseases are some of such secondary disorders. In spite of the significant correlations between PTSD and heart diseases, spatial separation between the heart and brain (where PTSD is primarily active) prevents researchers from elucidating the mechanisms that bridge the two disorders. Our purpose was to identify genes linking PTSD and heart diseases. In this study, gene expression profiles of various murine tissues observed under various types of stress or without stress were analyzed in an integrated manner using tensor decomposition (TD). Based upon the obtained features, ∼ 400 genes were identified as candidate genes that may mediate heart diseases associated with PTSD. Various gene enrichment analyses supported biological reliability of the identified genes. Ten genes encoding protein-, DNA-, or mRNA-interacting proteins-ILF2, ILF3, ESR1, ESR2, RAD21, HTT, ATF2, NR3C1, TP53, and TP63-were found to be likely to regulate expression of most of these ∼ 400 genes and therefore are candidate primary genes that cause PTSD-mediated heart diseases. Approximately 400 genes in the heart were also found to be strongly affected by various drugs whose known adverse effects are related to heart diseases and/or fear memory conditioning; these data support the reliability of our findings. TD-based unsupervised feature extraction turned out to be a useful method for gene selection and successfully identified possible genes causing PTSD-mediated heart diseases.

  19. Leaf morphology in Cowpea [Vigna unguiculata (L. Walp]: QTL analysis, physical mapping and identifying a candidate gene using synteny with model legume species

    Directory of Open Access Journals (Sweden)

    Pottorff Marti

    2012-06-01

    Full Text Available Abstract Background Cowpea [Vigna unguiculata (L. Walp] exhibits a considerable variation in leaf shape. Although cowpea is mostly utilized as a dry grain and animal fodder crop, cowpea leaves are also used as a high-protein pot herb in many countries of Africa. Results Leaf morphology was studied in the cowpea RIL population, Sanzi (sub-globose leaf shape x Vita 7 (hastate leaf shape. A QTL for leaf shape, Hls (hastate leaf shape, was identified on the Sanzi x Vita 7 genetic map spanning from 56.54 cM to 67.54 cM distance on linkage group 15. SNP marker 1_0910 was the most significant over the two experiments, accounting for 74.7% phenotypic variance (LOD 33.82 in a greenhouse experiment and 71.5% phenotypic variance (LOD 30.89 in a field experiment. The corresponding Hls locus was positioned on the cowpea consensus genetic map on linkage group 4, spanning from 25.57 to 35.96 cM. A marker-trait association of the Hls region identified SNP marker 1_0349 alleles co-segregating with either the hastate or sub-globose leaf phenotype. High co-linearity was observed for the syntenic Hls region in Medicago truncatula and Glycine max. One syntenic locus for Hls was identified on Medicago chromosome 7 while syntenic regions for Hls were identified on two soybean chromosomes, 3 and 19. In all three syntenic loci, an ortholog for the EZA1/SWINGER (AT4G02020.1 gene was observed and is the candidate gene for the Hls locus. The Hls locus was identified on the cowpea physical map via SNP markers 1_0910, 1_1013 and 1_0992 which were identified in three BAC contigs; contig926, contig821 and contig25. Conclusions This study has demonstrated how integrated genomic resources can be utilized for a candidate gene approach. Identification of genes which control leaf morphology may be utilized to improve the quality of cowpea leaves for vegetable and or forage markets as well as contribute to more fundamental research understanding the control of leaf shape in

  20. Leaf morphology in Cowpea [Vigna unguiculata (L.) Walp]: QTL analysis, physical mapping and identifying a candidate gene using synteny with model legume species

    Science.gov (United States)

    2012-01-01

    Background Cowpea [Vigna unguiculata (L.) Walp] exhibits a considerable variation in leaf shape. Although cowpea is mostly utilized as a dry grain and animal fodder crop, cowpea leaves are also used as a high-protein pot herb in many countries of Africa. Results Leaf morphology was studied in the cowpea RIL population, Sanzi (sub-globose leaf shape) x Vita 7 (hastate leaf shape). A QTL for leaf shape, Hls (hastate leaf shape), was identified on the Sanzi x Vita 7 genetic map spanning from 56.54 cM to 67.54 cM distance on linkage group 15. SNP marker 1_0910 was the most significant over the two experiments, accounting for 74.7% phenotypic variance (LOD 33.82) in a greenhouse experiment and 71.5% phenotypic variance (LOD 30.89) in a field experiment. The corresponding Hls locus was positioned on the cowpea consensus genetic map on linkage group 4, spanning from 25.57 to 35.96 cM. A marker-trait association of the Hls region identified SNP marker 1_0349 alleles co-segregating with either the hastate or sub-globose leaf phenotype. High co-linearity was observed for the syntenic Hls region in Medicago truncatula and Glycine max. One syntenic locus for Hls was identified on Medicago chromosome 7 while syntenic regions for Hls were identified on two soybean chromosomes, 3 and 19. In all three syntenic loci, an ortholog for the EZA1/SWINGER (AT4G02020.1) gene was observed and is the candidate gene for the Hls locus. The Hls locus was identified on the cowpea physical map via SNP markers 1_0910, 1_1013 and 1_0992 which were identified in three BAC contigs; contig926, contig821 and contig25. Conclusions This study has demonstrated how integrated genomic resources can be utilized for a candidate gene approach. Identification of genes which control leaf morphology may be utilized to improve the quality of cowpea leaves for vegetable and or forage markets as well as contribute to more fundamental research understanding the control of leaf shape in legumes. PMID:22691139

  1. A comprehensive approach to identify reliable reference gene candidates to investigate the link between alcoholism and endocrinology in Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Faten A Taki

    Full Text Available Gender and hormonal differences are often correlated with alcohol dependence and related complications like addiction and breast cancer. Estrogen (E2 is an important sex hormone because it serves as a key protein involved in organism level signaling pathways. Alcoholism has been reported to affect estrogen receptor signaling; however, identifying the players involved in such multi-faceted syndrome is complex and requires an interdisciplinary approach. In many situations, preliminary investigations included a straight forward, yet informative biotechniques such as gene expression analyses using quantitative real time PCR (qRT-PCR. The validity of qRT-PCR-based conclusions is affected by the choice of reliable internal controls. With this in mind, we compiled a list of 15 commonly used housekeeping genes (HKGs as potential reference gene candidates in rat biological models. A comprehensive comparison among 5 statistical approaches (geNorm, dCt method, NormFinder, BestKeeper, and RefFinder was performed to identify the minimal number as well the most stable reference genes required for reliable normalization in experimental rat groups that comprised sham operated (SO, ovariectomized rats in the absence (OVX or presence of E2 (OVXE2. These rat groups were subdivided into subgroups that received alcohol in liquid diet or isocalroic control liquid diet for 12 weeks. Our results showed that U87, 5S rRNA, GAPDH, and U5a were the most reliable gene candidates for reference genes in heart and brain tissue. However, different gene stability ranking was specific for each tissue input combination. The present preliminary findings highlight the variability in reference gene rankings across different experimental conditions and analytic methods and constitute a fundamental step for gene expression assays.

  2. Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

    Directory of Open Access Journals (Sweden)

    Merok Marianne A

    2010-05-01

    Full Text Available Abstract Background Estimates suggest that up to 30% of colorectal cancers (CRC may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV (Roche NimbleGen, 385 000 oligo CGH array in microsatellite stable (MSS tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53 and 17 elderly patients with median age 79 years (range: 69-87. Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list. Results The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups. Conclusions Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late

  3. Efficient Culture Adaptation of Hepatitis C Virus Recombinants with Genotype-Specific Core-NS2 by Using Previously Identified Mutations

    DEFF Research Database (Denmark)

    Scheel, Troels Kasper Høyer; Gottwein, Judith M; Carlsen, Thomas H R

    2011-01-01

    Hepatitis C virus (HCV) is an important cause of chronic liver disease, and interferon-based therapy cures only 40 to 80% of patients, depending on HCV genotype. Research was accelerated by genotype 2a (strain JFH1) infectious cell culture systems. We previously developed viable JFH1-based...... mutations did not adapt to culture. Universal adaptive effects of mutations in NS3 (Q1247L, I1312V, K1398Q, R1408W, and Q1496L) and NS5A (V2418L) were investigated for JFH1-based genotype 1 to 5 core-NS2 recombinants; several mutations conferred adaptation to H77C (1a), J4 (1b), S52 (3a), and SA13 (5a......-specific patterns in HCV disease and control....

  4. Quantitative analysis of previously identified propionate-oxidizing bacteria and methanogens at different temperatures in an UASB reactor containing propionate as a sole carbon source.

    Science.gov (United States)

    Ban, Qiaoying; Li, Jianzheng; Zhang, Liguo; Jha, Ajay Kumar; Zhang, Yupeng

    2013-12-01

    Propionate degradation is crucial for maintaining the efficiency and stability of an anaerobic reactor. However, there was little information about the effects of ecological factor on propionate-oxidizing bacteria (POB). In current research, quantitative real-time fluorescence polymerase chain reaction (QPCR) of some identified POB and methanogens with a decrease in temperature in an upflow anaerobic sludge bed (UASB) reactor containing propionate as sole carbon source was investigated. The results showed that there were at least four identified POB, including Pelotomaculum schinkii, Pelotomaculum propionicum, Syntrophobacter fumaroxidans, and Syntrophobacter sulfatireducens, observed in this UASB reactor. Among them, P. schinkii was dominated during the whole operational period. Its quantity was 1.2 × 10(4) 16S rRNA gene copies per nanogram of DNA at 35 °C. A decrease in temperature from 35 to 30 °C led to P. schinkii to be increased by 1.8 times and then it was gradually reduced with a decrease in temperature from 30 to 25, 20, and 18 °C stepwise. A decrease in temperature from 35 to 20 °C did not make the amount of methanogens markedly changed, but hydrogenotrophic methanogens (Methanospirillum) and acetotrophic methanogens (Methanosaeta) at 18 °C were increased by an order of magnitude and 1.0 time, respectively, compared with other experimental conditions.

  5. Circulating levels of endocannabinoids and oxylipins altered by dietary lipids in older women are likely associated with previously identified gene targets.

    Science.gov (United States)

    Watkins, Bruce A; Kim, Jeffrey; Kenny, Anne; Pedersen, Theresa L; Pappan, Kirk L; Newman, John W

    2016-11-01

    Postmenopausal women (PMW) report marginal n-3 PUFA intakes and are at risk of chronic diseases associated with the skeletal, muscular, neuroendocrine, and cardiovascular systems. How n-3 PUFA affect the amounts of endocannabinoids (ECs) and oxylipins (OLs) of metabolic and physiologic importance in PMW is not clear. Based on our recent findings that dietary n-3 PUFA alter gene targets of the EC system and lower pro-inflammatory OL we proceeded to characterize these actions in blood of PMW. Our aim was to determine levels of the ECs, OLs, and global metabolites (GM) in white PMW (75±7y), randomized in a double-masked manner, from baseline to 6mo after receiving a fish oil supplement of n-3 PUFA (720mg 20:5n3+480mg 22:6n3/d, n=20) or placebo (1.8g oleic acid/d, n=20). ECs and OLs in serum were determined by UPLC-MS/MS and GM by GC-MS and LC-MS/MS. Plasma 20:5n3 and 22:6n3 levels increased in PMW given fish oil. EC n-6 acyl-ethanolamides, arachidonate-derived diols were decreased and 20:5n3 and 22:6n3 diols, epoxides, and alcohols were increased in PMW given fish oil. GM analysis revealed that n-3 PUFA supplementation increased renal steroid hormone and proteolytic metabolite levels in PMW. Herein, we confirm that gene targets of the EC system, previously found as modifiable by n-3 PUFA result in changes in the levels of ECs and OLs in PMW. This study shows phenotypic responses (in levels) to n-3 PUFA supplementation in PMW and increases of n-3 acyl-ethanolamide and n-3-derived OL of clinical considerations in aging. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. QTLs and Potential Candidate Genes for Heat Stress Tolerance Identified from the Mapping Populations Specifically Segregating for Fv/Fm in Wheat

    Directory of Open Access Journals (Sweden)

    Dew Kumari Sharma

    2017-09-01

    Full Text Available Despite the fact that Fv/Fm (maximum quantum efficiency of photosystem II is the most widely used parameter for a rapid non-destructive measure of stress detection in plants, there are barely any studies on the genetic understanding of this trait under heat stress. Our aim was to identify quantitative trait locus (QTL and the potential candidate genes linked to Fv/Fm for improved photosynthesis under heat stress in wheat (Triticum aestivum L.. Three bi-parental F2 mapping populations were generated by crossing three heat tolerant male parents (origin: Afghanistan and Pakistan selected for high Fv/Fm with a common heat susceptible female parent (origin: Germany selected for lowest Fv/Fm out of a pool of 1274 wheat cultivars of diverse geographic origin. Parents together with 140 F2 individuals in each population were phenotyped by Fv/Fm under heat stress (40°C for 3 days around anthesis. The Fv/Fm decreased by 6.3% in the susceptible parent, 1–2.5% in the tolerant parents and intermediately 4–6% in the mapping populations indicating a clear segregation for the trait. The three populations were genotyped with 34,955 DArTseq and 27 simple sequence repeat markers, out of which ca. 1800 polymorphic markers mapped to 27 linkage groups covering all the 21 chromosomes with a total genome length of about 5000 cM. Inclusive composite interval mapping resulted in the identification of one significant and heat-stress driven QTL in each population on day 3 of the heat treatment, two of which were located on chromosome 3B and one on chromosome 1D. These QTLs explained about 13–35% of the phenotypic variation for Fv/Fm with an additive effect of 0.002–0.003 with the positive allele for Fv/Fm originating from the heat tolerant parents. Approximate physical localization of these three QTLs revealed the presence of 12 potential candidate genes having a direct role in photosynthesis and/or heat tolerance. Besides providing an insight into the genetic

  7. Updated canine infection rates for Dirofilaria immitis in areas of Brazil previously identified as having a high incidence of heartworm-infected dogs.

    Science.gov (United States)

    Labarthe, Norma Vollmer; Paiva, Jonimar Pereira; Reifur, Larissa; Mendes-de-Almeida, Flavya; Merlo, Alexandre; Carvalho Pinto, Carlos Jose; Juliani, Paulo Sérgio; de Almeida, Maria Angela Ornelas; Alves, Leucio Câmara

    2014-11-07

    Canine heartworm infections were frequently diagnosed in Brazil before the new millennium. After the year 2000, the frequency of diagnosis showed a sharp decline; however, a few years later, new evidence indicated that the parasite was still present and that canine infection rates seemed to be increasing. Therefore, an updated survey of canine heartworm prevalence was conducted in several locations in south, southeast, and northeast Brazil. Dogs from 15 locations having previously reported a high prevalence of heartworm infection were included in the survey according to defined criteria, including the absence of treatment with a macrocyclic lactone for at least 1 year. Blood samples from 1531 dogs were evaluated by an in-clinic immunochromatography test kit (Witness® Heartworm, Zoetis, USA) for detection of Dirofilaria immitis antigen. At each location, epidemiologic data, including physical characteristics and clinical signs reported by owners or observed by veterinarians, were recorded on prepared forms for tabulation of results by location, clinical signs, and physical characteristics. The overall prevalence of canine heartworm infection was 23.1%, with evidence of heartworm-infected dogs detected in all 15 locations studied. There was a tendency for higher prevalence rates in environmentally protected areas, despite some locations having less-than-ideal environmental temperatures for survival of vector mosquitoes. Among physical characteristics, it was noted that dogs with predominantly white hair coats and residing in areas with a high (≥20%) prevalence of heartworm were less likely to have heartworm infection detected by a commercial heartworm antigen test kit than were dogs with other coat colors. In general, dogs older than 2 years were more frequently positive for D. immitis antigen than were younger dogs. Clinical signs of heartworm infections were rare or owners were unable to detect them, and could not be used for reliable prediction of the

  8. Delta-like ligand 4 identifies a previously uncharacterized population of inflammatory dendritic cells that plays important roles in eliciting allogeneic T cell responses in mice.

    Science.gov (United States)

    Mochizuki, Kazuhiro; Xie, Fang; He, Shan; Tong, Qing; Liu, Yongnian; Mochizuki, Izumi; Guo, Yajun; Kato, Koji; Yagita, Hideo; Mineishi, Shin; Zhang, Yi

    2013-04-01

    Graft-versus-host disease (GVHD) reflects an exaggerated inflammatory allogeneic T cell response in hosts receiving allogeneic hematopoietic stem cell transplantation (HSCT). Inhibition of pan-Notch receptor signaling in donor T cells causes reduction of GVHD. However, which Notch ligand(s) in what APCs is important for priming graft-versus-host reaction remains unknown. We demonstrate that δ-like ligand-4 (Dll4) and Dll4-positive (Dll4(high)) inflammatory dendritic cells (i-DCs) play important roles in eliciting allogeneic T cell responses. Host-type Dll4(high) i-DCs occurred in the spleen and intestine of HSCT mice during GVHD induction phase. These Dll4(high) i-DCs were CD11c(+)B220(+)PDCA-1(+), resembling plasmacytoid dentritic cells (pDCs) of naive mice. However, as compared with unstimulated pDCs, Dll4(high) i-DCs expressed higher levels of costimulatory molecules, Notch ligands Jagged1 and Jagged2, and CD11b, and produced more Ifnb and Il23 but less Il12. In contrast, Dll4-negative (Dll4(low)) i-DCs were CD11c(+)B220(-)PDCA-1(-), and had low levels of Jagged1. In vitro assays showed that Dll4(high) i-DCs induced significantly more IFN-γ- and IL-17-producing effector T cells (3- and 10-fold, respectively) than Dll4(low) i-DCs. This effect could be blocked by anti-Dll4 Ab. In vivo administration of Dll4 Ab reduced donor-alloreactive effector T cells producing IFN-γ and IL-17 in GVHD target organs, leading to reduction of GVHD and improved survival of mice after allogeneic HSCT. Our findings indicate that Dll4(high) i-DCs represent a previously uncharacterized i-DC population distinctive from steady state DCs and Dll4(low) i-DCs. Furthermore, Dll4 and Dll4(high) i-DCs may be beneficial targets for modulating allogeneic T cell responses, and could facilitate the discovery of human counterparts of mouse Dll4(high) i-DCs.

  9. Delta-like Ligand 4 Identifies a Previously Uncharacterized Population of Inflammatory Dendritic Cells That Plays Important Roles in Eliciting Allogeneic T-cell Responses in Mice1

    Science.gov (United States)

    Mochizuki, Kazuhiro; Xie, Fang; He, Shan; Tong, Qing; Liu, Yongnian; Mochizuki, Izumi; Guo, Yajun; Kato, Koji; Yagita, Hideo; Mineishi, Shin; Zhang, Yi

    2013-01-01

    Graft-versus-host disease (GVHD) reflects an exaggerated inflammatory allogeneic T-cell response in hosts receiving allogeneic hematopoietic stem cell transplantation (HSCT). Inhibition of pan-Notch receptor signaling in donor T cells causes reduction of GVHD. However, which Notch ligand(s) in what antigen-presenting cells are important for priming GVH reaction remains unknown. We demonstrate that δ-like ligand-4 (Dll4) and Dll4-positive (Dll4hi) inflammatory dendritic cells (i-DCs) play important roles in eliciting allogeneic T-cell responses. Host-type Dll4hi i-DCs occurred in the spleen and intestine of HSCT mice during GVHD induction phase. These Dll4hi i-DCs were CD11c+B220+PDCA-1+, resembling plasmacytoid DCs (pDCs) of naïve mice. However, as compared to unstimulated pDCs, Dll4hi i-DCs expressed higher levels of costimulatory molecules, Notch ligands Jagged1 and Jagged2 and CD11b and, produced more Ifnb and Il23 but less Il12. In contrast, Dll4-negative (Dll4lo) i-DCs were CD11c+B220−PDCA-1−, and had low levels of Jagged1. In vitro assays showed that Dll4hi i-DCs induced significantly more IFN-γ- and IL-17-producing effector T cells (3- and 10-fold, respectively) than Dll4lo i-DCs. This effect could be blocked by anti-Dll4 antibody. In vivo administration of Dll4 antibody reduced donor alloreactive effector T cells producing IFN-γ and IL-17 in GVHD target organs, leading to reduction of GVHD and improved survival of mice after allogeneic HSCT. Our findings indicate that Dll4hi i-DCs represent a previously uncharacterized i-DC population distinctive from steady state DCs and Dll4lo i-DCs. Furthermore, Dll4 and Dll4hi i-DCs may be beneficial targets for modulating allogeneic T-cell responses, and could facilitate the discovery of human counterparts of mouse Dll4hi i-DCs. PMID:23440416

  10. Integration of sequence data from a Consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene.

    Directory of Open Access Journals (Sweden)

    Yukinori Okada

    Full Text Available Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA. Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1, might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry and also in unrelated individuals from the general population (European ancestry. Through identity-by-descent (IBD mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009. We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2 × 10(-6. Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry, and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT. Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted.

  11. Transcriptomic analysis of the mussel Elliptio complanata identifies candidate stress-response genes and an abundance of novel or noncoding transcripts

    Science.gov (United States)

    Cornman, Robert S.; Robertson, Laura S.; Galbraith, Heather S.; Blakeslee, Carrie J.

    2014-01-01

    Mussels are useful indicator species of environmental stress and degradation, and the global decline in freshwater mussel diversity and abundance is of conservation concern. Elliptio complanata is a common freshwater mussel of eastern North America that can serve both as an indicator and as an experimental model for understanding mussel physiology and genetics. To support genetic components of these research goals, we assembled transcriptome contigs from Illumina paired-end reads. Despite efforts to collapse similar contigs, the final assembly was in excess of 136,000 contigs with an N50 of 982 bp. Even so, comparisons to the CEGMA database of conserved eukaryotic genes indicated that ∼20% of genes remain unrepresented. However, numerous candidate stress-response genes were present, and we identified lineage-specific patterns of diversification among molluscs for cytochrome P450 detoxification genes and two saccharide-modifying enzymes: 1,3 beta-galactosyltransferase and fucosyltransferase. Less than a quarter of contigs had protein-level similarity based on modest BLAST and Hmmer3 statistical thresholds. These results add comparative genomic resources for molluscs and suggest a wealth of novel proteins and noncoding transcripts.

  12. Genome-wide analysis of the CCCH zinc finger family identifies tissue specific and stress responsive candidates in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Pradhan, Seema; Kant, Chandra; Verma, Subodh; Bhatia, Sabhyata

    2017-01-01

    The CCCH zinc finger is a group of proteins characterised by a typical motif consisting of three cysteine residues and one histidine residue. These proteins have been reported to play important roles in regulation of plant growth, developmental processes and environmental responses. In the present study, genome wide analysis of the CCCH zinc finger gene family was carried out in the available chickpea genome. Various bioinformatics tools were employed to predict 58 CCCH zinc finger genes in chickpea (designated CarC3H1-58), which were analysed for their physio-chemical properties. Phylogenetic analysis classified the proteins into 12 groups in which members of a particular group had similar structural organization. Further, the numbers as well as the types of CCCH motifs present in the CarC3H proteins were compared with those from Arabidopsis and Medicago truncatula. Synteny analysis revealed valuable information regarding the evolution of this gene family. Tandem and segmental duplication events were identified and their Ka/Ks values revealed that the CarC3H gene family in chickpea had undergone purifying selection. Digital, as well as real time qRT-PCR expression analysis was performed which helped in identification of several CarC3H members that expressed preferentially in specific chickpea tissues as well as during abiotic stresses (desiccation, cold, salinity). Moreover, molecular characterization of an important member CarC3H45 was carried out. This study provides comprehensive genomic information about the important CCCH zinc finger gene family in chickpea. The identified tissue specific and abiotic stress specific CCCH genes could be potential candidates for further characterization to delineate their functional roles in development and stress.

  13. Saturated genic SNP mapping identified functional candidates and selection tools for the Pinus monticola Cr2 locus controlling resistance to white pine blister rust.

    Science.gov (United States)

    Liu, Jun-Jun; Sniezko, Richard A; Zamany, Arezoo; Williams, Holly; Wang, Ning; Kegley, Angelia; Savin, Douglas P; Chen, Hao; Sturrock, Rona N

    2017-09-01

    Molecular breeding incorporates efficient tools to increase rust resistance in five-needle pines. Susceptibility of native five-needle pines to white pine blister rust (WPBR), caused by the non-native invasive fungus Cronartium ribicola (J.C. Fisch.), has significantly reduced wild populations of these conifers in North America. Major resistance (R) genes against specific avirulent pathotypes have been found in several five-needle pine species. In this study, we screened genic SNP markers by comparative transcriptome and genetic association analyses and constructed saturated linkage maps for the western white pine (Pinus monticola) R locus (Cr2). Phenotypic segregation was measured by a hypersensitive reaction (HR)-like response on the needles and disease symptoms of cankered stems post inoculation by the C. ribicola avcr2 race. SNP genotypes were determined by HRM- and TaqMan-based SNP genotyping. Saturated maps of the Cr2-linkage group (LG) were constructed in three seed families using a total of 34 SNP markers within 21 unique genes. Cr2 was consistently flanked by contig_2142 (encoding a ruvb-like protein) and contig_3772 (encoding a delta-fatty acid desaturase) across the three seed families. Cr2 was anchored to the Pinus consensus LG-1, which differs from LGs where other R loci of Pinus species were mapped. GO annotation identified a set of NBS-LRR and other resistance-related genes as R candidates in the Cr2 region. Association of one nonsynonymous SNP locus of an NBS-LRR gene with Cr2-mediated phenotypes provides a valuable tool for marker-assisted selection (MAS), which will shorten the breeding cycle of resistance screening and aid in the restoration of WPBR-disturbed forest ecosystems. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  14. Genome-wide association identifies TBX5 as candidate gene for osteochondrosis providing a functional link to cartilage perfusion as initial factor

    Directory of Open Access Journals (Sweden)

    Noppawan eRangkasenee

    2013-05-01

    Full Text Available Osteochondrosis (OC is an orthopedic syndrome of the joints that occurs in children and adolescents and domestic animals, particularly pigs, horses, and dogs. OC is the most frequent cause of leg weakness in rapidly growing pigs causing animal welfare issues and economic losses. In this study, a genomewide association study (GWAS was performed using the Porcine 60k SNPChip in animals of the breed Large White (n=298 to identify chromosome regions and candidate genes associated with OC lesion scores. A total of 19 SNPs on chromosomes (SSC 3, 5, 8, 10, 14 and 18 were significantly associated with OC lesion scores (p-values ≤ 10-5. The SNPs MARC0098684, MARC00840086, MARC0093124 and ASGA0062794 at SSC14 36.1 to 38.2 Mb encompass a region of six linkage disequilibrium (LD blocks. The most significant SNP ASGA0062794 is located in a LD block spanning 465 kb and covering the gene encoding T-box transcription factor 5 (TBX5. A SNP (c.54T>C identified in TBX5 was significantly associated with OC lesions scores in a single marker analysis. TBX5 c.54T>C showed highest linkage disequilibrium with ASGA00627974 (r2=0.96 and superior association with OC lesion scores over other SNPs when included in the genome scan, whereas its treatment as an additional fixed effect in the GWAS statistical model led to a drop of significance of nearby markers. Moreover, real time PCR showed different transcript abundance of TBX5 in healthy and defect cartilage. The results imply that the association signal obtained on SCC14 is largely attributable to TBX5 c.54T>C likely to be in linkage disequilibrium with a regulatory polymorphism of TBX5. The transcription factor TBX5 interacts with GJA5 and MEF2C both being involved in vascularization. This study provides evidence for epistatic interaction of TBX5 and MEF2C, thus supporting deficiency of blood supply to growth cartilage as being fundamental for the initiation of osteochondrosis.

  15. Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion.

    Directory of Open Access Journals (Sweden)

    Tasnim Dayeh

    2014-03-01

    Full Text Available Impaired insulin secretion is a hallmark of type 2 diabetes (T2D. Epigenetics may affect disease susceptibility. To describe the human methylome in pancreatic islets and determine the epigenetic basis of T2D, we analyzed DNA methylation of 479,927 CpG sites and the transcriptome in pancreatic islets from T2D and non-diabetic donors. We provide a detailed map of the global DNA methylation pattern in human islets, β- and α-cells. Genomic regions close to the transcription start site showed low degrees of methylation and regions further away from the transcription start site such as the gene body, 3'UTR and intergenic regions showed a higher degree of methylation. While CpG islands were hypomethylated, the surrounding 2 kb shores showed an intermediate degree of methylation, whereas regions further away (shelves and open sea were hypermethylated in human islets, β- and α-cells. We identified 1,649 CpG sites and 853 genes, including TCF7L2, FTO and KCNQ1, with differential DNA methylation in T2D islets after correction for multiple testing. The majority of the differentially methylated CpG sites had an intermediate degree of methylation and were underrepresented in CpG islands (∼ 7% and overrepresented in the open sea (∼ 60%. 102 of the differentially methylated genes, including CDKN1A, PDE7B, SEPT9 and EXOC3L2, were differentially expressed in T2D islets. Methylation of CDKN1A and PDE7B promoters in vitro suppressed their transcriptional activity. Functional analyses demonstrated that identified candidate genes affect pancreatic β- and α-cells as Exoc3l silencing reduced exocytosis and overexpression of Cdkn1a, Pde7b and Sept9 perturbed insulin and glucagon secretion in clonal β- and α-cells, respectively. Together, our data can serve as a reference methylome in human islets. We provide new target genes with altered DNA methylation and expression in human T2D islets that contribute to perturbed insulin and glucagon secretion. These

  16. Genome-wide scan for visceral leishmaniasis in mixed-breed dogs identifies candidate genes involved in T helper cells and macrophage signaling

    Science.gov (United States)

    We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2....

  17. Systematic characterisation of disease associated balanced chromosome rearrangements by FISH: cytogenetically and genetically anchored YACs identify microdeletions and candidate regions for mental retardation genes

    DEFF Research Database (Denmark)

    Wirth, J; Nothwang, H G; van der Maarel, S

    1999-01-01

    Disease associated balanced chromosome rearrangements (DBCRs) have been instrumental in the isolation of many disease genes. To facilitate the molecular cytogenetic characterisation of DBCRs, we have generated a set of >1200 non-chimeric, cytogenetically and genetically anchored CEPH YACs...... the Mendelian Cytogenetics Network (MCN), a collaborative effort of, at present, 270 cytogenetic laboratories throughout the world. In this pilot study, we have characterised 10 different MR associated chromosome regions delineating candidate regions for MR. Five of these regions are narrowed to breakpoint...

  18. The Candidate

    OpenAIRE

    Osborn, John C

    2013-01-01

    ABSTRACT   The Candidate is an attempt to marry elements of journalism and gaming into a format that both entertains and educates the player. The Google-AP Scholarship, a new scholarship award that is given to several journalists a year to work on projects at the threshold of technology and journalism, funded the project. The objective in this prototype version of the game is to put the player in the shoes of a congressional candidate during an off-year election, specificall...

  19. The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates

    Directory of Open Access Journals (Sweden)

    Violeta Georgieva Tsonkova

    2018-02-01

    Conclusions: Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active cytokine induced caspase 3/7 apoptotic pathway and is responsive to ER stress initiation factors. The cells' ability to proliferate can be further increased by already known compounds as well as by novel peptides and proteins. Based on its robust performance during the functionality assessment assays, the EndoC-βH1 cell line was successfully used as a screening platform for identification of novel anti-diabetic drug candidates.

  20. RNA-seq transcriptome analysis of the immature seeds of two Brassica napus lines with extremely different thousand-seed weight to identify the candidate genes related to seed weight.

    Science.gov (United States)

    Geng, Xinxin; Dong, Na; Wang, Yuquan; Li, Gan; Wang, Lijun; Guo, Xuejiao; Li, Jiabing; Wen, Zhaopu; Wei, Wenhui

    2018-01-01

    Brassica napus is an important oilseed crop worldwide. Although seed weight is the main determinant of seed yield, few studies have focused on the molecular mechanisms that regulate seed weight in B. napus. In this study, the immature seeds of G-42 and 7-9, two B. napus doubled haploid (DH) lines with extremely different thousand-seed weight (TSW), were selected for a transcriptome analysis to determine the regulatory mechanisms underlying seed weight at the whole gene expression level and to identify candidate genes related to seed weight. A total of 2,251 new genes and 2,205 differentially expressed genes (DEGs) were obtained via RNA-seq (RNA sequencing). Among these genes, 1,747 (77.61%) new genes and 2020 (91.61%) DEGs were successfully annotated. Of these DEGs, 1,118 were up-regulated and 1,087 were down-regulated in the large-seed line. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis indicated that 15 DEGs were involved in ubiquitin-mediated proteolysis and proteasome pathways, which might participate in regulating seed weight. The Gene Ontology (GO) database indicated that 222 DEGs were associated with the biological process or molecular function categories related to seed weight, such as cell division, cell size and cell cycle regulation, seed development, nutrient reservoir activity, and proteasome-mediated ubiquitin-dependent protein catabolic processes. Moreover, 50 DEGs encoding key enzymes or proteins were identified that likely participate in regulating seed weight. A DEG (GSBRNA2T00037121001) identified by the transcriptome analysis was also previously identified in a quantitative trait locus (QTL) region for seed weight via SLAF-seq (Specific Locus Amplified Fragment sequencing). Finally, the expression of 10 DEGs with putative roles in seed weight and the expression of the DEG GSBRNA2T00037121001 were confirmed by a quantitative real-time reverse transcription PCR (qRT-PCR) analysis, and the results were consistent with the RNA

  1. A CATALOG OF MOVING GROUP CANDIDATES IN THE SOLAR NEIGHBORHOOD

    International Nuclear Information System (INIS)

    Zhao Jingkun; Zhao Gang; Chen Yuqin

    2009-01-01

    Based on the kernel estimator and wavelet technique, we have identified 22 moving group candidates in the solar neighborhood from a sample which includes around 14,000 dwarfs and 6000 giants. Six of them were previously known as the Hercules stream, the Sirus-UMa stream, the Hyades stream, the Caster group, the Pleiades stream, and the IC 2391; five of them have also been reported by other authors. 11 moving group candidates, not previously reported in the literature, show prominent structures in dwarf or giant samples. A catalog of moving group candidates in the solar neighborhood is presented in this work.

  2. The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates.

    Science.gov (United States)

    Tsonkova, Violeta Georgieva; Sand, Fredrik Wolfhagen; Wolf, Xenia Asbæk; Grunnet, Lars Groth; Kirstine Ringgaard, Anna; Ingvorsen, Camilla; Winkel, Louise; Kalisz, Mark; Dalgaard, Kevin; Bruun, Christine; Fels, Johannes Josef; Helgstrand, Charlotte; Hastrup, Sven; Öberg, Fredrik Kryh; Vernet, Erik; Sandrini, Michael Paolo Bastner; Shaw, Allan Christian; Jessen, Carsten; Grønborg, Mads; Hald, Jacob; Willenbrock, Hanni; Madsen, Dennis; Wernersson, Rasmus; Hansson, Lena; Jensen, Jan Nygaard; Plesner, Annette; Alanentalo, Tomas; Petersen, Maja Borup Kjær; Grapin-Botton, Anne; Honoré, Christian; Ahnfelt-Rønne, Jonas; Hecksher-Sørensen, Jacob; Ravassard, Philippe; Madsen, Ole D; Rescan, Claude; Frogne, Thomas

    2018-02-01

    To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation. Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins. Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate. By screening of various proteins and peptides, we found Bombesin (BB) receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation. ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST) was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion. Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active

  3. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    NARCIS (Netherlands)

    Vigorito, E.; Kuchenbaecker, K.B.; Beesley, J.; Adlard, J.; Agnarsson, B.A.; Andrulis, I.L.; Arun, B.K.; Barjhoux, L.; Belotti, M.; Benitez, J.; Berger, A.; Bojesen, A.; Bonanni, B.; Brewer, C.; Caldes, T.; Caligo, M.A.; Campbell, I.; Chan, S.B.; Claes, K.B.; Cohn, D.E.; Cook, J.; Daly, M.B.; Damiola, F.; Davidson, R.; Pauw, A. de; Delnatte, C.; Diez, O.; Domchek, S.M.; Dumont, M.; Durda, K.; Dworniczak, B.; Easton, D.F.; Eccles, D.; Edwinsdotter Ardnor, C.; Eeles, R.; Ejlertsen, B.; Ellis, S.; Evans, D.G.; Feliubadalo, L.; Fostira, F.; Foulkes, W.D.; Friedman, E.; Frost, D.; Gaddam, P.; Ganz, P.A.; Garber, J.; Garcia-Barberan, V.; Gauthier-Villars, M.; Gehrig, A.; Gerdes, A.M.; Giraud, S.; Godwin, A.K.; Goldgar, D.E.; Hake, C.R.; Hansen, T.V.; Healey, S.; Hodgson, S.; Hogervorst, F.B.; Houdayer, C.; Hulick, P.J.; Imyanitov, E.N.; Isaacs, C.; Izatt, L.; Izquierdo, A.; Jacobs, L; Jakubowska, A.; Janavicius, R.; Jaworska-Bieniek, K.; Jensen, U.B.; John, E.M.; Vijai, J.; Karlan, B.Y.; Kast, K.; Khan, S.; Kwong, A.; Laitman, Y.; Lester, J.; Lesueur, F.; Liljegren, A.; Lubinski, J.; Mai, P.L.; Manoukian, S.; Mazoyer, S.; Meindl, A.; Mensenkamp, A.R.; Montagna, M.; Nathanson, K.L.; Neuhausen, S.L.; Nevanlinna, H.; Niederacher, D.; Olah, E.; Olopade, O.I.; Ong, K.R.; Osorio, A.; Park, S.K.; Paulsson-Karlsson, Y.; Pedersen, I.S.; Peissel, B.; Peterlongo, P.; et al.,

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2

  4. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    DEFF Research Database (Denmark)

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 ...

  5. Potential relevance of pre-operative quality of life questionnaires to identify candidates for surgical treatment of genital prolapse: a pilot study

    Directory of Open Access Journals (Sweden)

    Chauvin Christian

    2012-03-01

    Full Text Available Abstract Background To evaluate prolapse-related symptoms, quality of life and sexuality of patients with validated questionnaires before and after surgery for genital prolapse and assess relevance of such an evaluation to select women for surgery. Methods From November 2009 to April 2010, 16 patients operated on for genital prolapse of grade greater than or equal to 2 (POP-Q classification were evaluated prospectively by three questionnaires of quality of life Pelvic Floor Distress Inventory (PFDI-20, Pelvic Floor Impact Questionnaire (PFIQ-7 and Pelvic Organ Prolaps/Urinary Incontinence Sexual Questionnaire (PISQ-12. Data were collected the day before surgery and 6 weeks postoperatively. Results Eleven patients had laparoscopic surgery and five vaginal surgery. There was a significant decrease in pelvic heaviness, vaginal discomfort and urinary symptoms after surgery. The score of symptoms of prolapse, the PFDI-20 score was 98.5 preoperatively and 31.8 postoperatively (p Conclusions This study suggests that surgery improves quality of life of patients with genital prolapse. Quality of life questionnaires could help select good candidates for surgery. Further studies are required to determine threshold to standardize indications of surgery.

  6. Integrated genomic profiling identifies candidate genes implicated in glioma-genesis and a novel LEO1-SLC12A1 fusion gene.

    Science.gov (United States)

    Bralten, Linda B C; Kloosterhof, Nanne K; Gravendeel, Lonneke A M; Sacchetti, Andrea; Duijm, Elza J; Kros, Johan M; van den Bent, Martin J; Hoogenraad, Casper C; Sillevis Smitt, Peter A E; French, Pim J

    2010-06-01

    We performed genotyping and exon-level expression profiling on 21 glioblastomas (GBMs) and 19 oligodendrogliomas (ODs) to identify genes involved in glioma initiation and/or progression. Low-copy number amplifications (2.5 7) were more frequently observed in GBMs; ODs generally have more heterozygous deletions per tumor. Four high-copy amplicons were identified in more than one sample and resulted in overexpression of the known oncogenes EGFR, MDM2, and CDK4. In the fourth amplicon, RBBP5, a member of the RB pathway, may act as a novel oncogene in GBMs. Not all hCNAs contain known genes, which may suggest that other transcriptional and/or regulatory elements are the target for amplification. Regions with most frequent allelic loss, both in ODs and GBMs, resulted in a reduced expression of known tumor suppressor genes. We identified a homozygous deletion spanning the Pragmin gene in one sample, but direct sequencing of all coding exons in 20 other glioma samples failed to detect additional genetic changes. Finally, we screened for fusion genes by identifying aberrant 5'-3' expression of genes that lie over regions of a copy number change. A fusion gene between exon 11 of LEO1 and exon 10 of SLC12A1 was identified. Our data show that integrated genomic profiling can identify genes involved in tumor initiation, and/or progression and can be used as an approach to identify novel fusion genes. (c) 2010 Wiley-Liss, Inc.

  7. Primary and Presidential Candidates

    DEFF Research Database (Denmark)

    Goddard, Joseph

    2012-01-01

    This article looks at primary and presidential candidates in 2008 and 2012. Evidence suggests that voters are less influenced by candidates’ color, gender, or religious observation than previously. Conversely, markers of difference remain salient in the imaginations of pollsters and journalists......, and appear in opinion polls and newspaper columns....

  8. Salivary miRNA profiles identify children with autism spectrum disorder, correlate with adaptive behavior, and implicate ASD candidate genes involved in neurodevelopment.

    Science.gov (United States)

    Hicks, Steven D; Ignacio, Cherry; Gentile, Karen; Middleton, Frank A

    2016-04-22

    Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that lacks adequate screening tools, often delaying diagnosis and therapeutic interventions. Despite a substantial genetic component, no single gene variant accounts for >1 % of ASD incidence. Epigenetic mechanisms that include microRNAs (miRNAs) may contribute to the ASD phenotype by altering networks of neurodevelopmental genes. The extracellular availability of miRNAs allows for painless, noninvasive collection from biofluids. In this study, we investigated the potential for saliva-based miRNAs to serve as diagnostic screening tools and evaluated their potential functional importance. Salivary miRNA was purified from 24 ASD subjects and 21 age- and gender-matched control subjects. The ASD group included individuals with mild ASD (DSM-5 criteria and Autism Diagnostic Observation Schedule) and no history of neurologic disorder, pre-term birth, or known chromosomal abnormality. All subjects completed a thorough neurodevelopmental assessment with the Vineland Adaptive Behavior Scales at the time of saliva collection. A total of 246 miRNAs were detected and quantified in at least half the samples by RNA-Seq and used to perform between-group comparisons with non-parametric testing, multivariate logistic regression and classification analyses, as well as Monte-Carlo Cross-Validation (MCCV). The top miRNAs were examined for correlations with measures of adaptive behavior. Functional enrichment analysis of the highest confidence mRNA targets of the top differentially expressed miRNAs was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), as well as the Simons Foundation Autism Database (AutDB) of ASD candidate genes. Fourteen miRNAs were differentially expressed in ASD subjects compared to controls (p adaptive behavior. These miRNAs have high specificity and cross-validated utility as a potential screening tool for ASD.

  9. Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case–control sample of schizophrenia

    DEFF Research Database (Denmark)

    Ingason, Andrés; Giegling, Ina; Harmann, AM

    2015-01-01

    Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA re...... schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders....

  10. CGMIM: Automated text-mining of Online Mendelian Inheritance in Man (OMIM to identify genetically-associated cancers and candidate genes

    Directory of Open Access Journals (Sweden)

    Jones Steven

    2005-03-01

    Full Text Available Abstract Background Online Mendelian Inheritance in Man (OMIM is a computerized database of information about genes and heritable traits in human populations, based on information reported in the scientific literature. Our objective was to establish an automated text-mining system for OMIM that will identify genetically-related cancers and cancer-related genes. We developed the computer program CGMIM to search for entries in OMIM that are related to one or more cancer types. We performed manual searches of OMIM to verify the program results. Results In the OMIM database on September 30, 2004, CGMIM identified 1943 genes related to cancer. BRCA2 (OMIM *164757, BRAF (OMIM *164757 and CDKN2A (OMIM *600160 were each related to 14 types of cancer. There were 45 genes related to cancer of the esophagus, 121 genes related to cancer of the stomach, and 21 genes related to both. Analysis of CGMIM results indicate that fewer than three gene entries in OMIM should mention both, and the more than seven-fold discrepancy suggests cancers of the esophagus and stomach are more genetically related than current literature suggests. Conclusion CGMIM identifies genetically-related cancers and cancer-related genes. In several ways, cancers with shared genetic etiology are anticipated to lead to further etiologic hypotheses and advances regarding environmental agents. CGMIM results are posted monthly and the source code can be obtained free of charge from the BC Cancer Research Centre website http://www.bccrc.ca/ccr/CGMIM.

  11. Immunohistochemical expression analysis of leucine-rich PPR-motif-containing protein (LRPPRC), a candidate colorectal cancer biomarker identified by shotgun proteomics using iTRAQ.

    Science.gov (United States)

    Nishio, Tomohisa; Kurabe, Nobuya; Goto-Inoue, Naoko; Nakamura, Toshio; Sugimura, Haruhiko; Setou, Mitsutoshi; Maekawa, Masato

    2017-08-01

    Colorectal cancer (CRC) is the fourth most frequent cause of cancer deaths in the world. Novel biomarkers for the diagnosis, prognosis, and treatment of CRC are required to improve the clinical strategy. We applied shotgun proteomics using isobaric tags for relative and absolute quantitation (iTRAQ) to identify novel biomarkers of CRC, and then we detected leucine-rich PPR-motif-containing protein (LRPPRC) expression in 83 normal colorectal tissues and 133 CRC tissues by immunohistochemistry. A total of 570 proteins were identified using iTRAQ. We validated the expression of LRPPRC protein by immunohistochemical analysis of the 77 proteins that showed expression changes in the cancer tissues >1.5-fold the levels in the normal tissues. The expression levels of LRPPRC were significantly higher in CRC tissues than those in normal colorectal tissues, and the expression levels were related with tumor differentiation and especially high in moderately differentiated CRC tissues. We identified a novel, differentially expressed protein, LRPPRC, which has the potential to serve as a molecular target for diagnosis and/or prognosis of CRC. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Synthetic lethal genetic interactions that decrease somatic cell proliferation in Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer drug target.

    Science.gov (United States)

    McLellan, Jessica; O'Neil, Nigel; Tarailo, Sanja; Stoepel, Jan; Bryan, Jennifer; Rose, Ann; Hieter, Philip

    2009-12-01

    Somatic mutations causing chromosome instability (CIN) in tumors can be exploited for selective killing of cancer cells by knockdown of second-site genes causing synthetic lethality. We tested and statistically validated synthetic lethal (SL) interactions between mutations in six Saccharomyces cerevisiae CIN genes orthologous to genes mutated in colon tumors and five additional CIN genes. To identify which SL interactions are conserved in higher organisms and represent potential chemotherapeutic targets, we developed an assay system in Caenorhabditis elegans to test genetic interactions causing synthetic proliferation defects in somatic cells. We made use of postembryonic RNA interference and the vulval cell lineage of C. elegans as a readout for somatic cell proliferation defects. We identified SL interactions between members of the cohesin complex and CTF4, RAD27, and components of the alternative RFC(CTF18) complex. The genetic interactions tested are highly conserved between S. cerevisiae and C. elegans and suggest that the alternative RFC components DCC1, CTF8, and CTF18 are ideal therapeutic targets because of their mild phenotype when knocked down singly in C. elegans. Furthermore, the C. elegans assay system will contribute to our knowledge of genetic interactions in a multicellular animal and is a powerful approach to identify new cancer therapeutic targets.

  13. LC-QTOF-MS identification of porcine-specific peptide in heat treated pork identifies candidate markers for meat species determination.

    Science.gov (United States)

    Sarah, S A; Faradalila, W N; Salwani, M S; Amin, I; Karsani, S A; Sazili, A Q

    2016-05-15

    The purpose of this study was to identify porcine-specific peptide markers from thermally processed meat that could differentiate pork from beef, chevon and chicken meat. In the initial stage, markers from tryptic digested protein of chilled, boiled and autoclaved pork were identified using LC-QTOF-MS. An MRM method was then established for verification. A thorough investigation of LC-QTOF-MS data showed that only seven porcine-specific peptides were consistently detected. Among these peptides, two were derived from lactate dehydrogenase, one from creatine kinase, and four from serum albumin protein. However, MRM could only detect four peptides (EVTEFAK, LVVITAGAR, FVIER and TVLGNFAAFVQK) that were consistently present in pork samples. In conclusion, meat species determination through a tandem mass spectrometry platform shows high potential in providing scientifically valid and reliable results even at peptide level. Besides, the specificity and selectivity offered by the proteomics approach also provide a robust platform for Halal authentication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. "URM candidates are encouraged to apply": a national study to identify effective strategies to enhance racial and ethnic faculty diversity in academic departments of medicine.

    Science.gov (United States)

    Peek, Monica E; Kim, Karen E; Johnson, Julie K; Vela, Monica B

    2013-03-01

    There is little evidence regarding which factors and strategies are associated with high proportions of underrepresented minority (URM) faculty in academic medicine. The authors conducted a national study of U.S. academic medicine departments to better understand the challenges, successful strategies, and predictive factors for enhancing racial and ethnic diversity among faculty (i.e., physicians with an academic position or rank). This was a mixed-methods study using quantitative and qualitative methods. The authors conducted a cross-sectional study of eligible departments of medicine in 125 accredited U.S. medical schools, dichotomized into low-URM (bottom 50%) versus high-URM rank (top 50%). They used t tests and chi-squared tests to compare departments by geographic region, academic school rank, city type, and composite measures of "diversity best practices." The authors also conducted semistructured in-depth interviews with a subsample from the highest- and lowest-quartile medical schools in terms of URM rank. Eighty-two medical schools responded (66%). Geographic region and academic rank were statistically associated with URM rank, but not city type or composite measures of diversity best practices. Key themes emerged from interviews regarding successful strategies for URM faculty recruitment and retention, including institutional leadership, the use of human capital and social relationships, and strategic deployment of institutional resources. Departments of medicine with high proportions of URM faculty employ a number of successful strategies and programs for recruitment and retention. More research is warranted to identify new successful strategies and to determine the impact of specific strategies on establishing and maintaining workforce diversity.

  15. Potential Gains in Life Expectancy from Reductions in Leading Causes of Death, Los Angeles County: a Quantitative Approach to Identify Candidate Diseases for Prevention and Burden Disparities Elimination.

    Science.gov (United States)

    Ho, Alex; Hameed, Heena; Lee, Alice W; Shih, Margaret

    2016-09-01

    Despite overall gains in life expectancy at birth among Los Angeles County residents, significant disparities persist across population subgroups. The purpose of this study was to quantify the potential sex- and race/ethnicity-specific gains in life expectancy had we been able to fully or partially eliminate the leading causes of death in Los Angeles County. Complete annual life tables for local residents were generated by applying the same method used for the National Center of Health Statistics US life tables published in 1999. Based on 2010 Los Angeles County mortality records, sex- and race/ethnicity-specific potential gains in life expectancy were calculated using scenarios of 10, 20, 50, and 100 % elimination of 12 major causes of death. Coronary heart disease, the leading cause of death, was found to be most impactful on life expectancy. Its hypothetical full elimination would result in life expectancy gains ranging from 2.2 years among white females to 3.7 years among black males. Gains from complete elimination of lung cancer and stroke ranked second, with almost an additional year of life for each gender. However, marked disparities across racial/ethnic groups were noted from the elimination of several other causes of death, such as homicide, from which the gain among black males exceeded 13 times more than their white counterparts. By differentially targeting specific causes of death in disease prevention, not only can findings of this study aid in efficiently narrowing racial/ethnic disparities, they can also provide a quantitative means to identify and rank priorities in local health policymaking.

  16. 275 Candidates and 149 Validated Planets Orbiting Bright Stars in K2 Campaigns 0–10

    Science.gov (United States)

    Mayo, Andrew W.; Vanderburg, Andrew; Latham, David W.; Bieryla, Allyson; Morton, Timothy D.; Buchhave, Lars A.; Dressing, Courtney D.; Beichman, Charles; Berlind, Perry; Calkins, Michael L.; Ciardi, David R.; Crossfield, Ian J. M.; Esquerdo, Gilbert A.; Everett, Mark E.; Gonzales, Erica J.; Hirsch, Lea A.; Horch, Elliott P.; Howard, Andrew W.; Howell, Steve B.; Livingston, John; Patel, Rahul; Petigura, Erik A.; Schlieder, Joshua E.; Scott, Nicholas J.; Schumer, Clea F.; Sinukoff, Evan; Teske, Johanna; Winters, Jennifer G.

    2018-03-01

    Since 2014, NASA’s K2 mission has observed large portions of the ecliptic plane in search of transiting planets and has detected hundreds of planet candidates. With observations planned until at least early 2018, K2 will continue to identify more planet candidates. We present here 275 planet candidates observed during Campaigns 0–10 of the K2 mission that are orbiting stars brighter than 13 mag (in Kepler band) and for which we have obtained high-resolution spectra (R = 44,000). These candidates are analyzed using the vespa package in order to calculate their false-positive probabilities (FPP). We find that 149 candidates are validated with an FPP lower than 0.1%, 39 of which were previously only candidates and 56 of which were previously undetected. The processes of data reduction, candidate identification, and statistical validation are described, and the demographics of the candidates and newly validated planets are explored. We show tentative evidence of a gap in the planet radius distribution of our candidate sample. Comparing our sample to the Kepler candidate sample investigated by Fulton et al., we conclude that more planets are required to quantitatively confirm the gap with K2 candidates or validated planets. This work, in addition to increasing the population of validated K2 planets by nearly 50% and providing new targets for follow-up observations, will also serve as a framework for validating candidates from upcoming K2 campaigns and the Transiting Exoplanet Survey Satellite, expected to launch in 2018.

  17. Ensemble candidate classification for the LOTAAS pulsar survey

    Science.gov (United States)

    Tan, C. M.; Lyon, R. J.; Stappers, B. W.; Cooper, S.; Hessels, J. W. T.; Kondratiev, V. I.; Michilli, D.; Sanidas, S.

    2018-03-01

    One of the biggest challenges arising from modern large-scale pulsar surveys is the number of candidates generated. Here, we implemented several improvements to the machine learning (ML) classifier previously used by the LOFAR Tied-Array All-Sky Survey (LOTAAS) to look for new pulsars via filtering the candidates obtained during periodicity searches. To assist the ML algorithm, we have introduced new features which capture the frequency and time evolution of the signal and improved the signal-to-noise calculation accounting for broad profiles. We enhanced the ML classifier by including a third class characterizing RFI instances, allowing candidates arising from RFI to be isolated, reducing the false positive return rate. We also introduced a new training data set used by the ML algorithm that includes a large sample of pulsars misclassified by the previous classifier. Lastly, we developed an ensemble classifier comprised of five different Decision Trees. Taken together these updates improve the pulsar recall rate by 2.5 per cent, while also improving the ability to identify pulsars with wide pulse profiles, often misclassified by the previous classifier. The new ensemble classifier is also able to reduce the percentage of false positive candidates identified from each LOTAAS pointing from 2.5 per cent (˜500 candidates) to 1.1 per cent (˜220 candidates).

  18. Scalar tetraquark candidates on the lattice

    International Nuclear Information System (INIS)

    Berlin, Joshua

    2017-01-01

    The topic of this thesis is the investigation of scalar tetraquark candidates from lattice QCD. It is motivated by a previous study originating in the twisted mass collaboration. The initial tetraquark candidate of choice is the a 0 (980), an isovector in the nonet of light scalars (J P =0 + ). This channel is still poorly understood. It displays an inverted mass hierarchy to what is expected from the conventional quark model and the a 0 (980) and f 0 (980) feature a surprising mass degeneracy. For this reasons the a 0 (980) is a long assumed tetraquark candidate in the literature. We follow a methodological approach by studying the sensitivity of the scalar spectrum with fully dynamical quarks to a large basis of two-quark and four-quark creation operators. Ultimately, the candidate has to be identified in the direct vicinity of two two-particles states, which is understandably inevitable for a tetraquark candidate. To succeed in this difficult task two-meson creation operators are essential to employ in this channel. By localized four-quark operators we intend to probe the Hamiltonian on eigenstates with a closely bound four-quark structure.

  19. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Science.gov (United States)

    Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-01-01

    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  20. PREVIOUS SECOND TRIMESTER ABORTION

    African Journals Online (AJOL)

    PNLC

    PREVIOUS SECOND TRIMESTER ABORTION: A risk factor for third trimester uterine rupture in three ... for accurate diagnosis of uterine rupture. KEY WORDS: Induced second trimester abortion - Previous uterine surgery - Uterine rupture. ..... scarred uterus during second trimester misoprostol- induced labour for a missed ...

  1. Robust and Comprehensive Analysis of 20 Osteoporosis Candidate Genes by Very High-Density Single-Nucleotide Polymorphism Screen Among 405 White Nuclear Families Identified Significant Association and Gene–Gene Interaction

    Science.gov (United States)

    Xiong, Dong-Hai; Shen, Hui; Zhao, Lan-Juan; Xiao, Peng; Yang, Tie-Lin; Guo, Yan; Wang, Wei; Guo, Yan-Fang; Liu, Yong-Jun; Recker, Robert R; Deng, Hong-Wen

    2007-01-01

    Many “novel” osteoporosis candidate genes have been proposed in recent years. To advance our knowledge of their roles in osteoporosis, we screened 20 such genes using a set of high-density SNPs in a large family-based study. Our efforts led to the prioritization of those osteoporosis genes and the detection of gene–gene interactions. Introduction We performed large-scale family-based association analyses of 20 novel osteoporosis candidate genes using 277 single nucleotide polymorphisms (SNPs) for the quantitative trait BMD variation and the qualitative trait osteoporosis (OP) at three clinically important skeletal sites: spine, hip, and ultradistal radius (UD). Materials and Methods One thousand eight hundred seventy-three subjects from 405 white nuclear families were genotyped and analyzed with an average density of one SNP per 4 kb across the 20 genes. We conducted association analyses by SNP- and haplotype-based family-based association test (FBAT) and performed gene–gene interaction analyses using multianalytic approaches such as multifactor-dimensionality reduction (MDR) and conditional logistic regression. Results and Conclusions We detected four genes (DBP, LRP5, CYP17, and RANK) that showed highly suggestive associations (10,000-permutation derived empirical global p ≤ 0.01) with spine BMD/OP; four genes (CYP19, RANK, RANKL, and CYP17) highly suggestive for hip BMD/OP; and four genes (CYP19, BMP2, RANK, and TNFR2) highly suggestive for UD BMD/OP. The associations between BMP2 with UD BMD and those between RANK with OP at the spine, hip, and UD also met the experiment-wide stringent criterion (empirical global p ≤ 0.0007). Sex-stratified analyses further showed that some of the significant associations in the total sample were driven by either male or female subjects. In addition, we identified and validated a two-locus gene–gene interaction model involving GCR and ESR2, for which prior biological evidence exists. Our results suggested the

  2. Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes

    DEFF Research Database (Denmark)

    Russell, Meaghan K; Longoni, Mauro; Wells, Julie

    2012-01-01

    expression profiling of developing embryonic diaphragms would help identify genes likely to be associated with diaphragm defects. We generated a time series of whole-transcriptome expression profiles from laser captured embryonic mouse diaphragms at embryonic day (E)11.5 and E12.5 when experimental...... perturbations lead to CDH phenotypes, and E16.5 when the diaphragm is fully formed. Gene sets defining biologically relevant pathways and temporal expression trends were identified by using a series of bioinformatic algorithms. These developmental sets were then compared with a manually curated list of genes...... previously shown to cause diaphragm defects in humans and in mouse models. Our integrative filtering strategy identified 27 candidates for CDH. We examined the diaphragms of knockout mice for one of the candidate genes, pre-B-cell leukemia transcription factor 1 (Pbx1), and identified a range of previously...

  3. A direct molecular link between the autism candidate gene RORa and the schizophrenia candidate MIR137

    Science.gov (United States)

    Devanna, Paolo; Vernes, Sonja C.

    2014-02-01

    Retinoic acid-related orphan receptor alpha gene (RORa) and the microRNA MIR137 have both recently been identified as novel candidate genes for neuropsychiatric disorders. RORa encodes a ligand-dependent orphan nuclear receptor that acts as a transcriptional regulator and miR-137 is a brain enriched small non-coding RNA that interacts with gene transcripts to control protein levels. Given the mounting evidence for RORa in autism spectrum disorders (ASD) and MIR137 in schizophrenia and ASD, we investigated if there was a functional biological relationship between these two genes. Herein, we demonstrate that miR-137 targets the 3'UTR of RORa in a site specific manner. We also provide further support for MIR137 as an autism candidate by showing that a large number of previously implicated autism genes are also putatively targeted by miR-137. This work supports the role of MIR137 as an ASD candidate and demonstrates a direct biological link between these previously unrelated autism candidate genes.

  4. Laparoscopy After Previous Laparotomy

    Directory of Open Access Journals (Sweden)

    Zulfo Godinjak

    2006-11-01

    Full Text Available Following the abdominal surgery, extensive adhesions often occur and they can cause difficulties during laparoscopic operations. However, previous laparotomy is not considered to be a contraindication for laparoscopy. The aim of this study is to present that an insertion of Veres needle in the region of umbilicus is a safe method for creating a pneumoperitoneum for laparoscopic operations after previous laparotomy. In the last three years, we have performed 144 laparoscopic operations in patients that previously underwent one or two laparotomies. Pathology of digestive system, genital organs, Cesarean Section or abdominal war injuries were the most common causes of previouslaparotomy. During those operations or during entering into abdominal cavity we have not experienced any complications, while in 7 patients we performed conversion to laparotomy following the diagnostic laparoscopy. In all patients an insertion of Veres needle and trocar insertion in the umbilical region was performed, namely a technique of closed laparoscopy. Not even in one patient adhesions in the region of umbilicus were found, and no abdominal organs were injured.

  5. QTLs and potential candidate genes for heat stress tolerance identified from the mapping populations specifically segregating for Fv/Fm in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari; Torp, Anna Maria; Rosenqvist, Eva

    2017-01-01

    Despite the fact that F-v/F-m (maximum quantum efficiency of photosystem II) is the most widely used parameter for a rapid non-destructive measure of stress detection in plants, there are barely any studies on the genetic understanding of this trait under heat stress. Our aim was to identify...... quantitative trait locus (QTL) and the potential candidate genes linked to F-v/F-m for improved photosynthesis under heat stress in wheat (Triticum aestivum L.). Three bi-parental F-2 mapping populations were generated by crossing three heat tolerant male parents (origin: Afghanistan and Pakistan) selected...... for high F-v/F-m with a common heat susceptible female parent (origin: Germany) selected for lowest F-v/F-m out of a pool of 1274 wheat cultivars of diverse geographic origin. Parents together with 140 F-2 individuals in each population were phenotyped by F-v/F-m under heat stress (40 degrees C for 3 days...

  6. Supernova remnant candidates in the ROSAT All-Sky Survey

    Science.gov (United States)

    Prinz, T.; Becker, W.

    2014-07-01

    Radio supernova remnants (SNRs) in the Galaxy comprise an incomplete sample of the SNR population due to various selection effects. ROSAT performed the first All-Sky Survey (RASS) with an imaging X-ray telescope and thus provided another window for finding SNRs. Schaudel (2003) searched the RASS for unknown SNRs and pinpointed about 210 candidates. Meanwhile, 14 new SNRs of his list were identified (cf. Prinz & Becker 2013 for a summary). Revisiting the RASS SNR candidates and applying more stringent selection criteria as well as taking archival XMM-Newton, Chandra and Fermi data into account the current list of RASS SNR candidates still comprises 73 sources. These sources are promising SNR candidates and studying them with e.g. eRosita will help to reveal their true nature. eRosita is an X-ray telescope which is supposed to be launched in 2016. It will perform an X-ray all-sky survey with a sensitivity of more than 10 times of what was available with ROSAT. It supports to continue the previous SNR identification campaign and may reveal other candidates not seen with ROSAT. We report on the current status of our supernova identification campaign, characterize the most promising candidates and give prospects for eRosita.

  7. 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...

  8. IDENTIFICATION OF NEW GAMMA-RAY BLAZAR CANDIDATES WITH MULTIFREQUENCY ARCHIVAL OBSERVATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Cowperthwaite, Philip S. [Department of Astronomy, University of Maryland, College Park, MD 20742-2421 (United States); Massaro, F. [SLAC National Laboratory and Kavli Institute for Particle Astrophysics and Cosmology, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); D' Abrusco, R.; Paggi, A.; Smith, Howard A. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Tosti, G., E-mail: pcowpert@umd.edu [Dipartimento di Fisica, Università Degli Studi di Perugia, I-06123 Perugia (Italy)

    2013-11-01

    Blazars are a highly variable, radio-loud subclass of active galactic nuclei. In order to better understand such objects we must be able to easily identify candidate blazars from the growing population of unidentified sources. Working toward this goal, we attempt to identify new gamma-ray blazar candidates from a sample of 102 previously unidentified sources. These sources are selected from The Astronomer's Telegram and the literature on the basis of non-periodic variability and multi-wavelength behavior. We then attempt to associate these objects to an IR counterpart in the Wide-field Infrared Survey Explorer all-sky survey. We are able to identify 16 candidate sources whose IR colors are consistent with those of the blazar population. Of those, 13 sources have IR colors indicative of being gamma-ray emitting blazar candidates. These sources all possess archival multi-wavelength observations that support their blazar-like nature.

  9. Recombinant foot-and-mouth disease virus (FMDV) non-structural protein 3A fused to enhanced green fluorescent protein (EGFP) as a candidate probe to identify FMDV-infected cattle in serosurveys.

    Science.gov (United States)

    Lotufo, Cecilia M; Bergmann, Ingrid E; Mattion, Nora M; Wilda, Maximiliano; Grigera, Pablo R

    2017-08-01

    Recombinant protein 3A-EGFP, a fusion construct between foot-and-mouth disease virus (FMDV) non-structural protein 3A and the enhanced green fluorescent protein (EGFP) was expressed in BL21-DE3 cells. The identity of the partially purified protein 3A-EGFP was confirmed by its reactivity with sera from cattle infected with FMDV and with a monoclonal antibody specific for FMDV-3ABC (MAb3H7) in Western blot assays. No reactivity was observed with sera from uninfected vaccinated animals. The performance of 3A-EGFP as an antigen in an indirect enzyme-linked immunosorbent assay (ELISA) was assessed and compared with that of a previously developed and validated capture ELISA that uses a 3ABC recombinant antigen (3ABC ELISA) and has been widely applied for serological surveys in Argentina. Parallel analysis of strongly and weakly positive reference sera from infected animals and 329 serum samples from uninfected vaccinated cattle showed that the 3A-EGFP antigen unequivocally identifies sera from FMDV-infected cattle with similar performance to its 3ABC counterpart. The 3A-EGFP ELISA is simpler and faster to perform than the 3ABC ELISA, since it does not require a capture step with a specific antibody. Moreover, the expression and storage of the recombinant 3A-EGFP is simplified by the absence of residual autoproteolytic activity associated to the 3C sequence. We conclude that the 3A-EGFP ELISA constitutes a promising screening method in serosurveys to determine whether or not animals are infected with FMDV.

  10. 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

  11. Leishmaniasis: vaccine candidates and perspectives.

    Science.gov (United States)

    Singh, Bhawana; Sundar, Shyam

    2012-06-06

    Leishmania is a protozoan parasite and a causative agent of the various clinical forms of leishmaniasis. High cost, resistance and toxic side effects of traditional drugs entail identification and development of therapeutic alternatives. The sound understanding of parasite biology is key for identifying novel drug targets, that can induce the cell mediated immunity (mainly CD4+ and CD8+ IFN-gamma mediated responses) polarized towards a Th1 response. These aspects are important in designing a new vaccine along with the consideration of the candidates with respect to their ability to raise memory response in order to improve the vaccine performance. This review is an effort to identify molecules according to their homology with the host and their ability to be used as potent vaccine candidates. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  12. Analysis of Polymorphic Membrane Protein Expression in Cultured Cells Identifies PmpA and PmpH of Chlamydia psittaci as Candidate Factors in Pathogenesis and Immunity to Infection.

    Science.gov (United States)

    Van Lent, Sarah; De Vos, Winnok H; Huot Creasy, Heather; Marques, Patricia X; Ravel, Jacques; Vanrompay, Daisy; Bavoil, Patrik; Hsia, Ru-Ching

    2016-01-01

    The polymorphic membrane protein (Pmp) paralogous families of Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia abortus are putative targets for Chlamydia vaccine development. To determine whether this is also the case for Pmp family members of C. psittaci, we analyzed transcription levels, protein production and localization of several Pmps of C. psittaci. Pmp expression profiles were characterized using quantitative real-time PCR (RT-qPCR), immunofluorescence (IF) and immuno-electron microscopy (IEM) under normal and stress conditions. We found that PmpA was highly produced in all inclusions as early as 12 hpi in all biological replicates. In addition, PmpA and PmpH appeared to be unusually accessible to antibody as determined by both immunofluorescence and immuno-electron microscopy. Our results suggest an important role for these Pmps in the pathogenesis of C. psittaci, and make them promising candidates in vaccine development.

  13. 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.

  14. Identification of genes from the Treacher Collins candidate region

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, M.; Dixon, J.; Edwards, S. [Univ. of California, Irvine, CA (United States)]|[Univ. of Manchester (United Kingdom)] [and others

    1994-09-01

    Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development. The TCOF1 locus has previously been mapped to chromosome 5q32-33. The candidate gene region has been defined as being between two flanking markers, ribosomal protein S14 (RPS14) and Annexin 6 (ANX6), by analyzing recombination events in affected individuals. It is estimated that the distance between these flanking markers is 500 kb by three separate analysis methods: (1) radiation hybrid mapping; (2) genetic linkage; and (3) YAC contig analysis. A cosmid contig which spans the candidate gene region for TCOF1 has been constructed by screening the Los Alamos National Laboratory flow-sorted chromosome 5 cosmid library. Cosmids were obtained by using a combination of probes generated from YAC end clones, Alu-PCR fragments from YACs, and asymmetric PCR fragments from both T7 and T3 cosmid ends. Exon amplifications, the selection of genomic coding sequences based upon the presence of functional splice acceptor and donor sites, was used to identify potential exon sequences. Sequences found to be conserved between species were then used to screen cDNA libraries in order to identify candidate genes. To date, four different cDNAs have been isolated from this region and are being analyzed as potential candidate genes for TCOF1. These include the genes encoding plasma glutathione peroxidase (GPX3), heparin sulfate sulfotransferase (HSST), a gene with homology to the ETS family of proteins and one which shows no homology to any known genes. Work is also in progress to identify and characterize additional cDNAs from the candidate gene region.

  15. PLANETARY CANDIDATES OBSERVED BY KEPLER IV: PLANET SAMPLE FROM Q1-Q8 (22 MONTHS)

    International Nuclear Information System (INIS)

    Burke, Christopher J.; Mullally, F.; Rowe, Jason F.; Thompson, Susan E.; Coughlin, Jeffrey L.; Caldwell, Douglas A.; Jenkins, Jon M.; Bryson, Stephen T.; Haas, Michael R.; Batalha, Natalie M.; Borucki, William J.; Christiansen, Jessie L.; Ciardi, David R.; Still, Martin; Barclay, Thomas; Chaplin, William J.; Clarke, Bruce D.; Cochran, William D.; Demory, Brice-Olivier; Esquerdo, Gilbert A.

    2014-01-01

    We provide updates to the Kepler planet candidate sample based upon nearly two years of high-precision photometry (i.e., Q1-Q8). From an initial list of nearly 13,400 threshold crossing events, 480 new host stars are identified from their flux time series as consistent with hosting transiting planets. Potential transit signals are subjected to further analysis using the pixel-level data, which allows background eclipsing binaries to be identified through small image position shifts during transit. We also re-evaluate Kepler Objects of Interest (KOIs) 1-1609, which were identified early in the mission, using substantially more data to test for background false positives and to find additional multiple systems. Combining the new and previous KOI samples, we provide updated parameters for 2738 Kepler planet candidates distributed across 2017 host stars. From the combined Kepler planet candidates, 472 are new from the Q1-Q8 data examined in this study. The new Kepler planet candidates represent ∼40% of the sample with R P ∼ 1 R ⊕ and represent ∼40% of the low equilibrium temperature (T eq < 300 K) sample. We review the known biases in the current sample of Kepler planet candidates relevant to evaluating planet population statistics with the current Kepler planet candidate sample

  16. Enthalpy screen of drug candidates.

    Science.gov (United States)

    Schön, Arne; Freire, Ernesto

    2016-11-15

    The enthalpic and entropic contributions to the binding affinity of drug candidates have been acknowledged to be important determinants of the quality of a drug molecule. These quantities, usually summarized in the thermodynamic signature, provide a rapid assessment of the forces that drive the binding of a ligand. Having access to the thermodynamic signature in the early stages of the drug discovery process will provide critical information towards the selection of the best drug candidates for development. In this paper, the Enthalpy Screen technique is presented. The enthalpy screen allows fast and accurate determination of the binding enthalpy for hundreds of ligands. As such, it appears to be ideally suited to aid in the ranking of the hundreds of hits that are usually identified after standard high throughput screening. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Candidate genes for migration do not distinguish migratory and non-migratory birds.

    Science.gov (United States)

    Lugo Ramos, Juan S; Delmore, Kira E; Liedvogel, Miriam

    2017-07-01

    Migratory traits in birds have been shown to have a strong heritable component and several candidate genes have been suggested to control these migratory traits. To investigate if the genetic makeup of one or a set of these candidate genes can be used to identify a general pattern between migratory and non-migratory birds, we extracted genomic sequence data for 25 hypothesised candidate genes for migration from 70 available genomes across all orders of Aves and characterised sequence divergence between migratory and non-migratory phenotypes. When examining each gene separately across all species, we did not identify any genetic variants in candidate genes that distinguished migrants from non-migrants; any resulting pattern was driven by the phylogenetic signal. This was true for each gene analysed independently, but also for concatenated sequence alignments of all candidate genes combined. We also attempted to distinguish between migrant and non-migrants using structural features at four candidate genes that have previously been reported to show associated with migratory behaviour but did not pick up a signal for migratory phenotype here either. Finally, a screen for dN/dS ratio across all focal candidate genes to probe for putative features of selection did not uncover a pattern, though this might not be expected given the broad phylogenetic scale used here. Our study demonstrates the potential of public genomic data to test for general patterns of migratory gene candidates in a cross-species comparative context, and raise questions on the applicability of candidate gene approaches in a macro-evolutionary context to understand the genetic architecture of migratory behaviour.

  18. Candidal infection in oral leukoplakia: a clinicopathologic study of 396 patients from eastern China.

    Science.gov (United States)

    Wu, Lan; Feng, Jinqiu; Shi, Linjun; Shen, Xuemin; Liu, Wei; Zhou, Zengtong

    2013-02-01

    Previous studies have suggested a link between the presence of Candida invasion and oral premalignant lesion. The objective of the current study was to investigate the clinicopathologic features of candidal infection in biopsies of a large retrospective cohort of patients with premalignant oral leukoplakia (n = 396) from eastern China and assess the clinical implications. Candidal hyphae were detected with periodic acid-Schiff staining of the biopsy samples. The results showed that 59 patients (15.9%) with oral leukoplakia were infected by Candida. The average age of the patients with candidal leukoplakia was 60.7 years with equal sex ratio. The tongue was the predominant site (66.1%). Epithelial hyperplasia and dysplasia were involved in 44.1% and 55.9% of patients, respectively. Multivariate analysis revealed that patient older than 60 years (odd ratio [OR], 2.28; P = .005), lesion located at the tongue (OR, 1.89; P = .038), and presence of dysplasia (OR, 2.02; P = .018) were significant risk factors of candidal infection in oral leukoplakia. Collectively, clinicopathologic features of candidal leukoplakia in eastern China were elucidated. A point to highlight was that we identified a subpopulation that was more liable to candidal infection. Elderly patients with oral tongue leukoplakia with epithelial dysplasia had much higher risk of candidal infection. Antifungal therapy was further recommended to be routine treatment of this subpopulation. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  19. Linkage mapping of candidate genes for induce resistance and growth promotion by trichoderma koningiopsis (th003) in tomato solanum lycopersicum

    International Nuclear Information System (INIS)

    Simbaqueba, Jaime; Cotes, Alba Marina; Barrero, Luz Stella

    2011-01-01

    Induced systemic resistance (ISR) is a mechanism by which plants enhance defenses against any stress condition. ISR and growth promotion are enhanced when tomato (Solanum lycopersicum) is inoculated with several strains of Trichoderma ssp. this study aims to genetically map tomato candidate genes involved in ISR and growth promotion induced by the Colombian native isolate Trichoderma koningiopsis th003. Forty-nine candidate genes previously identified on tomato plants treated with th003 and T. hamatum T382 strains were evaluated for polymorphisms and 16 of them were integrated on the highly saturated genetic linkage map named TOMATO EXPEN 2000. The location of six unigenes was similar to the location of resistance gene analogs (RGAS), defense related ests and resistance QTLs previously reported, suggesting new possible candidates for these quantitative trait loci (QTL) regions. The candidate gene-markers may be used for future ISR or growth promotion assisted selection in tomato.

  20. Vaccine candidates for malaria: what's new?

    Science.gov (United States)

    Takashima, Eizo; Morita, Masayuki; Tsuboi, Takafumi

    2016-01-01

    Although it is more than a decade since the parasite genome information was obtained, standardized novel genome-wide selection/prioritization strategies for candidacy of malaria vaccine antigens are still sought. In the quest to systematically identify candidates, it is impossible to overemphasize the usefulness of wheat germ cell-free technology in expressing quality proteins for the post-genome vaccine candidate discovery.

  1. Describing the Diapause-Preparatory Proteome of the Beetle Colaphellus bowringi and Identifying Candidates Affecting Lipid Accumulation Using Isobaric Tags for Mass Spectrometry-Based Proteome Quantification (iTRAQ

    Directory of Open Access Journals (Sweden)

    Daniel A. Hahn

    2017-04-01

    Full Text Available Prior to entering diapause, insects must prepare themselves physiologically to withstand the stresses of arresting their development for a lengthy period. While studies describing the biochemical and cellular milieu of the maintenance phase of diapause are accumulating, few studies have taken an “omics” approach to describing molecular events during the diapause preparatory phase. We used isobaric tags and mass spectrometry (iTRAQ to quantitatively compare the expression profiles of proteins identified during the onset of diapause preparation phase in the heads of adult female cabbage beetles, Colaphellus bowringi. A total of 3,175 proteins were identified, 297 of which were differentially expressed between diapause-destined and non-diapause-destined female adults and could therefore be involved in diapause preparation in this species. Comparison of identified proteins with protein function databases shows that many of these differentially expressed proteins enhanced in diapause destined beetles are involved in energy production and conversion, carbohydrate metabolism and transport, and lipid metabolism. Further hand annotation of differentially abundant peptides nominates several associated with stress hardiness, including HSPs and antioxidants, as well as neural development. In contrast, non-diapause destined beetles show substantial increases in cuticle proteins, suggesting additional post-emergence growth. Using RNA interference to silence a fatty acid-binding protein (FABP that was highly abundant in the head of diapause-destined females prevented the accumulation of lipids in the fat body, a common product of diapause preparation in this species and others. Surprisingly, RNAi against the FABP also affected the transcript abundance of several heat shock proteins. These results suggest that the identified differentially expressed proteins that play vital roles in lipid metabolism may also contribute somehow to enhanced hardiness to

  2. Black hole candidates

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Black hole candidates. In the case of X-ray sources such as Cyg X-1, the mass of the compact object inferred from combined optical and X-ray data, suggest M_compact object > 3.4 M_sun => Black Hole! A remarkable discovery!! Thus X-ray emitting binary systems ...

  3. Gallium-67 imaging in candidal esophagitis

    Energy Technology Data Exchange (ETDEWEB)

    Rundback, J.H.; Goldfarb, C.R.; Ongseng, F. (Beth Israel Medical Center, New York, NY (USA))

    1990-01-01

    Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis.

  4. Gallium-67 imaging in candidal esophagitis

    International Nuclear Information System (INIS)

    Rundback, J.H.; Goldfarb, C.R.; Ongseng, F.

    1990-01-01

    Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis

  5. 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

  6. Uterine rupture without previous caesarean delivery

    DEFF Research Database (Denmark)

    Thisted, Dorthe L. A.; H. Mortensen, Laust; Krebs, Lone

    2015-01-01

    OBJECTIVE: To determine incidence and patient characteristics of women with uterine rupture during singleton births at term without a previous caesarean delivery. STUDY DESIGN: Population based cohort study. Women with term singleton birth, no record of previous caesarean delivery and planned...... vaginal delivery (n=611,803) were identified in the Danish Medical Birth Registry (1997-2008). Medical records from women recorded with uterine rupture during labour were reviewed to ascertain events of complete uterine rupture. Relative Risk (RR) and adjusted Relative Risk Ratio (aRR) of complete uterine...... rupture with 95% confidence intervals (95% CI) were ascertained according to characteristics of the women and of the delivery. RESULTS: We identified 20 cases with complete uterine rupture. The incidence of complete uterine rupture among women without previous caesarean delivery was about 3...

  7. Supersymmetric Dark Matter Candidates

    CERN Document Server

    Ellis, John

    2010-01-01

    After reviewing the theoretical, phenomenological and experimental motivations for supersymmetric extensions of the Standard Model, we recall that supersymmetric relics from the Big Bang are expected in models that conserve R parity. We then discuss possible supersymmetric dark matter candidates, focusing on the lightest neutralino and the gravitino. In the latter case, the next-to-lightest supersymmetric particle is expected to be long-lived, and possible candidates include spartners of the tau lepton, top quark and neutrino. We then discuss the roles of the renormalization-group equations and electroweak symmetry breaking in delimiting the supersymmetric parameter space. We discuss in particular the constrained minimal extension of the Standard Model (CMSSM), in which the supersymmetry-breaking parameters are assumed to be universal at the grand unification scale, presenting predictions from a frequentist analysis of its parameter space. We also discuss astrophysical and cosmological constraints on gravitin...

  8. 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

  9. Evaluation of a Heart Transplant Candidate.

    Science.gov (United States)

    Lee, Sook Jin; Kim, Kyung Hee; Hong, Suk Keun; Hankins, Shelley

    2017-11-04

    Heart transplantation is the best option for irreversible and critically advanced heart failure. However, limited donor pool, the risk of rejection, infection, and right ventricular dysfunction in short-term post-transplant period, as well as, the development of coronary allograft vasculopathy and malignancy in the long-term post-transplant period limits the utility of heart transplantation for all comers with advanced heart failure. Therefore, selection of appropriate candidates is very important for the best short and long-term prognosis. In this article, we discuss the principles of selection of candidates and compare to the recently updated International Society for Heart and Lung Transplantation (ISHLT) listing criteria with the goal of updating current clinical practice. We found that while most of the recommendations in the new listing criteria are continuous with the previous criteria, updated recommendations are made on the risk stratification models in choosing transplantation candidates. Recommendation on hepatic dysfunction is not directly included in the updated ISHLT listing criteria; however, adoption of the Model for End-stage Liver Disease (MELD) score and modified MELD scores in the evaluation of risk are suggested in recent studies. In conclusion, evaluation of patient selection for heart transplantation should be comprehensive and individualized with respect to indications and the risk of comorbidities of candidates. With the advancement of mechanical circulatory support (MCS), the selection of heart transplantation candidate is continuously evolving and widened. MCS as bridge to candidacy should be considered when the candidate has potentially reversible risk factors for transplantation.

  10. Identification of Inherited Retinal Disease-Associated Genetic Variants in 11 Candidate Genes.

    Science.gov (United States)

    Astuti, Galuh D N; van den Born, L Ingeborgh; Khan, M Imran; Hamel, Christian P; Bocquet, Béatrice; Manes, Gaël; Quinodoz, Mathieu; Ali, Manir; Toomes, Carmel; McKibbin, Martin; El-Asrag, Mohammed E; Haer-Wigman, Lonneke; Inglehearn, Chris F; Black, Graeme C M; Hoyng, Carel B; Cremers, Frans P M; Roosing, Susanne

    2018-01-10

    Inherited retinal diseases (IRDs) display an enormous genetic heterogeneity. Whole exome sequencing (WES) recently identified genes that were mutated in a small proportion of IRD cases. Consequently, finding a second case or family carrying pathogenic variants in the same candidate gene often is challenging. In this study, we searched for novel candidate IRD gene-associated variants in isolated IRD families, assessed their causality, and searched for novel genotype-phenotype correlations. Whole exome sequencing was performed in 11 probands affected with IRDs. Homozygosity mapping data was available for five cases. Variants with minor allele frequencies ≤ 0.5% in public databases were selected as candidate disease-causing variants. These variants were ranked based on their: (a) presence in a gene that was previously implicated in IRD; (b) minor allele frequency in the Exome Aggregation Consortium database (ExAC); (c) in silico pathogenicity assessment using the combined annotation dependent depletion (CADD) score; and (d) interaction of the corresponding protein with known IRD-associated proteins. Twelve unique variants were found in 11 different genes in 11 IRD probands. Novel autosomal recessive and dominant inheritance patterns were found for variants in Small Nuclear Ribonucleoprotein U5 Subunit 200 ( SNRNP200 ) and Zinc Finger Protein 513 ( ZNF513 ), respectively. Using our pathogenicity assessment, a variant in DEAH-Box Helicase 32 ( DHX32 ) was the top ranked novel candidate gene to be associated with IRDs, followed by eight medium and lower ranked candidate genes. The identification of candidate disease-associated sequence variants in 11 single families underscores the notion that the previously identified IRD-associated genes collectively carry > 90% of the defects implicated in IRDs. To identify multiple patients or families with variants in the same gene and thereby provide extra proof for pathogenicity, worldwide data sharing is needed.

  11. Teachers Candidates' Reviews on Teacher Candidate Training System

    Science.gov (United States)

    Altintas, Sedat; Görgen, Izzet

    2017-01-01

    In our country, as a result of the appointment in some different disciplines, nearly 30000 teacher candidates could be a part of education system. Also, a new revision has been completed on teacher candidate training and it has been put into action. Teacher candidates have been trained for six months after they have been appointed. These teachers…

  12. Cochlear implant candidates with psychogenic hearing loss.

    Science.gov (United States)

    Kompis, Martin; Senn, Pascal; Mantokoudis, Georgios; Caversaccio, Marco

    2015-04-01

    Specific requests for cochlear implantations by persons with psychogenic hearing loss are a relatively new phenomenon. A number of features seems to be over-represented in this group of patients. The existence of these requests stresses the importance of auditory brainstem response (ABR) measurements before cochlear implantation. To describe the phenomenon of patients with psychogenic hearing losses specifically requesting cochlear implantation, and to gain first insights into the characteristics of this group. Analysis of all cases seen between 2004 and 2013 at the University Hospital of Bern, Switzerland. Four cochlear implant candidates with psychogenic hearing loss were identified. All were female, aged 23-51 years. Hearing thresholds ranged from 86 dB to 112 dB HL (pure-tone average 500-4000 Hz). ABRs and otoacoustic emissions (OAEs) showed bilaterally normal hearing in two subjects, and hearing thresholds between 30 and 50 dB in the other two subjects. Three subjects suffered from depression and one from a pathologic fear of cancer. Three had a history of five or more previous surgeries. Three were smokers and three reported other close family members with hearing losses. All four were hearing aid users at the time of presentation.

  13. Identify drug repurposing candidates by mining the protein data bank.

    Science.gov (United States)

    Moriaud, Fabrice; Richard, Stéphane B; Adcock, Stewart A; Chanas-Martin, Laetitia; Surgand, Jean-Sébastien; Ben Jelloul, Marouane; Delfaud, François

    2011-07-01

    Predicting off-targets by computational methods is gaining increasing interest in early-stage drug discovery. Here, we present a computational method based on full 3D comparisons of 3D structures. When a similar binding site is detected in the Protein Data Bank (PDB) (or any protein structure database), it is possible that the corresponding ligand also binds to that similar site. On one hand, this target hopping case is probably rare because it requires a high similarity between the binding sites. On the other hand, it could be a strong rational evidence to highlight possible off-target reactions and possibly a potential undesired side effect. This target-based drug repurposing can be extended a significant step further with the capability of searching the full surface of all proteins in the PDB, and therefore not relying on pocket detection. Using this approach, we describe how MED-SuMo reproduces the repurposing of tadalafil from PDE5A to PDE4A and a structure of PDE4A with tadalafil. Searching for local protein similarities generates more hits than for whole binding site similarities and therefore fragment repurposing is more likely to occur than for drug-sized compounds. In this work, we illustrate that by mining the PDB for proteins sharing similarities with the hinge region of protein kinases. The experimentally validated examples, biotin carboxylase and synapsin, are retrieved. Further to fragment repurposing, this approach can be applied to the detection of druggable sites from 3D structures. This is illustrated with detection of the protein kinase hinge motif in the HIV-RT non-nucleosidic allosteric site.

  14. 'Omics' approaches in tomato aimed at identifying candidate genes ...

    African Journals Online (AJOL)

    Tomato (Solanum lycopersicum) is one of the most important vegetables in the world with significant importance for human health and nutrition. This species has long served as model system for plant genetics, development, physiology, pathology, and fleshy fruit ripening, resulting in the accumulation of many genetic and ...

  15. University Offer Rates for Candidates from Different Ethnic Categories

    Science.gov (United States)

    Noden, Philip; Shiner, Michael; Modood, Tariq

    2014-01-01

    Previous research suggested that candidates from some black and minority ethnic groups were less likely to receive an offer of a place from an "old" university. These findings were disputed in a re-analysis carried out for HEFCE which found that only Pakistani candidates were significantly less likely to receive offers (from both…

  16. 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.

  17. Systematic Identification of Intracellular-Translocated Candidate Effectors in Edwardsiella piscicida

    Directory of Open Access Journals (Sweden)

    Lingzhi Zhang

    2018-02-01

    Full Text Available Many bacterial pathogens inject effectors directly into host cells to target a variety of host cellular processes and promote bacterial dissemination and survival. Identifying the bacterial effectors and elucidating their functions are central to understanding the molecular pathogenesis of these pathogens. Edwardsiella piscicida is a pathogen with a wide host range, and very few of its effectors have been identified to date. Here, based on the genes significantly regulated by macrophage infection, we identified 25 intracellular translocation-positive candidate effectors, including all five previously reported effectors, namely EseG, EseJ, EseH, EseK, and EvpP. A subsequent secretion analysis revealed diverse secretion patterns for the 25 effector candidates, suggesting that multiple transport pathways were involved in the internalization of these candidate effectors. Further, we identified two novel type VI secretion system (T6SS putative effectors and three outer membrane vesicles (OMV-dependent putative effectors among the candidate effectors described above, and further analyzed their contribution to bacterial virulence in a zebrafish model. This work demonstrates an effective approach for screening bacterial effectors and expands the effectors repertoire in E. piscicida.

  18. New open cluster candidates discovered in the XSTPS-GAC survey

    Science.gov (United States)

    Guo, Jin-Cheng; Zhang, Hua-Wei; Zhang, Hui-Hua; Liu, Xiao-Wei; Yuan, Hai-Bo; Huang, Yang; Wang, Song; Chen, Li; Zhao, Hai-Bin; Liu, Ji-Feng; Chen, Bing-Qiu; Xiang, Mao-Sheng; Tian, Zhi-Jia; Huo, Zhi-Ying; Wang, Chun

    2018-03-01

    The Xuyi Schmidt Telescope Photometric Survey of the Galactic Anti-center (XSTPS-GAC) is a photometric sky survey that covers nearly 6000 deg2 towards the Galactic Anti-center (GAC) in the g, r, i bands. Half of its survey field is located on the Galactic Anti-center disk, which makes XSTPS-GAC highly suitable to search for new open clusters in the GAC region. In this paper, we report new open cluster candidates discovered in this survey, as well as properties of these open cluster candidates, such as age, distance and reddening, derived by isochrone fitting in the color-magnitude diagram (CMD). These open cluster candidates are stellar density peaks detected in the star density maps by applying the method from Koposov et al. Each candidate is inspected in terms of its true color image composed from three XSTPS-GAC band images. Then its CMD is checked, in order to identify whether the central region stars have a clear isochrone-like trend differing from background stars. The parameters derived from isochrone fitting for these candidates are mainly based on three band photometry of XSTPS-GAC. Moreover, when these new candidates are able to be seen clearly in 2MASS data, their parameters are also derived based on the 2MASS (J – H, J) CMD. There are a total of 320 known open clusters rediscovered and 24 new open cluster candidates discovered in this work. Furthermore, the parameters of these new candidates, as well as another 11 previously known open clusters, are properly determined for the first time.

  19. Candidate high-redshift and primeval galaxies in Hubble Deep Field South

    Science.gov (United States)

    Clements, D. L.; Eales, S. A.; Baker, A. C.

    1999-09-01

    We present the results of colour selection of candidate high-redshift galaxies in Hubble Deep Field South (HDF-S) using the Lyman dropout scheme. The HDF-S data we discuss were taken in a number of different filters extending from the near-UV (F300W) to the infrared (F222M) in two different fields. This allows us to select candidates with redshifts from z~3 to z~12. We find 15 candidate z~3 objects (F300W dropouts), one candidate z~4 object (F450W dropout) and 16 candidate z~5 objects (F606W dropouts) in the ~4.7-arcmin^2 WFPC-2 field, and four candidate z~6 objects (optical dropouts) and one candidate z~8 object (F110W dropout) in the 0.84-arcmin^2 NICMOS-3 field. No F160W dropouts are found (z~12). We compare our selection technique with existing data for Hubble Deep Field North (HDF-N) and discuss alternative interpretations of the objects. We conclude that there are a number of lower redshift interlopers in the selections, including one previously identified object, and reject those objects most likely to be foreground contaminants. Even after this we conclude that the F606W dropout list is likely to still contain substantial foreground contamination. The lack of candidate very-high-redshift UV-luminous galaxies supports earlier conclusions by Lanzetta et al. We discuss the morphologies and luminosity functions of the high-redshift objects, and their cosmological implications.

  20. Tribological Tuft Testing Candidate Brush Seal Materials

    Science.gov (United States)

    DellaCorte, Chris

    1999-01-01

    This paper presents a tribological tuft test method of candidate brush seal materials in viewgraph form. The goals of the research are: 1) To develop test method to tribologically brush seal materials; 2) To evaluate materials to identify potential improvements and trends; and 3) Guide seal material development and selection.

  1. Concomitant and previous osteoporotic vertebral fractures.

    Science.gov (United States)

    Lenski, Markus; Büser, Natalie; Scherer, Michael

    2017-04-01

    Background and purpose - Patients with osteoporosis who present with an acute onset of back pain often have multiple fractures on plain radiographs. Differentiation of an acute osteoporotic vertebral fracture (AOVF) from previous fractures is difficult. The aim of this study was to investigate the incidence of concomitant AOVFs and previous OVFs in patients with symptomatic AOVFs, and to identify risk factors for concomitant AOVFs. Patients and methods - This was a prospective epidemiological study based on the Registry of Pathological Osteoporotic Vertebral Fractures (REPAPORA) with 1,005 patients and 2,874 osteoporotic vertebral fractures, which has been running since February 1, 2006. Concomitant fractures are defined as at least 2 acute short-tau inversion recovery (STIR-) positive vertebral fractures that happen concomitantly. A previous fracture is a STIR-negative fracture at the time of initial diagnostics. Logistic regression was used to examine the influence of various variables on the incidence of concomitant fractures. Results - More than 99% of osteoporotic vertebral fractures occurred in the thoracic and lumbar spine. The incidence of concomitant fractures at the time of first patient contact was 26% and that of previous fractures was 60%. The odds ratio (OR) for concomitant fractures decreased with a higher number of previous fractures (OR =0.86; p = 0.03) and higher dual-energy X-ray absorptiometry T-score (OR =0.72; p = 0.003). Interpretation - Concomitant and previous osteoporotic vertebral fractures are common. Risk factors for concomitant fractures are a low T-score and a low number of previous vertebral fractures in cases of osteoporotic vertebral fracture. An MRI scan of the the complete thoracic and lumbar spine with STIR sequence reduces the risk of under-diagnosis and under-treatment.

  2. Multiplexed mass spectrometry monitoring of biomarker candidates for osteoarthritis.

    Science.gov (United States)

    Fernández-Puente, Patricia; Calamia, Valentina; González-Rodríguez, Lucía; Lourido, Lucía; Camacho-Encina, María; Oreiro, Natividad; Ruiz-Romero, Cristina; Blanco, Francisco J

    2017-01-30

    The methods currently available for the diagnosis and monitoring of osteoarthritis (OA) are very limited and lack sensitivity. Being the most prevalent rheumatic disease, one of the most disabling pathologies worldwide and currently untreatable, there is a considerable interest pointed in the verification of specific biological markers for improving its diagnosis and disease progression studies. Considering the remarkable development of targeted proteomics methodologies in the frame of the Human Proteome Project, the aim of this work was to develop and apply a MRM-based method for the multiplexed analysis of a panel of 6 biomarker candidates for OA encoded by the Chromosome 16, and another 8 proteins identified in previous shotgun studies as related with this pathology, in specimens derived from the human joint and serum. The method, targeting 35 different peptides, was applied to samples from human articular chondrocytes, healthy and osteoarthritic cartilage, synovial fluid and serum. Subsequently, a verification analysis of the biomarker value of these proteins was performed by single point measurements on a set of 116 serum samples, leading to the identification of increased amounts of Haptoglobin and von Willebrand Factor in OA patients. Altogether, the present work provides a tool for the multiplexed monitoring of 14 biomarker candidates for OA, and verifies for the first time the increased amount of two of these circulating markers in patients diagnosed with this disease. We have developed an MRM method for the identification and relative quantification of a panel of 14 protein biomarker candidates for osteoarthritis. This method has been applied to analyze human articular chondrocytes, articular cartilage, synovial fluid, and finally a collection of 116 serum samples from healthy controls and patients suffering different degrees of osteoarthritis, in order to verify the biomarker usefulness of the candidates. HPT and VWF were validated as increased in OA

  3. SpeX Spectroscopy of Unresolved Very Low Mass Binaries. II. Identification of 14 Candidate Binaries with Late-M/Early-L and T Dwarf Components

    Science.gov (United States)

    Bardalez Gagliuffi, Daniella C.; Burgasser, Adam J.; Gelino, Christopher R.; Looper, Dagny L.; Nicholls, Christine P.; Schmidt, Sarah J.; Cruz, Kelle; West, Andrew A.; Gizis, John E.; Metchev, Stanimir

    2014-10-01

    Multiplicity is a key statistic for understanding the formation of very low mass (VLM) stars and brown dwarfs. Currently, the separation distribution of VLM binaries remains poorly constrained at small separations (candidates from a library of 815 spectra from the SpeX Prism Spectral Libraries. We present 11 new binary candidates, confirm 3 previously reported candidates, and rule out 2 previously identified candidates, all with primary and secondary spectral types in the range M7-L7 and T1-T8, respectively. We find that subdwarfs and blue L dwarfs are the primary contaminants in our sample and propose a method for segregating these sources. If confirmed by follow-up observations, these systems may add to the growing list of tight separation binaries, whose orbital properties may yield further insight into brown dwarf formation scenarios.

  4. 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.

  5. Five kepler target stars that show multiple transiting exoplanet candidates

    DEFF Research Database (Denmark)

    Steffen..[], Jason H.; Batalha, N. M.; Broucki, W J.

    2010-01-01

    We present and discuss five candidate exoplanetary systems identified with the Kepler spacecraft. These five systems show transits from multiple exoplanet candidates. Should these objects prove to be planetary in nature, then these five systems open new opportunities for the field of exoplanets...

  6. Searching for Be star candidates within large databases

    Directory of Open Access Journals (Sweden)

    Sabogal Beatriz

    2017-01-01

    Full Text Available Long time surveys yield many light curves among their byproducts, useful to identify candidate Be stars that can be confirmed by spectroscopic follow-ups. We present in this work different techniques we have used to find Be star candidates in the Galaxy, the Magellanic Clouds and the OGLE-IV Gaia South Ecliptic Pole Field.

  7. Identification and Validation of Candidate Genes Associated with Domesticated and Improved Traits in Soybean

    Directory of Open Access Journals (Sweden)

    Ling Zhou

    2016-07-01

    Full Text Available Soybean, an important source of vegetable oils and proteins for humans, has undergone significant phenotypic changes during domestication and improvement. However, there is limited knowledge about genes related to these domesticated and improved traits, such as flowering time, seed development, alkaline-salt tolerance, and seed oil content (SOC. In this study, more than 106,000 single nucleotide polymorphisms (SNPs were identified by restriction site associated DNA sequencing of 14 wild, 153 landrace, and 119 bred soybean accessions, and 198 candidate domestication regions (CDRs were identified via multiple genetic diversity analyses. Of the 1489 candidate domestication genes (CDGs within these CDRs, a total of 330 CDGs were related to the above four traits in the domestication, gene ontology (GO enrichment, gene expression, and pathway analyses. Eighteen, 60, 66, and 10 of the 330 CDGs were significantly associated with the above four traits, respectively. Of 134 trait-associated CDGs, 29 overlapped with previous CDGs, 11 were consistent with candidate genes in previous trait association studies, and 66 were covered by the domesticated and improved quantitative trait loci or their adjacent regions, having six common CDGs, such as one functionally characterized gene (. Of the 68 seed size (SS and SOC CDGs, 37 were further confirmed by gene expression analysis. In addition, eight genes were found to be related to artificial selection during modern breeding. Therefore, this study provides an integrated method for efficiently identifying CDGs and valuable information for domestication and genetic research.

  8. Automatic Classification of Kepler Planetary Transit Candidates

    Science.gov (United States)

    McCauliff, Sean D.; Jenkins, Jon M.; Catanzarite, Joseph; Burke, Christopher J.; Coughlin, Jeffrey L.; Twicken, Joseph D.; Tenenbaum, Peter; Seader, Shawn; Li, Jie; Cote, Miles

    2015-06-01

    In the first three years of operation, the Kepler mission found 3697 planet candidates (PCs) from a set of 18,406 transit-like features detected on more than 200,000 distinct stars. Vetting candidate signals manually by inspecting light curves and other diagnostic information is a labor intensive effort. Additionally, this classification methodology does not yield any information about the quality of PCs; all candidates are as credible as any other. The torrent of exoplanet discoveries will continue after Kepler, because a number of exoplanet surveys will have an even broader search area. This paper presents the application of machine-learning techniques to the classification of the exoplanet transit-like signals present in the Kepler light curve data. Transit-like detections are transformed into a uniform set of real-numbered attributes, the most important of which are described in this paper. Each of the known transit-like detections is assigned a class of PC; astrophysical false positive; or systematic, instrumental noise. We use a random forest algorithm to learn the mapping from attributes to classes on this training set. The random forest algorithm has been used previously to classify variable stars; this is the first time it has been used for exoplanet classification. We are able to achieve an overall error rate of 5.85% and an error rate for classifying exoplanets candidates of 2.81%.

  9. Lost Near-Earth Object Candidates

    Science.gov (United States)

    Veres, Peter; Farnocchia, Davide; Williams, Gareth; Keys, Sonia; Boardman, Ian; Holman, Matthew J.; Payne, Matthew J.

    2017-10-01

    The number of discovered Near-Earth Objects (NEOs) increases rapidly, currently exceeding 16,000 NEOs. 2016 was the most productive year ever with 1,888 NEO discoveries. The NEO discovery process typically begins with three to five detections of a previously unidentified object that are reported to the Minor Planet Center (MPC). According to the plane-of-sky motion, the MPC ranks all of the new candidate discoveries for the likelihood of being NEOs using the so-called digest score. If the digest score is greater than 65 the observations appear on the publicly accessible NEO Confirmation Page (NEOCP). Objects on the NEOCP are followed up in subsequent hours and days. When enough observations are collected to ensure that the object is real and that the orbit is determined, the NEO is officially announced with its new designation by a Minor Planet Electronic Circular. However, 14% of NEO candidates never get confirmed and are therefore lost due to the lack of follow-up observations. We analyzed the lost NEO candidates that appeared on NEOCP in 2013-2016 and investigated the reasons why they were not confirmed. In particular, we studied the properties of the lost NEO candidates with a digest score of 100 that were reported by the two most prolific discovery sites - Pan-STARRS1 (F51) and Mt. Lemmon Survey (G96). We derived their plane-of-sky positions and rates, brightness, and ephemeris uncertainties, and assessed correlations with the phase of the moon and seasonal effects apparent in the given observatory’s data. We concluded that lost NEO candidates typically have a larger rate of motion and larger uncertainties than those of confirmed objects. However, many of the lost candidates could be recovered. In fact, the 1-sigma plane-of-sky uncertainty was still within ±0.5 deg in 79% (F51) and 69% (G96) of the cases 24 hours after discovery and in 31% (F51) and 30% (G96) of the cases 48 hours after discovery. If all of the NEO candidates with a digest score of 100 had

  10. Validation of candidate genes putatively associated with resistance to SCMV and MDMV in maize (Zea mays L.) by expression profiling.

    Science.gov (United States)

    Uzarowska, Anna; Dionisio, Giuseppe; Sarholz, Barbara; Piepho, Hans-Peter; Xu, Mingliang; Ingvardsen, Christina Rønn; Wenzel, Gerhard; Lübberstedt, Thomas

    2009-02-02

    The potyviruses sugarcane mosaic virus (SCMV) and maize dwarf mosaic virus (MDMV) are major pathogens of maize worldwide. Two loci, Scmv1 and Scmv2, have ealier been shown to confer complete resistance to SCMV. Custom-made microarrays containing previously identified SCMV resistance candidate genes and resistance gene analogs were utilised to investigate and validate gene expression and expression patterns of isogenic lines under pathogen infection in order to obtain information about the molecular mechanisms involved in maize-potyvirus interactions. By employing time course microarray experiments we identified 68 significantly differentially expressed sequences within the different time points. The majority of differentially expressed genes differed between the near-isogenic line carrying Scmv1 resistance locus at chromosome 6 and the other isogenic lines. Most differentially expressed genes in the SCMV experiment (75%) were identified one hour after virus inoculation, and about one quarter at multiple time points. Furthermore, most of the identified mapped genes were localised outside the Scmv QTL regions. Annotation revealed differential expression of promising pathogenesis-related candidate genes, validated by qRT-PCR, coding for metallothionein-like protein, S-adenosylmethionine synthetase, germin-like protein or 26S ribosomal RNA. Our study identified putative candidate genes and gene expression patterns related to resistance to SCMV. Moreover, our findings support the effectiveness and reliability of the combination of different expression profiling approaches for the identification and validation of candidate genes. Genes identified in this study represent possible future targets for manipulation of SCMV resistance in maize.

  11. Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis

    DEFF Research Database (Denmark)

    Grauers, Anna; Wang, Jingwen; Einarsdottir, Elisabet

    2015-01-01

    , were Sanger sequenced in the 100 pooled samples. RESULTS: Of the four candidate genes, an intergenic variant, rs11190870, downstream of the LBX1 gene, showed a highly significant association to idiopathic scoliosis in 1,739 cases and 1,812 controls (p=7.0×10(-18)). We identified 20 novel variants...... that are significantly associated with idiopathic scoliosis in Asian and Caucasian populations, rs11190870 close to the LBX1 gene being the most replicated finding. PURPOSE: The aim of the present study was to investigate the genetics of idiopathic scoliosis in a Scandinavian cohort by performing a candidate gene study...... of four variants previously shown to be associated with idiopathic scoliosis and exome sequencing of idiopathic scoliosis patients with a severe phenotype to identify possible novel scoliosis risk variants. STUDY DESIGN: This was a case control study. PATIENT SAMPLE: A total of 1,739 patients...

  12. Do emotional intelligence and previous caring experience influence student nurse performance? A comparative analysis.

    Science.gov (United States)

    Stenhouse, Rosie; Snowden, Austyn; Young, Jenny; Carver, Fiona; Carver, Hannah; Brown, Norrie

    2016-08-01

    Reports of poor nursing care have focused attention on values based selection of candidates onto nursing programmes. Values based selection lacks clarity and valid measures. Previous caring experience might lead to better care. Emotional intelligence (EI) might be associated with performance, is conceptualised and measurable. To examine the impact of 1) previous caring experience, 2) emotional intelligence 3) social connection scores on performance and retention in a cohort of first year nursing and midwifery students in Scotland. A longitudinal, quasi experimental design. Adult and mental health nursing, and midwifery programmes in a Scottish University. Adult, mental health and midwifery students (n=598) completed the Trait Emotional Intelligence Questionnaire-short form and Schutte's Emotional Intelligence Scale on entry to their programmes at a Scottish University, alongside demographic and previous caring experience data. Social connection was calculated from a subset of questions identified within the TEIQue-SF in a prior factor and Rasch analysis. Student performance was calculated as the mean mark across the year. Withdrawal data were gathered. 598 students completed baseline measures. 315 students declared previous caring experience, 277 not. An independent-samples t-test identified that those without previous caring experience scored higher on performance (57.33±11.38) than those with previous caring experience (54.87±11.19), a statistically significant difference of 2.47 (95% CI, 0.54 to 4.38), t(533)=2.52, p=.012. Emotional intelligence scores were not associated with performance. Social connection scores for those withdrawing (mean rank=249) and those remaining (mean rank=304.75) were statistically significantly different, U=15,300, z=-2.61, p$_amp_$lt;0.009. Previous caring experience led to worse performance in this cohort. Emotional intelligence was not a useful indicator of performance. Lower scores on the social connection factor were associated

  13. Electoral Systems and Candidate Selection

    NARCIS (Netherlands)

    Hazan, Reuven Y.; Voerman, Gerrit

    Electoral systems at the national level and candidate selection methods at the party level are connected, maybe not causally but they do influence each other. More precisely, the electoral system constrains and conditions the parties' menu of choices concerning candidate selection. Moreover, in

  14. 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.

  15. Candidate glutamatergic neurons in the visual system of Drosophila.

    Directory of Open Access Journals (Sweden)

    Shamprasad Varija Raghu

    Full Text Available The visual system of Drosophila contains approximately 60,000 neurons that are organized in parallel, retinotopically arranged columns. A large number of these neurons have been characterized in great anatomical detail. However, studies providing direct evidence for synaptic signaling and the neurotransmitter used by individual neurons are relatively sparse. Here we present a first layout of neurons in the Drosophila visual system that likely release glutamate as their major neurotransmitter. We identified 33 different types of neurons of the lamina, medulla, lobula and lobula plate. Based on the previous Golgi-staining analysis, the identified neurons are further classified into 16 major subgroups representing lamina monopolar (L, transmedullary (Tm, transmedullary Y (TmY, Y, medulla intrinsic (Mi, Mt, Pm, Dm, Mi Am, bushy T (T, translobula plate (Tlp, lobula intrinsic (Lcn, Lt, Li, lobula plate tangential (LPTCs and lobula plate intrinsic (LPi cell types. In addition, we found 11 cell types that were not described by the previous Golgi analysis. This classification of candidate glutamatergic neurons fosters the future neurogenetic dissection of information processing in circuits of the fly visual system.

  16. Spectroscopic follow up of Kepler planet candidates

    DEFF Research Database (Denmark)

    Latham..[], D. W.; Cochran, W. D.; Marcy, G.W.

    2010-01-01

    and not planets, our strategy is to start with reconnaissance spectroscopy using smaller telescopes, to sort out and reject as many of the false positives as possible before going to Keck. During the first Kepler observing season in 2009, more than 100 nights of telescope time were allocated for this work, using......Spectroscopic follow-up observations play a crucial role in the confirmation and characterization of transiting planet candidates identified by Kepler. The most challenging part of this work is the determination of radial velocities with a precision approaching 1 m/s in order to derive masses from...... spectroscopic orbits. The most precious resource for this work is HIRES on Keck I, to be joined by HARPS-North on the William Herschel Telescope when that new spectrometer comes on line in two years. Because a large fraction of the planet candidates are in fact stellar systems involving eclipsing stars...

  17. Spectroscopic follow up of Kepler planet candidates

    DEFF Research Database (Denmark)

    Latham..[], D. W.; Cochran, W. D.; Marcy, G.W.

    2010-01-01

    Spectroscopic follow-up observations play a crucial role in the confirmation and characterization of transiting planet candidates identified by Kepler. The most challenging part of this work is the determination of radial velocities with a precision approaching 1 m/s in order to derive masses from...... spectroscopic orbits. The most precious resource for this work is HIRES on Keck I, to be joined by HARPS-North on the William Herschel Telescope when that new spectrometer comes on line in two years. Because a large fraction of the planet candidates are in fact stellar systems involving eclipsing stars...... and not planets, our strategy is to start with reconnaissance spectroscopy using smaller telescopes, to sort out and reject as many of the false positives as possible before going to Keck. During the first Kepler observing season in 2009, more than 100 nights of telescope time were allocated for this work, using...

  18. No Association between Personality and Candidate Gene Polymorphisms in a Wild Bird Population.

    Directory of Open Access Journals (Sweden)

    Hannah A Edwards

    Full Text Available Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4, and serotonin transporter (SERT. Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes.

  19. New Young Star Candidates in the Taurus-Auriga Region as Selected from WISE

    Science.gov (United States)

    Rebull, Luisa M.; Koenig, X.; Padgett, D.; Terebey, S.; McGehee, P.; Hillenbrand, L.; Knapp, G.; Leisawitz, D.; Liu, W.; Noriega-Crespo, A.; Ressler, M.; Stapelfeldt, K.; Fajardo-Acosta, S.; Mainzer, A.

    2012-01-01

    The Taurus Molecular Cloud subtends a large solid angle on the sky, in excess of 250 square degrees. 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 (WISE) 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 square degree 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.

  20. Psychological profile of Taiwanese female cosmetic surgery candidates: understanding their motivation for cosmetic surgery.

    Science.gov (United States)

    Chen, Hung-Chi; Karri, Vasu; Yu, Rwei-Ling; Chung, Kuo-Piao; Lu, Yi-Tien; Yang, Ming-Chin

    2010-06-01

    Psychological processes consisting of body image and self-esteem are considered key to the motivation for cosmetic surgery (CS). The current study aimed to investigate such processes as well as social support, perception of other people's opinion, and sex life satisfaction of Taiwanese female CS candidates. Further analyses were conducted to identify which processes predicted motivation for CS. Questionnaires comprising subscales of the Multidimensional Body-Self Relations Questionnaire, the Rosenberg Self-Esteem Scale, the Perception of Other Peoples' Opinion Scale, and social support and sex life questions were completed by Taiwanese female CS candidates (n = 85) preoperatively. The results were compared with those for a sex-matched nonsurgical control group (n = 105) as well as previously published data and reference norms. Correlation and multiple regression analysis also was conducted to identify any relationship between variables as well as which variable best predicted the likelihood of a patient having surgery. A total of 29 CS candidates (34.1%) reported before their surgical consultation that they would "very likely" or "likely" have CS, and 54 (63.5%) received support from all three social groups, namely, family, friends, and partner. The body image (appearance evaluation, orientation, and body area satisfaction) of the CS candidates was not significantly different from that of the control group. The former had significantly higher self-esteem and perception of other people's opinion scores. Self-esteem was positively correlated with appearance evaluation (r = 0.484; p self-esteem of the CS candidates opposes the view that low self-esteem is a principal motivating factor for CS.

  1. Typology of electoral candidates. Case study: Sorin Oprescu

    Directory of Open Access Journals (Sweden)

    Coman, C.

    2011-01-01

    Full Text Available By applying the content analysis technique of communication andby using analysis patterns such as the theory of rational choices, thedramaturgical model, the attraction model, the transactional analysis, this study identifies 4 typical categories of candidates to Romania’s presidency(elitist, dominating, reactive, sociable. In the analysis of the electoral itinerary of candidate Sorin Oprescu there are considered aspects such as identity, symbolism, volunteering, propagandas and media exposure, in order to make a SWOT analysis, thus facilitating the understanding of the candidate failure within the election process.

  2. Candidate region linkage analysis in twins discordant or concordant for depression symptomatology

    DEFF Research Database (Denmark)

    Christiansen, Lene; Tan, Q; Kruse, T A

    2009-01-01

    from 4,731 participants of the Longitudinal Study of Ageing Danish Twins. Our results showed suggestive evidence of linkage to this region with a peak LOD score of 1.91 for marker D12S1634 located at 148 cM, and thus indicates that the previously identified disease locus at 12q24 is also a general...... for a common susceptibility locus in affective disorders on chromosome 12q24. In this study we investigated the chromosome 12 candidate region for linkage to the mean level of depression symptomatology, over a 10-year follow-up, using a highly informative sample of concordant and discordant twin pairs selected...

  3. Caffeine Consumption Among Naval Aviation Candidates.

    Science.gov (United States)

    Sather, Thomas E; Williams, Ronald D; Delorey, Donald R; Woolsey, Conrad L

    2017-04-01

    Education frequently dictates students need to study for prolonged periods of time to adequately prepare for examinations. This is especially true with aviation preflight indoctrination (API) candidates who have to assimilate large volumes of information in a limited amount of time during API training. The purpose of this study was to assess caffeine consumption patterns (frequency, type, and volume) among naval aviation candidates attending API to determine the most frequently consumed caffeinated beverage and to examine if the consumption of a nonenergy drink caffeinated beverage was related to energy drink consumption. Data were collected by means of an anonymous 44-item survey administered and completed by 302 students enrolled in API at Naval Air Station Pensacola, FL. Results indicated the most frequently consumed caffeinated beverage consumed by API students was coffee (86.4%), with daily coffee consumption being approximately 28% and the most frequent pattern of consumption being 2 cups per day (85%). The least frequently consumed caffeinated beverages reported were energy drinks (52%) and energy shots (29.1%). The present study also found that the consumption patterns (weekly and daily) of caffeinated beverages (coffee and cola) were positively correlated to energy drink consumption patterns. Naval aviation candidates' consumption of caffeinated beverages is comparable to other college and high school cohorts. This study found that coffee and colas were the beverages of choice, with energy drinks and energy shots being the least frequently reported caffeinated beverages used. Additionally, a relationship between the consumption of caffeinated beverages and energy drinks was identified.Sather TE, Williams RD, Delorey DR, Woolsey CL. Caffeine consumption among naval aviation candidates. Aerosp Med Hum Perform. 2017; 88(4):399-405.

  4. Reducing stigma and discrimination: Candidate interventions

    Directory of Open Access Journals (Sweden)

    Kassam Aliya

    2008-04-01

    Full Text Available Abstract This paper proposes that stigma in relation to people with mental illness can be understood as a combination of problems of knowledge (ignorance, attitudes (prejudice and behaviour (discrimination. From a literature review, a series of candidate interventions are identified which may be effective in reducing stigmatisation and discrimination at the following levels: individuals with mental illness and their family members; the workplace; and local, national and international. The strongest evidence for effective interventions at present is for (i direct social contact with people with mental illness at the individual level, and (ii social marketing at the population level.

  5. 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...

  6. 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…

  7. Candidate genes in panic disorder

    DEFF Research Database (Denmark)

    Howe, A. S.; Buttenschön, Henriette N; Bani-Fatemi, A.

    2016-01-01

    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...

  8. TIME-SERIES SPECTROSCOPY OF TWO CANDIDATE DOUBLE DEGENERATES IN THE OPEN CLUSTER NGC 6633

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Kurtis A.; Chakraborty, Subho [Department of Physics and Astrophysics, Texas A and M University-Commerce, P.O. Box 3011, Commerce, TX, 75429 (United States); Serna-Grey, Donald [Department of Astronomy, University of Washington, Box 351580, Seattle, WA, 98195 (United States); Gianninas, A.; Canton, Paul A., E-mail: Kurtis.Williams@tamuc.edu [Homer L. Dodge Department of Physics and Astronomy, University of Oklahoma, 440 W. Brooks St., Norman, OK, 73019 (United States)

    2015-12-15

    SNe Ia are heavily used tools in precision cosmology, yet we still are not certain what the progenitor systems are. General plausibility arguments suggest there is potential for identifying double degenerate SN Ia progenitors in intermediate-age open star clusters. We present time-resolved high-resolution spectroscopy of two white dwarfs (WDs) in the field of the open cluster NGC 6633 that had previously been identified as candidate double degenerates in the cluster. However, three hours of continuous observations of each candidate failed to detect any significant radial velocity variations at the ≳10 km s{sup −1} level, making it highly unlikely that either WD is a double degenerate that will merge within a Hubble Time. The WD LAWDS NGC 6633 4 has a radial velocity inconsistent with cluster membership at the 2.5σ level, while the radial velocity of LAWDS NGC 6633 7 is consistent with cluster membership. We conservatively conclude that LAWDS 7 is a viable massive double degenerate candidate, though unlikely to be a Type Ia progenitor. Astrometric data from GAIA will likely be needed to determine if either WD is truly a cluster member.

  9. Candidate gene association studies in syndromic and non-syndromic cleft lip and palate

    Energy Technology Data Exchange (ETDEWEB)

    Daack-Hirsch, S.; Basart, A.; Frischmeyer, P. [Univ. of Iowa, IA (United States)] [and others

    1994-09-01

    Using ongoing case ascertainment through a birth defects registry, we have collected 219 nuclear families with non-syndromic cleft lip and/or palate and 111 families with a collection of syndromic forms. Syndromic cases include 24 with recognized forms and 72 with unrecognized syndromes. Candidate gene studies as well as genome-wide searches for evidence of microdeletions and isodisomy are currently being carried out. Candidate gene association studies, to date, have made use of PCR-based polymorphisms for TGFA, MSX1, CLPG13 (a CA repeat associated with a human homologue of a locus that results in craniofacial dysmorphogenesis in the mouse) and an STRP found in a Van der Woude syndrome microdeletion. Control tetranucleotide repeats, which insure that population-based differences are not responsible for any observed associations, are also tested. Studies of the syndromic cases have included the same list of candidate genes searching for evidence of microdeletions and a genome-wide search using tri- and tetranucleotide polymorphic markers to search for isodisomy or structural rearrangements. Significant associations have previously been identified for TGFA, and, in this report, identified for MSX1 and nonsyndromic cleft palate only (p = 0.04, uncorrected). Preliminary results of the genome-wide scan for isodisomy has returned no true positives and there has been no evidence for microdeletion cases.

  10. Candidate predisposing germline copy number variants in early onset colorectal cancer patients.

    Science.gov (United States)

    Brea-Fernandez, A J; Fernandez-Rozadilla, C; Alvarez-Barona, M; Azuara, D; Ginesta, M M; Clofent, J; de Castro, L; Gonzalez, D; Andreu, M; Bessa, X; Llor, X; Xicola, R; Jover, R; Castells, A; Castellvi-Bel, S; Capella, G; Carracedo, A; Ruiz-Ponte, C

    2017-05-01

    A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset. We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter. We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis. These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

  11. A Public Platform for the Verification of the Phenotypic Effect of Candidate Genes for Resistance to Aflatoxin Accumulation and Aspergillus flavus Infection in Maize

    Directory of Open Access Journals (Sweden)

    Xueyan Shan

    2011-06-01

    Full Text Available A public candidate gene testing pipeline for resistance to aflatoxin accumulation or Aspergillus flavus infection in maize is presented here. The pipeline consists of steps for identifying, testing, and verifying the association of selected maize gene sequences with resistance under field conditions. Resources include a database of genetic and protein sequences associated with the reduction in aflatoxin contamination from previous studies; eight diverse inbred maize lines for polymorphism identification within any maize gene sequence; four Quantitative Trait Loci (QTL mapping populations and one association mapping panel, all phenotyped for aflatoxin accumulation resistance and associated phenotypes; and capacity for Insertion/Deletion (InDel and SNP genotyping in the population(s for mapping. To date, ten genes have been identified as possible candidate genes and put through the candidate gene testing pipeline, and results are presented here to demonstrate the utility of the pipeline.

  12. EnviroAtlas - Candidate Areas for Ecological Restoration for the Conterminous United States

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset shows the candidate areas for ecological restoration, identified as close but geographically disjunct vegetated regions. Ecological...

  13. Placental complications after a previous cesarean section

    OpenAIRE

    Milošević Jelena; Lilić Vekoslav; Tasić Marija; Radović-Janošević Dragana; Stefanović Milan; Antić Vladimir

    2009-01-01

    Introduction The incidence of cesarean section has been rising in the past 50 years. With the increased number of cesarean sections, the number of pregnancies with the previous cesarean section rises as well. The aim of this study was to establish the influence of the previous cesarean section on the development of placental complications: placenta previa, placental abruption and placenta accreta, as well as to determine the influence of the number of previous cesarean sections on the complic...

  14. The SuperWASP catalogue of 4963 RR Lyr stars: identification of 983 Blazhko effect candidates

    Science.gov (United States)

    Greer, P. A.; Payne, S. G.; Norton, A. J.; Maxted, P. F. L.; Smalley, B.; West, R. G.; Wheatley, P. J.; Kolb, U. C.

    2017-10-01

    Aims: We set out to compile a catalogue of RRab pulsating variables in the SuperWASP archive and identify candidate Blazhko effect objects within this catalogue. We analysed their light curves and power spectra for correlations in their common characteristics to further our understanding of the phenomenon. Methods: Pulsation periods were found for each SWASP RRab object using phase dispersion minimisation techniques. Low frequency periodic signals detected in the CLEAN power spectra of RRab stars were matched with modulation sidebands and combined with pairs of sidebands to produce a list of candidate Blazhko periods. A novel technique was used in an attempt to identify Blazhko effect stars by comparing scatter at different parts of the folded light curve. Pulsation amplitudes were calculated based on phase folded light curves. Results: The SuperWASP RRab catalogue consists of 4963 objects of which 3397 are previously unknown. We discovered 983 distinct candidates for Blazhko effect objects, 613 of these being previously unknown in the literature as RR Lyrae stars, and 894 are previously unknown to be Blazhko effect stars. Correlations were investigated between the scatter of points on the light curve, the periods and amplitudes of the objects' pulsations, and those of the Blazhko effect. Conclusions: A statistical analysis has been performed on a large population of Blazhko effect stars from the wide-field SuperWASP survey. No correlations were found between the Blazhko period and other parameters including the Blazhko amplitude, although we confirmed a lower rate of occurrence of the Blazhko effect in long pulsation period objects. Full Tables 1 and 2 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/607/A11

  15. Replication of type 2 diabetes candidate genes variations in three geographically unrelated Indian population groups.

    Directory of Open Access Journals (Sweden)

    Shafat Ali

    Full Text Available Type 2 diabetes (T2D is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E-04 with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E-08 in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR<1.38 increased to OR = 2.44, (95%CI = 1.67-3.59 when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.

  16. Replication of type 2 diabetes candidate genes variations in three geographically unrelated Indian population groups.

    Science.gov (United States)

    Ali, Shafat; Chopra, Rupali; Manvati, Siddharth; Singh, Yoginder Pal; Kaul, Nabodita; Behura, Anita; Mahajan, Ankit; Sehajpal, Prabodh; Gupta, Subash; Dhar, Manoj K; Chainy, Gagan B N; Bhanwer, Amarjit S; Sharma, Swarkar; Bamezai, Rameshwar N K

    2013-01-01

    Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, ppopulation. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E-08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR = 2.44, (95%CI = 1.67-3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.

  17. Automatic Classification of Kepler Planetary Transit Candidates

    OpenAIRE

    McCauliff, Sean D.; Jenkins, Jon M.; Catanzarite, Joseph; Burke, Christopher J.; Coughlin, Jeffrey L.; Twicken, Joseph D.; Tenenbaum, Peter; Seader, Shawn; Li, Jie; Cote, Miles

    2014-01-01

    In the first three years of operation the Kepler mission found 3,697 planet candidates from a set of 18,406 transit-like features detected on over 200,000 distinct stars. Vetting candidate signals manually by inspecting light curves and other diagnostic information is a labor intensive effort. Additionally, this classification methodology does not yield any information about the quality of planet candidates; all candidates are as credible as any other candidate. The torrent of exoplanet disco...

  18. RARβ gene methylation is a candidate for primary glioblastoma ...

    African Journals Online (AJOL)

    and p15/INK4. These hypermethylated genes have been reported as a marker for prognosis, treatment pro- tocol selection and survival for GBM patients1,7. Abnormal DNA methylation of brain tumors was first discovered 20 years ago and previous methylation stud- ies for candidate genes in brain tissue have concentrated.

  19. Biomarker candidate discovery in Atlantic cod (Gadus morhua) continuously exposed to North Sea produced water from egg to fry

    DEFF Research Database (Denmark)

    Bohne-Kjersem, Anneli; Bache, Nicolai; Meier, Sonnich

    2010-01-01

    were able to compare the induced changes by PW to the mode of action of oestrogens. Changes in the proteome in response to exposure in whole cod fry (approximately 80 days post-hatching, dph) were detected by two-dimensional gel electrophoresis and image analysis and identified by MALDI-ToF-ToF mass...... spectrometry, using a newly developed cod EST database and the NCBI database. Many of the protein changes occurred at low levels (0.01% and 0.1% PW) of exposure, indicating putative biological responses at lower levels than previously detected. Using discriminant analysis, we identified a set of protein...... changes that may be useful as biomarker candidates of produced water (PW) and oestradiol exposure in Atlantic cod fry. The biomarker candidates discovered in this study may, following validation, prove effective as diagnostic tools in monitoring exposure and effects of discharges from the petroleum...

  20. Compatibility in the Biomphalaria glabrata/Echinostoma caproni model: new candidate genes evidenced by a suppressive subtractive hybridization approach.

    Science.gov (United States)

    Bouchut, A; Coustau, C; Gourbal, B; Mitta, G

    2007-04-01

    In order to elucidate mechanisms underlying snail/echinostome compatibility, numerous molecular studies comparing transcripts and proteins of Biomphalaria glabrata susceptible or resistant to Echinostoma caproni were undertaken. These studies focused on plasma and haemocytes of the two strains and revealed that some transcripts and/or proteins were differentially expressed between strains. The aim of the present study was to develop a complementary transcriptomic approach by constructing subtractive libraries. This work revealed some candidate transcripts already identified in previous studies (calcium-binding proteins and glycolytic enzymes) as well as novel candidate transcripts that were differentially represented between strains of B. glabrata. Among these newly identified genes, we revealed several genes potentially involved in immune processes encoding proteases, protease inhibitors, a lectin, an aplysianin-like molecule, and cell adhesion molecules.

  1. Serological profile of candidates for corneal donation

    Directory of Open Access Journals (Sweden)

    Adroaldo Lunardelli

    2014-10-01

    Full Text Available Objetive: The purpose of this study is to map the serological profile of candidates to corneal donation at Irmandade Santa Casa de Misericórdia de Porto Alegre, identifying the percentage of disposal by serology and the marker involved. Methods: There have been analised – retrospectively – the results of serology of all corneal donors, made between the period of 1st january 2006 and 31st december 2012. Data analised were related to age, gender and the results of serology pertinent to viral markers (HBsAg, anti-HBc, anti-HCV and anti-HIV, these, determined by immunosorbent tests (ELISA. Results: In the period of the study, there were 2476 corneal donors at the institution, with a major incidence on the male gender, on an average of 58.7 years old. 23% of retention because of serological unfitness was also identified, that is, 570 samples were non-negative to any of the used tests. The marker anti- HBc was the most prevalent on the studied population, followed by the Hepatitis C virus (HCV and by the Human Immunodeficiency Virus (HIV. Conclusion: From the data found through this study, it is essential to have the participation of an efficient service on the serological evaluation of the candidates to corneal donation, once the security of the receptor must be taken into consideration in a population of donors with 23% of unfitness prevalence, in which the most prevalent marker is the one of Hepatits B.

  2. Toward organometallic antischistosomal drug candidates.

    Science.gov (United States)

    Hess, Jeannine; Keiser, Jennifer; Gasser, Gilles

    2015-01-01

    In the recent years, there has been a growing interest in the use of novel approaches for the treatment of parasitic diseases such as schistosomiasis. Among the different approaches used, organometallic compounds were found to offer unique opportunities in the design of antiparasitic drug candidates. A ferrocenyl derivative, namely ferroquine, has even entered clinical trials as a novel antimalarial. In this short review, we report on the studies describing the use of organometallic compounds against schistosomiasis.

  3. 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...

  4. Preoperative screening: value of previous tests.

    Science.gov (United States)

    Macpherson, D S; Snow, R; Lofgren, R P

    1990-12-15

    To determine the frequency of tests done in the year before elective surgery that might substitute for preoperative screening tests and to determine the frequency of test results that change from a normal value to a value likely to alter perioperative management. Retrospective cohort analysis of computerized laboratory data (complete blood count, sodium, potassium, and creatinine levels, prothrombin time, and partial thromboplastin time). Urban tertiary care Veterans Affairs Hospital. Consecutive sample of 1109 patients who had elective surgery in 1988. At admission, 7549 preoperative tests were done, 47% of which duplicated tests performed in the previous year. Of 3096 previous results that were normal as defined by hospital reference range and done closest to the time of but before admission (median interval, 2 months), 13 (0.4%; 95% CI, 0.2% to 0.7%), repeat values were outside a range considered acceptable for surgery. Most of the abnormalities were predictable from the patient's history, and most were not noted in the medical record. Of 461 previous tests that were abnormal, 78 (17%; CI, 13% to 20%) repeat values at admission were outside a range considered acceptable for surgery (P less than 0.001, frequency of clinically important abnormalities of patients with normal previous results with those with abnormal previous results). Physicians evaluating patients preoperatively could safely substitute the previous test results analyzed in this study for preoperative screening tests if the previous tests are normal and no obvious indication for retesting is present.

  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. Quantitative trait loci mapping reveals candidate pathways regulating cell cycle duration in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Siwo Geoffrey

    2010-10-01

    Full Text Available Abstract Background Elevated parasite biomass in the human red blood cells can lead to increased malaria morbidity. The genes and mechanisms regulating growth and development of Plasmodium falciparum through its erythrocytic cycle are not well understood. We previously showed that strains HB3 and Dd2 diverge in their proliferation rates, and here use quantitative trait loci mapping in 34 progeny from a cross between these parent clones along with integrative bioinformatics to identify genetic loci and candidate genes that control divergences in cell cycle duration. Results Genetic mapping of cell cycle duration revealed a four-locus genetic model, including a major genetic effect on chromosome 12, which accounts for 75% of the inherited phenotype variation. These QTL span 165 genes, the majority of which have no predicted function based on homology. We present a method to systematically prioritize candidate genes using the extensive sequence and transcriptional information available for the parent lines. Putative functions were assigned to the prioritized genes based on protein interaction networks and expression eQTL from our earlier study. DNA metabolism or antigenic variation functional categories were enriched among our prioritized candidate genes. Genes were then analyzed to determine if they interact with cyclins or other proteins known to be involved in the regulation of cell cycle. Conclusions We show that the divergent proliferation rate between a drug resistant and drug sensitive parent clone is under genetic regulation and is segregating as a complex trait in 34 progeny. We map a major locus along with additional secondary effects, and use the wealth of genome data to identify key candidate genes. Of particular interest are a nucleosome assembly protein (PFL0185c, a Zinc finger transcription factor (PFL0465c both on chromosome 12 and a ribosomal protein L7Ae-related on chromosome 4 (PFD0960c.

  7. Automatic electromagnetic valve for previous vacuum

    International Nuclear Information System (INIS)

    Granados, C. E.; Martin, F.

    1959-01-01

    A valve which permits the maintenance of an installation vacuum when electric current fails is described. It also lets the air in the previous vacuum bomb to prevent the oil ascending in the vacuum tubes. (Author)

  8. Identification of Candidate Genes for Calcium and Magnesium Accumulation in Brassica napus L. by Association Genetics

    Directory of Open Access Journals (Sweden)

    Thomas D. Alcock

    2017-11-01

    Full Text Available Calcium (Ca and magnesium (Mg are essential plant nutrients and vital for human and animal nutrition. Biofortification of crops has previously been suggested to alleviate widespread human Ca and Mg deficiencies. In this study, new candidate genes influencing the leaf accumulation of Ca and Mg were identified in young Brassica napus plants using associative transcriptomics of ionomics datasets. A total of 247 and 166 SNP markers were associated with leaf Ca and Mg concentration, respectively, after false discovery rate correction and removal of SNPs with low second allele frequency. Gene expression markers at similar positions were also associated with leaf Ca and Mg concentration, including loci on chromosomes A10 and C2, within which lie previously identified transporter genes ACA8 and MGT7. Further candidate genes were selected from seven loci and the mineral composition of whole Arabidopsis thaliana shoots were characterized from lines mutated in orthologous genes. Four and two mutant lines had reduced shoot Ca and Mg concentration, respectively, compared to wild type plants. Three of these mutations were found to have tissue specific effects; notably reduced silique Ca in all three such mutant lines. This knowledge could be applied in targeted breeding, with the possibility of increasing Ca and Mg in plant tissue for improving human and livestock nutrition.

  9. Identifying web usage behavior of bank customers

    Science.gov (United States)

    Araya, Sandro; Silva, Mariano; Weber, Richard

    2002-03-01

    The bank Banco Credito e Inversiones (BCI) started its virtual bank in 1996 and its registered customers perform currently more than 10,000 Internet transactions daily, which typically cause les than 10% of traditional transaction costs. Since most of the customers are still not registered for online banking, one of the goals of the virtual bank is to increase then umber of registered customers. Objective of the presented work was to identify customers who are likely to perform online banking but still do not use this medium for their transactions. This objective has been reached by determining profiles of registered customers who perform many transactions online. Based on these profiles the bank's Data Warehouse is explored for twins of these heavy users that are still not registered for online banking. We applied clustering in order to group the registered customers into five classes. One of these classes contained almost 30% of all registered customers and could clearly be identified as class of heavy users. Next a neural network assigned online customers to the previously found five classes. Applying the network trained on online customers to all the bank customers identified twins of heavy users that, however had not performed online transactions so far. A mailing to these candidates informing about the advantages of online banking doubled the number of registrations compared to previous campaigns.

  10. Validation of candidate genes putatively associated with resistance to SCMV and MDMV in maize (Zea mays L. by expression profiling

    Directory of Open Access Journals (Sweden)

    Wenzel Gerhard

    2009-02-01

    Full Text Available Abstract Background The potyviruses sugarcane mosaic virus (SCMV and maize dwarf mosaic virus (MDMV are major pathogens of maize worldwide. Two loci, Scmv1 and Scmv2, have ealier been shown to confer complete resistance to SCMV. Custom-made microarrays containing previously identified SCMV resistance candidate genes and resistance gene analogs were utilised to investigate and validate gene expression and expression patterns of isogenic lines under pathogen infection in order to obtain information about the molecular mechanisms involved in maize-potyvirus interactions. Results By employing time course microarray experiments we identified 68 significantly differentially expressed sequences within the different time points. The majority of differentially expressed genes differed between the near-isogenic line carrying Scmv1 resistance locus at chromosome 6 and the other isogenic lines. Most differentially expressed genes in the SCMV experiment (75% were identified one hour after virus inoculation, and about one quarter at multiple time points. Furthermore, most of the identified mapped genes were localised outside the Scmv QTL regions. Annotation revealed differential expression of promising pathogenesis-related candidate genes, validated by qRT-PCR, coding for metallothionein-like protein, S-adenosylmethionine synthetase, germin-like protein or 26S ribosomal RNA. Conclusion Our study identified putative candidate genes and gene expression patterns related to resistance to SCMV. Moreover, our findings support the effectiveness and reliability of the combination of different expression profiling approaches for the identification and validation of candidate genes. Genes identified in this study represent possible future targets for manipulation of SCMV resistance in maize.

  11. Thyroid disease awareness is associated with high rates of identifying subjects with previously undiagnosed thyroid dysfunction

    OpenAIRE

    Canaris, Gay J; Tape, Thomas G; Wigton, Robert S

    2013-01-01

    Background Conventional screening for hypothyroidism is controversial. Although hypothyroidism is underdiagnosed, many organizations do not recommend screening, citing low disease prevalence in unselected populations. We studied attendees at a thyroid health fair, hypothesizing that certain patient characteristics would enhance the yield of testing. Methods We carried out an observational study of participants at a Michigan health fair that focused on thyroid disease. We collected patient-rep...

  12. Previously identified patellar tendinopathy risk factors differ between elite and sub-elite volleyball players.

    Science.gov (United States)

    Janssen, I; Steele, J R; Munro, B J; Brown, N A T

    2015-06-01

    Patellar tendinopathy is the most common knee injury incurred in volleyball, with its prevalence in elite athletes more than three times that of their sub-elite counterparts. The purpose of this study was to determine whether patellar tendinopathy risk factors differed between elite and sub-elite male volleyball players. Nine elite and nine sub-elite male volleyball players performed a lateral stop-jump block movement. Maximum vertical jump, training history, muscle extensibility and strength, three-dimensional landing kinematics (250 Hz), along with lower limb neuromuscular activation patterns (1500 Hz), and patellar tendon loading were collected during each trial. Multivariate analyses of variance (P volleyball players. Interventions designed to reduce landing frequency and improve quadriceps extensibility are recommended to reduce patellar tendinopathy prevalence in volleyball players. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. 77 FR 14594 - Additions to the Identifying Information for an Individual Previously Designated Pursuant to the...

    Science.gov (United States)

    2012-03-12

    ...., Bogota, Colombia; c/o CUBICAFE S.A., Bogota, Colombia; c/o CUBI CAFE CLICK CUBE MEXICO, S.A. DE C.V., Mexico City, Distrito Federal, Mexico; c/o DESARROLLO MINERO RESPONSABLE C.I. S.A.S., Bogota, Colombia; c..., Colombia; c/o INVERPUNTO DEL VALLE S.A., Cali, Colombia; c/o INVERSIONES CIFUENTES Y CIA. S. EN C...

  14. Candidate genes and single nucleotide polymorphisms associated with variation in residual feed intake in beef cattle.

    Science.gov (United States)

    Karisa, B K; Thomson, J; Wang, Z; Stothard, P; Moore, S S; Plastow, G S

    2013-08-01

    The candidate gene approach was used to identify genes associated with residual feed intake (RFI) in beef steers. The approach uses prior knowledge of gene functions to predict their biological role in the variation observed in a trait. It is suited to identify genes associated with complex traits where each gene has a relatively small effect. First, positional candidate genes were identified within the genomic positions of previously reported QTL associated with component traits related to RFI such as dry matter intake (DMI), growth, feed conversion ratio (FCR), average daily gain (ADG), and energy balance. Secondly, the positional candidate genes were prioritized into functional candidate genes according to their biological functions and their relationship with the biological processes associated with RFI including carbohydrate, fat and protein metabolism, thermoregulation, immunity and muscle activity. Single nucleotide polymorphisms (SNPs) located within the functional candidate genes were identified using mRNA sequences and prioritized into functional classes such as non-synonymous (nsSNP), synonymous (sSNP) or intronic SNP. A total of 117 nsSNP were considered as functional SNP and genotyped in steers at the University of Alberta ranch in Kinsella. Multiple marker association analysis in ASReml was performed using RFI data obtained from 531 beef steers. Twenty-five SNP were significantly associated with RFI (P < 0.05) accounting for 19.7% of the phenotypic variation. Using SIFT program to predict the effect of the SNP on the function of the corresponding protein, 3 of the 25 SNP were predicted to cause a significant effect on protein function (P < 0.05). One of the 3 SNP was located in the GHR gene and was also associated with a significant effect on the tertiary structure of the GHR protein (P < 0.05) as modeled using SWISSModel software. Least square means for each genotype were estimated and an over-dominance effect was observed for the SNP located in the

  15. Young massive stars in the ISOGAL survey. II. The catalogue of bright YSO candidates

    Science.gov (United States)

    Felli, M.; Testi, L.; Schuller, F.; Omont, A.

    2002-09-01

    The 7 and 15 mu m observations of selected fields in the Galactic Plane obtained with ISOCAM during the ISOGAL program offer a unique possibility to search for previously unknown YSOs, undetected by IRAS because of lower sensitivity or confusion problems. In a previous paper (Felli et al. \\cite{FCTOS00}) we established criteria of general validity to select YSOs from the much larger population of Post Main Sequence (Post-MS) stars present in the ISOGAL fields by comparing radio and IR observations of five fields located at l ~ +45deg. The selection was based primarily on the position of the point sources in the [15]-[7]-[15] diagram, which involves only ISOGAL data and allows to find possible YSOs using the survey data alone. In the present work we revise the adopted criteria by comparing radio-identified UC HII regions and ISOGAL observations over a much larger region. The main indications of the previous analysis are confirmed, but the criteria for selecting YSO candidates had to be revised to select only bright objects, in order to limit the contamination of the sample by Post-MS stars. The revised criteria ([15]le4 .5, [7]-[15]ge1 .8) are then used to extract YSO candidates from the ISOGAL Point Source Catalogue in preparation. We select a total of 715 YSO candidates, corresponding to ~ 2% of the sources with good detections at 7 and 15 mu m. The results are presented in a table form that provides an unique input list of small diameter, le 6 arcsec, Galactic YSO candidates. The global properties of the sample of YSO candidates are briefly discussed. This is paper No. 11 in a refereed journal based on data from the ISOGAL project. Based on observations with ISO, an ESA project with instruments funded by ESA Member States (especially the PI countries: France, Germany, The Netherlands and the UK) and with the participation of ISAS and NASA. Table 3 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http

  16. Corrosion Assessment of Candidate Materials for the SHINE Subcritical Assembly Vessel and Components FY15 Report

    Energy Technology Data Exchange (ETDEWEB)

    Pawel, Steven J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-01-01

    In the previous report of this series, a literature review was performed to assess the potential for substantial corrosion issues associated with the proposed SHINE process conditions to produce 99Mo. Following the initial review, substantial laboratory corrosion testing was performed emphasizing immersion and vapor-phase exposure of candidate alloys in a wide variety of solution chemistries and temperatures representative of potential exposure conditions. Stress corrosion cracking was not identified in any of the exposures up to 10 days at 80°C and 10 additional days at 93°C. Mechanical properties and specimen fracture face features resulting from slow-strain rate tests further supported a lack of sensitivity of these alloys to stress corrosion cracking. Fluid velocity was found not to be an important variable (0 to ~3 m/s) in the corrosion of candidate alloys at room temperature and 50°C. Uranium in solution was not found to adversely influence potential erosion-corrosion. Potentially intense radiolysis conditions slightly accelerated the general corrosion of candidate alloys, but no materials were observed to exhibit an annualized rate above 10 μm/y.

  17. Statistical Approaches to Candidate Biomarker Panel Selection.

    Science.gov (United States)

    Spratt, Heidi M; Ju, Hyunsu

    2016-01-01

    The statistical analysis of robust biomarker candidates is a complex process, and is involved in several key steps in the overall biomarker development pipeline (see Fig. 22.1, Chap. 19 ). Initially, data visualization (Sect. 22.1, below) is important to determine outliers and to get a feel for the nature of the data and whether there appear to be any differences among the groups being examined. From there, the data must be pre-processed (Sect. 22.2) so that outliers are handled, missing values are dealt with, and normality is assessed. Once the processed data has been cleaned and is ready for downstream analysis, hypothesis tests (Sect. 22.3) are performed, and proteins that are differentially expressed are identified. Since the number of differentially expressed proteins is usually larger than warrants further investigation (50+ proteins versus just a handful that will be considered for a biomarker panel), some sort of feature reduction (Sect. 22.4) should be performed to narrow the list of candidate biomarkers down to a more reasonable number. Once the list of proteins has been reduced to those that are likely most useful for downstream classification purposes, unsupervised or supervised learning is performed (Sects. 22.5 and 22.6, respectively).

  18. Confirmation of Kepler Planet Candidates around Giants

    Science.gov (United States)

    Sato, Bun-ei

    2014-01-01

    Detecting planetary transits is extremely valuable not only because it makes an independent confirmation of a planet from Doppler method but also because the photometric transits yield unambiguous information on planet masses and radii, and thus mean density and interior structure, and obliquity of planetary orbits. Planets around giants and subgiants have been intensively surveyed over the decade by precise radial velocity (RV) measurements, mainly from the viewpoint of planet searches around intermediate-mass (1.5-5M⊙) stars. The planets show remarkable properties in their masses and orbital parameters. Unfortunately, however, it is quite difficult to detect transiting ones around such evolved stars because of the large sizes of the host stars. Therefore, our understanding of properties of planets around intermediate-mass stars are still far behind from those around solar-like stars. In S13B, we made the first RV follow-up observations with HDS for the transiting planet candidates around giants found by Kepler space telescope, and identified promising candidates of true transiting planets. Here we propose to take additional RV data for them with HDS in order to make sure that the RV periodicity is the same as the transit one.

  19. Elemental abundances of solar sibling candidates

    Energy Technology Data Exchange (ETDEWEB)

    Ramírez, I.; Lambert, D. L.; Endl, M.; Cochran, W. D.; MacQueen, P. J. [McDonald Observatory and Department of Astronomy, University of Texas at Austin, 2515 Speedway, Stop C1400, Austin, Texas 78712-1205 (United States); Bajkova, A. T.; Bobylev, V. V. [Central (Pulkovo) Astronomical Observatory of RAS, 65/1, Pulkovskoye Chaussee, St. Petersburg 196140 (Russian Federation); Roederer, I. U. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Wittenmyer, R. A. [School of Physics, UNSW Australia, Sydney 2052 (Australia)

    2014-06-01

    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.

  20. Comparative transcriptomics and proteomics of three different aphid species identifies core and diverse effector sets.

    Science.gov (United States)

    Thorpe, Peter; Cock, Peter J A; Bos, Jorunn

    2016-03-02

    Aphids are phloem-feeding insects that cause significant economic losses to agriculture worldwide. While feeding and probing these insects deliver molecules, called effectors, inside their host to enable infestation. The identification and characterization of these effectors from different species that vary in their host range is an important step in understanding the infestation success of aphids and aphid host range variation. This study employs a multi-disciplinary approach based on transcriptome sequencing and proteomics to identify and compare effector candidates from the broad host range aphid Myzus persicae (green peach aphid) (genotypes O, J and F), and narrow host range aphids Myzus cerasi (black cherry aphid) and Rhopalosiphum padi (bird-cherry oat aphid). Using a combination of aphid transcriptome sequencing on libraries derived from head versus body tissues as well as saliva proteomics we were able to predict candidate effectors repertoires from the different aphid species and genotypes. Among the identified conserved or core effector sets, we identified a significant number of previously identified aphid candidate effectors indicating these proteins may be involved in general infestation strategies. Moreover, we identified aphid candidate effector sequences that were specific to one species, which are interesting candidates for further validation and characterization with regards to species-specific functions during infestation. We assessed our candidate effector repertoires for evidence of positive selection, and identified 49 candidates with DN/DS ratios >1. We noted higher rates of DN/DS ratios in predicted aphid effectors than non-effectors. Whether this reflects positive selection due to co-evolution with host plants, or increased neofunctionalization upon gene duplication remains to be investigated. Our work provides a comprehensive overview of the candidate effector repertoires from three different aphid species with varying host ranges

  1. Transcriptome network analysis reveals potential candidate genes for ankylosing spondylitis.

    Science.gov (United States)

    Zhu, Z-Q; Tang, J-S; Cao, X-J

    2013-12-01

    Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis and autoimmune disease. The main symptom of AS is inflammatory spinal pain; with time, some patients develop ankylosis and spinal immobility. We aim to find cure available for ankylosing spondylitis. We used the GSE11886 series to identify potential genes that related to AS to construct a regulation network. In the network, some of TFs and target genes have been proved related with AS in previous study, such as NFKB1, STAT1, STAT4, TNFSF10, IL2RA, and IL2RB. We also found some new TFs (Franscription Factors) and target genes response to AS, such as BXDC5, and EGFR. Further analysis indicated some significant pathways are associated with AS, including antigen processing and presentation and cytokine-cytokine receptor interaction, etc.; although not significant, there was evident that they play an important role in AS progression, such as apoptosis and systemic lupus erythematosus. Therefore, it is demonstrated that transcriptome network analysis is useful in identification of the candidate genes in AS.

  2. Candidíase em pacientes aidéticos

    Directory of Open Access Journals (Sweden)

    C.E.O.P. Campos

    1992-09-01

    Full Text Available Trinta e cinco aidéticos entre 19 e 55 anos admitidos e tratados de candidíase no Hospital Emílio Ribas, SP, com ELISA positivo para HIV e confirmado pelo Western Blot. Tuberculose em 9 sendo 2 com pericardite; neurotoxoplasmose em 6; neurocriptococose em 5; herpes labial em 4; pneumocistose em 3 e sarcoma de Kaposi em 2, achavam-se associadas. A concentração inibitória mínima 50% (MIC 50% para os azoles foi: ketoconazol= 2,2 µg/ml; itraconazol- 21,0 µg/ml; fluconazol = 19,0 µg/ml. O MIC 50% para ospolienos: nistatina- 50,0 µg/ml; anfotericina B= 0,12 µg/ml e para 5 fluorcitosina= 1,6 µg/ml nas 35 amostras de Candida isoladas. Testes não paramétricos de Siegel revelaram significante identificação (80% das Candida albicans na candidíase, e que a dose de AMB não modificou o número de óbitos, precoce e tardio, ocorridos nesses aidéticos. O uso prévio dos azoles e da nistatina explicaria, talvez, o elevado MIC 50% observado nas amostras de Candida isoladas.A total of 35 in patients admitted at Emilio Ribas Hospital - São Paulo, Brazil, with digestive candidiasis and AIDS clinical diagnostic were evaluated 10 month later, being 29 male and 6 female; white outnumbering black with age ranged from 30 to 50 years old. Agar Sabouraud culture and tube germinative tests identified 28 (80% Candida albicans out 35 strains. Minimum inhibitory concentration (MIC 50% was against azoles (ketoconazole= 2.2 µg/ml; itraconazole = 21.0 µg/ml and fluconazole- 19.0 µg/ml; polyenes (ny statine - 50.0 µg/ml and amphotericin B= 0.12 µg/ml and 5 fluorcytosine= 1.6µg/ml. Siegeltests showed significant Candida albicans proportions in strains isolated from 35 AIDS patients. There was no significant relation between AMB dosis and early or late death. Conclusions: candidiasis in AIDS patients showed high MIC 50% to azoles and nystatine and significant Candida albicans proportion in all strains isolated from AIDS patients. Previous amphotericin B

  3. INTRODUCTION Previous reports have documented a high ...

    African Journals Online (AJOL)

    pregnancy if they were married, educated, had dental insurance, previously used dental services when not pregnant, or had knowledge about the possible connection between oral health and pregnancy outcome8. The purpose of this study was to explore the factors determining good oral hygiene among pregnant women ...

  4. Empowerment perceptions of educational managers from previously ...

    African Journals Online (AJOL)

    The perceptions of educational manag ers from previously disadvantaged primary and high schools in the Nelson Mandela Metropole regarding the issue of empowerment are outlined and the perceptions of educational managers in terms of various aspects of empowerment at different levels reflected. A literature study ...

  5. Management of choledocholithiasis after previous gastrectomy.

    Science.gov (United States)

    Anwer, S; Egan, R; Cross, N; Guru Naidu, S; Somasekar, K

    2017-09-01

    Common bile duct stones in patients with a previous gastrectomy can be a technical challenge because of the altered anatomy. This paper presents the successful management of two such patients using non-traditional techniques as conventional endoscopic retrograde cholangiopancreatography was not possible.

  6. Laboratory Grouping Based on Previous Courses.

    Science.gov (United States)

    Doemling, Donald B.; Bowman, Douglas C.

    1981-01-01

    In a five-year study, second-year human physiology students were grouped for laboratory according to previous physiology and laboratory experience. No significant differences in course or board examination performance were found, though correlations were found between predental grade-point averages and grouping. (MSE)

  7. Early embryonic failure: Expression and imprinted status of candidate genes on human chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Sherman, L.S.; Bennett, P.R.; Moore, G.E. [Queen Charlotte`s and Chelsea Hospital, London (United Kingdom)

    1994-09-01

    Two cases of maternal uniparental (hetero)disomy for human chromosome 21 (mUPD21) have been identified in a systematic search for UPD in 23 cases of early embryonic failure (EEF). Bi-parental origin of the other chromosome pairs was confirmed using specific VNTR probes or dinucleotide repeat analysis. Both maternally and paternally derived isochromosomes 21q have previously been identified in two individuals with normal phenotypes. Full UPD21 has a different mechanism of origin than uniparental isochromosome 21q and its effect on imprinted genes and phenotypic outcome will therefore not necessarily be the same. EEF associated with mUPD21 suggests that developmentally important genes on HSA 21 may be imprinted such that they are only expressed from either the maternally or paternally derived alleles. We have searched for monoallelic expression of candidate genes on HSA 21 in human pregnancy (CBS, IFNAR, COL6A1) using intragenic DNA polymorphisms. These genes were chosen either because their murine homologues lie in imprinted regions or because they are potentially important in embryogenesis. Once imprinted candidate genes have been identified, their methylation status and expression in normal, early embryonic failure and uniparental disomy 21 pregnancies will be studied. At the same time, a larger number of cases of EEF are being examined to further investigate the incidence of UPD21 in this group.

  8. Candidates for office 2004-2006

    Science.gov (United States)

    Electronic polls for elections for 2004-2006 officers will open in early November 2003. In the 23 September issue of Eos, candidates' biographies and statements for Union Office and for four Sections were presented. Election material for candidates for the remaining Sections are presented here. All candidates' biographies and statements are on the Web at: http://www.agu.org/elections.

  9. Rapid fish stock depletion in previously unexploited seamounts: the ...

    African Journals Online (AJOL)

    Rapid fish stock depletion in previously unexploited seamounts: the case of Beryx splendens from the Sierra Leone Rise (Gulf of Guinea) ... A spectral analysis and red-noise spectra procedure (REDFIT) algorithm was used to identify the red-noise spectrum from the gaps in the observed time-series of catch per unit effort by ...

  10. The job satisfaction of principals of previously disadvantaged schools

    African Journals Online (AJOL)

    The aim of this study was to identify influences on the job satisfaction of previously disadvantaged school principals in North-West Province. Evans's theory of job satisfaction, morale and motivation was useful as a conceptual framework. A mixedmethods explanatory research design was important in discovering issues with ...

  11. The DES Bright Arcs Survey: Hundreds of Candidate Strongly Lensed Galaxy Systems from the Dark Energy Survey Science Verification and Year 1 Observations

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, H. T.; Buckley-Geer, E. J.; Lindgren, K. A.; Nord, B.; Gaitsch, H.; Gaitsch, S.; Lin, H.; Allam, S.; Odden, C.; Pellico, A.; Tucker, D. L.; Kuropatkin, N.; Soares-Santos, M. [Fermi National Accelerator Laboratory, P.O. Box 500, Batavia, IL 60510 (United States); Collett, T. E. [Institute of Cosmology and Gravitation, University of Portsmouth, Portsmouth, PO1 3FX (United Kingdom); Furlanetto, C.; Nightingale, J. [University of Nottingham, School of Physics and Astronomy, Nottingham NG7 2RD (United Kingdom); Gill, M. S. S. [SLAC National Accelerator Laboratory, Menlo Park, CA 94025 (United States); More, A. [Kavli IPMU (WPI), UTIAS, The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan); Costa, L. N. da; Neto, A. Fausti, E-mail: diehl@fnal.gov [Laboratório Interinstitucional de e-Astronomia—LIneA, Rua Gal. José Cristino 77, Rio de Janeiro, RJ—20921-400 (Brazil); Collaboration: DES Collaboration; and others

    2017-09-01

    We report the results of searches for strong gravitational lens systems in the Dark Energy Survey (DES) Science Verification and Year 1 observations. The Science Verification data span approximately 250 sq. deg. with a median i -band limiting magnitude for extended objects (10 σ ) of 23.0. The Year 1 data span approximately 2000 sq. deg. and have an i -band limiting magnitude for extended objects (10 σ ) of 22.9. As these data sets are both wide and deep, they are particularly useful for identifying strong gravitational lens candidates. Potential strong gravitational lens candidate systems were initially identified based on a color and magnitude selection in the DES object catalogs or because the system is at the location of a previously identified galaxy cluster. Cutout images of potential candidates were then visually scanned using an object viewer and numerically ranked according to whether or not we judged them to be likely strong gravitational lens systems. Having scanned nearly 400,000 cutouts, we present 374 candidate strong lens systems, of which 348 are identified for the first time. We provide the R.A. and decl., the magnitudes and photometric properties of the lens and source objects, and the distance (radius) of the source(s) from the lens center for each system.

  12. Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

    NARCIS (Netherlands)

    Asai, Y. (Yuka); Eslami, A. (Aida); van Ginkel, C.D. (C. Dorien); Akhabir, L. (Loubna); Wan, M. (Ming); Ellis, G. (George); Ben-Shoshan, M. (Moshe); Martino, D. (David); M.A. Ferreira (Manuel); Allen, K. (Katrina); Mazer, B. (Bruce); H. de Groot (Hans); N.W. de Jong (Nicolette); R. Gerth van Wijk (Roy); A.E.J. Dubois; Chin, R. (Rick); Cheuk, S. (Stephen); Hoffman, J. (Joshua); Jorgensen, E. (Eric); J.S. Witte (John); Melles, R.B. (Ronald B.); Hong, X. (Xiumei); Wang, X. (Xiaobin); J. Hui (Jennie); A.W. Musk (Arthur); M.L. Hunter (Michael); A. James (Alan); G.H. Koppelman (Gerard); A. Sandford (Andrew); Clarke, A.E. (Ann E.); D. Daley (Denise)

    2017-01-01

    textabstractBackground: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis.

  13. Undercover Stars Among Exoplanet Candidates

    Science.gov (United States)

    2005-03-01

    events by monitoring the brightness of a very large number of stars over extended time intervals. During the past years, it has also included a search for periodic, very shallow "dips" in the brightness of stars, caused by the regular transit of small orbiting objects (small stars, brown dwarfs [2] or Jupiter-size planets). The OGLE team has since announced 177 "planetary transit candidates" from their survey of several hundred thousand stars in three southern sky fields, one in the direction of the Galactic Centre, another within the Carina constellation and the third within the Centaurus/Musca constellations. The nature of the transiting object can however only be established by subsequent radial-velocity observations of the parent star. The size of the velocity variations (the amplitude) is directly related to the mass of the companion object and therefore allows discrimination between stars and planets as the cause of the observed brightness "dip". A Bonanza of Low-Mass Stars An international team of astronomers [3] has made use of the 8.2-m VLT Kueyen telescope for this work. Profiting from the multiplex capacity of the FLAMES/UVES facility that permits to obtain high-resolution spectra of up to 8 objects simultaneously, they have looked at 60 OGLE transit candidate stars, measuring their radial velocities with an accuracy of about 50 m/s [4]. This ambitious programme has so far resulted in the discovery of five new transiting exoplanets (see, e.g., ESO PR 11/04 for the announcement of two of those). Most of the other transit candidates identified by OGLE have turned out to be eclipsing binaries, that is, in most cases common, small and low-mass stars passing in front of a solar-like star. This additional wealth of data on small and light stars is a real bonanza for the astronomers. Constraining the Relation Between Mass and Radius Low-mass stars are exceptionally interesting objects, also because the physical conditions in their interiors have much in common with

  14. Reflections on Museums as Effective Field Sites for Teacher Candidates

    Science.gov (United States)

    Clark, Megan; Ensminger, David; Incandela, Colleen; Moisan, Heidi

    2016-01-01

    A unique partnership among six museums and Loyola University Chicago's "Teaching Learning and Leading with Schools and Communities" teacher preparation program provided cross-disciplinary field sites for understanding and witnessing developmental and learning theories. Pre-service teacher candidates were able to identify constructs and…

  15. Candidate New Rotavirus Species in Sheltered Dogs, Hungary

    OpenAIRE

    Mihalov-Kov?cs, Eszter; Gell?rt, ?kos; Marton, Szilvia; Farkas, Szilvia L.; Feh?r, Enik?; Oldal, Mikl?s; Jakab, Ferenc; Martella, Vito; B?nyai, Kriszti?n

    2015-01-01

    We identified unusual rotavirus strains in fecal specimens from sheltered dogs in Hungary by viral metagenomics. The novel rotavirus species displayed limited genome sequence homology to representatives of the 8 rotavirus species, A?H, and qualifies as a candidate new rotavirus species that we tentatively named Rotavirus I.

  16. Identification of putative candidate gene markers for grain zinc ...

    African Journals Online (AJOL)

    Nutrients in food crops can be enriched by adopting biofortification. Identifying the target quantitative trait loci (QTL) genes will help achieve biofortification with greater precision and accuracy. The objective of this experiment is to estimate grain zinc content, evaluation of candidate gene markers in recombinant inbred lines ...

  17. Primary School Teacher Candidates' Geometric Habits of Mind

    Science.gov (United States)

    Köse, Nilu¨fer Y.; Tanisli, Dilek

    2014-01-01

    Geometric habits of mind are productive ways of thinking that support learning and using geometric concepts. Identifying primary school teacher candidates' geometric habits of mind is important as they affect the development of their future students' geometric thinking. Therefore, this study attempts to determine primary school teachers' geometric…

  18. Generating Genome-Scale Candidate Gene Lists for Pharmacogenomics

    DEFF Research Database (Denmark)

    Hansen, Niclas Tue; Brunak, Søren; Altman, R. B.

    2009-01-01

    A critical task in pharmacogenomics is identifying genes that may be important modulators of drug response. High-throughput experimental methods are often plagued by false positives and do not take advantage of existing knowledge. Candidate gene lists can usefully summarize existing knowledge...

  19. Anti-Lyme Subunit Vaccines: Design and Development of Peptide-Based Vaccine Candidates.

    Science.gov (United States)

    Small, Christina M; Mwangi, Waithaka; Esteve-Gassent, Maria D

    2016-01-01

    Vaccinology today has been presented with several avenues to improve protection against infectious disease. The recent employment of the reverse vaccinology technique has changed the face of vaccine development against many pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Using this technique, genomics and in silico analyses come together to identify potentially antigenic epitopes in a high-throughput fashion. The forward methodology of vaccine development was used previously to generate the only licensed human vaccine for Lyme disease, which is no longer on the market. Using reverse vaccinology to identify new antigens and isolate specific epitopes to protect against B. burgdorferi, subunit vaccines will be generated that lack reactogenic and nonspecific epitopes, yielding more effective vaccine candidates. Additionally, novel epitopes are being utilized and are presently in the commercialization pipeline both for B. burgdorferi and other spirochaetal pathogens. The versatility and methodology of the subunit protein vaccine are described as it pertains to Lyme disease from conception to performance evaluation.

  20. Large-scale transcriptome analyses reveal new genetic marker candidates of head, neck, and thyroid cancer

    DEFF Research Database (Denmark)

    Reis, Eduardo M; Ojopi, Elida P B; Alberto, Fernando L

    2005-01-01

    A detailed genome mapping analysis of 213,636 expressed sequence tags (EST) derived from nontumor and tumor tissues of the oral cavity, larynx, pharynx, and thyroid was done. Transcripts matching known human genes were identified; potential new splice variants were flagged and subjected to manual...... amplification was selected by identifying transcripts that mapped to genomic regions previously known to be frequently amplified or deleted in head, neck, and thyroid tumors. Three of these markers were evaluated by quantitative reverse transcription-PCR in an independent set of individual samples. Along...... with detailed clinical data about tumor origin, the information reported here is now publicly available on a dedicated Web site as a resource for further biological investigation. This first in silico reconstruction of the head, neck, and thyroid transcriptomes points to a wealth of new candidate markers...

  1. Evaluation of proteinuria in healthy living kidney donor candidates.

    Science.gov (United States)

    Leischner, M P; Naratadam, G O; Hou, S H; Singh, A K; Leehey, D J

    2006-11-01

    Evaluation of living kidney donor candidates includes careful assessment for the presence or absence of kidney disease. Kidney donation has been considered to be at least relatively contraindicated if urinary total protein excretion is above the normal range. However, at the present time, there is no uniformly accepted level of urine total protein excretion that would exclude donation. Albumin excretion instead of total protein excretion as a criterion has not previously been evaluated. This was a prospective observational study over a 3-year period in a single tertiary care center designed to assess current selection criteria for kidney donation with respect to urine total protein and albumin excretion. Twenty four percent (25 of 105) of healthy adult kidney donor candidates had elevated urinary total protein excretion rates (150 to 292 mg/24 h). Of these 105 candidates, 39 had simultaneous measurements of both urinary total protein and albumin. Although one-third (13/39) had elevated 24-hour urine total protein values, none had elevated urine albumin excretion. Measurement of albumin, the most common single protein found in urine, appears to be helpful in the evaluation of proteinuria in donor candidates. Many healthy adult kidney donor candidates have mildly elevated total protein excretion but normal albumin excretion. We believe that such patients should not be excluded from donation.

  2. 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.

  3. Linkage study of nonsyndromic cleft lip with or without cleft palate using candidate genes and mapped polymorphic markers

    Energy Technology Data Exchange (ETDEWEB)

    Stein, J.D.; Nelson, L.D.; Conner, B.J. [Univ. of Texas, Houston (United States)] [and others

    1994-09-01

    Nonsyndromic cleft lip with or without cleft palate (CL(P)) involves fusion or growth failure of facial primordia during development. Complex segregation analysis of clefting populations suggest that an autosomal dominant gene may play a role in this common craniofacial disorder. We have ascertained 16 multigenerational families with CL(P) and tested linkage to 29 candidate genes and 139 mapped short tandem repeat markers. The candidate genes were selected based on their expression in craniofacial development or were identified through murine models. These include: TGF{alpha}, TGF{beta}1, TGF{beta}2, TGF{beta}3, EGF, EGFR, GRAS, cMyc, FGFR, Jun, JunB, PDFG{alpha}, PDGF{beta}, IGF2R, GCR Hox7, Hox8, Hox2B, twirler, 5 collagen and 3 extracellular matrix genes. Linkage was tested assuming an autosomal dominant model with sex-specific decreased penetrance. Linkage to all of the candidate loci was excluded in 11 families. RARA was tested and was not informative. However, haplotype analysis of markers flanking RARA on 17q allowed exclusion of this candidate locus. We have previously excluded linkage to 61 STR markers in 11 families. Seventy-eight mapped short tandem repeat markers have recently been tested in 16 families and 30 have been excluded. The remaining are being analyzed and an exclusion map is being developed based on the entire study results.

  4. New Young Star Candidates in the Taurus-Auriga Region as Selected from the Wide-Field Infrared Survey Explorer

    Science.gov (United States)

    Rebull, L. M.; Koenig, X. P.; Padgett, D. L.; Terebey, S.; McGehee, P. M.; Hillenbrand, L. A.; Knapp, G. R.; Leisawitz, D.; Liu, W.; Noriega-Crespo, A.; Ressler, M. E.; Stapelfeldt, K. R.; Fajardo-Acosta, S.; Mainzer, A.

    2011-09-01

    The Taurus Molecular Cloud subtends a large solid angle on the sky, in excess of 250 deg2. 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 deg2 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. Previously unknown organomagnesium compounds in astrochemical context

    OpenAIRE

    Ruf, Alexander

    2018-01-01

    We describe the detection of dihydroxymagnesium carboxylates (CHOMg) in astrochemical context. CHOMg was detected in meteorites via ultrahigh-resolving chemical analytics and represents a novel, previously unreported chemical class. Thus, chemical stability was probed via quantum chemical computations, in combination with experimental fragmentation techniques. Results propose the putative formation of green-chemical OH-Grignard-type molecules and triggered fundamental questions within chemica...

  6. [Placental complications after a previous cesarean section].

    Science.gov (United States)

    Milosević, Jelena; Lilić, Vekoslav; Tasić, Marija; Radović-Janosević, Dragana; Stefanović, Milan; Antić, Vladimir

    2009-01-01

    The incidence of cesarean section has been rising in the past 50 years. With the increased number of cesarean sections, the number of pregnancies with the previous cesarean section rises as well. The aim of this study was to establish the influence of the previous cesarean section on the development of placental complications: placenta previa, placental abruption and placenta accreta, as well as to determine the influence of the number of previous cesarean sections on the complication development. The research was conducted at the Clinic of Gynecology and Obstetrics in Nis covering 10-year-period (from 1995 to 2005) with 32358 deliveries, 1280 deliveries after a previous cesarean section, 131 cases of placenta previa and 118 cases of placental abruption. The experimental groups was presented by the cases of placenta previa or placental abruption with prior cesarean section in obstetrics history, opposite to the control group having the same conditions but without a cesarean section in medical history. The incidence of placenta previa in the control group was 0.33%, opposite to the 1.86% incidence after one cesarean section (pcesarean sections and as high as 14.28% after three cesarean sections in obstetric history. Placental abruption was recorded as placental complication in 0.33% pregnancies in the control group, while its incidence was 1.02% after one cesarean section (pcesarean sections. The difference in the incidence of intrapartal hysterectomy between the group with prior cesarean section (0.86%) and without it (0.006%) shows a high statistical significance (pcesarean section is an important risk factor for the development of placental complications.

  7. Robo-AO Kepler Survey. IV. The Effect of Nearby Stars on 3857 Planetary Candidate Systems

    Science.gov (United States)

    Ziegler, Carl; Law, Nicholas M.; Baranec, Christoph; Riddle, Reed; Duev, Dmitry A.; Howard, Ward; Jensen-Clem, Rebecca; Kulkarni, S. R.; Morton, Tim; Salama, Maïssa

    2018-04-01

    We present the overall statistical results from the Robo-AO Kepler planetary candidate survey, comprising of 3857 high-angular resolution observations of planetary candidate systems with Robo-AO, an automated laser adaptive optics system. These observations reveal previously unknown nearby stars blended with the planetary candidate host stars that alter the derived planetary radii or may be the source of an astrophysical false positive transit signal. In the first three papers in the survey, we detected 440 nearby stars around 3313 planetary candidate host stars. In this paper, we present observations of 532 planetary candidate host stars, detecting 94 companions around 88 stars; 84 of these companions have not previously been observed in high resolution. We also report 50 more-widely separated companions near 715 targets previously observed by Robo-AO. We derive corrected planetary radius estimates for the 814 planetary candidates in systems with a detected nearby star. If planetary candidates are equally likely to orbit the primary or secondary star, the radius estimates for planetary candidates in systems with likely bound nearby stars increase by a factor of 1.54, on average. We find that 35 previously believed rocky planet candidates are likely not rocky due to the presence of nearby stars. From the combined data sets from the complete Robo-AO KOI survey, we find that 14.5 ± 0.5% of planetary candidate hosts have a nearby star with 4″, while 1.2% have two nearby stars, and 0.08% have three. We find that 16% of Earth-sized, 13% of Neptune-sized, 14% of Saturn-sized, and 19% of Jupiter-sized planet candidates have detected nearby stars.

  8. Identifying sarcopenia.

    Science.gov (United States)

    Abellan van Kan, Gabor; Houles, Mathieu; Vellas, Bruno

    2012-09-01

    The present review describes and discusses the currently available definitions for sarcopenia from consensus studies. Different sarcopenia definitions have been proposed in these last years. Six main approaches to an operative definition of sarcopenia have been identified. Although the first definitions were solely based on the assessment of the amount of muscle mass, current definitions seem to consistently recognize a bi-dimensional nature of sarcopenia. So, these approaches imply the need of simultaneously assessing both age-related quantitative (i.e. amount of muscle mass) and qualitative (i.e. muscle strength and function) declines of skeletal muscle. Although current consensus exists about a bi-dimensional nature, the proposed approaches to measure sarcopenia are characterized by methodological differences. The majority of the operative definitions proposes to assess muscle mass as an index of appendicular muscle mass divided by squared height (evaluated by dual energy X-ray absorptiometry), assess strength using hand-held dynamometers, and assess function by evaluating gait speed at habitual pace over a short distance. Nevertheless, the clinically relevant thresholds and how to combine the three aspects in an operative definition in order to identify sarcopenia are heterogeneous. A main drawback is that supportive empirical data are missing for these conceptual definitions regarding the risk-assessment of different clinically significant adverse outcomes.

  9. Candidate worldviews for design theory

    DEFF Research Database (Denmark)

    Galle, Per

    2008-01-01

    Our growing body of design theory risks being infected by more inconsistency than is justifiable by genuine disagreement among design theorists. Taking my cue from C. S. Peirce, who argued that theory inevitably rests on basic metaphysical assumptions that theorists ought to be critically aware of......, I demonstrate how ‘insidious inconsistency’ may infect design theory if we ignore his admonition. As a possible remedy, I propose a method by which the philosophy of design may develop sound metaphysical foundations (‘worldviews’) for design theory – and generate philosophical insights into design...... at the same time. Examples are given of how the first steps of the method may be carried out and a number of candidate worldviews are outlined and briefly discussed. In its own way, each worldview answers certain fundamental questions about the nature of design. These include the ontological question of what...

  10. Genomic reconstruction of Shewanella oneidensis MR-1 metabolism reveals previously uncharacterized machinery for lactate utilization

    Energy Technology Data Exchange (ETDEWEB)

    Pinchuk, Grigoriy E.; Rodionov, Dmitry A.; Yang, Chen; Li, Xiaoqing; Osterman, Andrei L.; Dervyn, Etienne; Geydebrekht, Oleg V.; Reed, Samantha B.; Romine, Margaret F.; Collart, Frank R.; Scott, J.; Fredrickson, Jim K.; Beliaev, Alex S.

    2009-02-24

    The ability to utilize lactate as a sole source of carbon and energy is one of the key metabolic signatures of Shewanellae, a diverse group of dissimilatory metal reducing bacteria commonly found in aquatic and sedimentary environments. Nonetheless, homology searches failed to recognize orthologs of previously described bacterial D- or L-lactate oxidizing enzymes (Escherichia coli genes dld and lldD) in any of the 13 analyzed genomes of Shewanella spp. Using comparative genomic techniques, we identified a conserved chromosomal gene cluster in Shewanella oneidensis MR-1 (locus tag: SO1522-SO1518) containing lactate permease and candidate genes for both D- and L-lactate dehydrogenase enzymes. The predicted D-LDH gene (dldD, SO1521) is a distant homolog of FAD-dependent lactate dehydrogenase from yeast, whereas the predicted L-LDH is encoded by three genes with previously unknown functions (lldEGF, SO1520-19-18). Through a combination of genetic and biochemical techniques, we experimentally confirmed the predicted physiological role of these novel genes in S. oneidensis MR-1 and carried out successful functional validation studies in Escherichia coli and Bacillus subtilis. We conclusively showed that dldD and lldEFG encode fully functional D-and L-LDH enzymes, which catalyze the oxidation of the respective lactate stereoisomers to pyruvate. Notably, the S. oneidensis MR-1 LldEFG enzyme is the first described example of a multi-subunit lactate oxidase. Comparative analysis of >400 bacterial species revealed the presence of LldEFG and Dld in a broad range of diverse species accentuating the potential importance of these previously unknown proteins in microbial metabolism.

  11. Genetic determinants of facial clefting: analysis of 357 candidate genes using two national cleft studies from Scandinavia.

    Directory of Open Access Journals (Sweden)

    Astanand Jugessur

    Full Text Available Facial clefts are common birth defects with a strong genetic component. To identify fetal genetic risk factors for clefting, 1536 SNPs in 357 candidate genes were genotyped in two population-based samples from Scandinavia (Norway: 562 case-parent and 592 control-parent triads; Denmark: 235 case-parent triads.We used two complementary statistical methods, TRIMM and HAPLIN, to look for associations across these two national samples. TRIMM tests for association in each gene by using multi-SNP genotypes from case-parent triads directly without the need to infer haplotypes. HAPLIN on the other hand estimates the full haplotype distribution over a set of SNPs and estimates relative risks associated with each haplotype. For isolated cleft lip with or without cleft palate (I-CL/P, TRIMM and HAPLIN both identified significant associations with IRF6 and ADH1C in both populations, but only HAPLIN found an association with FGF12. For isolated cleft palate (I-CP, TRIMM found associations with ALX3, MKX, and PDGFC in both populations, but only the association with PDGFC was identified by HAPLIN. In addition, HAPLIN identified an association with ETV5 that was not detected by TRIMM.Strong associations with seven genes were replicated in the Scandinavian samples and our approach effectively replicated the strongest previously known association in clefting--with IRF6. Based on two national cleft cohorts of similar ancestry, two robust statistical methods and a large panel of SNPs in the most promising cleft candidate genes to date, this study identified a previously unknown association with clefting for ADH1C and provides additional candidates and analytic approaches to advance the field.

  12. PEACE: pulsar evaluation algorithm for candidate extraction - a software package for post-analysis processing of pulsar survey candidates

    Science.gov (United States)

    Lee, K. J.; Stovall, K.; Jenet, F. A.; Martinez, J.; Dartez, L. P.; Mata, A.; Lunsford, G.; Cohen, S.; Biwer, C. M.; Rohr, M.; Flanigan, J.; Walker, A.; Banaszak, S.; Allen, B.; Barr, E. D.; Bhat, N. D. R.; Bogdanov, S.; Brazier, A.; Camilo, F.; Champion, D. J.; Chatterjee, S.; Cordes, J.; Crawford, F.; Deneva, J.; Desvignes, G.; Ferdman, R. D.; Freire, P.; Hessels, J. W. T.; Karuppusamy, R.; Kaspi, V. M.; Knispel, B.; Kramer, M.; Lazarus, P.; Lynch, R.; Lyne, A.; McLaughlin, M.; Ransom, S.; Scholz, P.; Siemens, X.; Spitler, L.; Stairs, I.; Tan, M.; van Leeuwen, J.; Zhu, W. W.

    2013-07-01

    Modern radio pulsar surveys produce a large volume of prospective candidates, the majority of which are polluted by human-created radio frequency interference or other forms of noise. Typically, large numbers of candidates need to be visually inspected in order to determine if they are real pulsars. This process can be labour intensive. In this paper, we introduce an algorithm called Pulsar Evaluation Algorithm for Candidate Extraction (PEACE) which improves the efficiency of identifying pulsar signals. The algorithm ranks the candidates based on a score function. Unlike popular machine-learning-based algorithms, no prior training data sets are required. This algorithm has been applied to data from several large-scale radio pulsar surveys. Using the human-based ranking results generated by students in the Arecibo Remote Command Center programme, the statistical performance of PEACE was evaluated. It was found that PEACE ranked 68 per cent of the student-identified pulsars within the top 0.17 per cent of sorted candidates, 95 per cent within the top 0.34 per cent and 100 per cent within the top 3.7 per cent. This clearly demonstrates that PEACE significantly increases the pulsar identification rate by a factor of about 50 to 1000. To date, PEACE has been directly responsible for the discovery of 47 new pulsars, 5 of which are millisecond pulsars that may be useful for pulsar timing based gravitational-wave detection projects.

  13. 2MASS NIR photometry for 693 candidate globular clusters in M 31 and the Revised Bologna Catalogue

    Science.gov (United States)

    Galleti, S.; Federici, L.; Bellazzini, M.; Fusi Pecci, F.; Macrina, S.

    2004-03-01

    We have identified in the 2MASS database 693 known and candidate globular clusters in M 31. The 2MASS J, H, K magnitudes of these objects have been transformed to the same homogeneous photometric system of existing near infrared photometry of M 31 globulars, finally yielding J, H, K integrated photometry for 279 confirmed M 31 clusters, 406 unconfirmed candidates and 8 objects with controversial classification. Of these objects 529 lacked any previous estimate of their near infrared magnitudes. The newly assembled near infrared dataset has been implemented into a revised version of the Bologna Catalogue of M 31 globulars, with updated optical (UBVRI) photometry taken, when possible, from the most recent sources of CCD photometry available in the literature and transformed to a common photometric system. The final Revised Bologna Catalogue (available in electronic form) is the most comprehensive list presently available of confirmed and candidate M 31 globular clusters, with a total of 1164 entries. In particular, it includes 337 confirmed GCs, 688 GC candidates, 10 objects with controversial classification, 70 confirmed galaxies, 55 confirmed stars, and 4 H II regions lying within ˜3° from the center of the M 31 galaxy. Using the newly assembled database we show that the V-K color provides a powerful tool to discriminate between M 31 clusters and background galaxies, and we identify a sample of 83 globular cluster candidates, which is not likely to be contaminated by misclassified galaxies. Tables 2-4 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/416/917

  14. Optimization of hydraulic machinery by exploiting previous successful designs

    Energy Technology Data Exchange (ETDEWEB)

    Kyriacou, S A; Giannakoglou, K C [National Technical University of Athens, Parallel CFD and Optimization Unit, PO Box 64069, Athens 15710 (Greece); Weissenberger, S; Grafenberger, P, E-mail: stelios.Kyriacou@gmail.co [Andritz HYDRO, RD, Lunzerstrasse 78, 4031 Linz (Austria)

    2010-08-15

    A design-optimization method for hydraulic machinery is proposed. Optimal designs are obtained using the appropriate CFD evaluation software driven by an evolutionary algorithm which is also assisted by artificial neural networks used as surrogate evaluation models or metamodels. As shown in a previous IAHR paper by the same authors, such an optimization method substantially reduces the CPU cost, since the metamodels can discard numerous non-promising candidate solutions generated during the evolution, at almost negligible CPU cost, without evaluating them by means of the costly CFD tool. The present paper extends the optimization method of the previous paper by making it capable to accommodate and exploit pieces of useful information archived during previous relevant successful designs. So, instead of parameterizing the geometry of the hydraulic machine components, which inevitably leads to many design variables, enough to slow down the design procedure, in the proposed method all new designs are expressed as weighted combinations of the archived ones. The archived designs act as the design space bases. The role of the optimization algorithms is to find the set (or sets, for more than one objectives, where the Pareto front of non-dominated solutions is sought) of weight values, corresponding to the hydraulic machine configuration(s) with optimal performance. Since the number of weights is much less that the number of design variables of the conventional shape parameterization, the design space dimension reduces and the CPU cost of the metamodel-assisted evolutionary algorithm is much lower. The design of a Francis runner is used to demonstrate the capabilities of the proposed method.

  15. Hyper-Plurality of Candidates, Effectiveness of Democratic Representation and Regulation of Candidate Entry in India

    OpenAIRE

    Kaushik, Bhattacharya; Subrata K, Mitra

    2013-01-01

    The presence of large number of candidates in Indian elections had often evoked extremely strong policy recommendations from different expert groups. The major policy tool to control candidate entry in India had, however, been electoral deposit. Using panel data on elections in different states and UTs, our study estimates the impact of electoral deposit on candidate entry. Results suggest that increase in deposit had a substantial short-term negative impact on candidate entry. The candidate ...

  16. Mapping and candidate genes associated with saccharification yield in sorghum.

    Science.gov (United States)

    Wang, Yi-Hong; Acharya, Aniruddha; Burrell, A Millie; Klein, Robert R; Klein, Patricia E; Hasenstein, Karl H

    2013-11-01

    Sorghum (Sorghum bicolor (L.) Moench) is a high-yielding, stress tolerant energy crop for lignocellulosic-based biofuel production. Saccharification is a process by which hydrolytic enzymes break down lignocellulosic materials to fermentable sugars for biofuel production, and mapping and identifying genes underlying saccharification yield is an important first step to genetically improve the plant for higher biofuel productivity. In this study, we used the ICRISAT sorghum mini core germplasm collection and 14 739 single nucleotide polymorphism markers to map saccharification yield. Seven marker loci were associated with saccharification yield and five of these loci were syntenic with regions in the maize genome that contain quantitative trait loci underlying saccharification yield and cell wall component traits. Candidate genes from the seven loci were identified but must be validated, with the most promising candidates being β-tubulin, which determines the orientation of cellulose microfibrils in plant secondary cell walls, and NST1, a master transcription factor controlling secondary cell wall biosynthesis in fibers. Other candidate genes underlying the different saccharification loci included genes that play a role in vascular development and suberin deposition in plants. The identified loci and candidate genes provide information into the factors controlling saccharification yield and may facilitate increasing biofuel production in sorghum.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Non-Small Cell Lung Cancer as a Second Primary Among Patients With Previous Malignancy: Who Is at Risk?

    Science.gov (United States)

    Wu, Geena X; Nelson, Rebecca A; Kim, Jae Y; Raz, Dan J

    2017-09-01

    Patients with previous malignancies could be at increased risk of non-small cell lung cancer (NSCLC). However, the extent of the risk is unknown for many cancer types; thus, it is unclear who might benefit from screening. The Surveillance, Epidemiology, and End Results data set from 1992 to 2012 was used to identify patients with previous malignancies who received a diagnosis of NSCLC ≥ 6 months after their initial cancer diagnosis. Standardized incidence ratios (SIRs) for NSCLC were calculated as a ratio of the observed to expected cases adjusted by person-years at risk. Cancers with a SIR > 1.0 had a risk of NSCLC greater than expected. The analyses were stratified by sex, radiation therapy use, and histologic type. Among the cancer survivors, 32,058 developed NSCLC. Smoking-related (lung, head and neck, bladder) and hematologic malignancies, regardless of previous radiation therapy, had the greatest SIR for NSCLC (range, 1.97-4.88). Colorectal and renal cancer survivors also had an increased SIR for NSCLC (1.16 and 1.21, respectively). Women with previous pancreatic cancer treated with radiation, breast cancer with or without radiation therapy, and those with thyroid cancer demonstrated a greater SIR for lung adenocarcinoma. Men with previous irradiated prostate cancer also had an elevated SIR (1.08; 99% confidence interval, 1.01-1.15) for lung adenocarcinoma. Patients with melanoma, prostate or uterine cancer had a lower SIR for NSCLC than expected. Smoking-related malignancies had the greatest risk of NSCLC. Radiation therapy conferred an elevated risk of NSCLC for certain cancers. Melanoma, prostate, and uterine cancer survivors had a low risk of NSCLC. These results could help identify high-risk screening candidates in the growing population of cancer survivors. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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

  20. Does refining the phenotype improve replication rates? A review and replication of candidate gene studies on Major Depressive Disorder and Chronic Major Depressive Disorder.

    Science.gov (United States)

    Luo, Xiaochen; Stavrakakis, Nikolaos; Penninx, Brenda W; Bosker, Fokko J; Nolen, Willem A; Boomsma, Dorret I; de Geus, Eco J; Smit, Johan H; Snieder, Harold; Nolte, Ilja M; Hartman, Catharina A

    2016-03-01

    Replication has been poor for previously reported candidate genes involved in Major Depressive Disorder (MDD). One possible reason is phenotypic and genetic heterogeneity. The present study replicated genetic associations with MDD as defined in DSM-IV and with a more narrowly defined MDD subtype with a chronic and severe course. We first conducted a systematic review of genetic association studies on MDD published between September 2007 and June 2012 to identify all reported candidate genes. Genetic associations were then tested for all identified single nucleotide polymorphisms (SNPs) and the entire genes using data from the GAIN genome-wide association study (MDD: n = 1,352; chronic MDD subsample: n = 225; controls: n =  1,649). The 1,000 Genomes database was used as reference for imputation. From 157 studies identified inthe literature, 81 studies reported significant associations with MDD, involving 245 polymorphisms in 97 candidate genes, from which we were able to investigate 185 SNPs in 89 genes. We replicated nine candidate SNPs in eight genes for MDD and six in five genes for chronic MDD. However, these were not more than expected by chance. At gene level, we replicated 18 genes for MDD and 17 genes for chronic MDD, both significantly more than expected by chance. We showed that replication rates were improved for MDD compared to a previous, highly similar, replication study based on studies published before 2007. Effect sizes of the SNPs and replication rates of the candidate genes were improved in the chronic subsample compared to the full sample. Nonetheless, replication rates were still poor. © 2015 Wiley Periodicals, Inc.

  1. Books average previous decade of economic misery.

    Science.gov (United States)

    Bentley, R Alexander; Acerbi, Alberto; Ormerod, Paul; Lampos, Vasileios

    2014-01-01

    For the 20(th) century since the Depression, we find a strong correlation between a 'literary misery index' derived from English language books and a moving average of the previous decade of the annual U.S. economic misery index, which is the sum of inflation and unemployment rates. We find a peak in the goodness of fit at 11 years for the moving average. The fit between the two misery indices holds when using different techniques to measure the literary misery index, and this fit is significantly better than other possible correlations with different emotion indices. To check the robustness of the results, we also analysed books written in German language and obtained very similar correlations with the German economic misery index. The results suggest that millions of books published every year average the authors' shared economic experiences over the past decade.

  2. Integrated genomic analysis suggests MLL3 is a novel candidate susceptibility gene for familial nasopharyngeal carcinoma.

    Science.gov (United States)

    Sasaki, Mark M; Skol, Andrew D; Bao, Riyue; Rhodes, Lindsay V; Chambers, Rachelle; Vokes, Everett E; Cohen, Ezra E W; Onel, Kenan

    2015-08-01

    Little is known about genetic factors associated with nasopharyngeal carcinoma (NPC). To gain insight into NPC etiology, we performed whole exome sequencing on germline and tumor DNA from three closely related family members with NPC. The family was ascertained through the Pediatric Familial Cancer Clinic at The University of Chicago (Chicago, IL). The diagnosis of NPC was confirmed pathologically for each individual. For each sample sequenced, 97.3% of the exome was covered at 5×, with an average depth of 44×. Candidate germline and somatic variants associated with NPC were identified and prioritized using a custom pipeline. We discovered 72 rare deleterious germline variants in 56 genes shared by all three individuals. Of these, only three are in previously identified NPC-associated genes, all of which are located within MLL3, a gene known to be somatically altered in NPC. One variant introduces an early stop codon in MLL3, which predicts complete loss-of-function. Tumor DNA analysis revealed somatic mutations and Epstein-Barr virus (EBV) integration events; none, however, were shared among all three individuals. These data suggest that inherited mutations in MLL3 may have predisposed these three individuals from a single family to develop NPC, and may cooperate with individually acquired somatic mutations or EBV integration events in NPC etiology. Our finding is the first instance of a plausible candidate high penetrance inherited mutation predisposing to NPC. ©2015 American Association for Cancer Research.

  3. TGIF1 is a potential candidate gene for high myopia in ethnic Kashmiri population.

    Science.gov (United States)

    Ahmed, Ishfaq; Rasool, Shabhat; Jan, Tariq; Qureshi, Tariq; Naykoo, Niyaz A; Andrabi, Khurshid I

    2014-03-01

    High myopia is a complex disorder that imposes serious consequences on ocular health. Linkage analysis has identified several genetic loci with a series of potential candidate genes that reveal an ambiguous pattern of association with high myopia due to population heterogeneity. We have accordingly chosen to examine the prospect of association of one such gene [transforming growth β-induced factor 1 (TGIF1)] in population that is purely ethnic (Kashmiri) and represents a homogeneous cohort from Northern India. Cases with high myopia with a spherical equivalent of ≥-6 diopters (D) and emmetropic controls with spherical equivalent within ±0.5 D in one or both eyes represented by a sample size of 212 ethnic Kashmiri subjects and 239 matched controls. Genomic DNA was genotyped for sequence variations in TGIF1 gene and allele frequencies tested for Hardy-Weinberg disequilibrium. Potential association was evaluated using χ(2) or Fisher's exact test. Two previously reported missense variations C > T, rs4468717 (first base of codon 143) changing proline to serine and rs2229333 (second base of codon 143) changing proline to leucine were identified in exon 10 of TGIF1. Both variations exhibited possibly significant (p population. In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia. TGIF1 is a relevant candidate gene with potential to contribute in the genesis of high myopia.

  4. Induced vaginal birth after previous caesarean section

    Directory of Open Access Journals (Sweden)

    Akylbek Tussupkaliyev

    2016-11-01

    Full Text Available Introduction The rate of operative birth by Caesarean section is constantly rising. In Kazakhstan, it reaches 27 per cent. Research data confirm that the percentage of successful vaginal births after previous Caesarean section is 50–70 per cent. How safe the induction of vaginal birth after Caesarean (VBAC remains unclear. Methodology The studied techniques of labour induction were amniotomy of the foetal bladder with the vulsellum ramus, intravaginal administration of E1 prostaglandin (Misoprostol, and intravenous infusion of Oxytocin-Richter. The assessment of rediness of parturient canals was conducted by Bishop’s score; the labour course was assessed by a partogram. The effectiveness of labour induction techniques was assessed by the number of administered doses, the time of onset of regular labour, the course of labour and the postpartum period and the presence of complications, and the course of the early neonatal period, which implied the assessment of the child’s condition, described in the newborn development record. The foetus was assessed by medical ultrasound and antenatal and intranatal cardiotocography (CTG. Obtained results were analysed with SAS statistical processing software. Results The overall percentage of successful births with intravaginal administration of Misoprostol was 93 per cent (83 of cases. This percentage was higher than in the amniotomy group (relative risk (RR 11.7 and was similar to the oxytocin group (RR 0.83. Amniotomy was effective in 54 per cent (39 of cases, when it induced regular labour. Intravenous oxytocin infusion was effective in 94 per cent (89 of cases. This percentage was higher than that with amniotomy (RR 12.5. Conclusions The success of vaginal delivery after previous Caesarean section can be achieved in almost 70 per cent of cases. At that, labour induction does not decrease this indicator and remains within population boundaries.

  5. 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

  6. Discovery of Diffuse Dwarf Galaxy Candidates around M101

    Science.gov (United States)

    Bennet, P.; Sand, D. J.; Crnojević, D.; Spekkens, K.; Zaritsky, D.; Karunakaran, A.

    2017-11-01

    We have conducted a search of a 9 deg2 region of the Canada-France-Hawaii-Telescope Legacy Survey around the Milky Way analog M101 (D ˜ 7 Mpc), in order to look for previously unknown low-surface-brightness galaxies. This search has uncovered 38 new low-surface-brightness dwarf candidates, and confirmed 11 previously reported galaxies, all with central surface brightness μ(g, 0) > 23 mag arcsec-2, potentially extending the satellite luminosity function for the M101 group by ˜1.2 mag. The search was conducted using an algorithm that nearly automates the detection of diffuse dwarf galaxies. The candidates’ small sizes and low surface brightnesses mean that the faintest of these objects would likely be missed by traditional visual or computer detection techniques. The dwarf galaxy candidates span a range of -7.1 ≥ M g ≥ -10.2 and half-light radii of 118-540 pc at the distance of M101, and they are well fit by simple Sérsic surface brightness profiles. These properties are consistent with dwarfs in the Local Group, and to match the Local Group luminosity function, ˜10-20 of these candidates should be satellites of M101. Association with a massive host is supported by the lack of detected star formation and the overdensity of candidates around M101 compared to the field. The spatial distribution of the dwarf candidates is highly asymmetric, and concentrated to the northeast of M101, therefore distance measurements will be required to determine if these are genuine members of the M101 group.

  7. Centroid vetting of transiting planet candidates from the Next Generation Transit Survey

    Science.gov (United States)

    Günther, Maximilian N.; Queloz, Didier; Gillen, Edward; McCormac, James; Bayliss, Daniel; Bouchy, Francois; Walker, Simon. R.; West, Richard G.; Eigmüller, Philipp; Smith, Alexis M. S.; Armstrong, David J.; Burleigh, Matthew; Casewell, Sarah L.; Chaushev, Alexander P.; Goad, Michael R.; Grange, Andrew; Jackman, James; Jenkins, James S.; Louden, Tom; Moyano, Maximiliano; Pollacco, Don; Poppenhaeger, Katja; Rauer, Heike; Raynard, Liam; Thompson, Andrew P. G.; Udry, Stéphane; Watson, Christopher A.; Wheatley, Peter J.

    2017-11-01

    The Next Generation Transit Survey (NGTS), operating in Paranal since 2016, is a wide-field survey to detect Neptunes and super-Earths transiting bright stars, which are suitable for precise radial velocity follow-up and characterization. Thereby, its sub-mmag photometric precision and ability to identify false positives are crucial. Particularly, variable background objects blended in the photometric aperture frequently mimic Neptune-sized transits and are costly in follow-up time. These objects can best be identified with the centroiding technique: if the photometric flux is lost off-centre during an eclipse, the flux centroid shifts towards the centre of the target star. Although this method has successfully been employed by the Kepler mission, it has previously not been implemented from the ground. We present a fully automated centroid vetting algorithm developed for NGTS, enabled by our high-precision autoguiding. Our method allows detecting centroid shifts with an average precision of 0.75 milli-pixel (mpix), and down to 0.25 mpix for specific targets, for a pixel size of 4.97 arcsec. The algorithm is now part of the NGTS candidate vetting pipeline and automatically employed for all detected signals. Further, we develop a joint Bayesian fitting model for all photometric and centroid data, allowing to disentangle which object (target or background) is causing the signal, and what its astrophysical parameters are. We demonstrate our method on two NGTS objects of interest. These achievements make NGTS the first ground-based wide-field transit survey ever to successfully apply the centroiding technique for automated candidate vetting, enabling the production of a robust candidate list before follow-up.

  8. Event Sequence Variability in Healthy Swallowing: Building on Previous Findings

    OpenAIRE

    Molfenter, Sonja M.; Leigh, Chelsea; Steele, Catriona M.

    2014-01-01

    This study builds on previous work by Kendall, Leonard and McKenzie, which investigated event sequence variability for 12 paired-events during swallowing by healthy volunteers. They identified four event pairs, which always occurred in a stereotyped order as well as a most-common occurring overall order of events during swallowing. In the current study, we investigate overall event sequencing and the same four paired-events in a sample of swallows by healthy, young (under 45 years old) volunt...

  9. Antenatal diagnosis of Patau syndrome with previous anomalous baby

    OpenAIRE

    Keerthi Kocherla; Vasantha Kocherla

    2014-01-01

    Patau syndrome is the least common and most severe of the viable autosomal trisomies with median survival of fewer than 3 days was first identified as a cytogenetic syndrome in 1960. Patau syndrome is caused by an extra copy of chromosome 13. In this case report, we present antenatal imaging findings and gross foetal specimen correlation of foetus with Patau syndrome confirmed by karyotyping in third gravida who had significant previous obstetric history of gastrochisis in monochorionic and...

  10. IMA: Identifying disease-related genes using MeSH terms and association rules.

    Science.gov (United States)

    Kim, Jeongwoo; Bang, Changbae; Hwang, Hyeonseo; Kim, Doyoung; Park, Chihyun; Park, Sanghyun

    2017-12-01

    Genes play an important role in several diseases. Hence, in biology, identifying relationships between diseases and genes is important for the analysis of diseases, because mutated or dysregulated genes play an important role in pathogenesis. Here, we propose a method to identify disease-related genes using MeSH terms and association rules. We identified genes by analyzing the MeSH terms and extracted information on gene-gene interactions based on association rules. By integrating the extracted interactions, we constructed gene-gene networks and identified disease-related genes. We applied the proposed method to study five cancers, including prostate, lung, breast, stomach, and colorectal cancer, and demonstrated that the proposed method is more useful for identifying disease-related and candidate disease-related genes than previously published methods. In this study, we identified 20 genes for each disease. Among them, we presented 34 important candidate genes with evidence that supports the relationship of the candidate genes with diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Interaction of barley powdery mildew effector candidate CSEP0055 with the defence protein PR17c

    DEFF Research Database (Denmark)

    Zhang, Wenjing; Pedersen, Carsten; Kwaaitaal, Mark Adrianus Cornelis J

    2012-01-01

    A large number of effector candidates have been identified recently in powdery mildew fungi. However, their roles and how they perform their functions remain unresolved. In this study, we made use of host-induced gene silencing and confirmed that the secreted barley powdery mildew effector candid...

  12. Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data

    DEFF Research Database (Denmark)

    Batalha, Natalie M.; Rowe, Jason F.; Bryson, Stephen T.

    2012-01-01

    New transiting planet candidates are identified in sixteen months (May 2009 - September 2010) of data from the Kepler spacecraft. Nearly five thousand periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1,091 viable new planet candidates, bring...

  13. Evaluation of the lung allocation score in highly urgent and urgent lung transplant candidates in Eurotransplant

    NARCIS (Netherlands)

    Smits, Jacqueline M.; Nossent, George D.; de Vries, Erwin; Rahmel, Axel.; Meiser, Bruno; Strueber, Martin; Gottlieb, Jens

    BACKGROUND: The purpose of the study was to investigate the impact of the lung allocation score (LAS) on mortality among highly urgent (HU) and urgent (U) lung transplant (LTx) candidates in Eurotransplant (ET) and to identify useful additional parameters (LASplus). METHODS: All adult LTx candidates

  14. Harnessing gene expression networks to prioritize candidate epileptic encephalopathy genes.

    Science.gov (United States)

    Oliver, Karen L; Lukic, Vesna; Thorne, Natalie P; Berkovic, Samuel F; Scheffer, Ingrid E; Bahlo, Melanie

    2014-01-01

    We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets.

  15. Candidate genes detected in transcriptome studies are strongly dependent on genetic background.

    Directory of Open Access Journals (Sweden)

    Pernille Sarup

    2011-01-01

    Full Text Available Whole genome transcriptomic studies can point to potential candidate genes for organismal traits. However, the importance of potential candidates is rarely followed up through functional studies and/or by comparing results across independent studies. We have analysed the overlap of candidate genes identified from studies of gene expression in Drosophila melanogaster using similar technical platforms. We found little overlap across studies between putative candidate genes for the same traits in the same sex. Instead there was a high degree of overlap between different traits and sexes within the same genetic backgrounds. Putative candidates found using transcriptomics therefore appear very sensitive to genetic background and this can mask or override effects of treatments. The functional importance of putative candidate genes emerging from transcriptome studies needs to be validated through additional experiments and in future studies we suggest a focus on the genes, networks and pathways affecting traits in a consistent manner across backgrounds.

  16. 275 Candidates and 149 Validated Planets Orbiting Bright Stars in> K2 Campaigns 0–10

    DEFF Research Database (Denmark)

    Mayo, Andrew W.; Vanderburg, Andrew; Latham, David W.

    2018-01-01

    candidates observed during Campaigns 0–10 of the K2 mission that are orbiting stars brighter than 13 mag (in Kepler band) and for which we have obtained high-resolution spectra ( R = 44,000). These candidates are analyzed using the vespa package in order to calculate their false-positive probabilities (FPP......Since 2014, NASA’s K2 mission has observed large portions of the ecliptic plane in search of transiting planets and has detected hundreds of planet candidates. With observations planned until at least early 2018, K2 will continue to identify more planet candidates. We present here 275 planet...... and newly validated planets are explored. We show tentative evidence of a gap in the planet radius distribution of our candidate sample. Comparing our sample to the Kepler candidate sample investigated by Fulton et al., we conclude that more planets are required to quantitatively confirm the gap with K2...

  17. Do People 'Like' Candidates on Facebook?

    DEFF Research Database (Denmark)

    Nielsen, Rasmus Kleis

    The online popularity of a few exceptional candidates has led many to suggest that social media have given politicians powerful ways of communicating directly with voters. In this paper, we examine whether this is happening on a significant scale and show, based on analysis of 224 candidates invo...

  18. Trends in Teacher Candidates' Educational Beliefs.

    Science.gov (United States)

    Minor, Lynn C.; Onwuegbuzie, Anthony J.; Witcher, Ann E.; James, Terry L.

    This study examined trends in teacher candidates' educational beliefs over time. Participants were 84 teacher education candidates enrolled in several sections of an introductory-level education class for education majors at a southeastern university. They were administered the Witcher-Travers Survey of Educational Beliefs (WTSEB) both on the…

  19. A possible candidate for cold dark matter

    Indian Academy of Sciences (India)

    This additional scalar can be a viable candidate of cold dark matter (CDM) since the stability of is achieved by the application of Z 2 symmetry on . Considering as a possible candidate of CDM, Boltzmann's equation is solved to find the freeze-out temperature and relic density of for Higgs mass 120 GeV in the scalar ...

  20. 76 FR 36130 - Call for Candidates

    Science.gov (United States)

    2011-06-21

    ... FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Call for Candidates AGENCY: Federal Accounting... candidates. Any applicant who provided the Federal Accounting Standards Advisory Board (FASAB or the Board... to [email protected] ; by U.S. mail or commercial delivery service to: Federal Accounting Standards...

  1. Comparing Candidate Hospital Report Cards

    Energy Technology Data Exchange (ETDEWEB)

    Burr, T.L.; Rivenburgh, R.D.; Scovel, J.C.; White, J.M.

    1997-12-31

    We present graphical and analytical methods that focus on multivariate outlier detection applied to the hospital report cards data. No two methods agree which hospitals are unusually good or bad, so we also present ways to compare the agreement between two methods. We identify factors that have a significant impact on the scoring.

  2. Lactadherin is a candidate oviduct Lewis X trisaccharide receptor on porcine spermatozoa.

    Science.gov (United States)

    Silva, E; Frost, D; Li, L; Bovin, N; Miller, D J

    2017-05-01

    A recent study has demonstrated that porcine spermatozoa recognize with high affinity carbohydrate structures containing Lewis X motifs. Sperm adhesion to Lewis X is proposed to mediate sperm binding to the oviduct epithelium to form a reservoir. The objective of this study was to identify Lewis X-binding proteins from porcine spermatozoa as candidate receptors for oviduct glycans. To identify low-abundance proteins typically masked by proteins originating from seminal fluid, Lewis X candidate receptors were enriched from cauda epididymal boar spermatozoa. Plasma membrane preparations from cauda epididymal spermatozoa were subjected to RP-HPLC and glycan blotting assays to isolate and detect proteins that bind Lewis X. Following bottom-up LC-MS/MS analysis, among the two bands that bound sulfated Lewis X, ADAM5, which spermatozoa, was confidently identified. ADAM family members have been established as contributors to sperm entry into the oviduct. A second sulfated Lewis X-binding protein identified was the peripheral membrane protein lactadherin (also known as P47, SED1 and MFG-E8 in different species). The interaction between Lewis X and lactadherin was functionally important because competitive inhibition by soluble recombinant lactadherin reduced sperm binding to the oviduct epithelium. Furthermore, far-western blotting demonstrated that purified lactadherin could bind oviduct cells. In summary, these findings reveal that, in addition to the previously reported glycan affinity of accessory gland proteins that adhere to spermatozoa, multiple proteins intrinsic to spermatozoa have affinity for a specific oviduct glycan. Further, in addition to binding to the zona pellucida, lactadherin is now implicated in binding to oviduct glycans to promote formation of the sperm reservoir. © 2017 American Society of Andrology and European Academy of Andrology.

  3. Prevalence of Infraumbilical Adhesions in Women With Previous Laparoscopy

    Science.gov (United States)

    Ku, Lowell; Wong, Herb; Liu, C. Y.; Phelps, John Y.

    2007-01-01

    Background and Objectives: The aim of this study is to evaluate the prevalence of intraabdominal adhesions to the umbilicus following gynecologic laparoscopy through an umbilical incision. Methods: A retrospective review was performed of all gynecologic laparoscopic procedures in a private practice setting to identify patients with a repeat laparoscopy who had a history of a previous laparoscopy through an umbilical incision. Patients with a history of other surgeries were excluded. All repeat laparoscopies used a left upper quadrant entry technique where the abdominal cavity was surveyed for adhesions. We also reviewed adverse events attributable to the left upper quadrant entry approach. Results: We identified 151 patients who underwent a second laparoscopy and had a previous umbilical scar. Thirty-two of the 151 (21.2%) patients with a history of a laparoscopy had evidence of adhesions to the umbilical undersurface. No adverse events or injuries were attributed to the left upper quadrant entry technique. Conclusions: Adhesions to the umbilical undersurface occur in 21.2% of patients who have undergone a prior laparoscopy through an umbilical incision. For this reason, we recommend an alternate location for entry in patients with an umbilical scar from a previous laparoscopy. PMID:17651555

  4. Deep sequencing of 71 candidate genes to characterize variation associated with alcohol dependence

    Science.gov (United States)

    Clark, Shaunna L.; Adkins, Daniel E.; Kumar, Gaurav; Aberg, Karolina A.; Nerella, Sri; Xie, Linying; Collins, Ann L.; Crowley, James J.; Quackenbush, Corey R.; Hilliard, Christopher E.; Shabalin, Andrey A.; Vrieze, Scott I.; Peterson, Roseann E.; Copeland, William E.; Silberg, Judy L.; McGue, Matt; Maes, Hermine; Iacono, William G.; Sullivan, Patrick F.; Costello, Elizabeth J.; van den Oord, Edwin J.

    2017-01-01

    Background Previous genome-wide association studies (GWASs) have identified a number of putative risk loci for alcohol dependence (AD). However, only a few loci have replicated and these replicated variants only explain a small proportion of AD risk. Using an innovative approach, the goal of this study was to generate hypotheses about potentially causal variants for AD that can be explored further through functional studies. Methods We employed targeted capture of 71 candidate loci and flanking regions followed by next-generation deep sequencing (mean coverage 78X) in 806 European Americans. Regions included in our targeted capture library were genes identified through published GWAS of alcohol, all human alcohol and aldehyde dehydrogenases, reward system genes including dopaminegic and opioid receptors, prioritized candidate genes based on previous associations, and genes involved in the absorption, distribution, metabolism and excretion of drugs. We performed single locus tests to determine if any single variant was associated with AD symptom count. Sets of variants that overlapped with biologically meaningful annotations were tested for association in aggregate. Results No single, common variant was significantly associated with AD in our study. We did, however, find evidence for association with several variant sets. Two variant sets were significant at the q-value < 0.10 level: a genic enhancer for ADHFE1(p=1.47×10−05; q=0.019), an alcohol dehydrogenase, and ADORA1(p=5.29×10−05;q=0.035), an adenosine receptor that belongs to a G-protein coupled receptor gene family. Conclusions To our knowledge, this is the first sequencing study of AD to examine variants in entire genes, including flanking and regulatory regions. We found that in addition to protein coding variant sets, regulatory variant sets may play a role in AD. From these findings, we have generated initial functional hypotheses about how these sets may influence AD. PMID:28196272

  5. Identifying barriers to Muslim integration in France.

    Science.gov (United States)

    Adida, Claire L; Laitin, David D; Valfort, Marie-Anne

    2010-12-28

    Is there a Muslim disadvantage in economic integration for second-generation immigrants to Europe? Previous research has failed to isolate the effect that religion may have on an immigrant family's labor market opportunities because other factors, such as country of origin or race, confound the result. This paper uses a correspondence test in the French labor market to identify and measure this religious effect. The results confirm that in the French labor market, anti-Muslim discrimination exists: a Muslim candidate is 2.5 times less likely to receive a job interview callback than is his or her Christian counterpart. A high-n survey reveals, consistent with expectations from the correspondence test, that second-generation Muslim households in France have lower income compared with matched Christian households. The paper thereby contributes to both substantive debates on the Muslim experience in Europe and methodological debates on how to measure discrimination. Following the National Academy of Sciences' 2001 recommendations on combining a variety of methodologies and applying them to real-world situations, this research identifies, measures, and infers consequences of discrimination based on religious affiliation, controlling for potentially confounding factors, such as race and country of origin.

  6. Integrated Analysis Identifies Interaction Patterns between Small Molecules and Pathways

    Science.gov (United States)

    Li, Yan; Li, Weiguo; Chen, Xin; Sun, Jiatong; Chen, Huan; Lv, Sali

    2014-01-01

    Previous studies have indicated that the downstream proteins in a key pathway can be potential drug targets and that the pathway can play an important role in the action of drugs. So pathways could be considered as targets of small molecules. A link map between small molecules and pathways was constructed using gene expression profile, pathways, and gene expression of cancer cell line intervened by small molecules and then we analysed the topological characteristics of the link map. Three link patterns were identified based on different drug discovery implications for breast, liver, and lung cancer. Furthermore, molecules that significantly targeted the same pathways tended to treat the same diseases. These results can provide a valuable reference for identifying drug candidates and targets in molecularly targeted therapy. PMID:25114931

  7. Tests of candidate materials for particle bed reactors

    International Nuclear Information System (INIS)

    Horn, F.L.; Powell, J.R.; Wales, D.

    1987-01-01

    Rhenium metal hot frits and zirconium carbide-coated fuel particles appear suitable for use in flowing hydrogen to at least 2000 K, based on previous tests. Recent tests on alternate candidate cooled particle and frit materials are described. Silicon carbide-coated particles began to react with rhenium frit material at 1600 K, forming a molten silicide at 2000 K. Silicon carbide was extensively attacked by hydrogen at 2066 K for 30 minutes, losing 3.25% of its weight. Vitrous carbon was also rapidly attacked by hydrogen at 2123 K, losing 10% of its weight in two minutes. Long term material tests on candidate materials for closed cycle helium cooled particle bed fuel elements are also described. Surface imperfections were found on the surface of pyrocarbon-coated fuel particles after ninety days exposure to flowing (∼500 ppM) impure helium at 1143 K. The imperfections were superficial and did not affect particle strength

  8. Selection Methodology of H-1 Components as Potential Candidates for Performance Based Logistics Contracts

    National Research Council Canada - National Science Library

    Erickson, Jamie; Hutchins, Jim

    2008-01-01

    ...) explore methods of identifying components as PBL candidates specifically for the H-1 community, through an analysis of readiness data, interviews with subject matter experts and use of Crystal Ball...

  9. Candidate thermal energy storage technologies for solar industrial process heat applications

    Science.gov (United States)

    Furman, E. R.

    1979-01-01

    A number of candidate thermal energy storage system elements were identified as having the potential for the successful application of solar industrial process heat. These elements which include storage media, containment and heat exchange are shown.

  10. Towards the identification and quantification of candidate metabolites of tebuconazole fungicide.

    Science.gov (United States)

    El Azhari, Najoi; Dermou, Eftychia; Botteri, Lucio; Lucini, Luigi; Karas, Panagiotis; Karpouzas, Dimitris; Tsiamis, George; Martin-Laurent, Fabrice; Trevisan, Marco; Rossi, Riccardo; Ferrari, Federico

    2017-04-01

    Tebuconazole belongs to the family of triazole fungicides, used for crop protection and human health applications. In the environment, the dissipation of the parent molecule leads to the formation of metabolites that are of unknown identity or toxicity. In order to identify and determine the putative identity of those metabolites and their po- tential toxicity, a quadrupole time-of-flight (Q-TOF) approach is often used. Q-SAR ap- proaches help to predict their toxicity by comparing them to a known database of mole- cules with known properties. All together the information on the candidate by-products may help to select relevant sub-set of metabolites for further quantification by LC or GC coupled with MS. It is thereby possible to select putative toxic compounds for further quanti- fication using chemical analysis. Previous work allowed the identification of potential metabolites of tebuconazole. Triazole, triazolyl acetic acid and p-chlorophenol were suspected to result from the decomposition of tebuconazole. Tebuconazole degradation kinetics was followed for 125 days by quanti- fying the dissipation of the parent molecule and the emergence of the three candidate metabolites by LC/MS for tebuconazole, triazol and triazolyl acetate and by GC/MS for p- chlorophenol. The data allowed the proposition of several metabolic pathways.

  11. Identification of candidate genes for dyslexia susceptibility on chromosome 18.

    Directory of Open Access Journals (Sweden)

    Thomas S Scerri

    2010-10-01

    Full Text Available Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s conferring susceptibility by a two stage strategy of linkage and association analysis.Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R, dymeclin (DYM and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L.Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.

  12. Promising new vaccine candidates against Campylobacter in broilers.

    Directory of Open Access Journals (Sweden)

    Marine Meunier

    Full Text Available Campylobacter is the leading cause of human bacterial gastroenteritis in the European Union. Birds represent the main reservoir of the bacteria, and human campylobacteriosis mainly occurs after consuming and/or handling poultry meat. Reducing avian intestinal Campylobacter loads should impact the incidence of human diseases. At the primary production level, several measures have been identified to reach this goal, including vaccination of poultry. Despite many studies, however, no efficient vaccine is currently available. We have recently identified new vaccine candidates using the reverse vaccinology strategy. This study assessed the in vivo immune and protective potential of six newly-identified vaccine antigens. Among the candidates tested on Ross broiler chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1 significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g, with the concomitant development of a specific humoral immune response. In a second trial, cecal load reductions results were not statistically confirmed despite the induction of a strong immune response. These vaccine candidates need to be further investigated since they present promising features.

  13. Promising new vaccine candidates against Campylobacter in broilers

    Science.gov (United States)

    Meunier, Marine; Guyard-Nicodème, Muriel; Vigouroux, Estelle; Poezevara, Typhaine; Beven, Véronique; Quesne, S.; Bigault, Lionel; Amelot, Michel; Dory, Daniel

    2017-01-01

    Campylobacter is the leading cause of human bacterial gastroenteritis in the European Union. Birds represent the main reservoir of the bacteria, and human campylobacteriosis mainly occurs after consuming and/or handling poultry meat. Reducing avian intestinal Campylobacter loads should impact the incidence of human diseases. At the primary production level, several measures have been identified to reach this goal, including vaccination of poultry. Despite many studies, however, no efficient vaccine is currently available. We have recently identified new vaccine candidates using the reverse vaccinology strategy. This study assessed the in vivo immune and protective potential of six newly-identified vaccine antigens. Among the candidates tested on Ross broiler chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1) significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g, with the concomitant development of a specific humoral immune response. In a second trial, cecal load reductions results were not statistically confirmed despite the induction of a strong immune response. These vaccine candidates need to be further investigated since they present promising features. PMID:29176789

  14. 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.

  15. Natural Genetic Variation and Candidate Genes for Morphological Traits in Drosophila melanogaster

    Science.gov (United States)

    Carreira, Valeria Paula; Mensch, Julián; Hasson, Esteban; Fanara, Juan José

    2016-01-01

    Body size is a complex character associated to several fitness related traits that vary within and between species as a consequence of environmental and genetic factors. Latitudinal and altitudinal clines for different morphological traits have been described in several species of Drosophila and previous work identified genomic regions associated with such variation in D. melanogaster. However, the genetic factors that orchestrate morphological variation have been barely studied. Here, our main objective was to investigate genetic variation for different morphological traits associated to the second chromosome in natural populations of D. melanogaster along latitudinal and altitudinal gradients in Argentina. Our results revealed weak clinal signals and a strong population effect on morphological variation. Moreover, most pairwise comparisons between populations were significant. Our study also showed important within-population genetic variation, which must be associated to the second chromosome, as the lines are otherwise genetically identical. Next, we examined the contribution of different candidate genes to natural variation for these traits. We performed quantitative complementation tests using a battery of lines bearing mutated alleles at candidate genes located in the second chromosome and six second chromosome substitution lines derived from natural populations which exhibited divergent phenotypes. Results of complementation tests revealed that natural variation at all candidate genes studied, invected, Fasciclin 3, toucan, Reticulon-like1, jing and CG14478, affects the studied characters, suggesting that they are Quantitative Trait Genes for morphological traits. Finally, the phenotypic patterns observed suggest that different alleles of each gene might contribute to natural variation for morphological traits. However, non-additive effects cannot be ruled out, as wild-derived strains differ at myriads of second chromosome loci that may interact

  16. Rates of induced abortion in Denmark according to age, previous births and previous abortions

    Directory of Open Access Journals (Sweden)

    Marie-Louise H. Hansen

    2009-11-01

    Full Text Available Background: Whereas the effects of various socio-demographic determinants on a woman's risk of having an abortion are relatively well-documented, less attention has been given to the effect of previous abortions and births. Objective: To study the effect of previous abortions and births on Danish women's risk of an abortion, in addition to a number of demographic and personal characteristics. Data and methods: From the Fertility of Women and Couples Dataset we obtained data on the number of live births and induced abortions by year (1981-2001, age (16-39, county of residence and marital status. Logistic regression analysis was used to estimate the influence of the explanatory variables on the probability of having an abortion in a relevant year. Main findings and conclusion: A woman's risk of having an abortion increases with the number of previous births and previous abortions. Some interactions were was found in the way a woman's risk of abortion varies with calendar year, age and parity. The risk of an abortion for women with no children decreases while the risk of an abortion for women with children increases over time. Furthermore, the risk of an abortion decreases with age, but relatively more so for women with children compared to childless women. Trends for teenagers are discussed in a separate section.

  17. Aspirant candidate behaviour and progressive political ambition

    Directory of Open Access Journals (Sweden)

    Peter Allen

    2017-02-01

    Full Text Available In this paper we take account of the role of aspirant candidate behaviour in progressive political ambition, specifically how some individuals signal their political ambition to political actors by approaching them to discuss running for office. We examine how the effect of this behaviour compares to the more prominently studied effect of elite recruitment. We conclude that signalling behaviour by an aspirant candidate has a substantial effect, particularly with regard to actually acting on initial considerations of whether to stand, and that elite recruitment makes a difference but only in conjunction with the aspirant candidate themselves signalling their ambition to political actors.

  18. Mapping of Candidate Genes Involved in Bud Dormancy and Flowering Time in Sweet Cherry (Prunus avium).

    Science.gov (United States)

    Castède, Sophie; Campoy, José Antonio; Le Dantec, Loïck; Quero-García, José; Barreneche, Teresa; Wenden, Bénédicte; Dirlewanger, Elisabeth

    2015-01-01

    The timing of flowering in perennial plants is crucial for their survival in temperate climates and is regulated by the duration of bud dormancy. Bud dormancy release and bud break depend on the perception of cumulative chilling during endodormancy and heat during the bud development. The objectives of this work were to identify candidate genes involved in dormancy and flowering processes in sweet cherry, their mapping in two mapping progenies 'Regina' × 'Garnet' and 'Regina' × 'Lapins', and to select those candidate genes which co-localized with quantitative trait loci (QTLs) associated with temperature requirements for bud dormancy release and flowering. Based on available data on flowering processes in various species, a list of 79 candidate genes was established. The peach and sweet cherry orthologs were identified and primers were designed to amplify sweet cherry candidate gene fragments. Based on the amplified sequences of the three parents of the mapping progenies, SNPs segregations in the progenies were identified. Thirty five candidate genes were genetically mapped in at least one of the two progenies and all were in silico mapped. Co-localization between candidate genes and QTLs associated with temperature requirements and flowering date were identified for the first time in sweet cherry. The allelic composition of the candidate genes located in the major QTL for heat requirements and flowering date located on linkage group 4 have a significant effect on these two traits indicating their potential use for breeding programs in sweet cherry to select new varieties adapted to putative future climatic conditions.

  19. Haemophilus influenzae type f meningitis in a previously healthy boy

    DEFF Research Database (Denmark)

    Ronit, Andreas; Berg, Ronan M G; Bruunsgaard, Helle

    2013-01-01

    Non-serotype b strains of Haemophilus influenzae are extremely rare causes of acute bacterial meningitis in immunocompetent individuals. We report a case of acute bacterial meningitis in a 14-year-old boy, who was previously healthy and had been immunised against H influenzae serotype b (Hib......). The causative pathogen was identified as H influenzae serotype f (Hif), and was successfully treated with ceftriaxone. An immunological evaluation revealed transient low levels of immunoglobulins but no apparent immunodeficiency was found 2 years after the clinical insult....

  20. The long-term consequences of previous hyperthyroidism

    DEFF Research Database (Denmark)

    Hjelm Brandt Kristensen, Frans

    2015-01-01

    vascular state. While it is biologically plausible that these changes may induce long-term consequences, the insight into morbidity as well as mortality in patients with previous hyperthyroidism is limited. The reasons for this are a combination of inadequately powered studies, varying definitions......,400 non-hyperthyroid control individuals (matched for age and sex), all identified from a random 5% sample of the Danish background population (n=339,481). In the second study population, 625 same-sex twin pairs, discordant for hyperthyroidism, were included. For each individual, the degree of co...

  1. The Planck Catalogue of High-z source candidates

    Science.gov (United States)

    Montier, Ludovic

    2015-08-01

    The Planck satellite has provided the first FIR/submm all-sky survey with a sensitivity allowing us to identify the rarest, most luminous high-z dusty star-forming sources on the sky. It opens a new window on these extreme star-forming systems at redshift above 1.5, providing a powerful laboratory to study the mechanisms of galaxy evolution and enrichment in the frame of the large scale structure growth.I will describe how the Planck catalogue of high-z source candidates (PHz, Planck 2015 in prep.) has been built and charcaterized over 25% of the sky by selecting the brightest red submm sources at a 5' resolution. Follow-up observations with Herschel/SPIRE over 228 Planck candidates have shown that 93% of these candidates are actually overdensities of red sources with SEDs peaking at 350um (Planck Int. results. XXVII 2014). Complementarily to this population of objects, 12 Planck high-z candidates have been identified as strongly lensed star forming galaxies at redshift lying between 2.2 and 3.6 (Canameras et al 2015 subm.), with flux densities larger than 400 mJy up to 1 Jy at 350um, and strong magnification factors. These Planck lensed star-forming galaxies are the rarest brightest lensed in the submm range, providing a unique opportunity to extend the exploration of the star-forming system in this range of mass and redshift.I will detail further a specific analysis performed on a proto-cluster candidate, PHz G95.5-61.6, identified as a double structure at z=1.7 and z=2.03, using an extensive follow-up program (Flores-Cacho et al 2015 subm.). This is the first Planck proto-cluster candidate with spectroscopic confirmation, which opens a new field of statistical analysis about the evolution of dusty star-forming galaxies in such accreting structures.I will finally discuss how the PHz catalogue may help to answer some of the fundamental questions like: At what cosmic epoch did massive galaxy clusters form most of their stars? Is star formation more or less vigorous

  2. Incidence of previously undetected disease in routine paediatric otolaryngology admissions.

    Science.gov (United States)

    Zeitoun, H; Robinson, P

    1996-06-01

    The process of clerking routine pre-operative admissions involves the house officer taking a full medical history and performing a full physical examination. The diagnostic yield is thought to be low, and the educational value to the house officer is also small. This study addresses the question as to whether routine physical examination is always indicated. One hundred and nine children admitted for routine Otolaryngology procedures were prospectively studied to identify the importance of examination in the pre-operative assessment of patients. The results showed that 51 per cent of the children admitted had risk factors. The medical history was sufficient to identify these risk factors in all patients with the exception of one cardiac condition. This study concludes that a suitable alternative to the current process of clerking such as a standardized nurse history could be safely and efficiently undertaken. Eliminating the tiny percentage of previously unrecognized disease would be a prerequisite for such a change.

  3. Psychological aptitude evaluation of the special forces candidate.

    Science.gov (United States)

    Genoni, Luca; Jelmini, F; Lang, M; Muggli, F

    2017-02-01

    Changes in recruitment procedures reduced early dismissal rates from Swiss military basic recruitment schools; however, such improvements were not reflected in premature discharge rates from the special forces (SF) (Grenadier) recruitment school. A six-item questionnaire designed to identify recruits likely to be subject to premature dismissal on psychological or psychiatric grounds was developed and prospectively validated. The questionnaire was based on an analysis of medical and psychiatric/psychological records of 26 recruits dismissed from a SF recruitment school. Six items were identified that appeared to have prognostic value for early discharge. These six questions were submitted to the remaining applicants in the recruitment school by a suitably qualified psychologist or psychiatrist and effectively identified candidates who would be discharged early. Based on these results a 0-6 scale was developed and applied prospectively to subsequent Grenadier recruitment courses. Statistical analysis showed that 75% of candidates with the lowest scores would eventually complete the course and that no candidates with highest scores would subsequently complete the recruitment course. Prospective studies in subsequent recruitment courses candidates with high scores were classified as not qualified to enter the course, and those with intermediate scores were subject to additional in-depth interviews with a psychologist or psychiatrist to determine their suitability. In the following courses a correlation was established between the questionnaire score and week of discharge for those discharged. Application of this method during subsequent recruitment courses has reduced early dismissal from Swiss SF recruitment schools. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Whole Genome Sequencing-Based Mapping and Candidate Identification of Mutations from Fixed Zebrafish Tissue.

    Science.gov (United States)

    Sanchez, Nicholas E; Harty, Breanne L; O'Reilly-Pol, Thomas; Ackerman, Sarah D; Herbert, Amy L; Holmgren, Melanie; Johnson, Stephen L; Gray, Ryan S; Monk, Kelly R

    2017-10-05

    As forward genetic screens in zebrafish become more common, the number of mutants that cannot be identified by gross morphology or through transgenic approaches, such as many nervous system defects, has also increased. Screening for these difficult-to-visualize phenotypes demands techniques such as whole-mount in situ hybridization (WISH) or antibody staining, which require tissue fixation. To date, fixed tissue has not been amenable for generating libraries for whole genome sequencing (WGS). Here, we describe a method for using genomic DNA from fixed tissue and a bioinformatics suite for WGS-based mapping of zebrafish mutants. We tested our protocol using two known zebrafish mutant alleles, gpr126 st49 and egr2b fh227 , both of which cause myelin defects. As further proof of concept we mapped a novel mutation, stl64 , identified in a zebrafish WISH screen for myelination defects. We linked stl64 to chromosome 1 and identified a candidate nonsense mutation in the F-box and WD repeat domain containing 7 ( fbxw7 ) gene. Importantly, stl64 mutants phenocopy previously described fbxw7 vu56 mutants, and knockdown of fbxw7 in wild-type animals produced similar defects, demonstrating that stl64 disrupts fbxw7 Together, these data show that our mapping protocol can map and identify causative lesions in mutant screens that require tissue fixation for phenotypic analysis. Copyright © 2017 Sanchez et al.

  5. Near-infrared spectroscopic observations of massive young stellar object candidates in the central molecular zone

    Science.gov (United States)

    Nandakumar, G.; Schultheis, M.; Feldmeier-Krause, A.; Schödel, R.; Neumayer, N.; Matteucci, F.; Ryde, N.; Rojas-Arriagada, A.; Tej, A.

    2018-01-01

    Context. The central molecular zone (CMZ) is a 200 pc region around the Galactic centre. The study of star formation in the central part of the Milky Way is of great interest as it provides a template for the closest galactic nuclei. Aims: We present a spectroscopic follow-up of photometrically selected young stellar object (YSO) candidates in the CMZ of the Galactic centre. Our goal is to quantify the contamination of this YSO sample by reddened giant stars with circumstellar envelopes and to determine the star formation rate (SFR) in the CMZ. Methods: We obtained KMOS low-resolution near-infrared spectra (R 4000) between 2.0 and 2.5 μm of sources, many of which have been previously identified by mid-infrared photometric criteria as massive YSOs in the Galactic centre. Our final sample consists of 91 stars with good signal-to-noise ratio. We separated YSOs from cool late-type stars based on spectral features of CO and Brγ at 2.3 μm and 2.16 μm, respectively. We made use of spectral energy distribution (SED) model fits to the observed photometric data points from 1.25 to 24 μm to estimate approximate masses for the YSOs. Results: Using the spectroscopically identified YSOs in our sample, we confirm that existing colour-colour diagrams and colour-magnitude diagrams are unable to efficiently separate YSOs and cool late-type stars. In addition, we define a new colour-colour criterion that separates YSOs from cool late-type stars in the H-KS vs. H -[8.0] diagram. We use this new criterion to identify YSO candidates in the |l| Chile, programme number 097.C-0208(A).

  6. Congruency sequence effects are driven by previous-trial congruency, not previous-trial response conflict

    OpenAIRE

    Weissman, Daniel H.; Carp, Joshua

    2013-01-01

    Congruency effects in distracter interference tasks are often smaller after incongruent trials than after congruent trials. However, the sources of such congruency sequence effects (CSEs) are controversial. The conflict monitoring model of cognitive control links CSEs to the detection and resolution of response conflict. In contrast, competing theories attribute CSEs to attentional or affective processes that vary with previous-trial congruency (incongruent vs. congruent). The present study s...

  7. Candidate preferences and expectations of election outcomes

    Science.gov (United States)

    Delavande, Adeline; Manski, Charles F.

    2012-01-01

    Analysis of data from the American Life Panel shows that in the presidential election of 2008 and in multiple statewide elections in 2010, citizens exhibited large differences in their expectations of election outcomes. Expectations were strongly positively associated with candidate preferences, persons tending to believe that their preferred candidate is more likely to win the election. Committed supporters of opposing candidates regularly differed by 20–30% in their assessments of the likelihood that each candidate would win. These findings contribute evidence on the false consensus effect, the empirical regularity that own preferences tend to be positively associated with perceptions of social preferences. We used unique measures of preferences and perceptions that enabled respondents to express uncertainty flexibly. We studied a setting that would a priori seem inhospitable to false consensus—one where persons have little private information on social preferences but substantial common knowledge provided by media reports of election polls. PMID:22355121

  8. Candidate preferences and expectations of election outcomes.

    Science.gov (United States)

    Delavande, Adeline; Manski, Charles F

    2012-03-06

    Analysis of data from the American Life Panel shows that in the presidential election of 2008 and in multiple statewide elections in 2010, citizens exhibited large differences in their expectations of election outcomes. Expectations were strongly positively associated with candidate preferences, persons tending to believe that their preferred candidate is more likely to win the election. Committed supporters of opposing candidates regularly differed by 20-30% in their assessments of the likelihood that each candidate would win. These findings contribute evidence on the false consensus effect, the empirical regularity that own preferences tend to be positively associated with perceptions of social preferences. We used unique measures of preferences and perceptions that enabled respondents to express uncertainty flexibly. We studied a setting that would a priori seem inhospitable to false consensus--one where persons have little private information on social preferences but substantial common knowledge provided by media reports of election polls.

  9. Evaluating historical candidate genes for schizophrenia

    DEFF Research Database (Denmark)

    Farrell, M S; Werge, T; Sklar, P

    2015-01-01

    Prior to the genome-wide association era, candidate gene studies were a major approach in schizophrenia genetics. In this invited review, we consider the current status of 25 historical candidate genes for schizophrenia (for example, COMT, DISC1, DTNBP1 and NRG1). The initial study for 24...... of these genes explicitly evaluated common variant hypotheses about schizophrenia. Our evaluation included a meta-analysis of the candidate gene literature, incorporation of the results of the largest genomic study yet published for schizophrenia, ratings from informed researchers who have published...... on these genes, and ratings from 24 schizophrenia geneticists. On the basis of current empirical evidence and mostly consensual assessments of informed opinion, it appears that the historical candidate gene literature did not yield clear insights into the genetic basis of schizophrenia. A likely reason why...

  10. 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...

  11. Characterization of nanoparticles as candidate reference materials

    International Nuclear Information System (INIS)

    Martins Ferreira, E.H.; Robertis, E. de; Landi, S.M.; Gouvea, C.P.; Archanjo, B.S.; Almeida, C.A.; Araujo, J.R. de; Kuznetsov, O.; Achete, C.A.

    2013-01-01

    We report the characterization of three different nanoparticles (silica, silver and multi-walled carbon nanotubes) as candidate reference material. We focus our analysis on the size distribution of those particles as measured by different microscopy techniques. (author)

  12. Cattle Candidate Genes for Milk Production Traits

    OpenAIRE

    KADLEC, Tomáš

    2012-01-01

    The aim of this thesis is to make an overview of important candidate genes affecting milk yield and milk quality parameters, with an emphasis on genes associated with the quantity and quality of milk proteins and milk fat.

  13. Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

    NARCIS (Netherlands)

    Asai, Yuka; Eslami, Aida; van Ginkel, C Dorien; Akhabir, Loubna; Wan, Ming; Ben-Shoshan, Moshe; Martino, David; Ferreira, Manuel A; Allen, Katrina; Mazer, Bruce; de Jong, Nicolette W; Gerth van Wijk, Roy N; Dubois, Anthony E J; Chin, Rick; Cheuk, Steven; Hoffman, Joshua; Jorgensen, Eric; Witte, John S; Melles, Ronald B; Hong, Xiumei; Wang, Xiaobin; Hui, Jennie; Musk, Arthur W Bill; Hunter, Michael; James, Alan L; Koppelman, Gerard H; Sandford, Andrew J; Clarke, Ann E; Daley, Denise

    BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously PA loci were identified in FLG and HLA in candidate gene studies, and loci in HLA in a genome-wide association study and meta-analysis. OBJECTIVE: To investigate genetic susceptibility

  14. Trypanosoma equiperdum Low Molecular Weight Proteins As Candidates for Specific Serological Diagnosis of Dourine

    Directory of Open Access Journals (Sweden)

    Mirella Luciani

    2018-03-01

    Full Text Available The diagnosis of dourine can be difficult because the clinical signs of this disease in horses are similar to those of surra, caused by Trypanosoma evansi. Moreover, T. equiperdum and T. evansi are closely related and, so far, they cannot be distinguished using serological tests. In a previous work, the T. equiperdum protein pattern recognized by antibodies from dourine-infected horses and the humoral immune response kinetics were investigated by immunoblotting assay; a total of 20 sera from naturally and experimentally infected horses and from healthy animals were tested. Immunoblotting analysis showed that antibodies from infected horses specifically bind T. equiperdum low molecular weight proteins (from 16 to 35 kDa, which are not recognized by antibodies from uninfected horses. In this work, we tested other 615 sera (7 from naturally infected horses and 608 sera from healthy horses and donkeys: results confirmed the data obtained previously. In addition, six SDS-PAGE bands with molecular weight ranging from 10 to 37 kDa were analyzed by mass spectrometry, in order to identify immunogenic proteins that could be used as biomarkers for the diagnosis of dourine. A total of 167 proteins were identified. Among them, 37 were found unique for T. equiperdum. Twenty-four of them could represent possible candidate diagnostic antigens for the development of serological tests specific for T. equiperdum.

  15. Indico CONFERENCE: Candidate participant's registration/application

    CERN Multimedia

    CERN. Geneva; Ferreira, Pedro

    2017-01-01

    In this tutorial you are going to learn how to apply as a candidate participant (if the event requires approval from the event manager) or to register (if participation to the event doesn't require approval from an event manager) to the conference using the registration form for the event. You are also going to learn how to approve a candidate participant's application as an event manager.

  16. A Refined Catalogue of Phoenix Dwarf Galaxy Giant Star Candidates

    Science.gov (United States)

    Tobolewski, Joshua; Siegel, M.; Palma, C.; Charlton, J.

    2005-12-01

    Continuing our studies of the Phoenix dwarf irregular galaxy and its extended tidal structure, we present the results of a survey using improved photometry with the Washington M-T2-DDO51 photometric method. The three-filter method has the ability to discriminate low surface-gravity giant stars from high surface gravity dwarfs and has proven successful at showing extended distributions of giant stars in other dSph satellites of the Milky Way. Our survey of Phoenix, the most distant (Rgc > 400kpc) of the Milky Way's bound satellites, was taken over a 0.5 square degree region obtained with the CTIO 4-meter telescope and Mosaic II camera. Relying on conservative cuts in photometric error and stellar shape parameter space, our photometry provides a clean list of extratidal giant star candidates. We find 250 giant candidates in our survey that pass both color-magnitude and color-color constraint cuts. Of these, we have roughly 29 candidate giant stars that lie outside the tidal radius of Phoenix. This number of candidate extratidal stars has not been adjusted for background contamination. Further investigations are required to determine if any of these stars were once bound to Phoenix. Using the entire sample of candidate giant stars associated with Phoenix, we also see structural differences in the spatial distribution of high and low metallicity giant stars within the galaxy. Similar differences in the spatial distribution of young and old stars in Phoenix have been noted by other authors. Finally, we compare our photometric selection of Phoenix stars with spectroscopically verified giant stars from Gallart et al (2001) and find that our selection process is successful in identifying these stars as giants, suggesting a high efficiency in selecting giants. We gratefully acknowledge funding for this work from an NSF REU supplement and grant AST 0306884.

  17. Building blocks for automated elucidation of metabolites: natural product-likeness for candidate ranking.

    Science.gov (United States)

    Jayaseelan, Kalai Vanii; Steinbeck, Christoph

    2014-07-05

    In metabolomics experiments, spectral fingerprints of metabolites with no known structural identity are detected routinely. Computer-assisted structure elucidation (CASE) has been used to determine the structural identities of unknown compounds. It is generally accepted that a single 1D NMR spectrum or mass spectrum is usually not sufficient to establish the identity of a hitherto unknown compound. When a suite of spectra from 1D and 2D NMR experiments supplemented with a molecular formula are available, the successful elucidation of the chemical structure for candidates with up to 30 heavy atoms has been reported previously by one of the authors. In high-throughput metabolomics, usually 1D NMR or mass spectrometry experiments alone are conducted for rapid analysis of samples. This method subsequently requires that the spectral patterns are analyzed automatically to quickly identify known and unknown structures. In this study, we investigated whether additional existing knowledge, such as the fact that the unknown compound is a natural product, can be used to improve the ranking of the correct structure in the result list after the structure elucidation process. To identify unknowns using as little spectroscopic information as possible, we implemented an evolutionary algorithm-based CASE mechanism to elucidate candidates in a fully automated fashion, with input of the molecular formula and 13C NMR spectrum of the isolated compound. We also tested how filters like natural product-likeness, a measure that calculates the similarity of the compounds to known natural product space, might enhance the performance and quality of the structure elucidation. The evolutionary algorithm is implemented within the SENECA package for CASE reported previously, and is available for free download under artistic license at http://sourceforge.net/projects/seneca/. The natural product-likeness calculator is incorporated as a plugin within SENECA and is available as a GUI client and

  18. National Vocational Qualifications: the candidates' experience.

    Science.gov (United States)

    Isaac, Susan

    2007-03-01

    To examine the experience of studying for an National Vocational Qualification (NVQ) by past and present candidates in the library and information science sector, their reasons for choosing this qualification and its impact on completion. Following a review of the literature, a number of NVQ candidates were interviewed using a semi-structured questionnaire. Candidates were contacted via e-mail through NVQ Centres and the LondonLinks e-mail list. There is a focus on health libraries as the flexibility and work-based nature of NVQs enable more staff to access training and education in this sector, despite the not uncommon low levels of staffing. NVQ Centres have gained experience since NVQs were launched 10 years ago. More support is offered to candidates and a number of issues such as isolation, are no longer a problem. An interesting result was the high number of candidates who had gone on to higher education following the completion of an NVQ. The NVQ is a useful method of providing staff with an opportunity to gain a recognized qualification. A significant number of candidates reported that the NVQ was ultimately a positive experience that improved their working practices. It can be an important first step for non-professional staff, but the future remains uncertain.

  19. Event sequence variability in healthy swallowing: building on previous findings.

    Science.gov (United States)

    Molfenter, Sonja M; Leigh, Chelsea; Steele, Catriona M

    2014-04-01

    This study builds on previous work by Kendall, Leonard, and McKenzie, which investigated event sequence variability for 12 paired events during swallowing by healthy volunteers. They identified four event pairs that always occurred in a stereotyped order and a most common occurring overall order of events during swallowing. In the current study, we investigated overall event sequencing and the same four paired events in a sample of swallows by healthy young (under 45 years old) volunteers. Data were collected during a 16-swallow lateral videofluoroscopy protocol, which included manipulations of bolus volume, barium density, bolus viscosity, and swallow cueing. Our results agreed with previous findings that variable event sequencing is found in healthy swallowing, and, in regard to obligatory sequencing of two paired events, movement of the arytenoids toward the base of the epiglottis begins prior to upper esophageal sphincter (UES) opening and maximum hyolaryngeal approximation occurs after UES opening. However, our data failed to replicate the previous findings that there is obligatory sequencing of maximum pharyngeal constriction after maximal UES distension and the UES opens before bolus arrival at the UES. The most common observed overall event sequence reported by Kendall et al. was observed in only 4/293 swallows in our dataset. Manipulations of bolus volume, bolus viscosity, barium concentration, swallow cueing, and swallow repetitions could not completely account for the differences observed between the two studies.

  20. Probiotic Candidates from Fish Pond Water in Central Java Indonesia

    Science.gov (United States)

    Harjuno Condro Haditomo, Alfabetian; Desrina; Sarjito; Budi Prayitno, S.

    2018-02-01

    Aeromonas hydrophilla is a major bacterial pathogen of intensive fresh water fish culture in Indonesia. An alternative method to control the pathogen is using probiotics. Probiotics is usually consist of live microorganisms which when administered in adequate amounts confer a health benefits on host. The aim of this research was to determine the probiotic candidates against A. hydrophilla which identified based on the 16S rDNA gene sequences. This research was started with field survey to obtained the probiotic candidate and continue with laboratory experiment. Probiotic candidates were isolated from fish pond water located in Boyolali, and Banjarnegara Regency, Central Java, Indonesia. A total of 133 isolates bacteria were isolated and cultured on to TSA, TSB and GSP medium. Out of 133 isolates only 30 isolates showed inhibition to A.hydrophilla activity. Three promising isolates were identified with PCR using primer for 16S rDNA. Based on 16S rDNA sequence analysis, all three isolates were belong to Bacillus genus. Isolate CKlA21, CKlA28, and CBA14 respectively were closely related to Bacillus sp. 13843 (GenBank accession no. JN874760.1 -100% homology), Bacillus subtilis strain H13 (GenBank accession no.KT907045.1 -- 99% homology), and Bacillus sp. strain 22-4 (GenBank accession no. KX816417.1 -- 97% homology).

  1. Five Kepler target stars that show multiple transiting exoplanet candidates

    Energy Technology Data Exchange (ETDEWEB)

    Steffen, Jason H.; /Fermilab; Batalha, Natalie M.; /San Jose State U.; Borucki, William J.; /NASA, Ames; Buchhave, Lars A.; /Harvard-Smithsonian Ctr. Astrophys. /Bohr Inst.; Caldwell, Douglas A.; /NASA, Ames /SETI Inst., Mtn. View; Cochran, William D.; /Texas U.; Endl, Michael; /Texas U.; Fabrycky, Daniel C.; /Harvard-Smithsonian Ctr. Astrophys.; Fressin, Francois; /Harvard-Smithsonian Ctr. Astrophys.; Ford, Eric B.; /Florida U.; Fortney, Jonathan J.; /UC, Santa Cruz, Phys. Dept. /NASA, Ames

    2010-06-01

    We present and discuss five candidate exoplanetary systems identified with the Kepler spacecraft. These five systems show transits from multiple exoplanet candidates. Should these objects prove to be planetary in nature, then these five systems open new opportunities for the field of exoplanets and provide new insights into the formation and dynamical evolution of planetary systems. We discuss the methods used to identify multiple transiting objects from the Kepler photometry as well as the false-positive rejection methods that have been applied to these data. One system shows transits from three distinct objects while the remaining four systems show transits from two objects. Three systems have planet candidates that are near mean motion commensurabilities - two near 2:1 and one just outside 5:2. We discuss the implications that multitransiting systems have on the distribution of orbital inclinations in planetary systems, and hence their dynamical histories; as well as their likely masses and chemical compositions. A Monte Carlo study indicates that, with additional data, most of these systems should exhibit detectable transit timing variations (TTV) due to gravitational interactions - though none are apparent in these data. We also discuss new challenges that arise in TTV analyses due to the presence of more than two planets in a system.

  2. 11 CFR 9033.1 - Candidate and committee agreements.

    Science.gov (United States)

    2010-01-01

    ... candidate. (7) The candidate and the candidate's authorized committee(s) will permit an audit and... pursuant to 11 CFR part 9039. The candidate and authorized committee(s) shall facilitate the audit by... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate and committee agreements. 9033.1...

  3. Prevalence and significance of previously undiagnosed rheumatic diseases in pregnancy.

    Science.gov (United States)

    Spinillo, Arsenio; Beneventi, Fausta; Ramoni, Véronique; Caporali, Roberto; Locatelli, Elena; Simonetta, Margherita; Cavagnoli, Chiara; Alpini, Claudia; Albonico, Giulia; Prisco, Elena; Montecucco, Carlomaurizio

    2012-06-01

    The objective of this study was to evaluate the rates of previously undiagnosed rheumatic diseases during the first trimester of pregnancy and their impact on the pregnancy outcome. Pregnant women in their first trimester were screened using a two-step approach using a self-administered 10-item questionnaire and subsequent testing for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies and lupus anticoagulant) and evaluation by a rheumatologist. Overall, the complications of pregnancy evaluated included fetal loss, pre-eclampsia, gestational diabetes, fetal growth restriction, delivery at less than 34 weeks, neonatal resuscitation and admission to the neonatal intensive care unit. Out of the 2458 women screened, the authors identified 62 (2.5%) women with previously undiagnosed undifferentiated connective tissue disease (UCTD) and 24 (0.98%) women with previously undiagnosed definite systemic rheumatic disease. The prevalences were seven (0.28%) for systemic lupus erythematosus and Sjogren's syndrome, six (0.24%) for rheumatoid arthritis, three (0.12%) for antiphospholipid syndrome and one (0.04%) for systemic sclerosis. In multiple exact logistic regression, after adjustment for potential confounders, the OR of overall complications of pregnancy were 2.81 (95% CI 1.29 to 6.18) in women with UCTD and 4.57 (95% CI 1.57 to 13.57) in those with definite diseases, respectively, compared with asymptomatic controls. In our population approximately 2.5% and 1% of first trimester pregnant women had a previously undiagnosed UCTD and definite systemic rheumatic disease, respectively. These conditions were associated with significant negative effects on the outcome of pregnancy.

  4. Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

    Science.gov (United States)

    Martins, Karen A.; Jahrling, Peter B.; Bavari, Sina; Kuhn, Jens H.

    2016-01-01

    Summary Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. PMID:27160784

  5. Identifying flares in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H

    2016-01-01

    to flare, with escalation planned in 61%. CONCLUSIONS: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with...... Set. METHODS: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares...

  6. Genetics of osteoporosis: searching for candidate genes for bone fragility.

    Science.gov (United States)

    Rocha-Braz, Manuela G M; Ferraz-de-Souza, Bruno

    2016-08-01

    The pathogenesis of osteoporosis, a common disease with great morbidity and mortality, comprises environmental and genetic factors. As with other complex disorders, the genetic basis of osteoporosis has been difficult to identify. Nevertheless, several approaches have been undertaken in the past decades in order to identify candidate genes for bone fragility, including the study of rare monogenic syndromes with striking bone phenotypes (e.g. osteogenesis imperfecta and osteopetroses), the analysis of individuals or families with extreme osteoporotic phenotypes (e.g. idiopathic juvenile and pregnancy-related osteoporosis), and, chiefly, genome-wide association studies (GWAS) in large populations. Altogether, these efforts have greatly increased the understanding of molecular mechanisms behind bone remodelling, which has rapidly translated into the development of novel therapeutic strategies, exemplified by the tales of cathepsin K (CTSK) and sclerostin (SOST). Additional biological evidence of involvement in bone physiology still lacks for several candidate genes arisen from GWAS, opening an opportunity for the discovery of new mechanisms regulating bone strength, particularly with the advent of high-throughput genomic technologies. In this review, candidate genes for bone fragility will be presented in comprehensive tables and discussed with regard to how their association with osteoporosis emerged, highlighting key players such as LRP5, WNT1 and PLS3. Current limitations in our understanding of the genetic contribution to osteoporosis, such as yet unidentified genetic modifiers, may be overcome in the near future with better genotypic and phenotypic characterisation of large populations and the detailed study of candidate genes in informative individuals with marked phenotype.

  7. NeuroRDF: semantic integration of highly curated data to prioritize biomarker candidates in Alzheimer's disease.

    Science.gov (United States)

    Iyappan, Anandhi; Kawalia, Shweta Bagewadi; Raschka, Tamara; Hofmann-Apitius, Martin; Senger, Philipp

    2016-07-08

    Neurodegenerative diseases are incurable and debilitating indications with huge social and economic impact, where much is still to be learnt about the underlying molecular events. Mechanistic disease models could offer a knowledge framework to help decipher the complex interactions that occur at molecular and cellular levels. This motivates the need for the development of an approach integrating highly curated and heterogeneous data into a disease model of different regulatory data layers. Although several disease models exist, they often do not consider the quality of underlying data. Moreover, even with the current advancements in semantic web technology, we still do not have cure for complex diseases like Alzheimer's disease. One of the key reasons accountable for this could be the increasing gap between generated data and the derived knowledge. In this paper, we describe an approach, called as NeuroRDF, to develop an integrative framework for modeling curated knowledge in the area of complex neurodegenerative diseases. The core of this strategy lies in the usage of well curated and context specific data for integration into one single semantic web-based framework, RDF. This increases the probability of the derived knowledge to be novel and reliable in a specific disease context. This infrastructure integrates highly curated data from databases (Bind, IntAct, etc.), literature (PubMed), and gene expression resources (such as GEO and ArrayExpress). We illustrate the effectiveness of our approach by asking real-world biomedical questions that link these resources to prioritize the plausible biomarker candidates. Among the 13 prioritized candidate genes, we identified MIF to be a potential emerging candidate due to its role as a pro-inflammatory cytokine. We additionally report on the effort and challenges faced during generation of such an indication-specific knowledge base comprising of curated and quality-controlled data. Although many alternative approaches

  8. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus.

    Science.gov (United States)

    Ray, Ann; Kinch, Lisa N; de Souza Santos, Marcela; Grishin, Nick V; Orth, Kim; Salomon, Dor

    2016-07-26

    Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells. The pan-genome of the genus Vibrio is a potential reservoir of unidentified toxins that can provide insight into how members of this genus have successfully risen as emerging pathogens worldwide. We focused on Vibrio proteolyticus, a marine bacterium that was previously implicated in virulence toward marine animals, and characterized its interaction with eukaryotic cells. We found that this bacterium causes actin cytoskeleton rearrangements and leads to cell death. Using a

  9. Identification of Robust Hypoxia Biomarker Candidates from Fin of Medaka (Oryzias latipes)✰

    Science.gov (United States)

    Zhang, Ziping; Wells, Melissa C.; Boswell, Mikki G.; Beldorth, Ion; Kirk, Lyndsey M.; Wang, Yilei; Wang, Shulong; Savage, Markita; Walter, Ronald B.; Booth, Rachell E.

    2011-01-01

    Aquatic hypoxia caused by organic pollution and eutrophication is a pressing worldwide water pollution problem. Better methods for monitoring oxygen levels are needed to assist efforts to maintain and protect the health of natural aquatic environments. In this project, we used a Japanese ricefish (medaka, Oryzias latipes) 8K oligonucleotide array as a platform to identify potential hypoxic biomarkers in different organs (fin, gill, liver and brain) upon exposure to hypoxia. The microarray results were validated by qRT-PCR employing a subset of candidate biomarkers. Interestingly, the largest number and most significant of hypoxia responding array features were detected in hypoxia exposed fin tissues. We identified 173 array features that exhibited a significant response (over 2 fold change in expression) upon exposure to hypoxic conditions and validated a subset of these by quantitative RT-PCR. These gene targets were subjected to annotation and gene ontology mining. Positively identifiable gene targets that may be useful for development of a rapid and accurate biomarker test using fin clips are discussed in relation to previous reports on hypoxia responsive genes. PMID:21664487

  10. Candidate genes associated with bud dormancy release in blackcurrant (Ribes nigrum L.

    Directory of Open Access Journals (Sweden)

    Hedley Peter E

    2010-09-01

    Full Text Available Abstract Background The detrimental effects of mild winter temperatures on the consistency of cropping of blackcurrant (Ribes nigrum L. in parts of Europe have led to increasing interest in the genetic control of dormancy release in this species. This study examined patterns of gene expression in leaf buds of blackcurrant to identify key differential changes in these profiles around the time of budbreak. Results Using leaf bud tissue of blackcurrant, a cDNA library was generated as a source of blackcurrant ESTs for construction of a custom microarray, which was used to identify differential gene expression during dormancy release. Gene activity was lowest in early stages of dormancy, increasing to reach a maximum around the time of budbreak. Genes with significantly changing expression profiles were clustered and evidence is provided for the transient activity of genes previously associated with dormancy processes in other species. Expression profiling identified candidate genes which were mapped onto a blackcurrant genetic linkage map containing budbreak-related QTL. Three genes, which putatively encode calmodulin-binding protein, beta tubulin and acetyl CoA carboxylase respectively, were found to co-localise with budbreak QTL. Conclusions This study provides insight into the genetic control of dormancy transition in blackcurrant, identifying key changes in gene expression around budbreak. Genetic mapping of ESTs enabled the identification of genes which co-localise with previously-characterised blackcurrant QTL, and it is concluded that these genes have probable roles in release of dormancy and can therefore provide a basis for the development of genetic markers for future breeding deployment.

  11. Investigation of variable star candidates in the globular cluster NGC 5024 (M53)

    Science.gov (United States)

    Bramich, D. M.; Arellano Ferro, A.; Jaimes, R. Figuera; Giridhar, Sunetra

    2012-08-01

    We have performed a careful investigation of the 74 candidate variable stars presented by Safonova & Stalin. For this purpose we used our data base of imaging and light curves from Arellano Ferro et al. We find that two candidates are known variable stars, eight candidates were discovered first by Arellano Ferro et al., but would not have been known to Safonova & Stalin at the time of their paper submission, while four candidates are new variables. Three of the new variables are SX Phe type and one is a semiregular (SR) type red giant variable. We also tentatively confirm the presence of true variability in two other candidates, and we are unable to investigate another four candidates because they are not in our data base. However, we find that the remaining 54 candidate variable stars are spurious detections where systematic trends in the light curves have been mistaken for true variability. We believe that the erroneous detections are caused by the adoption of a very low detection threshold used to identify these candidates.

  12. The Naïve Murine Cornea as a Model System to Identify Novel Endogenous Regulators of Lymphangiogenesis: TRAIL and rtPA.

    Science.gov (United States)

    Regenfuß, Birgit; Dreisow, Marie-Luise; Hos, Deniz; Masli, Sharmila; Bock, Felix; Cursiefen, Claus

    2015-06-01

    In the murine cornea, which is an established model for analyzing pathologic lymphatic vessel growth, phenotypic heterogeneity of the endogenous lymphatic vessels in the limbus of the cornea was previously described. In this study, the cornea of BALB/c, C57BL/6, and FVB mice with different limbal lymphangiogenic phenotypes was analyzed to identify novel candidates potentially influencing lymphatic vessel growth. Pathway specific expression analysis of the cornea was performed to identify novel candidate genes. Corneal protein expression of the respective candidates was analyzed by fluorescent immunohistochemistry. The effect of the candidates on proliferation of human dermal lymphatic endothelial cells (HDLECs) was analyzed by BrdU proliferation ELISA. Thirteen genes were differentially regulated in corneas of mouse strains with more endogenous limbal lymphatic vessels (high-lymphangiogenic) (C57BL/6) compared to mouse strains with less endogenous limbal lymphatic vessels (low-lymphangiogenic) (BALB/c, FVB). Two candidates, Tumor necrosis factor (ligand) superfamily member 10 (Tnfsf10/Trail) and Plasminogen activator, tissue (Plat/tPA) were expressed in the cornea of BALB/c and C57BL/6 mice on the protein level. In vitro, Trail and recombinant tPA inhibited the proliferation of human dermal lymphatic endothelial cells. Molecular analysis of the naive cornea in mouse strains with different limbal lymphatic phenotypes is a valuable model to identify novel endogenous regulators of lymphangiogenesis.

  13. Developing Potential Candidates of Preclinical Preeclampsia

    Science.gov (United States)

    Founds, Sandra; Zeng, Xuemei; Lykins, David; Roberts, James M.

    2015-01-01

    The potential for developing molecules of interest in preclinical preeclampsia from candidate genes that were discovered on gene expression microarray analysis has been challenged by limited access to additional first trimester trophoblast and decidual tissues. The question of whether these candidates encode secreted proteins that may be detected in maternal circulation early in pregnancy has been investigated using various proteomic methods. Pilot studies utilizing mass spectrometry based proteomic assays, along with enzyme linked immunosorbent assays (ELISAs), and Western immunoblotting in first trimester samples are reported. The novel targeted mass spectrometry methods led to robust multiple reaction monitoring assays. Despite detection of several candidates in early gestation, challenges persist. Future antibody-based studies may lead to a novel multiplex protein panel for screening or detection to prevent or mitigate preeclampsia. PMID:26580600

  14. Developing Potential Candidates of Preclinical Preeclampsia

    Directory of Open Access Journals (Sweden)

    Sandra Founds

    2015-11-01

    Full Text Available The potential for developing molecules of interest in preclinical preeclampsia from candidate genes that were discovered on gene expression microarray analysis has been challenged by limited access to additional first trimester trophoblast and decidual tissues. The question of whether these candidates encode secreted proteins that may be detected in maternal circulation early in pregnancy has been investigated using various proteomic methods. Pilot studies utilizing mass spectrometry based proteomic assays, along with enzyme linked immunosorbent assays (ELISAs, and Western immunoblotting in first trimester samples are reported. The novel targeted mass spectrometry methods led to robust multiple reaction monitoring assays. Despite detection of several candidates in early gestation, challenges persist. Future antibody-based studies may lead to a novel multiplex protein panel for screening or detection to prevent or mitigate preeclampsia.

  15. PHOTOMETRIC TYPE Ia SUPERNOVA CANDIDATES FROM THE THREE-YEAR SDSS-II SN SURVEY DATA

    International Nuclear Information System (INIS)

    Sako, Masao; Connolly, Brian; Gladney, Larry; Bassett, Bruce; Dilday, Benjamin; Cambell, Heather; Lampeitl, Hubert; Nichol, Robert C.; Frieman, Joshua A.; Kessler, Richard; Marriner, John; Miquel, Ramon; Schneider, Donald P.; Smith, Mathew; Sollerman, Jesper

    2011-01-01

    We analyze the three-year Sloan Digital Sky Survey II (SDSS-II) Supernova (SN) Survey data and identify a sample of 1070 photometric Type Ia supernova (SN Ia) candidates based on their multiband light curve data. This sample consists of SN candidates with no spectroscopic confirmation, with a subset of 210 candidates having spectroscopic redshifts of their host galaxies measured while the remaining 860 candidates are purely photometric in their identification. We describe a method for estimating the efficiency and purity of photometric SN Ia classification when spectroscopic confirmation of only a limited sample is available, and demonstrate that SN Ia candidates from SDSS-II can be identified photometrically with ∼91% efficiency and with a contamination of ∼6%. Although this is the largest uniform sample of SN candidates to date for studying photometric identification, we find that a larger spectroscopic sample of contaminating sources is required to obtain a better characterization of the background events. A Hubble diagram using SN candidates with no spectroscopic confirmation, but with host galaxy spectroscopic redshifts, yields a distance modulus dispersion that is only ∼20%-40% larger than that of the spectroscopically confirmed SN Ia sample alone with no significant bias. A Hubble diagram with purely photometric classification and redshift-distance measurements, however, exhibits biases that require further investigation for precision cosmology.

  16. Evaluation of the Knowledge and Misconceptions of Science Teacher Candidates in Turkey Regarding the Greenhouse Effect through the Use of Drawings

    Science.gov (United States)

    Aksan, Zeynep; Çelikler, Dilek

    2015-01-01

    The aim of this study was to identify, through the use drawings, the knowledge and misconceptions of science teacher candidates regarding the greenhouse effect, and to thereby categorize their level of knowledge on this subject. The study was conducted with a group of 327 science teacher candidates. In this study, science teacher candidates were…

  17. Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes

    DEFF Research Database (Denmark)

    Laugesen, Caroline Schmidt; Ostri, Christoffer; Brynskov, Troels

    2017-01-01

    PURPOSE: There is little information about the efficacy of intravitreal vascular endothelial growth factor (VEGF) inhibition in vitrectomized eyes. This study aimed to evaluate the efficacy of anti-VEGF (ranibizumab) on diabetic macular oedema in previously vitrectomized eyes. METHODS: A nationwide...... retrospective review of medical records from 2010 to 2013. RESULTS: We identified 33 previously vitrectomized eyes in 28 patients treated with ranibizumab injections for diabetic macular oedema. Median follow-up was 323 days (interquartile range 72-1404 days). Baseline mean visual acuity was 0.57 logMAR (95% CI...... 0.13-1.01) before injections. After an average of 4.7 injections (range 1-15), mean visual acuity remained stable at 0.54 logMAR (95% CI 0.13-0.95) with a mean improvement of 0.03 (p = 0. 45, 95% CI -0.12 to 0.06). In 12 eyes (36%), visual acuity improved 0.1 logMAR or more, in 12 eyes (36%), vision...

  18. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus

    Directory of Open Access Journals (Sweden)

    Ann Ray

    2016-07-01

    Full Text Available Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells.

  19. Kidnapping Detection and Recognition in Previous Unknown Environment

    Directory of Open Access Journals (Sweden)

    Yang Tian

    2017-01-01

    Full Text Available An unaware event referred to as kidnapping makes the estimation result of localization incorrect. In a previous unknown environment, incorrect localization result causes incorrect mapping result in Simultaneous Localization and Mapping (SLAM by kidnapping. In this situation, the explored area and unexplored area are divided to make the kidnapping recovery difficult. To provide sufficient information on kidnapping, a framework to judge whether kidnapping has occurred and to identify the type of kidnapping with filter-based SLAM is proposed. The framework is called double kidnapping detection and recognition (DKDR by performing two checks before and after the “update” process with different metrics in real time. To explain one of the principles of DKDR, we describe a property of filter-based SLAM that corrects the mapping result of the environment using the current observations after the “update” process. Two classical filter-based SLAM algorithms, Extend Kalman Filter (EKF SLAM and Particle Filter (PF SLAM, are modified to show that DKDR can be simply and widely applied in existing filter-based SLAM algorithms. Furthermore, a technique to determine the adapted thresholds of metrics in real time without previous data is presented. Both simulated and experimental results demonstrate the validity and accuracy of the proposed method.

  20. A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases

    Directory of Open Access Journals (Sweden)

    Karp Peter D

    2004-06-01

    Full Text Available Abstract Background The PathoLogic program constructs Pathway/Genome databases by using a genome's annotation to predict the set of metabolic pathways present in an organism. PathoLogic determines the set of reactions composing those pathways from the enzymes annotated in the organism's genome. Most annotation efforts fail to assign function to 40–60% of sequences. In addition, large numbers of sequences may have non-specific annotations (e.g., thiolase family protein. Pathway holes occur when a genome appears to lack the enzymes needed to catalyze reactions in a pathway. If a protein has not been assigned a specific function during the annotation process, any reaction catalyzed by that protein will appear as a missing enzyme or pathway hole in a Pathway/Genome database. Results We have developed a method that efficiently combines homology and pathway-based evidence to identify candidates for filling pathway holes in Pathway/Genome databases. Our program not only identifies potential candidate sequences for pathway holes, but combines data from multiple, heterogeneous sources to assess the likelihood that a candidate has the required function. Our algorithm emulates the manual sequence annotation process, considering not only evidence from homology searches, but also considering evidence from genomic context (i.e., is the gene part of an operon? and functional context (e.g., are there functionally-related genes nearby in the genome? to determine the posterior belief that a candidate has the required function. The method can be applied across an entire metabolic pathway network and is generally applicable to any pathway database. The program uses a set of sequences encoding the required activity in other genomes to identify candidate proteins in the genome of interest, and then evaluates each candidate by using a simple Bayes classifier to determine the probability that the candidate has the desired function. We achieved 71% precision at a

  1. ESA M3 mission candidate EChO

    Science.gov (United States)

    Puig, L.; Isaak, K. G.; Escudero, I.; Martin, D.; Crouzet, P.-E.; Rando, N.

    2011-09-01

    The Exoplanet Characterisation Observatory (EChO) is a medium class mission candidate within the science program Cosmic Vision 2015-2025 of the European Space Agency. It was selected in February 2011 as one of 4 M3 mission candidates to enter an assessment phase. The assessment activities start with the definition of science and mission requirements as well as of a preliminary model payload, followed by an internal Concurrent Design Facility (CDF) study. Parallel industrial studies will follow in 2012, after which the 4 missions will be reviewed to identify candidates entering definition phase studies in 2013. EChO aims at characterising the atmosphere of known transiting exoplanets, potentially from giant Hot Jupiters down to Super-Earths orbiting in the habitable zone of M-dwarf stars. It will use a 1 m class telescope, feeding a spectrometer covering the wave lengths from 0.4 to 11 microns with a potential extension to 16 microns. While spatial differentiation of the exoplanet and its host star is not necessary, spectral differentiation will be achieved by making differential measurements of in- and out- of transit frames to cancel the star signal. This paper describes critical requirements, and gives an overview of the model payload design. It also reports on the results of the CDF.

  2. 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…

  3. Blood-Based Biomarker Candidates of Cerebral Amyloid Using PiB PET in Non-Demented Elderly

    Science.gov (United States)

    Westwood, Sarah; Leoni, Emanuela; Hye, Abdul; Lynham, Steven; Khondoker, Mizanur R.; Ashton, Nicholas J.; Kiddle, Steven J.; Baird, Alison L.; Sainz-Fuertes, Ricardo; Leung, Rufina; Graf, John; Hehir, Cristina Tan; Baker, David; Cereda, Cristina; Bazenet, Chantal; Ward, Malcolm; Thambisetty, Madhav; Lovestone, Simon

    2018-01-01

    Increasingly, clinical trials for Alzheimer’s disease (AD) are being conducted earlier in the disease phase and with biomarker confirmation using in vivo amyloid PET imaging or CSF tau and Aβ measures to quantify pathology. However, making such a pre-clinical AD diagnosis is relatively costly and the screening failure rate is likely to be high. Having a blood-based marker that would reduce such costs and accelerate clinical trials through identifying potential participants with likely pre-clinical AD would be a substantial advance. In order to seek such a candidate biomarker, discovery phase proteomic analyses using 2DGE and gel-free LC-MS/MS for high and low molecular weight analytes were conducted on longitudinal plasma samples collected over a 12-year period from non-demented older individuals who exhibited a range of 11C-PiB PET measures of amyloid load. We then sought to extend our discovery findings by investigating whether our candidate biomarkers were also associated with brain amyloid burden in disease, in an independent cohort. Seven plasma proteins, including A2M, Apo-A1, and multiple complement proteins, were identified as pre-clinical biomarkers of amyloid burden and were consistent across three time points (p biomarker signature indicative of AD pathology at a stage long before the onset of clinical disease manifestation. As in previous studies, acute phase reactants and inflammatory markers dominate this signature. PMID:27031486

  4. Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel candidate driver genes.

    Science.gov (United States)

    Caburet, Sandrine; Anttonen, Mikko; Todeschini, Anne-Laure; Unkila-Kallio, Leila; Mestivier, Denis; Butzow, Ralf; Veitia, Reiner A

    2015-04-10

    Ovarian granulosa cell tumors (GCTs) are the most frequent sex cord-stromal tumors. Several studies have shown that a somatic mutation leading to a C134W substitution in the transcription factor FOXL2 appears in more than 95% of adult-type GCTs. Its pervasive presence suggests that FOXL2 is the main cancer driver gene. However, other mutations and genomic changes might also contribute to tumor formation and/or progression. We have performed a combined comparative genomic hybridization and transcriptomic analyses of 10 adult-type GCTs to obtain a picture of the genomic landscape of this cancer type and to identify new candidate co-driver genes. Our results, along with a review of previous molecular studies, show the existence of highly recurrent chromosomal imbalances (especially, trisomy 14 and monosomy 22) and preferential co-occurrences (i.e. trisomy 14/monosomy 22 and trisomy 7/monosomy 16q). In-depth analyses showed the presence of recurrently broken, amplified/duplicated or deleted genes. Many of these genes, such as AKT1, RUNX1 and LIMA1, are known to be involved in cancer and related processes. Further genomic explorations suggest that they are functionally related. Our combined analysis identifies potential candidate genes, whose alterations might contribute to adult-type GCT formation/progression together with the recurrent FOXL2 somatic mutation.

  5. Search for Electromagnetic Counterparts to LIGO-Virgo Candidates: Expanded Very Large Array Observations

    Science.gov (United States)

    Lazio, Joseph; Keating, Katie; Jenet, F. A.; Kassim, N. E.

    2011-01-01

    This paper summarizes a search for radio wavelength counterparts to candidate gravitational wave events. The identification of an electromagnetic counterpart could provide a more complete understanding of a gravitational wave event, including such characteristics as the location and the nature of the progenitor. We used the Expanded Very Large Array (EVLA) to search six galaxies which were identified as potential hosts for two candidate gravitational wave events. We summarize our procedures and discuss preliminary results.

  6. Co-localization of growth QTL with differentially expressed candidate genes in rainbow trout.

    Science.gov (United States)

    Kocmarek, Andrea L; Ferguson, Moira M; Danzmann, Roy G

    2015-09-01

    We tested whether genes differentially expressed between large and small rainbow trout co-localized with familial QTL regions for body size. Eleven chromosomes, known from previous work to house QTL for weight and length in rainbow trout, were examined for QTL in half-sibling families produced in September (1 XY male and 1 XX neomale) and December (1 XY male). In previous studies, we identified 108 candidate genes for growth expressed in the liver and white muscle in a subset of the fish used in this study. These gene sequences were BLASTN aligned against the rainbow trout and stickleback genomes to determine their location (rainbow trout) and inferred location based on synteny with the stickleback genome. Across the progeny of all three males used in the study, 63.9% of the genes with differential expression appear to co-localize with the QTL regions on 6 of the 11 chromosomes tested in these males. Genes that co-localized with QTL in the mixed-sex offspring of the two XY males primarily showed up-regulation in the muscle of large fish and were related to muscle growth, metabolism, and the stress response.

  7. Meta-analysis and candidate gene mining of low-phosphorus tolerance in maize.

    Science.gov (United States)

    Zhang, Hongwei; Uddin, Mohammed Shalim; Zou, Cheng; Xie, Chuanxiao; Xu, Yunbi; Li, Wen-Xue

    2014-03-01

    Plants with tolerance to low-phosphorus (P) can grow better under low-P conditions, and understanding of genetic mechanisms of low-P tolerance can not only facilitate identifying relevant genes but also help to develop low-P tolerant cultivars. QTL meta-analysis was conducted after a comprehensive review of the reports on QTL mapping for low-P tolerance-related traits in maize. Meta-analysis produced 23 consensus QTL (cQTL), 17 of which located in similar chromosome regions to those previously reported to influence root traits. Meanwhile, candidate gene mining yielded 215 genes, 22 of which located in the cQTL regions. These 22 genes are homologous to 14 functionally characterized genes that were found to participate in plant low-P tolerance, including genes encoding miR399s, Pi transporters and purple acid phosphatases. Four cQTL loci (cQTL2-1, cQTL5-3, cQTL6-2, and cQTL10-2) may play important roles for low-P tolerance because each contains more original QTL and has better consistency across previous reports. © 2014 Institute of Botany, Chinese Academy of Sciences.

  8. Candidate z~8-9 Galaxies from WFC3 Imaging

    OpenAIRE

    Lorenzoni, Silvio; Bunker, Andrew; Wilkins, Stephen; Stanway, Elizabeth; Jarvis, Matt; Caruana, Joseph

    2010-01-01

    We present a search for galaxies at 7.6 < z < 9.8 using the latest Hubble Space Telescope/Wide Field Camera 3 (WFC3) near-infrared data, based on the Lyman-break technique. We search for galaxies which have large (Y−J) colours (the ‘Y-drops’) on account of the Lyman α forest absorption, and with (J−H) colours inconsistent with being low-redshift contaminants. We identify 24 candidates at redshift z≈ 8–9 (15 are robust and a further nine more marginal but consistent with being high redshift) o...

  9. Identification of candidate genes associated with leaf senescence in cultivated sunflower (Helianthus annuus L..

    Directory of Open Access Journals (Sweden)

    Sebastian Moschen

    Full Text Available Cultivated sunflower (Helianthus annuus L., an important source of edible vegetable oil, shows rapid onset of senescence, which limits production by reducing photosynthetic capacity under specific growing conditions. Carbon for grain filling depends strongly on light interception by green leaf area, which diminishes during grain filling due to leaf senescence. Transcription factors (TFs regulate the progression of leaf senescence in plants and have been well explored in model systems, but information for many agronomic crops remains limited. Here, we characterize the expression profiles of a set of putative senescence associated genes (SAGs identified by a candidate gene approach and sunflower microarray expression studies. We examined a time course of sunflower leaves undergoing natural senescence and used quantitative PCR (qPCR to measure the expression of 11 candidate genes representing the NAC, WRKY, MYB and NF-Y TF families. In addition, we measured physiological parameters such as chlorophyll, total soluble sugars and nitrogen content. The expression of Ha-NAC01, Ha-NAC03, Ha-NAC04, Ha-NAC05 and Ha-MYB01 TFs increased before the remobilization rate increased and therefore, before the appearance of the first physiological symptoms of senescence, whereas Ha-NAC02 expression decreased. In addition, we also examined the trifurcate feed-forward pathway (involving ORE1, miR164, and ethylene insensitive 2 previously reported for Arabidopsis. We measured transcription of Ha-NAC01 (the sunflower homolog of ORE1 and Ha-EIN2, along with the levels of miR164, in two leaves from different stem positions, and identified differences in transcription between basal and upper leaves. Interestingly, Ha-NAC01 and Ha-EIN2 transcription profiles showed an earlier up-regulation in upper leaves of plants close to maturity, compared with basal leaves of plants at pre-anthesis stages. These results suggest that the H. annuus TFs characterized in this work could

  10. Identification of candidate genes associated with leaf senescence in cultivated sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Moschen, Sebastian; Bengoa Luoni, Sofia; Paniego, Norma B; Hopp, H Esteban; Dosio, Guillermo A A; Fernandez, Paula; Heinz, Ruth A

    2014-01-01

    Cultivated sunflower (Helianthus annuus L.), an important source of edible vegetable oil, shows rapid onset of senescence, which limits production by reducing photosynthetic capacity under specific growing conditions. Carbon for grain filling depends strongly on light interception by green leaf area, which diminishes during grain filling due to leaf senescence. Transcription factors (TFs) regulate the progression of leaf senescence in plants and have been well explored in model systems, but information for many agronomic crops remains limited. Here, we characterize the expression profiles of a set of putative senescence associated genes (SAGs) identified by a candidate gene approach and sunflower microarray expression studies. We examined a time course of sunflower leaves undergoing natural senescence and used quantitative PCR (qPCR) to measure the expression of 11 candidate genes representing the NAC, WRKY, MYB and NF-Y TF families. In addition, we measured physiological parameters such as chlorophyll, total soluble sugars and nitrogen content. The expression of Ha-NAC01, Ha-NAC03, Ha-NAC04, Ha-NAC05 and Ha-MYB01 TFs increased before the remobilization rate increased and therefore, before the appearance of the first physiological symptoms of senescence, whereas Ha-NAC02 expression decreased. In addition, we also examined the trifurcate feed-forward pathway (involving ORE1, miR164, and ethylene insensitive 2) previously reported for Arabidopsis. We measured transcription of Ha-NAC01 (the sunflower homolog of ORE1) and Ha-EIN2, along with the levels of miR164, in two leaves from different stem positions, and identified differences in transcription between basal and upper leaves. Interestingly, Ha-NAC01 and Ha-EIN2 transcription profiles showed an earlier up-regulation in upper leaves of plants close to maturity, compared with basal leaves of plants at pre-anthesis stages. These results suggest that the H. annuus TFs characterized in this work could play important

  11. Enhancing Advocacy Skills of Teacher Candidates

    Science.gov (United States)

    Holmes, Melissa A.; Herrera, Socorro G.

    2009-01-01

    This case study explores the dynamics of enhancing the capacities of teacher candidates in the Bilingual/Bicultural Education Students Interacting to Obtain Success (BESITOS) recruitment and retention program to advocate for culturally and linguistically diverse (CLD) students. Herrera and Murry's advocacy framework provides the theoretical…

  12. 1998 astronaut candidates tour KSC facilities

    Science.gov (United States)

    1999-01-01

    On the grounds of the Kennedy Space Center, members of the 1998 astronaut candidate class (Group 17) watch as candidate Tracy E. Caldwell (Ph.D.) practices using firefighting equipment during fire training. The class is at KSC for training activities, including a flight awareness program, plus touring the OPF, VAB, SSPF, SSME Processing Facility, launch pads, SLF, Apollo/Saturn V Center, and the crew quarters. The other U.S. candidates in the '98 class are Clayton C. Anderson, Lee J. Archambault, Gregory E. Chamitoff (Ph.D.), Timothy J. Creamer, Christopher J. Ferguson, Michael J. Foreman, Michael E. Fossum, Kenneth T. Ham, Patricia C. Hilliard (M.D.), Gregory C. Johnson, Gregory H. Johnson, Stanley G. Love (Ph.D.), Leland D. Melvin, Barbara R. Morgan, William A. Oefelein, John D. Olivas (Ph.D.), Nicholas J.M. Patrick (Ph.D.), Alan G. Poindexter, Garrett E. Reisman (Ph.D.), Steven R. Swanson, Douglas H. Wheelock, Sunita L. Williams, Neil W. Woodward III, George D. Zamka; and the international candidates are Leopold Eyharts, Paolo Nespoli, Hans Schlegel, Roberto Vittori, Bjarni V. Tryggvason, and Marcos Pontes.

  13. Promoting Team Leadership Skills in Doctoral Candidates

    Science.gov (United States)

    Suleiman, Mahmoud; Whetton, Danny

    2014-01-01

    Doctoral programs can serve as an optimal opportunity for candidates to engage in tasks and activities to transform them and their schools. The paradigm shifts in such preparation involve moving from sitting and getting to making and taking. Most importantly, it requires building leadership skills and styles necessary to bring about desired change…

  14. Candidal Leukoplakia on Patient with Removable Denture

    Directory of Open Access Journals (Sweden)

    Shiril Paskalis

    2013-07-01

    Full Text Available Candida infection is a common problem in patients using removable dentures, with the most frequent type is denture stomatitis. But other type of candidal infection could also happen in these patients, such as candidal leukoplakia. We reported a 61 years old female patient who complained a painful lesion under her lower removable denture. Oral examination revealed white plaque that could not be rubbed over an ulcer on the lingual part of alveolar processes under the lower removable denture plate, and also an erythematous area on palatum durum above the upper full denture. The patient was suspected to have candidal leukoplakia on the lingual part of the mandible and denture stomatitis on the palate area. The treatment consisted of nystatin oral suspension, chlorhexidine solution, multivitamins, along with denture replacement and oral health education. The entire lesion resolved within 2 months therapy. Candidal infection treatment on denture patient needs not only medication or denture replacement, but also patient compliance to achieve maximal result.

  15. Microlensing Binaries with Candidate Brown Dwarf Companions

    DEFF Research Database (Denmark)

    Shin, I.-G; Han, C.; Gould, A.

    2012-01-01

    Brown dwarfs are important objects because they may provide a missing link between stars and planets, two populations that have dramatically different formation histories. In this paper, we present the candidate binaries with brown dwarf companions that are found by analyzing binary microlensing...... with well-covered light curves increases with new-generation searches....

  16. Fuzzy Treatment of Candidate Outliers in Measurements

    Directory of Open Access Journals (Sweden)

    Giampaolo E. D'Errico

    2012-01-01

    Full Text Available Robustness against the possible occurrence of outlying observations is critical to the performance of a measurement process. Open questions relevant to statistical testing for candidate outliers are reviewed. A novel fuzzy logic approach is developed and exemplified in a metrology context. A simulation procedure is presented and discussed by comparing fuzzy versus probabilistic models.

  17. Query by image example: The CANDID approach

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, P.M.; Cannon, M. [Los Alamos National Lab., NM (United States). Computer Research and Applications Group; Hush, D.R. [Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Electrical and Computer Engineering

    1995-02-01

    CANDID (Comparison Algorithm for Navigating Digital Image Databases) was developed to enable content-based retrieval of digital imagery from large databases using a query-by-example methodology. A user provides an example image to the system, and images in the database that are similar to that example are retrieved. The development of CANDID was inspired by the N-gram approach to document fingerprinting, where a ``global signature`` is computed for every document in a database and these signatures are compared to one another to determine the similarity between any two documents. CANDID computes a global signature for every image in a database, where the signature is derived from various image features such as localized texture, shape, or color information. A distance between probability density functions of feature vectors is then used to compare signatures. In this paper, the authors present CANDID and highlight two results from their current research: subtracting a ``background`` signature from every signature in a database in an attempt to improve system performance when using inner-product similarity measures, and visualizing the contribution of individual pixels in the matching process. These ideas are applicable to any histogram-based comparison technique.

  18. Transiently expressed pattern during myogenesis and candidate ...

    Indian Academy of Sciences (India)

    Navya

    useful information about this gene and its candidate miRNAs in goose. Key words: Tmem8C, Myoblast ... proliferation and cell growth by controlling the G(1)- to S-phase transition in the cell cycle, and reducing the hyperplasia of .... architecture retrieval tool of BLAST (http://www.ncbi.nlm.nih.gov/BLAST). SignalP3.0 server.

  19. Shortlisted candidates for Accounts / Admin Assistant

    Indian Academy of Sciences (India)

    user

    Indian Academy of Sciences. Bengaluru. The following shortlisted candidates have been sent call letters for written test to be held on Friday, 29th January 2016 at Academy Office, Sadashivanagar, Bengaluru. ADMINISTRATIVE ASSISTANT. (29 January 2016, 9:30 – 11:00 a.m.). ACCOUNTS ASSISTANT. (29 January 2016 ...

  20. Investigation of previously implicated genetic variants in chronic tic disorders

    DEFF Research Database (Denmark)

    Abdulkadir, Mohamed; Londono, Douglas; Gordon, Derek

    2017-01-01

    with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were...

  1. Genome-wide association analysis reveals genetic loci and candidate genes for feeding behavior and eating efficiency in Duroc boars.

    Directory of Open Access Journals (Sweden)

    Rongrong Ding

    Full Text Available Efficient use of feed resources is a challenge in the pork industry because the largest variability in expenditure is attributed to the cost of fodder. Efficiency of feeding is directly related to feeding behavior. In order to identify genomic regions controlling feeding behavior and eating efficiency traits, 338 Duroc boars were used in this study. The Illumina Porcine SNP60K BeadChip was used for genotyping. Data pertaining to individual daily feed intake (DFI, total daily time spent in feeder (TPD, number of daily visits to feeder (NVD, average duration of each visit (TPV, mean feed intake per visit (FPV, mean feed intake rate (FR, and feed conversion ratio (FCR were collected for these pigs. Despite the limited sample size, the genome-wide association study was acceptable to detect candidate regions association with feeding behavior and eating efficiency traits in pigs. We detected three genome-wide (P < 1.40E-06 and 11 suggestive (P < 2.79E-05 single nucleotide polymorphism (SNP-trait associations. Six SNPs were located in genomic regions where quantitative trait loci (QTLs have previously been reported for feeding behavior and eating efficiency traits in pigs. Five candidate genes (SERPINA3, MYC, LEF1, PITX2, and MAP3K14 with biochemical and physiological roles that were relevant to feeding behavior and eating efficiency were discovered proximal to significant or suggestive markers. Gene ontology analysis indicated that most of the candidate genes were involved in the development of the hypothalamus (GO:0021854, P < 0.0398. Our results provide new insights into the genetic basis of feeding behavior and eating efficiency in pigs. Furthermore, some significant SNPs identified in this study could be incorporated into artificial selection programs for Duroc-related pigs to select for increased feeding efficiency.

  2. The Association Study between Twenty One Polymorphisms in Seven Candidate Genes and Coronary Heart Diseases in Chinese Han Population.

    Directory of Open Access Journals (Sweden)

    Barrak F Alobeidy

    Full Text Available Previous genome-wide association studies (GWAS in multiple populations identified several genetic loci for coronary heart diseases (CHD. Here we utilized a 2-stage candidate gene association strategy in Chinese Han population to shed light on the putative association between several metabolic-related candidate genes and CHD. At the 1(st stage, 190 patients with CHD and 190 controls were genotyped through the MassARRAY platform. At the 2(nd stage, a larger sample including 400 patients and 392 controls was genotyped by the High Resolution Melt (HRM method to confirm or rule out the associations with CHD. MLXIP expression level was quantified by the real time PCR in 65 peripheral blood samples. From the 21 studied single nucleotide polymorphisms (SNPs of seven candidate genes: MLXIPL, MLXIP, MLX, ADIPOR1, VDR, SREBF1 and NR1H3, only one tag SNP rs4758685 (T→C was found to be statistically associated with CHD (P-value = 0.02, Odds ratio (OR of 0.83. After adjustment for the age, sex, lipid levels and diabetes, the association remained significant (P-value = 0.03. After adjustment for the hypertension, P-value became 0.20 although there was a significant difference in the allele distribution between the CHD patients with hypertension and the controls (P-value = 0.04, 406 vs 582. In conclusion, among the 21 tested SNPs, we identified a novel association between rs4758685 of MLXIP gene and CHD. The C allele of common variant rs4758685 interacted with hypertension, and was found to be protective against CHD in both allelic and genotypic models in Chinese Han population.

  3. Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data

    Energy Technology Data Exchange (ETDEWEB)

    Batalha, Natalie M.; /San Jose State U.; Rowe, Jason F.; /NASA, Ames; Bryson, Stephen T.; /NASA, Ames; Barclay, Thomas; /NASA, Ames; Burke, Christopher J.; /NASA, Ames; Caldwell, Douglas A.; /NASA, Ames; Christiansen, Jessie L.; /NASA, Ames; Mullally, Fergal; /NASA, Ames; Thompson, Susan E.; /NASA, Ames; Brown, Timothy M.; /Las Cumbres Observ.; Dupree, Andrea K.; /Harvard-Smithsonian Ctr. Astrophys. /UC, Santa Cruz

    2012-02-01

    New transiting planet candidates are identified in sixteen months (May 2009 - September 2010) of data from the Kepler spacecraft. Nearly five thousand periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1091 viable new planet candidates, bringing the total count up to over 2,300. Improved vetting metrics are employed, contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multiquarter photo-center offsets derived from difference image analysis which identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the new candidates. Ephemerides (transit epoch, T{sub 0}, and orbital period, P) are tabulated as well as the products of light curve modeling: reduced radius (R{sub P}/R{sub {star}}), reduced semi-major axis (d/R{sub {star}}), and impact parameter (b). The largest fractional increases are seen for the smallest planet candidates (197% for candidates smaller than 2R{sub {circle_plus}} compared to 52% for candidates larger than 2R{sub {circle_plus}}) and those at longer orbital periods (123% for candidates outside of 50 day orbits versus 85% for candidates inside of 50 day orbits). The gains are larger than expected from increasing the observing window from thirteen months (Quarter 1 - Quarter 5) to sixteen months (Quarter 1 - Quarter 6). This demonstrates the benefit of continued development of pipeline analysis software. The fraction of all host stars with multiple candidates has grown from 17% to 20%, and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the Habitable Zone are forthcoming if, indeed, such planets are abundant.

  4. Analysis of Sequenced Genomes of Xanthomonas perforans Identifies Candidate Targets for Resistance Breeding in Tomato.

    Science.gov (United States)

    Timilsina, Sujan; Abrahamian, Peter; Potnis, Neha; Minsavage, Gerald V; White, Frank F; Staskawicz, Brian J; Jones, Jeffrey B; Vallad, Gary E; Goss, Erica M

    2016-10-01

    Bacterial disease management is a challenge for modern agriculture due to rapid changes in pathogen populations. Genome sequences for hosts and pathogens provide detailed information that facilitates effector-based breeding strategies. Tomato genotypes have gene-for-gene resistance to the bacterial spot pathogen Xanthomonas perforans. The bacterial spot populations in Florida shifted from tomato race 3 to 4, such that the corresponding tomato resistance gene no longer recognizes the effector protein AvrXv3. Genome sequencing showed variation in effector profiles among race 4 strains collected in 2006 and 2012 and compared with a race 3 strain collected in 1991. We examined variation in putative targets of resistance among Florida strains of X. perforans collected from 1991 to 2006. Consistent with race change, avrXv3 was present in race 3 strains but nonfunctional in race 4 strains due to multiple independent mutations. Effectors xopJ4 and avrBs2 were unchanged in all strains. The effector avrBsT was absent in race 3 strains collected in the 1990s but present in race 3 strains collected in 2006 and nearly all race 4 strains. These changes in effector profiles suggest that xopJ4 and avrBsT are currently the best targets for resistance breeding against bacterial spot in tomato.

  5. Candidate genes for limiting cholestatic intestinal injury identified by gene expression profiling

    OpenAIRE

    Alaish, Samuel M; Timmons, Jennifer; Smith, Alexis; Buzza, Marguerite S; Murphy, Ebony; Zhao, Aiping; Sun, Yezhou; Turner, Douglas J; Shea-Donahue, Terez; Antalis, Toni M; Cross, Alan; Dorsey, Susan G

    2013-01-01

    The lack of bile flow from the liver into the intestine can have devastating complications including hepatic failure, sepsis, and even death. This pathologic condition known as cholestasis can result from etiologies as diverse as total parenteral nutrition (TPN), hepatitis, and pancreatic cancer. The intestinal injury associated with cholestasis has been shown to result in decreased intestinal resistance, increased bacterial translocation, and increased endotoxemia. Anecdotal clinical evidenc...

  6. Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence

    NARCIS (Netherlands)

    Fernandez-Castillo, N.; Cabana-Dominguez, J.; Soriano, J.; Sanchez-Mora, C.; Roncero, C.; Grau-Lopez, L.; Ros-Cucurull, E.; Daigre, C.; Donkelaar, M.M.J. van; Franke, B.; Casas, M.; Ribases, M.; Cormand, B.

    2015-01-01

    Cocaine reward and reinforcing effects are mediated mainly by dopaminergic neurotransmission. In this study, we aimed at evaluating gene expression changes induced by acute cocaine exposure on SH-SY5Y-differentiated cells, which have been widely used as a dopaminergic neuronal model. Expression

  7. An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates.

    Science.gov (United States)

    Hawley, Robert G; Chen, Yuzhong; Riz, Irene; Zeng, Chen

    2012-05-04

    In this study, we utilized an integrated bioinformatics and computational biology approach in search of new BH3-only proteins belonging to the BCL2 family of apoptotic regulators. The BH3 (BCL2 homology 3) domain mediates specific binding interactions among various BCL2 family members. It is composed of an amphipathic α-helical region of approximately 13 residues that has only a few amino acids that are highly conserved across all members. Using a generalized motif, we performed a genome-wide search for novel BH3-containing proteins in the NCBI Consensus Coding Sequence (CCDS) database. In addition to known pro-apoptotic BH3-only proteins, 197 proteins were recovered that satisfied the search criteria. These were categorized according to α-helical content and predictive binding to BCL-xL (encoded by BCL2L1) and MCL-1, two representative anti-apoptotic BCL2 family members, using position-specific scoring matrix models. Notably, the list is enriched for proteins associated with autophagy as well as a broad spectrum of cellular stress responses such as endoplasmic reticulum stress, oxidative stress, antiviral defense, and the DNA damage response. Several potential novel BH3-containing proteins are highlighted. In particular, the analysis strongly suggests that the apoptosis inhibitor and DNA damage response regulator, AVEN, which was originally isolated as a BCL-xL-interacting protein, is a functional BH3-only protein representing a distinct subclass of BCL2 family members.

  8. Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney

    NARCIS (Netherlands)

    Westland, R.; Verbitsky, M.; Vukojevic, K.; Perry, B.J.; Fasel, D.A.; Zwijnenburg, P.J.; Bokenkamp, A.; Gille, J.J.P.; Saraga-Babic, M.; Ghiggeri, G.M.; D'Agati, V.D.; Schreuder, M.F.; Gharavi, A.G.; Wijk, J.A. van; Sanna-Cherchi, S.

    2015-01-01

    Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic

  9. In silico analysis for identifying potential vaccine candidates against Staphylococcus aureus

    OpenAIRE

    Delfani, Somayeh; Imani Fooladi, Abbas Ali; Mobarez, Ashraf Mohabati; Emaneini, Mohammad; Amani, Jafar; Sedighian, Hamid

    2015-01-01

    Purpose Staphylococcus aureus is one of the most important causes of nosocomial and community-acquired infections. The increasing incidence of multiple antibiotic-resistant S. aureus strains and the emergence of vancomycin resistant S. aureus strains have placed renewed interest on alternative means of prevention and control of infection. S. aureus produces a variety of virulence factors, so a multi-subunit vaccine will be more successful for preventing S. aureus infections than a mono-subuni...

  10. Comparative Transcriptome Analysis Identifies Candidate Genes Related to Skin Color Differentiation in Red Tilapia

    OpenAIRE

    Zhu, Wenbin; Wang, Lanmei; Dong, Zaijie; Chen, Xingting; Song, Feibiao; Liu, Nian; Yang, Hui; Fu, Jianjun

    2016-01-01

    Red tilapia is becoming more popular for aquaculture production in China in recent years. However, the pigmentation differentiation in genetic breeding is the main problem limiting its development of commercial red tilapia culture and the genetic basis of skin color variation is still unknown. In this study, we conducted Illumina sequencing of transcriptome on three color variety red tilapia. A total of 224,895,758 reads were generated, resulting in 160,762 assembled contigs that were used as...

  11. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

    NARCIS (Netherlands)

    Yuen, Ryan K C; Merico, Daniele; Bookman, Matt; Howe, Jennifer L.; Thiruvahindrapuram, Bhooma; Patel, Rohan V.; Whitney, Joe; Deflaux, Nicole; Bingham, Jonathan; Wang, Zhuozhi; Pellecchia, Giovanna; Buchanan, Janet A.; Walker, Susan; Marshall, Christian R.; Uddin, Mohammed; Zarrei, Mehdi; Deneault, Eric; D'Abate, Lia; Chan, Ada J S; Koyanagi, Stephanie; Paton, Tara; Pereira, Sergio L.; Hoang, Ny; Engchuan, Worrawat; Higginbotham, Edward J.; Ho, Karen; Lamoureux, Sylvia; Li, Weili; MacDonald, Jeffrey R.; Nalpathamkalam, Thomas; Sung, Wilson W L; Tsoi, Fiona J.; Wei, John; Xu, Lizhen; Tasse, Anne Marie; Kirby, Emily; Van Etten, William; Twigger, Simon; Roberts, Wendy; Drmic, Irene; Jilderda, Sanne; Modi, Bonnie Mackinnon; Kellam, Barbara; Szego, Michael; Cytrynbaum, Cheryl; Weksberg, Rosanna; Zwaigenbaum, Lonnie; Woodbury-Smith, Marc; Brian, Jessica; Senman, Lili; Iaboni, Alana; Doyle-Thomas, Krissy; Thompson, Ann; Chrysler, Christina; Leef, Jonathan; Savion-Lemieux, Tal; Smith, Isabel M.; Liu, Xudong; Nicolson, Rob; Seifer, Vicki; Fedele, Angie; Cook, Edwin H.; Dager, Stephen; Estes, Annette; Gallagher, Louise; Malow, Beth A.; Parr, Jeremy R.; Spence, Sarah J.; Vorstman, Jacob; Frey, Brendan J.; Robinson, James T.; Strug, Lisa J.; Fernandez, Bridget A.; Elsabbagh, Mayada; Carter, Melissa T.; Hallmayer, Joachim; Knoppers, Bartha M.; Anagnostou, Evdokia; Szatmari, Peter; Ring, Robert H.; Glazer, David; Pletcher, Mathew T.; Scherer, Stephen W.

    2017-01-01

    We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information,

  12. Effective Drug Delivery in Diffuse Intrinsic Pontine Glioma: A Theoretical Model to Identify Potential Candidates

    Directory of Open Access Journals (Sweden)

    Fatma E. El-Khouly

    2017-10-01

    Full Text Available Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG, patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB. We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED may increase their therapeutic potential. Physicochemical properties (lipophilicity, molecular weight, and charge in physiological environment of anticancer drugs historically and currently administered to DIPG patients, that affect passive diffusion over the BBB, were included in the model. Subsequently, the likelihood of BBB passage of these drugs was ascertained, as well as their potential for intratumoral administration via CED. As only non-molecularly charged, lipophilic, and relatively small sized drugs are likely to passively diffuse through the BBB, out of 51 drugs modeled, only 8 (15%—carmustine, lomustine, erlotinib, vismodegib, lenalomide, thalidomide, vorinostat, and mebendazole—are theoretically qualified for systemic administration in DIPG. Local administration via CED might create more therapeutic options, excluding only positively charged drugs and drugs that are either prodrugs and/or only available as oral formulation. A wide variety of drugs have been administered systemically to DIPG patients. Our model shows that only few are likely to penetrate the BBB via passive diffusion, which may partly explain the lack of efficacy. Drug distribution via CED is less dependent on physicochemical properties and may increase the therapeutic options for DIPG.

  13. Effective Drug Delivery in Diffuse Intrinsic Pontine Glioma : A Theoretical Model to Identify Potential Candidates

    NARCIS (Netherlands)

    El-Khouly, Fatma E; van Vuurden, Dannis G; Stroink, Thom; Hulleman, Esther; Kaspers, Gertjan J L; Hendrikse, N Harry; Veldhuijzen van Zanten, Sophie E M

    2017-01-01

    Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG), patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB). We aim to develop a theoretical model including

  14. Models of self-peptide sampling by developing T cells identify candidate mechanisms of thymic selection.

    Directory of Open Access Journals (Sweden)

    Iren Bains

    Full Text Available Conventional and regulatory T cells develop in the thymus where they are exposed to samples of self-peptide MHC (pMHC ligands. This probabilistic process selects for cells within a range of responsiveness that allows the detection of foreign antigen without excessive responses to self. Regulatory T cells are thought to lie at the higher end of the spectrum of acceptable self-reactivity and play a crucial role in the control of autoimmunity and tolerance to innocuous antigens. While many studies have elucidated key elements influencing lineage commitment, we still lack a full understanding of how thymocytes integrate signals obtained by sampling self-peptides to make fate decisions. To address this problem, we apply stochastic models of signal integration by T cells to data from a study quantifying the development of the two lineages using controllable levels of agonist peptide in the thymus. We find two models are able to explain the observations; one in which T cells continually re-assess fate decisions on the basis of multiple summed proximal signals from TCR-pMHC interactions; and another in which TCR sensitivity is modulated over time, such that contact with the same pMHC ligand may lead to divergent outcomes at different stages of development. Neither model requires that T(conv and T(reg are differentially susceptible to deletion or that the two lineages need qualitatively different signals for development, as have been proposed. We find additional support for the variable-sensitivity model, which is able to explain apparently paradoxical observations regarding the effect of partial and strong agonists on T(conv and T(reg development.

  15. Survey of Candidate Genes for Maize Resistance to Infection by Aspergillus flavus and/or Aflatoxin Contamination

    Science.gov (United States)

    Hawkins, Leigh K.; Tang, Juliet D.; Tomashek, John; Alves Oliveira, Dafne; Ogunola, Oluwaseun F.; Smith, J. Spencer; Williams, W. Paul

    2018-01-01

    Many projects have identified candidate genes for resistance to aflatoxin accumulation or Aspergillus flavus infection and growth in maize using genetic mapping, genomics, transcriptomics and/or proteomics studies. However, only a small percentage of these candidates have been validated in field conditions, and their relative contribution to resistance, if any, is unknown. This study presents a consolidated list of candidate genes identified in past studies or in-house studies, with descriptive data including genetic location, gene annotation, known protein identifiers, and associated pathway information, if known. A candidate gene pipeline to test the phenotypic effect of any maize DNA sequence on aflatoxin accumulation resistance was used in this study to determine any measurable effect on polymorphisms within or linked to the candidate gene sequences, and the results are published here. PMID:29385107

  16. VLT multi-epoch radial velocity survey toward NGC 6253. Analysis of three transiting planetary candidates

    Science.gov (United States)

    Montalto, M.; Villanova, S.; Koppenhoefer, J.; Piotto, G.; Desidera, S.; de Marchi, F.; Poretti, E.; Bedin, L. R.; Saviane, I.

    2011-11-01

    Context. One of the most metal-rich open cluster of the Galaxy, NGC 6253 is a target of special interest in the search for extrasolar planets, the study of stellar populations, and the chemical/dynamical evolution of the Galactic disk. Aims: We present the results of two photometric campaigns and a VLT multi-epoch radial velocity survey toward the open cluster NGC 6253. We complement our analysis with photometric, proper motion, and radial velocity data available from previous studies of this cluster, and analyze three planetary candidates found in the field of NGC 6253. Methods: We derived homogeneous radial velocity measurements for stars located at the turn-off, sub-giant, red-giant branch, red-clump, and blue straggler regions of the cluster. We also analyzed a comparison sample of surrounding field stars. Spectra were obtained with the UVES and GIRAFFE spectrographs at the VLT during three epochs in August 2008. Results: The three UVES measurements acquired for our brightest transiting candidate (V = 15.26) are all consistent within their errors (200 m/s), but were acquired at very similar orbital phases. The mean radial velocity of this object is not consistent with the cluster recession velocity, which rules out cluster membership except in the case of a binary system. This star is worth further analysis with high-precision spectroscopy. For our faintest candidate (V = 18.247), we were able to exclude the observed transits being caused by a close-by stellar companion, but more precise measurements will be needed to derive an orbital fit and to study other possible scenarios. For the remaining candidate, no measurements were acquired probably because of bad fiber positioning. The mean radial velocity of the cluster is (overline{RV_cl±overline{σ_cl})=(-29.11±0.85)} km s-1. Using both radial velocities and proper motions, we identified 35 cluster members. Our results are in good agreement with past radial velocity and photometric measurements. Furthermore

  17. Teacher Candidates' Learning Strategies and Academic Self-Efficacy Levels: Is There a Relation between the Two?

    Science.gov (United States)

    Akçaoglu, Mustafa Öztürk

    2016-01-01

    The current study aimed to identify teacher candidates' learning strategies and academic self-efficacy levels. Furthermore, the correlations between these variables and gender and departments were looked into. The study was mainly descriptive and correlational. The sample of the study consisted of 256 teacher candidates enrolled at a faculty of…

  18. Validation of candidate genes