Sample records for multiple markers analyzed

  1. Multiple Brain Markers are Linked to Age-Related Variation in Cognition

    PubMed Central

    Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

    2016-01-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

  2. Versican and its associated molecules: potential diagnostic markers for multiple myeloma.

    PubMed

    Gupta, Nidhi; Khan, Rehan; Kumar, Raman; Kumar, Lalit; Sharma, Alpana

    2015-03-10

    Multiple myeloma (MM) represents a malignancy of B-cells characterized by proliferation of malignant plasma cells in the bone marrow (BM). Versican (VCAN), an extracellular matrix (ECM) protein, appears to be involved in multiple processes in several cancers. Identifying optimum diagnostic markers and delineating its association with disease severity might be important for controlling MM. Expression of VCAN and its associated molecules (β-catenin, β1 integrin and FAK) were investigated in 60 subjects to evaluate their usefulness as diagnostic marker. Circulatory and molecular levels of above molecules were analyzed in their BM and Blood using ELISA, Q-PCR and western blotting along with their ROC curve analysis. Circulatory levels of VCAN, β-catenin and FAK were significantly higher in patients with varying significance in each stage. β-Catenin and FAK intracellular levels were significantly elevated in patients. mRNA levels of all molecules were significantly higher in BMMNCs while VCAN and β-catenin also showed increase in PBMCs. Upregulation of these molecules was also observed at protein level. ROC curve analysis for VCAN showed absolute combination of sensitivity and specificity for diagnosis in serum. Significant elevation of VCAN and its associated molecules imply their role in MM. Optimal sensitivity and specificity of VCAN might utilize its importance as potential marker for active disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Multiple capillary biochemical analyzer

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1995-08-08

    A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibers to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands. 21 figs.

  4. Multiple capillary biochemical analyzer

    DOEpatents

    Dovichi, Norman J.; Zhang, Jian Z.

    1995-01-01

    A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibres to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands.

  5. [Application of Multiple Genetic Markers in a Case of Determination of Half Sibling].

    PubMed

    Yang, Xue; Shi, Mei-sen; Yuan, Li; Lu, Di

    2016-02-01

    A case of half sibling was determined with multiple genetic markers, which could be potentially applied for determination of half sibling relationship from same father. Half sibling relationship was detected by 39 autosomal STR genetic markers, 23 Y-chromosomal STR genetic markers and 12 X -chromosomal STR genetic markers among ZHAO -1, ZHAO -2, ZHAO -3, ZHAO -4, and ZHAO-5. According to autosomal STR, Y-STR and X-STR genotyping results, it was determined that ZHAO-4 (alleged half sibling) was unrelated with ZHAO-1 and ZHAO-2; however, ZHAO-3 (alleged half sibling), ZHAO-5 (alleged half sibling) shared same genetic profile with ZHAO-1, and ZHAO-2 from same father. It is reliable to use multiple genetic markers and family gene reconstruction to determine half sibling relationship from same father, but it is difficult to determination by calculating half sibling index with ITO and discriminant functions.

  6. Multiple-clone infections of Plasmodium vivax: definition of a panel of markers for molecular epidemiology.

    PubMed

    de Souza, Aracele M; de Araújo, Flávia C F; Fontes, Cor J F; Carvalho, Luzia H; de Brito, Cristiana F A; de Sousa, Taís N

    2015-08-25

    Plasmodium vivax infections commonly contain multiple genetically distinct parasite clones. The detection of multiple-clone infections depends on several factors, such as the accuracy of the genotyping method, and the type and number of the molecular markers analysed. Characterizing the multiplicity of infection has broad implications that range from population genetic studies of the parasite to malaria treatment and control. This study compared and evaluated the efficiency of neutral and non-neutral markers that are widely used in studies of molecular epidemiology to detect the multiplicity of P. vivax infection. The performance of six markers was evaluated using 11 mixtures of DNA with well-defined proportions of two different parasite genotypes for each marker. These mixtures were generated by mixing cloned PCR products or patient-derived genomic DNA. In addition, 51 samples of natural infections from the Brazil were genotyped for all markers. The PCR-capillary electrophoresis-based method was used to permit direct comparisons among the markers. The criteria for differentiating minor peaks from artifacts were also evaluated. The analysis of DNA mixtures showed that the tandem repeat MN21 and the polymorphic blocks 2 (msp1B2) and 10 (msp1B10) of merozoite surface protein-1 allowed for the estimation of the expected ratio of both alleles in the majority of preparations. Nevertheless, msp1B2 was not able to detect the majority of multiple-clone infections in field samples; it identified only 6 % of these infections. The merozoite surface protein-3 alpha and microsatellites (PvMS6 and PvMS7) did not accurately estimate the relative clonal proportions in artificial mixtures, but the microsatellites performed well in detecting natural multiple-clone infections. Notably, the use of a less stringent criterion to score rare alleles significantly increased the sensitivity of the detection of multi-clonal infections. Depending on the type of marker used, a considerable

  7. Machine-Learned Data Structures of Lipid Marker Serum Concentrations in Multiple Sclerosis Patients Differ from Those in Healthy Subjects.

    PubMed

    Lötsch, Jörn; Thrun, Michael; Lerch, Florian; Brunkhorst, Robert; Schiffmann, Susanne; Thomas, Dominique; Tegder, Irmgard; Geisslinger, Gerd; Ultsch, Alfred

    2017-06-07

    Lipid metabolism has been suggested to be a major pathophysiological mechanism of multiple sclerosis (MS). With the increasing knowledge about lipid signaling, acquired data become increasingly complex making bioinformatics necessary in lipid research. We used unsupervised machine-learning to analyze lipid marker serum concentrations, pursuing the hypothesis that for the most relevant markers the emerging data structures will coincide with the diagnosis of MS. Machine learning was implemented as emergent self-organizing feature maps (ESOM) combined with the U*-matrix visualization technique. The data space consisted of serum concentrations of three main classes of lipid markers comprising eicosanoids ( d = 11 markers), ceramides ( d = 10), and lyosophosphatidic acids ( d = 6). They were analyzed in cohorts of MS patients ( n = 102) and healthy subjects ( n = 301). Clear data structures in the high-dimensional data space were observed in eicosanoid and ceramides serum concentrations whereas no clear structure could be found in lysophosphatidic acid concentrations. With ceramide concentrations, the structures that had emerged from unsupervised machine-learning almost completely overlapped with the known grouping of MS patients versus healthy subjects. This was only partly provided by eicosanoid serum concentrations. Thus, unsupervised machine-learning identified distinct data structures of bioactive lipid serum concentrations. These structures could be superimposed with the known grouping of MS patients versus healthy subjects, which was almost completely possible with ceramides. Therefore, based on the present analysis, ceramides are first-line candidates for further exploration as drug-gable targets or biomarkers in MS.

  8. Machine-Learned Data Structures of Lipid Marker Serum Concentrations in Multiple Sclerosis Patients Differ from Those in Healthy Subjects

    PubMed Central

    Lötsch, Jörn; Thrun, Michael; Lerch, Florian; Brunkhorst, Robert; Schiffmann, Susanne; Thomas, Dominique; Tegder, Irmgard; Geisslinger, Gerd; Ultsch, Alfred

    2017-01-01

    Lipid signaling has been suggested to be a major pathophysiological mechanism of multiple sclerosis (MS). With the increasing knowledge about lipid signaling, acquired data become increasingly complex making bioinformatics necessary in lipid research. We used unsupervised machine-learning to analyze lipid marker serum concentrations, pursuing the hypothesis that for the most relevant markers the emerging data structures will coincide with the diagnosis of MS. Machine learning was implemented as emergent self-organizing feature maps (ESOM) combined with the U*-matrix visualization technique. The data space consisted of serum concentrations of three main classes of lipid markers comprising eicosanoids (d = 11 markers), ceramides (d = 10), and lyosophosphatidic acids (d = 6). They were analyzed in cohorts of MS patients (n = 102) and healthy subjects (n = 301). Clear data structures in the high-dimensional data space were observed in eicosanoid and ceramides serum concentrations whereas no clear structure could be found in lysophosphatidic acid concentrations. With ceramide concentrations, the structures that had emerged from unsupervised machine-learning almost completely overlapped with the known grouping of MS patients versus healthy subjects. This was only partly provided by eicosanoid serum concentrations. Thus, unsupervised machine-learning identified distinct data structures of bioactive lipid serum concentrations. These structures could be superimposed with the known grouping of MS patients versus healthy subjects, which was almost completely possible with ceramides. Therefore, based on the present analysis, ceramides are first-line candidates for further exploration as drug-gable targets or biomarkers in MS. PMID:28590455

  9. A basket two-part model to analyze medical expenditure on interdependent multiple sectors.

    PubMed

    Sugawara, Shinya; Wu, Tianyi; Yamanishi, Kenji

    2018-05-01

    This study proposes a novel statistical methodology to analyze expenditure on multiple medical sectors using consumer data. Conventionally, medical expenditure has been analyzed by two-part models, which separately consider purchase decision and amount of expenditure. We extend the traditional two-part models by adding the step of basket analysis for dimension reduction. This new step enables us to analyze complicated interdependence between multiple sectors without an identification problem. As an empirical application for the proposed method, we analyze data of 13 medical sectors from the Medical Expenditure Panel Survey. In comparison with the results of previous studies that analyzed the multiple sector independently, our method provides more detailed implications of the impacts of individual socioeconomic status on the composition of joint purchases from multiple medical sectors; our method has a better prediction performance.

  10. Multiple marker screening test: identification of fetal cystic hygroma, hydrops, and sex chromosome aneuploidy.

    PubMed

    Wenstrom, K D; Boots, L R; Cosper, P C

    1996-01-01

    The goal of this study was to determine if the multiple marker screening test (maternal serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotrophin, and maternal age) detects fetal Turner syndrome or just cystic hygroma/hydrops. Multiple marker screening tests from 4 groups were compared: 1) Turner syndrome with hydrops/ hygroma group (n = 10) = fetuses with cystic hygroma/hydrops and a 45X karyotype, 2) Turner syndrome without hydrops/hygroma (n = 9) = sonographically unremarkable fetal Turner syndrome or Turner mosaic, 3) hydrops group (n = 8) = all cases of fetal cystic hygroma/hydrops excluding Turner syndrome, 4) sex chromosome aneuploidy group (n = 16) = other sonographically normal fetal sex chromosome aneuploidies. Positive screening tests (Down syndrome risk > or = 1:190 or MSAFP > or = 2.5 MOM) were found in 60% (6/10) of the Turner syndrome with hydrops/hygroma group, but only 11% (1/9) of the Turner syndrome without hydrops/hygroma group (P = .04). The incidence of positive screening tests in the Hydrops group was 75% (6/8), while it was only 12.5% (2/16) in the other sex chromosome aneuploidy group. We conclude that the multiple marker screening test identifies fetuses with cystic hygroma/hydrops, and may do so independently of the etiology of the hydrops.

  11. FASMA: a service to format and analyze sequences in multiple alignments.

    PubMed

    Costantini, Susan; Colonna, Giovanni; Facchiano, Angelo M

    2007-12-01

    Multiple sequence alignments are successfully applied in many studies for under- standing the structural and functional relations among single nucleic acids and protein sequences as well as whole families. Because of the rapid growth of sequence databases, multiple sequence alignments can often be very large and difficult to visualize and analyze. We offer a new service aimed to visualize and analyze the multiple alignments obtained with different external algorithms, with new features useful for the comparison of the aligned sequences as well as for the creation of a final image of the alignment. The service is named FASMA and is available at http://bioinformatica.isa.cnr.it/FASMA/.

  12. Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays.

    PubMed

    Gao, Wanlei; Wang, Wentao; Yao, Shihua; Wu, Shan; Zhang, Honglian; Zhang, Jishen; Jing, Fengxiang; Mao, Hongju; Jin, Qinghui; Cong, Hui; Jia, Chunping; Zhang, Guojun; Zhao, Jianlong

    2017-03-15

    Assay of multiple serum tumor markers such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), and neuron specific enolase (NSE), is important for the early diagnosis of lung cancer. Dickkopf-1 (DKK1), a novel serological and histochemical biomarker, was recently reported to be preferentially expressed in lung cancer. Four target proteins were sandwiched by capture antibodies attached to microarrays and detection antibodies carried on modified gold nanoparticles. Optical signals generated by the sandwich structures were amplified by gold deposition with HAuCl 4 and H 2 O 2 , and were observable by microscopy or the naked eye. The four tumor markers were subsequently measured in 106 lung cancer patients and 42 healthy persons. The assay was capable of detecting multiple biomarkers in serum sample at concentration of <1 ng mL -1 in 1 h. Combined detection of the four tumor markers highly improved the sensitivity (to 87.74%) for diagnosis of lung cancer compared with sensitivity of single markers. A rapid, highly sensitive co-detection method for multiple biomarkers based on gold nanoparticles and microarrays was developed. In clinical use, it would be expected to improve the early diagnosis of lung cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Rapid and Accurate Multiple Testing Correction and Power Estimation for Millions of Correlated Markers

    PubMed Central

    Han, Buhm; Kang, Hyun Min; Eskin, Eleazar

    2009-01-01

    With the development of high-throughput sequencing and genotyping technologies, the number of markers collected in genetic association studies is growing rapidly, increasing the importance of methods for correcting for multiple hypothesis testing. The permutation test is widely considered the gold standard for accurate multiple testing correction, but it is often computationally impractical for these large datasets. Recently, several studies proposed efficient alternative approaches to the permutation test based on the multivariate normal distribution (MVN). However, they cannot accurately correct for multiple testing in genome-wide association studies for two reasons. First, these methods require partitioning of the genome into many disjoint blocks and ignore all correlations between markers from different blocks. Second, the true null distribution of the test statistic often fails to follow the asymptotic distribution at the tails of the distribution. We propose an accurate and efficient method for multiple testing correction in genome-wide association studies—SLIDE. Our method accounts for all correlation within a sliding window and corrects for the departure of the true null distribution of the statistic from the asymptotic distribution. In simulations using the Wellcome Trust Case Control Consortium data, the error rate of SLIDE's corrected p-values is more than 20 times smaller than the error rate of the previous MVN-based methods' corrected p-values, while SLIDE is orders of magnitude faster than the permutation test and other competing methods. We also extend the MVN framework to the problem of estimating the statistical power of an association study with correlated markers and propose an efficient and accurate power estimation method SLIP. SLIP and SLIDE are available at http://slide.cs.ucla.edu. PMID:19381255

  14. Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers.

    PubMed

    Genser, Bernd; Fischer, Joachim E; Figueiredo, Camila A; Alcântara-Neves, Neuza; Barreto, Mauricio L; Cooper, Philip J; Amorim, Leila D; Saemann, Marcus D; Weichhart, Thomas; Rodrigues, Laura C

    2016-05-20

    Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated. We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. The proposed analytical approach may be especially useful to quantify complex immune

  15. Cerebrospinal fluid inflammatory markers in patients with multiple sclerosis: a pilot study.

    PubMed

    Matejčíková, Z; Mareš, J; Přikrylová Vranová, H; Klosová, J; Sládková, V; Doláková, J; Zapletalová, J; Kaňovský, P

    2015-02-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Autoimmune inflammation is common in the early stages of MS. This stage is followed by the neurodegenerative process. The result of these changes is axon and myelin breakdown. Although MS is according to McDonald's revised diagnostic criteria primarily a clinical diagnosis, paraclinical investigation methods are an important part in the diagnosis of MS. In common practice, magnetic resonance imaging of the brain and spinal cord, examination of cerebrospinal fluid (CSF) and examination of visual evoked potentials are used. There are an increasing number of studies dealing with biomarkers in CSF and their role in the diagnosis and treatment of MS. We hypothesized that the levels of some markers could be changed in MS in comparison with controls. We studied five inflammatory markers [interleukin-6 (IL-6), interleukin-8, interleukin-10 (IL-10), beta-2-microglobulin, orosomucoid]. CSF and serum levels of inflammatory markers were assessed in 38 patients with newly diagnosed MS meeting McDonald's revised diagnostic criteria and in 28 subjects as a control group (CG). Levels of beta-2-microglobulin and interleukin-8 in CSF were found to be significantly higher in MS patients in comparison to CG (p < 0.001 resp. p = 0.007). No differences in other CSF markers (IL-6, IL-10 and orosomucoid) and serum levels of all markers between both groups were found. The levels of two studied inflammatory markers were found to be increased at the time of first clinical symptoms of MS. Research on the role of inflammatory and neurodegenerative markers in MS should continue.

  16. Surrogate endpoints in clinical trials of chronic kidney disease progression: moving from single to multiple risk marker response scores.

    PubMed

    Schievink, Bauke; Mol, Peter G M; Lambers Heerspink, Hiddo J

    2015-11-01

    There is increased interest in developing surrogate endpoints for clinical trials of chronic kidney disease progression, as the established clinically meaningful endpoint end-stage renal disease requires large and lengthy trials to assess drug efficacy. We describe recent developments in the search for novel surrogate endpoints. Declines in estimated glomerular filtration rate (eGFR) of 30% or 40% and albuminuria have been proposed as surrogates for end-stage renal disease. However, changes in eGFR or albuminuria may not be valid under all circumstances as drugs always have effects on multiple renal risk markers. Changes in each of these other 'off-target' risk markers can alter renal risk (either beneficially or adversely), and can thereby confound the relationship between surrogates that are based on single risk markers and renal outcome. Risk algorithms that integrate the short-term drug effects on multiple risk markers to predict drug effects on hard renal outcomes may therefore be more accurate. The validity of these risk algorithms is currently investigated. Given that drugs affect multiple renal risk markers, risk scores that integrate these effects are a promising alternative to using eGFR decline or albuminuria. Proper validation is required before these risk scores can be implemented.

  17. Integrating Multiple Data Sources for Combinatorial Marker Discovery: A Study in Tumorigenesis.

    PubMed

    Bandyopadhyay, Sanghamitra; Mallik, Saurav

    2018-01-01

    Identification of combinatorial markers from multiple data sources is a challenging task in bioinformatics. Here, we propose a novel computational framework for identifying significant combinatorial markers ( s) using both gene expression and methylation data. The gene expression and methylation data are integrated into a single continuous data as well as a (post-discretized) boolean data based on their intrinsic (i.e., inverse) relationship. A novel combined score of methylation and expression data (viz., ) is introduced which is computed on the integrated continuous data for identifying initial non-redundant set of genes. Thereafter, (maximal) frequent closed homogeneous genesets are identified using a well-known biclustering algorithm applied on the integrated boolean data of the determined non-redundant set of genes. A novel sample-based weighted support ( ) is then proposed that is consecutively calculated on the integrated boolean data of the determined non-redundant set of genes in order to identify the non-redundant significant genesets. The top few resulting genesets are identified as potential s. Since our proposed method generates a smaller number of significant non-redundant genesets than those by other popular methods, the method is much faster than the others. Application of the proposed technique on an expression and a methylation data for Uterine tumor or Prostate Carcinoma produces a set of significant combination of markers. We expect that such a combination of markers will produce lower false positives than individual markers.

  18. A discrimination index for selecting markers of tumor growth dynamic across multiple cancer studies with a cure fraction.

    PubMed

    Rouam, Sigrid; Broët, Philippe

    2013-08-01

    To identify genomic markers with consistent effect on tumor dynamics across multiple cancer series, discrimination indices based on proportional hazards models can be used since they do not depend heavily on the sample size. However, the underlying assumption of proportionality of the hazards does not always hold, especially when the studied population is a mixture of cured and uncured patients, like in early-stage cancers. We propose a novel index that quantifies the capability of a genomic marker to separate uncured patients, according to their time-to-event outcomes. It allows to identify genomic markers characterizing tumor growth dynamic across multiple studies. Simulation results show that our index performs better than classical indices based on the Cox model. It is neither affected by the sample size nor the cure rate fraction. In a cross-study of early-stage breast cancers, the index allows to select genomic markers with a potential consistent effect on tumor growth dynamics. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

    PubMed Central

    Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

    2016-01-01

    The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

  20. Stereotactic core needle breast biopsy marker migration: An analysis of factors contributing to immediate marker migration.

    PubMed

    Jain, Ashali; Khalid, Maria; Qureshi, Muhammad M; Georgian-Smith, Dianne; Kaplan, Jonah A; Buch, Karen; Grinstaff, Mark W; Hirsch, Ariel E; Hines, Neely L; Anderson, Stephan W; Gallagher, Katherine M; Bates, David D B; Bloch, B Nicolas

    2017-11-01

    To evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors. This retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration. Of the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1-6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration. Multiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration. • Breast biopsy marker migration is documented in 13% of 268 procedures. • Marker migration is affected by physical, biological, and pathological factors. • Breast density, marker shape, needle approach etc. affect migration. • Study demonstrates marker migration prevalence; marker design improvements are needed.

  1. Analyzing Student Confidence in Classroom Voting with Multiple Choice Questions

    ERIC Educational Resources Information Center

    Stewart, Ann; Storm, Christopher; VonEpps, Lahna

    2013-01-01

    The purpose of this paper is to present results of a recent study in which students voted on multiple choice questions in mathematics courses of varying levels. Students used clickers to select the best answer among the choices given; in addition, they were also asked whether they were confident in their answer. In this paper we analyze data…

  2. Multiple large solar lentigos on the upper back as clinical markers of past severe sunburn: a case-control study.

    PubMed

    Derancourt, C; Bourdon-Lanoy, E; Grob, J-J; Guillaume, J-C; Bernard, P; Bastuji-Garin, S

    2007-01-01

    Multiple solar lentigos commonly seen on the upper back and shoulders of adults are classically considered as a sign of photodamage, although epidemiological studies are scarce. To assess whether these lesions are clinical markers of past severe sunburn. A case-control study in two outpatient dermatology clinics in French university hospitals. Past episodes of moderate and severe sunburn were compared between 145 adult patients with multiple solar lentigos on the upper back and 145 matched controls. In multivariate analysis adjusted for potential confounders, recalled episodes of sunburn during childhood, adolescence and adulthood were independently associated with the presence of multiple solar lentigos (adjusted odds ratios, 95% confidence intervals: 2.3 (1.1-5.2) and 28.1 (10.4-75.6) for moderate and severe sunburn, respectively). Multiple solar lentigos on the upper back and shoulders of adults are potential clinical markers of past severe sunburn which may thus be used to identify a population at higher risk of developing cutaneous malignant melanoma.

  3. Analysis of multiple enteric viral targets as sewage markers in coral reefs

    USGS Publications Warehouse

    Lipp, Erin K.; Futch, J. Carrie; Griffin, Dale W.

    2007-01-01

    Water and coral mucus samples were collected from throughout the Florida Keys National Marine Sanctuary and the Dry Tortugas for three years and were analyzed for human enteric viruses (enteroviruses, noroviruses, hepatitis A virus and adenoviruses) as conservative markers of human sewage using molecular methods. Of the 100 coral and water samples collected, 40 contained genetic material from one or more human enteric viruses. DNA-based adenoviruses were detected widely, in 37.8% of samples and at 91% of stations, including ‘pristine’ reefs in the Dry Tortugas; however, the detection rate was ⩽12% for the RNA-based enteroviruses and noroviruses (hepatitis A virus was never detected). The disparity between the prevalence of RNA- and DNA-based viruses suggests the need for additional work to determine the utility of adenovirus as marker of human sewage.

  4. Comparative evaluation of Plateletworks, Multiplate analyzer and Platelet function analyzer-200 in cardiology patients.

    PubMed

    Kim, Jeeyong; Cho, Chi Hyun; Jung, Bo Kyeung; Nam, Jeonghun; Seo, Hong Seog; Shin, Sehyun; Lim, Chae Seung

    2018-04-14

    The objective of this study was to comparatively evaluate three commercial whole-blood platelet function analyzer systems: Platelet Function Analyzer-200 (PFA; Siemens Canada, Mississauga, Ontario, Canada), Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), and Plateletworks Combo-25 kit (PLW; Helena Laboratories, Beaumont, TX, USA). Venipuncture was performed on 160 patients who visited a department of cardiology. Pairwise agreement among the three platelet function assays was assessed using Cohen's kappa coefficient and percent agreement within the reference limit. Kappa values with the same agonists were poor between PFA-collagen (COL; agonist)/adenosine diphosphate (ADP) and MP-ADP (-0.147), PFA-COL/ADP and PLW-ADP (0.089), MP-ADP and PLW-ADP (0.039), PFA-COL/ADP and MP-COL (-0.039), and between PFA-COL/ADP and PLW-COL (-0.067). Nonetheless, kappa values for the same assay principle with a different agonist were slightly higher between PFA-COL/ADP and PFA-COL/EPI (0.352), MP-ADP and MP-COL (0.235), and between PLW-ADP and PLW-COL (0.247). The range of percent agreement values was 38.7% to 73.8%. Therefore, various measurements of platelet function by more than one method were needed to obtain a reliable interpretation of platelet function considering low kappa coefficient and modest percent agreement rates among 3 different platelet function tests.

  5. Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis.

    PubMed

    Yang, Hua; Xia, Bing-Qing; Jiang, Bo; Wang, Guozhen; Yang, Yi-Peng; Chen, Hao; Li, Bing-Sheng; Xu, An-Gao; Huang, Yun-Bo; Wang, Xin-Ying

    2013-08-01

    The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the χ(2) test and Q statistic; subgroup analysis was also conducted. A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation

  6. Analysis of Genome-Wide Association Studies with Multiple Outcomes Using Penalization

    PubMed Central

    Liu, Jin; Huang, Jian; Ma, Shuangge

    2012-01-01

    Genome-wide association studies have been extensively conducted, searching for markers for biologically meaningful outcomes and phenotypes. Penalization methods have been adopted in the analysis of the joint effects of a large number of SNPs (single nucleotide polymorphisms) and marker identification. This study is partly motivated by the analysis of heterogeneous stock mice dataset, in which multiple correlated phenotypes and a large number of SNPs are available. Existing penalization methods designed to analyze a single response variable cannot accommodate the correlation among multiple response variables. With multiple response variables sharing the same set of markers, joint modeling is first employed to accommodate the correlation. The group Lasso approach is adopted to select markers associated with all the outcome variables. An efficient computational algorithm is developed. Simulation study and analysis of the heterogeneous stock mice dataset show that the proposed method can outperform existing penalization methods. PMID:23272092

  7. Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

    PubMed

    Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas

    2018-03-01

    The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

  8. Analyzing the multiple-target-multiple-agent scenario using optimal assignment algorithms

    NASA Astrophysics Data System (ADS)

    Kwok, Kwan S.; Driessen, Brian J.; Phillips, Cynthia A.; Tovey, Craig A.

    1997-09-01

    This work considers the problem of maximum utilization of a set of mobile robots with limited sensor-range capabilities and limited travel distances. The robots are initially in random positions. A set of robots properly guards or covers a region if every point within the region is within the effective sensor range of at least one vehicle. We wish to move the vehicles into surveillance positions so as to guard or cover a region, while minimizing the maximum distance traveled by any vehicle. This problem can be formulated as an assignment problem, in which we must optimally decide which robot to assign to which slot of a desired matrix of grid points. The cost function is the maximum distance traveled by any robot. Assignment problems can be solved very efficiently. Solution times for one hundred robots took only seconds on a silicon graphics crimson workstation. The initial positions of all the robots can be sampled by a central base station and their newly assigned positions communicated back to the robots. Alternatively, the robots can establish their own coordinate system with the origin fixed at one of the robots and orientation determined by the compass bearing of another robot relative to this robot. This paper presents example solutions to the multiple-target-multiple-agent scenario using a matching algorithm. Two separate cases with one hundred agents in each were analyzed using this method. We have found these mobile robot problems to be a very interesting application of network optimization methods, and we expect this to be a fruitful area for future research.

  9. Comparative usefulness of inflammatory markers to indicate bacterial infection-analyzed according to blood culture results and related clinical factors.

    PubMed

    Nishikawa, Hirokazu; Shirano, Michinori; Kasamatsu, Yu; Morimura, Ayumi; Iida, Ko; Kishi, Tomomi; Goto, Tetsushi; Okamoto, Saki; Ehara, Eiji

    2016-01-01

    To assess relationships of inflammatory markers and 2 related clinical factors with blood culture results, we retrospectively investigated inpatients' blood culture and blood chemistry findings that were recorded from January to December 2014 using electronic medical records and analyzed the data of 852 subjects (426 culture-positive and 426 culture-negative). Results suggested that the risk of positive blood culture statistically increased as inflammatory marker levels and the number of related factors increased. Concerning the effectiveness of inflammatory markers, when the outcome definition was also changed for C-reactive protein (CRP), the odds ratio had a similar value, whereas when the outcome definition of blood culture positivity was used for procalcitonin (PCT), the greatest effectiveness of that was detected. Therefore, the current results suggest that PCT is more useful than CRP as an auxiliary indication of bacterial infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Multiple template-based fluoroscopic tracking of lung tumor mass without implanted fiducial markers

    NASA Astrophysics Data System (ADS)

    Cui, Ying; Dy, Jennifer G.; Sharp, Gregory C.; Alexander, Brian; Jiang, Steve B.

    2007-10-01

    Precise lung tumor localization in real time is particularly important for some motion management techniques, such as respiratory gating or beam tracking with a dynamic multi-leaf collimator, due to the reduced clinical tumor volume (CTV) to planning target volume (PTV) margin and/or the escalated dose. There might be large uncertainties in deriving tumor position from external respiratory surrogates. While tracking implanted fiducial markers has sufficient accuracy, this procedure may not be widely accepted due to the risk of pneumothorax. Previously, we have developed a technique to generate gating signals from fluoroscopic images without implanted fiducial markers using a template matching method (Berbeco et al 2005 Phys. Med. Biol. 50 4481-90, Cui et al 2007 Phys. Med. Biol. 52 741-55). In this paper, we present an extension of this method to multiple-template matching for directly tracking the lung tumor mass in fluoroscopy video. The basic idea is as follows: (i) during the patient setup session, a pair of orthogonal fluoroscopic image sequences are taken and processed off-line to generate a set of reference templates that correspond to different breathing phases and tumor positions; (ii) during treatment delivery, fluoroscopic images are continuously acquired and processed; (iii) the similarity between each reference template and the processed incoming image is calculated; (iv) the tumor position in the incoming image is then estimated by combining the tumor centroid coordinates in reference templates with proper weights based on the measured similarities. With different handling of image processing and similarity calculation, two such multiple-template tracking techniques have been developed: one based on motion-enhanced templates and Pearson's correlation score while the other based on eigen templates and mean-squared error. The developed techniques have been tested on six sequences of fluoroscopic images from six lung cancer patients against the reference

  11. Prediction of Response to Sorafenib in Hepatocellular Carcinoma: A Putative Marker Panel by Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS).

    PubMed

    Kim, Hyunsoo; Yu, Su Jong; Yeo, Injun; Cho, Young Youn; Lee, Dong Hyeon; Cho, Yuri; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Sungyoung; Jun, Jongsoo; Park, Taesung; Yoon, Jung-Hwan; Kim, Youngsoo

    2017-07-01

    Sorafenib is the only standard treatment for unresectable hepatocellular carcinoma (HCC), but it provides modest survival benefits over placebo, necessitating predictive biomarkers of the response to sorafenib. Serum samples were obtained from 115 consecutive patients with HCC before sorafenib treatment and analyzed by multiple reaction monitoring-mass spectrometry (MRM-MS) and ELISA to quantify candidate biomarkers. We verified a triple-marker panel to be predictive of the response to sorafenib by MRM-MS, comprising CD5 antigen-like (CD5L), immunoglobulin J (IGJ), and galectin-3-binding protein (LGALS3BP), in HCC patients. This panel was a significant predictor (AUROC > 0.950) of the response to sorafenib treatment, having the best cut-off value (0.4) by multivariate analysis. In the training set, patients who exceeded this cut-off value had significantly better overall survival (median, 21.4 months) than those with lower values (median, 8.6 months; p = 0.001). Further, a value that was lower than this cutoff was an independent predictor of poor overall survival [hazard ratio (HR), 2.728; 95% confidence interval (CI), 1.312-5.672; p = 0.007] and remained an independent predictive factor of rapid progression (HR, 2.631; 95% CI, 1.448-4.780; p = 0.002). When applied to the independent validation set, levels of the cut-off value for triple-marker panel maintained their prognostic value for poor clinical outcomes. On the contrast, the triple-marker panel was not a prognostic factor for patients who were treated with transarterial chemoembolization (TACE). The discriminatory signature of a triple-marker panel provides new insights into targeted proteomic biomarkers for individualized sorafenib therapy. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Generating Multiple Imputations for Matrix Sampling Data Analyzed with Item Response Models.

    ERIC Educational Resources Information Center

    Thomas, Neal; Gan, Nianci

    1997-01-01

    Describes and assesses missing data methods currently used to analyze data from matrix sampling designs implemented by the National Assessment of Educational Progress. Several improved methods are developed, and these models are evaluated using an EM algorithm to obtain maximum likelihood estimates followed by multiple imputation of complete data…

  13. Identification of Single- and Multiple-Class Specific Signature Genes from Gene Expression Profiles by Group Marker Index

    PubMed Central

    Tsai, Yu-Shuen; Aguan, Kripamoy; Pal, Nikhil R.; Chung, I-Fang

    2011-01-01

    Informative genes from microarray data can be used to construct prediction model and investigate biological mechanisms. Differentially expressed genes, the main targets of most gene selection methods, can be classified as single- and multiple-class specific signature genes. Here, we present a novel gene selection algorithm based on a Group Marker Index (GMI), which is intuitive, of low-computational complexity, and efficient in identification of both types of genes. Most gene selection methods identify only single-class specific signature genes and cannot identify multiple-class specific signature genes easily. Our algorithm can detect de novo certain conditions of multiple-class specificity of a gene and makes use of a novel non-parametric indicator to assess the discrimination ability between classes. Our method is effective even when the sample size is small as well as when the class sizes are significantly different. To compare the effectiveness and robustness we formulate an intuitive template-based method and use four well-known datasets. We demonstrate that our algorithm outperforms the template-based method in difficult cases with unbalanced distribution. Moreover, the multiple-class specific genes are good biomarkers and play important roles in biological pathways. Our literature survey supports that the proposed method identifies unique multiple-class specific marker genes (not reported earlier to be related to cancer) in the Central Nervous System data. It also discovers unique biomarkers indicating the intrinsic difference between subtypes of lung cancer. We also associate the pathway information with the multiple-class specific signature genes and cross-reference to published studies. We find that the identified genes participate in the pathways directly involved in cancer development in leukemia data. Our method gives a promising way to find genes that can involve in pathways of multiple diseases and hence opens up the possibility of using an existing

  14. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, Norman J.; Zhang, Jian Z.

    1996-01-01

    A multiple capillary biochemical analyzer for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal to noise ratio.

  15. & Source apportionment of particulate matter in the United States and associations with lung inflammatory Markers

    EPA Science Inventory

    Size-fractionated particulate matter (PM) samples were collected from six U.S. cities and chemically analyzed as part of the Multiple Air Pollutant Study. Particles were administered to cultured lung cells and the production of three different proinflammatory markers was measured...

  16. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1996-10-22

    A multiple capillary biochemical analyzer is disclosed for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal-to-noise ratio. 12 figs.

  17. Genetic Biodiversity of Italian Olives (Olea europaea) Germplasm Analyzed by SSR Markers

    PubMed Central

    Vendramin, Giuseppe Giovanni; Chiappetta, Adriana

    2014-01-01

    The olive is an important fruit species cultivated for oil and table olives in Italy and the Mediterranean basin. The conservation of cultivated plants in ex situ collections is essential for the optimal management and use of their genetic resources. The largest ex situ olive germplasm collection consists of approximately 500 Italian olive varieties and corresponding to 85% of the total Italian olive germplasm is maintained at the Consiglio per la Ricerca e sperimentazione per l'Agricoltura, Centro di Ricerca per l'Olivicoltura e l'Industria Olearia (CRA-OLI), in Italy. In this work, eleven preselected nuclear microsatellite markers were used to assess genetic diversity, population structure, and gene flows with the aim of assembling a core collection. The dendrogram obtained utilizing the unweighted pair group method highlights the presence of homonymy and synonymy in olive tree datasets analyzed in this study. 439 different unique genotype profiles were obtained with this combination of 11 loci nSSR, representing 89.8% of the varieties analyzed. The remaining 10.2% comprises different variety pairs in which both accessions are genetically indistinguishable. Clustering analysis performed using BAPS software detected seven groups in Italian olive germplasm and gene flows were determined among identified clusters. We proposed an Italian core collection of 23 olive varieties capturing all detected alleles at microsatellites. The information collected in this study regarding the CRA-OLI ex situ collection can be used for breeding programs, for germplasm conservation, and for optimizing a strategy for the management of olive gene pools. PMID:24723801

  18. Using Next Generation Sequencing for Multiplexed Trait-Linked Markers in Wheat

    PubMed Central

    Bernardo, Amy; Wang, Shan; St. Amand, Paul; Bai, Guihua

    2015-01-01

    With the advent of next generation sequencing (NGS) technologies, single nucleotide polymorphisms (SNPs) have become the major type of marker for genotyping in many crops. However, the availability of SNP markers for important traits of bread wheat ( Triticum aestivum L.) that can be effectively used in marker-assisted selection (MAS) is still limited and SNP assays for MAS are usually uniplex. A shift from uniplex to multiplex assays will allow the simultaneous analysis of multiple markers and increase MAS efficiency. We designed 33 locus-specific markers from SNP or indel-based marker sequences that linked to 20 different quantitative trait loci (QTL) or genes of agronomic importance in wheat and analyzed the amplicon sequences using an Ion Torrent Proton Sequencer and a custom allele detection pipeline to determine the genotypes of 24 selected germplasm accessions. Among the 33 markers, 27 were successfully multiplexed and 23 had 100% SNP call rates. Results from analysis of "kompetitive allele-specific PCR" (KASP) and sequence tagged site (STS) markers developed from the same loci fully verified the genotype calls of 23 markers. The NGS-based multiplexed assay developed in this study is suitable for rapid and high-throughput screening of SNPs and some indel-based markers in wheat. PMID:26625271

  19. Fingolimod modulates multiple neuroinflammatory markers in a mouse model of Alzheimer's disease.

    PubMed

    Aytan, Nurgul; Choi, Ji-Kyung; Carreras, Isabel; Brinkmann, Volker; Kowall, Neil W; Jenkins, Bruce G; Dedeoglu, Alpaslan

    2016-04-27

    Sphingosine 1-phosphate (SP1) receptors may be attractive targets for modulation of inflammatory processes in neurodegenerative diseases. Recently fingolimod, a functional S1P1 receptor antagonist, was introduced for treatment of multiple sclerosis. We postulated that anti-inflammatory mechanisms of fingolimod might also be protective in Alzheimer's disease (AD). Therefore, we treated a mouse model of AD, the 5xFAD model, with two doses of fingolimod (1 and 5 mg/kg/day) and measured the response of numerous markers of Aβ pathology as well as inflammatory markers and neurochemistry using biochemical, immunohistochemistry and high resolution magic angle spinning magnetic resonance spectroscopy (MRS). In mice at 3 months of age, we found that fingolimod decreased plaque density as well as soluble plus insoluble Aβ measured by ELISA. Fingolimod also decreased GFAP staining and the number of activated microglia. Taurine has been demonstrated to play a role as an endogenous anti-inflammatory molecule. Taurine levels, measured using MRS, showed a very strong inverse correlation with GFAP levels and ELISA measurements of Aβ, but not with plaque density or activated microglia levels. MRS also showed an effect of fingolimod on glutamate levels. Fingolimod at 1 mg/kg/day provided better neuroprotection than 5 mg/kg/day. Together, these data suggest a potential therapeutic role for fingolimod in AD.

  20. Continuous fetal head flexion as a marker for prenatal diagnosis of lethal multiple pterygium syndrome: a case report.

    PubMed

    Hasegawa, Akihiro; Hanaoka, Mieko; Murakoshi, Takeshi

    2017-07-01

    Lethal multiple pterygium syndrome (LMPS) is a fatal hereditary disease associated with abnormalities such as pterygium-induced congenital contractures. Fetal hydrops is present in more than half of all patients with LMPS, and all patients with LMPS are either stillborn or die in the early neonatal period. Ultrasonography findings for the prenatal diagnosis of LMPS include the detection of cutaneous webbing at multiple joints, multiple joint contractures, absent limb movement, and increased nuchal translucency. Here, we describe a patient who was diagnosed as having LMPS due to continuous fetal head flexion, despite the absence of the usual characteristics of the condition, including pterygium at the joints. Thus, continuous fetal head flexion can be a useful marker for prenatally diagnosing LMPS.

  1. Analyzing public inputs to multiple objective decisions on national forests using conjoint analysis

    Treesearch

    Donald F. Dennis

    1998-01-01

    Faced with multiple objectives, national forest managers and planners need a means to solicit and analyze public preferences and values. A conjoint ranking survey was designed to solicit public preferences for various levels of timber harvesting, wildlife habitats, hiking trails, snowmobile use, and off-road-vehicle (ORV) access on the Green Mountain National Forest....

  2. Stability of Markers Used for Real-Time Tumor Tracking After Percutaneous Intrapulmonary Placement

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Voort van Zyp, Noelle C. van der, E-mail: n.vandervoortvanzyp@erasmusmc.nl; Hoogeman, Mischa S.; Water, Steven van de

    2011-11-01

    Purpose: To determine the stability of markers used for real-time tumor tracking after percutaneous intrapulmonary placement. Methods and Materials: A total of 42 patients with 44 lesions, 111 markers, and {>=}2 repeat computed tomography (CT) scans were studied. The tumor on the repeat CT scans was registered with the tumor on the planning CT scan. Next, the three-dimensional marker coordinates were determined on the planning CT scan and repeat CT scans. Marker stability was analyzed by the displacement of the markers and the displacement of the center of mass (COM) of the marker configurations. In addition, we assessed the reliabilitymore » of using the intermarker distance as a check for displacements in the COM of the marker configurations. Results: The median marker displacement was 1.3 mm (range, 0.1-53.6). The marker displacement was >5 mm in 12% of the markers and >10 mm in 5% of the markers. The causes of marker displacement >5 mm included marker migration (2 of 13) and target volume changes (5 of 13). Nonsynchronous tumor and marker movement during breathing might have been responsible for the displacements >5 mm in the other 6 of 13 markers. The median displacement in the COM of the marker configurations was 1.0 mm (range, 0.1-23.3). Displacements in the COM of the marker configurations of {>=}2.0 mm were detected by changes in the intermarker distance of >1.5 mm in 96% of the treatment fractions. Conclusion: The median marker displacement was small (1.3 mm). Nevertheless, displacements >5 mm occurred in 12% of the markers. Therefore, we recommend the implantation of multiple markers because multiple markers will enable a quick and reliable check of marker displacement by determining the change in the intermarker distance. A displacement in the COM of the marker configuration of {>=}2.0 mm was almost always detected (96%) by a change in the distance between the markers of >1.5 mm. This enabled the displaced marker to be disabled, such that tumor

  3. Identification of fecal contamination sources in water using host-associated markers.

    PubMed

    Krentz, Corinne A; Prystajecky, Natalie; Isaac-Renton, Judith

    2013-03-01

    In British Columbia, Canada, drinking water is tested for total coliforms and Escherichia coli, but there is currently no routine follow-up testing to investigate fecal contamination sources in samples that test positive for indicator bacteria. Reliable microbial source tracking (MST) tools to rapidly test water samples for multiple fecal contamination markers simultaneously are currently lacking. The objectives of this study were (i) to develop a qualitative MST tool to identify fecal contamination from different host groups, and (ii) to evaluate the MST tool using water samples with evidence of fecal contamination. Singleplex and multiplex polymerase chain reaction (PCR) were used to test (i) water from polluted sites and (ii) raw and drinking water samples for presence of bacterial genetic markers associated with feces from humans, cattle, seagulls, pigs, chickens, and geese. The multiplex MST assay correctly identified suspected contamination sources in contaminated waterways, demonstrating that this test may have utility for heavily contaminated sites. Most raw and drinking water samples analyzed using singleplex PCR contained at least one host-associated marker. Singleplex PCR was capable of detecting host-associated markers in small sample volumes and is therefore a promising tool to further analyze water samples submitted for routine testing and provide information useful for water quality management.

  4. The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers.

    PubMed

    Schievink, Bauke; de Zeeuw, Dick; Parving, Hans-Henrik; Rossing, Peter; Lambers Heerspink, Hiddo Jan

    2015-10-01

    Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes. Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI). SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, P < 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA-2. In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings. © 2015 The British Pharmacological Society.

  5. Applicability of SCAR markers to food genomics: olive oil traceability.

    PubMed

    Pafundo, Simona; Agrimonti, Caterina; Maestri, Elena; Marmiroli, Nelson

    2007-07-25

    DNA analysis with molecular markers has opened a shortcut toward a genomic comprehension of complex organisms. The availability of micro-DNA extraction methods, coupled with selective amplification of the smallest extracted fragments with molecular markers, could equally bring a breakthrough in food genomics: the identification of original components in food. Amplified fragment length polymorphisms (AFLPs) have been instrumental in plant genomics because they may allow rapid and reliable analysis of multiple and potentially polymorphic sites. Nevertheless, their direct application to the analysis of DNA extracted from food matrixes is complicated by the low quality of DNA extracted: its high degradation and the presence of inhibitors of enzymatic reactions. The conversion of an AFLP fragment to a robust and specific single-locus PCR-based marker, therefore, could extend the use of molecular markers to large-scale analysis of complex agro-food matrixes. In the present study is reported the development of sequence characterized amplified regions (SCARs) starting from AFLP profiles of monovarietal olive oils analyzed on agarose gel; one of these was used to identify differences among 56 olive cultivars. All the developed markers were purposefully amplified in olive oils to apply them to olive oil traceability.

  6. Fingolimod modulates multiple neuroinflammatory markers in a mouse model of Alzheimer’s disease

    PubMed Central

    Aytan, Nurgul; Choi, Ji-Kyung; Carreras, Isabel; Brinkmann, Volker; Kowall, Neil W.; Jenkins, Bruce G.; Dedeoglu, Alpaslan

    2016-01-01

    Sphingosine 1-phosphate (SP1) receptors may be attractive targets for modulation of inflammatory processes in neurodegenerative diseases. Recently fingolimod, a functional S1P1 receptor antagonist, was introduced for treatment of multiple sclerosis. We postulated that anti-inflammatory mechanisms of fingolimod might also be protective in Alzheimer’s disease (AD). Therefore, we treated a mouse model of AD, the 5xFAD model, with two doses of fingolimod (1 and 5 mg/kg/day) and measured the response of numerous markers of Aβ pathology as well as inflammatory markers and neurochemistry using biochemical, immunohistochemistry and high resolution magic angle spinning magnetic resonance spectroscopy (MRS). In mice at 3 months of age, we found that fingolimod decreased plaque density as well as soluble plus insoluble Aβ measured by ELISA. Fingolimod also decreased GFAP staining and the number of activated microglia. Taurine has been demonstrated to play a role as an endogenous anti-inflammatory molecule. Taurine levels, measured using MRS, showed a very strong inverse correlation with GFAP levels and ELISA measurements of Aβ, but not with plaque density or activated microglia levels. MRS also showed an effect of fingolimod on glutamate levels. Fingolimod at 1 mg/kg/day provided better neuroprotection than 5 mg/kg/day. Together, these data suggest a potential therapeutic role for fingolimod in AD. PMID:27117087

  7. Maximization of Markers Linked in Coupling for Tetraploid Potatoes via Monoparental Haploids

    PubMed Central

    Bartkiewicz, Annette M.; Chilla, Friederike; Terefe-Ayana, Diro; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhard; Linde, Marcus; Debener, Thomas

    2018-01-01

    Haploid potato populations derived from a single tetraploid donor constitute an efficient strategy to analyze markers segregating from a single donor genotype. Analysis of marker segregation in populations derived from crosses between polysomic tetraploids is complicated by a maximum of eight segregating alleles, multiple dosages of the markers and problems related to linkage analysis of marker segregation in repulsion. Here, we present data on two monoparental haploid populations generated by prickle pollination of two tetraploid cultivars with Solanum phureja and genotyped with the 12.8 k SolCAP single nucleotide polymorphism (SNP) array. We show that in a population of monoparental haploids, the number of biallelic SNP markers segregating in linkage to loci from the tetraploid donor genotype is much larger than in putative crosses of this genotype to a diverse selection of 125 tetraploid cultivars. Although this strategy is more laborious than conventional breeding, the generation of haploid progeny for efficient marker analysis is straightforward if morphological markers and flow cytometry are utilized to select true haploid progeny. The level of introgressed fragments from S. phureja, the haploid inducer, is very low, supporting its suitability for genetic analysis. Mapping with single-dose markers allowed the analysis of quantitative trait loci (QTL) for four phenotypic traits. PMID:29868076

  8. Multiple reaction monitoring targeted LC-MS analysis of potential cell death marker proteins for increased bioprocess control.

    PubMed

    Albrecht, Simone; Kaisermayer, Christian; Reinhart, David; Ambrose, Monica; Kunert, Renate; Lindeberg, Anna; Bones, Jonathan

    2018-05-01

    The monitoring of protein biomarkers for the early prediction of cell stress and death is a valuable tool for process characterization and efficient biomanufacturing control. A representative set of six proteins, namely GPDH, PRDX1, LGALS1, CFL1, TAGLN2 and MDH, which were identified in a previous CHO-K1 cell death model using discovery LC-MS E was translated into a targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM-MS) platform and verified. The universality of the markers was confirmed in a cell growth model for which three Chinese hamster ovary host cell lines (CHO-K1, CHO-S, CHO-DG44) were grown in batch culture in two different types of basal media. LC-MRM-MS was also applied to spent media (n = 39) from four perfusion biomanufacturing series. Stable isotope-labelled peptide analogues and a stable isotope-labelled monoclonal antibody were used for improved protein quantitation and simultaneous monitoring of the workflow reproducibility. Significant increases in protein concentrations were observed for all viability marker proteins upon increased dead cell numbers and allowed for discrimination of spent media with dead cell densities below and above 1 × 10 6  dead cells/mL which highlights the potential of the selected viability marker proteins in bioprocess control. Graphical abstract Overview of the LC-MRM-MS workflow for the determination of proteomic markers in conditioned media from the bioreactor that correlate with CHO cell death.

  9. Integrative prescreening in analysis of multiple cancer genomic studies

    PubMed Central

    2012-01-01

    Background In high throughput cancer genomic studies, results from the analysis of single datasets often suffer from a lack of reproducibility because of small sample sizes. Integrative analysis can effectively pool and analyze multiple datasets and provides a cost effective way to improve reproducibility. In integrative analysis, simultaneously analyzing all genes profiled may incur high computational cost. A computationally affordable remedy is prescreening, which fits marginal models, can be conducted in a parallel manner, and has low computational cost. Results An integrative prescreening approach is developed for the analysis of multiple cancer genomic datasets. Simulation shows that the proposed integrative prescreening has better performance than alternatives, particularly including prescreening with individual datasets, an intensity approach and meta-analysis. We also analyze multiple microarray gene profiling studies on liver and pancreatic cancers using the proposed approach. Conclusions The proposed integrative prescreening provides an effective way to reduce the dimensionality in cancer genomic studies. It can be coupled with existing analysis methods to identify cancer markers. PMID:22799431

  10. PFAAT version 2.0: a tool for editing, annotating, and analyzing multiple sequence alignments.

    PubMed

    Caffrey, Daniel R; Dana, Paul H; Mathur, Vidhya; Ocano, Marco; Hong, Eun-Jong; Wang, Yaoyu E; Somaroo, Shyamal; Caffrey, Brian E; Potluri, Shobha; Huang, Enoch S

    2007-10-11

    By virtue of their shared ancestry, homologous sequences are similar in their structure and function. Consequently, multiple sequence alignments are routinely used to identify trends that relate to function. This type of analysis is particularly productive when it is combined with structural and phylogenetic analysis. Here we describe the release of PFAAT version 2.0, a tool for editing, analyzing, and annotating multiple sequence alignments. Support for multiple annotations is a key component of this release as it provides a framework for most of the new functionalities. The sequence annotations are accessible from the alignment and tree, where they are typically used to label sequences or hyperlink them to related databases. Sequence annotations can be created manually or extracted automatically from UniProt entries. Once a multiple sequence alignment is populated with sequence annotations, sequences can be easily selected and sorted through a sophisticated search dialog. The selected sequences can be further analyzed using statistical methods that explicitly model relationships between the sequence annotations and residue properties. Residue annotations are accessible from the alignment viewer and are typically used to designate binding sites or properties for a particular residue. Residue annotations are also searchable, and allow one to quickly select alignment columns for further sequence analysis, e.g. computing percent identities. Other features include: novel algorithms to compute sequence conservation, mapping conservation scores to a 3D structure in Jmol, displaying secondary structure elements, and sorting sequences by residue composition. PFAAT provides a framework whereby end-users can specify knowledge for a protein family in the form of annotation. The annotations can be combined with sophisticated analysis to test hypothesis that relate to sequence, structure and function.

  11. Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

    PubMed

    Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C; Otto, Markus; Tumani, Hayrettin

    2015-07-31

    Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs.

  12. Flow cytometric discrimination of seven lineage markers by using two fluorochromes

    PubMed Central

    Boin, Francesco; Giardino Torchia, Maria Letizia; Borrello, Ivan; Noonan, Kimberly A.; Neil, Matthew; Soloski, Mark J.

    2017-01-01

    Flow cytometry is the primary immunological technique used to analyze multiple parameters on complex cell populations. We present a staining method that identifies major human mononuclear lymphoid and myeloid populations (CD4+ and CD8+ T cells, γδ T cells, B cells, NK cells and monocytes), using only two fluorochromes and a minimal number of cells. Our approach increases the number of markers recordable on most flow cytometers allowing for a deeper and more comprehensive immunophenotyping. PMID:29190813

  13. Analyzing and Integrating Models of Multiple Text Comprehension

    ERIC Educational Resources Information Center

    List, Alexandra; Alexander, Patricia A.

    2017-01-01

    We introduce a special issue featuring four theoretical models of multiple text comprehension. We present a central framework for conceptualizing the four models in this special issue. Specifically, we chart the models according to how they consider learner, texts, task, and context factors in explaining multiple text comprehension. In addition,…

  14. Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer.

    PubMed

    Bossard, N; Descotes, F; Bremond, A G; Bobin, Y; De Saint Hilaire, P; Golfier, F; Awada, A; Mathevet, P M; Berrerd, L; Barbier, Y; Estève, J

    2003-11-01

    The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

  15. Analyzing Association Mapping in Pedigree-Based GWAS Using a Penalized Multitrait Mixed Model

    PubMed Central

    Liu, Jin; Yang, Can; Shi, Xingjie; Li, Cong; Huang, Jian; Zhao, Hongyu; Ma, Shuangge

    2017-01-01

    Genome-wide association studies (GWAS) have led to the identification of many genetic variants associated with complex diseases in the past 10 years. Penalization methods, with significant numerical and statistical advantages, have been extensively adopted in analyzing GWAS. This study has been partly motivated by the analysis of Genetic Analysis Workshop (GAW) 18 data, which have two notable characteristics. First, the subjects are from a small number of pedigrees and hence related. Second, for each subject, multiple correlated traits have been measured. Most of the existing penalization methods assume independence between subjects and traits and can be suboptimal. There are a few methods in the literature based on mixed modeling that can accommodate correlations. However, they cannot fully accommodate the two types of correlations while conducting effective marker selection. In this study, we develop a penalized multitrait mixed modeling approach. It accommodates the two different types of correlations and includes several existing methods as special cases. Effective penalization is adopted for marker selection. Simulation demonstrates its satisfactory performance. The GAW 18 data are analyzed using the proposed method. PMID:27247027

  16. Association between a Healthy Lifestyle Score and Inflammatory Markers among Puerto Rican adults

    PubMed Central

    Sotos-Prieto, M; Bhupathiraju, SN; Falcon, LM; Gao, X; Tucker, KL; Mattei, J

    2016-01-01

    Background and Aims The relationship between multiple lifestyle components analyzed in combination and inflammation remains understudied. We aimed to assess the association between a Healthy Lifestyle Score (HLS) that includes adherence to five behavioral components (diet, physical activity and sedentary behaviors, smoking, social support and network, and sleep) and inflammatory markers, as well as the role of the HLS in inflammation among individuals with cardiometabolic conditions, in Puerto Rican adults. Methods and Results In a cross-sectional study of 842 Puerto Ricans adults (aged 45–75 y) living in Boston, MA, the HLS (range=0–190; maximum indicative of healthiest adherence) was analyzed for association with three inflammatory markers: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). In multivariable-adjusted models, the HLS was inversely associated with IL-6 (β±SE =−0.55 ± 0.13; P<0.001) and TNF-α (−0.39 ± 0.13; P=0.004). The dietary and smoking components were associated with both inflammatory markers independently of the other HLS components. Significant inverse associations were observed for each 20-unit increase in HLS and IL-6 and TNF-α for participants with hypertension (n=600; β±SE = −0.58 ± 0.16; −0.46 ± 0.16, respectively) and with overweight/obesity (n=743; β±SE = −0.59 ± 0.13; −0.50 ± 0.14, respectively), but not for those with diabetes (n=187) or heart disease (n=192). The HLS was not associated with CRP, after adjustment for potential confounders. Conclusion Higher adherence to multiple lifestyle behaviors was associated with lower concentrations of inflammatory markers. Because low-grade inflammation may precede chronic diseases, following an overall healthy lifestyle may help lower risk of these diseases. PMID:26838054

  17. Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

    PubMed Central

    Abdelhak, Ahmed; Junker, Andreas; Brettschneider, Johannes; Kassubek, Jan; Ludolph, Albert C.; Otto, Markus; Tumani, Hayrettin

    2015-01-01

    Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs. PMID:26263977

  18. Multiple marker abundance profiling: combining selected reaction monitoring and data-dependent acquisition for rapid estimation of organelle abundance in subcellular samples

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hooper, Cornelia M.; Stevens, Tim J.; Saukkonen, Anna

    Measuring changes in protein or organelle abundance in the cell is an essential, but challenging aspect of cell biology. Frequently-used methods for determining organelle abundance typically rely on detection of a very few marker proteins, so are unsatisfactory. In silico estimates of protein abundances from publicly available protein spectra can provide useful standard abundance values but contain only data from tissue proteomes, and are not coupled to organelle localization data. A new protein abundance score, the normalized protein abundance scale (NPAS), expands on the number of scored proteins and the scoring accuracy of lower-abundance proteins in Arabidopsis. NPAS was combinedmore » with subcellular protein localization data, facilitating quantitative estimations of organelle abundance during routine experimental procedures. A suite of targeted proteomics markers for subcellular compartment markers was developed, enabling independent verification of in silico estimates for relative organelle abundance. Estimation of relative organelle abundance was found to be reproducible and consistent over a range of tissues and growth conditions. In silico abundance estimations and localization data have been combined into an online tool, multiple marker abundance profiling, available in the SUBA4 toolbox (http://suba.live).« less

  19. Multiple marker abundance profiling: combining selected reaction monitoring and data-dependent acquisition for rapid estimation of organelle abundance in subcellular samples

    DOE PAGES

    Hooper, Cornelia M.; Stevens, Tim J.; Saukkonen, Anna; ...

    2017-10-12

    Measuring changes in protein or organelle abundance in the cell is an essential, but challenging aspect of cell biology. Frequently-used methods for determining organelle abundance typically rely on detection of a very few marker proteins, so are unsatisfactory. In silico estimates of protein abundances from publicly available protein spectra can provide useful standard abundance values but contain only data from tissue proteomes, and are not coupled to organelle localization data. A new protein abundance score, the normalized protein abundance scale (NPAS), expands on the number of scored proteins and the scoring accuracy of lower-abundance proteins in Arabidopsis. NPAS was combinedmore » with subcellular protein localization data, facilitating quantitative estimations of organelle abundance during routine experimental procedures. A suite of targeted proteomics markers for subcellular compartment markers was developed, enabling independent verification of in silico estimates for relative organelle abundance. Estimation of relative organelle abundance was found to be reproducible and consistent over a range of tissues and growth conditions. In silico abundance estimations and localization data have been combined into an online tool, multiple marker abundance profiling, available in the SUBA4 toolbox (http://suba.live).« less

  20. Genomic markers for decision making: what is preventing us from using markers?

    PubMed

    Coyle, Vicky M; Johnston, Patrick G

    2010-02-01

    The advent of novel genomic technologies that enable the evaluation of genomic alterations on a genome-wide scale has significantly altered the field of genomic marker research in solid tumors. Researchers have moved away from the traditional model of identifying a particular genomic alteration and evaluating the association between this finding and a clinical outcome measure to a new approach involving the identification and measurement of multiple genomic markers simultaneously within clinical studies. This in turn has presented additional challenges in considering the use of genomic markers in oncology, such as clinical study design, reproducibility and interpretation and reporting of results. This Review will explore these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the use of putative genomic markers in the clinic. Despite these rapid technological advances there is still a paucity of genomic markers in routine clinical use at present. A rational and focused approach to the evaluation and validation of genomic markers is needed, whereby analytically validated markers are investigated in clinical studies that are adequately powered and have pre-defined patient populations and study endpoints. Furthermore, novel adaptive clinical trial designs, incorporating putative genomic markers into prospective clinical trials, will enable the evaluation of these markers in a rigorous and timely fashion. Such approaches have the potential to facilitate the implementation of such markers into routine clinical practice and consequently enable the rational and tailored use of cancer therapies for individual patients.

  1. Prognostic value of HMGB1 and oxidative stress markers in multiple trauma patients: A single-centre prospective study.

    PubMed

    Polito, Francesca; Cicciu', Marco; Aguennouz, Mohammed; Cucinotta, Maria; Cristani, Mariateresa; Lauritano, Floriana; Sindoni, Alessandro; Gioffre'-Florio, Maria; Fama, Fausto

    2016-09-01

    Serious multiple traumatic injuries may rapidly become fatal or be complicated by a life-threatening sequelae leading to a significant increase of the mortality rate. Trauma scoring systems are used to evaluate the critical status of the patient and recently many different biomarkers have been taken into account to better estimate the potential clinical outcome. The aim of the present study is to analyse the expression pattern of high-mobility group box-1 (HMGB1), oxidative stress markers and nuclear factor erythroid 2-related (Nrf2) in critically ill traumatic patients (at hospital admittance and after 6 and 24 h), in order to find out their potential role as early post-traumatic predictors markers. Forty-seven patients admitted for multiple trauma and 15 healthy participants were prospectively recruited. Eight patients (17%) died within 92 h of admission; this subgroup of patients presented the highest severity scores and their HMGB1 expression levels were significantly correlated with ISS, whereas patients with higher ISS exhibited higher levels of HMGB1 (P <0.001). Our study suggests the role of HMGB1 as a predictive biomarker of outcome in injured patients and hypothesizes the protective role of Nrf2 in bringing down the oxidative stress and HMGB1 release; measuring HMGB1 in combination with Nrf2 might represent a potentially useful tool in the early detection of post-trauma complications. © The Author(s) 2016.

  2. Meta-markers for the differential diagnosis of lung cancer and lung disease.

    PubMed

    Kim, Yong-In; Ahn, Jung-Mo; Sung, Hye-Jin; Na, Sang-Su; Hwang, Jaesung; Kim, Yongdai; Cho, Je-Yoel

    2016-10-04

    Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical information were analyzed using a logistic regression analysis to select model for the best 'meta-marker', or combination of biomarkers for differential diagnosis. Also, under consideration of statistical interaction, variables having low significance as a single factor but statistically influencing on meta-marker model were selected. Using this probabilistic classification, the best meta-marker was determined to be made up of two proteins SERPINA4 and PON1 with age factor. This meta-marker showed an enhanced differential diagnostic capability (AUC=0.915) for distinguishing the two patient groups. Our results suggest that a statistical model can determine optimal meta-markers, which may have better specificity and sensitivity than a single biomarker and thus improve the differential diagnosis of lung cancer and lung disease patients. Diagnosing lung cancer commonly involves the use of radiographic methods. However, an imaging-based diagnosis may fail to differentiate lung cancer from non-cancerous lung disease. In this study, we examined several serum proteins in the sera of 198 lung cancer and non-cancerous lung disease patients by multiple-reaction monitoring. We then used a combination of variables to generate a meta-marker model that is useful as a differential diagnostic biomarker. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status.

    PubMed

    Papathanasiou, Athanasios; Messinis, Lambros; Zampakis, Petros; Papathanasopoulos, Panagiotis

    2017-09-01

    Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Studies of HVC Plasticity in Adult Canaries Reveal Social Effects and Sex Differences as Well as Limitations of Multiple Markers Available to Assess Adult Neurogenesis

    PubMed Central

    Shevchouk, Olesya T.; Ball, Gregory F.; Cornil, Charlotte A.

    2017-01-01

    In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new neurons. We simultaneously used three independent markers to investigate HVC neurogenesis in male and female canaries. Males were castrated, implanted with testosterone and housed either alone (M), with a female (M-F) or with another male (M-M) while females were implanted with 17β-estradiol and housed with a male (F-M). All subjects received injections of the two thymidine analogues, BrdU and of EdU, respectively 21 and 10 days before brain collection. Cells containing BrdU or EdU or expressing doublecortin (DCX), which labels newborn neurons, were quantified. Social context and sex differentially affected total BrdU+, EdU+, BrdU+EdU- and DCX+ populations. M-M males had a higher density of BrdU+ cells in the ventricular zone adjacent to HVC and of EdU+ in HVC than M-F males. M birds had a higher ratio of BrdU+EdU- to EdU+ cells than M-F subjects suggesting higher survival of newer neurons in the former group. Total number of HVC DCX+ cells was lower in M-F than in M-M males. Sex differences were also dependent of the type of marker used. Several technical limitations associated with the use of these multiple markers were also identified. These results indicate that proliferation, recruitment and survival of new neurons can be independently affected by environmental conditions and effects can only be fully discerned through the use of multiple neurogenesis markers. PMID:28141859

  5. Studies of HVC Plasticity in Adult Canaries Reveal Social Effects and Sex Differences as Well as Limitations of Multiple Markers Available to Assess Adult Neurogenesis.

    PubMed

    Shevchouk, Olesya T; Ball, Gregory F; Cornil, Charlotte A; Balthazart, Jacques

    2017-01-01

    In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new neurons. We simultaneously used three independent markers to investigate HVC neurogenesis in male and female canaries. Males were castrated, implanted with testosterone and housed either alone (M), with a female (M-F) or with another male (M-M) while females were implanted with 17β-estradiol and housed with a male (F-M). All subjects received injections of the two thymidine analogues, BrdU and of EdU, respectively 21 and 10 days before brain collection. Cells containing BrdU or EdU or expressing doublecortin (DCX), which labels newborn neurons, were quantified. Social context and sex differentially affected total BrdU+, EdU+, BrdU+EdU- and DCX+ populations. M-M males had a higher density of BrdU+ cells in the ventricular zone adjacent to HVC and of EdU+ in HVC than M-F males. M birds had a higher ratio of BrdU+EdU- to EdU+ cells than M-F subjects suggesting higher survival of newer neurons in the former group. Total number of HVC DCX+ cells was lower in M-F than in M-M males. Sex differences were also dependent of the type of marker used. Several technical limitations associated with the use of these multiple markers were also identified. These results indicate that proliferation, recruitment and survival of new neurons can be independently affected by environmental conditions and effects can only be fully discerned through the use of multiple neurogenesis markers.

  6. Intraovarian markers of follicular and oocyte maturation.

    PubMed

    Pellicer, A; Diamond, M P; DeCherney, A H; Naftolin, F

    1987-08-01

    The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.

  7. Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study

    PubMed Central

    Rosovsky, Rachel; Hong, Fangxin; Tocco, Deanna; Connell, Brendan; Mitsiades, Constantine; Schlossman, Robert; Ghobrial, Irene; Lockridge, Leslie; Warren, Diane; Bradwin, Gary; Doyle, Mary; Munshi, Nikhil; Soiffer, Robert J.; Anderson, Kenneth C.; Weller, Edie; Richardson, Paul

    2014-01-01

    Summary In this prospective study of patients with relapsed and/or refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40 mg/day on days 1–4, 9–12, and 17–21 of each 28-day cycle) and 9 received weekly dexamethasone (40 mg/day on days 1, 8, 15, and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P = 0·05), fibrinogen (P = 0·008), plasminogen activator inhibitor-1 (P < 0·001), homocysteine (P = 0·002), and P-selectin (P < 0·001) during therapy. Compared with weekly dexamethasone, pulsed dexamethasone was associated with significantly greater variation in mean adjusted relative values of fibrinogen, P-selectin, and vascular endothelial growth factor (P < 0·001 for all comparisons), although there was no apparent association with VTE incidence. Lenalidomide plus dexamethasone affects endothelial stress marker levels in patients with advanced MM. The higher variation seen with pulsed dexamethasone suggests greater endothelial stress with this approach. PMID:23240658

  8. Sparse Group Penalized Integrative Analysis of Multiple Cancer Prognosis Datasets

    PubMed Central

    Liu, Jin; Huang, Jian; Xie, Yang; Ma, Shuangge

    2014-01-01

    SUMMARY In cancer research, high-throughput profiling studies have been extensively conducted, searching for markers associated with prognosis. Because of the “large d, small n” characteristic, results generated from the analysis of a single dataset can be unsatisfactory. Recent studies have shown that integrative analysis, which simultaneously analyzes multiple datasets, can be more effective than single-dataset analysis and classic meta-analysis. In most of existing integrative analysis, the homogeneity model has been assumed, which postulates that different datasets share the same set of markers. Several approaches have been designed to reinforce this assumption. In practice, different datasets may differ in terms of patient selection criteria, profiling techniques, and many other aspects. Such differences may make the homogeneity model too restricted. In this study, we assume the heterogeneity model, under which different datasets are allowed to have different sets of markers. With multiple cancer prognosis datasets, we adopt the AFT (accelerated failure time) model to describe survival. This model may have the lowest computational cost among popular semiparametric survival models. For marker selection, we adopt a sparse group MCP (minimax concave penalty) approach. This approach has an intuitive formulation and can be computed using an effective group coordinate descent algorithm. Simulation study shows that it outperforms the existing approaches under both the homogeneity and heterogeneity models. Data analysis further demonstrates the merit of heterogeneity model and proposed approach. PMID:23938111

  9. Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?

    PubMed

    Casoni, F; Merelli, E; Bedin, R; Sola, P; Bertolotto, A; Faglioni, P

    2004-01-01

    Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

  10. Association between a Healthy Lifestyle Score and inflammatory markers among Puerto Rican adults.

    PubMed

    Sotos-Prieto, M; Bhupathiraju, S N; Falcon, L M; Gao, X; Tucker, K L; Mattei, J

    2016-03-01

    The relationship between multiple lifestyle components analyzed in combination and inflammation remains understudied. We aimed to assess the association between a Healthy Lifestyle Score (HLS) that includes adherence to five behavioral components (diet, physical activity and sedentary behaviors, smoking, social support and network, and sleep) and inflammatory markers, as well as the role of the HLS in inflammation among individuals with cardiometabolic conditions, in Puerto Rican adults. In a cross-sectional study of 842 Puerto Ricans adults (aged 45-75 y) living in Boston, MA, the HLS (range = 0-190; maximum indicative of healthiest adherence) was analyzed for association with three inflammatory markers: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). In multivariable-adjusted models, the HLS was inversely associated with IL-6 (β ± SE = -0.55 ± 0.13; P < 0.001) and TNF-α (-0.39 ± 0.13; P = 0.004). The dietary and smoking components were associated with both inflammatory markers independently of the other HLS components. Significant inverse associations were observed for each 20-unit increase in HLS and IL-6 and TNF-α for participants with hypertension (n = 600; β ± SE = -0.58 ± 0.16; -0.46 ± 0.16, respectively) and with overweight/obesity (n = 743; β ± SE = -0.59 ± 0.13; -0.50 ± 0.14, respectively), but not for those with diabetes (n = 187) or heart disease (n = 192). The HLS was not associated with CRP, after adjustment for potential confounders. Higher adherence to multiple lifestyle behaviors was associated with lower concentrations of inflammatory markers. Because low-grade inflammation may precede chronic diseases, following an overall healthy lifestyle may help lower risk of these diseases. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II

  11. Simultaneous 3D localization of multiple MR-visible markers in fully reconstructed MR images: proof-of-concept for subsecond position tracking.

    PubMed

    Thörmer, Gregor; Garnov, Nikita; Moche, Michael; Haase, Jürgen; Kahn, Thomas; Busse, Harald

    2012-04-01

    To determine whether a greatly reduced spatial resolution of fully reconstructed projection MR images can be used for the simultaneous 3D localization of multiple MR-visible markers and to assess the feasibility of a subsecond position tracking for clinical purposes. Miniature, inductively coupled RF coils were imaged in three orthogonal planes with a balanced steady-state free precession (SSFP) sequence and automatically localized using a two-dimensional template fitting and a subsequent three-dimensional (3D) matching of the coordinates. Precision, accuracy, speed and robustness of 3D localization were assessed for decreasing in-plane resolutions (0.6-4.7 mm). The feasibility of marker tracking was evaluated at the lowest resolution by following a robotically driven needle on a complex 3D trajectory. Average 3D precision and accuracy, sensitivity and specificity of localization ranged between 0.1 and 0.4 mm, 0.5 and 1.0 mm, 100% and 95%, and 100% and 96%, respectively. At the lowest resolution, imaging and localization took ≈350 ms and provided an accuracy of ≈1.0 mm. In the tracking experiment, the needle was clearly depicted on the oblique scan planes defined by the markers. Image-based marker localization at a greatly reduced spatial resolution is considered a feasible approach to monitor reference points or rigid instruments at subsecond update rates. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses.

    PubMed

    Vermeulen, Roel; Saberi Hosnijeh, Fatemeh; Bodinier, Barbara; Portengen, Lützen; Liquet, Benoît; Garrido-Manriquez, Javiera; Lokhorst, Henk; Bergdahl, Ingvar A; Kyrtopoulos, Soterios A; Johansson, Ann-Sofie; Georgiadis, Panagiotis; Melin, Beatrice; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Vineis, Paolo; Castagné, Raphaële; Chadeau-Hyam, Marc; Botsivali, Maria; Chatziioannou, Aristotelis; Valavanis, Ioannis; Kleinjans, Jos C S; de Kok, Theo M C M; Keun, Hector C; Athersuch, Toby J; Kelly, Rachel; Lenner, Per; Hallmans, Goran; Stephanou, Euripides G; Myridakis, Antonis; Kogevinas, Manolis; Fazzo, Lucia; De Santis, Marco; Comba, Pietro; Bendinelli, Benedetta; Kiviranta, Hannu; Rantakokko, Panu; Airaksinen, Riikka; Ruokojarvi, Paivi; Gilthorpe, Mark; Fleming, Sarah; Fleming, Thomas; Tu, Yu-Kang; Lundh, Thomas; Chien, Kuo-Liong; Chen, Wei J; Lee, Wen-Chung; Kate Hsiao, Chuhsing; Kuo, Po-Hsiu; Hung, Hung; Liao, Shu-Fen

    2018-04-18

    Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10 -4 ) and transforming growth factor alpha (TGF-α, p = 6.5 × 10 -5 ) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p = 7.8 × 10 -7 ), TGF-α (p = 4.08 × 10 -5 ), fractalkine (p = 1.12 × 10 -3 ), monocyte chemotactic protein-3 (p = 1.36 × 10 -4 ), macrophage inflammatory protein 1-alpha (p = 4.6 × 10 -4 ) and vascular endothelial growth factor (p = 4.23 × 10 -5 ). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that Granulocyte-macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth-factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL. © 2018 The Authors International

  13. Characterization and transferability of microsatellite markers of the cultivated peanut (Arachis hypogaea)

    PubMed Central

    Gimenes, Marcos A; Hoshino, Andrea A; Barbosa, Andrea VG; Palmieri, Dario A; Lopes, Catalina R

    2007-01-01

    Background The genus Arachis includes Arachis hypogaea (cultivated peanut) and wild species that are used in peanut breeding or as forage. Molecular markers have been employed in several studies of this genus, but microsatellite markers have only been used in few investigations. Microsatellites are very informative and are useful to assess genetic variability, analyze mating systems and in genetic mapping. The objectives of this study were to develop A. hypogaea microsatellite loci and to evaluate the transferability of these markers to other Arachis species. Results Thirteen loci were isolated and characterized using 16 accessions of A. hypogaea. The level of variation found in A. hypogaea using microsatellites was higher than with other markers. Cross-transferability of the markers was also high. Sequencing of the fragments amplified using the primer pair Ah11 from 17 wild Arachis species showed that almost all wild species had similar repeated sequence to the one observed in A. hypogaea. Sequence data suggested that there is no correlation between taxonomic relationship of a wild species to A. hypogaea and the number of repeats found in its microsatellite loci. Conclusion These results show that microsatellite primer pairs from A. hypogaea have multiple uses. A higher level of variation among A. hypogaea accessions can be detected using microsatellite markers in comparison to other markers, such as RFLP, RAPD and AFLP. The microsatellite primers of A. hypogaea showed a very high rate of transferability to other species of the genus. These primer pairs provide important tools to evaluate the genetic variability and to assess the mating system in Arachis species. PMID:17326826

  14. Frameworking memory and serotonergic markers.

    PubMed

    Meneses, Alfredo

    2017-07-26

    The evidence for neural markers and memory is continuously being revised, and as evidence continues to accumulate, herein, we frame earlier and new evidence. Hence, in this work, the aim is to provide an appropriate conceptual framework of serotonergic markers associated with neural activity and memory. Serotonin (5-hydroxytryptamine [5-HT]) has multiple pharmacological tools, well-characterized downstream signaling in mammals' species, and established 5-HT neural markers showing new insights about memory functions and dysfunctions, including receptors (5-HT1A/1B/1D, 5-HT2A/2B/2C, and 5-HT3-7), transporter (serotonin transporter [SERT]) and volume transmission present in brain areas involved in memory. Bidirectional influence occurs between 5-HT markers and memory/amnesia. A growing number of researchers report that memory, amnesia, or forgetting modifies neural markers. Diverse approaches support the translatability of using neural markers and cerebral functions/dysfunctions, including memory formation and amnesia. At least, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors and SERT seem to be useful neural markers and therapeutic targets. Hence, several mechanisms cooperate to achieve synaptic plasticity or memory, including changes in the expression of neurotransmitter receptors and transporters.

  15. A traffic analyzer for multiple SpaceWire links

    NASA Astrophysics Data System (ADS)

    Liu, Scige J.; Giusi, Giovanni; Di Giorgio, Anna M.; Vertolli, Nello; Galli, Emanuele; Biondi, David; Farina, Maria; Pezzuto, Stefano; Spinoglio, Luigi

    2014-07-01

    Modern space missions are becoming increasingly complex: the interconnection of the units in a satellite is now a network of terminals linked together through routers, where devices with different level of automation and intelligence share the same data-network. The traceability of the network transactions is performed mostly at terminal level through log analysis and hence it is difficult to verify in real time the reliability of the interconnections and the interchange protocols. To improve and ease the traffic analysis in a SpaceWire network we implemented a low-level link analyzer, with the specific goal to simplify the integration and test phases in the development of space instrumentation. The traffic analyzer collects signals coming from pod probes connected in-series on the interested links between two SpaceWire terminals. With respect to the standard traffic analyzers, the design of this new tool includes the possibility to internally reshape the LVDS signal. This improvement increases the robustness of the analyzer towards environmental noise effects and guarantees a deterministic delay on all analyzed signals. The analyzer core is implemented on a Xilinx FPGA, programmed to decode the bidirectional LVDS signals at Link and Network level. Successively, the core packetizes protocol characters in homogeneous sets of time ordered events. The analyzer provides time-tagging functionality for each characters set, with a precision down to the FPGA Clock, i.e. about 20nsec in the adopted HW environment. The use of a common time reference for each character stream allows synchronous performance measurements. The collected information is then routed to an external computer for quick analysis: this is done via high-speed USB2 connection. With this analyzer it is possible to verify the link performances in terms of induced delays in the transmitted signals. A case study focused on the analysis of the Time-Code synchronization in presence of a SpaceWire Router is

  16. An omnibus test for family-based association studies with multiple SNPs and multiple phenotypes.

    PubMed

    Lasky-Su, Jessica; Murphy, Amy; McQueen, Matthew B; Weiss, Scott; Lange, Christoph

    2010-06-01

    We propose an omnibus family-based association test (MFBAT) that can be applied to multiple markers and multiple phenotypes and that has only one degree of freedom. The proposed test statistic extends current FBAT methodology to incorporate multiple markers as well as multiple phenotypes. Using simulation studies, power estimates for the proposed methodology are compared with the standard methodologies. On the basis of these simulations, we find that MFBAT substantially outperforms other methods, including haplotypic approaches and doing multiple tests with single single-nucleotide polymorphisms (SNPs) and single phenotypes. The practical relevance of the approach is illustrated by an application to asthma in which SNP/phenotype combinations are identified and reach overall significance that would not have been identified using other approaches. This methodology is directly applicable to cases in which there are multiple SNPs, such as candidate gene studies, cases in which there are multiple phenotypes, such as expression data, and cases in which there are multiple phenotypes and genotypes, such as genome-wide association studies that incorporate expression profiles as phenotypes. This program is available in the PBAT analysis package.

  17. Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

    NASA Astrophysics Data System (ADS)

    Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

    To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

  18. Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

    PubMed

    Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

    2014-10-01

    We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

  19. Prevalence of heroin markers in urine for pain management patients.

    PubMed

    Knight, Julie; Puet, Brandi L; DePriest, Anne; Heltsley, Rebecca; Hild, Cheryl; Black, David L; Robert, Timothy; Caplan, Yale H; Cone, Edward J

    2014-10-01

    Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (multiple heroin markers may be useful to assess for

  20. CombiROC: an interactive web tool for selecting accurate marker combinations of omics data.

    PubMed

    Mazzara, Saveria; Rossi, Riccardo L; Grifantini, Renata; Donizetti, Simone; Abrignani, Sergio; Bombaci, Mauro

    2017-03-30

    Diagnostic accuracy can be improved considerably by combining multiple markers, whose performance in identifying diseased subjects is usually assessed via receiver operating characteristic (ROC) curves. The selection of multimarker signatures is a complicated process that requires integration of data signatures with sophisticated statistical methods. We developed a user-friendly tool, called CombiROC, to help researchers accurately determine optimal markers combinations from diverse omics methods. With CombiROC data from different domains, such as proteomics and transcriptomics, can be analyzed using sensitivity/specificity filters: the number of candidate marker panels rising from combinatorial analysis is easily optimized bypassing limitations imposed by the nature of different experimental approaches. Leaving to the user full control on initial selection stringency, CombiROC computes sensitivity and specificity for all markers combinations, performances of best combinations and ROC curves for automatic comparisons, all visualized in a graphic interface. CombiROC was designed without hard-coded thresholds, allowing a custom fit to each specific data: this dramatically reduces the computational burden and lowers the false negative rates given by fixed thresholds. The application was validated with published data, confirming the marker combination already originally described or even finding new ones. CombiROC is a novel tool for the scientific community freely available at http://CombiROC.eu.

  1. Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

    PubMed

    Sormani, Maria Pia

    2017-03-01

    Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

  2. Multi-hazard Assessment and Scenario Toolbox (MhAST): A Framework for Analyzing Compounding Effects of Multiple Hazards

    NASA Astrophysics Data System (ADS)

    Sadegh, M.; Moftakhari, H.; AghaKouchak, A.

    2017-12-01

    Many natural hazards are driven by multiple forcing variables, and concurrence/consecutive extreme events significantly increases risk of infrastructure/system failure. It is a common practice to use univariate analysis based upon a perceived ruling driver to estimate design quantiles and/or return periods of extreme events. A multivariate analysis, however, permits modeling simultaneous occurrence of multiple forcing variables. In this presentation, we introduce the Multi-hazard Assessment and Scenario Toolbox (MhAST) that comprehensively analyzes marginal and joint probability distributions of natural hazards. MhAST also offers a wide range of scenarios of return period and design levels and their likelihoods. Contribution of this study is four-fold: 1. comprehensive analysis of marginal and joint probability of multiple drivers through 17 continuous distributions and 26 copulas, 2. multiple scenario analysis of concurrent extremes based upon the most likely joint occurrence, one ruling variable, and weighted random sampling of joint occurrences with similar exceedance probabilities, 3. weighted average scenario analysis based on a expected event, and 4. uncertainty analysis of the most likely joint occurrence scenario using a Bayesian framework.

  3. Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis.

    PubMed

    Miyake, Hiromu; Li, Bo; Lee, Carol; Koike, Yuhki; Chen, Yong; Seo, Shogo; Pierro, Agostino

    2018-05-01

    Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls. Serum ALT level was higher in NEC (p<0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p<0.05, TNF-α: p<0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p<0.01, PCNA: p<0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p<0.05) and protein (p<0.01) levels. Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome. Level IV. Copyright © 2018. Published by Elsevier Inc.

  4. Method of analyzing multiple sample simultaneously by detecting absorption and systems for use in such a method

    DOEpatents

    Yeung, Edward S.; Gong, Xiaoyi

    2004-09-07

    The present invention provides a method of analyzing multiple samples simultaneously by absorption detection. The method comprises: (i) providing a planar array of multiple containers, each of which contains a sample comprising at least one absorbing species, (ii) irradiating the planar array of multiple containers with a light source and (iii) detecting absorption of light with a detetion means that is in line with the light source at a distance of at leaat about 10 times a cross-sectional distance of a container in the planar array of multiple containers. The absorption of light by a sample indicates the presence of an absorbing species in it. The method can further comprise: (iv) measuring the amount of absorption of light detected in (iii) indicating the amount of the absorbing species in the sample. Also provided by the present invention is a system for use in the abov metho.The system comprises; (i) a light source comrnpising or consisting essentially of at leaat one wavelength of light, the absorption of which is to be detected, (ii) a planar array of multiple containers, and (iii) a detection means that is in line with the light source and is positioned in line with and parallel to the planar array of multiple contiainers at a distance of at least about 10 times a cross-sectional distance of a container.

  5. Novel applications of multitask learning and multiple output regression to multiple genetic trait prediction.

    PubMed

    He, Dan; Kuhn, David; Parida, Laxmi

    2016-06-15

    Given a set of biallelic molecular markers, such as SNPs, with genotype values encoded numerically on a collection of plant, animal or human samples, the goal of genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Genetic trait prediction is usually represented as linear regression models. In many cases, for the same set of samples and markers, multiple traits are observed. Some of these traits might be correlated with each other. Therefore, modeling all the multiple traits together may improve the prediction accuracy. In this work, we view the multitrait prediction problem from a machine learning angle: as either a multitask learning problem or a multiple output regression problem, depending on whether different traits share the same genotype matrix or not. We then adapted multitask learning algorithms and multiple output regression algorithms to solve the multitrait prediction problem. We proposed a few strategies to improve the least square error of the prediction from these algorithms. Our experiments show that modeling multiple traits together could improve the prediction accuracy for correlated traits. The programs we used are either public or directly from the referred authors, such as MALSAR (http://www.public.asu.edu/~jye02/Software/MALSAR/) package. The Avocado data set has not been published yet and is available upon request. dhe@us.ibm.com. © The Author 2016. Published by Oxford University Press.

  6. Tumour markers in diagnosis and management.

    PubMed

    Warnes, T W; Smith, A

    1987-01-01

    The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease

  7. GenPlay Multi-Genome, a tool to compare and analyze multiple human genomes in a graphical interface.

    PubMed

    Lajugie, Julien; Fourel, Nicolas; Bouhassira, Eric E

    2015-01-01

    Parallel visualization of multiple individual human genomes is a complex endeavor that is rapidly gaining importance with the increasing number of personal, phased and cancer genomes that are being generated. It requires the display of variants such as SNPs, indels and structural variants that are unique to specific genomes and the introduction of multiple overlapping gaps in the reference sequence. Here, we describe GenPlay Multi-Genome, an application specifically written to visualize and analyze multiple human genomes in parallel. GenPlay Multi-Genome is ideally suited for the comparison of allele-specific expression and functional genomic data obtained from multiple phased genomes in a graphical interface with access to multiple-track operation. It also allows the analysis of data that have been aligned to custom genomes rather than to a standard reference and can be used as a variant calling format file browser and as a tool to compare different genome assembly, such as hg19 and hg38. GenPlay is available under the GNU public license (GPL-3) from http://genplay.einstein.yu.edu. The source code is available at https://github.com/JulienLajugie/GenPlay. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Genotype-Based Association Mapping of Complex Diseases: Gene-Environment Interactions with Multiple Genetic Markers and Measurement Error in Environmental Exposures

    PubMed Central

    Lobach, Irvna; Fan, Ruzone; Carroll, Raymond T.

    2011-01-01

    With the advent of dense single nucleotide polymorphism genotyping, population-based association studies have become the major tools for identifying human disease genes and for fine gene mapping of complex traits. We develop a genotype-based approach for association analysis of case-control studies of gene-environment interactions in the case when environmental factors are measured with error and genotype data are available on multiple genetic markers. To directly use the observed genotype data, we propose two genotype-based models: genotype effect and additive effect models. Our approach offers several advantages. First, the proposed risk functions can directly incorporate the observed genotype data while modeling the linkage disequihbrium information in the regression coefficients, thus eliminating the need to infer haplotype phase. Compared with the haplotype-based approach, an estimating procedure based on the proposed methods can be much simpler and significantly faster. In addition, there is no potential risk due to haplotype phase estimation. Further, by fitting the proposed models, it is possible to analyze the risk alleles/variants of complex diseases, including their dominant or additive effects. To model measurement error, we adopt the pseudo-likelihood method by Lobach et al. [2008]. Performance of the proposed method is examined using simulation experiments. An application of our method is illustrated using a population-based case-control study of association between calcium intake with the risk of colorectal adenoma development. PMID:21031455

  9. Reduced antioxidant capacity and increased subclinical inflammation markers in prepubescent obese children and their relationship with nutritional markers and metabolic parameters.

    PubMed

    Vehapoglu, Aysel; Turkmen, Serdar; Goknar, Nilufer; Özer, Ömer Faruk

    2016-11-01

    There are associations between some inflammatory and oxidative markers and obesity in adults, but whether prepubescent children of different weights also have such markers has not been studied. We investigated multiple inflammatory markers and levels of erythrocyte oxidant/antioxidant enzymes in prepubescent children of different weights. Children aged 2-11 years were divided into three groups: 80 were underweight, 90 were obese but otherwise healthy, and 80 were healthy age- and sex-matched children of normal-weight. We analyzed inflammatory markers and the total oxidant status, total antioxidant status (TAS), and total thiol level were also determined, and the oxidative stress index was calculated as an indicator of the degree of oxidative stress. The obese group exhibited higher levels of fasting glucose, insulin, total cholesterol, triglycerides, the homeostatic model assessment of insulin resistance (HOMA-IR), and the homeostatic model assessment of β-cell function (HOMA-β), C-reactive protein (CRP), neutrophils, and neutrophil/lymphocyte ratio (NLR), as well as lower TAS and total thiol levels than the other two groups (all P < 0.001). Moreover, TAS and total thiols were negatively correlated with age in the obese group (r = -0.212, P = 0.001; r = -0.231, P < 0.001, respectively). CRP levels in plasma were positively correlated with the body mass index (BMI), insulin and glucose levels, HOMA-IR, HOMA-β, WBC and neutrophil counts, and the NLR, and were negatively correlated with TAS and total thiol levels in the overall studied population. The coexistence of increased obesity-related subclinical inflammation and decreased antioxidant capacity can be observed even in prepubescence, and may eventually increase the risk of long-term vascular damage.

  10. Developing single nucleotide polymorphism (SNP) markers from transcriptome sequences for identification of longan (Dimocarpus longan) germplasm

    PubMed Central

    Wang, Boyi; Tan, Hua-Wei; Fang, Wanping; Meinhardt, Lyndel W; Mischke, Sue; Matsumoto, Tracie; Zhang, Dapeng

    2015-01-01

    Longan (Dimocarpus longan Lour.) is an important tropical fruit tree crop. Accurate varietal identification is essential for germplasm management and breeding. Using longan transcriptome sequences from public databases, we developed single nucleotide polymorphism (SNP) markers; validated 60 SNPs in 50 longan germplasm accessions, including cultivated varieties and wild germplasm; and designated 25 SNP markers that unambiguously identified all tested longan varieties with high statistical rigor (P<0.0001). Multiple trees from the same clone were verified and off-type trees were identified. Diversity analysis revealed genetic relationships among analyzed accessions. Cultivated varieties differed significantly from wild populations (Fst=0.300; P<0.001), demonstrating untapped genetic diversity for germplasm conservation and utilization. Within cultivated varieties, apparent differences between varieties from China and those from Thailand and Hawaii indicated geographic patterns of genetic differentiation. These SNP markers provide a powerful tool to manage longan genetic resources and breeding, with accurate and efficient genotype identification. PMID:26504559

  11. Identify super quality markers from prototype-based pharmacokinetic markers of Tangzhiqing tablet (TZQ) based on in vitro dissolution/ permeation and in vivo absorption correlations.

    PubMed

    Li, Ziqiang; Liu, Jia; Li, Yazhuo; Du, Xi; Li, Yanfen; Wang, Ruihua; Lv, Chunxiao; He, Xin; Wang, Baohe; Huang, Yuhong; Zhang, Deqin

    2018-06-01

    A quality marker (Q-marker) is defined as an inherent chemical compound that is used for the quality control of a drug. Its biological activities are closely related to safety and therapeutic effects. Generally, a multiple-component herbal medicine may have many Q-markers. We therefore proposed a concept of "super Q-marker" satisfying both the criterion of Q-markers and PK-markers to be used in more effective quality control of herbal medicine. The first aim was to find suitable prototype-based PK-markers from Tangzhiqing tablets (TZQ), a Chinese patent medicine. Then super Q-markers were expected to be identified from the prototype-based PK-markers based on an in vitro-in vivo correlation study. Potentially eligible prototype-based PK-markers were identified in a single- and multiple-dose pharmacokinetic study on TZQ in 30 healthy volunteers. The in vitro dissolution and permeation profiles of the prototype-based PK-markers of TZQ were evaluated by the physiologically-based drug dissolution/absorption simulating system (DDASS). An in vitro-in vivo correlation analysis was conducted between the dissolution/permeation behaviors in DDASS and the actual absorption profiles in human to test the transferability and traceability of the promising super Q-markers for TZQ. In human, plasma paeoniflorin and nuciferine as prototype-based PK-markers exhibited the appropriate pharmacokinetic properties, including dose-dependent systemic exposure (AUC, C max ) and a proper elimination half-life (1∼3h). In DDASS, it was predicted that paeoniflorin and nuciferine are highly permeable but the absorption rates are primarily limited by the dissolution rates. Moreover, the established in vitro-in vivo correlations of paeoniflorin and nuciferine were in support of the super Q-markers features. Paeoniflorin and nuciferine are identified as the super Q-markers from the prototype-based PK-markers of TZQ based on findings from a combination of in vitro, in vivo, and in vitro-in vivo

  12. Identification of molecular markers associated with mite resistance in coconut (Cocos nucifera L.).

    PubMed

    Shalini, K V; Manjunatha, S; Lebrun, P; Berger, A; Baudouin, L; Pirany, N; Ranganath, R M; Prasad, D Theertha

    2007-01-01

    Coconut mite (Aceria guerreronis 'Keifer') has become a major threat to Indian coconut (Coçcos nucifera L.) cultivators and the processing industry. Chemical and biological control measures have proved to be costly, ineffective, and ecologically undesirable. Planting mite-resistant coconut cultivars is the most effective method of preventing yield loss and should form a major component of any integrated pest management stratagem. Coconut genotypes, and mite-resistant and -susceptible accessions were collected from different parts of South India. Thirty-two simple sequence repeat (SSR) and 7 RAPD primers were used for molecular analyses. In single-marker analysis, 9 SSR and 4 RAPD markers associated with mite resistance were identified. In stepwise multiple regression analysis of SSRs, a combination of 6 markers showed 100% association with mite infestation. Stepwise multiple regression analysis for RAPD data revealed that a combination of 3 markers accounted for 83.86% of mite resistance in the selected materials. Combined stepwise multiple regression analysis of RAPD and SSR data showed that a combination of 5 markers explained 100% of the association with mite resistance in coconut. Markers associated with mite resistance are important in coconut breeding programs and will facilitate the selection of mite-resistant plants at an early stage as well as mother plants for breeding programs.

  13. An Adaptive Association Test for Multiple Phenotypes with GWAS Summary Statistics.

    PubMed

    Kim, Junghi; Bai, Yun; Pan, Wei

    2015-12-01

    We study the problem of testing for single marker-multiple phenotype associations based on genome-wide association study (GWAS) summary statistics without access to individual-level genotype and phenotype data. For most published GWASs, because obtaining summary data is substantially easier than accessing individual-level phenotype and genotype data, while often multiple correlated traits have been collected, the problem studied here has become increasingly important. We propose a powerful adaptive test and compare its performance with some existing tests. We illustrate its applications to analyses of a meta-analyzed GWAS dataset with three blood lipid traits and another with sex-stratified anthropometric traits, and further demonstrate its potential power gain over some existing methods through realistic simulation studies. We start from the situation with only one set of (possibly meta-analyzed) genome-wide summary statistics, then extend the method to meta-analysis of multiple sets of genome-wide summary statistics, each from one GWAS. We expect the proposed test to be useful in practice as more powerful than or complementary to existing methods. © 2015 WILEY PERIODICALS, INC.

  14. DIFFERENTIAL ANALYZER

    DOEpatents

    Sorensen, E.G.; Gordon, C.M.

    1959-02-10

    Improvements in analog eomputing machines of the class capable of evaluating differential equations, commonly termed differential analyzers, are described. In general form, the analyzer embodies a plurality of basic computer mechanisms for performing integration, multiplication, and addition, and means for directing the result of any one operation to another computer mechanism performing a further operation. In the device, numerical quantities are represented by the rotation of shafts, or the electrical equivalent of shafts.

  15. Expert judgment on markers to deter inadvertent human intrusion into the Waste Isolation Pilot Plant

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trauth, K.M.; Hora, S.C.; Guzowski, R.V.

    1993-11-01

    The expert panel identified basic principles to guide current and future marker development efforts: (1) the site must be marked, (2) message(s) must be truthful and informative, (3) multiple components within a marker system, (4) multiple means of communication (e.g., language, pictographs, scientific diagrams), (5) multiple levels of complexity within individual messages on individual marker system elements, (6) use of materials with little recycle value, and (7) international effort to maintain knowledge of the locations and contents of nuclear waste repositories. The efficacy of the markers in deterring inadvertent human intrusion was estimated to decrease with time, with the probabilitymore » function varying with the mode of intrusion (who is intruding and for what purpose) and the level of technological development of the society. The development of a permanent, passive marker system capable of surviving and remaining interpretable for 10,000 years will require further study prior to implementation.« less

  16. Analyzing Multiple-Choice Questions by Model Analysis and Item Response Curves

    NASA Astrophysics Data System (ADS)

    Wattanakasiwich, P.; Ananta, S.

    2010-07-01

    In physics education research, the main goal is to improve physics teaching so that most students understand physics conceptually and be able to apply concepts in solving problems. Therefore many multiple-choice instruments were developed to probe students' conceptual understanding in various topics. Two techniques including model analysis and item response curves were used to analyze students' responses from Force and Motion Conceptual Evaluation (FMCE). For this study FMCE data from more than 1000 students at Chiang Mai University were collected over the past three years. With model analysis, we can obtain students' alternative knowledge and the probabilities for students to use such knowledge in a range of equivalent contexts. The model analysis consists of two algorithms—concentration factor and model estimation. This paper only presents results from using the model estimation algorithm to obtain a model plot. The plot helps to identify a class model state whether it is in the misconception region or not. Item response curve (IRC) derived from item response theory is a plot between percentages of students selecting a particular choice versus their total score. Pros and cons of both techniques are compared and discussed.

  17. Molecular characterization and identification of markers for toxic and non-toxic varieties of Jatropha curcas L. using RAPD, AFLP and SSR markers.

    PubMed

    Sudheer Pamidimarri, D V N; Singh, Sweta; Mastan, Shaik G; Patel, Jalpa; Reddy, Muppala P

    2009-07-01

    Jatropha curcas L., a multipurpose shrub has acquired significant economic importance for its seed oil which can be converted to biodiesel, is emerging as an alternative to petro-diesel. The deoiled seed cake remains after oil extraction is toxic and cannot be used as a feed despite having best nutritional contents. No quantitative and qualitative differences were observed between toxic and non-toxic varieties of J. curcas except for phorbol esters content. Development of molecular marker will enable to differentiate non-toxic from toxic variety in a mixed population and also help in improvement of the species through marker assisted breeding programs. The present investigation was undertaken to characterize the toxic and non-toxic varieties at molecular level and to develop PCR based molecular markers for distinguishing non-toxic from toxic or vice versa. The polymorphic markers were successfully identified specific to non-toxic and toxic variety using RAPD and AFLP techniques. Totally 371 RAPD, 1,442 AFLP markers were analyzed and 56 (15.09%) RAPD, 238 (16.49%) AFLP markers were found specific to either of the varieties. Genetic similarity between non-toxic and toxic verity was found to be 0.92 by RAPD and 0.90 by AFLP fingerprinting. In the present study out of 12 microsatellite markers analyzed, seven markers were found polymorphic. Among these seven, jcms21 showed homozygous allele in the toxic variety. The study demonstrated that both RAPD and AFLP techniques were equally competitive in identifying polymorphic markers and differentiating both the varieties of J. curcas. Polymorphism of SSR markers prevailed between the varieties of J. curcas. These RAPD and AFLP identified markers will help in selective cultivation of specific variety and along with SSRs these markers can be exploited for further improvement of the species through breeding and Marker Assisted Selection (MAS).

  18. Should "Multiple Imputations" Be Treated as "Multiple Indicators"?

    ERIC Educational Resources Information Center

    Mislevy, Robert J.

    1993-01-01

    Multiple imputations for latent variables are constructed so that analyses treating them as true variables have the correct expectations for population characteristics. Analyzing multiple imputations in accordance with their construction yields correct estimates of population characteristics, whereas analyzing them as multiple indicators generally…

  19. Cell Free DNA and Procalcitonin as Early Markers of Complications in ICU Patients with Multiple Trauma and Major Surgery.

    PubMed

    Ahmed, Asmaa I; Soliman, Randa A; Samir, Shereif

    2016-12-01

    Cell free DNA (cfDNA) was recently suggested as a new marker of sepsis and poor outcome in ICU patients. Procalcitonin has also been the focus of attention as an early marker for systemic inflammation and sepsis. cfDNA, procalcitonin (PCT), C-reactive protein (CRP), and lactate levels were measured in 30 ICU patients with multiple trauma or after major surgery on the first day of admission and on 5th and 7th days for PCT, CRP, and lactate. cfDNA was measured by real-time PCR, PCT by ELISA, CRP immunoturbidimetrically, and lactate spectrophotometrically. SOFA score and Injury Severity Score (ISS) for trauma patients were calculated. Significantly higher levels of cfDNA were observed in non-survivor patients in comparison to survivors and in patients with sepsis in comparison to those without sepsis (p = 0.002 and p = 0.02, respectively). The ROC curve was calculated for cfDNA as a predictor of outcome, the area under the curve (AUC) was 0.847 (95% CI: 0.669 - 0.952), at a cutoff value of 15500 ng/µL, sensitivity = 83.3%, specificity = 77.8% (p < 0.0001). As a prognostic marker of sepsis, the AUC for cfDNA was 0.788 (95% CI: 0.601 - 0.915), sensitivity = 56.25%, specificity = 100% (p = 0.0007). Day 5 PCT levels significantly correlated with SOFA scores on day 5, ISS on admission (p < 0.001 and p = 0.028, respectively), and a significant elevation of its levels was observed in non-survivor patients compared to survivors (p = 0.001). As a predictor of sepsis, PCT showed a sensitivity of 81.3%, specificity of 100% on day 5, (AUC: 0.987, 95% CI: 0.955 - 1.00); at a cutoff value of 202.90 pg/mL (p = 0.001). As a predictor of outcome, PCT on day 5 showed a sensitivity of 94.0% and a specificity of 78.0% at a cutoff value of 194.40 pg/mL (p = 0.001). Day 1 CRP correlated with ISS on admission, and on day 5 it correlated with SOFA score 5, while lactate correlated with length of stay on days 1, 5, and 7, and its levels were significantly higher in non-survivors on days 5

  20. Insights into population ecology and sexual selection in snakes through the application of DNA-based genetic markers.

    PubMed

    Gibbs, H L; Weatherhead, P J

    2001-01-01

    Hypervariable genetic markers have revolutionized studies of kinship, behavioral ecology, and population biology in vertebrate groups such as birds, but their use in snakes remains limited. To illustrate the value of such markers in snakes, we review studies that have used microsatellite DNA loci to analyze local population differentiation and parentage in snakes. Four ecologically distinct species of snakes all show evidence for differentiation at small spatial scales (2-15 km), but with substantial differences among species. This result highlights how genetic analysis can reveal hidden aspects of the natural history of difficult-to-observe taxa, and it raises important questions about the ecological factors that may contribute to restricted gene flow. A 3-year study of genetic parentage in marked populations of the northern water snake showed that (1) participation in mating aggregations was a poor predictor of genetic-based measures of reproductive success; (2) multiple paternity was high, yet there was no detectable fitness advantage to multiple mating by females; and (3) the opportunity for selection was far higher in males than in females due to a larger variance in male reproductive success, and yet this resulted in no detectable selection on morphological variation in males. Thus genetic markers have provided accurate measures of individual reproductive success in this species, an important step toward resolving the adaptive significance of key features including multiple paternity and reversed sexual size dimorphism. Overall these studies illustrate how genetic analyses of snakes provide previously unobtainable information of long-standing interest to behavioral ecologists.

  1. Mark-recapture with multiple, non-invasive marks.

    PubMed

    Bonner, Simon J; Holmberg, Jason

    2013-09-01

    Non-invasive marks, including pigmentation patterns, acquired scars, and genetic markers, are often used to identify individuals in mark-recapture experiments. If animals in a population can be identified from multiple, non-invasive marks then some individuals may be counted twice in the observed data. Analyzing the observed histories without accounting for these errors will provide incorrect inference about the population dynamics. Previous approaches to this problem include modeling data from only one mark and combining estimators obtained from each mark separately assuming that they are independent. Motivated by the analysis of data from the ECOCEAN online whale shark (Rhincodon typus) catalog, we describe a Bayesian method to analyze data from multiple, non-invasive marks that is based on the latent-multinomial model of Link et al. (2010, Biometrics 66, 178-185). Further to this, we describe a simplification of the Markov chain Monte Carlo algorithm of Link et al. (2010, Biometrics 66, 178-185) that leads to more efficient computation. We present results from the analysis of the ECOCEAN whale shark data and from simulation studies comparing our method with the previous approaches. © 2013, The International Biometric Society.

  2. Nonparametric rank regression for analyzing water quality concentration data with multiple detection limits.

    PubMed

    Fu, Liya; Wang, You-Gan

    2011-02-15

    Environmental data usually include measurements, such as water quality data, which fall below detection limits, because of limitations of the instruments or of certain analytical methods used. The fact that some responses are not detected needs to be properly taken into account in statistical analysis of such data. However, it is well-known that it is challenging to analyze a data set with detection limits, and we often have to rely on the traditional parametric methods or simple imputation methods. Distributional assumptions can lead to biased inference and justification of distributions is often not possible when the data are correlated and there is a large proportion of data below detection limits. The extent of bias is usually unknown. To draw valid conclusions and hence provide useful advice for environmental management authorities, it is essential to develop and apply an appropriate statistical methodology. This paper proposes rank-based procedures for analyzing non-normally distributed data collected at different sites over a period of time in the presence of multiple detection limits. To take account of temporal correlations within each site, we propose an optimal linear combination of estimating functions and apply the induced smoothing method to reduce the computational burden. Finally, we apply the proposed method to the water quality data collected at Susquehanna River Basin in United States of America, which clearly demonstrates the advantages of the rank regression models.

  3. Multiple target drug cocktail design for attacking the core network markers of four cancers using ligand-based and structure-based virtual screening methods

    PubMed Central

    2015-01-01

    Background Computer-aided drug design has a long history of being applied to discover new molecules to treat various cancers, but it has always been focused on single targets. The development of systems biology has let scientists reveal more hidden mechanisms of cancers, but attempts to apply systems biology to cancer therapies remain at preliminary stages. Our lab has successfully developed various systems biology models for several cancers. Based on these achievements, we present the first attempt to combine multiple-target therapy with systems biology. Methods In our previous study, we identified 28 significant proteins--i.e., common core network markers--of four types of cancers as house-keeping proteins of these cancers. In this study, we ranked these proteins by summing their carcinogenesis relevance values (CRVs) across the four cancers, and then performed docking and pharmacophore modeling to do virtual screening on the NCI database for anti-cancer drugs. We also performed pathway analysis on these proteins using Panther and MetaCore to reveal more mechanisms of these cancer house-keeping proteins. Results We designed several approaches to discover targets for multiple-target cocktail therapies. In the first one, we identified the top 20 drugs for each of the 28 cancer house-keeping proteins, and analyzed the docking pose to further understand the interaction mechanisms of these drugs. After screening for duplicates, we found that 13 of these drugs could target 11 proteins simultaneously. In the second approach, we chose the top 5 proteins with the highest summed CRVs and used them as the drug targets. We built a pharmacophore and applied it to do virtual screening against the Life-Chemical library for anti-cancer drugs. Based on these results, wet-lab bio-scientists could freely investigate combinations of these drugs for multiple-target therapy for cancers, in contrast to the traditional single target therapy. Conclusions Combination of systems biology

  4. Identification of molecular markers associated with fruit traits in olive and assessment of olive core collection with AFLP markers and fruit traits.

    PubMed

    Ipek, M; Seker, M; Ipek, A; Gul, M K

    2015-03-31

    The purpose of this study was to characterize olive core collection with amplified fragment length polymorphism (AFLP) markers and fruit traits and to determine AFLP markers significantly associated with these fruit characters in olive. A total of 168 polymorphic AFLP markers generated by five primer combinations and nine fruit traits were used to characterize relationships between 18 olive cultivars. Although all olive cultivars were discriminated from each other by either AFLP markers (<0.75 similarity level) or fruit traits, clustering based on the AFLP markers and fruit traits was not significantly correlated (r = 0.13). Partial clustering of olive cultivars by AFLP markers according to their geographical origin was observed. Associations of AFLP markers with fruits were determined using a multiple-regression analysis with stepwise addition of AFLP markers. Significant associations between eight AFLP markers and fruit traits were identified. While five AFLP markers demonstrated significant negative correlation with fruit and stone weight, width and length and total polyphenols (P < 0.05), three AFLP markers displayed significant positive correlation with α-tocopherol and γ-tocopherol (P < 0.01). This is the first report on the association of molecular markers with fruit traits in olive. Molecular markers associated with morphological and agronomic traits could be utilized for the breeding of olive cultivars. However, the association power of these markers needs to be confirmed in larger populations, and highly correlated markers should then be converted to PCR-based DNA markers such as sequence-characterized amplified region markers for better utilization.

  5. Comparison of genetic diversity and population structure of Pacific Coast whitebark pine across multiple markers

    Treesearch

    Andrew D. Bower; Bryce A. Richardson; Valerie Hipkins; Regina Rochefort; Carol Aubry

    2011-01-01

    Analysis of "neutral" molecular markers and "adaptive" quantitative traits are common methods of assessing genetic diversity and population structure. Molecular markers typically reflect the effects of demographic and stochastic processes but are generally assumed to not reflect natural selection. Conversely, quantitative (or "adaptive")...

  6. Frailty Markers and Treatment Decisions in Patients Seen in Oncogeriatric Clinics: Results from the ASRO Pilot Study.

    PubMed

    Farcet, Anaïs; de Decker, Laure; Pauly, Vanessa; Rousseau, Frédérique; Bergman, Howard; Molines, Catherine; Retornaz, Frédérique

    2016-01-01

    Comprehensive Geriatric Assessment (CGA) is the gold standard to help oncologists select the best cancer treatment for their older patients. Some authors have suggested that the concept of frailty could be a more useful approach in this population. We investigated whether frailty markers are associated with treatment recommendations in an oncogeriatric clinic. This prospective study included 70 years and older patients with solid tumors and referred for an oncogeriatric assessment. The CGA included nine domains: autonomy, comorbidities, medication, cognition, nutrition, mood, neurosensory deficits, falls, and social status. Five frailty markers were assessed (nutrition, physical activity, energy, mobility, and strength). Patients were categorized as Frail (three or more frailty markers), pre-frail (one or two frailty markers), or not-frail (no frailty marker). Treatment recommendations were classified into two categories: standard treatment with and without any changes and supportive/palliative care. Multiple logistic regression models were used to analyze factors associated with treatment recommendations. 217 patients, mean age 83 years (± Standard deviation (SD) 5.3), were included. In the univariate analysis, number of frailty markers, grip strength, physical activity, mobility, nutrition, energy, autonomy, depression, Eastern Cooperative Oncology Group Scale of Performance Status (ECOG-PS), and falls were significantly associated with final treatment recommendations. In the multivariate analysis, the number of frailty markers and basic Activities of Daily Living (ADL) were significantly associated with final treatment recommendations (p<0.001 and p = 0.010, respectively). Frailty markers are associated with final treatment recommendations in older cancer patients. Longitudinal studies are warranted to better determine their use in a geriatric oncology setting.

  7. DC-Analyzer-facilitated combinatorial strategy for rapid directed evolution of functional enzymes with multiple mutagenesis sites.

    PubMed

    Wang, Xiong; Zheng, Kai; Zheng, Huayu; Nie, Hongli; Yang, Zujun; Tang, Lixia

    2014-12-20

    Iterative saturation mutagenesis (ISM) has been shown to be a powerful method for directed evolution. In this study, the approach was modified (termed M-ISM) by combining the single-site saturation mutagenesis method with a DC-Analyzer-facilitated combinatorial strategy, aiming to evolve novel biocatalysts efficiently in the case where multiple sites are targeted simultaneously. Initially, all target sites were explored individually by constructing single-site saturation mutagenesis libraries. Next, the top two to four variants in each library were selected and combined using the DC-Analyzer-facilitated combinatorial strategy. In addition to site-saturation mutagenesis, iterative saturation mutagenesis also needed to be performed. The advantages of M-ISM over ISM were that the screening effort is greatly reduced, and the entire M-ISM procedure was less time-consuming. The M-ISM strategy was successfully applied to the randomization of halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) when five interesting sites were targeted simultaneously. After screening 900 clones in total, six positive mutants were obtained. These mutants exhibited 4.0- to 9.3-fold higher k(cat) values than did the wild-type HheC toward 1,3-dichloro-2-propanol. However, with the ISM strategy, the best hit showed a 5.9-fold higher k(cat) value toward 1,3-DCP than the wild-type HheC, which was obtained after screening 4000 clones from four rounds of mutagenesis. Therefore, M-ISM could serve as a simple and efficient version of ISM for the randomization of target genes with multiple positions of interest.

  8. Adaptive marker-free registration using a multiple point strategy for real-time and robust endoscope electromagnetic navigation.

    PubMed

    Luo, Xiongbiao; Wan, Ying; He, Xiangjian; Mori, Kensaku

    2015-02-01

    Registration of pre-clinical images to physical space is indispensable for computer-assisted endoscopic interventions in operating rooms. Electromagnetically navigated endoscopic interventions are increasingly performed at current diagnoses and treatments. Such interventions use an electromagnetic tracker with a miniature sensor that is usually attached at an endoscope distal tip to real time track endoscope movements in a pre-clinical image space. Spatial alignment between the electromagnetic tracker (or sensor) and pre-clinical images must be performed to navigate the endoscope to target regions. This paper proposes an adaptive marker-free registration method that uses a multiple point selection strategy. This method seeks to address an assumption that the endoscope is operated along the centerline of an intraluminal organ which is easily violated during interventions. We introduce an adaptive strategy that generates multiple points in terms of sensor measurements and endoscope tip center calibration. From these generated points, we adaptively choose the optimal point, which is the closest to its assigned the centerline of the hollow organ, to perform registration. The experimental results demonstrate that our proposed adaptive strategy significantly reduced the target registration error from 5.32 to 2.59 mm in static phantoms validation, as well as from at least 7.58 mm to 4.71 mm in dynamic phantom validation compared to current available methods. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. IPAT: a freely accessible software tool for analyzing multiple patent documents with inbuilt landscape visualizer.

    PubMed

    Ajay, Dara; Gangwal, Rahul P; Sangamwar, Abhay T

    2015-01-01

    Intelligent Patent Analysis Tool (IPAT) is an online data retrieval tool, operated based on text mining algorithm to extract specific patent information in a predetermined pattern into an Excel sheet. The software is designed and developed to retrieve and analyze technology information from multiple patent documents and generate various patent landscape graphs and charts. The software is C# coded in visual studio 2010, which extracts the publicly available patent information from the web pages like Google Patent and simultaneously study the various technology trends based on user-defined parameters. In other words, IPAT combined with the manual categorization will act as an excellent technology assessment tool in competitive intelligence and due diligence for predicting the future R&D forecast.

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

    PubMed

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

    2013-04-01

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

  11. EINVis: a visualization tool for analyzing and exploring genetic interactions in large-scale association studies.

    PubMed

    Wu, Yubao; Zhu, Xiaofeng; Chen, Jian; Zhang, Xiang

    2013-11-01

    Epistasis (gene-gene interaction) detection in large-scale genetic association studies has recently drawn extensive research interests as many complex traits are likely caused by the joint effect of multiple genetic factors. The large number of possible interactions poses both statistical and computational challenges. A variety of approaches have been developed to address the analytical challenges in epistatic interaction detection. These methods usually output the identified genetic interactions and store them in flat file formats. It is highly desirable to develop an effective visualization tool to further investigate the detected interactions and unravel hidden interaction patterns. We have developed EINVis, a novel visualization tool that is specifically designed to analyze and explore genetic interactions. EINVis displays interactions among genetic markers as a network. It utilizes a circular layout (specially, a tree ring view) to simultaneously visualize the hierarchical interactions between single nucleotide polymorphisms (SNPs), genes, and chromosomes, and the network structure formed by these interactions. Using EINVis, the user can distinguish marginal effects from interactions, track interactions involving more than two markers, visualize interactions at different levels, and detect proxy SNPs based on linkage disequilibrium. EINVis is an effective and user-friendly free visualization tool for analyzing and exploring genetic interactions. It is publicly available with detailed documentation and online tutorial on the web at http://filer.case.edu/yxw407/einvis/. © 2013 WILEY PERIODICALS, INC.

  12. Longitudinal Neuroimaging Hippocampal Markers for Diagnosing Alzheimer's Disease.

    PubMed

    Platero, Carlos; Lin, Lin; Tobar, M Carmen

    2018-05-21

    Hippocampal atrophy measures from magnetic resonance imaging (MRI) are powerful tools for monitoring Alzheimer's disease (AD) progression. In this paper, we introduce a longitudinal image analysis framework based on robust registration and simultaneous hippocampal segmentation and longitudinal marker classification of brain MRI of an arbitrary number of time points. The framework comprises two innovative parts: a longitudinal segmentation and a longitudinal classification step. The results show that both steps of the longitudinal pipeline improved the reliability and the accuracy of the discrimination between clinical groups. We introduce a novel approach to the joint segmentation of the hippocampus across multiple time points; this approach is based on graph cuts of longitudinal MRI scans with constraints on hippocampal atrophy and supported by atlases. Furthermore, we use linear mixed effect (LME) modeling for differential diagnosis between clinical groups. The classifiers are trained from the average residue between the longitudinal marker of the subjects and the LME model. In our experiments, we analyzed MRI-derived longitudinal hippocampal markers from two publicly available datasets (Alzheimer's Disease Neuroimaging Initiative, ADNI and Minimal Interval Resonance Imaging in Alzheimer's Disease, MIRIAD). In test/retest reliability experiments, the proposed method yielded lower volume errors and significantly higher dice overlaps than the cross-sectional approach (volume errors: 1.55% vs 0.8%; dice overlaps: 0.945 vs 0.975). To diagnose AD, the discrimination ability of our proposal gave an area under the receiver operating characteristic (ROC) curve (AUC) [Formula: see text] 0.947 for the control vs AD, AUC [Formula: see text] 0.720 for mild cognitive impairment (MCI) vs AD, and AUC [Formula: see text] 0.805 for the control vs MCI.

  13. L-split marker for augmented reality in aircraft assembly

    NASA Astrophysics Data System (ADS)

    Han, Pengfei; Zhao, Gang

    2016-04-01

    In order to improve the performance of conventional square markers widely used by marker-based augmented reality systems in aircraft assembly environments, an L-split marker is proposed. Every marker consists of four separate L-shaped parts and each of them contains partial information about the marker. Geometric features of the L-shape, which are more discriminate than the symmetrical square shape adopted by conventional markers, are used to detect proposed markers from the camera images effectively. The marker is split into four separate parts in order to improve the robustness to occlusion and curvature to some extent. The registration process can be successfully completed as long as three parts are detected (up to about 80% of the area could be occluded). Moreover, when we attach the marker on nonplanar surfaces, the curvature status of the marker can be roughly analyzed with every part's normal direction, which can be obtained since their six corners have been explicitly determined in the previous detection process. And based on the marker design, new detection and recognition algorithms are proposed and detailed. The experimental results show that the marker and the algorithms are effective.

  14. [Immunological Markers in Organ Transplantation].

    PubMed

    Beckmann, J H; Heits, N; Braun, F; Becker, T

    2017-04-01

    The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.

  15. Introduction of new genetic markers on human chromosomes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Satoh, Hitoshi; Barrett, J.C.; Oshimura, Mitsuo

    1991-03-01

    The purpose of this study was to use DNA transfection and microcell chromosome transfer techniques to engineer a human chromosome containing multiple biochemical markers for which selectable growth conditions exist. The starting chromosome was a t(X;3)(3pter{yields}3p12::Xq26{yields}Xpter) chromosome from a reciprocal translocation in the normal human fibroblast cell line GM0439. This chromosome was transferred to a HPRT (hypoxanthine phosphoribosyltransferase)-deficient mouse A9 cell line by microcell fusion and selected under growth conditions for the HPRT gene on the human t(X;3) chromosome. A resultant HAT-resistant cell line (A9(GM0439)-1) contained a single human t(X;3) chromosome. These results demonstrate that microcell chromosome transfer can bemore » used to select chromosomes containing multiple markers.« less

  16. Y-Chromosome Markers for the Red Fox.

    PubMed

    Rando, Halie M; Stutchman, Jeremy T; Bastounes, Estelle R; Johnson, Jennifer L; Driscoll, Carlos A; Barr, Christina S; Trut, Lyudmila N; Sacks, Benjamin N; Kukekova, Anna V

    2017-09-01

    The de novo assembly of the red fox (Vulpes vulpes) genome has facilitated the development of genomic tools for the species. Efforts to identify the population history of red foxes in North America have previously been limited by a lack of information about the red fox Y-chromosome sequence. However, a megabase of red fox Y-chromosome sequence was recently identified over 2 scaffolds in the reference genome. Here, these scaffolds were scanned for repeated motifs, revealing 194 likely microsatellites. Twenty-three of these loci were selected for primer development and, after testing, produced a panel of 11 novel markers that were analyzed alongside 2 markers previously developed for the red fox from dog Y-chromosome sequence. The markers were genotyped in 76 male red foxes from 4 populations: 7 foxes from Newfoundland (eastern Canada), 12 from Maryland (eastern United States), and 9 from the island of Great Britain, as well as 48 foxes of known North American origin maintained on an experimental farm in Novosibirsk, Russia. The full marker panel revealed 22 haplotypes among these red foxes, whereas the 2 previously known markers alone would have identified only 10 haplotypes. The haplotypes from the 4 populations clustered primarily by continent, but unidirectional gene flow from Great Britain and farm populations may influence haplotype diversity in the Maryland population. The development of new markers has increased the resolution at which red fox Y-chromosome diversity can be analyzed and provides insight into the contribution of males to red fox population diversity and patterns of phylogeography. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Molecular marker systems for Oenothera genetics.

    PubMed

    Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G; Greiner, Stephan

    2008-11-01

    The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome-genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9.8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed.

  18. Multiple SNP Markers Reveal Fine-Scale Population and Deep Phylogeographic Structure in European Anchovy (Engraulis encrasicolus L.)

    PubMed Central

    Zarraonaindia, Iratxe; Iriondo, Mikel; Albaina, Aitor; Pardo, Miguel Angel; Manzano, Carmen; Grant, W. Stewart; Irigoien, Xabier; Estonba, Andone

    2012-01-01

    Geographic surveys of allozymes, microsatellites, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have detected several genetic subdivisions among European anchovy populations. However, these studies have been limited in their power to detect some aspects of population structure by the use of a single or a few molecular markers, or by limited geographic sampling. We use a multi-marker approach, 47 nDNA and 15 mtDNA single nucleotide polymorphisms (SNPs), to analyze 626 European anchovies from the whole range of the species to resolve shallow and deep levels of population structure. Nuclear SNPs define 10 genetic entities within two larger genetically distinctive groups associated with oceanic variables and different life-history traits. MtDNA SNPs define two deep phylogroups that reflect ancient dispersals and colonizations. These markers define two ecological groups. One major group of Iberian-Atlantic populations is associated with upwelling areas on narrow continental shelves and includes populations spawning and overwintering in coastal areas. A second major group includes northern populations in the North East (NE) Atlantic (including the Bay of Biscay) and the Mediterranean and is associated with wide continental shelves with local larval retention currents. This group tends to spawn and overwinter in oceanic areas. These two groups encompass ten populations that differ from previously defined management stocks in the Alboran Sea, Iberian-Atlantic and Bay of Biscay regions. In addition, a new North Sea-English Channel stock is defined. SNPs indicate that some populations in the Bay of Biscay are genetically closer to North Western (NW) Mediterranean populations than to other populations in the NE Atlantic, likely due to colonizations of the Bay of Biscay and NW Mediterranean by migrants from a common ancestral population. Northern NE Atlantic populations were subsequently established by migrants from the Bay of Biscay. Populations along the Iberian

  19. [Studies of marker screening efficiency and corresponding influencing factors in QTL composite interval mapping].

    PubMed

    Gao, Yong-Ming; Wan, Ping

    2002-06-01

    Screening markers efficiently is the foundation of mapping QTLs by composite interval mapping. Main and interaction markers distinguished, besides using background control for genetic variation, could also be used to construct intervals of two-way searching for mapping QTLs with epistasis, which can save a lot of calculation time. Therefore, the efficiency of marker screening would affect power and precision of QTL mapping. A doubled haploid population with 200 individuals and 5 chromosomes was constructed, with 50 markers evenly distributed at 10 cM space. Among a total of 6 QTLs, one was placed on chromosome I, two linked on chromosome II, and the other three linked on chromosome IV. QTL setting included additive effects and epistatic effects of additive x additive, the corresponding QTL interaction effects were set if data were collected under multiple environments. The heritability was assumed to be 0.5 if no special declaration. The power of marker screening by stepwise regression, forward regression, and three methods for random effect prediction, e.g. best linear unbiased prediction (BLUP), linear unbiased prediction (LUP) and adjusted unbiased prediction (AUP), was studied and compared through 100 Monte Carlo simulations. The results indicated that the marker screening power by stepwise regression at 0.1, 0.05 and 0.01 significant level changed from 2% to 68%, the power changed from 2% to 72% by forward regression. The larger the QTL effects, the higher the marker screening power. While the power of marker screening by three random effect prediction was very low, the maximum was only 13%. That suggested that regression methods were much better than those by using the approaches of random effect prediction to identify efficient markers flanking QTLs, and forward selection method was more simple and efficient. The results of simulation study on heritability showed that heightening of both general heritability and interaction heritability of genotype x

  20. Effects of ivermectin on Danio rerio: a multiple endpoint approach: behaviour, weight and subcellular markers.

    PubMed

    Domingues, I; Oliveira, R; Soares, A M V M; Amorim, M J B

    2016-04-01

    Ivermectin (IVM) is a broad acting antihelmintic used in various veterinary pharmaceuticals. It has been shown that IVM enters the aquatic compartment and adversely affects organisms including fish. This study is based on the hypothesis that long term exposure to IVM affects fish and thus, the main objective was to assess the chronic effects of 0.25 and 25 µg IVM/L to zebrafish using multiple endpoints representative of several levels of biological organization: weight, behaviour (swimming and feeding) and subcellular markers including biomarkers for oestrogenicity (vitellogenin-VTG), oxidative stress (catalase-CAT and glutathione-S-transferase-GST) and neurotransmission (cholinesterase-ChE). Concentrations as low as 0.25 µg IVM/L disrupted the swimming behaviour, causing fish to spend more time at the bottom of aquaria. Such reduction of the swimming performance affected the feeding ability which is likely responsible for the weight loss. The effects on weight were gender differentiated, being more pronounced in males (0.25 µg IVM/L) than in females (25 µg IVM/L). Fish exposed to 25 µg/L exhibited darker coloration and mild curvature of the spine. No effects on VTG and AChE were observed, but a reduction on CAT and GST levels was observed in fish exposed to 25 µg IVM/L, although these alterations probably only reflect the general condition of the fish which was significantly compromised at this concentration. Despite that predicted environmental concentrations of IVM are below 0.25 µg/L, the behavioural effects may be translated into important ecological impacts, e.g. at predator-prey interactions where fish competitive advantage can be decreased. Future work should address the link between behaviour disruption and population fitness. The current study was based on a one experiment and multiple endpoint (anchored) approach, allowing the results to be integrated and linked towards a mechanistic understanding.

  1. Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.

    PubMed

    Joslyn, Geoff; Brush, Gerry; Robertson, Margaret; Smith, Tom L; Kalmijn, Jelger; Schuckit, Marc; White, Raymond L

    2008-12-23

    As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P < 0.025) with several LR phenotypes in a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

  2. Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production.

    PubMed

    Camilleri, Emily T; Gustafson, Michael P; Dudakovic, Amel; Riester, Scott M; Garces, Catalina Galeano; Paradise, Christopher R; Takai, Hideki; Karperien, Marcel; Cool, Simon; Sampen, Hee-Jeong Im; Larson, A Noelle; Qu, Wenchun; Smith, Jay; Dietz, Allan B; van Wijnen, Andre J

    2016-08-11

    Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105, and CD44) is used to define MSCs, identification of functionally relevant cell surface markers would provide more robust release criteria and options for quality control. In addition, cell surface expression may distinguish between MSCs from different sources, including bone marrow-derived MSCs and clinical-grade adipose-derived MSCs (AMSCs) grown in human platelet lysate (hPL). In this work we utilized quantitative PCR, flow cytometry, and RNA-sequencing to characterize AMSCs grown in hPL and validated non-classical markers in 15 clinical-grade donors. We characterized the surface marker transcriptome of AMSCs, validated the expression of classical markers, and identified nine non-classical markers (i.e., CD36, CD163, CD271, CD200, CD273, CD274, CD146, CD248, and CD140B) that may potentially discriminate AMSCs from other cell types. More importantly, these markers exhibit variability in cell surface expression among different cell isolates from a diverse cohort of donors, including freshly prepared, previously frozen, or proliferative state AMSCs and may be informative when manufacturing cells. Our study establishes that clinical-grade AMSCs expanded in hPL represent a homogeneous cell culture population according to classical markers,. Additionally, we validated new biomarkers for further AMSC characterization that may provide novel information guiding the development of new release criteria. Use of Autologous Bone Marrow Aspirate Concentrate in Painful Knee Osteoarthritis (BMAC): Clinicaltrials.gov NCT01931007 . Registered August 26, 2013. MSC for Occlusive Disease of the Kidney: Clinicaltrials.gov NCT01840540 . Registered April 23, 2013. Mesenchymal Stem Cell Therapy in Multiple

  3. Molecular markers: Implications for cytopathology and specimen collection.

    PubMed

    VanderLaan, Paul A

    2015-08-01

    Cytologic specimens obtained through minimally invasive biopsy techniques are increasingly being used as principle diagnostic specimens for tumors arising in multiple sites. The number and scope of ancillary tests performed on these specimens have grown substantially over the past decade, including many molecular markers that not only can aid in formulating accurate and specific diagnoses but also can provide prognostic or therapeutic information to help direct clinical decisions. Thus, the cytopathologist needs to ensure that adequate material is collected and appropriately processed for the study of relevant molecular markers, many of which are specific to tumor site. This brief review covers considerations for effective cytologic specimen collection and processing to ensure diagnostic and testing success. In addition, a general overview is provided of molecular markers pertinent to tumors from a variety of sites. The recognition of these established and emerging molecular markers by cytopathologists is an important step toward realizing the promise of personalized medicine. © 2015 American Cancer Society.

  4. Phylogeography and postglacial recolonization of Europe by Rhinolophus hipposideros: evidence from multiple genetic markers.

    PubMed

    Dool, Serena E; Puechmaille, Sébastien J; Dietz, Christian; Juste, Javier; Ibáñez, Carlos; Hulva, Pavel; Roué, Stéphane G; Petit, Eric J; Jones, Gareth; Russo, Danilo; Toffoli, Roberto; Viglino, Andrea; Martinoli, Adriano; Rossiter, Stephen J; Teeling, Emma C

    2013-08-01

    The demographic history of Rhinolophus hipposideros (lesser horseshoe bat) was reconstructed across its European, North African and Middle-Eastern distribution prior to, during and following the most recent glaciations by generating and analysing a multimarker data set. This data set consisted of an X-linked nuclear intron (Bgn; 543 bp), mitochondrial DNA (cytb-tRNA-control region; 1630 bp) and eight variable microsatellite loci for up to 373 individuals from 86 localities. Using this data set of diverse markers, it was possible to determine the species' demography at three temporal stages. Nuclear intron data revealed early colonization into Europe from the east, which pre-dates the Quaternary glaciations. The mtDNA data supported multiple glacial refugia across the Mediterranean, the largest of which were found in the Ibero-Maghreb region and an eastern location (Anatolia/Middle East)-that were used by R. hipposideros during the most recent glacial cycles. Finally, microsatellites provided the most recent information on these species' movements since the Last Glacial Maximum and suggested that lineages that had diverged into glacial refugia, such as in the Ibero-Maghreb region, have remained isolated. These findings should be used to inform future conservation management strategies for R. hipposideros and show the power of using a multimarker data set for phylogeographic studies. © 2013 John Wiley & Sons Ltd.

  5. A study on software-based sensing technology for multiple object control in AR video.

    PubMed

    Jung, Sungmo; Song, Jae-Gu; Hwang, Dae-Joon; Ahn, Jae Young; Kim, Seoksoo

    2010-01-01

    Researches on Augmented Reality (AR) have recently received attention. With these, the Machine-to-Machine (M2M) market has started to be active and there are numerous efforts to apply this to real life in all sectors of society. To date, the M2M market has applied the existing marker-based AR technology in entertainment, business and other industries. With the existing marker-based AR technology, a designated object can only be loaded on the screen from one marker and a marker has to be added to load on the screen the same object again. This situation creates a problem where the relevant marker'should be extracted and printed in screen so that loading of the multiple objects is enabled. However, since the distance between markers will not be measured in the process of detecting and copying markers, the markers can be overlapped and thus the objects would not be augmented. To solve this problem, a circle having the longest radius needs to be created from a focal point of a marker to be copied, so that no object is copied within the confines of the circle. In this paper, software-based sensing technology for multiple object detection and loading using PPHT has been developed and overlapping marker control according to multiple object control has been studied using the Bresenham and Mean Shift algorithms.

  6. Genetic evolutionary taboo search for optimal marker placement in infrared patient setup

    NASA Astrophysics Data System (ADS)

    Riboldi, M.; Baroni, G.; Spadea, M. F.; Tagaste, B.; Garibaldi, C.; Cambria, R.; Orecchia, R.; Pedotti, A.

    2007-09-01

    In infrared patient setup adequate selection of the external fiducial configuration is required for compensating inner target displacements (target registration error, TRE). Genetic algorithms (GA) and taboo search (TS) were applied in a newly designed approach to optimal marker placement: the genetic evolutionary taboo search (GETS) algorithm. In the GETS paradigm, multiple solutions are simultaneously tested in a stochastic evolutionary scheme, where taboo-based decision making and adaptive memory guide the optimization process. The GETS algorithm was tested on a group of ten prostate patients, to be compared to standard optimization and to randomly selected configurations. The changes in the optimal marker configuration, when TRE is minimized for OARs, were specifically examined. Optimal GETS configurations ensured a 26.5% mean decrease in the TRE value, versus 19.4% for conventional quasi-Newton optimization. Common features in GETS marker configurations were highlighted in the dataset of ten patients, even when multiple runs of the stochastic algorithm were performed. Including OARs in TRE minimization did not considerably affect the spatial distribution of GETS marker configurations. In conclusion, the GETS algorithm proved to be highly effective in solving the optimal marker placement problem. Further work is needed to embed site-specific deformation models in the optimization process.

  7. PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress

    PubMed Central

    Jiang, Lingyan; Luo, Xiuquan; Shi, Jingxue; Sun, Hong; Sun, Qing; Sheikh, M Saeed

    2011-01-01

    We have previously cloned and characterized a novel p53 and DNA damage-regulated gene named PDRG1. PDRG1 was found to be differentially regulated by ultraviolet (UV) radiation and p53. In this study, we further investigated stress regulation of PDRG1 and found it to be selectively regulated by agents that induce genotoxic stress (DNA damage). Using cancer profiling arrays, we also investigated PDRG1 expression in matching normal and tumor samples representing various malignancies and found its expression to be upregulated in multiple malignancies including cancers of the colon, rectum, ovary, lung, stomach, breast and uterus when compared to their respective matched normal tissues. Western blot and immunohistochemical analyses were also performed on select specimen sets of colon cancers and matching normal tissues and the results also indicated PDRG1 overexpression in tumors relative to normal tissues. To gain insight into the function of PDRG1, we performed PDRG1 knockdown in human colon cancer cells and found its depletion to result in marked slowdown of tumor cell growth. These results suggest that PDRG1 may be linked to cell growth regulation. Yeast two-hybrid screening also led to the identification of PDCD7, CIZ1 and MAP1S as PDRG1-interacting proteins that are involved in apoptosis and cell cycle regulation which further implicate PDRG1 in controlling cell growth regulation. Taken together, our results indicate that PDRG1 expression is increased in multiple human malignancies suggesting it to be a high-value novel tumor marker that could play a role in cancer development and/or progression. PMID:21193842

  8. Computer-analyzed facial expression as a surrogate marker for autism spectrum social core symptoms.

    PubMed

    Owada, Keiho; Kojima, Masaki; Yassin, Walid; Kuroda, Miho; Kawakubo, Yuki; Kuwabara, Hitoshi; Kano, Yukiko; Yamasue, Hidenori

    2018-01-01

    To develop novel interventions for autism spectrum disorder (ASD) core symptoms, valid, reliable, and sensitive longitudinal outcome measures are required for detecting symptom change over time. Here, we tested whether a computerized analysis of quantitative facial expression measures could act as a marker for core ASD social symptoms. Facial expression intensity values during a semi-structured socially interactive situation extracted from the Autism Diagnostic Observation Schedule (ADOS) were quantified by dedicated software in 18 high-functioning adult males with ASD. Controls were 17 age-, gender-, parental socioeconomic background-, and intellectual level-matched typically developing (TD) individuals. Statistical analyses determined whether values representing the strength and variability of each facial expression element differed significantly between the ASD and TD groups and whether they correlated with ADOS reciprocal social interaction scores. Compared with the TD controls, facial expressions in the ASD group appeared more "Neutral" (d = 1.02, P = 0.005, PFDR < 0.05) with less variation in Neutral expression (d = 1.08, P = 0.003, PFDR < 0.05). Their expressions were also less "Happy" (d = -0.78, P = 0.038, PFDR > 0.05) with lower variability in Happy expression (d = 1.10, P = 0.003, PFDR < 0.05). Moreover, the stronger Neutral facial expressions in the ASD participants were positively correlated with poorer ADOS reciprocal social interaction scores (ρ = 0.48, P = 0.042). These findings indicate that our method for quantitatively measuring reduced facial expressivity during social interactions can be a promising marker for core ASD social symptoms.

  9. Relationship between pulmonary and systemic markers of exposure to multiple types of welding particulate matter.

    PubMed

    Erdely, Aaron; Salmen-Muniz, Rebecca; Liston, Angie; Hulderman, Tracy; Zeidler-Erdely, Patti C; Antonini, James M; Simeonova, Petia P

    2011-09-05

    Welding results in a unique and complex occupational exposure. Recent epidemiological studies have shown an increased risk of cardiovascular disease following welding fume exposure. In this study, we compared the induction of pulmonary and systemic inflammation following exposure to multiple types of welding fumes. Mice were exposed to 340μg of manual metal arc stainless steel (MMA-SS), gas metal arc-SS (GMA-SS) or GMA-mild steel (GMA-MS) by pharyngeal aspiration. Mice were sacrificed at 4 and 24h post-exposure to evaluate various parameters of pulmonary and systemic inflammation. Alterations in pulmonary gene expression by a custom designed TaqMan array showed minimal differences between the fumes at 4h. Conversely at 24h, gene expression changes were further increased by SS but not GMA-MS exposure. These findings were associated with the surrogate marker of systemic inflammation, liver acute phase gene induction. Interestingly, stress response genes in cardiovascular tissues were only increased following MMA-SS exposure. These effects were related to the initial level of pulmonary cytotoxicity, as measured by lactate dehydrogenase activity, which was greatest following MMA-SS exposure. In conclusion, varying types of welding fumes elicit quantitatively different systemic inflammatory and/or stress responses. Published by Elsevier Ireland Ltd.

  10. Motion capture for human motion measuring by using single camera with triangle markers

    NASA Astrophysics Data System (ADS)

    Takahashi, Hidenori; Tanaka, Takayuki; Kaneko, Shun'ichi

    2005-12-01

    This study aims to realize a motion capture for measuring 3D human motions by using single camera. Although motion capture by using multiple cameras is widely used in sports field, medical field, engineering field and so on, optical motion capture method with one camera is not established. In this paper, the authors achieved a 3D motion capture by using one camera, named as Mono-MoCap (MMC), on the basis of two calibration methods and triangle markers which each length of side is given. The camera calibration methods made 3D coordinates transformation parameter and a lens distortion parameter with Modified DLT method. The triangle markers enabled to calculate a coordinate value of a depth direction on a camera coordinate. Experiments of 3D position measurement by using the MMC on a measurement space of cubic 2 m on each side show an average error of measurement of a center of gravity of a triangle marker was less than 2 mm. As compared with conventional motion capture method by using multiple cameras, the MMC has enough accuracy for 3D measurement. Also, by putting a triangle marker on each human joint, the MMC was able to capture a walking motion, a standing-up motion and a bending and stretching motion. In addition, a method using a triangle marker together with conventional spherical markers was proposed. Finally, a method to estimate a position of a marker by measuring the velocity of the marker was proposed in order to improve the accuracy of MMC.

  11. A Study on Software-based Sensing Technology for Multiple Object Control in AR Video

    PubMed Central

    Jung, Sungmo; Song, Jae-gu; Hwang, Dae-Joon; Ahn, Jae Young; Kim, Seoksoo

    2010-01-01

    Researches on Augmented Reality (AR) have recently received attention. With these, the Machine-to-Machine (M2M) market has started to be active and there are numerous efforts to apply this to real life in all sectors of society. To date, the M2M market has applied the existing marker-based AR technology in entertainment, business and other industries. With the existing marker-based AR technology, a designated object can only be loaded on the screen from one marker and a marker has to be added to load on the screen the same object again. This situation creates a problem where the relevant marker’should be extracted and printed in screen so that loading of the multiple objects is enabled. However, since the distance between markers will not be measured in the process of detecting and copying markers, the markers can be overlapped and thus the objects would not be augmented. To solve this problem, a circle having the longest radius needs to be created from a focal point of a marker to be copied, so that no object is copied within the confines of the circle. In this paper, software-based sensing technology for multiple object detection and loading using PPHT has been developed and overlapping marker control according to multiple object control has been studied using the Bresenham and Mean Shift algorithms. PMID:22163444

  12. Serotonin, neural markers, and memory

    PubMed Central

    Meneses, Alfredo

    2015-01-01

    Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence. PMID:26257650

  13. Evaluation of Lumipulse® G1200 for the measurement of six tumor markers: Comparison with AIA® 2000.

    PubMed

    de Rancher, Marie-Aude Robert; Oudart, Jean-Baptiste; Maquart, François-Xavier; Monboisse, Jean Claude; Ramont, Laurent

    2016-11-01

    Tumor marker assays are daily practiced, for screening and follow up of cancers. Interassay precision is an important parameter for the interpretation of the kinetics of the markers, in order to conclude to the efficiency or failure of treatment. The aim of this study was to compare two automated Immunoassay analyzers, Lumipulse® G1200 and AIA® 2000. Both analyzers used an immunoassay system but with different antibodies. Six tumor markers commonly used were studied: AFP, PSA, CA 19-9, CA 15-3, CA 125 and CEA. 253 samples have been collected over a period of one month and analyzed by both analyzers. Regression of Passing-Badblock and Bland-Altman diagram were used to analyze the results for AFP (n=36), PSA (n=39), CA-125 (n=40), CA 15-3 (n=40), CA 19-9 (n=46) and CEA (n=52) were performed. Analytical performances of Lumipulse® G1200 highlighted the good inter-run and intra-run precision of the analyzer. We obtained a good correlation coefficient between Lumipulse G1200® and AIA 2000®, >0.96 for most markers except CA 19-9 which provided a correlation coefficient significantly lower than that obtained with other markers. The concordance for all markers was >94% except for CA 19-9 (83.7%). This study showed a good correlation between the two analyzers and, therefore, a transfer from one analyzer to the other is possible for the different markers studied. However, we found here the classical difficulty to transfer this type of analysis, due to the absence of method standardization. This difficulty was particularly illustrated by CA19-9. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  14. Detecting a hierarchical genetic population structure via Multi-InDel markers on the X chromosome

    PubMed Central

    Fan, Guang Yao; Ye, Yi; Hou, Yi Ping

    2016-01-01

    Detecting population structure and estimating individual biogeographical ancestry are very important in population genetics studies, biomedical research and forensics. Single-nucleotide polymorphism (SNP) has long been considered to be a primary ancestry-informative marker (AIM), but it is constrained by complex and time-consuming genotyping protocols. Following up on our previous study, we propose that a multi-insertion-deletion polymorphism (Multi-InDel) with multiple haplotypes can be useful in ancestry inference and hierarchical genetic population structures. A validation study for the X chromosome Multi-InDel marker (X-Multi-InDel) as a novel AIM was conducted. Genetic polymorphisms and genetic distances among three Chinese populations and 14 worldwide populations obtained from the 1000 Genomes database were analyzed. A Bayesian clustering method (STRUCTURE) was used to discern the continental origins of Europe, East Asia, and Africa. A minimal panel of ten X-Multi-InDels was verified to be sufficient to distinguish human ancestries from three major continental regions with nearly the same efficiency of the earlier panel with 21 insertion-deletion AIMs. Along with the development of more X-Multi-InDels, an approach using this novel marker has the potential for broad applicability as a cost-effective tool toward more accurate determinations of individual biogeographical ancestry and population stratification. PMID:27535707

  15. Molecular markers of neuropsychological functioning and Alzheimer's disease.

    PubMed

    Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O'Bryant, Sid

    2015-03-01

    The current project sought to examine molecular markers of neuropsychological functioning among elders with and without Alzheimer's disease (AD) and determine the predictive ability of combined molecular markers and select neuropsychological tests in detecting disease presence. Data were analyzed from 300 participants (n = 150, AD and n = 150, controls) enrolled in the Texas Alzheimer's Research and Care Consortium. Linear regression models were created to examine the link between the top five molecular markers from our AD blood profile and neuropsychological test scores. Logistical regressions were used to predict AD presence using serum biomarkers in combination with select neuropsychological measures. Using the neuropsychological test with the least amount of variance overlap with the molecular markers, the combined neuropsychological test and molecular markers was highly accurate in detecting AD presence. This work provides the foundation for the generation of a point-of-care device that can be used to screen for AD.

  16. Monte Carlo simulations on marker grouping and ordering.

    PubMed

    Wu, J; Jenkins, J; Zhu, J; McCarty, J; Watson, C

    2003-08-01

    Four global algorithms, maximum likelihood (ML), sum of adjacent LOD score (SALOD), sum of adjacent recombinant fractions (SARF) and product of adjacent recombinant fraction (PARF), and one approximation algorithm, seriation (SER), were used to compare the marker ordering efficiencies for correctly given linkage groups based on doubled haploid (DH) populations. The Monte Carlo simulation results indicated the marker ordering powers for the five methods were almost identical. High correlation coefficients were greater than 0.99 between grouping power and ordering power, indicating that all these methods for marker ordering were reliable. Therefore, the main problem for linkage analysis was how to improve the grouping power. Since the SER approach provided the advantage of speed without losing ordering power, this approach was used for detailed simulations. For more generality, multiple linkage groups were employed, and population size, linkage cutoff criterion, marker spacing pattern (even or uneven), and marker spacing distance (close or loose) were considered for obtaining acceptable grouping powers. Simulation results indicated that the grouping power was related to population size, marker spacing distance, and cutoff criterion. Generally, a large population size provided higher grouping power than small population size, and closely linked markers provided higher grouping power than loosely linked markers. The cutoff criterion range for achieving acceptable grouping power and ordering power differed for varying cases; however, combining all situations in this study, a cutoff criterion ranging from 50 cM to 60 cM was recommended for achieving acceptable grouping power and ordering power for different cases.

  17. [Future challenges in multiple sclerosis].

    PubMed

    Fernández, Óscar

    2014-12-01

    Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Analyzing latent state-trait and multiple-indicator latent growth curve models as multilevel structural equation models

    PubMed Central

    Geiser, Christian; Bishop, Jacob; Lockhart, Ginger; Shiffman, Saul; Grenard, Jerry L.

    2013-01-01

    Latent state-trait (LST) and latent growth curve (LGC) models are frequently used in the analysis of longitudinal data. Although it is well-known that standard single-indicator LGC models can be analyzed within either the structural equation modeling (SEM) or multilevel (ML; hierarchical linear modeling) frameworks, few researchers realize that LST and multivariate LGC models, which use multiple indicators at each time point, can also be specified as ML models. In the present paper, we demonstrate that using the ML-SEM rather than the SL-SEM framework to estimate the parameters of these models can be practical when the study involves (1) a large number of time points, (2) individually-varying times of observation, (3) unequally spaced time intervals, and/or (4) incomplete data. Despite the practical advantages of the ML-SEM approach under these circumstances, there are also some limitations that researchers should consider. We present an application to an ecological momentary assessment study (N = 158 youths with an average of 23.49 observations of positive mood per person) using the software Mplus (Muthén and Muthén, 1998–2012) and discuss advantages and disadvantages of using the ML-SEM approach to estimate the parameters of LST and multiple-indicator LGC models. PMID:24416023

  19. A High Density Consensus Genetic Map of Tetraploid Cotton That Integrates Multiple Component Maps through Molecular Marker Redundancy Check

    PubMed Central

    Blenda, Anna; Fang, David D.; Rami, Jean-François; Garsmeur, Olivier; Luo, Feng; Lacape, Jean-Marc

    2012-01-01

    A consensus genetic map of tetraploid cotton was constructed using six high-density maps and after the integration of a sequence-based marker redundancy check. Public cotton SSR libraries (17,343 markers) were curated for sequence redundancy using 90% as a similarity cutoff. As a result, 20% of the markers (3,410) could be considered as redundant with some other markers. The marker redundancy information had been a crucial part of the map integration process, in which the six most informative interspecific Gossypium hirsutum×G. barbadense genetic maps were used for assembling a high density consensus (HDC) map for tetraploid cotton. With redundant markers being removed, the HDC map could be constructed thanks to the sufficient number of collinear non-redundant markers in common between the component maps. The HDC map consists of 8,254 loci, originating from 6,669 markers, and spans 4,070 cM, with an average of 2 loci per cM. The HDC map presents a high rate of locus duplications, as 1,292 markers among the 6,669 were mapped in more than one locus. Two thirds of the duplications are bridging homoeologous AT and DT chromosomes constitutive of allopolyploid cotton genome, with an average of 64 duplications per AT/DT chromosome pair. Sequences of 4,744 mapped markers were used for a mutual blast alignment (BBMH) with the 13 major scaffolds of the recently released Gossypium raimondii genome indicating high level of homology between the diploid D genome and the tetraploid cotton genetic map, with only a few minor possible structural rearrangements. Overall, the HDC map will serve as a valuable resource for trait QTL comparative mapping, map-based cloning of important genes, and better understanding of the genome structure and evolution of tetraploid cotton. PMID:23029214

  20. Self-excising Cre/mutant lox marker recycling system for multiple gene integrations and consecutive gene deletions in Aspergillus oryzae.

    PubMed

    Zhang, Silai; Ban, Akihiko; Ebara, Naoki; Mizutani, Osamu; Tanaka, Mizuki; Shintani, Takahiro; Gomi, Katsuya

    2017-04-01

    In this study, we developed a self-excising Cre/loxP-mediated marker recycling system with mutated lox sequences to introduce a number of biosynthetic genes into Aspergillus oryzae. To construct the self-excising marker cassette, both the selectable marker, the Aspergillus nidulans adeA gene, and the Cre recombinase gene (cre), conditionally expressed by the xylanase-encoding gene promoter, were designed to be located between the mutant lox sequences, lox66 and lox71. However, construction of the plasmid failed, possibly owing to a slight expression of cre downstream of the fungal gene promoter in Escherichia coli. Hence, to avoid the excision of the cassette in E. coli, a 71-bp intron of the A. oryzae xynG2 gene was inserted into the cre gene. The A. oryzae adeA deletion mutant was transformed with the resulting plasmid in the presence of glucose, and the transformants were cultured in medium containing xylose as the sole carbon source. PCR analysis of genomic DNA from resultant colonies revealed the excision of both the marker and Cre expression construct, indicating that the self-excising marker cassette was efficient at removing the selectable marker. Using the marker recycling system, hyperproduction of kojic acid could be achieved in A. oryzae by the introduction of two genes that encode oxidoreductase and transporter. Furthermore, we also constructed an alternative marker recycling cassette bearing the A. nidulans pyrithiamine resistant gene (ptrA) as a dominant selectable marker. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Molecular Marker Systems for Oenothera Genetics

    PubMed Central

    Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G.; Greiner, Stephan

    2008-01-01

    The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome–genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9·8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed. PMID:18791241

  2. Combinations of Multiple Neuroimaging Markers using Logistic Regression for Auxiliary Diagnosis of Alzheimer Disease and Mild Cognitive Impairment.

    PubMed

    Mao, Nini; Liu, Yunting; Chen, Kewei; Yao, Li; Wu, Xia

    2018-06-05

    Multiple neuroimaging modalities have been developed providing various aspects of information on the human brain. Used together and properly, these complementary multimodal neuroimaging data integrate multisource information which can facilitate a diagnosis and improve the diagnostic accuracy. In this study, 3 types of brain imaging data (sMRI, FDG-PET, and florbetapir-PET) were fused in the hope to improve diagnostic accuracy, and multivariate methods (logistic regression) were applied to these trimodal neuroimaging indices. Then, the receiver-operating characteristic (ROC) method was used to analyze the outcomes of the logistic classifier, with either each index, multiples from each modality, or all indices from all 3 modalities, to investigate their differential abilities to identify the disease. With increasing numbers of indices within each modality and across modalities, the accuracy of identifying Alzheimer disease (AD) increases to varying degrees. For example, the area under the ROC curve is above 0.98 when all the indices from the 3 imaging data types are combined. Using a combination of different indices, the results confirmed the initial hypothesis that different biomarkers were potentially complementary, and thus the conjoint analysis of multiple information from multiple sources would improve the capability to identify diseases such as AD and mild cognitive impairment. © 2018 S. Karger AG, Basel.

  3. A case of false mother included with 46 autosomal STR markers.

    PubMed

    Li, Li; Lin, Yuan; Liu, Yan; Zhu, Ruxin; Zhao, Zhenmin; Que, Tingzhi

    2015-01-01

    For solving a maternity case, 19 autosomal short tandem repeats (STRs) were amplified using the AmpFℓSTR(®) Sinofiler(TM) kit and PowerPlex(®) 16 System. Additional 27 autosomal STR loci were analyzed using two domestic kits AGCU 21+1 and STRtyper-10G. The combined maternity index (CMI) was calculated to be 3.3 × 10(13), but the putative mother denied that she had given birth to the child. In order to reach an accurate conclusion, further testing of 20 X-chromosomal short tandem repeats (X-STRs), 40 single nucleotide polymorphism (SNP) loci, and mitochondrial DNA (mtDNA) was carried out. The putative mother and the boy shared at least one allele at all 46 tested autosomal STR loci. But, according to the profile data of 20 X-STR and 40 SNP markers, different genotypes at 13 X-STR loci and five SNP loci excluded maternity. Mitochondrial profiles also clearly excluded the mother as a parent of the son because they have multiple differences. It was finally found that the putative mother is the sister of the biological father. Different kinds of genetic markers needfully supplement the use of autosomal STR loci in case where the putative parent is suspected to be related to the true parent.

  4. Pigmentary Markers in Danes – Associations with Quantitative Skin Colour, Nevi Count, Familial Atypical Multiple-Mole, and Melanoma Syndrome

    PubMed Central

    Johansen, Peter; Andersen, Jeppe Dyrberg; Madsen, Linnea Nørgård; Ullum, Henrik; Glud, Martin; Børsting, Claus; Gniadecki, Robert; Morling, Niels

    2016-01-01

    To investigate whether pigmentation genes involved in the melanogenic pathway (melanogenesis) contributed to melanoma predisposition, we compared pigmentary genetics with quantitative skin pigmentation measurements, the number of atypical nevi, the total nevus count, and the familial atypical multiple mole and melanoma (FAMMM) syndrome. We typed 32 pigmentary SNP markers and sequenced MC1R in 246 healthy individuals and 116 individuals attending periodic control for malignant melanoma development, 50 of which were diagnosed with FAMMM. It was observed that individuals with any two grouped MC1R variants (missense, NM_002386:c. 456C > A (p.TYR152*), or NM_002386:c.83_84insA (p.Asn29Glnfs*14) had significantly (p<0.001) lighter skin pigmentation of the upper-inner arm than those with none or one MC1R variant. We did not observe any significant association of the MC1R variants with constitutive pigmentation measured on the buttock area. We hypothesize that the effect of MC1R variants on arm pigmentation is primarily reflecting the inability to tan when subjected to UVR. A gender specific effect on skin pigmentation was also observed, and it was found that the skin pigmentation of females on average were darker than that of males (p<0.01). We conclude that MC1R variants are associated with quantitative skin colour in a lightly pigmented Danish population. We did not observe any association between any pigmentary marker and the FAMMM syndrome. We suggest that the genetics of FAMMM is not related to the genetics of the pigmentary pathway. PMID:26938746

  5. Comparison of two different methods of preoperative marking for toric intraocular lens implantation: bubble marker versus pendulum marker.

    PubMed

    Farooqui, Javed Hussain; Koul, Archana; Dutta, Ranjan; Shroff, Noshir Minoo

    2016-01-01

    To compare the accuracy of two different methods of preoperative marking for toric intraocular lens (IOL) implantation, bubble marker versus pendulum marker, as a means of establishing the reference point for the final alignment of the toric IOL to achieve an outcome as close as possible to emmetropia. Toric IOLs were implanted in 180 eyes of 110 patients. One group (55 patients) had preoperative marking of both eyes done with bubble marker (ASICO AE-2791TBL) and the other group (55 patients) with pendulum marker (Rumex(®)3-193). Reference marks were placed at 3-, 6-, and 9-o'clock positions on the limbus. Slit-lamp photographs were analyzed using Adobe Photoshop (version 7.0). Amount of alignment error (in degrees) induced in each group was measured. Mean absolute rotation error in the preoperative marking in the horizontal axis was 2.42±1.71 in the bubble marker group and 2.83±2.31in the pendulum marker group (P=0.501). Sixty percent of the pendulum group and 70% of the bubble group had rotation error ≤3 (P=0.589), and 90% eyes of the pendulum group and 96.7% of the bubble group had rotation error ≤5 (P=0.612). Both preoperative marking techniques result in approximately 3 of alignment error. Both marking techniques are simple, predictable, reproducible and easy to perform.

  6. The forensic value of X-linked markers in mixed-male DNA analysis.

    PubMed

    He, HaiJun; Zha, Lagabaiyila; Cai, JinHong; Huang, Jian

    2018-05-04

    Autosomal genetic markers and Y chromosome markers have been widely applied in analysis of mixed stains at crime scenes by forensic scientists. However, true genotype combinations are often difficult to distinguish using autosomal markers when similar amounts of DNA are contributed by multiple donors. In addition, specific individuals cannot be determined by Y chromosomal markers because male relatives share the same Y chromosome. X-linked markers, possessing characteristics somewhere intermediate between autosomes and the Y chromosome, are less universally applied in criminal casework. In this paper, X markers are proposed to apply to male mixtures because their true genes can be more easily and accurately recognized than the decision of the genotypes of AS markers. In this study, an actual two-man mixed stain from a forensic case file and simulated male-mixed DNA were examined simultaneously with the X markers and autosomal markers. Finally, the actual mixture was separated successfully by the X markers, although it was unresolved by AS-STRs, and the separation ratio of the simulated mixture was much higher using Chr X tools than with AS methods. We believe X-linked markers provide significant advantages in individual discrimination of male mixtures that should be further applied to forensic work.

  7. Using dynamic programming to improve fiducial marker localization

    NASA Astrophysics Data System (ADS)

    Wan, Hanlin; Ge, Jiajia; Parikh, Parag

    2014-04-01

    Fiducial markers are used in a wide range of medical imaging applications. In radiation therapy, they are often implanted near tumors and used as motion surrogates that are tracked with fluoroscopy. We propose a novel and robust method based on dynamic programming (DP) for retrospectively localizing radiopaque fiducial markers in fluoroscopic images. Our method was compared to template matching (TM) algorithms on 407 data sets from 24 patients. We found that the performance of TM varied dramatically depending on the template used (ranging from 47% to 92% of data sets with a mean error <1 mm). DP by itself requires no template and performed as well as the best TM method, localizing the markers in 91% of the data sets with a mean error <1 mm. Finally, by combining DP and TM, we were able to localize the markers in 99% of the data sets with a mean error <1 mm, regardless of the template used. Our results show that DP can be a powerful tool for analyzing tumor motion, capable of accurately locating fiducial markers in fluoroscopic images regardless of marker type, shape, and size.

  8. Conserved Nonexonic Elements: A Novel Class of Marker for Phylogenomics.

    PubMed

    Edwards, Scott V; Cloutier, Alison; Baker, Allan J

    2017-11-01

    Noncoding markers have a particular appeal as tools for phylogenomic analysis because, at least in vertebrates, they appear less subject to strong variation in GC content among lineages. Thus far, ultraconserved elements (UCEs) and introns have been the most widely used noncoding markers. Here we analyze and study the evolutionary properties of a new type of noncoding marker, conserved nonexonic elements (CNEEs), which consists of noncoding elements that are estimated to evolve slower than the neutral rate across a set of species. Although they often include UCEs, CNEEs are distinct from UCEs because they are not ultraconserved, and, most importantly, the core region alone is analyzed, rather than both the core and its flanking regions. Using a data set of 16 birds plus an alligator outgroup, and ∼3600-∼3800 loci per marker type, we found that although CNEEs were less variable than bioinformatically derived UCEs or introns and in some cases exhibited a slower approach to branch resolution as determined by phylogenomic subsampling, the quality of CNEE alignments was superior to those of the other markers, with fewer gaps and missing species. Phylogenetic resolution using coalescent approaches was comparable among the three marker types, with most nodes being fully and congruently resolved. Comparison of phylogenetic results across the three marker types indicated that one branch, the sister group to the passerine + falcon clade, was resolved differently and with moderate (>70%) bootstrap support between CNEEs and UCEs or introns. Overall, CNEEs appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Systematic Biologists.

  9. Conserved Nonexonic Elements: A Novel Class of Marker for Phylogenomics

    PubMed Central

    Cloutier, Alison; Baker, Allan J.

    2017-01-01

    Abstract Noncoding markers have a particular appeal as tools for phylogenomic analysis because, at least in vertebrates, they appear less subject to strong variation in GC content among lineages. Thus far, ultraconserved elements (UCEs) and introns have been the most widely used noncoding markers. Here we analyze and study the evolutionary properties of a new type of noncoding marker, conserved nonexonic elements (CNEEs), which consists of noncoding elements that are estimated to evolve slower than the neutral rate across a set of species. Although they often include UCEs, CNEEs are distinct from UCEs because they are not ultraconserved, and, most importantly, the core region alone is analyzed, rather than both the core and its flanking regions. Using a data set of 16 birds plus an alligator outgroup, and ∼3600–∼3800 loci per marker type, we found that although CNEEs were less variable than bioinformatically derived UCEs or introns and in some cases exhibited a slower approach to branch resolution as determined by phylogenomic subsampling, the quality of CNEE alignments was superior to those of the other markers, with fewer gaps and missing species. Phylogenetic resolution using coalescent approaches was comparable among the three marker types, with most nodes being fully and congruently resolved. Comparison of phylogenetic results across the three marker types indicated that one branch, the sister group to the passerine + falcon clade, was resolved differently and with moderate (>70%) bootstrap support between CNEEs and UCEs or introns. Overall, CNEEs appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis. PMID:28637293

  10. Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis.

    PubMed

    Kroth, Julia; Ciolac, Dumitru; Fleischer, Vinzenz; Koirala, Nabin; Krämer, Julia; Muthuraman, Muthuraman; Luessi, Felix; Bittner, Stefan; Gonzalez-Escamilla, Gabriel; Zipp, Frauke; Meuth, Sven G; Groppa, Sergiu

    2017-12-01

    Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSF IgA and CSF IgM showed higher functional disability at follow-up. CSF markers of blood-brain barrier integrity and specific immune response forecast emerging gray matter pathology and disease progression in MS.

  11. Endoscopy/EUS-guided fiducial marker placement in patients with esophageal cancer: a comparative analysis of 3 types of markers.

    PubMed

    Machiels, Melanie; van Hooft, Jeanin; Jin, Peng; van Berge Henegouwen, Mark I; van Laarhoven, Hanneke M; Alderliesten, Tanja; Hulshof, Maarten C

    2015-10-01

    Markers placed at the borders of esophageal tumors are potentially useful to facilitate radiotherapy (RT) target delineation, which offers the possibility of image-guided RT. To evaluate and compare the feasibility and technical benefit of endoscopy/EUS-guided marker placement of 3 different types of markers in patients with esophageal cancer referred for RT. Prospective, single-center, feasibility and comparative study. Tertiary-care medical center. Thirty patients with esophageal cancer who were referred for RT. Patients underwent endoscopy/EUS-guided implantation of 1 type of marker. A solid gold marker (SM) with fixed dimensions, a flexible coil-shaped gold marker (FM) with hand-cut length (2-10 mm), and a radiopaque hydrogel marker (HG) were used. Technical feasibility and adverse events were registered. CT scans and cone-beam CT scans (CBCT) acquired during RT were analyzed to determine and compare the visibility and continuous clear visibility of the implanted markers. Technical feasibility, technical benefit, and adverse events of 3 types of markers. A total of 101 markers were placed in 30 patients. Implantation was technically feasible in all patients without grade 3 to 4 adverse events. Two patients with asymptomatic mediastinitis and one with asymptomatic pneumothorax were seen. Visibility on CT scan of all 3 types of implanted markers was adequate for target delineation. Eighty percent of FMs remained continuously visible over the treatment period on CBCT, significantly better than SMs (63%) and HGs (11%) (P = .015). When we selected FMs ≥5 mm, 90.5% remained visible on CBCT between implantation and the end of RT. Single-center, nonrandomized design. Endoscopy/EUS-guided fiducial marker placement for esophageal cancer is both safe and feasible and can be used for target volume delineation purposes on CT. Our results imply a significant advantage of FMs over SMs and HGs, regarding visibility and continuous clear visibility over the treatment period

  12. A Comparative Study of Intensity Markers in Engineering and Applied Linguistics

    ERIC Educational Resources Information Center

    Behnam, Biook; Mirzapour, Fatemeh

    2012-01-01

    Writers use intensity markers as one of strategies in order to negotiate their claims and to make their writings persuasive and credible. This study is an attempt to examine the type, frequency, and functions of intensity markers in research articles of two disciplines of Applied Linguistics and Electrical Engineering by analyzing surface…

  13. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study

    PubMed Central

    Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

    2016-01-01

    The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. PMID:26785711

  14. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study.

    PubMed

    Riccio, Paolo; Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

    2016-03-01

    The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. © 2016 by the Society for Experimental Biology and Medicine.

  15. Serum soluble interleukin-2 receptor level is more sensitive than angiotensin-converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement.

    PubMed

    Thi Hong Nguyen, Chuyen; Kambe, Naotomo; Kishimoto, Izumi; Ueda-Hayakawa, Ikuko; Okamoto, Hiroyuki

    2017-07-01

    Skin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin-2 receptor (sIL-2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL-2R compared with two other common markers, angiotensin-converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL-2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL-2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL-2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression-specific signs by imaging analysis. Receiver-operator curve analysis showed that sIL-2R was a better marker at the threshold cut-off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL-2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow-up period. In conclusion, sIL-2R may be considered a good marker for diagnosis and a potential indicator of disease activity. © 2017 Japanese Dermatological Association.

  16. Increasing serum levels of vitamin A, D and E are associated with alterations of different inflammation markers in patients with multiple sclerosis.

    PubMed

    Røsjø, Egil; Myhr, Kjell-Morten; Løken-Amsrud, Kristin Ingeleiv; Bakke, Søren Jacob; Beiske, Antonie G; Bjerve, Kristian S; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Benth, Jūratė Saltytė; Torkildsen, Øivind; Wergeland, Stig; Michelsen, Annika E; Aukrust, Pål; Ueland, Thor; Holmøy, Trygve

    2014-06-15

    To explore the relationships between vitamin A, D and E and inflammation in relapsing remitting multiple sclerosis, we assessed their associations with 11 inflammation markers in 9 serial serum samples from 85 patients, before and during interferon-β1a treatment. A negative association was found between vitamin A and pentraxin 3 independent of interferon-β1a use, whereas positive associations between vitamin D and interleukin-1 receptor antagonist and secreted frizzled-related protein 3 were seen before, and between vitamin E and chemokine (C-X-C motif) ligand 16 during interferon-β1a treatment. These findings suggest associations with diverse inflammatory pathways, which may be differentially influenced by interferon-β1a treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Cell-surface marker discovery for lung cancer

    PubMed Central

    Cohen, Allison S.; Khalil, Farah K.; Welsh, Eric A.; Schabath, Matthew B.; Enkemann, Steven A.; Davis, Andrea; Zhou, Jun-Min; Boulware, David C.; Kim, Jongphil; Haura, Eric B.; Morse, David L.

    2017-01-01

    Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients. PMID:29371917

  18. Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains.

    PubMed

    Kim, Yunjung; Feng, Sheng; Zeng, Zhao-Bang

    2008-05-01

    A map of the background levels of disequilibrium between nearby markers can be useful for association mapping studies. In order to assess the background levels of linkage disequilibrium (LD), multilocus LD measures are more advantageous than pairwise LD measures because the combined analysis of pairwise LD measures is not adequate to detect simultaneous allele associations among multiple markers. Various multilocus LD measures based on haplotypes have been proposed. However, most of these measures provide a single index of association among multiple markers and does not reveal the complex patterns and different levels of LD structure. In this paper, we employ non-homogeneous, multiple order Markov Chain models as a statistical framework to measure and partition the LD among multiple markers into components due to different orders of marker associations. Using a sliding window of multiple markers on phased haplotype data, we compute corresponding likelihoods for different Markov Chain (MC) orders in each window. The log-likelihood difference between the lowest MC order model (MC0) and the highest MC order model in each window is used as a measure of the total LD or the overall deviation from the gametic equilibrium for the window. Then, we partition the total LD into lower order disequilibria and estimate the effects from two-, three-, and higher order disequilibria. The relationship between different orders of LD and the log-likelihood difference involving two different orders of MC models are explored. By applying our method to the phased haplotype data in the ENCODE regions of the HapMap project, we are able to identify high/low multilocus LD regions. Our results reveal that the most LD in the HapMap data is attributed to the LD between adjacent pairs of markers across the whole region. LD between adjacent pairs of markers appears to be more significant in high multilocus LD regions than in low multilocus LD regions. We also find that as the multilocus total LD

  19. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  20. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  1. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  2. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  3. 21 CFR 862.2150 - Continuous flow sequential multiple chemistry analyzer for clinical use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Continuous flow sequential multiple chemistry..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2150 Continuous flow sequential multiple chemistry...

  4. Application of multiple geochemical markers to investigate organic pollution in a dynamic coastal zone.

    PubMed

    Liu, Liang-Ying; Wang, Ji-Zhong; Wong, Charles S; Qiu, Jian-Wen; Zeng, Eddy Y

    2013-02-01

    Multiple geochemical markers, including aliphatic hydrocarbons (n-alkanes), linear alkylbenzenes (LABs), and polycyclic aromatic hydrocarbons (PAHs), were employed to relate sediment organic chemical pollution in the coastal zone off South China to socioeconomic development there. Concentrations of Σn-C(15-35) (n-alkanes with 15-35 carbon atoms), ΣLAB (sum of C(10) to C(13) LABs), and Σ(26) PAH (sum of 26 PAH compounds) ranged from 110 to 3,160, 11 to 160, and 26 to 600 ng/g, with medians of 730, 40, and 230 ng/g, respectively. Natural hydrocarbons were mainly derived from terrestrial higher plant waxes, and in minor amounts from aquatic plankton and bacteria. Compositions of LABs indicated that considerable amounts of poorly treated wastewater had been directly discharged or transported to the eastern and western coastal areas of Guangdong Province. In addition, anthropogenic hydrocarbons were derived largely from vehicular emissions and combustion of domestic coal and biomass and to a lesser extent from oil spills. Eastern and western coastal sediments contained higher levels of LABs but lower levels of PAHs than those of the Pearl River Estuary, a coastal area of the Pearl River Delta. This spatial pattern of organic pollution was consistent with chemical use patterns. The eastern and western regions of Guangdong Province are economically less developed than the Pearl River Delta region, where more domestic wastewater treatment plants have been built. However, greater amounts of energy are consumed in the latter region to produce more combustion-derived PAH contamination. Copyright © 2012 SETAC.

  5. Comparison of two different methods of preoperative marking for toric intraocular lens implantation: bubble marker versus pendulum marker

    PubMed Central

    Farooqui, Javed Hussain; Koul, Archana; Dutta, Ranjan; Shroff, Noshir Minoo

    2016-01-01

    AIM To compare the accuracy of two different methods of preoperative marking for toric intraocular lens (IOL) implantation, bubble marker versus pendulum marker, as a means of establishing the reference point for the final alignment of the toric IOL to achieve an outcome as close as possible to emmetropia. METHODS Toric IOLs were implanted in 180 eyes of 110 patients. One group (55 patients) had preoperative marking of both eyes done with bubble marker (ASICO AE-2791TBL) and the other group (55 patients) with pendulum marker (Rumex®3-193). Reference marks were placed at 3-, 6-, and 9-o'clock positions on the limbus. Slit-lamp photographs were analyzed using Adobe Photoshop (version 7.0). Amount of alignment error (in degrees) induced in each group was measured. RESULTS Mean absolute rotation error in the preoperative marking in the horizontal axis was 2.42±1.71 in the bubble marker group and 2.83±2.31in the pendulum marker group (P=0.501). Sixty percent of the pendulum group and 70% of the bubble group had rotation error ≤3 (P=0.589), and 90% eyes of the pendulum group and 96.7% of the bubble group had rotation error ≤5 (P=0.612). CONCLUSION Both preoperative marking techniques result in approximately 3 of alignment error. Both marking techniques are simple, predictable, reproducible and easy to perform. PMID:27275425

  6. Association analysis and marker development for grain quality traits using USDA diverse rice germplasm collections

    USDA-ARS?s Scientific Manuscript database

    New molecular markers are being designed and validated for grain quality improvement based on computationally assisted analysis of genome wide association study (GWAS) findings across multiple panels and multiple grain quality traits. The traits include grain dimensions, apparent amylose content (A...

  7. Recent advances in development of marker-free transgenic plants: regulation and biosafety concern.

    PubMed

    Tuteja, Narendra; Verma, Shiv; Sahoo, Ranjan Kumar; Raveendar, Sebastian; Reddy, I N Bheema Lingeshwara

    2012-03-01

    During the efficient genetic transformation of plants with the gene of interest, some selectable marker genes are also used in order to identify the transgenic plant cells or tissues. Usually, antibiotic- or herbicide-selective agents and their corresponding resistance genes are used to introduce economically valuable genes into crop plants. From the biosafety authority and consumer viewpoints, the presence of selectable marker genes in released transgenic crops may be transferred to weeds or pathogenic microorganisms in the gastrointestinal tract or soil, making them resistant to treatment with herbicides or antibiotics, respectively. Sexual crossing also raises the problem of transgene expression because redundancy of transgenes in the genome may trigger homology-dependent gene silencing. The future potential of transgenic technologies for crop improvement depends greatly on our abilities to engineer stable expression of multiple transgenic traits in a predictable fashion and to prevent the transfer of undesirable transgenic material to non-transgenic crops and related species. Therefore, it is now essential to develop an efficient marker-free transgenic system. These considerations underline the development of various approaches designed to facilitate timely elimination of transgenes when their function is no longer needed. Due to the limiting number of available selectable marker genes, in future the stacking of transgenes will be increasingly desirable. The production of marker-free transgenic plants is now a critical requisite for their commercial deployment and also for engineering multiple and complex trait. Here we describe the current technologies to eliminate the selectable marker genes (SMG) in order to develop marker-free transgenic plants and also discuss the regulation and biosafety concern of genetically modified (GM) crops.

  8. Haplotype-Based Genome-Wide Prediction Models Exploit Local Epistatic Interactions Among Markers

    PubMed Central

    Jiang, Yong; Schmidt, Renate H.; Reif, Jochen C.

    2018-01-01

    Genome-wide prediction approaches represent versatile tools for the analysis and prediction of complex traits. Mostly they rely on marker-based information, but scenarios have been reported in which models capitalizing on closely-linked markers that were combined into haplotypes outperformed marker-based models. Detailed comparisons were undertaken to reveal under which circumstances haplotype-based genome-wide prediction models are superior to marker-based models. Specifically, it was of interest to analyze whether and how haplotype-based models may take local epistatic effects between markers into account. Assuming that populations consisted of fully homozygous individuals, a marker-based model in which local epistatic effects inside haplotype blocks were exploited (LEGBLUP) was linearly transformable into a haplotype-based model (HGBLUP). This theoretical derivation formally revealed that haplotype-based genome-wide prediction models capitalize on local epistatic effects among markers. Simulation studies corroborated this finding. Due to its computational efficiency the HGBLUP model promises to be an interesting tool for studies in which ultra-high-density SNP data sets are studied. Applying the HGBLUP model to empirical data sets revealed higher prediction accuracies than for marker-based models for both traits studied using a mouse panel. In contrast, only a small subset of the traits analyzed in crop populations showed such a benefit. Cases in which higher prediction accuracies are observed for HGBLUP than for marker-based models are expected to be of immediate relevance for breeders, due to the tight linkage a beneficial haplotype will be preserved for many generations. In this respect the inheritance of local epistatic effects very much resembles the one of additive effects. PMID:29549092

  9. Haplotype-Based Genome-Wide Prediction Models Exploit Local Epistatic Interactions Among Markers.

    PubMed

    Jiang, Yong; Schmidt, Renate H; Reif, Jochen C

    2018-05-04

    Genome-wide prediction approaches represent versatile tools for the analysis and prediction of complex traits. Mostly they rely on marker-based information, but scenarios have been reported in which models capitalizing on closely-linked markers that were combined into haplotypes outperformed marker-based models. Detailed comparisons were undertaken to reveal under which circumstances haplotype-based genome-wide prediction models are superior to marker-based models. Specifically, it was of interest to analyze whether and how haplotype-based models may take local epistatic effects between markers into account. Assuming that populations consisted of fully homozygous individuals, a marker-based model in which local epistatic effects inside haplotype blocks were exploited (LEGBLUP) was linearly transformable into a haplotype-based model (HGBLUP). This theoretical derivation formally revealed that haplotype-based genome-wide prediction models capitalize on local epistatic effects among markers. Simulation studies corroborated this finding. Due to its computational efficiency the HGBLUP model promises to be an interesting tool for studies in which ultra-high-density SNP data sets are studied. Applying the HGBLUP model to empirical data sets revealed higher prediction accuracies than for marker-based models for both traits studied using a mouse panel. In contrast, only a small subset of the traits analyzed in crop populations showed such a benefit. Cases in which higher prediction accuracies are observed for HGBLUP than for marker-based models are expected to be of immediate relevance for breeders, due to the tight linkage a beneficial haplotype will be preserved for many generations. In this respect the inheritance of local epistatic effects very much resembles the one of additive effects. Copyright © 2018 Jiang et al.

  10. Correlations between female breast density and biochemical markers.

    PubMed

    Kim, Ji-Hye; Lee, Hae-Kag; Cho, Jae-Hwan; Park, Hyong-Keun; Yang, Han-Jun

    2015-07-01

    [Purpose] The aim of this study was to identify biochemical markers related to breast density. The study was performed with 200 patients who received mammography and biochemical marker testing between March 1, 2014 to October 1, 2014. [Subjects and Methods] Following the American College of Radiology, Breast Imaging Reporting and Data System (ACR BI-RADS), breast parenchymal pattern density from mammography was categorized into four grades: grade 1, almost entirely fat; grade 2, fibroglandular densities; grade 3, heterogeneously dense; and grade 4, extremely dense. Regarding biochemical markers, subjects underwent blood and urine tests after a 12-h fast. We analyzed correlations among breast density, general characteristics, and biochemical markers. [Results] Breast density-related factors were age, height, weight, body mass index (BMI), hematocrit, MCH, RDW, AST, ALT, ALP, uric acid, γGT, triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol. [Conclusion] The results can be used as basic and comparative data for the prevention and early control of breast cancer.

  11. NABIC marker database: A molecular markers information network of agricultural crops.

    PubMed

    Kim, Chang-Kug; Seol, Young-Joo; Lee, Dong-Jun; Jeong, In-Seon; Yoon, Ung-Han; Lee, Gang-Seob; Hahn, Jang-Ho; Park, Dong-Suk

    2013-01-01

    In 2013, National Agricultural Biotechnology Information Center (NABIC) reconstructs a molecular marker database for useful genetic resources. The web-based marker database consists of three major functional categories: map viewer, RSN marker and gene annotation. It provides 7250 marker locations, 3301 RSN marker property, 3280 molecular marker annotation information in agricultural plants. The individual molecular marker provides information such as marker name, expressed sequence tag number, gene definition and general marker information. This updated marker-based database provides useful information through a user-friendly web interface that assisted in tracing any new structures of the chromosomes and gene positional functions using specific molecular markers. The database is available for free at http://nabic.rda.go.kr/gere/rice/molecularMarkers/

  12. How Different Marker Sets Affect Joint Angles in Inverse Kinematics Framework.

    PubMed

    Mantovani, Giulia; Lamontagne, Mario

    2017-04-01

    The choice of marker set is a source of variability in motion analysis. Studies exist which assess the performance of marker sets when direct kinematics is used, but these results cannot be extrapolated to the inverse kinematic framework. Therefore, the purpose of this study was to examine the sensitivity of kinematic outcomes to inter-marker set variability in an inverse kinematic framework. The compared marker sets were plug-in-gait, University of Ottawa motion analysis model and a three-marker-cluster marker set. Walking trials of 12 participants were processed in opensim. The coefficient of multiple correlations was very good for sagittal (>0.99) and transverse (>0.92) plane angles, but worsened for the transverse plane (0.72). Absolute reliability indices are also provided for comparison among studies: minimum detectable change values ranged from 3 deg for the hip sagittal range of motion to 16.6 deg of the hip transverse range of motion. Ranges of motion of hip and knee abduction/adduction angles and hip and ankle rotations were significantly different among the three marker configurations (P < 0.001), with plug-in-gait producing larger ranges of motion. Although the same model was used for all the marker sets, the resulting minimum detectable changes were high and clinically relevant, which warns for caution when comparing studies that use different marker configurations, especially if they differ in the joint-defining markers.

  13. Multiplex-Ready Technology for mid-throughput genotyping of molecular markers.

    PubMed

    Bonneau, Julien; Hayden, Matthew

    2014-01-01

    Screening molecular markers across large populations in breeding programs is generally time consuming and expensive. The Multiplex-Ready Technology (MRT) (Hayden et al., BMC genomics 9:80, 2008) was created to optimize polymorphism screening and genotyping using standardized PCR reaction conditions. The flexibility of this method maximizes the number of markers (up to 24 markers SSR or SNP, ideally small PCR product <500 bp and highly polymorphic) by using fluorescent dye (VIC, FAM, NED, and PET) and a semiautomated DNA fragment analyzer (ABI3730) capillary electrophoresis for large numbers of DNA samples (96 or 384 samples).

  14. Qualitative Evaluation of Fiducial Markers for Radiotherapy Imaging

    PubMed Central

    Chan, Maria F.; Cohen, Gil’ad N.; Deasy, Joseph O.

    2016-01-01

    Purpose To evaluate visibility, artifacts, and distortions of various commercial markers in magnetic resonance imaging (MRI), computer tomography (CT), and ultrasound imaging used for radiotherapy planning and treatment guidance. Methods We compare 2 solid gold markers, 4 gold coils, and 1 polymer marker from 3 vendors. Imaging modalities used were 3-T and 1.5-T GE MRIs, Siemens Sequoia 512 Ultrasound, Phillips Big Bore CT, Varian Trilogy linear accelerator (cone-beam CT [CBCT], on-board imager kilovoltage [OBI-kV], electronic portal imaging device megavoltage [EPID-MV]), and Medtronic O-ARM CBCT. Markers were imaged in a 30 × 30 × 10 cm3 custom bolus phantom. In one experiment, Surgilube was used around the markers to reduce air gaps. Images were saved in Digital Imaging and Communications in Medicine (DICOM) format and analyzed using an in-house software. Profiles across the markers were used for objective comparison of the markers’ signals. The visibility and artifacts/distortions produced by each marker were assessed qualitatively and quantitatively. Results All markers are visible in CT, CBCT, OBI-kV, and ultrasound. Gold markers below 0.75 mm in diameter are not visible in EPID-MV images. The larger the markers, the more CT and CBCT image artifacts there are, yet the degree of the artifact depends on scan parameters and the scanner itself. Visibility of gold coils of 0.75 mm diameter or larger is comparable across all imaging modalities studied. The polymer marker causes minimal artifacts in CT and CBCT but has poor visibility in EPID-MV. Gold coils of 0.5 mm exhibit poor visibility in MRI and EPID-MV due to their small size. Gold markers are more visible in 3-T T1 gradient-recalled echo than in 1.5-T T1 fast spin-echo, depending on the scan sequence. In this study, all markers are clearly visible on ultrasound. Conclusion All gold markers are visible in CT, CBCT, kV, and ultrasound; however, only the large diameter markers are visible in MV. When MR and

  15. Direct Detection of Insertion/Deletion Polymorphisms in an Autosomal Region by Analyzing High-Density Markers in Individual Spermatozoa

    PubMed Central

    Pramanik, Sreemanta; Li, Honghua

    2002-01-01

    Direct polymerase chain reaction (PCR) detection of insertion/deletion (indel) polymorphisms requires sample homozygosity. For the indel polymorphisms that have the deletion allele with a relatively low frequency in the autosomal regions, direct PCR detection becomes difficult or impossible. The present study is, to our knowledge, the first designed to directly detect indel polymorphisms in a human autosomal region (i.e., the immunoglobulin VH region), through use of single haploid sperm cells as subjects. Unique marker sequences (n=32), spaced at ∼5-kb intervals, were selected near the 3′ end of the VH region. A two-round multiplex PCR protocol was used to amplify these sequences from single sperm samples from nine unrelated healthy donors. The parental haplotypes of the donors were determined by examining the presence or absence of these markers. Seven clustered markers in 6 of the 18 haplotypes were missing and likely represented a 35–40-kb indel polymorphism. The genotypes of the donors, with respect to this polymorphism, perfectly matched the expectation under Hardy-Weinberg equilibrium. Three VH gene segments, of which two are functional, are affected by this polymorphism. According to these results, >10% of individuals in the human population may not have these gene segments in their genome, and ∼44% may have only one copy of these gene segments. The biological impact of this polymorphism would be very interesting to study. The approach used in the present study could be applied to understand the physical structure and diversity of all other autosomal regions. PMID:12442231

  16. Marker development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adams, M.R.

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  17. Linking the potato genome to the conserved ortholog set (COS) markers

    PubMed Central

    2013-01-01

    Background Conserved ortholog set (COS) markers are an important functional genomics resource that has greatly improved orthology detection in Asterid species. A comprehensive list of these markers is available at Sol Genomics Network (http://solgenomics.net/) and many of these have been placed on the genetic maps of a number of solanaceous species. Results We amplified over 300 COS markers from eight potato accessions involving two diploid landraces of Solanum tuberosum Andigenum group (formerly classified as S. goniocalyx, S. phureja), and a dihaploid clone derived from a modern tetraploid cultivar of S. tuberosum and the wild species S. berthaultii, S. chomatophilum, and S. paucissectum. By BLASTn (Basic Local Alignment Search Tool of the NCBI, National Center for Biotechnology Information) algorithm we mapped the DNA sequences of these markers into the potato genome sequence. Additionally, we mapped a subset of these markers genetically in potato and present a comparison between the physical and genetic locations of these markers in potato and in comparison with the genetic location in tomato. We found that most of the COS markers are single-copy in the reference genome of potato and that the genetic location in tomato and physical location in potato sequence are mostly in agreement. However, we did find some COS markers that are present in multiple copies and those that map in unexpected locations. Sequence comparisons between species show that some of these markers may be paralogs. Conclusions The sequence-based physical map becomes helpful in identification of markers for traits of interest thereby reducing the number of markers to be tested for applications like marker assisted selection, diversity, and phylogenetic studies. PMID:23758607

  18. T-cell receptor V sub. alpha. and C sub. alpha. alleles associated with multiple sclerosis and myasthenia gravis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oksenberg, J.R.; Cavalli-Sforza, L.L.; Steinman, L.

    1989-02-01

    Polymorphic markers in genes encoding the {alpha} chain of the human T-cell receptor (TcR) have been detected by Southern blot analysis in Pss I digests. Polymorphic bands were observed at 6.3 and 2.0 kilobases (kb) with frequencies of 0.30 and 0.44, respectively, in the general population. Using the polymerase chain reaction (PCR) method, the authors amplified selected sequences derived from the full-length TcR {alpha} cDNA probe. These PcR products were used as specific probes to demonstrate that the 6.3-kb polymorphic fragment hybridizes to the variable (V)-region probe and the 2.0-kb fragment hybridizes to the constant (C)-region probe. Segregation of themore » polymorphic bands was analyzed in family studies. To look for associations between these markers and autoimmune diseases, the authors have studied the restriction fragment length polymorphism distribution of the Pss I markers in patients with multiple sclerosis, myasthenia gravis, and Graves disease. Significant differences in the frequency of the polymorphic V{sub {alpha}} and C{sub {alpha}} markers were identified between patients and healthy individuals.« less

  19. Using Multiple Metrics to Analyze Trends and Sensitivity of Climate Variability in New York City

    NASA Astrophysics Data System (ADS)

    Huang, J.; Towey, K.; Booth, J. F.; Baez, S. D.

    2017-12-01

    As the overall temperature of Earth continues to warm, changes in the Earth's climate are being observed through extreme weather events, such as heavy precipitation events and heat waves. This study examines the daily precipitation and temperature record of the greater New York City region during the 1979-2014 period. Daily station observations from three greater New York City airports: John F. Kennedy (JFK), LaGuardia (LGA) and Newark (EWR), are used in this study. Multiple statistical metrics are used in this study to analyze trends and variability in temperature and precipitation in the greater New York City region. The temperature climatology reveals a distinct seasonal cycle, while the precipitation climatology exhibits greater annual variability. Two types of thresholds are used to examine the variability of extreme events: extreme threshold and daily anomaly threshold. The extreme threshold indicates how the strength of the overall maximum is changing whereas the daily anomaly threshold indicates if the strength of the daily maximum is changing over time. We observed an increase in the frequency of anomalous daily precipitation events over the last 36 years, with the greatest frequency occurring in 2011. The most extreme precipitation events occur during the months of late summer through early fall, with approximately four expected extreme events occurring per year during the summer and fall. For temperature, the greatest frequency and variation in temperature anomalies occur during winter and spring. In addition, temperature variance is also analyzed to determine if there is greater day-to-day temperature variability today than in the past.

  20. Direct bonded HOPG - Analyzer support without background source

    NASA Astrophysics Data System (ADS)

    Groitl, Felix; Kitaura, Hidetoshi; Nishiki, Naomi; Rønnow, Henrik M.

    2018-04-01

    A new production process allows a direct bonding of HOPG crystals on Si wafers. This new method facilitates the production of analyzer crystals with support structure without the use of additional, background inducing fixation material, e.g. glue, wax and screws. This new method is especially interesting for the upcoming generation of CAMEA-type multiplexing spectrometers. These instruments allow for a drastic performance increase due to the increased angular coverage and multiple energy analysis. Exploiting the transparency of multiple HOPG for cold neutrons, a consecutive arrangement of HOPG analyzer crystals per Q-channel can be achieved. This implies that neutrons travel through up to 10 arrays of analyzer crystals before reaching the analyzer corresponding to their energy. Hence, a careful choice of the fixation method for the analyzer crystals in regards to transparency and background is necessary. Here, we present first results on the diffraction and mechanical performance of direct bonded analyzer crystals.

  1. GTA: a game theoretic approach to identifying cancer subnetwork markers.

    PubMed

    Farahmand, S; Goliaei, S; Ansari-Pour, N; Razaghi-Moghadam, Z

    2016-03-01

    The identification of genetic markers (e.g. genes, pathways and subnetworks) for cancer has been one of the most challenging research areas in recent years. A subset of these studies attempt to analyze genome-wide expression profiles to identify markers with high reliability and reusability across independent whole-transcriptome microarray datasets. Therefore, the functional relationships of genes are integrated with their expression data. However, for a more accurate representation of the functional relationships among genes, utilization of the protein-protein interaction network (PPIN) seems to be necessary. Herein, a novel game theoretic approach (GTA) is proposed for the identification of cancer subnetwork markers by integrating genome-wide expression profiles and PPIN. The GTA method was applied to three distinct whole-transcriptome breast cancer datasets to identify the subnetwork markers associated with metastasis. To evaluate the performance of our approach, the identified subnetwork markers were compared with gene-based, pathway-based and network-based markers. We show that GTA is not only capable of identifying robust metastatic markers, it also provides a higher classification performance. In addition, based on these GTA-based subnetworks, we identified a new bonafide candidate gene for breast cancer susceptibility.

  2. Utility of the PFA-100 instrument and the novel multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease.

    PubMed

    Mueller, Thomas; Dieplinger, Benjamin; Poelz, Werner; Haltmayer, Meinhard

    2009-12-01

    This study evaluated the utility of the PFA-100 and the Multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease. Platelet function was determined with the PFA-100 using collagen+epinephrine (CEPI) and collagen+adenosine-5'-diphosphate (CADP) cartridges, and with whole blood impedance aggregometry using the Multiplate ASPI and ADP+PG tests (aggregation triggered with arachidonic acid and ADP+ prostaglandin E1, respectively). Four study groups were identified from the 154 patients enrolled: patients without antiplatelet therapy, patients with 100 mg aspirin daily but without clopidogrel treatment, patients with 75 mg clopidogrel daily but without aspirin treatment, and patients with both 100 mg aspirin daily plus 75 mg clopidogrel daily. It was found that the PFA-100 instrument is useful for detection of aspirin but not for detection of a clopidogrel effect, while the Multiplate analyzer is useful for specific detection of both aspirin and clopidogrel effects on platelet function.

  3. Molecular markers in well-differentiated thyroid cancer.

    PubMed

    D'Cruz, Anil K; Vaish, Richa; Vaidya, Abhishek; Nixon, Iain J; Williams, Michelle D; Vander Poorten, Vincent; López, Fernando; Angelos, Peter; Shaha, Ashok R; Khafif, Avi; Skalova, Alena; Rinaldo, Alessandra; Hunt, Jennifer L; Ferlito, Alfio

    2018-06-01

    Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

  4. Epigenetic markers in circulating cell-free DNA as prognostic markers for survival of castration-resistant prostate cancer patients.

    PubMed

    Hendriks, Rianne J; Dijkstra, Siebren; Smit, Frank P; Vandersmissen, Johan; Van de Voorde, Hendrik; Mulders, Peter F A; van Oort, Inge M; Van Criekinge, Wim; Schalken, Jack A

    2018-04-01

    Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. In this prospective study, patients were included before starting new treatment after developing CRPC. The blood samples were collected prior to start of the treatment and at three time points thereafter. cfDNA was extracted from 1.5 mL of plasma and before performing a methylation-specific PCR, bisulfate modification was carried out. The median levels of cfDNA, GSTP1, and APC copies in the baseline samples of CRPC patients (n = 47) were higher than in controls (n = 30). In the survival analysis, the group with baseline marker levels below median had significant less PCa-related deaths (P-values <0.02) and did not reach the median survival point. The survival distributions for the groups were statistically significant for the cfDNA concentration, GSTP1 and APC copies, as well as PSA combined with GSTP1 + APC (P-values <0.03). Furthermore, there were strong positive correlations between PSA and marker response after starting treatment (P-values <0.04). In conclusion, this study showed the kinetics of methylated cfDNA (GSTP1 and APC) in plasma of CRPC patients after starting treatment. Furthermore, the value of the markers before treatment is prognostic for overall survival. These results are promising for developing a test to guide treatment-decision-making for CRPC patients. © 2018 The Authors. The Prostate Published by Wiley Periodicals, Inc.

  5. Identification of marker chromosomes in thirteen patients using FISH probing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Daniel, A.; Malafiej, P.; Preece, K.

    1994-10-15

    Fourteen marker chromosomes were studied by FISH (fluorescence in-situ hybridization) in cytogenetic preparations from 13 patients. The derived markers were identified as one isodicentric bisatellited mar(22), one fragment sized r(X), one fragment sized r(Y), one i(18p), small autosomal ring markers in three different patients derived from chromosomes 2, 8, and 8, a marker comprised of 9p and part of 9qh, and 3 bisatellited apparently monocentric markers; one of each from chromosomes 13 or 21, 14 or 22, and 15. Two fragment sized small ring markers in one patient and a small ring marker in another were negative with all twenty-twomore » different probes used. In addition, the small ring marker Y chromosome that was found in a boy with karyotype 46, X, -Y, +mar was negative with both pDXZ1 and pDYZ3. This anomaly of negative results with the battery of centromeric alphoid probes can be explained if one breakpoint for some small ring markers is very near to or within the centromere. The literature was reviewed for Distamycin A/DAPI negative small ring markers that were present as extra chromosomes. There were only single published cases of most small rings but there were three r(8) cases, two r(1) cases, two r(12) cases, and two r(20) cases, uncomplicated by the presence of other chromosome abnormalities. In pooled data, 18/23 (about 80%) were developmentally and/or phenotypically abnormal. Some patients (5/23, about 20%) with small rings were dysmorphic without intellectual handicap. Of 28 such patients with small ring markers (Distamycin/Dapi negative) in pooled data there are 6 (about 20%) with multiple markers mostly derived from different chromosomes. This is a very high figure and would suggest that the ring formation events, although involving different chromosomes, must be related and must be an indicator of the mechanism of origin of this group of markers. 14 refs., 3 figs., 3 tabs.« less

  6. Distinctive mitochondrial genome of Calanoid copepod Calanus sinicus with multiple large non-coding regions and reshuffled gene order: Useful molecular markers for phylogenetic and population studies

    PubMed Central

    2011-01-01

    Background Copepods are highly diverse and abundant, resulting in extensive ecological radiation in marine ecosystems. Calanus sinicus dominates continental shelf waters in the northwest Pacific Ocean and plays an important role in the local ecosystem by linking primary production to higher trophic levels. A lack of effective molecular markers has hindered phylogenetic and population genetic studies concerning copepods. As they are genome-level informative, mitochondrial DNA sequences can be used as markers for population genetic studies and phylogenetic studies. Results The mitochondrial genome of C. sinicus is distinct from other arthropods owing to the concurrence of multiple non-coding regions and a reshuffled gene arrangement. Further particularities in the mitogenome of C. sinicus include low A + T-content, symmetrical nucleotide composition between strands, abbreviated stop codons for several PCGs and extended lengths of the genes atp6 and atp8 relative to other copepods. The monophyletic Copepoda should be placed within the Vericrustacea. The close affinity between Cyclopoida and Poecilostomatoida suggests reassigning the latter as subordinate to the former. Monophyly of Maxillopoda is rejected. Within the alignment of 11 C. sinicus mitogenomes, there are 397 variable sites harbouring three 'hotspot' variable sites and three microsatellite loci. Conclusion The occurrence of the circular subgenomic fragment during laboratory assays suggests that special caution should be taken when sequencing mitogenomes using long PCR. Such a phenomenon may provide additional evidence of mitochondrial DNA recombination, which appears to have been a prerequisite for shaping the present mitochondrial profile of C. sinicus during its evolution. The lack of synapomorphic gene arrangements among copepods has cast doubt on the utility of gene order as a useful molecular marker for deep phylogenetic analysis. However, mitochondrial genomic sequences have been valuable markers for

  7. Molecular markers in bladder cancer: Novel research frontiers.

    PubMed

    Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

    2015-01-01

    Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools

  8. Neutrality of miniSTR D22S1045 marker by Ewing's sarcoma phenotype.

    PubMed

    Silva, Deborah S B S; Raimann, Paulo E; Moro, Tatiane; Picanço, Juliane B; Abujamra, Ana L; de Farias, Caroline B; Roesler, Rafael; Brunetto, Algemir L; Alho, Clarice S

    2013-11-01

    Neutrality investigations of markers with forensic use are important to see if a phenotypic trait is being expressed in relation to the alleles of the marker. MiniSTR marker D22S1045 (locus 22q12.3) is localized near the breakpoint region of the EWS gene (22q12.2), which leads to the development of Ewing's Sarcoma. Analyzing allele frequencies and linkage disequilibrium in Ewing's sarcoma patients and non-affected populations, we found that the marker mD22S1045 was neutral when related to Ewing's Sarcoma. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Nanotechnology-based electrochemical detection strategies for hypertension markers.

    PubMed

    Madhurantakam, Sasya; Babu, K Jayanth; Rayappan, John Bosco Balaguru; Krishnan, Uma Maheswari

    2018-09-30

    Hypertension results due to dysfunction of different metabolic pathways leading to the increased risk of cerebral ischemia, atherosclerosis, cardiovascular and inflammatory disorders. Hypertension has been considered a one of the major contributors to metabolic syndrome and is often referred to as a 'silent killer'. Its incidence is on the rise across the globe owing to the drastic life style changes. The diagnosis of hypertension had been traditionally carried out through measurement of systolic and diastolic blood pressure but in most cases, this form of diagnosis is too late and the disease has already caused organ damage. Therefore, early detection of hypertension by monitoring subtle changes in specific biochemical markers from body fluids can minimize the risk of organ damage. However, a single marker may be insufficient for accurate diagnosis of hypertension thereby necessitating quantification of multiple markers. Concerted efforts to identify key markers for hypertension and their quantification, especially using chemical and biosensors, are underway in different parts of the world. Constant evolution of the sensing elements and transduction strategies have contributed to significant improvements in the diagnosis field, especially in the context of sensitivity, response time and selectivity and this when applied to the detection of hypertension markers may prove beneficial. This review summarizes advances in the field of sensor technology towards the detection of biologically relevant entities, arrays and the next generation 'lab-on-a-chip' systems for hypertension. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Fecal Molecular Markers for Colorectal Cancer Screening

    PubMed Central

    Kanthan, Rani; Senger, Jenna-Lynn; Kanthan, Selliah Chandra

    2012-01-01

    Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer. PMID:22969796

  11. Two-locus diseas models with two marker loci: The power of affected-sib-pair tests

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Knapp, M.; Seuchter, S.A.; Bauer, M.P.

    1994-11-01

    Recently, Schork et al. found that two-trait-locus, two-marker-locus (parametric) linkage analysis can provide substantially more linkage information than can standard one-trait-locus, one-marker-locus methods. However, because of the increased burden of computation, Schork et al. do not expect that their approach will be applied in an initial genome scan. Further, the specification of a suitable two-locus segregation model can be crucial. Affected-sib-pair tests are computationally simple and do not require an explicit specification of the disease model. In the past, however, these tests mainly have been applied to data with a single marker locus. Here, we consider sib-pair tests that makemore » it possible to analyze simultaneously two marker loci. The power of these tests is investigated for different (epistatic and heterogeneous) two-trait-locus models, each trait locus being linked to one of the marker loci. We compare these tests both with the test that is optimal for a certain model and with the strategy that analyzes each marker locus separately. The results indicate that a straightforward extension of the well-known mean test for two marker loci can be much more powerful than single-marker-locus analysis and that its power is only slightly inferior to the power of the optimal test. 21 refs., 5 figs., 2 tabs.« less

  12. Inflamm-aging does not simply reflect increases in pro-inflammatory markers.

    PubMed

    Morrisette-Thomas, Vincent; Cohen, Alan A; Fülöp, Tamàs; Riesco, Éléonor; Legault, Véronique; Li, Qing; Milot, Emmanuel; Dusseault-Bélanger, Françis; Ferrucci, Luigi

    2014-07-01

    Many biodemographic studies use biomarkers of inflammation to understand or predict chronic disease and aging. Inflamm-aging, i.e. chronic low-grade inflammation during aging, is commonly characterized by pro-inflammatory biomarkers. However, most studies use just one marker at a time, sometimes leading to conflicting results due to complex interactions among the markers. A multidimensional approach allows a more robust interpretation of the various relationships between the markers. We applied principal component analysis (PCA) to 19 inflammatory biomarkers from the InCHIANTI study. We identified a clear, stable structure among the markers, with the first axis explaining inflammatory activation (both pro- and anti-inflammatory markers loaded strongly and positively) and the second axis innate immune response. The first but not the second axis was strongly correlated with age (r=0.56, p<0.0001, r=0.08 p=0.053), and both were strongly predictive of mortality (hazard ratios per PCA unit (95% CI): 1.33 (1.16-1.53) and 0.87 (0.76-0.98) respectively) and multiple chronic diseases, but in opposite directions. Both axes were more predictive than any individual markers for baseline chronic diseases and mortality. These results show that PCA can uncover a novel biological structure in the relationships among inflammatory markers, and that key axes of this structure play important roles in chronic disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Use of SSR markers for DNA fingerprinting and diversity analysis of Pakistani sugarcane (Saccharum spp. hybrids) cultivars

    USDA-ARS?s Scientific Manuscript database

    In recent years SSR markers have been used widely for genetic analysis. The objective of this study was to use an SSR-based marker system to develop the molecular fingerprints and analyze the genetic relationship of sugarcane cultivars grown in Pakistan. Twenty-one highly polymorphic SSR markers wer...

  14. Improving the Flight Path Marker Symbol on Rotorcraft Synthetic Vision Displays

    NASA Technical Reports Server (NTRS)

    Szoboszlay, Zoltan P.; Hardy, Gordon H.; Welsh, Terence M.

    2004-01-01

    Two potential improvements to the flight path marker symbol were evaluated on a panel-mounted, synthetic vision, primary flight display in a rotorcraft simulation. One concept took advantage of the fact that synthetic vision systems have terrain height information available ahead of the aircraft. For this first concept, predicted altitude and ground track information was added to the flight path marker. In the second concept, multiple copies of the flight path marker were displayed at 3, 4, and 5 second prediction times as compared to a single prediction time of 3 seconds. Objective and subjective data were collected for eight rotorcraft pilots. The first concept produced significant improvements in pilot attitude control, ground track control, workload ratings, and preference ratings. The second concept did not produce significant differences in the objective or subjective measures.

  15. Genomic-based multiple-trait evaluation in Eucalyptus grandis using dominant DArT markers.

    PubMed

    Cappa, Eduardo P; El-Kassaby, Yousry A; Muñoz, Facundo; Garcia, Martín N; Villalba, Pamela V; Klápště, Jaroslav; Marcucci Poltri, Susana N

    2018-06-01

    We investigated the impact of combining the pedigree- and genomic-based relationship matrices in a multiple-trait individual-tree mixed model (a.k.a., multiple-trait combined approach) on the estimates of heritability and on the genomic correlations between growth and stem straightness in an open-pollinated Eucalyptus grandis population. Additionally, the added advantage of incorporating genomic information on the theoretical accuracies of parents and offspring breeding values was evaluated. Our results suggested that the use of the combined approach for estimating heritabilities and additive genetic correlations in multiple-trait evaluations is advantageous and including genomic information increases the expected accuracy of breeding values. Furthermore, the multiple-trait combined approach was proven to be superior to the single-trait combined approach in predicting breeding values, in particular for low-heritability traits. Finally, our results advocate the use of the combined approach in forest tree progeny testing trials, specifically when a multiple-trait individual-tree mixed model is considered. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Single nucleotide polymorphism markers for genetic mapping in Drosophila melanogaster

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoskins, Roger A.; Phan, Alexander C.; Naeemuddin, Mohammed

    2001-04-16

    For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that have recently revolutionized human, mouse and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila using an STS-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that the genome. The majority of these markers are single nucleotide polymorphisms (SNPs) and sequences for these variants are provided in an accessible format. The average density of the new markersmore » is 1 marker per 225 kb on the autosomes and 1 marker per 1 Mb on the X chromosome. We include in this survey a set of P-element strains that provide additional utility for high-resolution mapping. We demonstrate one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community.« less

  17. Quantum-dot-based suspension microarray for multiplex detection of lung cancer markers: preclinical validation and comparison with the Luminex xMAP® system

    NASA Astrophysics Data System (ADS)

    Bilan, Regina; Ametzazurra, Amagoia; Brazhnik, Kristina; Escorza, Sergio; Fernández, David; Uríbarri, María; Nabiev, Igor; Sukhanova, Alyona

    2017-03-01

    A novel suspension multiplex immunoassay for the simultaneous specific detection of lung cancer markers in bronchoalveolar lavage fluid (BALF) clinical samples based on fluorescent microspheres having different size and spectrally encoded with quantum dots (QDEM) was developed. The designed suspension immunoassay was validated for the quantitative detection of three lung cancer markers in BALF samples from 42 lung cancer patients and 10 control subjects. Tumor markers were detected through simultaneous formation of specific immune complexes consisting of a capture molecule, the target antigen, and biotinylated recognition molecule on the surface of the different QDEM in a mixture. The immune complexes were visualized by fluorescently labeled streptavidin and simultaneously analyzed using a flow cytometer. Preclinical validation of the immunoassay was performed and results were compared with those obtained using an alternative 3-plex immunoassay based on Luminex xMAP® technology, developed on classical organic fluorophores. The comparison showed that the QDEM and xMAP® assays yielded almost identical results, with clear discrimination between control and clinical samples. Thus, developed QDEM technology can become a good alternative to xMAP® assays permitting analysis of multiple protein biomarkers using conventional flow cytometers.

  18. Quantum-dot-based suspension microarray for multiplex detection of lung cancer markers: preclinical validation and comparison with the Luminex xMAP® system

    PubMed Central

    Bilan, Regina; Ametzazurra, Amagoia; Brazhnik, Kristina; Escorza, Sergio; Fernández, David; Uríbarri, María; Nabiev, Igor; Sukhanova, Alyona

    2017-01-01

    A novel suspension multiplex immunoassay for the simultaneous specific detection of lung cancer markers in bronchoalveolar lavage fluid (BALF) clinical samples based on fluorescent microspheres having different size and spectrally encoded with quantum dots (QDEM) was developed. The designed suspension immunoassay was validated for the quantitative detection of three lung cancer markers in BALF samples from 42 lung cancer patients and 10 control subjects. Tumor markers were detected through simultaneous formation of specific immune complexes consisting of a capture molecule, the target antigen, and biotinylated recognition molecule on the surface of the different QDEM in a mixture. The immune complexes were visualized by fluorescently labeled streptavidin and simultaneously analyzed using a flow cytometer. Preclinical validation of the immunoassay was performed and results were compared with those obtained using an alternative 3-plex immunoassay based on Luminex xMAP® technology, developed on classical organic fluorophores. The comparison showed that the QDEM and xMAP® assays yielded almost identical results, with clear discrimination between control and clinical samples. Thus, developed QDEM technology can become a good alternative to xMAP® assays permitting analysis of multiple protein biomarkers using conventional flow cytometers. PMID:28300171

  19. Association between passive smoking and salivary markers related to periodontitis.

    PubMed

    Nishida, Nobuko; Yamamoto, Yumiko; Tanaka, Muneo; Maeda, Kazuhiko; Kataoka, Kosuke; Nakayama, Kunio; Morimoto, Kanehisa; Shizukuishi, Satoshi

    2006-10-01

    The mechanism of passive smoking in terms of development of periodontitis has not been investigated. This study examined the effect of passive smoking on salivary markers related to periodontitis. Periodontal status was evaluated on the basis of probing pocket depth and clinical attachment level in 273 workers. Salivary marker levels were determined by enzyme assay including enzyme-linked immunosorbent assay. Six periodontal pathogens in saliva were assessed using real-time PCR methodology. Non-, passive and active smokers were defined as subjects exhibiting salivary cotinine levels of 0 (53 subjects), 1-7 (118) and > or = 8 ng/ml (102). Levels of salivary markers, including IL-1beta, lactoferrin, albumin and aspartate aminotransferase (AST), were elevated significantly in passive smokers relative to non-smokers. Additionally, these marker levels, with the exception of IL-1beta, decreased significantly in active smokers in comparison with passive smokers. However, no meaningful differences in percentages of periodontal pathogens were observed between non- and passive smokers. Multiple linear regression analyses were performed for each marker utilizing age, gender, cotinine level and periodontal status as independent variables. IL-1beta, albumin and AST were independently associated with cotinine level. Passive smoke exposure leads to elevation of IL-1beta, albumin and AST levels in saliva.

  20. Decreased serum levels of sCD40L and IL-31 correlate in treated patients with Relapsing-Remitting Multiple Sclerosis.

    PubMed

    de J Guerrero-García, José; Rojas-Mayorquín, Argelia E; Valle, Yeminia; Padilla-Gutiérrez, Jorge R; Castañeda-Moreno, Víctor A; Mireles-Ramírez, Mario A; Muñoz-Valle, José F; Ortuño-Sahagún, Daniel

    2018-01-01

    The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS. Therefore, sCD40L and IL-31 must be taken into account as possible prognostic markers when analyzing the disease progress of MS in order to provide more personalized treatment. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Lessons from mouse chimaera experiments with a reiterated transgene marker: revised marker criteria and a review of chimaera markers.

    PubMed

    Keighren, Margaret A; Flockhart, Jean; Hodson, Benjamin A; Shen, Guan-Yi; Birtley, James R; Notarnicola-Harwood, Antonio; West, John D

    2015-08-01

    Recent reports of a new generation of ubiquitous transgenic chimaera markers prompted us to consider the criteria used to evaluate new chimaera markers and develop more objective assessment methods. To investigate this experimentally we used several series of fetal and adult chimaeras, carrying an older, multi-copy transgenic marker. We used two additional independent markers and objective, quantitative criteria for cell selection and cell mixing to investigate quantitative and spatial aspects of developmental neutrality. We also suggest how the quantitative analysis we used could be simplified for future use with other markers. As a result, we recommend a five-step procedure for investigators to evaluate new chimaera markers based partly on criteria proposed previously but with a greater emphasis on examining the developmental neutrality of prospective new markers. These five steps comprise (1) review of published information, (2) evaluation of marker detection, (3) genetic crosses to check for effects on viability and growth, (4) comparisons of chimaeras with and without the marker and (5) analysis of chimaeras with both cell populations labelled. Finally, we review a number of different chimaera markers and evaluate them using the extended set of criteria. These comparisons indicate that, although the new generation of ubiquitous fluorescent markers are the best of those currently available and fulfil most of the criteria required of a chimaera marker, further work is required to determine whether they are developmentally neutral.

  2. Molecular Markers and Cotton Genetic Improvement: Current Status and Future Prospects

    PubMed Central

    Malik, Waqas; Iqbal, Muhammad Zaffar; Ali Khan, Asif; Qayyum, Abdul; Ali Abid, Muhammad; Noor, Etrat; Qadir Ahmad, Muhammad; Hasan Abbasi, Ghulam

    2014-01-01

    Narrow genetic base and complex allotetraploid genome of cotton (Gossypium hirsutum L.) is stimulating efforts to avail required polymorphism for marker based breeding. The availability of draft genome sequence of G. raimondii and G. arboreum and next generation sequencing (NGS) technologies facilitated the development of high-throughput marker technologies in cotton. The concepts of genetic diversity, QTL mapping, and marker assisted selection (MAS) are evolving into more efficient concepts of linkage disequilibrium, association mapping, and genomic selection, respectively. The objective of the current review is to analyze the pace of evolution in the molecular marker technologies in cotton during the last ten years into the following four areas: (i) comparative analysis of low- and high-throughput marker technologies available in cotton, (ii) genetic diversity in the available wild and improved gene pools of cotton, (iii) identification of the genomic regions within cotton genome underlying economic traits, and (iv) marker based selection methodologies. Moreover, the applications of marker technologies to enhance the breeding efficiency in cotton are also summarized. Aforementioned genomic technologies and the integration of several other omics resources are expected to enhance the cotton productivity and meet the global fiber quantity and quality demands. PMID:25401149

  3. Identification of quality markers of Yuanhu Zhitong tablets based on integrative pharmacology and data mining.

    PubMed

    Li, Ke; Li, Junfang; Su, Jin; Xiao, Xuefeng; Peng, Xiujuan; Liu, Feng; Li, Defeng; Zhang, Yi; Chong, Tao; Xu, Haiyu; Liu, Changxiao; Yang, Hongjun

    2018-03-07

    The quality evaluation of traditional Chinese medicine (TCM) formulations is needed to guarantee the safety and efficacy. In our laboratory, we established interaction rules between chemical quality control and biological activity evaluations to study Yuanhu Zhitong tablets (YZTs). Moreover, a quality marker (Q-marker) has recently been proposed as a new concept in the quality control of TCM. However, no appropriate methods are available for the identification of Q-markers from the complex TCM systems. We aimed to use an integrative pharmacological (IP) approach to further identify Q-markers from YZTs through the integration of multidisciplinary knowledge. In addition, data mining was used to determine the correlation between multiple constituents of this TCM and its bioactivity to improve quality control. The IP approach was used to identify the active constituents of YZTs and elucidate the molecular mechanisms by integrating chemical and biosynthetic analyses, drug metabolism, and network pharmacology. Data mining methods including grey relational analysis (GRA) and least squares support vector machine (LS-SVM) regression techniques, were used to establish the correlations among the constituents and efficacy, and dose efficacy in multiple dimensions. Seven constituents (tetrahydropalmatine, α-allocryptopine, protopine, corydaline, imperatorin, isoimperatorin, and byakangelicin) were identified as Q-markers of YZT using IP based on their high abundance, specific presence in the individual herbal constituents and the product, appropriate drug-like properties, and critical contribution to the bioactivity of the mixture of YZT constituents. Moreover, three Q-markers (protopine, α-allocryptopine, and corydaline) were highly correlated with the multiple bioactivities of the YZTs, as found using data mining. Finally, three constituents (tetrahydropalmatine, corydaline, and imperatorin) were chosen as minimum combinations that both distinguished the authentic

  4. Acquisition of the Korean Imperfective Aspect Markers "-ko iss-" and "-a iss-" by Japanese Learners: A Multiple-Factor Account

    ERIC Educational Resources Information Center

    Ryu, Ju-Yeon; Horie, Kaoru; Shirai, Yasuhiro

    2015-01-01

    Although cross-linguistic research on second language tense-aspect acquisition has uncovered universal tendencies concerning the association between verbal semantics and tense-aspect markers, it is still unclear what mechanisms underlie this link. This study investigates the acquisition of two imperfective aspect markers ("-ko iss-" and…

  5. Fluctuating asymmetry as risk marker for stress and structural defects in a toxicologic experiment.

    PubMed

    Breno, Matteo; Bots, Jessica; De Schaepdrijver, Luc; Van Dongen, Stefan

    2013-08-01

    Fluctuating asymmetry (the directionally random asymmetry of bilateral structures, FA) is commonly used as a measure of developmental instability, and may increase with stress. As several studies reported a relation between FA and developmental abnormalities, we investigate whether FA could be an additional perhaps more sensitive marker of developmental toxicity. The aim of this work is analyzing patterns of FA in multiple traits in a large dataset of rabbit fetuses, which were prenatally exposed to a toxic compound and sacrificed just before natural delivery. Gravid females were exposed to three doses of this compound, inducing abnormalities in the fetuses at the high dose only. The average FA, however, was already higher than control in rabbit fetuses of the low-dose group but did not further increase with higher concentrations. Moreover, the increase in FA differed between traits, with the hindlimbs showing the strongest response. In addition, we did not find any association between FA and the presence of fetal abnormalities at the individual level. Although these results suggest that FA may act as "an early warning system," we did not find a dose-response relationship with increasing stress and effects were trait-specific. Further testing is needed before FA may be considered as a sensitive marker in developmental toxicity studies. © 2013 Wiley Periodicals, Inc.

  6. [Analysis of biochemical markers in serum of guinea pigs after death caused by hypothermia].

    PubMed

    Li, Shi-ying; Deng, Kai-fei; Shao, Yu; Li, Zheng-dong; Qin, Zhi-qiang; Chen, Yi-jiu; Huang, Ping

    2014-08-01

    To explore the changes and rules of biochemical markers in serum of guinea pigs after death caused by hypothermia and to provide references for fatal hypothermia diagnosis by serum biochemical markers. Twenty guinea pigs were randomly divided into experimental group and control group. The guinea pigs in the experimental group were kept at -30 °C until death, while the ones in control group were decapitated after same survival intervals at 25 °C. The serum was extracted from the whole blood of right ventricular immediately. Subsequently, a series of serum biochemical markers were analyzed by auto bio-chemical analyzer. The levels of glucose, uric acid, creatinine and urea nitrogen in the experimental group were significantly higher than those in control group, respectively (P<0.05). Compared with the control group, the levels of total protein and albumin were significantly lower in the experimental group (P<0.05). There were no significantly differences of the levels of other markers such as serum enzymes and ions observed between the two groups. There are characteristic changes of some specific serum biochemical markers in fatal hypothermia, which may be potentially useful for auxiliary diagnosis of fatal hypothermia.

  7. Trends in plant research using molecular markers.

    PubMed

    Garrido-Cardenas, Jose Antonio; Mesa-Valle, Concepción; Manzano-Agugliaro, Francisco

    2018-03-01

    A deep bibliometric analysis has been carried out, obtaining valuable parameters that facilitate the understanding around the research in plant using molecular markers. The evolution of the improvement in the field of agronomy is fundamental for its adaptation to the new exigencies that the current world context raises. In addition, within these improvements, this article focuses on those related to the biotechnology sector. More specifically, the use of DNA markers that allow the researcher to know the set of genes associated with a particular quantitative trait or QTL. The use of molecular markers is widely extended, including: restriction fragment length polymorphism, random-amplified polymorphic DNA, amplified fragment length polymorphism, microsatellites, and single-nucleotide polymorphisms. In addition to classical methodology, new approaches based on the next generation sequencing are proving to be fundamental. In this article, a historical review of the molecular markers traditionally used in plants, since its birth and how the new molecular tools facilitate the work of plant breeders is carried out. The evolution of the most studied cultures from the point of view of molecular markers is also reviewed and other parameters whose prior knowledge can facilitate the approach of researchers to this field of research are analyzed. The bibliometric analysis of molecular markers in plants shows that top five countries in this research are: US, China, India, France, and Germany, and from 2013, this research is led by China. On the other hand, the basic research using Arabidopsis is deeper in France and Germany, while other countries focused its efforts in their main crops as the US for wheat or maize, while China and India for wheat and rice.

  8. Developing, Analyzing, and Using Distractors for Multiple-Choice Tests in Education: A Comprehensive Review

    ERIC Educational Resources Information Center

    Gierl, Mark J.; Bulut, Okan; Guo, Qi; Zhang, Xinxin

    2017-01-01

    Multiple-choice testing is considered one of the most effective and enduring forms of educational assessment that remains in practice today. This study presents a comprehensive review of the literature on multiple-choice testing in education focused, specifically, on the development, analysis, and use of the incorrect options, which are also…

  9. Sewage pollution in urban stormwater runoff as evident from the widespread presence of multiple microbial and chemical source tracking markers.

    PubMed

    Sidhu, J P S; Ahmed, W; Gernjak, W; Aryal, R; McCarthy, D; Palmer, A; Kolotelo, P; Toze, S

    2013-10-01

    The concurrence of human sewage contamination in urban stormwater runoff (n=23) from six urban catchments across Australia was assessed by using both microbial source tracking (MST) and chemical source tracking (CST) markers. Out of 23 stormwater samples human adenovirus (HAv), human polyomavirus (HPv) and the sewage-associated markers; Methanobrevibacter smithii nifH and Bacteroides HF183 were detected in 91%, 56%, 43% and 96% of samples, respectively. Similarly, CST markers paracetamol (87%), salicylic acid (78%) acesulfame (96%) and caffeine (91%) were frequently detected. Twenty one samples (91%) were positive for six to eight sewage related MST and CST markers and remaining two samples were positive for five and four markers, respectively. A very good consensus (>91%) observed between the concurrence of the HF183, HAv, acesulfame and caffeine suggests good predictability of the presence of HAv in samples positive for one of the three markers. High prevalence of HAv (91%) also suggests that other enteric viruses may also be present in the stormwater samples which may pose significant health risks. This study underscores the benefits of employing a set of MST and CST markers which could include monitoring for HF183, adenovirus, caffeine and paracetamol to accurately detect human sewage contamination along with credible information on the presence of human enteric viruses, which could be used for more reliable public health risk assessments. Based on the results obtained in this study, it is recommended that some degree of treatment of captured stormwater would be required if it were to be used for non-potable purposes. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  10. Transient partial permeabilization with saponin enables cellular barcoding prior to surface marker staining1

    PubMed Central

    Behbehani, Gregory K.; Thom, Colin; Zunder, Eli R.; Finck, Rachel; Gaudilliere, Brice; Fragiadakis, Gabriela K.; Fantl, Wendy J.; Nolan, Garry P.

    2015-01-01

    Fluorescent cellular barcoding and mass-tag cellular barcoding are cytometric methods that enable high sample throughput, minimize inter-sample variation, and reduce reagent consumption. Previously employed barcoding protocols require that barcoding be performed after surface marker staining, complicating combining the technique with measurement of alcohol-sensitive surface epitopes. This report describes a method of barcoding fixed cells after a transient partial permeabilization with 0.02% saponin that results in efficient and consistent barcode staining with fluorescent or mass-tagged reagents while preserving surface marker staining. This approach simplifies barcoding protocols and allows direct comparison of surface marker staining of multiple samples without concern for variations in the antibody cocktail volume, antigen-antibody ratio, or machine sensitivity. Using this protocol, cellular barcoding can be used to reliably detect subtle differences in surface marker expression. PMID:25274027

  11. Selectively active markers for solving of the partial occlusion problem in matchmoving and chromakeying workflow

    NASA Astrophysics Data System (ADS)

    Mazurek, Przemysław

    2013-09-01

    Matchmoving (Match Moving) is the process used for the estimation of camera movements for further integration of acquired video image with computer graphics. The estimation of movements is possible using pattern recognition, 2D and 3D tracking algorithms. The main problem for the workflow is the partial occlusion of markers by the actor, because manual rotoscoping is necessary for fixing of the chroma-keyed footage. In the paper, the partial occlusion problem is solved using the invented, selectively active electronic markers. The sensor network with multiple infrared links detects occlusion state (no-occlusion, partial, full) and switch LED's based markers.

  12. Iterative h-minima-based marker-controlled watershed for cell nucleus segmentation.

    PubMed

    Koyuncu, Can Fahrettin; Akhan, Ece; Ersahin, Tulin; Cetin-Atalay, Rengul; Gunduz-Demir, Cigdem

    2016-04-01

    Automated microscopy imaging systems facilitate high-throughput screening in molecular cellular biology research. The first step of these systems is cell nucleus segmentation, which has a great impact on the success of the overall system. The marker-controlled watershed is a technique commonly used by the previous studies for nucleus segmentation. These studies define their markers finding regional minima on the intensity/gradient and/or distance transform maps. They typically use the h-minima transform beforehand to suppress noise on these maps. The selection of the h value is critical; unnecessarily small values do not sufficiently suppress the noise, resulting in false and oversegmented markers, and unnecessarily large ones suppress too many pixels, causing missing and undersegmented markers. Because cell nuclei show different characteristics within an image, the same h value may not work to define correct markers for all the nuclei. To address this issue, in this work, we propose a new watershed algorithm that iteratively identifies its markers, considering a set of different h values. In each iteration, the proposed algorithm defines a set of candidates using a particular h value and selects the markers from those candidates provided that they fulfill the size requirement. Working with widefield fluorescence microscopy images, our experiments reveal that the use of multiple h values in our iterative algorithm leads to better segmentation results, compared to its counterparts. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

  13. A SPR biosensor based on signal amplification using antibody-QD conjugates for quantitative determination of multiple tumor markers

    PubMed Central

    Wang, Huan; Wang, Xiaomei; Wang, Jue; Fu, Weiling; Yao, Chunyan

    2016-01-01

    The detection of tumor markers is very important in early cancer diagnosis; however, tumor markers are usually present at very low concentrations, especially in the early stages of tumor development. Surface plasmon resonance (SPR) is widely used to detect biomolecular interactions; it has inherent advantages of being high-throughput, real-time, and label-free technique. However, its sensitivity needs essential improvement for practical applications. In this study, we developed a signal amplification strategy using antibody-quantum dot (QD) conjugates for the sensitive and quantitative detection of α-fetoprotein (AFP), carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA 21-1) in clinical samples. The use of a dual signal amplification strategy using AuNP-antibody and antibody-QD conjugates increased the signal amplification by 50-folds. The constructed SPR biosensor showed a detection limit as low as 0.1 ng/mL for AFP, CEA, and CYFRA 21-1. Moreover, the results obtained using this SPR biosensor were consistent with those obtained using the electrochemiluminescence method. Thus, the constructed SPR biosensor provides a highly sensitive and specific approach for the detection of tumor markers. This SPR biosensor can be expected to be readily applied for the detection of other tumor markers and can offer a potentially powerful solution for tumor screening. PMID:27615417

  14. Chloroplast genome resources and molecular markers differentiate rubber dandelion species from weedy relatives.

    PubMed

    Zhang, Yingxiao; Iaffaldano, Brian J; Zhuang, Xiaofeng; Cardina, John; Cornish, Katrina

    2017-02-02

    Rubber dandelion (Taraxacum kok-saghyz, TK) is being developed as a domestic source of natural rubber to meet increasing global demand. However, the domestication of TK is complicated by its colocation with two weedy dandelion species, Taraxacum brevicorniculatum (TB) and the common dandelion (Taraxacum officinale, TO). TB is often present as a seed contaminant within TK accessions, while TO is a pandemic weed, which may have the potential to hybridize with TK. To discriminate these species at the molecular level, and facilitate gene flow studies between the potential rubber crop, TK, and its weedy relatives, we generated genomic and marker resources for these three dandelion species. Complete chloroplast genome sequences of TK (151,338 bp), TO (151,299 bp), and TB (151,282 bp) were obtained using the Illumina GAII and MiSeq platforms. Chloroplast sequences were analyzed and annotated for all the three species. Phylogenetic analysis within Asteraceae showed that TK has a closer genetic distance to TB than to TO and Taraxacum species were most closely related to lettuce (Lactuca sativa). By sequencing multiple genotypes for each species and testing variants using gel-based methods, four chloroplast Single Nucleotide Polymorphism (SNP) variants were found to be fixed between TK and TO in large populations, and between TB and TO. Additionally, Expressed Sequence Tag (EST) resources developed for TO and TK permitted the identification of five nuclear species-specific SNP markers. The availability of chloroplast genomes of these three dandelion species, as well as chloroplast and nuclear molecular markers, will provide a powerful genetic resource for germplasm differentiation and purification, and the study of potential gene flow among Taraxacum species.

  15. Salivary Markers of Inflammation in Response to Acute Stress

    PubMed Central

    Slavish, Danica C.; Graham-Engeland, Jennifer E.; Smyth, Joshua M.; Engeland, Christopher G.

    2014-01-01

    There is burgeoning interest in the ability to detect inflammatory markers in response to stress within naturally occurring social contexts and/or across multiple time points per day within individuals. Salivary collection is a less invasive process than current methods of blood collection and enables intensive naturalistic methodologies, such as those involving extensive repeated measures per day over time. Yet the reliability and validity of saliva-based to blood-based inflammatory biomarkers in response to stress remains unclear. We review and synthesize the published studies that have examined salivary markers of inflammation following exposure to an acute laboratory stressor. Results from each study are reviewed by analyte (IL-1β, TNF-α, IL-6, IL-2, IL-4, IL-10, IL-12, CRP) and stress type (social-cognitive and exercise-physical), after which methodological issues and limitations are addressed. Although the literature is limited, several inflammatory markers (including IL-1β, TNF-α, and IL-6) have been reliably determined from saliva and have increased significantly in response to stress across multiple studies, with effect sizes ranging from very small to very large. Although CRP from saliva has been associated with CRP in circulating blood more consistently than other biomarkers have been associated with their counterparts in blood, evidence demonstrating it reliably responds to acute stress is absent. Although the current literature is presently too limited to allow broad assertion that inflammatory biomarkers determined from saliva are valuable for examining acute stress responses, this review suggests that specific targets may be valid and highlights specific areas of need for future research. PMID:25205395

  16. Development of novel genic microsatellite markers from transcriptome sequencing in sugar maple (Acer saccharum Marsh.).

    PubMed

    Harmon, Monica; Lane, Thomas; Staton, Margaret; Coggeshall, Mark V; Best, Teodora; Chen, Chien-Chih; Liang, Haiying; Zembower, Nicole; Drautz-Moses, Daniela I; Hwee, Yap Zhei; Schuster, Stephan C; Schlarbaum, Scott E; Carlson, John E; Gailing, Oliver

    2017-08-08

    Sugar maple (Acer saccharum Marsh.) is a hardwood tree species native to northeastern North America and economically valued for its wood and sap. Yet, few molecular genetic resources have been developed for this species to date. Microsatellite markers have been a useful tool in population genetics, e.g., to monitor genetic variation and to analyze gene flow patterns. The objective of this study is to develop a reference transcriptome and microsatellite markers in sugar maple. A set of 117,861 putative unique transcripts were assembled using 29.2 Gb of RNA sequencing data derived from different tissues and stress treatments. From this set of sequences a total of 1068 microsatellite motifs were identified. Out of 58 genic microsatellite markers tested on a population of 47 sugar maple trees in upper Michigan, 22 amplified well, of which 16 were polymorphic and 6 were monomorphic. Values for expected heterozygosity varied from 0.224 to 0.726 for individual loci. Of the 16 polymorphic markers, 15 exhibited transferability to other Acer L. species. Genic microsatellite markers can be applied to analyze genetic variation in potentially adaptive genes relative to genomic reference markers as a basis for the management of sugar maple genetic resources in the face of climate change.

  17. [The epidemiological trends connected with detection of HIV, HCV, HBV and syphilis markers in blood donors in the years 2006-2009].

    PubMed

    Rudowska, Ewa; Basta, Lidia; Piwowarska, Grazyna; Drybańska, Bozena; Dylag, Stanisław

    2011-03-01

    In the recent years a great progress has been documented in infection prevention. There is more possibilities responsible for infection and its transmission. To analyze obtained epidemiological data concerned to detected infection in blood donors in the area of Blood Bank in Katowice in the years 2006-2009. Statistic calculations taking account of confirmed infections in the years 2006-2009 were analyzed in first-time donors and multiple donors, and for all donors. Tests confirming infection were performed in the IHiT in Warsaw, in RBC in Katowice, confirmation test for syphilis in the RBC in Warsaw. Only the positive confirmed results are taken into account and presented in summary. In first-time donors more frequently the markers of infection: HCV and HBV dozens of times, HIV and syphilis several times were detected. In the group of first-time donors a downward trend was detected in the number of detected infections HBV and HCV In the group of multiple donors the downward trend was documented in the number of detected antibodies associated to syphilis. In the group of multiple donors the number of detected HIV infections has been increased in the years 2008 and 2009. For monitoring trends of each type of infections, a period of four-years is not sufficiently long. This data needs a further observations.

  18. Application of epigenetic markers in molecular breeding of the swine.

    PubMed

    Zhang, Ke; Feng, Guang-de; Zhang, Bao-yun; Xiang, Wei; Chen, Long; Yang, Fang; Chu, Ming-xing; Wang, Ping-qing

    2016-07-20

    Livestock phenotypes are determined by the interaction of a variety of factors, including the genome, the epigenome and the environment. Epigenetics refers to gene expression changes without DNA sequence alterations. Epigenetic markers mainly include DNA methylation, histone modifications, non-coding RNAs, and imprinting genes. More and more researches show that epigenetic markers play an important role in the traits of pigs by modulating phenotype changes via gene expression. However, the role of epigenetic markers has caught little attention in swine breeding. The mechanism that influences important traits of swine has not been analyzed in detail, and it still lacks adequate scientific basis for practical applications. From the aspects of nutrition, diseases, important economic traits and trans-generational inheritance, we summarize the research, application prospects and challenges in the field of utilizing epigenetic markers in molecular breeding of pigs, thus providing a more comprehensive theoretical basis to promote more rapid research development in this field.

  19. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  20. Salivary markers of oxidative stress in oral diseases

    PubMed Central

    Tóthová, L'ubomíra; Kamodyová, Natália; Červenka, Tomáš; Celec, Peter

    2015-01-01

    Saliva is an interesting alternative diagnostic body fluid with several specific advantages over blood. These include non-invasive and easy collection and related possibility to do repeated sampling. One of the obstacles that hinders the wider use of saliva for diagnosis and monitoring of systemic diseases is its composition, which is affected by local oral status. However, this issue makes saliva very interesting for clinical biochemistry of oral diseases. Periodontitis, caries, oral precancerosis, and other local oral pathologies are associated with oxidative stress. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by reactive oxygen species can be measured in saliva. Clinical studies have shown an association with oral pathologies at least for some of the established salivary markers of oxidative stress. This association is currently limited to the population level and none of the widely used markers can be applied for individual diagnostics. Oxidative stress seems to be of local oral origin, but it is currently unclear whether it is caused by an overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants. Interventional studies, both, in experimental animals as well as humans indicate that antioxidant treatment could prevent or slow-down the progress of periodontitis. This makes the potential clinical use of salivary markers of oxidative stress even more attractive. This review summarizes basic information on the most commonly used salivary markers of oxidative damage, antioxidant status, and carbonyl stress and the studies analyzing these markers in patients with caries or periodontitis. PMID:26539412

  1. Immunohistochemical detection of a hypoxia marker in spontaneous canine tumours.

    PubMed Central

    Cline, J. M.; Thrall, D. E.; Page, R. L.; Franko, A. J.; Raleigh, J. A.

    1990-01-01

    An immunoperoxidase technique has been used to detect the in vivo binding of a 2-nitroimidazole hypoxia marker in histochemical sections of a variety of excised canine tumours. The binding occurred 10-12 cell diameters away from tumour blood vessels, consistent with the expected location of hypoxic cells in tissues in which oxygen concentration gradients are established by diffusion. Hypoxic fractions ranging from 4 to 13% have been estimated on the basis of morphometric analysis of multiple tumour sections. The binding of the marker was restricted to the cytoplasm of the cells. The marker appeared in regions adjacent to necrosis but also in regions free of necrosis. As in earlier autoradiography studies, binding was occasionally observed in cells adjacent to tumour blood vessels. Generally, binding to normal tissues was not observed. However, binding to smooth muscle cells surrounding arterioles in some sections of normal tissue and tumour tissue was observed. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1701659

  2. Synteny between the Pro/sup +/ marker and human glutamate oxaloacetate transaminase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jones, C.

    1975-01-01

    Chinese hamster ovary cells with a specific auxotrophy for proline were fused with human cells from a variety of sources and the resulting hybrids analyzed for human genetic markers. Of 63 hybrid clones examined, 27 possessed both proline and cytoplasmic glutamate oxaloacetate transaminase markers; 36 had neither; and no clones were found possessing one and not the other. These results constitute evidence that the proline and glutamate oxaloacetate transaminase markers are syntenic. Evidence for absence of synteny between these and a variety of other human genes is presented. Biochemical tracer experiments established that the proline biosynthetic pathway through glutamate hasmore » been restored in the Pro/sup +/ hybrids.« less

  3. Proteomics research to discover markers: what can we learn from Netflix?

    PubMed

    Ransohoff, David F

    2010-02-01

    Research in the field of proteomics to discover markers for detection of cancer has produced disappointing results, with few markers gaining US Food and Drug Administration approval, and few claims borne out when subsequently tested in rigorous studies. What is the role of better mathematical or statistical analysis in improving the situation? This article examines whether a recent successful Netflix-sponsored competition using mathematical analysis to develop a prediction model for movie ratings of individual subscribers can serve to improve studies of markers in the field of proteomics. Netflix developed a database of movie preferences of individual subscribers using a longitudinal cohort research design. Groups of researchers then competed to develop better ways to analyze the data. Against this background, the strengths and weaknesses of research design are reviewed, contrasting the Netflix design with that of studies of biomarkers to detect cancer. Such biomarker studies generally have less-strong design, lower numbers of outcomes, and greater difficulty in even just measuring predictors and outcomes, so the fundamental data that will be used in mathematical analysis tend to be much weaker than in other kinds of research. If the fundamental data that will be analyzed are not strong, then better analytic methods have limited use in improving the situation. Recognition of this situation is an important first step toward improving the quality of clinical research about markers to detect cancer.

  4. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

    2009-01-01

    Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

  5. Evaluating surrogate endpoints, prognostic markers, and predictive markers: Some simple themes.

    PubMed

    Baker, Stuart G; Kramer, Barnett S

    2015-08-01

    A surrogate endpoint is an endpoint observed earlier than the true endpoint (a health outcome) that is used to draw conclusions about the effect of treatment on the unobserved true endpoint. A prognostic marker is a marker for predicting the risk of an event given a control treatment; it informs treatment decisions when there is information on anticipated benefits and harms of a new treatment applied to persons at high risk. A predictive marker is a marker for predicting the effect of treatment on outcome in a subgroup of patients or study participants; it provides more rigorous information for treatment selection than a prognostic marker when it is based on estimated treatment effects in a randomized trial. We organized our discussion around a different theme for each topic. "Fundamentally an extrapolation" refers to the non-statistical considerations and assumptions needed when using surrogate endpoints to evaluate a new treatment. "Decision analysis to the rescue" refers to use the use of decision analysis to evaluate an additional prognostic marker because it is not possible to choose between purely statistical measures of marker performance. "The appeal of simplicity" refers to a straightforward and efficient use of a single randomized trial to evaluate overall treatment effect and treatment effect within subgroups using predictive markers. The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers. © The Author(s) 2014.

  6. Single Nucleotide Polymorphism Markers for Genetic Mapping in Drosophila melanogaster

    PubMed Central

    Hoskins, Roger A.; Phan, Alexander C.; Naeemuddin, Mohammed; Mapa, Felipa A.; Ruddy, David A.; Ryan, Jessica J.; Young, Lynn M.; Wells, Trent; Kopczynski, Casey; Ellis, Michael C.

    2001-01-01

    For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that recently have revolutionized human, mouse, and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila by using a sequence tagged site-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that span the genome. Most of these markers are single nucleotide polymorphisms and sequences for these variants are provided in an accessible format. The average density of the new markers is one per 225 kb on the autosomes and one per megabase on the X chromosome. We include in this survey a set of P-element strains that provide additional use for high-resolution mapping. We show one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community. PMID:11381036

  7. Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year disability in multiple sclerosis.

    PubMed

    Uher, Tomas; Vaneckova, Manuela; Sobisek, Lukas; Tyblova, Michaela; Seidl, Zdenek; Krasensky, Jan; Ramasamy, Deepa; Zivadinov, Robert; Havrdova, Eva; Kalincik, Tomas; Horakova, Dana

    2017-01-01

    Disease progression and treatment efficacy vary among individuals with multiple sclerosis. Reliable predictors of individual disease outcomes are lacking. To examine the accuracy of the early prediction of 12-year disability outcomes using clinical and magnetic resonance imaging (MRI) parameters. A total of 177 patients from the original Avonex-Steroids-Azathioprine study were included. Participants underwent 3-month clinical follow-ups. Cox models were used to model the associations between clinical and MRI markers at baseline or after 12 months with sustained disability progression (SDP) over the 12-year observation period. At baseline, T2 lesion number, T1 and T2 lesion volumes, corpus callosum (CC), and thalamic fraction were the best predictors of SDP (hazard ratio (HR) = 1.7-4.6; p ⩽ 0.001-0.012). At 12 months, Expanded Disability Status Scale (EDSS) and its change, number of new or enlarging T2 lesions, and CC volume % change were the best predictors of SDP over the follow-up (HR = 1.7-3.5; p ⩽  0.001-0.017). A composite score was generated from a subset of the best predictors of SDP. Scores of ⩾4 had greater specificity (90%-100%) and were associated with greater cumulative risk of SDP (HR = 3.2-21.6; p < 0.001) compared to the individual predictors. The combination of established MRI and clinical indices with MRI volumetric predictors improves the prediction of SDP over long-term follow-up and may provide valuable information for therapeutic decisions.

  8. Multiple point mutations in a shuttle vector propagated in human cells: evidence for an error-prone DNA polymerase activity.

    PubMed

    Seidman, M M; Bredberg, A; Seetharam, S; Kraemer, K H

    1987-07-01

    Mutagenesis was studied at the DNA-sequence level in human fibroblast and lymphoid cells by use of a shuttle vector plasmid, pZ189, containing a suppressor tRNA marker gene. In a series of experiments, 62 plasmids were recovered that had two to six base substitutions in the 160-base-pair marker gene. Approximately 20-30% of the mutant plasmids that were recovered after passing ultraviolet-treated pZ189 through a repair-proficient human fibroblast line contained these multiple mutations. In contrast, passage of ultraviolet-treated pZ189 through an excision-repair-deficient (xeroderma pigmentosum) line yielded only 2% multiple base substitution mutants. Introducing a single-strand nick in otherwise unmodified pZ189 adjacent to the marker, followed by passage through the xeroderma pigmentosum cells, resulted in about 66% multiple base substitution mutants. The multiple mutations were found in a 160-base-pair region containing the marker gene but were rarely found in an adjacent 170-base-pair region. Passing ultraviolet-treated or nicked pZ189 through a repair-proficient human B-cell line also yielded multiple base substitution mutations in 20-33% of the mutant plasmids. An explanation for these multiple mutations is that they were generated by an error-prone polymerase while filling gaps. These mutations share many of the properties displayed by mutations in the immunoglobulin hypervariable regions.

  9. Novel Filtration Markers for GFR Estimation

    PubMed Central

    Inker, Lesley A.; Coresh, Josef; Levey, Andrew S.; Eckfeldt, John H.

    2017-01-01

    Creatinine-based glomerular filtration rate estimation (eGFRcr) has been improved and refined since the 1970s through both the Modification of Diet in Renal Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD-EPI) equation in 2009, with current clinical practice dependent primarily on eGFR for accurate assessment of GFR. However, researchers and clinicians have recognized limitations of relying on creatinine as the only filtration marker, which can lead to inaccurate GFR estimates in certain populations due to the influence of non-GFR determinants of serum or plasma creatinine. Therefore, recent literature has proposed incorporation of multiple serum or plasma filtration markers into GFR estimation to improve precision and accuracy and decrease the impact of non-GFR determinants for any individual biomarker. To this end, the CKD-EPI combined creatinine-cystatin C equation (eGFRcr-cys) was developed in 2012 and demonstrated superior accuracy to equations relying on creatinine or cystatin C alone (eGFRcr or eGFRcys). Now, the focus has broadened to include additional novel filtration markers to further refine and improve GFR estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two filtration markers with established assays that have been proposed as candidates for improving both GFR estimation and risk prediction. GFR estimating equations based on B2M and BTP have been developed and validated, with the CKD-EPI combined BTP-B2M equation (eGFRBTP-B2M) demonstrating similar performance to eGFR and eGFR. Additionally, several studies have demonstrated that both B2M and BTP are associated with outcomes in CKD patients, including cardiovascular events, ESRD and mortality. This review will primarily focus on these two biomarkers, and will highlight efforts to identify additional candidate biomarkers through metabolomics-based approaches. PMID:29333147

  10. Using genetic markers to orient the edges in quantitative trait networks: the NEO software.

    PubMed

    Aten, Jason E; Fuller, Tova F; Lusis, Aldons J; Horvath, Steve

    2008-04-15

    Systems genetic studies have been used to identify genetic loci that affect transcript abundances and clinical traits such as body weight. The pairwise correlations between gene expression traits and/or clinical traits can be used to define undirected trait networks. Several authors have argued that genetic markers (e.g expression quantitative trait loci, eQTLs) can serve as causal anchors for orienting the edges of a trait network. The availability of hundreds of thousands of genetic markers poses new challenges: how to relate (anchor) traits to multiple genetic markers, how to score the genetic evidence in favor of an edge orientation, and how to weigh the information from multiple markers. We develop and implement Network Edge Orienting (NEO) methods and software that address the challenges of inferring unconfounded and directed gene networks from microarray-derived gene expression data by integrating mRNA levels with genetic marker data and Structural Equation Model (SEM) comparisons. The NEO software implements several manual and automatic methods for incorporating genetic information to anchor traits. The networks are oriented by considering each edge separately, thus reducing error propagation. To summarize the genetic evidence in favor of a given edge orientation, we propose Local SEM-based Edge Orienting (LEO) scores that compare the fit of several competing causal graphs. SEM fitting indices allow the user to assess local and overall model fit. The NEO software allows the user to carry out a robustness analysis with regard to genetic marker selection. We demonstrate the utility of NEO by recovering known causal relationships in the sterol homeostasis pathway using liver gene expression data from an F2 mouse cross. Further, we use NEO to study the relationship between a disease gene and a biologically important gene co-expression module in liver tissue. The NEO software can be used to orient the edges of gene co-expression networks or quantitative trait

  11. A marker placement laser device for improving repeatability in 3D-foot motion analysis.

    PubMed

    Kalkum, Eva; van Drongelen, Stefan; Mussler, Johannes; Wolf, Sebastian I; Kuni, Benita

    2016-02-01

    In 3D gait analysis, the repeated positioning of markers is associated with a high error rate, particularly when using a complex foot model with many markers. Therefore, a marker placement laser device was developed that ensures a reliable repositioning of markers. We report the development and reliability of this device for the foot at different tape conditions. In 38 subjects, markers were placed at the foot according to the Heidelberg foot measurement method. Subjects were tested barefoot and barefoot with three different tape conditions. For all conditions, a static standing trial was captured. We analyzed differences in distances between markers and the intra-class correlation coefficients (ICC). Small differences between the conditions (0.03-3.28 mm) and excellent ICCs (0.91-0.97 mm) were found for all parameters. The laser marker placement device appeared to be a reliable method to place markers on a tape at previously palpated positions and ensures an exact position. The device could find a wide application in different clinical research fields. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. HAL: a hierarchical format for storing and analyzing multiple genome alignments.

    PubMed

    Hickey, Glenn; Paten, Benedict; Earl, Dent; Zerbino, Daniel; Haussler, David

    2013-05-15

    Large multiple genome alignments and inferred ancestral genomes are ideal resources for comparative studies of molecular evolution, and advances in sequencing and computing technology are making them increasingly obtainable. These structures can provide a rich understanding of the genetic relationships between all subsets of species they contain. Current formats for storing genomic alignments, such as XMFA and MAF, are all indexed or ordered using a single reference genome, however, which limits the information that can be queried with respect to other species and clades. This loss of information grows with the number of species under comparison, as well as their phylogenetic distance. We present HAL, a compressed, graph-based hierarchical alignment format for storing multiple genome alignments and ancestral reconstructions. HAL graphs are indexed on all genomes they contain. Furthermore, they are organized phylogenetically, which allows for modular and parallel access to arbitrary subclades without fragmentation because of rearrangements that have occurred in other lineages. HAL graphs can be created or read with a comprehensive C++ API. A set of tools is also provided to perform basic operations, such as importing and exporting data, identifying mutations and coordinate mapping (liftover). All documentation and source code for the HAL API and tools are freely available at http://github.com/glennhickey/hal. hickey@soe.ucsc.edu or haussler@soe.ucsc.edu Supplementary data are available at Bioinformatics online.

  13. Impact of age on markers of HIV-1 disease

    PubMed Central

    Pirrone, Vanessa; Libon, David J; Sell, Christian; Lerner, Chad A; Nonnemacher, Michael R; Wigdahl, Brian

    2013-01-01

    Aging is a complicated process characterized by a progressive loss of homeostasis, which results in an increased vulnerability to multiple diseases. HIV-1-infected patients demonstrate a premature aging phenotype and develop certain age-related diseases earlier in their lifespan than what is seen in the general population. Age-related comorbidities may include the development of bone disease, metabolic disorders, neurologic impairment and immunosenescence. Age also appears to have an effect on traditional markers of HIV-1 disease progression, including CD4+ T-cell count and viral load. These effects are not only a consequence of HIV-1 infection, but in many cases, are also linked to antiretroviral therapy. This review summarizes the complex interplay between HIV-1 infection and aging, and the impact that aging has on markers of HIV-1 disease. PMID:23596462

  14. Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic Project on Lung Cancer.

    PubMed

    Monsó, Eduard; Montuenga, Luis M; Sánchez de Cos, Julio; Villena, Cristina

    2015-09-01

    The aim of the Clinical and Molecular Staging of Stage I-IIp Lung Cancer Project is to identify molecular variables that improve the prognostic and predictive accuracy of TMN classification in stage I/IIp non-small cell lung cancer (NSCLC). Clinical data and lung tissue, tumor and blood samples will be collected from 3 patient cohorts created for this purpose. The prognostic protein signature will be validated from these samples, and micro-RNA, ALK, Ros1, Pdl-1, and TKT, TKTL1 y G6PD expression will be analyzed. Tissue inflammatory markers and stromal cell markers will also be analyzed. Methylation of p16, DAPK, RASSF1a, APC and CDH13 genes in the tissue samples will be determined, and inflammatory markers in peripheral blood will also be analyzed. Variables that improve the prognostic and predictive accuracy of TNM in NSCLC by molecular staging may be identified from this extensive analytical panel. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  15. Performance evaluation of LUMIPULSE G1200 autoimmunoanalyzer for the detection of serum hepatitis B virus markers.

    PubMed

    Choi, Seung Jun; Park, Yongjung; Lee, Eun Young; Kim, Sinyoung; Kim, Hyon-Suk

    2013-05-01

    We evaluated recently introduced automated immunoassay analyzer LUMIPULSE G1200 (Fujirebio, Inc., Tokyo, Japan) for detecting serologic hepatitis B virus (HBV) markers by comparison with the results by ARCHITECT i4000SR (Abbott, Abbott Park, IL). Precision performance was evaluated over 20 days. HBV surface antigen (HBsAg), HBV e antigen (HBeAg), antibodies to HBV core antigen (anti-HBc), antibodies to HBeAg (anti-HBe), and antibodies to HBsAg (anti-HBs) in a total of 1,000 serum samples were assessed by the two analyzers. Discrepant results were retested by COBAS e411 (Roche Diagnostics, Mannheim, Germany). LUMIPULSE showed excellent precision performance of total imprecision less than 3.5% coefficient of variation. The qualitative results between the two analyzers were agreed with each other in 92.0-99.8% of the specimens according to the different HBV markers. The degrees of reactions for HBeAg were moderately correlated between the two analyzers (r = 0.60), and those of other HBV markers were well correlated (r = 0.80 or greater). However, there were 183 discrepancies among 1,000 cases, and most of them showed degree of reaction around the cutoff values. LUMIPULSE G1200 showed well-concordant results with ARCITHECT for hepatitis B serologic tests. However, results near the cutoff values would need to be retested with other immunoassay or molecular methods, when the serological profiles of HBV markers are unusual or are not correlated to the clinical conditions of the patient, due to discrepancies between the immunoassay analyzers. © 2013 Wiley Periodicals, Inc.

  16. Markers of neuroinflammation and neuronal injury in bipolar disorder: Relation to prospective clinical outcomes.

    PubMed

    Isgren, Anniella; Sellgren, Carl; Ekman, Carl-Johan; Holmén-Larsson, Jessica; Blennow, Kaj; Zetterberg, Henrik; Jakobsson, Joel; Landén, Mikael

    2017-10-01

    Neuroimmune mechanisms have been linked to the pathophysiology of bipolar disorder based on studies of biomarkers in plasma, cerebrospinal fluid (CSF), and postmortem brain tissue. There are, however, no longitudinal studies investigating if CSF markers of neuroinflammation and neuronal injury predict clinical outcomes in patients with bipolar disorder. We have in previous studies found higher CSF concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1/CCL-2), chitinase-3-like protein 1 (CHI3L1/YKL-40), and neurofilament light chain (NF-L) in euthymic patients with bipolar disorder compared with controls. Here, we investigated the relationship of these CSF markers of neuroinflammation and neuronal injury with clinical outcomes in a prospective study. 77 patients with CSF analyzed at baseline were followed for 6-7years. Associations of baseline biomarkers with clinical outcomes (manic/hypomanic and depressive episodes, suicide attempts, psychotic symptoms, inpatient care, GAF score change) were investigated. Baseline MCP-1 concentrations were positively associated with manic/hypomanic episodes and inpatient care during follow-up. YKL-40 concentrations were negatively associated with manic/hypomanic episodes and with occurrence of psychotic symptoms. The prospective negative association between YKL-40 and manic/hypomanic episodes survived multiple testing correction. Concentrations of IL-8 and NF-L were not associated with clinical outcomes. High concentrations of these selected CSF markers of neuroinflammation and neuronal injury at baseline were not consistently associated with poor clinical outcomes in this prospective study. The assessed proteins may be involved in adaptive immune processes or reflect a state of vulnerability for bipolar disorder rather than being of predictive value for disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Multiview marker-free registration of forest terrestrial laser scanner data with embedded confidence metrics

    DOE PAGES

    Kelbe, David; Oak Ridge National Lab.; van Aardt, Jan; ...

    2016-10-18

    Terrestrial laser scanning has demonstrated increasing potential for rapid comprehensive measurement of forest structure, especially when multiple scans are spatially registered in order to reduce the limitations of occlusion. Although marker-based registration techniques (based on retro-reflective spherical targets) are commonly used in practice, a blind marker-free approach is preferable, insofar as it supports rapid operational data acquisition. To support these efforts, we extend the pairwise registration approach of our earlier work, and develop a graph-theoretical framework to perform blind marker-free global registration of multiple point cloud data sets. Pairwise pose estimates are weighted based on their estimated error, in ordermore » to overcome pose conflict while exploiting redundant information and improving precision. The proposed approach was tested for eight diverse New England forest sites, with 25 scans collected at each site. Quantitative assessment was provided via a novel embedded confidence metric, with a mean estimated root-mean-square error of 7.2 cm and 89% of scans connected to the reference node. Lastly, this paper assesses the validity of the embedded multiview registration confidence metric and evaluates the performance of the proposed registration algorithm.« less

  18. Dissecting the phyloepidemiology of Trypanosoma cruzi I (TcI) in Brazil by the use of high resolution genetic markers.

    PubMed

    Roman, Fabiola; das Chagas Xavier, Samanta; Messenger, Louisa A; Pavan, Márcio G; Miles, Michael A; Jansen, Ana María; Yeo, Matthew

    2018-05-01

    Trypanosoma cruzi, the causal agent of Chagas disease, is monophyletic but genetically heterogeneous. It is currently represented by six genetic lineages (Discrete Typing Units, DTUs) designated TcI-TcVI. TcI is the most geographically widespread and genetically heterogeneous lineage, this as is evidenced by a wide range of genetic markers applied to isolates spanning a vast geographic range in Latin America. In total, 78 TcI isolated from hosts and vectors distributed in 5 different biomes of Brazil, were analyzed using 6 nuclear housekeeping genes, 25 microsatellite loci and one mitochondrial marker. Nuclear markers reveal substantial genetic diversity, significant gene flow between biomes, incongruence in phylogenies, and haplotypic analysis indicative of intra-DTU genetic exchange. Phylogenetic reconstructions based on mitochondrial and nuclear loci were incongruent, and consistent with introgression. Structure analysis of microsatellite data reveals that, amongst biomes, the Amazon is the most genetically diverse and experiences the lowest level of gene flow. Investigation of population structure based on the host species/genus, indicated that Didelphis marsupialis might play a role as the main disperser of TcI. The present work considers a large TcI sample from different hosts and vectors spanning multiple ecologically diverse biomes in Brazil. Importantly, we combine fast and slow evolving markers to contribute to the epizootiological understanding of TcI in five distinct Brazilian biomes. This constitutes the first instance in which MLST analysis was combined with the use of MLMT and maxicircle markers to evaluate the genetic diversity of TcI isolates in Brazil. Our results demonstrate the existence of substantial genetic diversity and the occurrence of introgression events. We provide evidence of genetic exchange in TcI isolates from Brazil and of the relative isolation of TcI in the Amazon biome. We observe the absence of strict associations with Tc

  19. Fast internal marker tracking algorithm for onboard MV and kV imaging systems

    PubMed Central

    Mao, W.; Wiersma, R. D.; Xing, L.

    2008-01-01

    Intrafraction organ motion can limit the advantage of highly conformal dose techniques such as intensity modulated radiation therapy (IMRT) due to target position uncertainty. To ensure high accuracy in beam targeting, real-time knowledge of the target location is highly desired throughout the beam delivery process. This knowledge can be gained through imaging of internally implanted radio-opaque markers with fluoroscopic or electronic portal imaging devices (EPID). In the case of MV based images, marker detection can be problematic due to the significantly lower contrast between different materials in comparison to their kV-based counterparts. This work presents a fully automated algorithm capable of detecting implanted metallic markers in both kV and MV images with high consistency. Using prior CT information, the algorithm predefines the volumetric search space without manual region-of-interest (ROI) selection by the user. Depending on the template selected, both spherical and cylindrical markers can be detected. Multiple markers can be simultaneously tracked without indexing confusion. Phantom studies show detection success rates of 100% for both kV and MV image data. In addition, application of the algorithm to real patient image data results in successful detection of all implanted markers for MV images. Near real-time operational speeds of ∼10 frames∕sec for the detection of five markers in a 1024×768 image are accomplished using an ordinary PC workstation. PMID:18561670

  20. Multiplex pyrosequencing of InDel markers for forensic DNA analysis.

    PubMed

    Bus, Magdalena M; Karas, Ognjen; Allen, Marie

    2016-12-01

    The capillary electrophoresis (CE) technology is commonly used for fragment length separation of markers in forensic DNA analysis. In this study, pyrosequencing technology was used as an alternative and rapid tool for the analysis of biallelic InDel (insertion/deletion) markers for individual identification. The DNA typing is based on a subset of the InDel markers that are included in the Investigator ® DIPplex Kit, which are sequenced in a multiplex pyrosequencing analysis. To facilitate the analysis of degraded DNA, the polymerase chain reaction (PCR) fragments were kept short in the primer design. Samples from individuals of Swedish origin were genotyped using the pyrosequencing strategy and analysis of the Investigator ® DIPplex markers with CE. A comparison between the pyrosequencing and CE data revealed concordant results demonstrating a robust and correct genotyping by pyrosequencing. Using optimal marker combination and a directed dispensation strategy, five markers could be multiplexed and analyzed simultaneously. In this proof-of-principle study, we demonstrate that multiplex InDel pyrosequencing analysis is possible. However, further studies on degraded samples, lower DNA quantities, and mixtures will be required to fully optimize InDel analysis by pyrosequencing for forensic applications. Overall, although CE analysis is implemented in most forensic laboratories, multiplex InDel pyrosequencing offers a cost-effective alternative for some applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Development of simple sequence repeat markers and diversity analysis in alfalfa (Medicago sativa L.).

    PubMed

    Wang, Zan; Yan, Hongwei; Fu, Xinnian; Li, Xuehui; Gao, Hongwen

    2013-04-01

    Efficient and robust molecular markers are essential for molecular breeding in plant. Compared to dominant and bi-allelic markers, multiple alleles of simple sequence repeat (SSR) markers are particularly informative and superior in genetic linkage map and QTL mapping in autotetraploid species like alfalfa. The objective of this study was to enrich SSR markers directly from alfalfa expressed sequence tags (ESTs). A total of 12,371 alfalfa ESTs were retrieved from the National Center for Biotechnology Information. Total 774 SSR-containing ESTs were identified from 716 ESTs. On average, one SSR was found per 7.7 kb of EST sequences. Tri-nucleotide repeats (48.8 %) was the most abundant motif type, followed by di-(26.1 %), tetra-(11.5 %), penta-(9.7 %), and hexanucleotide (3.9 %). One hundred EST-SSR primer pairs were successfully designed and 29 exhibited polymorphism among 28 alfalfa accessions. The allele number per marker ranged from two to 21 with an average of 6.8. The PIC values ranged from 0.195 to 0.896 with an average of 0.608, indicating a high level of polymorphism of the EST-SSR markers. Based on the 29 EST-SSR markers, assessment of genetic diversity was conducted and found that Medicago sativa ssp. sativa was clearly different from the other subspecies. The high transferability of those EST-SSR markers was also found for relative species.

  2. A consensus genetic map of sorghum that integrates multiple component maps and high-throughput diversity array technology (DArT) markers

    USDA-ARS?s Scientific Manuscript database

    This final consensus map has allowed us to map a larger number of markers than possible in any individual map of sorghum, to obtain a more complete coverage of the sorghum genome and to fill a number of gaps on individual maps. In addition to overall general consistency of marker order across indiv...

  3. Investigation and Analysis of Genetic Diversity of Diospyros Germplasms Using SCoT Molecular Markers in Guangxi.

    PubMed

    Deng, Libao; Liang, Qingzhi; He, Xinhua; Luo, Cong; Chen, Hu; Qin, Zhenshi

    2015-01-01

    Knowledge about genetic diversity and relationships among germplasms could be an invaluable aid in diospyros improvement strategies. This study was designed to analyze the genetic diversity and relationship of local and natural varieties in Guangxi Zhuang Autonomous Region of China using start codon targeted polymorphism (SCoT) markers. The accessions of 95 diospyros germplasms belonging to four species Diospyros kaki Thunb, D. oleifera Cheng, D. kaki var. silverstris Mak, and D. lotus Linn were collected from different eco-climatic zones in Guangxi and were analyzed using SCoT markers. Results indicated that the accessions of 95 diospyros germplasms could be distinguished using SCoT markers, and were divided into three groups at similarity coefficient of 0.608; these germplasms that belong to the same species were clustered together; of these, the degree of genetic diversity of the natural D. kaki var. silverstris Mak population was richest among the four species; the geographical distance showed that the 12 natural populations of D. kaki var. silverstris Mak were divided into two groups at similarity coefficient of 0.19. Meanwhile, in order to further verify the stable and useful of SCoT markers in diospyros germplasms, SSR markers were also used in current research to analyze the genetic diversity and relationship in the same diospyros germplasms. Once again, majority of germplasms that belong to the same species were clustered together. Thus SCoT markers were stable and especially useful for analysis of the genetic diversity and relationship in diospyros germplasms. The molecular characterization and diversity assessment of diospyros were very important for conservation of diospyros germplasm resources, meanwhile for diospyros improvement.

  4. Investigation and Analysis of Genetic Diversity of Diospyros Germplasms Using SCoT Molecular Markers in Guangxi

    PubMed Central

    He, Xinhua; Luo, Cong; Chen, Hu; Qin, Zhenshi

    2015-01-01

    Background Knowledge about genetic diversity and relationships among germplasms could be an invaluable aid in diospyros improvement strategies. Methods This study was designed to analyze the genetic diversity and relationship of local and natural varieties in Guangxi Zhuang Autonomous Region of China using start codon targeted polymorphism (SCoT) markers. The accessions of 95 diospyros germplasms belonging to four species Diospyros kaki Thunb, D. oleifera Cheng, D. kaki var. silverstris Mak, and D. lotus Linn were collected from different eco-climatic zones in Guangxi and were analyzed using SCoT markers. Results Results indicated that the accessions of 95 diospyros germplasms could be distinguished using SCoT markers, and were divided into three groups at similarity coefficient of 0.608; these germplasms that belong to the same species were clustered together; of these, the degree of genetic diversity of the natural D. kaki var. silverstris Mak population was richest among the four species; the geographical distance showed that the 12 natural populations of D. kaki var. silverstris Mak were divided into two groups at similarity coefficient of 0.19. Meanwhile, in order to further verify the stable and useful of SCoT markers in diospyros germplasms, SSR markers were also used in current research to analyze the genetic diversity and relationship in the same diospyros germplasms. Once again, majority of germplasms that belong to the same species were clustered together. Thus SCoT markers were stable and especially useful for analysis of the genetic diversity and relationship in diospyros germplasms. Discussion The molecular characterization and diversity assessment of diospyros were very important for conservation of diospyros germplasm resources, meanwhile for diospyros improvement. PMID:26317414

  5. Correlates and Risk Markers for Sleep Disturbance in Participants of the Autism Treatment Network

    ERIC Educational Resources Information Center

    Hollway, Jill A.; Aman, Michael G.; Butter, Eric

    2013-01-01

    We explored possible cognitive, behavioral, emotional, and physiological risk markers for sleep disturbance in children with autism spectrum disorders. Data from 1,583 children in the Autism Treatment Network were analyzed. Approximately 45 potential predictors were analyzed using hierarchical regression modeling. As medication could confound…

  6. Tracking multiple surgical instruments in a near-infrared optical system.

    PubMed

    Cai, Ken; Yang, Rongqian; Lin, Qinyong; Wang, Zhigang

    2016-12-01

    Surgical navigation systems can assist doctors in performing more precise and more efficient surgical procedures to avoid various accidents. The near-infrared optical system (NOS) is an important component of surgical navigation systems. However, several surgical instruments are used during surgery, and effectively tracking all of them is challenging. A stereo matching algorithm using two intersecting lines and surgical instrument codes is proposed in this paper. In our NOS, the markers on the surgical instruments can be captured by two near-infrared cameras. After automatically searching and extracting their subpixel coordinates in the left and right images, the coordinates of the real and pseudo markers are determined by the two intersecting lines. Finally, the pseudo markers are removed to achieve accurate stereo matching by summing the codes for the distances between a specific marker with the other two markers on the surgical instrument. Experimental results show that the markers on the different surgical instruments can be automatically and accurately recognized. The NOS can accurately track multiple surgical instruments.

  7. CHEMICAL MARKERS OF HUMAN WASTE ...

    EPA Pesticide Factsheets

    Giving public water authorities another tool to monitor and measure levels of human waste contamination of waters simply and rapidly would enhance public protection. Most of the methods used today detect such contamination by quantifying microbes occurring in feces in high enough densities that they can be measured easily. However, most of these microbes, for example E. coli, do not serve as specific markers for any one host species and many can have origins other than feces. As an alternative, chemicals shed in feces and urine might be used to detect human waste contamination of environmental waters. One potential chemical marker of human waste is the compound urobilin. Urobilin is one of the final by-products of hemoglobin breakdown. Urobilin is excreted in both the urine and feces from many mammals, particularly humans. Source waters from 21 sites in New England, Nevada, and Michigan were extracted using hydrophilic-lipophilic balance (HLB) cartridges and then analyzed by high performance liquid chromatography-electrospray-mass spectrometry (HPLC-ES-MS). As a marker of human waste, urobilin was detected in many of the source waters at concentrations ranging from not detectable to 300 ng/L. Besides urobilin, zithromycin, an antibiotic widely prescribed for human-use only in the US, was also detected in many of these waters, with concentrations ranging from not detectable to 77 ng/L. This methodology, using both urobilin and azithromycin (or any other human-use

  8. Defining Success in Adult Basic Education Settings: Multiple Stakeholders, Multiple Perspectives

    PubMed Central

    Tighe, Elizabeth L.; Barnes, Adrienne E.; Connor, Carol M.; Steadman, Sharilyn C.

    2015-01-01

    This study employed quantitative and qualitative research approaches to investigate what constitutes “success” in Adult Basic Education (ABE) programs from the perspectives of multiple educational stakeholders: the state funding agency, the teachers, and the students. Success was defined in multiple ways. In the quantitative section of the study, we computed classroom value-added scores (used as a metric of the state’s definition of success) to identify more and less effective ABE classrooms in two Florida counties. In the qualitative section of the study, we observed and conducted interviews with teachers and students in the selected classrooms to investigate how these stakeholders defined success in ABE. Iterative consideration of the qualitative data revealed three principal markers of success: (a) instructional strategies and teacher-student interactions; (b) views on standardized testing; and (c) student motivational factors. In general, classrooms with higher value-added scores were characterized by multiple instructional approaches, positive and collaborative teacher-student interactions, and students engaging in goal setting and citing motivational factors such as family and personal fulfillment. The implications for ABE programs are discussed. PMID:26279590

  9. Serum cystatin C level is associated with carotid arterial wall elasticity in subjects with type 2 diabetes mellitus: A potential marker of early-stage atherosclerosis.

    PubMed

    Kaneko, Rei; Sawada, Shojiro; Tokita, Ai; Honkura, Rieko; Tamura, Noriko; Kodama, Shinjiro; Izumi, Tomohito; Takahashi, Kei; Uno, Kenji; Imai, Junta; Yamada, Tetsuya; Miyachi, Yukiya; Hasegawa, Hideyuki; Kanai, Hiroshi; Ishigaki, Yasushi; Katagiri, Hideki

    2018-05-01

    Detection of early-stage atherosclerosis in type 2 diabetes mellitus (T2DM) patients is important for preventing cardiovascular disease. A phased tracking method for evaluating arterial wall elasticity sensitively detects early-stage atherosclerosis. However, biochemical markers for early-stage atherosclerosis have yet to be established. This cross-sectional study enrolled 180 T2DM patients, who were classified as not having atherosclerosis according to the carotid intima-media thickness (IMT) criteria. We measured serum cystatin C, the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR), and analyzed the associations between these markers and arterial wall elasticity (Eθ), IMT and the cardio-ankle velocity index. Multiple linear regression analyses revealed that cystatin C was significantly associated with Eθ, while neither eGFR nor ACR showed an association. Furthermore, among the examined atherosclerotic markers, Eθ was most reliably associated with cystatin C. Additionally, the association between cystatin C and Eθ disappeared in the low elasticity subgroup, which included subjects in whom no atherosclerotic changes had yet been initiated. In T2DM patients without apparent arterial wall thickening, cystatin C is strongly and independently associated with arterial wall elasticity, which reflects the degree of subclinical atherosclerosis. Thus, cystatin C is a potentially useful marker of early-stage atherosclerosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Evaluating surrogate endpoints, prognostic markers, and predictive markers — some simple themes

    PubMed Central

    Baker, Stuart G.; Kramer, Barnett S.

    2014-01-01

    Background A surrogate endpoint is an endpoint observed earlier than the true endpoint (a health outcome) that is used to draw conclusions about the effect of treatment on the unobserved true endpoint. A prognostic marker is a marker for predicting the risk of an event given a control treatment; it informs treatment decisions when there is information on anticipated benefits and harms of a new treatment applied to persons at high risk. A predictive marker is a marker for predicting the effect of treatment on outcome in a subgroup of patients or study participants; it provides more rigorous information for treatment selection than a prognostic marker when it is based on estimated treatment effects in a randomized trial. Methods We organized our discussion around a different theme for each topic. Results “Fundamentally an extrapolation” refers to the non-statistical considerations and assumptions needed when using surrogate endpoints to evaluate a new treatment. “Decision analysis to the rescue” refers to use the use of decision analysis to evaluate an additional prognostic marker because it is not possible to choose between purely statistical measures of marker performance. “The appeal of simplicity” refers to a straightforward and efficient use of a single randomized trial to evaluate overall treatment effect and treatment effect within subgroups using predictive markers. Conclusion The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers. PMID:25385934

  11. Development of Cymbidium ensifolium genic-SSR markers and their utility in genetic diversity and population structure analysis in cymbidiums.

    PubMed

    Li, Xiaobai; Jin, Feng; Jin, Liang; Jackson, Aaron; Huang, Cheng; Li, Kehu; Shu, Xiaoli

    2014-12-05

    Cymbidium is a genus of 68 species in the orchid family, with extremely high ornamental value. Marker-assisted selection has proven to be an effective strategy in accelerating plant breeding for many plant species. Analysis of cymbidiums genetic background by molecular markers can be of great value in assisting parental selection and breeding strategy design, however, in plants such as cymbidiums limited genomic resources exist. In order to obtain efficient markers, we deep sequenced the C. ensifolium transcriptome to identify simple sequence repeats derived from gene regions (genic-SSR). The 7,936 genic-SSR markers were identified. A total of 80 genic-SSRs were selected, and primers were designed according to their flanking sequences. Of the 80 genic-SSR primer sets, 62 were amplified in C. ensifolium successfully, and 55 showed polymorphism when cross-tested among 9 Cymbidium species comprising 59 accessions. Unigenes containing the 62 genic-SSRs were searched against Non-redundant (Nr), Gene Ontology database (GO), eukaryotic orthologous groups (KOGs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The search resulted in 53 matching Nr sequences, of which 39 had GO terms, 18 were assigned to KOGs, and 15 were annotated with KEGG. Genetic diversity and population structure were analyzed based on 55 polymorphic genic-SSR data among 59 accessions. The genetic distance averaged 0.3911, ranging from 0.016 to 0.618. The polymorphic index content (PIC) of 55 polymorphic markers averaged 0.407, ranging from 0.033 to 0.863. A model-based clustering analysis revealed that five genetic groups existed in the collection. Accessions from the same species were typically grouped together; however, C. goeringii accessions did not always form a separate cluster, suggesting that C. goeringii accessions were polyphyletic. The genic-SSR identified in this study constitute a set of markers that can be applied across multiple Cymbidium species and used for the evaluation

  12. Molecular diversity analysis of Tetradium ruticarpum (WuZhuYu) in China based on inter-primer binding site (iPBS) markers and inter-simple sequence repeat (ISSR) markers.

    PubMed

    Xu, Jing-Yuan; Zhu, Yan; Yi, Ze; Wu, Gang; Xie, Guo-Yong; Qin, Min-Jian

    2018-01-01

    "Wu zhu yu", which is obtained from the dried unripe fruits of Tetradium ruticarpum (A. Jussieu) T. G. Hartley, has been used as a traditional Chinese medicine for treatment of headaches, abdominal colic, and hypertension for thousands of years. The present study was designed to assess the molecular genetic diversity among 25 collected accessions of T. ruticarpum (Wu zhu yu in Chinese) from different areas of China, based on inter-primer binding site (iPBS) markers and inter-simple sequence repeat (ISSR) markers. Thirteen ISSR primers generated 151 amplification bands, of which 130 were polymorphic. Out of 165 bands that were amplified using 10 iPBS primers, 152 were polymorphic. The iPBS markers displayed a higher proportion of polymorphic loci (PPL = 92.5%) than the ISSR markers (PPL = 84.9%). The results showed that T. ruticarpum possessed high loci polymorphism and genetic differentiation occurred in this plant. The combined data of iPBS and ISSR markers scored on 25 accessions produced five clusters that approximately matched the geographic distribution of the species. The results indicated that both iPBS and ISSR markers were reliable and effective tools for analyzing the genetic diversity in T. ruticarpum. Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  13. A Population Genetics Model of Marker-Assisted Selection

    PubMed Central

    Luo, Z. W.; Thompson, R.; Woolliams, J. A.

    1997-01-01

    A deterministic two-loci model was developed to predict genetic response to marker-assisted selection (MAS) in one generation and in multiple generations. Formulas were derived to relate linkage disequilibrium in a population to the proportion of additive genetic variance used by MAS, and in turn to an extra improvement in genetic response over phenotypic selection. Predictions of the response were compared to those predicted by using an infinite-loci model and the factors affecting efficiency of MAS were examined. Theoretical analyses of the present study revealed the nonlinearity between the selection intensity and genetic response in MAS. In addition to the heritability of the trait and the proportion of the marker-associated genetic variance, the frequencies of the selectively favorable alleles at the two loci, one marker and one quantitative trait locus, were found to play an important role in determining both the short- and long-term efficiencies of MAS. The evolution of linkage disequilibrium and thus the genetic response over several generations were predicted theoretically and examined by simulation. MAS dissipated the disequilibrium more quickly than drift alone. In some cases studied, the rate of dissipation was as large as that to be expected in the circumstance where the true recombination fraction was increased by three times and selection was absent. PMID:9215918

  14. Analyzing Multiple Outcomes in Clinical Research Using Multivariate Multilevel Models

    PubMed Central

    Baldwin, Scott A.; Imel, Zac E.; Braithwaite, Scott R.; Atkins, David C.

    2014-01-01

    Objective Multilevel models have become a standard data analysis approach in intervention research. Although the vast majority of intervention studies involve multiple outcome measures, few studies use multivariate analysis methods. The authors discuss multivariate extensions to the multilevel model that can be used by psychotherapy researchers. Method and Results Using simulated longitudinal treatment data, the authors show how multivariate models extend common univariate growth models and how the multivariate model can be used to examine multivariate hypotheses involving fixed effects (e.g., does the size of the treatment effect differ across outcomes?) and random effects (e.g., is change in one outcome related to change in the other?). An online supplemental appendix provides annotated computer code and simulated example data for implementing a multivariate model. Conclusions Multivariate multilevel models are flexible, powerful models that can enhance clinical research. PMID:24491071

  15. Polymorphic Microsatellite Markers for the Tetrapolar Anther-Smut Fungus Microbotryum saponariae Based on Genome Sequencing

    PubMed Central

    Fortuna, Taiadjana M.; Snirc, Alodie; Badouin, Hélène; Gouzy, Jérome; Siguenza, Sophie; Esquerre, Diane; Le Prieur, Stéphanie; Shykoff, Jacqui A.; Giraud, Tatiana

    2016-01-01

    Background Anther-smut fungi belonging to the genus Microbotryum sterilize their host plants by aborting ovaries and replacing pollen by fungal spores. Sibling Microbotryum species are highly specialized on their host plants and they have been widely used as models for studies of ecology and evolution of plant pathogenic fungi. However, most studies have focused, so far, on M. lychnidis-dioicae that parasitizes the white campion Silene latifolia. Microbotryum saponariae, parasitizing mainly Saponaria officinalis, is an interesting anther-smut fungus, since it belongs to a tetrapolar lineage (i.e., with two independently segregating mating-type loci), while most of the anther-smut Microbotryum fungi are bipolar (i.e., with a single mating-type locus). Saponaria officinalis is a widespread long-lived perennial plant species with multiple flowering stems, which makes its anther-smut pathogen a good model for studying phylogeography and within-host multiple infections. Principal Findings Here, based on a generated genome sequence of M. saponariae we developed 6 multiplexes with a total of 22 polymorphic microsatellite markers using an inexpensive and efficient method. We scored these markers in fungal individuals collected from 97 populations across Europe, and found that the number of their alleles ranged from 2 to 11, and their expected heterozygosity from 0.01 to 0.58. Cross-species amplification was examined using nine other Microbotryum species parasitizing hosts belonging to Silene, Dianthus and Knautia genera. All loci were successfully amplified in at least two other Microbotryum species. Significance These newly developed markers will provide insights into the population genetic structure and the occurrence of within-host multiple infections of M. saponariae. In addition, the draft genome of M. saponariae, as well as one of the described markers will be useful resources for studying the evolution of the breeding systems in the genus Microbotryum and the

  16. Magnetic-activated cell sorting for sperm preparation reduces spermatozoa with apoptotic markers and improves the acrosome reaction in couples with unexplained infertility.

    PubMed

    Lee, Tsung-Hsien; Liu, Chung-Hsien; Shih, Yang-Tse; Tsao, Hui-Mei; Huang, Chun-Chia; Chen, Hsiu-Hui; Lee, Maw-Sheng

    2010-04-01

    Couples with unexplained infertility (UI) tend to have low fertilization rates with current IVF procedures. Here, we attempted to identify spermatozoa with apoptotic markers in couples with UI and unsuccessful intrauterine insemination (IUI) and we investigated the efficiency and benefit of magnetic-activated cell sorting (MACS) for sperm preparation in such patients. Sixty couples with UI and two IUI failures were recruited. The sperm were prepared by conventional density gradient centrifugation (DGC) and divided into two aliquots. One aliquot was used as a control and the other was further processed by MACS (D + M). Apoptotic markers were identified using fluorescence-labeled dye and flow cytometry, including externalization of phosphatidylserine (EPS), disrupted mitochondrial membrane potential (MMP) and DNA fragmentation. The fertilization potential of prepared spermatozoa was analyzed by basic semen analysis, computer-aided sperm analysis and the induced acrosome reaction test (IART). After DGC, spermatozoa showed 18.6% EPS, 28.3% disrupted MMP and 13.5% DNA fragmentation. Numbers of spermatozoa with apoptotic markers were significantly reduced by D + M, versus DGC alone (P < 0.001). Although the motility of spermatozoa was slightly decreased after MACS, most sperm motion characteristics were not impaired. Interestingly, the IART significantly improved after D + M, versus DGC alone, especially for the couples with a normal hemizona assay (P < 0.001). The spermatozoa prepared by D + M showed a reduced level of apoptotic markers. Improvement in the IART suggests a high fertilization potential of the processed spermatozoa. The identification of apoptotic markers and use of MACS may be helpful in directing the management plan for patients with UI and multiple IUI failures.

  17. Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

    PubMed

    Papagiorgis, Petros Christakis

    2016-05-01

    Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

  18. Efficiency of RAPD versus SSR markers for determining genetic diversity among popcorn lines.

    PubMed

    Leal, A A; Mangolin, C A; do Amaral, A T; Gonçalves, L S A; Scapim, C A; Mott, A S; Eloi, I B O; Cordovés, V; da Silva, M F P

    2010-01-05

    Using only one type of marker to quantify genetic diversity generates results that have been questioned in terms of reliability, when compared to the combined use of different markers. To compare the efficiency of the use of single versus multiple markers, we quantified genetic diversity among 10 S(7) inbred popcorn lines using both RAPD and SSR markers, and we evaluated how well these two types of markers discriminated the popcorn genotypes. These popcorn genotypes: "Yellow Pearl Popcorn" (P1-1 and P1-5), "Zélia" (P1-2 and P1-4), "Curagua" (P1-3), "IAC 112" (P9-1 and P9-2), "Avati Pichinga" (P9-3 and P9-5), and "Pisankalla" (P9-4) have different soil and climate adaptations. Using RAPD marker analysis, each primer yielded bands of variable intensities that were easily detected, as well as non-specific bands, which were discarded from the analysis. The nine primers used yielded 126 bands, of which 104 were classified as polymorphic, giving an average of 11.6 polymorphisms per primer. Using SSR procedures, the number of alleles per locus ranged from two to five, giving a total of 47 alleles for the 14 SSR loci. When comparing the groups formed using SSR and RAPD markers, there were similarities in the combinations of genotypes from the same genealogy. Correlation between genetic distances obtained through RAPD and SSR markers was relatively high (0.5453), indicating that both techniques are efficient for evaluating genetic diversity in the genotypes of popcorn that we evaluated, though RAPDs yielded more polymorphisms.

  19. Concept and simulation study of a novel localization method for robotic endoscopic capsules using multiple positron emission markers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Than, Trung Duc, E-mail: dtt581@uowmail.edu.au; Alici, Gursel, E-mail: gursel@uow.edu.au; Zhou, Hao, E-mail: hz467@uowmail.edu.au

    2014-07-15

    Purpose: Over the last decade, wireless capsule endoscope has been the tool of choice for noninvasive inspection of the gastrointestinal tract, especially in the small intestine. However, the latest clinical products have not been equipped with a sufficiently accurate localization system which makes it difficult to determine the location of intestinal abnormalities, and to apply follow-up interventions such as biopsy or drug delivery. In this paper, the authors present a novel localization method based on tracking three positron emission markers embedded inside an endoscopic capsule. Methods: Three spherical {sup 22}Na markers with diameters of less than 1 mm are embeddedmore » in the cover of the capsule. Gamma ray detectors are arranged around a patient body to detect coincidence gamma rays emitted from the three markers. The position of each marker can then be estimated using the collected data by the authors’ tracking algorithm which consists of four consecutive steps: a method to remove corrupted data, an initialization method, a clustering method based on the Fuzzy C-means clustering algorithm, and a failure prediction method. Results: The tracking algorithm has been implemented inMATLAB utilizing simulation data generated from the Geant4 Application for Emission Tomography toolkit. The results show that this localization method can achieve real-time tracking with an average position error of less than 0.4 mm and an average orientation error of less than 2°. Conclusions: The authors conclude that this study has proven the feasibility and potential of the proposed technique in effectively determining the position and orientation of a robotic endoscopic capsule.« less

  20. Pre-treatment red blood cell distribution width provides prognostic information in multiple myeloma.

    PubMed

    Zhou, Di; Xu, Peipei; Peng, Miaoxin; Shao, Xiaoyan; Wang, Miao; Ouyang, Jian; Chen, Bing

    2018-06-01

    The red blood cell distribution width (RDW), a credible marker for abnormal erythropoiesis, has recently been studied as a prognostic factor in oncology, but its role in multiple myeloma (MM) hasn't been thoroughly investigated. We performed a retrospective study in 162 patients with multiple myeloma. Categorical parameters were analyzed using Pearson chi-squared test. The Mann-Whitney and Wilcoxon tests were used for group comparisons. Comparisons of repeated samples data were analyzed with the general linear model repeated-measures procedure. The Kaplan-Meier product-limit method was used to determine OS and PFS, and the differences were assessed by the log-rank test. High RDW baseline was significantly associated with indexes including haemoglobin, bone marrow plasma cell infiltration, and cytogenetics risk stratification. After chemotherapy, the overall response rate (ORR) decreased as RDW baseline increased. In 24 patients with high RDW baseline, it was revealed RDW value decreased when patients achieved complete remission (CR), but increased when the disease progressed. The normal-RDW baseline group showed both longer overall survival (OS) and progression-free survival (PFS) than the high-RDW baseline group. Our study suggests pre-treatment RDW level is a prognostic factor in MM and should be regarded as an important parameter for assessment of therapeutic efficiency. Copyright © 2018. Published by Elsevier B.V.

  1. Development and mapping of DArT markers within the Festuca - Lolium complex

    PubMed Central

    Kopecký, David; Bartoš, Jan; Lukaszewski, Adam J; Baird, James H; Černoch, Vladimír; Kölliker, Roland; Rognli, Odd Arne; Blois, Helene; Caig, Vanessa; Lübberstedt, Thomas; Studer, Bruno; Shaw, Paul; Doležel, Jaroslav; Kilian, Andrzej

    2009-01-01

    Background Grasses are among the most important and widely cultivated plants on Earth. They provide high quality fodder for livestock, are used for turf and amenity purposes, and play a fundamental role in environment protection. Among cultivated grasses, species within the Festuca-Lolium complex predominate, especially in temperate regions. To facilitate high-throughput genome profiling and genetic mapping within the complex, we have developed a Diversity Arrays Technology (DArT) array for five grass species: F. pratensis, F. arundinacea, F. glaucescens, L. perenne and L. multiflorum. Results The DArTFest array contains 7680 probes derived from methyl-filtered genomic representations. In a first marker discovery experiment performed on 40 genotypes from each species (with the exception of F. glaucescens for which only 7 genotypes were used), we identified 3884 polymorphic markers. The number of DArT markers identified in every single genotype varied from 821 to 1852. To test the usefulness of DArTFest array for physical mapping, DArT markers were assigned to each of the seven chromosomes of F. pratensis using single chromosome substitution lines while recombinants of F. pratensis chromosome 3 were used to allocate the markers to seven chromosome bins. Conclusion The resources developed in this project will facilitate the development of genetic maps in Festuca and Lolium, the analysis on genetic diversity, and the monitoring of the genomic constitution of the Festuca × Lolium hybrids. They will also enable marker-assisted selection for multiple traits or for specific genome regions. PMID:19832973

  2. Impact of glatiramer acetate on paraclinical markers of neuroprotection in multiple sclerosis: A prospective observational clinical trial.

    PubMed

    Ehling, Rainer; Di Pauli, Franziska; Lackner, Peter; Rainer, Carolyn; Kraus, Viktoria; Hegen, Harald; Lutterotti, Andreas; Kuenz, Bettina; De Zordo, Tobias; Schocke, Michael; Glatzl, Susanne; Löscher, Wolfgang N; Deisenhammer, Florian; Reindl, Markus; Berger, Thomas

    2015-10-15

    Data from in vitro and animal studies support a neuroprotective role of glatiramer acetate (GA) in multiple sclerosis (MS). We investigated prospectively whether treatment with GA leads to clinical and paraclinical changes associated with neuroprotection in patients with relapsing-remitting (RR) MS. Primary aim of this clinical study was to determine serum BDNF levels in RR-MS patients who were started on GA as compared to patients who remained therapy-naive throughout 24 months. Secondary outcomes included relapses and EDSS, cognition, quality of life, fatigue and depression, BDNF expression levels on peripheral immune cells (FACS, RT-PCR), serum anti-myelin basic peptide (MBP) antibody status, evoked potential and cerebral MRI studies. While GA treatment did not alter serum levels or expression levels on peripheral immune cells of BDNF over time it resulted in a transient increase of serum IgG antibody response to MBP, mainly due to subtype IgG1 (p<0.05), after 3 months. However, no significant differences were found between GA treated and therapy-naive patients with regard to serum BDNF and intracellular BDNF expression levels, nerve conduction (including median and tibial nerve somatosensory, pattern-shift visual and upper and lower limb motor evoked potentials) or MRI (including volume of hyperintense lesions, volume of hypointense lesions after CE, mean diffusivity and fractional anisotropy) outcome parameters. In conclusion, our findings do not support a major impact of GA treatment on paraclinical markers of neuroprotection in human RR-MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. A fuzzy integral method based on the ensemble of neural networks to analyze fMRI data for cognitive state classification across multiple subjects.

    PubMed

    Cacha, L A; Parida, S; Dehuri, S; Cho, S-B; Poznanski, R R

    2016-12-01

    The huge number of voxels in fMRI over time poses a major challenge to for effective analysis. Fast, accurate, and reliable classifiers are required for estimating the decoding accuracy of brain activities. Although machine-learning classifiers seem promising, individual classifiers have their own limitations. To address this limitation, the present paper proposes a method based on the ensemble of neural networks to analyze fMRI data for cognitive state classification for application across multiple subjects. Similarly, the fuzzy integral (FI) approach has been employed as an efficient tool for combining different classifiers. The FI approach led to the development of a classifiers ensemble technique that performs better than any of the single classifier by reducing the misclassification, the bias, and the variance. The proposed method successfully classified the different cognitive states for multiple subjects with high accuracy of classification. Comparison of the performance improvement, while applying ensemble neural networks method, vs. that of the individual neural network strongly points toward the usefulness of the proposed method.

  4. Molecular cloning and characterization of markers and cytokines for equid myeloid cells.

    PubMed

    Steinbach, Falko; Stark, Robert; Ibrahim, Sherif; Gawad, Eman Abd-El; Ludwig, Hanns; Walter, Jakob; Commandeur, Ulrich; Mauel, Susanne

    2005-10-18

    The myeloid cell system comprises of monocytes, macrophages (MPhi), dendritic cells (DC), Kupffer cells, osteoclasts or microglia and is also known as the mononuclear phagocytic system (MPS). Essential cytokines to differentiate or activate these cells include GM-CSF or IL-4. Important markers for characterization include CD1, CD14, CD68, CD163 and CD206. All these markers, however, were not cloned or further characterized in equids by use of monoclonal antibodies earlier. To overcome this problem with the present study, two approaches were used. First, we cloned equine cytokines and markers, and second we analyzed cross-reactivity of human homologues or anti-human monoclonal antibodies. For cloning of equine cytokines and markers, we used degenerate primers delineated from other species, or equine-specific primers based on previous information in Genbank. Flow cytometry was used to determine the expression of markers on myeloid cells. Cross-reactivity could be shown for anti-human CD14, CD163 and mannose receptor (CD206) mAbs. Surface markers such as CD1 and CD68 that distinguish MPhi and DC were cloned and sequenced. According to blast homology, equine CD1a and CD1b could be identified and distinguished. With the resulting information, dendritic cells and macrophages of horses may be characterized.

  5. Systems Analyze Water Quality in Real Time

    NASA Technical Reports Server (NTRS)

    2010-01-01

    A water analyzer developed under Small Business Innovation Research (SBIR) contracts with Kennedy Space Center now monitors treatment processes at water and wastewater facilities around the world. Originally designed to provide real-time detection of nutrient levels in hydroponic solutions for growing plants in space, the ChemScan analyzer, produced by ASA Analytics Inc., of Waukesha, Wisconsin, utilizes spectrometry and chemometric algorithms to automatically analyze multiple parameters in the water treatment process with little need for maintenance, calibration, or operator intervention. The company has experienced a compound annual growth rate of 40 percent over its 15-year history as a direct result of the technology's success.

  6. Teaching Multiplication and Multiplication Tables by the Application of Finger Multiplication

    ERIC Educational Resources Information Center

    Bahadir, Elif

    2017-01-01

    Developments in mathematics education tend to emphasize mathematics teaching with the help of activities that will allow the students to create these concepts rather than to make them memorize mathematical rules. The purpose of this study is to analyze the applicability of the application of multiplication with fingers developed by the researcher.…

  7. Serum tumor markers in breast cancer: are they of clinical value?

    PubMed

    Duffy, Michael J

    2006-03-01

    Although multiple serum-based tumor markers have been described for breast cancer, such as CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2 (the extracellular domain), the most widely used are CA 15-3 and CEA. The literature relevant to serum tumor markers in breast cancer was reviewed. Particular attention was given to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. Because of a lack of sensitivity for early disease and lack of specificity, none of the available markers is of value for the detection of early breast cancer. High preoperative concentrations of CA 15-3 are, however, associated with adverse patient outcome. Although serial determinations of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of approximately 2-9 months, the clinical value of this lead time remains to be determined. Serum markers, however, are the only validated approach for monitoring treatment in patients with advanced disease that cannot be evaluated by use of conventional criteria. CA 15-3 is one of the first circulating prognostic factors for breast cancer. Preoperative concentrations thus might be combined with existing prognostic factors for predicting outcome in patients with newly diagnosed breast cancer. At present, the most important clinical application of CA 15-3 is in monitoring therapy in patients with advanced breast cancer that is not assessable by existing clinical or radiologic procedures.

  8. Evaluation of Hands-On Clinical Exam Performance Using Marker-less Video Tracking.

    PubMed

    Azari, David; Pugh, Carla; Laufer, Shlomi; Cohen, Elaine; Kwan, Calvin; Chen, Chia-Hsiung Eric; Yen, Thomas Y; Hu, Yu Hen; Radwin, Robert

    2014-09-01

    This study investigates the potential of using marker-less video tracking of the hands for evaluating hands-on clinical skills. Experienced family practitioners attending a national conference were recruited and asked to conduct a breast examination on a simulator that simulates different clinical presentations. Videos were made of the clinician's hands during the exam and video processing software for tracking hand motion to quantify hand motion kinematics was used. Practitioner motion patterns indicated consistent behavior of participants across multiple pathologies. Different pathologies exhibited characteristic motion patterns in the aggregate at specific parts of an exam, indicating consistent inter-participant behavior. Marker-less video kinematic tracking therefore shows promise in discriminating between different examination procedures, clinicians, and pathologies.

  9. The Evolution of Prognostic Factors in Multiple Myeloma

    PubMed Central

    Hassanein, Mona; Rasheed, Walid; Aljurf, Mahmoud; Alsharif, Fahad

    2017-01-01

    Multiple myeloma (MM) is a heterogeneous hematologic malignancy involving the proliferation of plasma cells derived by different genetic events contributing to the development, progression, and prognosis of this disease. Despite improvement in treatment strategies of MM over the last decade, the disease remains incurable. All efforts are currently focused on understanding the prognostic markers of the disease hoping to incorporate the new therapeutic modalities to convert the disease into curable one. We present this comprehensive review to summarize the current standard prognostic markers used in MM along with novel techniques that are still in development and highlight their implications in current clinical practice. PMID:28321258

  10. Microsatellite analysis and marker development in garlic: distribution in EST sequence, genetic diversity analysis, and marker transferability across Alliaceae.

    PubMed

    Barboza, Karina; Beretta, Vanesa; Kozub, Perla C; Salinas, Cecilia; Morgenfeld, Mauro M; Galmarini, Claudio R; Cavagnaro, Pablo F

    2018-04-28

    Allium vegetables, such as garlic and onion, have understudied genomes and limited molecular resources, hindering advances in genetic research and breeding of these species. In this study, we characterized and compared the simple sequence repeats (SSR) landscape in the transcriptomes of garlic and related Allium (A. cepa, A. fistulosum, and A. tuberosum) and non-Allium monocot species. In addition, 110 SSR markers were developed from garlic ESTs, and they were characterized-along with 112 previously developed SSRs-at various levels, including transferability across Alliaceae species, and their usefulness for genetic diversity analysis. Among the Allium species analyzed, garlic ESTs had the highest overall SSR density, the lowest frequency of trinucleotides, and the highest of di- and tetranucleotides. When compared to more distantly related monocots, outside the Asparagales order, it was evident that ESTs of Allium species shared major commonalities with regards to SSR density, frequency distribution, sequence motifs, and GC content. A significant fraction of the SSR markers were successfully transferred across Allium species, including crops for which no SSR markers have been developed yet, such as leek, shallot, chives, and elephant garlic. Diversity analysis of garlic cultivars with selected SSRs revealed 36 alleles, with 2-5 alleles/locus, and PIC = 0.38. Cluster analysis grouped the accessions according to their flowering behavior, botanical variety, and ecophysiological characteristics. Results from this study contribute to the characterization of Allium transcriptomes. The new SSR markers developed, along with the data from the polymorphism and transferability analyses, will aid in assisting genetic research and breeding in garlic and other Allium.

  11. Potential metabolite markers of schizophrenia.

    PubMed

    Yang, J; Chen, T; Sun, L; Zhao, Z; Qi, X; Zhou, K; Cao, Y; Wang, X; Qiu, Y; Su, M; Zhao, A; Wang, P; Yang, P; Wu, J; Feng, G; He, L; Jia, W; Wan, C

    2013-01-01

    Schizophrenia is a severe mental disorder that affects 0.5-1% of the population worldwide. Current diagnostic methods are based on psychiatric interviews, which are subjective in nature. The lack of disease biomarkers to support objective laboratory tests has been a long-standing bottleneck in the clinical diagnosis and evaluation of schizophrenia. Here we report a global metabolic profiling study involving 112 schizophrenic patients and 110 healthy subjects, who were divided into a training set and a test set, designed to identify metabolite markers. A panel of serum markers consisting of glycerate, eicosenoic acid, β-hydroxybutyrate, pyruvate and cystine was identified as an effective diagnostic tool, achieving an area under the receiver operating characteristic curve (AUC) of 0.945 in the training samples (62 patients and 62 controls) and 0.895 in the test samples (50 patients and 48 controls). Furthermore, a composite panel by the addition of urine β-hydroxybutyrate to the serum panel achieved a more satisfactory accuracy, which reached an AUC of 1 in both the training set and the test set. Multiple fatty acids and ketone bodies were found significantly (P<0.01) elevated in both the serum and urine of patients, suggesting an upregulated fatty acid catabolism, presumably resulting from an insufficiency of glucose supply in the brains of schizophrenia patients.

  12. Metabolite and transcript markers for the prediction of potato drought tolerance.

    PubMed

    Sprenger, Heike; Erban, Alexander; Seddig, Sylvia; Rudack, Katharina; Thalhammer, Anja; Le, Mai Q; Walther, Dirk; Zuther, Ellen; Köhl, Karin I; Kopka, Joachim; Hincha, Dirk K

    2018-04-01

    Potato (Solanum tuberosum L.) is one of the most important food crops worldwide. Current potato varieties are highly susceptible to drought stress. In view of global climate change, selection of cultivars with improved drought tolerance and high yield potential is of paramount importance. Drought tolerance breeding of potato is currently based on direct selection according to yield and phenotypic traits and requires multiple trials under drought conditions. Marker-assisted selection (MAS) is cheaper, faster and reduces classification errors caused by noncontrolled environmental effects. We analysed 31 potato cultivars grown under optimal and reduced water supply in six independent field trials. Drought tolerance was determined as tuber starch yield. Leaf samples from young plants were screened for preselected transcript and nontargeted metabolite abundance using qRT-PCR and GC-MS profiling, respectively. Transcript marker candidates were selected from a published RNA-Seq data set. A Random Forest machine learning approach extracted metabolite and transcript markers for drought tolerance prediction with low error rates of 6% and 9%, respectively. Moreover, by combining transcript and metabolite markers, the prediction error was reduced to 4.3%. Feature selection from Random Forest models allowed model minimization, yielding a minimal combination of only 20 metabolite and transcript markers that were successfully tested for their reproducibility in 16 independent agronomic field trials. We demonstrate that a minimum combination of transcript and metabolite markers sampled at early cultivation stages predicts potato yield stability under drought largely independent of seasonal and regional agronomic conditions. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  13. Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration

    PubMed Central

    2012-01-01

    Background The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist consists of 20 items to report for published tumor marker prognostic studies. It was developed to address widespread deficiencies in the reporting of such studies. In this paper we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report. Methods REMARK recommends including a transparent and full description of research goals and hypotheses, subject selection, specimen and assay considerations, marker measurement methods, statistical design and analysis, and study results. Each checklist item is explained and accompanied by published examples of good reporting, and relevant empirical evidence of the quality of reporting. We give prominence to discussion of the 'REMARK profile', a suggested tabular format for summarizing key study details. Summary The paper provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. To encourage dissemination of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration, this article has also been published in PLoS Medicine. PMID:22642691

  14. Phylogenetic and microsatellite markers for Tulasnella (Tulasnellaceae) mycorrhizal fungi associated with Australian orchids.

    PubMed

    Ruibal, Monica P; Peakall, Rod; Smith, Leon M; Linde, Celeste C

    2013-03-01

    Phylogenetic and microsatellite markers were developed for Tulasnella mycorrhizal fungi to investigate fungal species identity and diversity. These markers will be useful in future studies investigating the phylogenetic relationship of the fungal symbionts, specificity of orchid-mycorrhizal associations, and the role of mycorrhizae in orchid speciation within several orchid genera. • We generated partial genome sequences of two Tulasnella symbionts originating from Chiloglottis and Drakaea orchid species with 454 genome sequencing. Cross-genus transferability across mycorrhizal symbionts associated with multiple genera of Australian orchids (Arthrochilus, Chiloglottis, Drakaea, and Paracaleana) was found for seven phylogenetic loci. Five loci showed cross-transferability to Tulasnella from other orchid genera, and two to Sebacina. Furthermore, 11 polymorphic microsatellite loci were developed for Tulasnella from Chiloglottis. • Highly informative markers were obtained, allowing investigation of mycorrhizal diversity of Tulasnellaceae associated with a wide variety of terrestrial orchids in Australia and potentially worldwide.

  15. Multiple Spectral-Spatial Classification Approach for Hyperspectral Data

    NASA Technical Reports Server (NTRS)

    Tarabalka, Yuliya; Benediktsson, Jon Atli; Chanussot, Jocelyn; Tilton, James C.

    2010-01-01

    A .new multiple classifier approach for spectral-spatial classification of hyperspectral images is proposed. Several classifiers are used independently to classify an image. For every pixel, if all the classifiers have assigned this pixel to the same class, the pixel is kept as a marker, i.e., a seed of the spatial region, with the corresponding class label. We propose to use spectral-spatial classifiers at the preliminary step of the marker selection procedure, each of them combining the results of a pixel-wise classification and a segmentation map. Different segmentation methods based on dissimilar principles lead to different classification results. Furthermore, a minimum spanning forest is built, where each tree is rooted on a classification -driven marker and forms a region in the spectral -spatial classification: map. Experimental results are presented for two hyperspectral airborne images. The proposed method significantly improves classification accuracies, when compared to previously proposed classification techniques.

  16. Population genetic data of 38 insertion-deletion markers in six populations of the northern fringe of the Iberian Peninsula.

    PubMed

    Cardoso, Sergio; Sevillano, Rubén; Gamarra, David; Santurtún, Ana; Martínez-Jarreta, Begoña; de Pancorbo, Marian M

    2017-03-01

    Insertion-deletions have been reported very useful markers for forensic purposes. To further deepen in this matter, 38 non-coding bi-allelic autosomal indels were analyzed in 575 individuals representing six populations from the northern fringe of the Iberian Peninsula. Autochthonous populations from the Basque Country, northern Navarre, the Pas Valley in Cantabria and Aragon were analyzed, together with non-autochthonous populations from the Basque Country and northern Navarre. At the intra-population level, all loci analyzed were in Hardy-Weinberg equilibrium except for marker rs33917182 in autochthonous Basques. Linkage disequilibrium (LD) test did not reveal statistically significant allelic association between the different loci pairs in all six populations. Forensic parameters proved to be highly informative in the six populations analyzed, even if a scenario with population substructure and local inbreeding was considered for match probability calculations, and the potential of this indels set to be used in combination with other genetic markers is remarkable. As for inter-population analyses, in general terms the six populations showed low but statistically significant genetic distances. However, though this indels set efficiently differentiate between main ancestries, it does not allow an accurate separation at a local level and, for the time being, their combination with other informative markers is needed to maximize the power to accurately differentiate populations with close genetic ancestry. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Genome-Scale Screen for DNA Methylation-Based Detection Markers for Ovarian Cancer

    PubMed Central

    Houshdaran, Sahar; Shen, Hui; Widschwendter, Martin; Daxenbichler, Günter; Long, Tiffany; Marth, Christian; Laird-Offringa, Ite A.; Press, Michael F.; Dubeau, Louis; Siegmund, Kimberly D.; Wu, Anna H.; Groshen, Susan; Chandavarkar, Uma; Roman, Lynda D.; Berchuck, Andrew; Pearce, Celeste L.; Laird, Peter W.

    2011-01-01

    Background The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer. Methodology/Principal Findings We used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels. We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients. Conclusions/Significance We implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers. PMID:22163280

  18. Comparison of the effectiveness of ISJ and SSR markers and detection of outlier loci in conservation genetics of Pulsatilla patens populations

    PubMed Central

    Szczecińska, Monika

    2016-01-01

    Background Research into the protection of rare and endangered plant species involves genetic analyses to determine their genetic variation and genetic structure. Various categories of genetic markers are used for this purpose. Microsatellites, also known as simple sequence repeats (SSR), are the most popular category of markers in population genetics research. In most cases, microsatellites account for a large part of the noncoding DNA and exert a neutral effect on the genome. Neutrality is a desirable feature in evaluations of genetic differences between populations, but it does not support analyses of a population’s ability to adapt to a given environment or its evolutionary potential. Despite the numerous advantages of microsatellites, non-neutral markers may supply important information in conservation genetics research. They are used to evaluate adaptation to specific environmental conditions and a population’s adaptive potential. The aim of this study was to compare the level of genetic variation in Pulsatilla patens populations revealed by neutral SSR markers and putatively adaptive ISJ markers (intron-exon splice junction). Methods The experiment was conducted on 14 Polish populations of P. patens and three P. patens populations from the nearby region of Vitebsk in Belarus. A total of 345 individuals were examined. Analyses were performed with the use of eight SSR primers specific to P. patens and three ISJ primers. Results SSR markers revealed a higher level of genetic variation than ISJ markers (He = 0.609, He = 0.145, respectively). An analysis of molecular variance (AMOVA) revealed that, the overall genetic diversity between the analyzed populations defined by parameters FST and ΦPT for SSR (20%) and ΦPT for ISJ (21%) markers was similar. Analysis conducted in the Structure program divided analyzed populations into two groups (SSR loci) and three groups (ISJ markers). Mantel test revealed correlations between the geographic distance and genetic

  19. Prognostic value of unrelated atypical serum immunofixation patterns during multiple myeloma therapy.

    PubMed

    Guimarães, Cristina; Bergantim, Rui; Ramalho, Renata; Couto, Nuno; Guimarães, João T; Trigo, Fernanda

    2012-06-26

    Autologous stem cell transplantation (ASCT) is the gold standard therapy for suitable multiple myeloma (MM) patients after induction with high dose therapy. To date, the evidence of a reliable marker of prognosis in these cases remains scarce. Our aim was to evaluate appearance of unrelated atypical serum immunofixation patterns (ASIPs) as a marker of prognosis in MM patients submitted to ASCT. We retrospectively analysed data from 65 patients. Interestingly, we observed that presence of ASIPs was associated with longer progression-free survival and longer overall survival. Our results suggested that presence of ASIPs could be a novel marker of good prognosis in MM patients submitted to ASCT.

  20. Herbs and spices: characterization and quantitation of biologically-active markers for routine quality control by multiple headspace solid-phase microextraction combined with separative or non-separative analysis.

    PubMed

    Sgorbini, Barbara; Bicchi, Carlo; Cagliero, Cecilia; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia

    2015-01-09

    Herbs and spices are used worldwide as food flavoring, thus determination of their identity, origin, and quality is mandatory for safe human consumption. An analysis strategy based on separative (HS-SPME-GC-MS) and non-separative (HS-SPME-MS) approaches is proposed for the volatile fraction of herbs and spices, for quality control and to quantify the aromatic markers with a single analysis directly on the plant material as such. Eight-to-ten lots of each of the following herbs/spices were considered: cloves (Syzygium aromaticum (L.) Merr. & Perry), American peppertree (Schinus molle L.), black pepper and white pepper (Piper nigrum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.). Homogeneity, origin, and chemotypes of the investigated lots of each herb/spice were defined by fingerprinting, through statistical elaboration with principal component analysis (PCA). Characterizing aromatic markers were directly quantified on the solid matrix through multiple headspace extraction-HS-SPME (MHS-SPME). Reliable results were obtained with both separative and non-separative methods (where the latter were applicable); the two were in full agreement, RSD% ranging from 1.8 to 7.7% for eugenol in cloves, 2.2-18.4% for carvacrol+thymol in thyme, and 3.1-16.8% for thujones in sage. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Mapping of AFLP markers linked to seed coat colour loci in Brassica juncea (L.) Czern.

    PubMed

    Sabharwal, V; Negi, M S; Banga, S S; Lakshmikumaran, M

    2004-06-01

    Association mapping of the seed-coat colour with amplified fragment length polymorphism (AFLP) markers was carried out in 39 Brassica juncea lines. The lines had genetically diverse parentages and varied for seed-coat colour and other morphological characters. Eleven AFLP primer combinations were used to screen the 39 B. juncea lines, and a total of 335 polymorphic bands were detected. The bands were analysed for association with seed-coat colour using multiple regression analysis. This analysis revealed 15 markers associated with seed-coat colour, obtained with eight AFLP primer combinations. The marker E-ACA/M-CTG(350 )explained 69% of the variation in seed-coat colour. This marker along with markers E-AAC/M-CTC(235 )and E-AAC/M-CTA(250) explained 89% of the total variation. The 15 associated markers were validated for linkage with the seed-coat colour loci using a recombinant inbred line (RIL) mapping population. Bands were amplified with the eight AFLP primer combinations in 54 RIL progenies. Of the 15 associated markers, 11 mapped on two linkage groups. Eight markers were placed on linkage group 1 at a marker density of 6.0 cM, while the remaining three were mapped on linkage group 2 at a marker density of 3.6 cM. Marker E-ACA/M-CTG(350 )co-segregated with Gene1 controlling seed-coat colour; it was specific for yellow seed-coat colour and mapped to linkage group 1. Marker E-AAC/M-CTC(235) (AFLP8), which had been studied previously, was present on linkage group 2; it was specific for brown seed-coat colour. Since AFLP markers are not adapted for large-scale applications in plant breeding, it is important to convert these to sequence-characterised amplified region (SCAR) markers. Marker E-AAC/M-CTC(235) (AFLP8) had been previously converted into a SCAR. Work is in progress to convert the second of the linked markers, E-ACA/M-CTG(350), to a SCAR. The two linked AFLP markers converted to SCARs will be useful for developing yellow-seeded B. juncea lines by means of

  2. Multiple paternity in the freshwater snail, Potamopyrgus antipodarum

    PubMed Central

    Soper, Deanna M; Delph, Lynda F; Lively, Curt M

    2012-01-01

    Mating multiply may incur costs, such as exposure to predators and to sexually transmitted diseases. Nevertheless, it may be favored, in spite of these costs, as a way to increase the genetic diversity of offspring through fertilization by multiple males. Here, we tested for multiple paternity in a freshwater snail (Potamopyrgus antipodarum), which is host to several species of sterilizing trematode worms. Using microsatellites markers, we found multiple paternity in two different snail populations, with as many as seven males fertilizing a single female. In addition, high evenness of sire fertilization was found within individual broods. Multiple paternity can occur for a variety of reasons; however, given that these populations experience high risk of infection by a sterilizing trematode, one potential explanation may be that multiple paternity and high evenness of sire fertilizations increase the chances of the production of parasite-resistant offspring. PMID:23301182

  3. hSAGEing: an improved SAGE-based software for identification of human tissue-specific or common tumor markers and suppressors.

    PubMed

    Yang, Cheng-Hong; Chuang, Li-Yeh; Shih, Tsung-Mu; Chang, Hsueh-Wei

    2010-12-17

    SAGE (serial analysis of gene expression) is a powerful method of analyzing gene expression for the entire transcriptome. There are currently many well-developed SAGE tools. However, the cross-comparison of different tissues is seldom addressed, thus limiting the identification of common- and tissue-specific tumor markers. To improve the SAGE mining methods, we propose a novel function for cross-tissue comparison of SAGE data by combining the mathematical set theory and logic with a unique "multi-pool method" that analyzes multiple pools of pair-wise case controls individually. When all the settings are in "inclusion", the common SAGE tag sequences are mined. When one tissue type is in "inclusion" and the other types of tissues are not in "inclusion", the selected tissue-specific SAGE tag sequences are generated. They are displayed in tags-per-million (TPM) and fold values, as well as visually displayed in four kinds of scales in a color gradient pattern. In the fold visualization display, the top scores of the SAGE tag sequences are provided, along with cluster plots. A user-defined matrix file is designed for cross-tissue comparison by selecting libraries from publically available databases or user-defined libraries. The hSAGEing tool provides a combination of friendly cross-tissue analysis and an interface for comparing SAGE libraries for the first time. Some up- or down-regulated genes with tissue-specific or common tumor markers and suppressors are identified computationally. The tool is useful and convenient for in silico cancer transcriptomic studies and is freely available at http://bio.kuas.edu.tw/hSAGEing.

  4. Multiple homicides.

    PubMed

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  5. The concept of multiple hormonal dysregulation.

    PubMed

    Maggio, Marcello; Cattabiani, Chiara; Lauretani, Fulvio; Ferrucci, Luigi; Luci, Michele; Valenti, Giorgio; Ceda, Gianpaolo

    2010-01-01

    Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones that remain stable and anabolic hormones (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Despite the multiple hormonal dysregulation occurring with age, the prevalent line of research in the last decades has tried to explain many age-related phenomena as consequence of one single hormonal derangement with disappointing results. In this review we will list the relationship between hormonal anabolic deficiency and frailty and mortality in older population, providing evidence to the notion that multiple hormonal dysregulation rather than change in single anabolic hormone is a powerful marker of poor health status and mortality.

  6. Dissecting the phyloepidemiology of Trypanosoma cruzi I (TcI) in Brazil by the use of high resolution genetic markers

    PubMed Central

    das Chagas Xavier, Samanta; Messenger, Louisa A.; Pavan, Márcio G.; Miles, Michael A.; Jansen, Ana María; Yeo, Matthew

    2018-01-01

    Background Trypanosoma cruzi, the causal agent of Chagas disease, is monophyletic but genetically heterogeneous. It is currently represented by six genetic lineages (Discrete Typing Units, DTUs) designated TcI-TcVI. TcI is the most geographically widespread and genetically heterogeneous lineage, this as is evidenced by a wide range of genetic markers applied to isolates spanning a vast geographic range in Latin America. Methodology/Principal findings In total, 78 TcI isolated from hosts and vectors distributed in 5 different biomes of Brazil, were analyzed using 6 nuclear housekeeping genes, 25 microsatellite loci and one mitochondrial marker. Nuclear markers reveal substantial genetic diversity, significant gene flow between biomes, incongruence in phylogenies, and haplotypic analysis indicative of intra-DTU genetic exchange. Phylogenetic reconstructions based on mitochondrial and nuclear loci were incongruent, and consistent with introgression. Structure analysis of microsatellite data reveals that, amongst biomes, the Amazon is the most genetically diverse and experiences the lowest level of gene flow. Investigation of population structure based on the host species/genus, indicated that Didelphis marsupialis might play a role as the main disperser of TcI. Conclusions/Significance The present work considers a large TcI sample from different hosts and vectors spanning multiple ecologically diverse biomes in Brazil. Importantly, we combine fast and slow evolving markers to contribute to the epizootiological understanding of TcI in five distinct Brazilian biomes. This constitutes the first instance in which MLST analysis was combined with the use of MLMT and maxicircle markers to evaluate the genetic diversity of TcI isolates in Brazil. Our results demonstrate the existence of substantial genetic diversity and the occurrence of introgression events. We provide evidence of genetic exchange in TcI isolates from Brazil and of the relative isolation of TcI in the Amazon

  7. PB-1: The Relationship Between Anti Apoptotic Marker (BCL-2) and Biochemical Markers in Type 2 Diabetes Patients

    PubMed Central

    Damitri, TD; Faridah, AR; Imran, Y; Hasnan, J.

    2006-01-01

    Purpose : To investigate the expression of anti apoptotic marker (bcl-2) and the level of biochemical markers in type 2 diabetes patients. METHODS : A cross-sectional study was conducted from August 2003 to November 2005. Forty one type 2 diabetes patients and 36 non diabetes (control) subjects aged between 20 to 70 years were included in this study. Blood samples were collected for fasting plasma glucose (FPG), triglycerides (TG), Total cholesterol (TC), High density lipoprotein cholesterol (HDLC), Low density lipoprotein cholesterol (LDLC) and analyzed in the Chemical Pathology laboratory, while glycosylated hemoglobin A1c (A1C) was analyzed in the Endocrine laboratory. The skin biopsy tissue samples were stained with immunohistochemistry (IHC) stain for expression of bcl-2 in the Pathology laboratory. RESULTS : There was a significant difference (p<0.001) between both groups for mean FPG (diabetics=11.02±4.25, control=4.41±1.12 mmol/L), HDLC (diabetics=1.00±0.38, control=1.47±0.72 mmol/L) and A1C (diabetics=9.50±2.24%, control=5.00±0.67%). However, there was no significant difference for TG, TC, and LDLC between both groups. Interestingly, the difference of mean bcl-2 expression were very highly significant (p<0.001) when compared between both groups. Mean bcl-2 expression was dibetics= 1.88±0.33 and control= 1.47±0.51. Positive bcl-2 expression was found in only 5 (12.2%) diabetics while 36 (87.8%) diabetics showed negative expression. Positive bcl-2 expression was observed in 19 (52.8%) controls while 17 (47.2%) showed negative expression. CONCLUSION : The expression of anti apoptotic marker bcl-2 was increased in non diabetic subjects in order to prevent cell death. However, the reduced expression of bcl-2 in diabetic patients may be associated with programmed cell death. The detailed mechanism for the gene expression of bcl-2 may help us to understand how bcl-2 is involved in apoptosis in diabetic microvasculature complications.

  8. Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

    PubMed

    Kündig, Pascale; Giesen, Charlotte; Jackson, Hartland; Bodenmiller, Bernd; Papassotirolopus, Bärbel; Freiberger, Sandra Nicole; Aquino, Catharine; Opitz, Lennart; Varga, Zsuzsanna

    2018-05-08

    Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas. We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis. No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas. Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the

  9. Single Cell Assay for Analyzing Single Cell Exosome and Endocrine Secretion and Cancer Markers

    NASA Astrophysics Data System (ADS)

    Chiu, Yu-Jui

    To understand the inhomogeneity of cells in biological systems, there is a growing demand for the capability to characterize the properties of individual single cells. Since single cell studies require continuous monitoring of the cell behaviors instead of a snapshot test at a single time point, an effective single-cell assay that can support time lapsed studies in a high throughput manner is desired. Most currently available single-cell technologies cannot provide proper environments to sustain cell growth and cannot provide, for appropriate cell types, proliferation of single cells and convenient, non-invasive tests of single cell behaviors from molecular markers. In this dissertation, I present a highly versatile single-cell assay that can accommodate different cellular types, enable easy and efficient single cell loading and culturing, and be suitable for the study of effects of in-vitro environmental factors in combination with drug screening. The salient features of the assay are the non-invasive collection and surveying of single cell secretions at different time points and massively parallel translocation of single cells by user defined criteria, producing very high compatibility to the downstream process such as single cell qPCR and sequencing. Above all, the acquired information is quantitative -- for example, one of the studies is measured by the number of exosomes each single cell secretes for a given time period. Therefore, our single-cell assay provides a convenient, low-cost, and enabling tool for quantitative, time lapsed studies of single cell properties.

  10. Fiducial Marker Placement

    MedlinePlus

    ... such as stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) , or proton therapy . Fiducial markers are small ... Proton Therapy Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT) Images related to Fiducial Marker Placement Sponsored ...

  11. Efficiency gain of marker-assisted backcrossing by sequentially increasing marker densities over generations.

    PubMed

    Prigge, Vanessa; Melchinger, Albrecht E; Dhillon, Baldev S; Frisch, Matthias

    2009-06-01

    Expenses for marker assays are the major costs in marker-assisted backcrossing programs for the transfer of target genes from a donor into the genetic background of a recipient genotype. Our objectives were to (1) investigate the effect of employing sequentially increasing marker densities over backcross generations on the recurrent parent genome (RPG) recovery and the number of marker data points (MDP) required, and (2) determine optimum designs for attaining RPG thresholds of 93-98% with a minimum number of MDP. We simulated the introgression of one dominant target gene for genome models of sugar beet (Beta vulgaris L.) and maize (Zea mays L.) with varying marker distances of 5-80 cM and population sizes of 30-250 plants across BC(1) to BC(3) generations. Employing less dense maps in early backcross generations resulted in savings of over 50% in the number of required MDP compared with using a constant set of markers and was accompanied only by small reductions in the attained RPG values. The optimum designs were characterized by increasing marker densities and increasing population sizes in advanced generations for both genome models. We conclude that increasing simultaneously the marker density and the population size from early to advanced backcross generations results in gene introgression with a minimum number of required MDP.

  12. Skin marker placement by technologist prior to knee MRI helps identify clinically relevant pathologies.

    PubMed

    Wadhwa, Vibhor; Weissman, Eric; Hayashi, Daichi; Xi, Yin; Chhabra, Avneesh

    2017-12-15

    Majority of musculoskeletal cross-sectional imaging requests have a non-revealing and non-specific clinical history of pain. However, the location of pain is very relevant towards arriving at a specific orthopedic diagnosis. The purpose of this research was to study the impact of skin marker placement and training of technologists prior to knee MRI in detection of clinically important findings. Total 200 consecutive left knee MRIs were evaluated before and after technologist training with regards to marker placement at the site of clinical symptoms or palpable finding. Marker location in relation to the knee was recorded and important findings were classified as correlated important finding, non-correlated important finding, other compartment important finding in non-correlated cases, and diffuse abnormality, i.e. tri-compartmental cartilage defects in both correlated and non-correlated cases. Differences among scans before and after technologist training were analyzed. The marker placement was observed in higher proportion of patients in post-training scans (78% vs 60%, p = 0.00). The most common location of the marker was in anterior or anterolateral knee (32% and 34% cases, respectively). The marker-important finding correlation was also higher post training, but not statistically significant (53% versus 38%, p = 0.57). Important findings correlated with the marker in more than 50% of the scans in the post-training set. Marker placement can aid in detection of clinically important imaging finding and technologist training aids in increased rates of marker placement and improved correlation.

  13. A male and female RNA marker to infer sex in forensic analysis.

    PubMed

    van den Berge, M; Sijen, T

    2017-01-01

    In forensics, DNA profiling is used for the identification of the donor of a trace, while messenger RNA (mRNA) profiling can be applied to identify the cellular origin such as body fluids or organ tissues. The presence of male cell material can be readily assessed by the incorporation of Y-chromosomal markers in quantitation or STR profiling systems. However, no forensic marker exists to positively identify female cell material; merely the presence of female DNA is deduced from the absence of a Y peak, or unbalanced X-Y signals at the Amelogenin locus or unbalanced response of the total and Y-specific quantifier. The presence of two X-chromosomes in female cells invokes dosage compensation, which is achieved through inactivation of one of the X-chromosomes in females. Since this process involves specific RNA molecules, identification of female cellular material may be possible through RNA profiling. Additionally, male material may be identified through RNAs expressed from the Y-chromosome. RNAs preferentially expressed in either sex were assessed for their potential to act as sex markers in forensic RNA assays. To confirm sex-specificity, body fluids and organ tissues of multiple donors of either sex were tested. Additionally, sensitivity of the markers and the suitability of positively identifying male-female mixtures were assessed and degraded samples were used to assess performance of the markers in forensic settings. The addition of sex-specific markers is of added informative value in any RNA profiling system and both markers were incorporated into existing RNA assays that either target body fluids or organs. These are the first forensic assays that enable positive identification of female cellular material. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Assessment of genome origins and genetic diversity in the genus Eleusine with DNA markers.

    PubMed

    Salimath, S S; de Oliveira, A C; Godwin, I D; Bennetzen, J L

    1995-08-01

    Finger millet (Eleusine coracana), an allotetraploid cereal, is widely cultivated in the arid and semiarid regions of the world. Three DNA marker techniques, restriction fragment length polymorphism (RFLP), randomly amplified polymorphic DNA (RAPD), and inter simple sequence repeat amplification (ISSR), were employed to analyze 22 accessions belonging to 5 species of Eleusine. An 8 probe--3 enzyme RFLP combination, 18 RAPD primers, and 6 ISSR primers, respectively, revealed 14, 10, and 26% polymorphism in 17 accessions of E. coracana from Africa and Asia. These results indicated a very low level of DNA sequence variability in the finger millets but did allow each line to be distinguished. The different Eleusine species could be easily identified by DNA marker technology and the 16% intraspecific polymorphism exhibited by the two analyzed accessions of E. floccifolia suggested a much higher level of diversity in this species than in E. coracana. Between species, E. coracana and E. indica shared the most markers, while E. indica and E. tristachya shared a considerable number of markers, indicating that these three species form a close genetic assemblage within the Eleusine. Eleusine floccifolia and E. compressa were found to be the most divergent among the species examined. Comparison of RFLP, RAPD, and ISSR technologies, in terms of the quantity and quality of data output, indicated that ISSRs are particularly promising for the analysis of plant genome diversity.

  15. The effect of single and multiple infections on atopy and wheezing in children

    PubMed Central

    Alcantara-Neves, Neuza Maria; Veiga, Rafael Valente; Dattoli, Vitor Camilo Cavalcante; Fiaccone, Rosimeire Leovigildo; Esquivel, Renata; Cruz, Álvaro Augusto; Cooper, Philip John; Rodrigues, Laura Cunha; Barreto, Maurício Lima

    2016-01-01

    Background The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. Objective We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. Methods Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. Results Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. Conclusion The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms. PMID:22035877

  16. The effect of single and multiple infections on atopy and wheezing in children.

    PubMed

    Alcantara-Neves, Neuza Maria; Veiga, Rafael Valente; Dattoli, Vitor Camilo Cavalcante; Fiaccone, Rosimeire Leovigildo; Esquivel, Renata; Cruz, Álvaro Augusto; Cooper, Philip John; Rodrigues, Laura Cunha; Barreto, Maurício Lima

    2012-02-01

    The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  17. Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension

    PubMed Central

    Browning, James; Schroeder, Joyce D.; Shandas, Robin; Kheyfets, Vitaly O.; Buckner, J. Kern; Hunter, Kendall S.; Hertzberg, Jean R.; Fenster, Brett E.

    2016-01-01

    Abstract Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e′). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = −0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e′ (Rho = 0.63, P = 0.001), and lateral e′ (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e′ (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency. PMID:27162613

  18. Marker vaccine strategies and candidate CSFV marker vaccines.

    PubMed

    Dong, Xiao-Nan; Chen, Ying-Hua

    2007-01-04

    Classical swine fever (CSF) is an economically important highly contagious disease of swine worldwide. Classical swine fever virus (CSFV) is its etiological agent, and the only natural hosts are domestic pigs and wild boars. Although field CSFV strains vary in the virulence, they all result in serious losses in pig industry. Highly virulent field strains generally cause acute disease and high mortality; moderately virulent field strains raise subacute or chronic infections; postnatal infection by low virulent field strains produces subclinical infection and mortality in the new-born piglets. CSFV can cross the placental barrier, and this transplacental transmission usually results in mortality of fetuses and birth of congenitally infected pigs with a late-onset disease and death. Two main strategies to control CSF epidemic are systematic prophylactic vaccination with live attenuated vaccines (such as C-strain) and non-vaccination stamping-out policy. But neither of them is satisfying enough. Marker vaccine and companion serological diagnostic test is thought to be a promising strategy for future control and eradication of CSF. During the past 15 years, various candidate marker vaccines were constructed and evaluated in the animal experiments, including recombinant chimeric vaccines, recombinant deletion vaccines, DNA vaccines, subunit vaccines and peptide vaccines. Among them, two subunit vaccines entered the large scale marker vaccine trial of EU in 1999. Although they failed to fulfil all the demands of the Scientific Veterinary Committee, they successfully induced solid immunity against CSFV in the vaccinated pigs. It can be expected that new potent marker vaccines might be commercially available and used in systematic prophylactic vaccination campaign or emergency vaccination in the next 15 years. Here, we summarized current strategies and candidate CSFV marker vaccines. These strategies and methods are also helpful for the development of new

  19. Enzyme markers in inbred rat strains: genetics of new markers and strain profiles.

    PubMed

    Adams, M; Baverstock, P R; Watts, C H; Gutman, G A

    1984-08-01

    Twenty-six inbred strains of the laboratory rat (Rattus norvegicus) were examined for electrophoretic variation at an estimated 97 genetic loci. In addition to previously documented markers, variation was observed for the enzymes aconitase, aldehyde dehydrogenase, and alkaline phosphatase. The genetic basis of these markers (Acon-1, Ahd-2, and Akp-1) was confirmed. Linkage analysis between 35 pairwise comparisons revealed that the markers Fh-1 and Pep-3 are linked. The strain profiles of the 25 inbred strains at 11 electrophoretic markers are given.

  20. Using Nucleon Multiplicities to Analyze Anti-Neutrino Interactions with Nuclei

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elkins, Miranda J.

    The most commonly used, simple interaction models have not accurately described the nuclear effects on either neutrino-nucleus or anti-neutrino-nucleus interactions. Comparison of data collected by the MINERvA experiment and these models shows a discrepancy in the reconstructed hadronic energy distribution at momentum transfers below 0.8 GeV. Two nuclear model effects that were previously not modeled are possible culprits of this discrepancy. The first is known as random-phase-approximation and the second is the addition of a meson exchange current process, also known as two-particle two-hole due to its result in two particles leaving the nucleus with two holes left in theirmore » place. For the first time a neutron counting software algorithm has been created and used to compare the multiplicity and spatial distributions of neutrons between the simulation and data. There is localized sensitivity to the RPA and 2p2h effects and both help the simulation better describe the data. Ad ditional systematic or model effects are present which cause the simulation to overproduce neutrons, and potential causes are discussed.« less

  1. Serum Adipocytokine Levels as Surrogate Markers for Disease Activity of Crohn's Disease.

    PubMed

    Kim, Su Hwan; Jang, Seung Hyeon; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Kim, You Sun; Han, Dong Soo; Kim, Joo Sung

    2017-05-01

    Determining inflammatory activity is crucial for assessing disease activity and for tailoring therapy in patients with Crohn׳s disease (CD). This study aimed to evaluate adipocytokine levels in patients with CD and to determine whether they can serve as surrogate markers for disease activity. Serum samples and information regarding the clinical features of patients in the CD Network Project registry were collected from March 2009 to February 2012. Patients with CD and disease duration of at least 2 years were enrolled in this study. Fasting serum leptin, adiponectin, obestatin and ghrelin levels were measured, and their correlation with clinical features of the patients was analyzed. Serum adipocytokine levels were evaluated according to disease activity as determined by CD activity index score. A total of 153 patients with CD were included. Serum ghrelin levels negatively correlated with patient age (P = 0.041) and age at diagnosis (P = 0.017), and positively correlated with C-reactive protein (CRP) levels (P = 0.017). Multiple regression analysis showed that serum ghrelin levels were related only to CRP levels (P = 0.032). Like ghrelin, serum leptin levels were also related to CRP levels (P < 0.001). Obestatin and adiponectin levels were not related to CRP levels. Serum adipocytokine levels did not significantly differ across different disease locations or behaviors. Serum ghrelin levels were significantly lower in patients with CD with a history of surgery than in those without (P = 0.007). Serum ghrelin and leptin levels may be useful as surrogate markers for disease activity in patients with CD. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  2. Is hepcidin a new cardiovascular risk marker in polycystic ovary syndrome?

    PubMed

    Gözdemir, Elif; Kaygusuz, Ikbal; Kafalı, Hasan

    2013-01-01

    Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities and carries a number of cardiovascular risk factors. Low-grade chronic inflammation has been thought to play a role in the pathogenesis of atherosclerosis and PCOS patients have an increased rate of subclinical inflammation. In the present study, considering the major role that hepcidin plays in the regulation of iron metabolism and as an inflammatory marker, we investigated hepcidin in PCOS patients and its role in predicting cardiovascular disease (CVD) development. Forty patients with PCOS and 40 age- and body mass index-matched healthy controls were included in the study. Iron metabolites, insulin resistance (IR), inflammatory markers and hepcidin levels were analyzed. IR parameters, inflammatory markers, iron parameters and hepcidin levels were similar between the PCOS and control groups. While the inflammatory markers were significantly high in the overweight and obese PCOS subgroup, the hepcidin levels were also high but this elevation was not statistically significant. Obesity is the principle mechanism of chronic inflammation and IR in PCOS patients. C-reactive protein and interleukin-6 should be used to predict and follow the risk of CVD development in PCOS cases. Hepcidin may be used as an additional marker in the follow-up of PCOS patients in the future. Copyright © 2013 S. Karger AG, Basel.

  3. One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk.

    PubMed

    Gylling, Björn; Myte, Robin; Ulvik, Arve; Ueland, Per M; Midttun, Øivind; Schneede, Jörn; Hallmans, Göran; Häggström, Jenny; Johansson, Ingegerd; Van Guelpen, Bethany; Palmqvist, Richard

    2018-05-22

    One-carbon metabolism biomarkers are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs. We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk. Furthermore, the relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1190 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5'-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression. We found that the ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Additionally, associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status). In conclusion, ratio-based B-vitamin markers were good predictors of total B-vitamin status and displayed similar associations as total B-vitamin status with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice. This article is protected by copyright. All rights reserved. © 2018 UICC.

  4. Serum levels of the immune activation marker neopterin change with age and gender and are modified by race, BMI, and percentage of body fat.

    PubMed

    Spencer, Monique E; Jain, Alka; Matteini, Amy; Beamer, Brock A; Wang, Nae-Yuh; Leng, Sean X; Punjabi, Naresh M; Walston, Jeremy D; Fedarko, Neal S

    2010-08-01

    Neopterin, a GTP metabolite expressed by macrophages, is a marker of immune activation. We hypothesize that levels of this serum marker alter with donor age, reflecting increased chronic immune activation in normal aging. In addition to age, we assessed gender, race, body mass index (BMI), and percentage of body fat (%fat) as potential covariates. Serum was obtained from 426 healthy participants whose age ranged from 18 to 87 years. Anthropometric measures included %fat and BMI. Neopterin concentrations were measured by competitive ELISA. The paired associations between neopterin and age, BMI, or %fat were analyzed by Spearman's correlation or by linear regression of log-transformed neopterin, whereas overall associations were modeled by multiple regression of log-transformed neopterin as a function of age, gender, race, BMI, %fat, and interaction terms. Across all participants, neopterin exhibited a positive association with age, BMI, and %fat. Multiple regression modeling of neopterin in women and men as a function of age, BMI, and race revealed that each covariate contributed significantly to neopterin values and that optimal modeling required an interaction term between race and BMI. The covariate %fat was highly correlated with BMI and could be substituted for BMI to yield similar regression coefficients. The association of age and gender with neopterin levels and their modification by race, BMI, or %fat reflect the biology underlying chronic immune activation and perhaps gender differences in disease incidence, morbidity, and mortality.

  5. Novel tetra-nucleotide microsatellite DNA markers for assessing the evolutionary genetics and demographics of Northern Snakehead (Channa argus) invading North America

    USGS Publications Warehouse

    King, Timothy L.; Johnson, Robin L.

    2011-01-01

    We document the isolation and characterization of 19 tetra-nucleotide microsatellite DNA markers in northern snakehead (Channa argus) fish that recently colonized Meadow Lake, New York City, New York. These markers displayed moderate levels of allelic diversity (averaging 6.8 alleles/locus) and heterozygosity (averaging 74.2%). Demographic analyses suggested that the Meadow Lake collection has not achieved mutation-drift equilibrium. These results were consistent with instances of deviations from Hardy–Weinberg equilibrium and the presence of some linkage disequilibrium. A comparison of individual pair-wise distances suggested the presence of multiple differentiated groups of related individuals. Results of all analyses are consistent with a pattern of multiple, recent introductions. The microsatellite markers developed for C. argus yielded sufficient genetic diversity to potentially: (1) delineate kinship; (2) elucidate fine-scale population structure; (3) define management (eradication) units; (4) estimate dispersal rates; (5) estimate population sizes; and (6) provide unique demographic perspectives of control or eradication effectiveness.

  6. Evaluation of the impact of genetic linkage in forensic identity and relationship testing for expanded DNA marker sets.

    PubMed

    Tillmar, Andreas O; Phillips, Chris

    2017-01-01

    Advances in massively parallel sequencing technology have enabled the combination of a much-expanded number of DNA markers (notably STRs and SNPs in one or combined multiplexes), with the aim of increasing the weight of evidence in forensic casework. However, when data from multiple loci on the same chromosome are used, genetic linkage can affect the final likelihood calculation. In order to study the effect of linkage for different sets of markers we developed the biostatistical tool ILIR, (Impact of Linkage on forensic markers for Identity and Relationship tests). The ILIR tool can be used to study the overall impact of genetic linkage for an arbitrary set of markers used in forensic testing. Application of ILIR can be useful during marker selection and design of new marker panels, as well as being highly relevant for existing marker sets as a way to properly evaluate the effects of linkage on a case-by-case basis. ILIR, implemented via the open source platform R, includes variation and genomic position reference data for over 40 STRs and 140 SNPs, combined with the ability to include additional forensic markers of interest. The use of the software is demonstrated with examples from several different established marker sets (such as the expanded CODIS core loci) including a review of the interpretation of linked genetic data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Development and genetic mapping of SSR markers in foxtail millet [Setaria italica (L.) P. Beauv.].

    PubMed

    Jia, Xiaoping; Zhang, Zhongbao; Liu, Yinghui; Zhang, Chengwei; Shi, Yunsu; Song, Yanchun; Wang, Tianyu; Li, Yu

    2009-02-01

    SSR markers are desirable markers in analysis of genetic diversity, quantitative trait loci mapping and gene locating. In this study, SSR markers were developed from two genomic libraries enriched for (GA)n and (CA)n of foxtail millet [Setaria italica (L.) P. Beauv.], a crop of historical importance in China. A total of 100 SSR markers among the 193 primer pairs detected polymorphism between two mapping parents of an F(2) population, i.e. "B100" of cultivated S. italica and "A10" of wild S. viridis. Excluding 14 markers with unclear amplifications, and five markers unlinked with any linkage group, a foxtail millet SSR linkage map was constructed by integrating 81 new developed SSR markers with 20 RFLP anchored markers. The 81 SSRs covered nine chromosomes of foxtail millet. The length of the map was 1,654 cM, with an average interval distance between markers of 16.4 cM. The 81 SSR markers were not evenly distributed throughout the nine chromosomes, with Ch.8 harbouring the least (3 markers) and Ch.9 harbouring the most (18 markers). To verify the usefulness of the SSR markers developed, 37 SSR markers were randomly chosen to analyze genetic diversity of 40 foxtail millet accessions. Totally 228 alleles were detected, with an average 6.16 alleles per locus. Polymorphism information content (PIC) value for each locus ranged from 0.413 to 0.847, with an average of 0.697. A positive correlation between PIC and number of alleles and between PIC and number of repeat unit were found [0.802 and 0.429, respectively (P < 0.01)]. UPGMA analysis revealed that the 40 foxtail millet cultivars could be grouped into five clusters in which the landraces' grouping was largely consistent with ecotypes while the breeding varieties from different provinces in China tended to be grouped together.

  8. Neonatal metabolic acidosis at birth: In search of a reliable marker.

    PubMed

    Racinet, C; Ouellet, P; Charles, F; Daboval, T

    2016-06-01

    A newborn may present acidemia on the umbilical artery blood which can result from respiratory acidosis or metabolic acidosis or be of mixed origin. Currently, in the absence of a satisfactory definition, the challenge is to determine the most accurate marker for metabolic acidosis, which can be deleterious for the neonate. We reviewed the methodological and physiological aspects of the perinatal literature to search for the best marker of NMA. Base deficit and pH have been criticized as the standard criteria to predict outcome. The proposed threshold of pathogenicity is not based on convincing studies. The algorithms of various blood gas analyzers differ and do not take into account the specific neonatal acid-base profile. Birth-related neonatal eucapnic pH is described as the most pertinent marker of NMA at birth. The various means of calculating this value and the level below which it seems to play a possible pathogenic role are presented. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Marker Registration Technique for Handwritten Text Marker in Augmented Reality Applications

    NASA Astrophysics Data System (ADS)

    Thanaborvornwiwat, N.; Patanukhom, K.

    2018-04-01

    Marker registration is a fundamental process to estimate camera poses in marker-based Augmented Reality (AR) systems. We developed AR system that creates correspondence virtual objects on handwritten text markers. This paper presents a new method for registration that is robust for low-content text markers, variation of camera poses, and variation of handwritten styles. The proposed method uses Maximally Stable Extremal Regions (MSER) and polygon simplification for a feature point extraction. The experiment shows that we need to extract only five feature points per image which can provide the best registration results. An exhaustive search is used to find the best matching pattern of the feature points in two images. We also compared performance of the proposed method to some existing registration methods and found that the proposed method can provide better accuracy and time efficiency.

  10. Genetic analysis of Melipona quadrifasciata LEP. (Hymenoptera: Apidae, Meliponinae) with RAPD markers.

    PubMed

    Waldschmidt, A M; Marco-Júnior, P; Barros, E G; Campos, L A O

    2002-11-01

    Melipona quadrifasciata ("mandaçaia") can be subdivided into two subspecies: M. q. anthidioides and M. q. quadrifasciata. In the present study we used RAPD markers to estimate intercolonial genetic variation among 69 colonies of Melipona quadrifasciata. Ten workers per colony were analyzed. The intercolony genetic distances based on RAPD markers ranged from 29.5% (colonies collected in the State of São Paulo vs colonies from the State of Minas Gerais) to 34.2% (São Paulo vs Santa Catarina). These results indicate a high genetic similarity among the colonies analyzed. According to the genetic distances two different groups could be distinguished. The first containing the samples from Santa Catarina region and the second, samples from Paraná, São Paulo, Minas Gerais, and Espírito Santo. Based on the molecular analysis, bees belonging to the different subspecies M. q. quadrifasciata (from Santa Catarina) and M. q. anthidiodes (from the other regions) were distinguished.

  11. A new automated multiple allergen simultaneous test-chemiluminescent assay (MAST-CLA) using an AP720S analyzer.

    PubMed

    Lee, Sungsil; Lim, Hwan Sub; Park, Jungyong; Kim, Hyon Suk

    2009-04-01

    In the diagnosis of atopic diseases, allergen detection is a crucial step. Multiple allergen simultaneous test-chemiluminescent assay (MAST-CLA) is a simple and noninvasive method for in vitro screening of allergen-specific IgE antibodies. The Korean Inhalant Panel test on 20 patients and Food Panel test on 19 patients were performed using the conventional manual MAST-CLA kit and the new automated MAST-CLA method (automated AP720S system for the Optigen Assay; Hitachi Chemical Diagnostics, Inc., USA) simultaneously. The results were evaluated for positive reactivity and concordance. The results of inhalant panel gave a relatively higher class level result than the food panel. The 8 patients out of 20 (40%) of the inhalation panel, and 9 patients out of 18 (47.4%) of the food panel showed 100% concordance between the 2 systems. Eighteen patients (90%) of the Inhalation Panel and sixteen patients (84.2%) of the Food Panel showed more than 91% concordance. These results suggest that the MAST-CLA assay using the new, automated AP720S analyzer performs well, showing a high concordance rate with conventional MAST-CLA. Compared to manual MAST-CLA, the automated AP720S system has a shorter assay time and uses a smaller serum volume (500 microl) along with other conveniences.

  12. Marker-assisted combination of major genes for pathogen resistance in potato.

    PubMed

    Gebhardt, C; Bellin, D; Henselewski, H; Lehmann, W; Schwarzfischer, J; Valkonen, J P T

    2006-05-01

    Closely linked PCR-based markers facilitate the tracing and combining of resistance factors that have been introgressed previously into cultivated potato from different sources. Crosses were performed to combine the Ry ( adg ) gene for extreme resistance to Potato virus Y (PVY) with the Gro1 gene for resistance to the root cyst nematode Globodera rostochiensis and the Rx1 gene for extreme resistance to Potato virus X (PVX), or with resistance to potato wart (Synchytrium endobioticum). Marker-assisted selection (MAS) using four PCR-based diagnostic assays was applied to 110 F1 hybrids resulting from four 2x by 4x cross-combinations. Thirty tetraploid plants having the appropriate marker combinations were selected and tested for presence of the corresponding resistance traits. All plants tested showed the expected resistant phenotype. Unexpectedly, the plants segregated for additional resistance to pathotypes 1, 2 and 6 of S. endobioticum, which was subsequently shown to be inherited from the PVY resistant parents of the crosses. The selected plants can be used as sources of multiple resistance traits in pedigree breeding and are available from a potato germplasm bank.

  13. The concept of multiple hormonal dysregulation

    PubMed Central

    Maggio, Marcello; Cattabiani, Chiara; Lauretani, Fulvio; Ferrucci, Luigi; Luci, Michele; Valenti, Giorgio; Ceda, Gianpaolo

    2016-01-01

    Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones that remain stable and anabolic hormones (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Despite the multiple hormonal dysregulation occurring with age, the prevalent line of research in the last decades has tried to explain many age-related phenomena as consequence of one single hormonal derangement with disappointing results. In this review we will list the relationship between hormonal anabolic deficiency and frailty and mortality in older population, providing evidence to the notion that multiple hormonal dysregulation rather than change in single anabolic hormone is a powerful marker of poor health status and mortality. (www.actabiomedica.it) PMID:20518188

  14. Development of a Multiple-Stage Differential Mobility Analyzer (MDMA)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Da-Ren; Cheng, Mengdawn

    2007-01-01

    A new DMA column has been designed with the capability of simultaneously extracting monodisperse particles of different sizes in multiple stages. We call this design a multistage DMA, or MDMA. A prototype MDMA has been constructed and experimentally evaluated in this study. The new column enables the fast measurement of particles in a wide size range, while preserving the powerful particle classification function of a DMA. The prototype MDMA has three sampling stages, capable of classifying monodisperse particles of three different sizes simultaneously. The scanning voltage operation of a DMA can be applied to this new column. Each stage ofmore » MDMA column covers a fraction of the entire particle size range to be measured. The covered size fractions of two adjacent stages of the MDMA are designed somewhat overlapped. The arrangement leads to the reduction of scanning voltage range and thus the cycling time of the measurement. The modular sampling stage design of the MDMA allows the flexible configuration of desired particle classification lengths and variable number of stages in the MDMA. The design of our MDMA also permits operation at high sheath flow, enabling high-resolution particle size measurement and/or reduction of the lower sizing limit. Using the tandem DMA technique, the performance of the MDMA, i.e., sizing accuracy, resolution, and transmission efficiency, was evaluated at different ratios of aerosol and sheath flowrates. Two aerosol sampling schemes were investigated. One was to extract aerosol flows at an evenly partitioned flowrate at each stage, and the other was to extract aerosol at a rate the same as the polydisperse aerosol flowrate at each stage. We detail the prototype design of the MDMA and the evaluation result on the transfer functions of the MDMA at different particle sizes and operational conditions.« less

  15. ESAP plus: a web-based server for EST-SSR marker development.

    PubMed

    Ponyared, Piyarat; Ponsawat, Jiradej; Tongsima, Sissades; Seresangtakul, Pusadee; Akkasaeng, Chutipong; Tantisuwichwong, Nathpapat

    2016-12-22

    Simple sequence repeats (SSRs) have become widely used as molecular markers in plant genetic studies due to their abundance, high allelic variation at each locus and simplicity to analyze using conventional PCR amplification. To study plants with unknown genome sequence, SSR markers from Expressed Sequence Tags (ESTs), which can be obtained from the plant mRNA (converted to cDNA), must be utilized. With the advent of high-throughput sequencing technology, huge EST sequence data have been generated and are now accessible from many public databases. However, SSR marker identification from a large in-house or public EST collection requires a computational pipeline that makes use of several standard bioinformatic tools to design high quality EST-SSR primers. Some of these computational tools are not users friendly and must be tightly integrated with reference genomic databases. A web-based bioinformatic pipeline, called EST Analysis Pipeline Plus (ESAP Plus), was constructed for assisting researchers to develop SSR markers from a large EST collection. ESAP Plus incorporates several bioinformatic scripts and some useful standard software tools necessary for the four main procedures of EST-SSR marker development, namely 1) pre-processing, 2) clustering and assembly, 3) SSR mining and 4) SSR primer design. The proposed pipeline also provides two alternative steps for reducing EST redundancy and identifying SSR loci. Using public sugarcane ESTs, ESAP Plus automatically executed the aforementioned computational pipeline via a simple web user interface, which was implemented using standard PHP, HTML, CSS and Java scripts. With ESAP Plus, users can upload raw EST data and choose various filtering options and parameters to analyze each of the four main procedures through this web interface. All input EST data and their predicted SSR results will be stored in the ESAP Plus MySQL database. Users will be notified via e-mail when the automatic process is completed and they can

  16. Students' Ability in Using Discourse Markers to Build Coherence in Compositions

    ERIC Educational Resources Information Center

    Patriana, Andhina W.; Rachmajanti, Sri; Mukminatien, Nur

    2016-01-01

    The study attempts to find out how Indonesian students apply Discourse Markers (DMs) to build coherence in English compositions. It employs a descriptive design, analyzing 52 target DMs and how they are used in 21 argumentative papers. The participants of the study were 21 Master's students majoring in English Language Teaching (ELT). The results…

  17. Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma

    PubMed Central

    Zhan, Cheng; Yan, Li; Wang, Lin; Sun, Yang; Wang, Xingxing; Lin, Zongwu; Zhang, Yongxing; Wang, Qun

    2015-01-01

    Background Immunohistochemical staining has been widely used in distinguishing lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC), which is of vital importance for the diagnosis and treatment of lung cancer. Due to the lack of a comprehensive analysis of different lung cancer subtypes, there may still be undiscovered markers with higher diagnostic accuracy. Methods Herein first, we systematically analyzed high-throughput data obtained from The Cancer Genome Atlas (TCGA) database. Combining differently expressed gene screening and receiver operating characteristic (ROC) curve analysis, we attempted to identify the genes which might be suitable as immunohistochemical markers in distinguishing LUAD from LUSC. Then we detected the expression of six of these genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in lung cancer sections using immunohistochemical staining. Results A number of genes were identified as candidate immunohistochemical markers with high sensitivity and specificity in distinguishing LUAD from LUSC. Then the staining results confirmed the potentials of the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in distinguishing LUAD from LUSC, and their sensitivity and specificity were not less than many commonly used markers. Conclusions The results revealed that the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) might be suitable markers in distinguishing LUAD from LUSC, and also validated the feasibility of our methods for identification of candidate markers from high-throughput data. PMID:26380766

  18. Leaf margin phenotype-specific restriction-site-associated DNA-derived markers for pineapple (Ananas comosus L.).

    PubMed

    Urasaki, Naoya; Goeku, Satoko; Kaneshima, Risa; Takamine, Tomonori; Tarora, Kazuhiko; Takeuchi, Makoto; Moromizato, Chie; Yonamine, Kaname; Hosaka, Fumiko; Terakami, Shingo; Matsumura, Hideo; Yamamoto, Toshiya; Shoda, Moriyuki

    2015-06-01

    To explore genome-wide DNA polymorphisms and identify DNA markers for leaf margin phenotypes, a restriction-site-associated DNA sequencing analysis was employed to analyze three bulked DNAs of F1 progeny from a cross between a 'piping-leaf-type' cultivar, 'Yugafu', and a 'spiny-tip-leaf-type' variety, 'Yonekura'. The parents were both Ananas comosus var. comosus. From the analysis, piping-leaf and spiny-tip-leaf gene-specific restriction-site-associated DNA sequencing tags were obtained and designated as PLSTs and STLSTs, respectively. The five PLSTs and two STSLTs were successfully converted to cleaved amplified polymorphic sequence (CAPS) or simple sequence repeat (SSR) markers using the sequence differences between alleles. Based on the genotyping of the F1 with two SSR and three CAPS markers, the five PLST markers were mapped in the vicinity of the P locus, with the closest marker, PLST1_SSR, being located 1.5 cM from the P locus. The two CAPS markers from STLST1 and STLST3 perfectly assessed the 'spiny-leaf type' as homozygotes of the recessive s allele of the S gene. The recombination value between the S locus and STLST loci was 2.4, and STLSTs were located 2.2 cM from the S locus. SSR and CAPS markers are applicable to marker-assisted selection of leaf margin phenotypes in pineapple breeding.

  19. Nitrogen Cycle Evaluation (NiCE) Chip for the Simultaneous Analysis of Multiple N-Cycle Associated Genes.

    PubMed

    Oshiki, Mamoru; Segawa, Takahiro; Ishii, Satoshi

    2018-02-02

    Various microorganisms play key roles in the Nitrogen (N) cycle. Quantitative PCR (qPCR) and PCR-amplicon sequencing of the N cycle functional genes allow us to analyze the abundance and diversity of microbes responsible in the N transforming reactions in various environmental samples. However, analysis of multiple target genes can be cumbersome and expensive. PCR-independent analysis, such as metagenomics and metatranscriptomics, is useful but expensive especially when we analyze multiple samples and try to detect N cycle functional genes present at relatively low abundance. Here, we present the application of microfluidic qPCR chip technology to simultaneously quantify and prepare amplicon sequence libraries for multiple N cycle functional genes as well as taxon-specific 16S rRNA gene markers for many samples. This approach, named as N cycle evaluation (NiCE) chip, was evaluated by using DNA from pure and artificially mixed bacterial cultures and by comparing the results with those obtained by conventional qPCR and amplicon sequencing methods. Quantitative results obtained by the NiCE chip were comparable to those obtained by conventional qPCR. In addition, the NiCE chip was successfully applied to examine abundance and diversity of N cycle functional genes in wastewater samples. Although non-specific amplification was detected on the NiCE chip, this could be overcome by optimizing the primer sequences in the future. As the NiCE chip can provide high-throughput format to quantify and prepare sequence libraries for multiple N cycle functional genes, this tool should advance our ability to explore N cycling in various samples. Importance. We report a novel approach, namely Nitrogen Cycle Evaluation (NiCE) chip by using microfluidic qPCR chip technology. By sequencing the amplicons recovered from the NiCE chip, we can assess diversities of the N cycle functional genes. The NiCE chip technology is applicable to analyze the temporal dynamics of the N cycle gene

  20. Efficacy of Fish Oil on Serum of TNFα, IL-1β, and IL-6 Oxidative Stress Markers in Multiple Sclerosis Treated with Interferon Beta-1b

    PubMed Central

    Ramirez-Ramirez, V.; Macias-Islas, M. A.; Ortiz, G. G.; Pacheco-Moises, F.; Torres-Sanchez, E. D.; Sorto-Gomez, T. E.; Cruz-Ramos, J. A.; Orozco-Aviña, G.; Celis de la Rosa, A. J.

    2013-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNFα levels; secondary outcomes were IL-1β 1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNFα, IL-1β, IL-6, and nitric oxide metabolites compared with placebo group (P ≤ 0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found. Conclusion. Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS. PMID:23861993

  1. Analysis of four microsatellite markers on the long arm of chromosome 9 by meiotic recombination in flow-sorted single sperm

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Furlong, R.A.; Goudie, D.R.; Carter, N.P.

    1993-06-01

    Meiotic recombination in flow-sorted single sperm was used to analyze four highly polymorphic microsatellite markers on the long arm of chromosome 9. The microsatellites comprised three tightly linked markers: 9CMP1 (D9S109), 9CMP2 (D9S127), and D9S53, which map to 9q31, and a reference marker, ASS, which is located in 9q34.1. Haplotypes of single sperm were assessed by using PCR in a single-step multiplex reaction to amplify each locus. Recombinant haplotypes were identified by their relative infrequency and were analyzed using THREELOC, a maximum-likelihood-analysis program, and an adaptation of CRI-MAP. The most likely order of these markers was cen-D9S109-D9S127-D9S53-ASS-tel with D9S109, D9S127,more » and D9S53 being separated by a genetic distance of approximately 3%. The order of the latter three markers did not however achieve statistical significance using the THREELOC program. 21 refs., 2 figs., 4 tabs.« less

  2. Identification of milling and baking quality QTL in multiple soft wheat mapping populations.

    PubMed

    Cabrera, Antonio; Guttieri, Mary; Smith, Nathan; Souza, Edward; Sturbaum, Anne; Hua, Duc; Griffey, Carl; Barnett, Marla; Murphy, Paul; Ohm, Herb; Uphaus, Jim; Sorrells, Mark; Heffner, Elliot; Brown-Guedira, Gina; Van Sanford, David; Sneller, Clay

    2015-11-01

    Two mapping approaches were use to identify and validate milling and baking quality QTL in soft wheat. Two LG were consistently found important for multiple traits and we recommend the use marker-assisted selection on specific markers reported here. Wheat-derived food products require a range of characteristics. Identification and understanding of the genetic components controlling end-use quality of wheat is important for crop improvement. We assessed the underlying genetics controlling specific milling and baking quality parameters of soft wheat including flour yield, softness equivalent, flour protein, sucrose, sodium carbonate, water absorption and lactic acid, solvent retention capacities in a diversity panel and five bi-parental mapping populations. The populations were genotyped with SSR and DArT markers, with markers specific for the 1BL.1RS translocation and sucrose synthase gene. Association analysis and composite interval mapping were performed to identify quantitative trait loci (QTL). High heritability was observed for each of the traits evaluated, trait correlations were consistent over populations, and transgressive segregants were common in all bi-parental populations. A total of 26 regions were identified as potential QTL in the diversity panel and 74 QTL were identified across all five bi-parental mapping populations. Collinearity of QTL from chromosomes 1B and 2B was observed across mapping populations and was consistent with results from the association analysis in the diversity panel. Multiple regression analysis showed the importance of the two 1B and 2B regions and marker-assisted selection for the favorable alleles at these regions should improve quality.

  3. Novel method to load multiple genes onto a mammalian artificial chromosome.

    PubMed

    Tóth, Anna; Fodor, Katalin; Praznovszky, Tünde; Tubak, Vilmos; Udvardy, Andor; Hadlaczky, Gyula; Katona, Robert L

    2014-01-01

    Mammalian artificial chromosomes are natural chromosome-based vectors that may carry a vast amount of genetic material in terms of both size and number. They are reasonably stable and segregate well in both mitosis and meiosis. A platform artificial chromosome expression system (ACEs) was earlier described with multiple loading sites for a modified lambda-integrase enzyme. It has been shown that this ACEs is suitable for high-level industrial protein production and the treatment of a mouse model for a devastating human disorder, Krabbe's disease. ACEs-treated mutant mice carrying a therapeutic gene lived more than four times longer than untreated counterparts. This novel gene therapy method is called combined mammalian artificial chromosome-stem cell therapy. At present, this method suffers from the limitation that a new selection marker gene should be present for each therapeutic gene loaded onto the ACEs. Complex diseases require the cooperative action of several genes for treatment, but only a limited number of selection marker genes are available and there is also a risk of serious side-effects caused by the unwanted expression of these marker genes in mammalian cells, organs and organisms. We describe here a novel method to load multiple genes onto the ACEs by using only two selectable marker genes. These markers may be removed from the ACEs before therapeutic application. This novel technology could revolutionize gene therapeutic applications targeting the treatment of complex disorders and cancers. It could also speed up cell therapy by allowing researchers to engineer a chromosome with a predetermined set of genetic factors to differentiate adult stem cells, embryonic stem cells and induced pluripotent stem (iPS) cells into cell types of therapeutic value. It is also a suitable tool for the investigation of complex biochemical pathways in basic science by producing an ACEs with several genes from a signal transduction pathway of interest.

  4. Development of Protoporphyrinogen Oxidase as an Efficient Selection Marker for Agrobacterium tumefaciens-Mediated Transformation of Maize

    PubMed Central

    Li, Xianggan; Volrath, Sandy L.; Nicholl, David B.G.; Chilcott, Charles E.; Johnson, Marie A.; Ward, Eric R.; Law, Marcus D.

    2003-01-01

    In this article, we report the isolation of plant protoporphyrinogen oxidase (PPO) genes and the isolation of herbicide-tolerant mutants. Subsequently, an Arabidopsis double mutant (Y426M + S305L) was used to develop a selectable marker system for Agrobacterium tumefaciens-mediated transformation of maize (Zea mays) and to obtain multiple events tolerant to the PPO family of herbicides. Maize transformants were produced via butafenacil selection using a flexible light regime to increase selection pressure. Butafenacil selection per se did not change transgene copy number distribution relative to other selectable marker systems, but the most tolerant events identified in the greenhouse were more likely to contain multiple copies of the introduced mutant PPO gene. To date, more than 2,500 independent transgenic maize events have been produced using butafenacil selection. The high frequency of A. tumefaciens-mediated transformation via PPO selection enabled us to obtain single-copy transgenic maize lines tolerant to field levels of butafenacil. PMID:12972658

  5. Multiple Origins of Mutations in the mdr1 Gene—A Putative Marker of Chloroquine Resistance in P. vivax

    PubMed Central

    Schousboe, Mette L.; Ranjitkar, Samir; Rajakaruna, Rupika S.; Amerasinghe, Priyanie H.; Morales, Francisco; Pearce, Richard; Ord, Rosalyn; Leslie, Toby; Rowland, Mark; Gadalla, Nahla B.; Konradsen, Flemming; Bygbjerg, Ib C.; Roper, Cally; Alifrangis, Michael

    2015-01-01

    Background Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR). Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored. Objective In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS) loci flanking the Pvmdr1 gene. Methods We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS) markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles. Results SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5), 13.3% (n = 28) of the samples were single mutant MYF, 63.0% of samples (n = 133) were double mutant MYL, and 21.3% (n = 45) were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD) between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He), was seen in the complete sample set (He = 0.99), while He estimates for individual loci ranged from 0.00–0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant

  6. Selected oxidative stress markers in a South American crocodilian species.

    PubMed

    Furtado-Filho, Orlando V; Polcheira, Cássia; Machado, Daniel P; Mourão, Guilherme; Hermes-Lima, Marcelo

    2007-01-01

    Crocodilians and other diving vertebrates experience hypoperfusion and hypoxia of several internal organs during long dives. At the end of a dive, reperfusion of aerated blood may cause a physiologically relevant oxidative stress. In this study, we analyzed selected markers of oxidative stress in eight organs of normoxic Paraguayan caiman (Caiman yacare) captured in the Brazilian Pantanal wetlands during the winter of 2001 (six mature-adult males and eight young-adult males; AD-1 and YA-1 groups, respectively), and during the summer of 2002 (six young-adult males (YA-2 group), ten hatchlings and five embryos). Lipid peroxidation products determined by three different assays were generally highest in brain, liver and kidney (in comparison with all other organs), and lowest in white muscles from the tail and hind legs. Liver and kidney showed the highest levels of carbonyl protein, while brain showed low levels. Intermediate levels of oxidative stress markers were mostly found in the heart ventricles and lung. Differences in oxidative stress markers between AD-1 and YA-1 were organ-specific, showing no age-related correlation. However, most oxidative stress markers in YA-2 organs were either higher than (by 1.4- to 3.7-fold) or not significantly different from respective values in hatchlings organs. This pattern (hatchlings versus young-adults) was confirmed using correlation analysis of individual caiman size versus levels of oxidative damage markers in four organs. The higher level of oxidative stress markers in young-adults possibly relates to the fast growth rate (and thus, increased oxidative metabolic rate) of C. yacare in the first years of life. Differences in oxidative stress markers between YA-1 and YA-2 were also observed and were ascribed to seasonal changes in free radical metabolism. These results in normoxic C. yacare represent the first step towards understanding the age-related physiological oxidative stress of a diving reptile from a seasonally

  7. Implications of Artefacts Reduction in the Planning CT Originating from Implanted Fiducial Markers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kassim, Iskandar, E-mail: i.binkassim@erasmusmc.n; Joosten, Hans; Barnhoorn, Jaco C.

    The efficacy of metal artefact reduction (MAR) software to suppress artefacts in reconstructed computed tomography (CT) images originating from small metal objects, like tumor markers and surgical clips, was evaluated. In addition, possible implications of using digital reconstructed radiographs (DRRs), based on the MAR CT images, for setup verification were analyzed. A phantom and 15 patients with different tumor sites and implanted markers were imaged with a multislice CT scanner. The raw image data was reconstructed both with the clinically used filtered-backprojection (FBP) and with the MAR software. Using the MAR software, improvements in image quality were often observed inmore » CT slices with markers or clips. Especially when several markers were located near to each other, fewer streak artefacts were observed than with the FBP algorithm. In addition, the shape and size of markers could be identified more accurately, reducing the contoured marker volumes by a factor of 2. For the phantom study, the CT numbers measured near to the markers corresponded more closely to the expected values. However, the MAR images were slightly more smoothed compared with the images reconstructed with FBP. For 8 prostate cancer patients in this study, the interobserver variation in 3D marker definition was similar (<0.4 mm) when using DRRs based on either FBP or MAR CT scans. Automatic marker matches also showed a similar success rate. However, differences in automatic match results up to 1 mm, caused by differences in the marker definition, were observed, which turned out to be (borderline) statistically significant (p = 0.06) for 2 patients. In conclusion, the MAR software might improve image quality by suppressing metal artefacts, probably allowing for a more reliable delineation of structures. When implanted markers or clips are used for setup verification, the accuracy may slightly be improved as well, which is relevant when using very tight clinical target volume (CTV

  8. Targeted mapping and linkage analysis of morphological isozyme, and RAPD markers in peach.

    PubMed

    Chaparro, J X; Werner, D J; O'Malley, D; Sederoff, R R

    1994-02-01

    Nine different F2 families of peach [Prunus persica (L.) Batsch] were analyzed for linkage relationships between 14 morphological and two isozyme loci. Linkage was detected between weeping (We) and white flower (W), 33 cM; double flower (Dl) and pillar (Br), 10 cM; and flesh color (Y) and malate dehydrogenase (Mdh1), 26 cM. A leaf variant phenotypically distinct from the previously reported wavy-leaf (Wa) mutant in peach was found in progeny of 'Davie II'. The new willow-leaf character (designated Wa2) was closely linked (0.4 cM) to a new dwarf phenotype (designated Dw3). Two families derived from the pollen-fertile cultivar 'White Glory' segregated for pollen sterility, but segregation did not follow a 3∶1 ratio. Evidence is presented suggesting that 'White Glory' possesses a pollen-sterility gene (designated Ps2) that is non-allelic to the previously reported pollen-sterility gene (Ps) in peach. Ps2 was linked to both weeping (We-Ps2, 15.5 cM) and white flower (Ps2-W, 25.3 cM). A genomic map of peach containing 83 RAPD, one isozyme, and four morphological markers was generated using an F2 family obtained by selfing an NC174RL x 'Pillar' F1. A total of 83 RAPD markers were assigned to 15 linkage groups. Various RAPD markers were linked to morphological traits. Bulked segregant analysis was used to identify RAPD markers flanking the red-leaf (Gr) and Mdh1 loci in the NC174RL x 'Pillar' and 'Marsun' x 'White Glory' F2 families, respectively. Three markers flanking Mdh1 and ten markers flanking Gr were identified. The combination of RAPD markers and bulked segregant analysis provides an efficient method of identifying markers flanking traits of interest. Markers linked to traits that can only be scored late in development are potentially useful for marker-aided selection in trees. Alternatives for obtaining additional map order information for repulsion-phase markers in large F2 populations are proposed.

  9. Phylogenetic and microsatellite markers for Tulasnella (Tulasnellaceae) mycorrhizal fungi associated with Australian orchids1

    PubMed Central

    Ruibal, Monica P.; Peakall, Rod; Smith, Leon M.; Linde, Celeste C.

    2013-01-01

    • Premise of the study: Phylogenetic and microsatellite markers were developed for Tulasnella mycorrhizal fungi to investigate fungal species identity and diversity. These markers will be useful in future studies investigating the phylogenetic relationship of the fungal symbionts, specificity of orchid–mycorrhizal associations, and the role of mycorrhizae in orchid speciation within several orchid genera. • Methods and Results: We generated partial genome sequences of two Tulasnella symbionts originating from Chiloglottis and Drakaea orchid species with 454 genome sequencing. Cross-genus transferability across mycorrhizal symbionts associated with multiple genera of Australian orchids (Arthrochilus, Chiloglottis, Drakaea, and Paracaleana) was found for seven phylogenetic loci. Five loci showed cross-transferability to Tulasnella from other orchid genera, and two to Sebacina. Furthermore, 11 polymorphic microsatellite loci were developed for Tulasnella from Chiloglottis. • Conclusions: Highly informative markers were obtained, allowing investigation of mycorrhizal diversity of Tulasnellaceae associated with a wide variety of terrestrial orchids in Australia and potentially worldwide. PMID:25202528

  10. Prevalence of Skin Lesions in Familial Adenomatous Polyposis: A Marker for Presymptomatic Diagnosis?

    PubMed Central

    Cattani, Nadja; Trueb, Swantje; de Lorenzo, Rosaria; Albertini, Mauro; Bontognali, Emanuele; Itin, Christoph; Schaub, Nathalie; Itin, Peter H.

    2011-01-01

    Background and Aims. Benign skin tumors such as lipomas, fibromas, and epidermal cysts are among the extracolonic manifestations of familial adenomatous polyposis (FAP). Readily detectable by inspection, they could serve as presymptomatic diagnostic markers to identify FAP patients. We therefore prospectively determined the prevalence of cutaneous lesions in genetically confirmed adenomatous polyposis coli (APC) mutation carriers and assessed their potential usefulness in the identification of FAP patients. Methods. Whole-skin examination was performed in 56 adult APC mutation carriers, compared with a control group (n = 116). In addition, FAP patients were investigated for the presence of congenital hypertrophy of the retinal pigment epithelium (CHRPE), an established clinical marker for FAP, and a detailed review of medical records was performed. Results. Nearly half of all FAP patients (48.2%) had at least one FAP-associated skin lesion, compared with one third (34.5%) of controls. Only multiple lipomas and combined skin lesions were significantly more prevalent in APC mutation carriers. CHRPE was observed in 22 (43.1%) of 51 FAP patients, including 14 (37.8%) of 37 individuals with APC mutations outside the CHRPE-associated region between codons 311 and 1465. Conclusions. Despite a significantly higher prevalence of multiple lipomas, occurring at younger age, and combined skin lesions in APC mutation carriers, the low diagnostic sensitivity of FAP-associated skin lesions precludes their use as markers for FAP in clinical practice. Based on our findings, the common CHRPE-associated region should be extended to APC codons 148-2043. PMID:22135120

  11. Monitoring of 30 marker candidates in early Parkinson disease as progression markers

    PubMed Central

    Zimmermann, Johannes; Sixel-Döring, Friederike; Focke, Niels K.; Wicke, Tamara; Ebentheuer, Jens; Schaumburg, Martina; Lang, Elisabeth; Trautmann, Ellen; Zetterberg, Henrik; Taylor, Peggy; Friede, Tim; Trenkwalder, Claudia

    2016-01-01

    Objective: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106). Methods: Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). Results: A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09–0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06–0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24–0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25–0.64), and RBD by PSG (d 0.37; CI 0.19–0.55) as well as VBM units of cortical gray matter (d −0.2; CI −0.3 to −0.09) and hippocampus (d −0.15; CI −0.27 to −0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d −0.19; CI −0.36 to −0.02) and 2 depression scales (Beck Depression Inventory d −0.18; CI −0.36 to 0; Montgomery-Åsberg Depression Rating Scale d −0.26; CI −0.47 to −0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants. Conclusions: Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression. PMID:27164658

  12. Monitoring of 30 marker candidates in early Parkinson disease as progression markers.

    PubMed

    Mollenhauer, Brit; Zimmermann, Johannes; Sixel-Döring, Friederike; Focke, Niels K; Wicke, Tamara; Ebentheuer, Jens; Schaumburg, Martina; Lang, Elisabeth; Trautmann, Ellen; Zetterberg, Henrik; Taylor, Peggy; Friede, Tim; Trenkwalder, Claudia

    2016-07-12

    This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106). Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09-0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06-0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24-0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25-0.64), and RBD by PSG (d 0.37; CI 0.19-0.55) as well as VBM units of cortical gray matter (d -0.2; CI -0.3 to -0.09) and hippocampus (d -0.15; CI -0.27 to -0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d -0.19; CI -0.36 to -0.02) and 2 depression scales (Beck Depression Inventory d -0.18; CI -0.36 to 0; Montgomery-Åsberg Depression Rating Scale d -0.26; CI -0.47 to -0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants. Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression. © 2016 American Academy of Neurology.

  13. A predictive assessment of genetic correlations between traits in chickens using markers.

    PubMed

    Momen, Mehdi; Mehrgardi, Ahmad Ayatollahi; Sheikhy, Ayoub; Esmailizadeh, Ali; Fozi, Masood Asadi; Kranis, Andreas; Valente, Bruno D; Rosa, Guilherme J M; Gianola, Daniel

    2017-02-01

    Genomic selection has been successfully implemented in plant and animal breeding programs to shorten generation intervals and accelerate genetic progress per unit of time. In practice, genomic selection can be used to improve several correlated traits simultaneously via multiple-trait prediction, which exploits correlations between traits. However, few studies have explored multiple-trait genomic selection. Our aim was to infer genetic correlations between three traits measured in broiler chickens by exploring kinship matrices based on a linear combination of measures of pedigree and marker-based relatedness. A predictive assessment was used to gauge genetic correlations. A multivariate genomic best linear unbiased prediction model was designed to combine information from pedigree and genome-wide markers in order to assess genetic correlations between three complex traits in chickens, i.e. body weight at 35 days of age (BW), ultrasound area of breast meat (BM) and hen-house egg production (HHP). A dataset with 1351 birds that were genotyped with the 600 K Affymetrix platform was used. A kinship kernel (K) was constructed as K = λ G + (1 - λ)A, where A is the numerator relationship matrix, measuring pedigree-based relatedness, and G is a genomic relationship matrix. The weight (λ) assigned to each source of information varied over the grid λ = (0, 0.2, 0.4, 0.6, 0.8, 1). Maximum likelihood estimates of heritability and genetic correlations were obtained at each λ, and the "optimum" λ was determined using cross-validation. Estimates of genetic correlations were affected by the weight placed on the source of information used to build K. For example, the genetic correlation between BW-HHP and BM-HHP changed markedly when λ varied from 0 (only A used for measuring relatedness) to 1 (only genomic information used). As λ increased, predictive correlations (correlation between observed phenotypes and predicted breeding values) increased and mean

  14. Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice.

    PubMed

    May, Randal; Riehl, Terrence E; Hunt, Clayton; Sureban, Sripathi M; Anant, Shrikant; Houchen, Courtney W

    2008-03-01

    In the gut, tumorigenesis arises from intestinal or colonic crypt stem cells. Currently, no definitive markers exist that reliably identify gut stem cells. Here, we used the putative stem cell marker doublecortin and CaM kinase-like-1 (DCAMKL-1) to examine radiation-induced stem cell apoptosis and adenomatous polyposis coli (APC)/multiple intestinal neoplasia (min) mice to determine the effects of APC mutation on DCAMKL-1 expression. Immunoreactive DCAMKL-1 staining was demonstrated in the intestinal stem cell zone. Furthermore, we observed apoptosis of the cells negative for DCAMKL-1 at 6 hours. We found DNA damage in all the cells in the crypt region, including the DCAMKL-1-positive cells. We also observed stem cell apoptosis and mitotic DCAMKL-1-expressing cells 24 hours after irradiation. Moreover, in APC/min mice, DCAMKL-1-expressing cells were negative for proliferating cell nuclear antigen and nuclear beta-catenin in normal-appearing intestine. However, beta-catenin was nuclear in DCAMKL-1-positive cells in adenomas. Thus, nuclear translocation of beta-catenin distinguishes normal and adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing novel chemotherapeutic agents.

  15. Molecular genetic characterization of lasquerella new industrial crop using DArTseq markers

    USDA-ARS?s Scientific Manuscript database

    DArTseq, a new SNP-based marker platform, was developed and used to analyze the genetic diversity of the US germplasm collection of lesquerella. Lesquerella is a new oilseed crop in the Brassica family found native in the American Southwest. The potential of the species as a domestic source of indu...

  16. Exploring Geochemical Markers of the Anthropocene in River Sediments: Southern New England

    NASA Astrophysics Data System (ADS)

    Tran, J.

    2015-12-01

    The sedimentary record of New England is complex. From glacial till to colonial land use to the industrial revolution, any sediment preserved is intertwined and muddled by humans. Recent studies support the idea that any anthropogenic markers in the sediment record are site specific. Southern New England is marked by a myriad of practices including farming, charcoal kilns, hatting, mill dams, and iron furnaces. While specific markers of the anthropocene have been identified, little work has been done to correlate and quantify these noted markers across multiple basins. Specifically, a combination of x-ray fluorescence (XRF), x-ray diffraction (XRD), and grain size analysis were done on sediment cores taken within Southern New England across various watersheds. We present a combination of geochemical analysis and detrital zircon geochronology in order identify and account for basin differences. This in turn results in a more comprehensive trans-basin understanding of the anthropocene in this region. We observe strong evidence that supports the idea of geochemical markers anthropocene which include an increase in Mercury and Lead content in the sediments. Additionally, in basins where mill dams are present we observe sediment records consistent with flood events and dam degradation. While still fairly novel and understudied, our results provide insight to the much often question topic of the anthropocene in relation to this particular region and the potential pitfalls of doing large scale anthropogenic dating.

  17. Analysis of the discriminative methods for diagnosis of benign and malignant solitary pulmonary nodules based on serum markers.

    PubMed

    Wang, Wanping; Liu, Mingyue; Wang, Jing; Tian, Rui; Dong, Junqiang; Liu, Qi; Zhao, Xianping; Wang, Yuanfang

    2014-01-01

    Screening indexes of tumor serum markers for benign and malignant solitary pulmonary nodules (SPNs) were analyzed to find the optimum method for diagnosis. Enzyme-linked immunosorbent assays, an automatic immune analyzer and radioimmunoassay methods were used to examine the levels of 8 serum markers in 164 SPN patients, and the sensitivity for differential diagnosis of malignant or benign SPN was compared for detection using a single plasma marker or a combination of markers. The results for serological indicators that closely relate to benign and malignant SPNs were screened using the Fisher discriminant analysis and a non-conditional logistic regression analysis method, respectively. The results were then verified by the k-means clustering analysis method. The sensitivity when using a combination of serum markers to detect SPN was higher than that using a single marker. By Fisher discriminant analysis, cytokeratin 19 fragments (CYFRA21-1), carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and breast cancer antigen (CA153), which relate to the benign and malignant SPNs, were screened. Through non-conditional logistic regression analysis, CYFRA21-1, SCC and CA153 were obtained. Using the k-means clustering analysis, the cophenetic correlation coefficient (0.940) obtained by the Fisher discriminant analysis was higher than that obtained with logistic regression analysis (0.875). This study indicated that the Fisher discriminant analysis functioned better in screening out serum markers to recognize the benign and malignant SPN. The combined detection of CYFRA21-1, CA125, SCC and CA153 is an effective way to distinguish benign and malignant SPN, and will find an important clinical application in the early diagnosis of SPN. © 2014 S. Karger GmbH, Freiburg.

  18. DNA typing of Pakistani cattle breeds Tharparkar and Red Sindhi by microsatellite markers.

    PubMed

    Azam, Amber; Babar, Masroor Ellahi; Firyal, Sehrish; Anjum, Aftab Ahmad; Akhtar, Nabeela; Asif, Muhammad; Hussain, Tanveer

    2012-02-01

    Microsatellite markers are used for any individual identity and breed characterization in animals that is an efficient and successful way of investigation. They are used for multiple purposes as genetic detectors including, rapid mutation rate, high level of polymorphism, and range of variety of microsatellite markers available. A panel of 19 microsatellite markers was developed for breed characterization in Tharparkar and Red Sindhi breeds of cattle in Pakistan. Forty four blood samples of cattle (each breed) were collected from Department of Livestock Management, Sindh Agriculture University, Tandojam, Tando Qaiser, Tharparkar Cattle Farm Nabi sar Road, Umer Kot, Sindh, and Govt. Red Sindhi Cattle Breeding Farm, Tando Muhammad Khan Pakistan. Breed characterization was 100% successful. Average PIC, He and Power of Exclusion values were found to be 0.91, 0.62 and 13.28, respectively. Pattern of allelic frequencies of most of the microsatellite markers were clearly distinct between two breeds. As a result of present study a reliable, efficient and very informative panel of microsatellite markers was successfully developed which was capable to interpret individual identity, forensic cases and breed characterization in cattle. This facility is ready to be provided to local cattle breeder at commercial level for DNA testing of cattle. This study will also be highly helpful for breed conservation of cattle. In addition this study can also become a basis to open up new disciplines of animal forensics in Pakistan.

  19. Multiple metals predict prolactin and thyrotropin (TSH) levels in men

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meeker, John D., E-mail: meekerj@umich.edu; Rossano, Mary G.; Protas, Bridget

    2009-10-15

    Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated withmore » arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications.« less

  20. DOMINO: development of informative molecular markers for phylogenetic and genome-wide population genetic studies in non-model organisms.

    PubMed

    Frías-López, Cristina; Sánchez-Herrero, José F; Guirao-Rico, Sara; Mora, Elisa; Arnedo, Miquel A; Sánchez-Gracia, Alejandro; Rozas, Julio

    2016-12-15

    The development of molecular markers is one of the most important challenges in phylogenetic and genome wide population genetics studies, especially in studies with non-model organisms. A highly promising approach for obtaining suitable markers is the utilization of genomic partitioning strategies for the simultaneous discovery and genotyping of a large number of markers. Unfortunately, not all markers obtained from these strategies provide enough information for solving multiple evolutionary questions at a reasonable taxonomic resolution. We have developed Development Of Molecular markers In Non-model Organisms (DOMINO), a bioinformatics tool for informative marker development from both next generation sequencing (NGS) data and pre-computed sequence alignments. The application implements popular NGS tools with new utilities in a highly versatile pipeline specifically designed to discover or select personalized markers at different levels of taxonomic resolution. These markers can be directly used to study the taxa surveyed for their design, utilized for further downstream PCR amplification in a broader set taxonomic scope, or exploited as suitable templates to bait design for target DNA enrichment techniques. We conducted an exhaustive evaluation of the performance of DOMINO via computer simulations and illustrate its utility to find informative markers in an empirical dataset. DOMINO is freely available from www.ub.edu/softevol/domino CONTACT: elsanchez@ub.edu or jrozas@ub.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Simple sequence repeat marker loci discovery using SSR primer.

    PubMed

    Robinson, Andrew J; Love, Christopher G; Batley, Jacqueline; Barker, Gary; Edwards, David

    2004-06-12

    Simple sequence repeats (SSRs) have become important molecular markers for a broad range of applications, such as genome mapping and characterization, phenotype mapping, marker assisted selection of crop plants and a range of molecular ecology and diversity studies. With the increase in the availability of DNA sequence information, an automated process to identify and design PCR primers for amplification of SSR loci would be a useful tool in plant breeding programs. We report an application that integrates SPUTNIK, an SSR repeat finder, with Primer3, a PCR primer design program, into one pipeline tool, SSR Primer. On submission of multiple FASTA formatted sequences, the script screens each sequence for SSRs using SPUTNIK. The results are parsed to Primer3 for locus-specific primer design. The script makes use of a Web-based interface, enabling remote use. This program has been written in PERL and is freely available for non-commercial users by request from the authors. The Web-based version may be accessed at http://hornbill.cspp.latrobe.edu.au/

  2. Bone metabolism markers and vitamin D in adolescent cyclists.

    PubMed

    Olmedillas, Hugo; Gonzalez-Agüero, Alejandro; Rapún-López, Marta; Gracia-Marco, Luis; Gomez-Cabello, Alba; Pradas de la Fuente, Francisco; Moreno, Luís A; Casajús, José A; Vicente-Rodríguez, Germán

    2018-02-03

    This study aimed to describe bone metabolic activity in adolescent competitive cyclists compared to age-matched controls. The main result is that younger subjects present a higher bone turnover than the older ones. Moreover, cyclists under the age of 17 have higher scores on all markers than age-matched controls. The purpose of this study was to describe bone metabolic activity in adolescent competitive cyclists compared to age-matched controls. Twenty-two male adolescent cyclists between 14 and 20 years (y) and 20 age-matched controls participated in this study. Serum osteocalcin (OC), aminoterminal propeptide of type I procollagen (PINP), and β-isomerized C-telopeptides (β-CTX) were analyzed by electrochemiluminescence immunoassay (ECLIA); plasma 25 hydroxyvitamin D [25(OH)D] was analyzed by enzyme-linked immunosorbent assay (ELISA). Analysis of variance revealed no significant differences in bone metabolism markers and vitamin D between cyclists and controls. Cyclists over 17 y had a significantly lower concentration in bone formation and resorption biochemical markers compared to cyclists under 17 y (all P < 0.05). Moreover, controls over 17 y presented lower concentration for PINP (P < 0.05) compared to their peers under 17 y. Comparisons between cyclists and controls under 17 y revealed higher concentrations of OC and PINP (P < 0.05) in cyclists. Group interaction by age was found for OC, PINP, and β-CTX (P < 0.01). Cyclists over 17 y had higher concentrations of [25(OH)D] (P < 0.05) than age-matched controls. The present results support the idea that cycling during adolescence may be associated to a decrease in bone turnover that may affect bone health later in life.

  3. Are bone turnover markers capable of predicting callus consolidation during bone healing?

    PubMed

    Klein, P; Bail, H J; Schell, H; Michel, R; Amthauer, H; Bragulla, H; Duda, G N

    2004-07-01

    The aim of this study was to determine the ability of the following bone turnover markers to monitor the course of callus consolidation during bone healing: Carboxy-terminal propeptide of procollagen type I (PICP), skeletal alkaline phosphatase (sALP), and amino-terminal propeptide of type III procollagen (PIlINP). Since interfragmentary movements have been proven to possess the ability to document the progression of bone healing in experimental studies, correlations between bone turnover markers and interfragmentary movements in vivo were investigated. Therefore, two different types of osteosyntheses representing different mechanical situations at the fracture site were compared in an ovine osteotomy model. Blood samples were taken preoperatively and postoperatively in weekly intervals over a nine-week healing period. At the same intervals, interfragmentary movements were measured in all sheep. After nine weeks, animals were sacrificed and the tibiae were evaluated both mechanically and histologically. Wide interindividual ranges were observed for all bone turnover markers. The systemic PICP level did not increase with callus consolidation. The bone-healing model seemed to influence the systemic level of PIIINP and sALP but no general correlation between bone turnover markers and interfragmentary movements could be detected. No differences between the different types of osteosyntheses and thus the different mechanical situations were observed. All analyzed markers failed as general predictors for the course of callus consolidation during bone healing.

  4. Real-time airborne particle analyzer

    DOEpatents

    Reilly, Peter T.A.

    2012-10-16

    An aerosol particle analyzer includes a laser ablation chamber, a gas-filled conduit, and a mass spectrometer. The laser ablation chamber can be operated at a low pressure, which can be from 0.1 mTorr to 30 mTorr. The ablated ions are transferred into a gas-filled conduit. The gas-filled conduit reduces the electrical charge and the speed of ablated ions as they collide and mix with buffer gases in the gas-filled conduit. Preferably, the gas filled-conduit includes an electromagnetic multipole structure that collimates the nascent ions into a beam, which is guided into the mass spectrometer. Because the gas-filled conduit allows storage of vast quantities of the ions from the ablated particles, the ions from a single ablated particle can be analyzed multiple times and by a variety of techniques to supply statistically meaningful analysis of composition and isotope ratios.

  5. Utility of MRI versus tumor markers for post-treatment surveillance of marker-positive CNS germ cell tumors.

    PubMed

    Cheung, Victoria; Segal, Devorah; Gardner, Sharon L; Zagzag, David; Wisoff, Jeffrey H; Allen, Jeffrey C; Karajannis, Matthias A

    2016-09-01

    Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.

  6. A set of autosomal multiple InDel markers for forensic application and population genetic analysis in the Chinese Xinjiang Hui group.

    PubMed

    Xie, Tong; Guo, Yuxin; Chen, Ling; Fang, Yating; Tai, Yunchun; Zhou, Yongsong; Qiu, Pingming; Zhu, Bofeng

    2018-07-01

    In recent years, insertion/deletion (InDel) markers have become a promising and useful supporting tool in forensic identification cases and biogeographic research field. In this study, 30 InDel loci were explored to reveal the genetic diversities and genetic relationships between Chinese Xinjiang Hui group and the 25 previously reported populations using various biostatistics methods such as forensic statistical parameter analysis, phylogenetic reconstruction, multi-dimensional scaling, principal component analysis, and STRUCTURE analysis. No deviations from Hardy-Weinberg equilibrium tests were found at all 30 loci in the Chinese Xinjiang Hui group. The observed heterozygosity and expected heterozygosity ranged from 0.1971 (HLD118) to 0.5092 (HLD92), 0.2222 (HLD118) to 0.5000 (HLD6), respectively. The cumulative probability of exclusion and combined power of discrimination were 0.988849 and 0.99999999999378, respectively, which indicated that these 30 loci could be qualified for personal identification and used as complementary genetic markers for paternity tests in forensic cases. The results of present research based on the different methods of population genetic analysis revealed that the Chinese Xinjiang Hui group had close relationships with most Chinese groups, especially Han populations. In spite of this, for a better understanding of genetic background of the Chinese Xinjiang Hui group, more molecular genetic markers such as ancestry informative markers, single nucleotide polymorphisms (SNPs), and copy number variations will be conducted in future studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Evaluation of Bovine Feces-Associated Microbial Source Tracking Markers and Their Correlations with Fecal Indicators and Zoonotic Pathogens in a Brisbane, Australia, Reservoir

    PubMed Central

    Sritharan, T.; Palmer, A.; Sidhu, J. P. S.; Toze, S.

    2013-01-01

    This study was aimed at evaluating the host specificity and host sensitivity of two bovine feces-associated bacterial (BacCow-UCD and cowM3) and one viral [bovine adenovirus (B-AVs)] microbial source tracking (MST) markers by screening 130 fecal and wastewater samples from 10 target and nontarget host groups in southeast Queensland, Australia. In addition, 36 water samples were collected from a reservoir and tested for the occurrence of all three bovine feces-associated markers along with fecal indicator bacteria (FIB), Campylobacter spp., Escherichia coli O157, and Salmonella spp. The overall host specificity values of the BacCow-UCD, cowM3, and B-AVs markers to differentiate between bovine and other nontarget host groups were 0.66, 0.88, and 1.00, respectively (maximum value of 1.00). The overall host sensitivity values of these markers, however, in composite bovine wastewater and individual bovine fecal DNA samples were 0.93, 0.90, and 0.60, respectively (maximum value of 1.00). Among the 36 water samples tested, 56%, 22%, and 6% samples were PCR positive for the BacCow-UCD, cowM3, and B-AVs markers, respectively. Among the 36 samples tested, 50% and 14% samples were PCR positive for the Campylobacter 16S rRNA and E. coli O157 rfbE genes, respectively. Based on the results, we recommend that multiple bovine feces-associated markers be used if possible for bovine fecal pollution tracking. Nonetheless, the presence of the multiple bovine feces-associated markers along with the presence of potential zoonotic pathogens indicates bovine fecal pollution in the reservoir water samples. Further research is required to understand the decay rates of these markers in relation to FIB and zoonotic pathogens. PMID:23417003

  8. Analyzing Virtual Physics Simulations with Tracker

    NASA Astrophysics Data System (ADS)

    Claessens, Tom

    2017-12-01

    In the physics teaching community, Tracker is well known as a user-friendly open source video analysis software, authored by Douglas Brown. With this tool, the user can trace markers indicated on a video or on stroboscopic photos and perform kinematic analyses. Tracker also includes a data modeling tool that allows one to fit some theoretical equations of motion onto experimentally obtained data. In the field of particle mechanics, Tracker has been effectively used for learning and teaching about projectile motion, "toss up" and free-fall vertical motion, and to explain the principle of mechanical energy conservation. Also, Tracker has been successfully used in rigid body mechanics to interpret the results of experiments with rolling/slipping cylinders and moving rods. In this work, I propose an original method in which Tracker is used to analyze virtual computer simulations created with a physics-based motion solver, instead of analyzing video recording or stroboscopic photos. This could be an interesting approach to study kinematics and dynamics problems in physics education, in particular when there is no or limited access to physical labs. I demonstrate the working method with a typical (but quite challenging) problem in classical mechanics: a slipping/rolling cylinder on a rough surface.

  9. Multiple markers and multiple individuals refine true seal phylogeny and bring molecules and morphology back in line.

    PubMed

    Fulton, Tara Lynn; Strobeck, Curtis

    2010-04-07

    Despite decades of study, some aspects of Phocidae (Pinnipedia, Carnivora) phylogeny still remain unresolved. Using the largest novel dataset to date, including all extant phocids and comprising 15 nuclear and 13 mitochondrial genes, we illustrate the utility of including multiple individuals per species in resolving rapid radiations, and provide new insight into phocid phylogeny. In line with longstanding morphological views, Pusa is recovered as monophyletic for the first time with genetic data. The data are also used to explore the relationship between genetic distance and taxonomic rank. Intraspecific sampling also highlights the discrepancy between molecular and morphological rates of evolution within Phocidae.

  10. Leaf margin phenotype-specific restriction-site-associated DNA-derived markers for pineapple (Ananas comosus L.)

    PubMed Central

    Urasaki, Naoya; Goeku, Satoko; Kaneshima, Risa; Takamine, Tomonori; Tarora, Kazuhiko; Takeuchi, Makoto; Moromizato, Chie; Yonamine, Kaname; Hosaka, Fumiko; Terakami, Shingo; Matsumura, Hideo; Yamamoto, Toshiya; Shoda, Moriyuki

    2015-01-01

    To explore genome-wide DNA polymorphisms and identify DNA markers for leaf margin phenotypes, a restriction-site-associated DNA sequencing analysis was employed to analyze three bulked DNAs of F1 progeny from a cross between a ‘piping-leaf-type’ cultivar, ‘Yugafu’, and a ‘spiny-tip-leaf-type’ variety, ‘Yonekura’. The parents were both Ananas comosus var. comosus. From the analysis, piping-leaf and spiny-tip-leaf gene-specific restriction-site-associated DNA sequencing tags were obtained and designated as PLSTs and STLSTs, respectively. The five PLSTs and two STSLTs were successfully converted to cleaved amplified polymorphic sequence (CAPS) or simple sequence repeat (SSR) markers using the sequence differences between alleles. Based on the genotyping of the F1 with two SSR and three CAPS markers, the five PLST markers were mapped in the vicinity of the P locus, with the closest marker, PLST1_SSR, being located 1.5 cM from the P locus. The two CAPS markers from STLST1 and STLST3 perfectly assessed the ‘spiny-leaf type’ as homozygotes of the recessive s allele of the S gene. The recombination value between the S locus and STLST loci was 2.4, and STLSTs were located 2.2 cM from the S locus. SSR and CAPS markers are applicable to marker-assisted selection of leaf margin phenotypes in pineapple breeding. PMID:26175625

  11. Development of cost-effective Hordeum chilense DNA markers: molecular aids for marker-assisted cereal breeding.

    PubMed

    Hernández, P; Dorado, G; Ramírez, M C; Laurie, D A; Snape, J W; Martín, A

    2003-01-01

    Hordeum chilense is a potential source of useful genes for wheat breeding. The use of this wild species to increase genetic variation in wheat will be greatly facilitated by marker-assisted introgression. In recent years, the search for the most suitable DNA marker system for tagging H. chilense genomic regions in a wheat background has lead to the development of RAPD and SCAR markers for this species. RAPDs represent an easy way of quickly generating suitable introgression markers, but their use is limited in heterogeneous wheat genetic backgrounds. SCARs are more specific assays, suitable for automatation or multiplexing. Direct sequencing of RAPD products is a cost-effective approach that reduces labour and costs for SCAR development. The use of SSR and STS primers originally developed for wheat and barley are additional sources of genetic markers. Practical applications of the different marker approaches for obtaining derived introgression products are described.

  12. A new series of yeast shuttle vectors for the recovery and identification of multiple plasmids from Saccharomyces cerevisiae.

    PubMed

    Frazer, LilyAnn Novak; O'Keefe, Raymond T

    2007-09-01

    The availability of Saccharomyces cerevisiae yeast strains with multiple auxotrophic markers allows the stable introduction and selection of more than one yeast shuttle vector containing marker genes that complement the auxotrophic markers. In certain experimental situations there is a need to recover more than one shuttle vector from yeast. To facilitate the recovery and identification of multiple plasmids from S. cerevisiae, we have constructed a series of plasmids based on the pRS series of yeast shuttle vectors. Bacterial antibiotic resistance genes to chloramphenicol, kanamycin and zeocin have been combined with the yeast centromere sequence (CEN6), the autonomously replicating sequence (ARSH4) and one of the four yeast selectable marker genes (HIS3, TRP1, LEU2 or URA3) from the pRS series of vectors. The 12 plasmids produced differ in antibiotic resistance and yeast marker gene within the backbone of the multipurpose plasmid pBluescript II. The newly constructed vectors show similar mitotic stability to the original pRS vectors. In combination with the ampicillin-resistant pRS series of yeast shuttle vectors, these plasmids now allow the recovery and identification in bacteria of up to four different vectors from S. cerevisiae. Copyright (c) 2007 John Wiley & Sons, Ltd.

  13. Comparison of LUMIPULSE(®) G1200 With Kryptor and Modular E170 for the Measurement of Seven Tumor Markers.

    PubMed

    Marlet, Julien; Bernard, Maguy

    2016-01-01

    Tumor marker measurements are becoming essential for prognosis and follow-up of patients in oncology. In this context, we aimed to compare a new analyzer, Lumipulse(®) G1200 (Fujirebio group, distributed in Europe by the Innogenetics group) with Kryptor(®) (Thermo Fisher Scientific B.R.A.H.M.S, Asnières, France) and Modular(®) Elecsys E170 (Roche Diagnostics, Meylan, France) for the measurement of seven tumor markers: PSA, AFP, CEA, CA 15-3, CA 125, CA 19-9, and Cyfra 21-1. A total of 471 serum samples from patients with elevated tumor markers and 100 serum from healthy patients were analyzed with Lumipulse(®) G1200 and either Kryptor(®) (for AFP) or Modular(®) (for the six other markers). The good precision of Lumipulse(®) G1200 assays was confirmed with CVs < 2.5% and < 5.0%, obtained, respectively, for within-run imprecision and intermediate imprecision (except for Cyfra 21-1: CV < 13%). For all markers, Lumipulse results were well correlated with Modular or Kryptor results (r ≥ 0.94). Concordance of results interpretation was > 95% and tumor marker kinetics were all similar. We confirmed the analytical performances of Lumipulse(®) tumor marker assays except for the CYFRA 21-1 assay for which performances were poor in this study. We noticed a few discrepancies for the CEA assay. Besides, values obtained for CA 19-9 were higher with Lumipulse leading to a bias (slope = 1.5). But for the four other tumor markers assays (PSA, AFP, CA 125, CA 15-3), the results were directly transferable between Lumipulse and Kryptor or Modular, thus facilitating an eventual substitution of one system by another. © 2014 Wiley Periodicals, Inc.

  14. Genetic diversity of the Arctic fox using SRAP markers.

    PubMed

    Zhang, M; Bai, X J

    2013-12-04

    Sequence-related amplified polymorphism (SRAP) is a recently developed molecular marker technique that is stable, simple, reliable, and achieves moderate to high numbers of codominant markers. This study is the first to apply SRAP markers in a mammal, namely the Arctic fox. In order to investigate the genetic diversity of the Arctic fox and to provide a reference for use of its germplasm, we analyzed 7 populations of Arctic fox by SRAP. The genetic similarity coefficient, genetic distance, proportion of polymorphic loci, total genetic diversity (Ht), genetic diversity within populations (Hs), and genetic differentiation (Gst) were calculated using the Popgene software package. The results indicated abundant genetic diversity among the different populations of Arctic fox studied in China. The genetic similarity coefficient ranged from 0.1694 to 0.0417, genetic distance ranged from 0.8442 to 0.9592, and the proportion of polymorphic loci was smallest in the TS group. Genetic diversity ranged from 0.2535 to 0.3791, Ht was 0.3770, Hs was 0.3158, Gst was 0.1624, and gene flow (Nm) was estimated at 2.5790. Thus, a high level of genetic diversity and many genetic relationships were found in the populations of Arctic fox evaluated in this study.

  15. Validation of a combined autosomal/Y-chromosomal STR approach for analyzing typical biological stains in sexual-assault cases.

    PubMed

    Purps, Josephine; Geppert, Maria; Nagy, Marion; Roewer, Lutz

    2015-11-01

    DNA testing is an established part of the investigation and prosecution of sexual assault. The primary purpose of DNA evidence is to identify a suspect and/or to demonstrate sexual contact. However, due to highly uneven proportions of female and male DNA in typical stains, routine autosomal analysis often fails to detect the DNA of the assailant. To evaluate the forensic efficiency of the combined application of autosomal and Y-chromosomal short tandem repeat (STR) markers, we present a large retrospective casework study of probative evidence collected in sexual-assault cases. We investigated up to 39 STR markers by testing combinations of the 16-locus NGMSElect kit with both the 23-locus PowerPlex Y23 and the 17-locus Yfiler kit. Using this dual approach we analyzed DNA extracts from 2077 biological stains collected in 287 cases over 30 months. To assess the outcome of the combined approach in comparison to stand-alone autosomal analysis we evaluated informative DNA profiles. Our investigation revealed that Y-STR analysis added up to 21% additional, highly informative (complete, single-source) profiles to the set of reportable autosomal STR profiles for typical stains collected in sexual-assault cases. Detection of multiple male contributors was approximately three times more likely with Y-chromosomal profiling than with autosomal STR profiling. In summary, 1/10 cases would have remained inconclusive (and could have been dismissed) if Y-STR analysis had been omitted from DNA profiling in sexual-assault cases. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  16. Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

    PubMed Central

    Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

    2015-01-01

    Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

  17. Hemostatic Abnormalities in Multiple Myeloma Patients

    PubMed Central

    Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

    2018-01-01

    Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

  18. Explorative Function in Williams Syndrome Analyzed through a Large-Scale Task with Multiple Rewards

    ERIC Educational Resources Information Center

    Foti, F.; Petrosini, L.; Cutuli, D.; Menghini, D.; Chiarotti, F.; Vicari, S.; Mandolesi, L.

    2011-01-01

    This study aimed to evaluate spatial function in subjects with Williams syndrome (WS) by using a large-scale task with multiple rewards and comparing the spatial abilities of WS subjects with those of mental age-matched control children. In the present spatial task, WS participants had to explore an open space to search nine rewards placed in…

  19. Multispecies Adulteration Detection of Camellia Oil by Chemical Markers.

    PubMed

    Dou, Xinjing; Mao, Jin; Zhang, Liangxiao; Xie, Huali; Chen, Lin; Yu, Li; Ma, Fei; Wang, Xiupin; Zhang, Qi; Li, Peiwu

    2018-01-25

    Adulteration of edible oils has attracted attention from more researchers and consumers in recent years. Complex multispecies adulteration is a commonly used strategy to mask the traditional adulteration detection methods. Most of the researchers were only concerned about single targeted adulterants, however, it was difficult to identify complex multispecies adulteration or untargeted adulterants. To detect adulteration of edible oil, identification of characteristic markers of adulterants was proposed to be an effective method, which could provide a solution for multispecies adulteration detection. In this study, a simple method of multispecies adulteration detection for camellia oil (adulterated with soybean oil, peanut oil, rapeseed oil) was developed by quantifying chemical markers including four isoflavones, trans-resveratrol and sinapic acid, which used liquid chromatography tandem mass spectrometry (LC-MS/MS) combined with solid phase extraction (SPE). In commercial camellia oil, only two of them were detected of daidzin with the average content of 0.06 ng/g while other markers were absent. The developed method was highly sensitive as the limits of detection (LODs) ranged from 0.02 ng/mL to 0.16 ng/mL and the mean recoveries ranged from 79.7% to 113.5%, indicating that this method was reliable to detect potential characteristic markers in edible oils. Six target compounds for pure camellia oils, soybean oils, peanut oils and rapeseed oils had been analyzed to get the results. The validation results indicated that this simple and rapid method was successfully employed to determine multispecies adulteration of camellia oil adulterated with soybean, peanut and rapeseed oils.

  20. Value of 18F-FDG PET/CT Combined With Tumor Markers in the Evaluation of Ascites.

    PubMed

    Han, Na; Sun, Xun; Qin, Chunxia; Hassan Bakari, Khamis; Wu, Zhijian; Zhang, Yongxue; Lan, Xiaoli

    2018-05-01

    The purpose of this study is to investigate the value of 18 F-FDG PET/CT combined with assessment of tumor markers in serum or ascites for the diagnosing and determining the prognosis of benign and malignant ascites. Patients with ascites of unknown cause who underwent evaluation with FDG PET/CT were included in this retrospective study. The maximum standardized uptake value (SUV max ) and levels of the tumor markers carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen (CEA) in serum and ascites were recorded. The diagnostic values of FDG PET/CT, CEA and CA-125 levels in serum or ascites, and the combination of imaging plus tumor marker assessment were evaluated. Factors that were predictive of survival were also analyzed. A total of 177 patients were included. Malignant ascites was eventually diagnosed in 104 patients, and benign ascites was diagnosed in the remaining 73 patients. With the use of FDG PET/CT, 44 patients (42.3%) were found to have primary tumors. The sensitivity, specificity, and accuracy of FDG PET/CT were 92.3%, 83.6%, and 88.7%, respectively. CA-125 levels in serum and ascites showed much better sensitivity than did CEA levels, but they showed significantly lower specificity. If the combination of tumor markers and FDG PET/CT was analyzed, the sensitivity, specificity, and accuracy of tumor markers in serum were 96.6%, 78.1%, and 88.7%, and those of tumor markers in ascites were 97.7%, 80.0%, and 90.4%, respectively. Sex may be an important factor affecting survival time (hazard ratio, 0.471; p = 0.004), but age, CEA level, and FDG PET/CT findings could not predict survival. FDG PET/CT combined with assessment of tumor markers, especially CEA, increased the efficacy of diagnosis of ascites of unknown causes. Male sex conferred a poorer prognosis, whereas age, CEA level, and FDG uptake had no predictive significance in patients with malignant ascites.

  1. In-traffic air pollution exposure and CC16, blood coagulation, and inflammation markers in healthy adults.

    PubMed

    Zuurbier, Moniek; Hoek, Gerard; Oldenwening, Marieke; Meliefste, Kees; Krop, Esmeralda; van den Hazel, Peter; Brunekreef, Bert

    2011-10-01

    Exposure to traffic-related air pollution is a risk factor for cardiovascular events, probably involving mechanisms of inflammation and coagulation. Little is known about effects of the short exposures encountered while participating in traffic. The objective of the study was to examine effects of exposure of commuters to air pollution on cardiovascular biomarkers. Thirty-four healthy adult volunteers commuted for 2 hr by bus, car, or bicycle during the morning rush hour. During the commute, exposure to particle number, particulate matter (PM) ≤ 2.5 µm in aerodynamic diameter (PM2.5), PM ≤ 10 µm in diameter (PM10), and soot was measured. We estimated inhaled doses based on heart rate monitoring. Shortly before exposure and 6 hr after exposure, blood samples were taken and analyzed for CC16 (Clara cell protein 16), blood cell count, coagulation markers, and inflammation markers. Between June 2007 and June 2008, 352 pre- and postexposure blood samples were collected on 47 test days. We used mixed models to analyze the associations between exposure and changes in health parameters. We observed no consistent associations between the air pollution exposures and doses and the various biomarkers that we investigated. Air pollution exposure during commuting was not consistently associated with acute changes in inflammation markers, blood cell counts, or blood coagulation markers.

  2. A Review of Microsatellite Markers and Their Applications in Rice Breeding Programs to Improve Blast Disease Resistance

    PubMed Central

    Miah, Gous; Rafii, Mohd Y.; Ismail, Mohd R.; Puteh, Adam B.; Rahim, Harun A.; Islam, Kh. Nurul; Latif, Mohammad Abdul

    2013-01-01

    Over the last few decades, the use of molecular markers has played an increasing role in rice breeding and genetics. Of the different types of molecular markers, microsatellites have been utilized most extensively, because they can be readily amplified by PCR and the large amount of allelic variation at each locus. Microsatellites are also known as simple sequence repeats (SSR), and they are typically composed of 1–6 nucleotide repeats. These markers are abundant, distributed throughout the genome and are highly polymorphic compared with other genetic markers, as well as being species-specific and co-dominant. For these reasons, they have become increasingly important genetic markers in rice breeding programs. The evolution of new biotypes of pests and diseases as well as the pressures of climate change pose serious challenges to rice breeders, who would like to increase rice production by introducing resistance to multiple biotic and abiotic stresses. Recent advances in rice genomics have now made it possible to identify and map a number of genes through linkage to existing DNA markers. Among the more noteworthy examples of genes that have been tightly linked to molecular markers in rice are those that confer resistance or tolerance to blast. Therefore, in combination with conventional breeding approaches, marker-assisted selection (MAS) can be used to monitor the presence or lack of these genes in breeding populations. For example, marker-assisted backcross breeding has been used to integrate important genes with significant biological effects into a number of commonly grown rice varieties. The use of cost-effective, finely mapped microsatellite markers and MAS strategies should provide opportunities for breeders to develop high-yield, blast resistance rice cultivars. The aim of this review is to summarize the current knowledge concerning the linkage of microsatellite markers to rice blast resistance genes, as well as to explore the use of MAS in rice breeding

  3. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro

    PubMed Central

    Chhor, Vibol; Le Charpentier, Tifenn; Lebon, Sophie; Oré, Marie-Virgine; Celador, Idoia Lara; Josserand, Julien; Degos, Vincent; Jacotot, Etienne; Hagberg, Henrik; Sävman, Karin; Mallard, Carina; Gressens, Pierre; Fleiss, Bobbi

    2013-01-01

    Microglia mediate multiple facets of neuroinflammation, including cytotoxicity, repair, regeneration, and immunosuppression due to their ability to acquire diverse activation states, or phenotypes. Modulation of microglial phenotype is an appealing neurotherapeutic strategy but a comprehensive study of classical and more novel microglial phenotypic markers in vitro is lacking. The aim of this study was to outline the temporal expression of a battery of phenotype markers from polarised microglia to generate an in vitro tool for screening the immunomodulatory potential of novel compounds. We characterised expression of thirty-one macrophage/microglial phenotype markers in primary microglia over time (4, 12, 36, and 72 h), using RT-qPCR or multiplex protein assay. Firstly, we selected Interleukin-4 (IL-4) and lipopolysaccharide (LPS) as the strongest M1–M2 polarising stimuli, from six stimuli tested. At each time point, markers useful to identify that microglia were M1 included iNOS, Cox-2 and IL-6 and a loss of M2a markers. Markers useful for quantifying M2b-immunomodulatory microglia included, increased IL-1RA and SOCS3 and for M2a-repair and regeneration, included increased arginase-1, and a loss of the M1 and M2b markers were discriminatory. Additional markers were regulated at fewer time points, but are still likely important to monitor when assessing the immunomodulatory potential of novel therapies. Further, to facilitate identification of how novel immunomodulatory treatments alter the functional affects of microglia, we characterised how the soluble products from polarised microglia affected the type and rate of neuronal death; M1/2b induced increasing and M2a-induced decreasing neuronal loss. We also assessed any effects of prior activation state, to provide a way to identify how a novel compound may alter phenotype depending on the stage of injury/insult progression. We identified generally that a prior M1/2b reduced the ability of microglia to switch to

  4. Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.

    PubMed

    Yaron, Y; Cherry, M; Kramer, R L; O'Brien, J E; Hallak, M; Johnson, M P; Evans, M I

    1999-10-01

    We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.

  5. Four small supernumerary marker chromosomes derived from chromosomes 6, 8, 11 and 12 in a patient with minimal clinical abnormalities: a case report

    PubMed Central

    2010-01-01

    Introduction Small supernumerary marker chromosomes are still a problem in cytogenetic diagnostic and genetic counseling. This holds especially true for the rare cases with multiple small supernumerary marker chromosomes. Most such cases are reported to be clinically severely affected due to the chromosomal imbalances induced by the presence of small supernumerary marker chromosomes. Here we report the first case of a patient having four different small supernumerary marker chromosomes which, apart from slight developmental retardation in youth and non-malignant hyperpigmentation, presented no other clinical signs. Case presentation Our patient was a 30-year-old Caucasian man, delivered by caesarean section because of macrosomy. At birth he presented with bilateral cryptorchidism but no other birth defects. At age of around two years he showed psychomotor delay and a bilateral convergent strabismus. Later he had slight learning difficulties, with normal social behavior and now lives an independent life as an adult. Apart from hypogenitalism, he has multiple hyperpigmented nevi all over his body, short feet with pes cavus and claw toes. At age of 30 years, cytogenetic and molecular cytogenetic analysis revealed a karyotype of 50,XY,+min(6)(:p11.1-> q11.1:),+min(8)(:p11.1->q11.1:),+min(11)(:p11.11->q11:),+min(12)(:p11.2~12->q10:), leading overall to a small partial trisomy in 12p11.1~12.1. Conclusions Including this case, four single case reports are available in the literature with a karyotype 50,XN,+4mar. For prenatally detected multiple small supernumerary marker chromosomes in particular we learn from this case that such a cytogenetic condition may be correlated with a positive clinical outcome. PMID:20682055

  6. Exploiting Multiple Levels of Parallelism in Sparse Matrix-Matrix Multiplication

    DOE PAGES

    Azad, Ariful; Ballard, Grey; Buluc, Aydin; ...

    2016-11-08

    Sparse matrix-matrix multiplication (or SpGEMM) is a key primitive for many high-performance graph algorithms as well as for some linear solvers, such as algebraic multigrid. The scaling of existing parallel implementations of SpGEMM is heavily bound by communication. Even though 3D (or 2.5D) algorithms have been proposed and theoretically analyzed in the flat MPI model on Erdös-Rényi matrices, those algorithms had not been implemented in practice and their complexities had not been analyzed for the general case. In this work, we present the first implementation of the 3D SpGEMM formulation that exploits multiple (intranode and internode) levels of parallelism, achievingmore » significant speedups over the state-of-the-art publicly available codes at all levels of concurrencies. We extensively evaluate our implementation and identify bottlenecks that should be subject to further research.« less

  7. QTL mapping for fruit quality in Citrus using DArTseq markers.

    PubMed

    Curtolo, Maiara; Cristofani-Yaly, Mariângela; Gazaffi, Rodrigo; Takita, Marco Aurélio; Figueira, Antonio; Machado, Marcos Antonio

    2017-04-12

    Citrus breeding programs have many limitations associated with the species biology and physiology, requiring the incorporation of new biotechnological tools to provide new breeding possibilities. Diversity Arrays Technology (DArT) markers, combined with next-generation sequencing, have wide applicability in the construction of high-resolution genetic maps and in quantitative trait locus (QTL) mapping. This study aimed to construct an integrated genetic map using full-sib progeny derived from Murcott tangor and Pera sweet orange and DArTseq™ molecular markers and to perform QTL mapping of twelve fruit quality traits. A controlled Murcott x Pera crossing was conducted at the Citrus Germplasm Repository at the Sylvio Moreira Citrus Centre of the Agronomic Institute (IAC) located in Cordeirópolis, SP, in 1997. In 2012, 278 F 1 individuals out of a family of 312 confirmed hybrid individuals were analyzed for fruit traits and genotyped using the DArTseq markers. Using OneMap software to obtain the integrated genetic map, we considered only the DArT loci that showed no segregation deviation. The likelihood ratio and the genomic information from the available Citrus sinensis L. Osbeck genome were used to determine the linkage groups (LGs). The resulting integrated map contained 661 markers in 13 LGs, with a genomic coverage of 2,774 cM and a mean density of 0.23 markers/cM. The groups were assigned to the nine Citrus haploid chromosomes; however, some of the chromosomes were represented by two LGs due the lack of information for a single integration, as in cases where markers segregated in a 3:1 fashion. A total of 19 QTLs were identified through composite interval mapping (CIM) of the 12 analyzed fruit characteristics: fruit diameter (cm), height (cm), height/diameter ratio, weight (g), rind thickness (cm), segments per fruit, total soluble solids (TSS, %), total titratable acidity (TTA, %), juice content (%), number of seeds, TSS/TTA ratio and number of fruits per

  8. Biological pathways, candidate genes and molecular markers associated with quality-of-life domains: an update

    PubMed Central

    Sprangers, Mirjam A.G.; Thong, Melissa S.Y.; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A.; Singh, Jasvinder A.; Sloan, Jeff A.

    2014-01-01

    Background There is compelling evidence of a genetic foundation of patient-reported QOL. Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. Objectives The objective is to provide an updated overview of the biological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. Methods We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Results Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Conclusions Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL. PMID:24604075

  9. Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update.

    PubMed

    Sprangers, Mirjam A G; Thong, Melissa S Y; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A; Singh, Jasvinder A; Sloan, Jeff A

    2014-09-01

    There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL.

  10. Selecting soybean resistant to the cyst nematode Heterodera glycines using simple sequence repeat (microssatellite) markers.

    PubMed

    Espindola, S M C G; Hamawaki, O T; Oliveira, A P; Hamawaki, C D L; Hamawaki, R L; Takahashi, L M

    2016-03-11

    The soybean cyst nematode (SCN) is a major cause of soybean yield reduction. The objective of this study was to evaluate the efficiency of marker-assisted selection to identify genotypes resistant to SCN race 3 infection, using Sat_168 and Sat-141 resistance quantitative trait loci. The experiment was carried out under greenhouse conditions, using soybean populations originated from crosses between susceptible and resistant parent stock: CD-201 (susceptible) and Foster IAC (resistant), Conquista (susceptible) and S83-30 (resistant), La-Suprema (susceptible) and S57-11 (resistant), and Parecis (susceptible) and S65-50 (resistant). Plants were inoculated with SCN and evaluated according to the female index (FI), those with FI < 10% were classified as resistant to nematode infection. Plants were genotyped for SCN resistance using microsatellite markers Sat-141 and Sat_168. Marker selection efficiency was analyzed by a contingency table, taking into account genotypic versus phenotypic evaluations for each line. These markers were shown to be useful tool for selection of SCN race 3.

  11. Identification and Validation of SNP Markers Linked to Dwarf Traits Using SLAF-Seq Technology in Lagerstroemia

    PubMed Central

    Ju, Yiqian; Jiao, Yao; Feng, Lu; Pan, Huitang; Cheng, Tangren; Zhang, Qixiang

    2016-01-01

    The genetic control of plant architecture is a promising approach to breed desirable cultivars, particularly in ornamental flowers. In this study, the F1 population (142 seedlings) derived from Lagerstroemia fauriei (non-dwarf) × L. indica ‘Pocomoke’ (dwarf) was phenotyped for six traits (plant height (PH), internode length (IL), internode number, primary lateral branch height (PLBH), secondary lateral branch height and primary branch number), and the IL and PLBH traits were positively correlated with the PH trait and considered representative indexes of PH. Fifty non-dwarf and dwarf seedlings were pooled and subjected to a specific-locus amplified fragment sequencing (SLAF-seq) method, which screened 1221 polymorphic markers. A total of 3 markers segregating between bulks were validated in the F1 population, with the M16337 and M38412 markers highly correlated with the IL trait and the M25207 marker highly correlated with the PLBH trait. These markers provide a predictability of approximately 80% using a single marker (M25207) and a predictability of 90% using marker combinations (M16337 + M25207) in the F1 population, which revealed that the IL and the PLBH traits, especially the PLBH, were the decisive elements for PH in terms of molecular regulation. Further validation was performed in the BC1 population and a set of 28 Lagerstroemia stocks using allele-specific PCR (AS-PCR) technology, and the results showed the stability and reliability of the SNP markers and the co-determination of PH by multiple genes. Our findings provide an important theoretical and practical basis for the early prediction and indirect selection of PH using the IL and the PLBH, and the detected SNPs may be useful for marker-assisted selection (MAS) in crape myrtle. PMID:27404662

  12. Genetic diversity of loquat germplasm (Eriobotrya japonica (Thunb) Lindl) assessed by SSR markers.

    PubMed

    Soriano, José Miguel; Romero, Carlos; Vilanova, Santiago; Llácer, Gerardo; Badenes, María Luisa

    2005-02-01

    Genetic relationships among 40 loquat (Eriobotrya japonica (Thunb) Lindl) accessions that originated from different countries and that are part of the germplasm collection of the Instituto Valenciano de Investigaciones Agrarias (IVIA) (Valencia, Spain) were evaluated using microsatellites. Thirty primer pairs flanking microsatellites previously identified in Malus x domestica (Borkh.) were assayed. Thirteen of them amplified polymorphic products and unambiguously distinguished 34 genotypes from the 40 accessions analyzed. Six accessions showing identical marker patterns were Spanish local varieties thought to have been derived from 'Algerie' by a mutational process very common in loquat species. A total of 39 alleles were detected in the population studied, with a mean value of 2.4 alleles per locus. The expected and observed heterozygosities were 0.46 and 51% on average, respectively, leading to a negative value of the Wright's fixation index (-0.20). The values of these parameters indicate a smaller degree of genetic diversity in the set of loquat accessions analyzed than in other members of the Rosaceae family. Unweighted pair-group method (UPGMA) cluster analysis, based on Nei's genetic distance, generally grouped genotypes according to their geographic origins and pedigrees. The high number of alleles and the high expected heterozygosity detected with SSR markers developed in Malus x domestica (Borkh.) make them a suitable tool for loquat cultivar identification, confirming microsatellite marker transportability among genera in the Rosaceae family.

  13. Stable MSAP markers for the distinction of Vitis vinifera cv Pinot noir clones.

    PubMed

    Ocaña, Juan; Walter, Bernard; Schellenbaum, Paul

    2013-11-01

    Grapevine is one of the most economically important fruit crops. Molecular markers have been used to study grapevine diversity. For instance, simple sequence repeats are a powerful tool for identification of grapevine cultivars, while amplified fragment length polymorphisms have shown their usefulness in intra-varietal diversity studies. Other techniques such as sequence-specific amplified polymorphism are based on the presence of mobile elements in the genome, but their detection lies upon their activity. Relevant attention has been drawn toward epigenetic sources of variation. In this study, a set of Vitis vinifera cv Pinot noir clones were analyzed using the methylation-sensitive amplified polymorphism technique with isoschizomers MspI and HpaII. Nine out of fourteen selective primer combinations were informative and generated two types of polymorphic fragments which were categorized as "stable" and "unstable." In total, 23 stable fragments were detected and they discriminated 92.5 % of the studied clones. Detected stable polymorphisms were either common to several clones, restricted to a few clones or unique to a single clone. The identification of these stable epigenetic markers will be useful in clonal diversity studies. We highlight the relevance of stable epigenetic variation in V. vinifera clones and analyze at which level these markers could be applicable for the development of forthright techniques for clonal distinction.

  14. Analysis of Gene Expression Profiles of Soft Tissue Sarcoma Using a Combination of Knowledge-Based Filtering with Integration of Multiple Statistics

    PubMed Central

    Doi, Ayano; Ichinohe, Risa; Ikuyo, Yoriko; Takahashi, Teruyoshi; Marui, Shigetaka; Yasuhara, Koji; Nakamura, Tetsuro; Sugita, Shintaro; Sakamoto, Hiromi; Yoshida, Teruhiko; Hasegawa, Tadashi

    2014-01-01

    The diagnosis and treatment of soft tissue sarcomas (STS) have been difficult. Of the diverse histological subtypes, undifferentiated pleomorphic sarcoma (UPS) is particularly difficult to diagnose accurately, and its classification per se is still controversial. Recent advances in genomic technologies provide an excellent way to address such problems. However, it is often difficult, if not impossible, to identify definitive disease-associated genes using genome-wide analysis alone, primarily because of multiple testing problems. In the present study, we analyzed microarray data from 88 STS patients using a combination method that used knowledge-based filtering and a simulation based on the integration of multiple statistics to reduce multiple testing problems. We identified 25 genes, including hypoxia-related genes (e.g., MIF, SCD1, P4HA1, ENO1, and STAT1) and cell cycle- and DNA repair-related genes (e.g., TACC3, PRDX1, PRKDC, and H2AFY). These genes showed significant differential expression among histological subtypes, including UPS, and showed associations with overall survival. STAT1 showed a strong association with overall survival in UPS patients (logrank p = 1.84×10−6 and adjusted p value 2.99×10−3 after the permutation test). According to the literature, the 25 genes selected are useful not only as markers of differential diagnosis but also as prognostic/predictive markers and/or therapeutic targets for STS. Our combination method can identify genes that are potential prognostic/predictive factors and/or therapeutic targets in STS and possibly in other cancers. These disease-associated genes deserve further preclinical and clinical validation. PMID:25188299

  15. SU-E-T-300: Spatial Variations of Multiple Off-Axial Targets for a Single Isocenter SRS Treatment Plan in ExacTrac 6D Robotic Couch System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, S; Tseng, T

    2014-06-01

    Purpose: To evaluate the spatial variations of multiple off-axial targets for a single isocenter stereotactic radiosurgery (SRS) treatment plan in ExacTrac 6D robotic couch system (BrainLab AG). Methods: Five metallic ball bearing (BB) markers were placed sparsely in 3D off-axial locations (non-coplanar) inside a skull phantom as the representatives of multiple targets mimicking multiple brain metastases. The locations of the BB markers were carefully chosen to minimize overlapping of each other in a port imaging detector plane. The skull phantom was immobilized by a frameless mask and CT scanned with a BrainLab Head and Neck Localizer using a GE Optimamore » MDCT scanner. The CT images were exported to iPlan software (BrainLab AG) and a multiple target PTV was drawn by combining all the contours of the BBs. The margin of the MLC opening was selected as 3 mm expansion outward. Two coplanar arc beams were placed to generate a single isocenter SRS plan to treat the PTV. The arc beams were delivered using Novalis Tx system with portal imaging acquisition mode per 10% temporal resolution. The locations of the BBs were visualized and analyzed with respect to the MLC aperture in the treatment plan similar to the Winston-Lutz test. Results: All the BBs were clearly identified inside the MLC openings. The positional errors for the BBs were overall less than 1 mm along the rotational path of the two arcs. Conclusion: This study verified that the spatial deviations of multiple off-axial targets for a single isocenter SRS treatment plan is within sub-millimeter range in ExacTrac 6D robotic couch system. Accompanied with the Winston-Lutz test, this test will quality-assure the spatial accuracies of the isocenter as well as the positions of multiple off-axial targets for the SRS treatment using a single isocenter multiple target treatment plan.« less

  16. A comparative analysis of gene-expression data of multiple cancer types.

    PubMed

    Xu, Kun; Cui, Juan; Olman, Victor; Yang, Qing; Puett, David; Xu, Ying

    2010-10-27

    A comparative study of public gene-expression data of seven types of cancers (breast, colon, kidney, lung, pancreatic, prostate and stomach cancers) was conducted with the aim of deriving marker genes, along with associated pathways, that are either common to multiple types of cancers or specific to individual cancers. The analysis results indicate that (a) each of the seven cancer types can be distinguished from its corresponding control tissue based on the expression patterns of a small number of genes, e.g., 2, 3 or 4; (b) the expression patterns of some genes can distinguish multiple cancer types from their corresponding control tissues, potentially serving as general markers for all or some groups of cancers; (c) the proteins encoded by some of these genes are predicted to be blood secretory, thus providing potential cancer markers in blood; (d) the numbers of differentially expressed genes across different cancer types in comparison with their control tissues correlate well with the five-year survival rates associated with the individual cancers; and (e) some metabolic and signaling pathways are abnormally activated or deactivated across all cancer types, while other pathways are more specific to certain cancers or groups of cancers. The novel findings of this study offer considerable insight into these seven cancer types and have the potential to provide exciting new directions for diagnostic and therapeutic development.

  17. Development of surface enhanced Raman scattering (SERS) spectroscopy monitoring of fuel markers to prevent fraud

    NASA Astrophysics Data System (ADS)

    Wilkinson, Timothy; Clarkson, John; White, Peter C.; Meakin, Nicholas; McDonald, Ken

    2013-05-01

    Governments often tax fuel products to generate revenues to support and stimulate their economies. They also subsidize the cost of essential fuel products. Fuel taxation and subsidization practices are both subject to fraud. Oil marketing companies also suffer from fuel fraud with loss of legitimate sales and additional quality and liability issues. The use of an advanced marking system to identify and control fraud has been shown to be effective in controlling illegal activity. DeCipher has developed surface enhanced Raman scattering (SERS) spectroscopy as its lead technology for measuring markers in fuel to identify and control malpractice. SERS has many advantages that make it highly suitable for this purpose. The SERS instruments are portable and can be used to monitor fuel at any point in the supply chain. SERS shows high specificity for the marker, with no false positives. Multiple markers can also be detected in a single SERS analysis allowing, for example, specific regional monitoring of fuel. The SERS analysis from fuel is also quick, clear and decisive, with a measurement time of less than 5 minutes. We will present results highlighting our development of the use of a highly stable silver colloid as a SERS substrate to measure the markers at ppb levels. Preliminary results from the use of a solid state SERS substrate to measure fuel markers will also be presented.

  18. Short communication: Comparison of 3 solid digesta passage markers in dairy cows.

    PubMed

    Lee, C; Hristov, A N

    2014-03-01

    This study investigated the usefulness of acid-detergent fiber-bound (15)N [acid detergent insoluble (ADI)-(15)N] as a solid digesta passage marker in dairy cows compared with chromium (Cr) and ytterbium (Yb) (as labeled fiber or forage, respectively). Intrinsically (ADI-(15)N) or extrinsically (Cr, Yb) labeled alfalfa hay was pulse-dosed intraruminally to 7 lactating dairy cows. Following marker administration, spot fecal samples were collected for up to 72 h for marker analyses. Urine and milk samples were also collected and analyzed for Yb and Cr. Fecal marker excretion data were processed using 2-compartment mathematical age-dependent/age-independent (Gn→G1) models. The rate of passage of the marker in the first, age-dependent compartment tended to be slower for Yb compared with Cr and ADI-(15)N, which resulted in a trend for longer mean retention time (MRT) in this compartment when Yb was used as a marker (19.0 h) compared with Cr and ADI-(15)N (14.5 and 13.9h, respectively). The rate constant of marker disappearance for the second or age-independent compartment tended to be greater for Yb compared with Cr and ADI-(15)N, which led to a shorter MRT of Yb in this compartment (15.6) versus ADI-(15)N (32.1) and Cr (24.8h). The cumulative MRT was greater for ADI-(15)N versus Cr and Yb (46.0, 39.3, and 34.4h, respectively). Total MRT of marker tended to be greater for ADI-(15)N than for Yb (46.6 vs. 36.6h, respectively). Urine and milk analyses data suggested no measurable losses of Yb along the digestive tract, but about 0.79% of Cr dosed intraruminally was secreted or excreted in milk and urine in the 48-h period following marker administration. Collectively, this study confirmed previous observations that ADI-(15)N can be used reliably as a solid digesta passage marker for ruminants, producing pre-duodenal and total-tract retention times similar to that of Cr-labeled fiber. Retention time in the age-independent compartment was underestimated when Yb was used as

  19. EvolMarkers: a database for mining exon and intron markers for evolution, ecology and conservation studies.

    PubMed

    Li, Chenhong; Riethoven, Jean-Jack M; Naylor, Gavin J P

    2012-09-01

    Recent innovations in next-generation sequencing have lowered the cost of genome projects. Nevertheless, sequencing entire genomes for all representatives in a study remains expensive and unnecessary for most studies in ecology, evolution and conservation. It is still more cost-effective and efficient to target and sequence single-copy nuclear gene markers for such studies. Many tools have been developed for identifying nuclear markers, but most of these have focused on particular taxonomic groups. We have built a searchable database, EvolMarkers, for developing single-copy coding sequence (CDS) and exon-primed-intron-crossing (EPIC) markers that is designed to work across a broad range of phylogenetic divergences. The database is made up of single-copy CDS derived from BLAST searches of a variety of metazoan genomes. Users can search the database for different types of markers (CDS or EPIC) that are common to different sets of input species with different divergence characteristics. EvolMarkers can be applied to any taxonomic group for which genome data are available for two or more species. We included 82 genomes in the first version of EvolMarkers and have found the methods to be effective across Placozoa, Cnidaria, Arthropod, Nematoda, Annelida, Mollusca, Echinodermata, Hemichordata, Chordata and plants. We demonstrate the effectiveness of searching for CDS markers within annelids and show how to find potentially useful intronic markers within the lizard Anolis. © 2012 Blackwell Publishing Ltd.

  20. A combination of molecular markers and clinical features improve the classification of pancreatic cysts.

    PubMed

    Springer, Simeon; Wang, Yuxuan; Dal Molin, Marco; Masica, David L; Jiao, Yuchen; Kinde, Isaac; Blackford, Amanda; Raman, Siva P; Wolfgang, Christopher L; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Ptak, Janine; Dobbyn, Lisa; Allen, Peter J; Klimstra, David S; Schattner, Mark A; Schmidt, C Max; Yip-Schneider, Michele; Cummings, Oscar W; Brand, Randall E; Zeh, Herbert J; Singhi, Aatur D; Scarpa, Aldo; Salvia, Roberto; Malleo, Giuseppe; Zamboni, Giuseppe; Falconi, Massimo; Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil; Hong, Seung-Mo; Song, Ki-Byung; Kim, Song Cheol; Swan, Niall; Murphy, Jean; Geoghegan, Justin; Brugge, William; Fernandez-Del Castillo, Carlos; Mino-Kenudson, Mari; Schulick, Richard; Edil, Barish H; Adsay, Volkan; Paulino, Jorge; van Hooft, Jeanin; Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi; Yamao, Kenji; Hijioka, Susuma; van der Merwe, Schalk; Goggins, Michael; Canto, Marcia Irene; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J; Cameron, John; Pittman, Meredith; Eshleman, James R; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Karchin, Rachel; Hruban, Ralph H; Vogelstein, Bert; Lennon, Anne Marie

    2015-11-01

    The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts

    PubMed Central

    Springer, Simeon; Wang, Yuxuan; Molin, Marco Dal; Masica, David L.; Jiao, Yuchen; Kinde, Isaac; Blackford, Amanda; Raman, Siva P.; Wolfgang, Christopher L.; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Ptak, Janine; Dobbyn, Lisa; Allen, Peter J.; Klimstra, David S.; Schattner, Mark A.; Schmidt, C. Max; Yip-Schneider, Michele; Cummings, Oscar W.; Brand, Randall E.; Zeh, Herbert J.; Singhi, Aatur D.; Scarpa, Aldo; Salvia, Roberto; Malleo, Giuseppe; Zamboni, Giuseppe; Falconi, Massimo; Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil; Hong, Seung-Mo; Song, Ki-Byung; Kim, Song Cheol; Swan, Niall; Murphy, Jean; Geoghegan, Justin; Brugge, William; Fernandez-Del Castillo, Carlos; Mino-Kenudson, Mari; Schulick, Richard; Edil, Barish H.; Adsay, Volkan; Paulino, Jorge; van Hooft, Jeanin; Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi; Yamao, Kenji; Hijioka, Susuma; van der Merwe, Schalk; Goggins, Michael; Canto, Marcia Irene; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J.; Cameron, John; Pittman, Meredith; Eshleman, James R.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Karchin, Rachel; Hruban, Ralph H.; Vogelstein, Bert; Lennon, Anne Marie

    2016-01-01

    Background & Aims The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. Methods We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid-pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53 and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers were compared with that of clinical markers, and a combination of molecular and clinical markers. Results We identified molecular markers and clinical features that classified cyst type with 90%–100% sensitivity and 92%–98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery, and could therefore reduce the number of unnecessary operations by 91%. Conclusions We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. PMID:26253305

  2. Molecular markers of paragangliomas/pheochromocytomas

    PubMed Central

    Zaretsky, Andrew R; Alekseev, Boris Y; Pokrovsky, Anatoly V; Golovyuk, Alexander L; Melnikova, Nataliya V; Stepanov, Oleg A; Kalinin, Dmitry V; Moskalev, Alexey A; Krasnov, George S; Dmitriev, Alexey A; Kudryavtseva, Anna V

    2017-01-01

    Paragangliomas/pheochromocytomas comprise rare tumors that arise from the extra-adrenal paraganglia, with an incidence of about 2 to 8 per million people each year. Approximately 40% of cases are due to genetic mutations in at least one out of more than 30 causative genes. About 2530% of pheochromocytomas/paragangliomas develop under the conditions of a hereditary tumor syndrome a third of which are caused by mutations in the VHL gene. Together, the gene mutations in this disorder have implicated multiple processes including signaling pathways, translation initiation, hypoxia regulation, protein synthesis, differentiation, survival, proliferation, and cell growth. The present review contemplates the mutations associated with the development of pheochromocytomas/paragangliomas and their potential to serve as specific markers of these tumors and their progression. These data will improve our understanding of the pathogenesis of these tumors and likely reveal certain features that may be useful for early diagnostics, malignancy prognostics, and the determination of new targets for disease therapeutics. PMID:28187001

  3. Robust estimation of the proportion of treatment effect explained by surrogate marker information.

    PubMed

    Parast, Layla; McDermott, Mary M; Tian, Lu

    2016-05-10

    In randomized treatment studies where the primary outcome requires long follow-up of patients and/or expensive or invasive obtainment procedures, the availability of a surrogate marker that could be used to estimate the treatment effect and could potentially be observed earlier than the primary outcome would allow researchers to make conclusions regarding the treatment effect with less required follow-up time and resources. The Prentice criterion for a valid surrogate marker requires that a test for treatment effect on the surrogate marker also be a valid test for treatment effect on the primary outcome of interest. Based on this criterion, methods have been developed to define and estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on the surrogate marker. These methods aim to identify useful statistical surrogates that capture a large proportion of the treatment effect. However, current methods to estimate this proportion usually require restrictive model assumptions that may not hold in practice and thus may lead to biased estimates of this quantity. In this paper, we propose a nonparametric procedure to estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on a potential surrogate marker and extend this procedure to a setting with multiple surrogate markers. We compare our approach with previously proposed model-based approaches and propose a variance estimation procedure based on a perturbation-resampling method. Simulation studies demonstrate that the procedure performs well in finite samples and outperforms model-based procedures when the specified models are not correct. We illustrate our proposed procedure using a data set from a randomized study investigating a group-mediated cognitive behavioral intervention for peripheral artery disease participants. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Real-time automatic fiducial marker tracking in low contrast cine-MV images

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Wei-Yang; Lin, Shu-Fang; Yang, Sheng-Chang

    2013-01-15

    /pixel). The standard deviations of the results from the 6 researchers are 2.3 and 2.6 pixels. The proposed framework takes about 128 ms to detect four markers in the first MV images and about 23 ms to track these markers in each of the subsequent images. Conclusions: The unified framework for tracking of multiple markers presented here can achieve marker detection accuracy similar to manual detection even in low-contrast cine-MV images. It can cope with shape deformations of fiducial markers at different gantry angles. The fast processing speed reduces the image processing portion of the system latency, therefore can improve the performance of real-time motion compensation.« less

  5. Genetic diversity of Cosmos species revealed by RAPD and ISSR markers.

    PubMed

    Rodríguez-Bernal, A; Piña-Escutia, J L; Vázquez-García, L M; Arzate-Fernández, A M

    2013-12-04

    The genus Cosmos is native of America and is constituted by 34 species; 28 of them are endemic of Mexico. The cosmos are used as a nematicide, antimalarial, and antioxidative agent. The aim of this study was to estimate the genetic diversity among 7 cosmos species based on random amplified polymorphic DNA (RAPD) and inter-simple sequences repeats (ISSR) markers. With RAPD markers, the obtained polymorphism was 91.7 % and the genetic diversity was 0.33, whereas these values were 65.6%, and 0.22 from ISSR markers, respectively, indicating the presence of high genetic diversity among the Cosmos species that were analyzed. The unweighted pair group method with arithmetic mean dendrograms that were obtained with both markers were notably similar, revealing 2 clusters and indicating a clear genetic differentiation among the Cosmos species that were assessed. The first cluster comprised the species Cosmos sulphureus, Cosmos pacificus, and Cosmos diversifolius, while the second cluster included the species Cosmos purpureus, Cosmos crithmifolius, Cosmos bipinnatus, and Cosmos parviflorus. Besides this, the Cosmos species were clustered according to their collection sites. The Mantel test corroborates the correlation between the genetic distance and the geographic altitude of each Cosmos species. The results suggest that it is necessary to preserve the Cosmos species in their natural habitat in addition to the germoplasm collection for ex situ conservation.

  6. Handheld Fluorescence Microscopy based Flow Analyzer.

    PubMed

    Saxena, Manish; Jayakumar, Nitin; Gorthi, Sai Siva

    2016-03-01

    Fluorescence microscopy has the intrinsic advantages of favourable contrast characteristics and high degree of specificity. Consequently, it has been a mainstay in modern biological inquiry and clinical diagnostics. Despite its reliable nature, fluorescence based clinical microscopy and diagnostics is a manual, labour intensive and time consuming procedure. The article outlines a cost-effective, high throughput alternative to conventional fluorescence imaging techniques. With system level integration of custom-designed microfluidics and optics, we demonstrate fluorescence microscopy based imaging flow analyzer. Using this system we have imaged more than 2900 FITC labeled fluorescent beads per minute. This demonstrates high-throughput characteristics of our flow analyzer in comparison to conventional fluorescence microscopy. The issue of motion blur at high flow rates limits the achievable throughput in image based flow analyzers. Here we address the issue by computationally deblurring the images and show that this restores the morphological features otherwise affected by motion blur. By further optimizing concentration of the sample solution and flow speeds, along with imaging multiple channels simultaneously, the system is capable of providing throughput of about 480 beads per second.

  7. VUV-Photoionization CES-Detector of Volatile Bio-Marker Molecules

    NASA Astrophysics Data System (ADS)

    Mustafaev, Alexander; Luneva, Nataliya; Panasyuk, George; Timofeev, Nikolay; Tsyganov, Alexander

    2014-10-01

    Energy spectra of characteristic electrons released via photoionization by vacuum ultraviolet (VUV) radiation of admixture molecules in the atmospheric air, not using traditional evacuated energy analyzers, can be determined by Collisional Electron Spectroscopy (CES) method. Some details of CES-photoionization sensor were described in. Our further developments are devoted to application of CES-detectors for a mobile continuous bio-chemical diagnostics. It is known that ``on breathing'' it is possible to find out volatile bio-marker molecules of a lot of diseases (lung cancer, tuberculosis, COPD, asthma, diabetes, kidney disease, mammary cancer, Crohn's disease, ulcerative colitis, etc). But today's weighty and expensive laboratory equipment (like GC MS) provides observation of these bio-markers only during patients' visits to a doctor. In this way we study pocket-size CES-sensor with micro-plasma krypton resonance radiation source (10.6 eV photons) for the photoionization detection of metabolic ammonia, ethanol, acetone and pentane molecules directly in atmospheric air.

  8. Systematic evaluation of markers used for the identification of human induced pluripotent stem cells

    PubMed Central

    Bharathan, Sumitha Prameela; Manian, Kannan Vrindavan; Aalam, Syed Mohammed Musheer; Palani, Dhavapriya; Deshpande, Prashant Ajit; Pratheesh, Mankuzhy Damodaran; Srivastava, Alok

    2017-01-01

    ABSTRACT Low efficiency of somatic cell reprogramming and heterogeneity among human induced pluripotent stem cells (hiPSCs) demand extensive characterization of isolated clones before their use in downstream applications. By monitoring human fibroblasts undergoing reprogramming for their morphological changes and expression of fibroblast (CD13), pluripotency markers (SSEA-4 and TRA-1-60) and a retrovirally expressed red fluorescent protein (RV-RFP), we compared the efficiency of these features to identify bona fide hiPSC colonies. The co-expression kinetics of fibroblast and pluripotency markers in the cells being reprogrammed and the emerging colonies revealed the heterogeneity within SSEA-4+ and TRA-1-60+ cells, and the inadequacy of these commonly used pluripotency markers for the identification of bona fide hiPSC colonies. The characteristic morphological changes in the emerging hiPSC colonies derived from fibroblasts expressing RV-RFP showed a good correlation between hiPSC morphology acquisition and silencing of RV-RFP and facilitated the easy identification of hiPSCs. The kinetics of retroviral silencing and pluripotency marker expression in emerging colonies suggested that combining both these markers could demarcate the stages of reprogramming with better precision than with pluripotency markers alone. Our results clearly demonstrate that the pluripotency markers that are routinely analyzed for the characterization of established iPSC colonies are not suitable for the isolation of pluripotent cells in the early stages of reprogramming, and silencing of retrovirally expressed reporter genes helps in the identification of colonies that have attained a pluripotent state and the morphology of human embryonic stem cells (hESCs). PMID:28089995

  9. Analysing the effect of multiple sclerosis on vitamin D related biochemical markers of bone remodelling.

    PubMed

    McKenna, Malachi J; Murray, Barbara; Lonergan, Roisin; Segurado, Ricardo; Tubridy, Niall; Kilbane, Mark T

    2018-03-01

    The Irish population is at risk of vitamin D deficiency during the winter months, but the secular trend over the past 40 years is for marked improvement. Multiple sclerosis (MS) is common in Ireland with a latitudinal pattern favouring highest incidence in northern regions; MS is linked strongly with vitamin D status as a causal factor. We sought firstly to study the relationship between vitamin D status and vitamin D-related bone biochemistry, and secondly to evaluate if MS had an independent effect on vitamin D related markers of bone remodelling. Using a case-control design of 165 pairs (MS patient and matched control) residing in three different geographic regions during winter months, we measured serum 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), C-terminal telopeptide of type I collagen (CTX) and total procollagen type I amino-terminal propeptide (PINP). Given the paired case-control design, associations were explored using mixed-effects linear regression analysis with the patient-control pair as a random effect and after log transformation of 25OHD. A two-way interaction effect was tested for vitamin D status (25OHD <30nmol/L) and the presence of MS on PTH, CTX, and PINP. In the total group, just over one-third (34.5%) had 25OHD <30nmol/L. PTH was elevated in 7.6%. CTX was not elevated in any case, and PINP was elevated in 4.5%. On mixed-effects linear regression analysis after adjusting for confounders (age, sex, renal function, and serum albumin), we demonstrated the principal determinant of 25OHD was geographical location (p<0.001), of PTH was 25OHD (p<0.001), of CTX was PTH (p<0.001), and of PINP was PTH (p<0.001). MS did not have an independent effect on PTH (p=0.921), CTX (p=0.912), or PINP (p=0.495). As regards an interaction effect, the presence of MS and 25OHD <30nmol/L was not significant but tended towards having lower PTH (p=0.207). In conclusion, in Ireland in winter only a minority had any abnormality in the secondary indices of

  10. Perfectionism and Polysomnography-Determined Markers of Poor Sleep

    PubMed Central

    Johann, Anna F.; Hertenstein, Elisabeth; Kyle, Simon D.; Baglioni, Chiara; Feige, Bernd; Nissen, Christoph; Riemann, Dieter; Spiegelhalder, Kai

    2017-01-01

    Study Objectives: Perfectionism has been suggested to represent a predisposing factor for poor sleep. However, previous studies have relied on self-reported measures. The association between perfectionism and poor sleep measured by polysomnography (PSG) warrants further investigation. Methods: The current retrospective exploratory study used the Frost Multidimensional Perfectionism Scale and PSG in an unselected sample of 334 consecutive sleep laboratory patients (140 males, 194 females, 44.6 ± 15.9 years). Data were analyzed using linear regression analyses. Results: High levels of perfectionism were associated with PSG-determined markers of poor sleep in the first sleep laboratory night. The total Frost Multidimensional Perfectionism Scale score was significantly associated with the number of nocturnal awakenings in the first sleep laboratory night. The subscales “concern over mistakes” and “personal standards” of perfectionism were significantly associated with markers of poor sleep. In contrast, there were only a few associations between perfectionism and PSG variables of the second sleep laboratory night. Conclusions: This pattern of results suggests that high levels of perfectionism may predispose individuals to sleep disturbances in the context of acute stressors. Thus, the influence of perfectionism on poor sleep should be further investigated to improve treatment. Citation: Johann AF, Hertenstein E, Kyle SD, Baglioni C, Feige B, Nissen C, Riemann D, Spiegelhalder K. Perfectionism and polysomnography-determined markers of poor sleep. J Clin Sleep Med. 2017;13(11):1319–1326. PMID:28992830

  11. Development and characterization of microsatellite markers for Morus spp. and assessment of their transferability to other closely related species

    PubMed Central

    2013-01-01

    Background Adoption of genomics based breeding has emerged as a promising approach for achieving comprehensive crop improvement. Such an approach is more relevant in the case of perennial species like mulberry. However, unavailability of genomic resources of co-dominant marker systems has been the major constraint for adopting molecular breeding to achieve genetic enhancement of Mulberry. The goal of this study was to develop and characterize a large number of locus specific genic and genomic SSR markers which can be effectively used for molecular characterization of mulberry species/genotypes. Result We analyzed a total of 3485 DNA sequences including genomic and expressed sequences (ESTs) of mulberry (Morus alba L.) genome. We identified 358 sequences to develop appropriate microsatellite primer pairs representing 222 genomic and 136 EST regions. Primers amplifying locus specific regions of Dudia white (a genotype of Morus alba L), were identified and 137 genomic and 51 genic SSR markers were standardized. A two pronged strategy was adopted to assess the applicability of these SSR markers using mulberry species and genotypes along with a few closely related species belonging to the family Moraceae viz., Ficus, Fig and Jackfruit. While 100% of these markers amplified specific loci on the mulberry genome, 79% were transferable to other related species indicating the robustness of these markers and the potential they hold in analyzing the molecular and genetic diversity among mulberry germplasm as well as other related species. The inherent ability of these markers in detecting heterozygosity combined with a high average polymorphic information content (PIC) of 0.559 ranging between 0.076 and 0.943 clearly demonstrates their potential as genomic resources in diversity analysis. The dissimilarity coefficient determined based on Neighbor joining method, revealed that the markers were successful in segregating the mulberry species, genotypes and other related species

  12. Identification of innovative potential quality markers in rocket and melon fresh-cut produce.

    PubMed

    Cavaiuolo, Marina; Cocetta, Giacomo; Bulgari, Roberta; Spinardi, Anna; Ferrante, Antonio

    2015-12-01

    Ready-to-eat fresh cut produce are exposed to pre- and postharvest abiotic stresses during the production chain. Our work aimed to identify stress responsive genes as new molecular markers of quality that can be widely applied to leaves and fruits and easily determined at any stage of the production chain. Stress responsive genes associated with quality losses were isolated in rocket and melon fresh-cut produce and their expression levels analyzed by quantitative real time PCR (qRT-PCR) at different time points after harvest at 20 °C and 4 °C. qRT-PCR results were supported by correlation analysis with physiological and biochemical determinations evaluated at the same conditions such as chlorophyll a fluorescence indices, total, reducing sugars, sucrose, ethylene, ascorbic acid, lipid peroxidation and reactive oxygen species. In both species the putative molecular markers increased their expression soon after harvest suggesting a possible use as novel and objective quality markers of fresh-cut produces. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years.

    PubMed

    Garcia-Martin, Elena; Ara, Jose R; Martin, Jesus; Almarcegui, Carmen; Dolz, Isabel; Vilades, Elisa; Gil-Arribas, Laura; Fernandez, Francisco J; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E; Satue, Maria

    2017-05-01

    To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. Observational and longitudinal study. One hundred patients with relapsing-remitting MS and 50 healthy controls. All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  14. Shape and size of the body vs. musculoskeletal stress markers.

    PubMed

    Myszka, Anna; Piontek, Janusz

    2010-01-01

    The objective of this paper is to assess the relationship between the degree of development of muscle attachment sites (musculoskeletal stress markers - MSM1) and the length and circumference measurements of long bones and the body build expressed with the reconstructed values of body height (BH) and body mass (BM). The bone material (102 male and 99 female skeletons) used in the study was collected in the medieval burial ground in Cedynia, Poland. The authors analyzed 10 musculoskeletal stress markers located on the scapula (2), humerus (2), radius (2), femur (2) and tibia (2). The frequency and the degree of expression of muscle attachment size was carried out using the scale prepared by Myszka (2007). The scale encompassed three degrees of expression of muscle attachment size. Only changes of robusticity type (nonpathological changes) were taken into account. The assessment of body build of individuals was carried out according to the method proposed by Vancata & Charvátová (2001). Body height was reconstructed from the length of the humerus and femur using eight equations. Body mass was reconstructed from the measurements of the breadth of the proximal and distal sections of the femur and tibia (mechanical method) using twenty one equations. The equations were developed for different reference populations. The same equations were used for men and women. The correlation between the MSM and the length and circumference measurements of the bones was analyzed using the principal components analysis and the Gamma correlation coefficient. The strength of the correlation between the reconstructed body build traits (BH, BM) and the moderate degree of musculoskeletal stress markers expression was studied based on the principal components method and the Pearson correlation coefficient. A linear correlation was found between musculoskeletal stress markers and the circumference measurements and the reconstructed body mass, but no relationship with body height and the

  15. Genetic diversity analysis among male and female Jojoba genotypes employing gene targeted molecular markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) markers

    PubMed Central

    Heikrujam, Monika; Kumar, Jatin; Agrawal, Veena

    2015-01-01

    To detect genetic variations among different Simmondsia chinensis genotypes, two gene targeted markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) were employed in terms of their informativeness and efficiency in analyzing genetic relationships among different genotypes. A total of 15 SCoT and 17 CBDP primers detected genetic polymorphism among 39 Jojoba genotypes (22 females and 17 males). Comparatively, CBDP markers proved to be more effective than SCoT markers in terms of percentage polymorphism as the former detecting an average of 53.4% and the latter as 49.4%. The Polymorphic information content (PIC) value and marker index (MI) of CBPD were 0.43 and 1.10, respectively which were higher than those of SCoT where the respective values of PIC and MI were 0.38 and 1.09. While comparing male and female genotype populations, the former showed higher variation in respect of polymorphic percentage and PIC, MI and Rp values over female populations. Nei's diversity (h) and Shannon index (I) were calculated for each genotype and found that the genotype “MS F” (in both markers) was highly diverse and genotypes “Q104 F” (SCoT) and “82–18 F” (CBDP) were least diverse among the female genotype populations. Among male genotypes, “32 M” (CBDP) and “MS M” (SCoT) revealed highest h and I values while “58-5 M” (both markers) was the least diverse. Jaccard's similarity co-efficient of SCoT markers ranged from 0.733 to 0.922 in female genotypes and 0.941 to 0.746 in male genotype population. Likewise, CBDP data analysis also revealed similarity ranging from 0.751 to 0.958 within female genotypes and 0.754 to 0.976 within male genotype populations thereby, indicating genetically diverse Jojoba population. Employing the NTSYS (Numerical taxonomy and multivariate analysis system) Version 2.1 software, both the markers generated dendrograms which revealed that all the Jojoba genotypes were clustered into two major groups

  16. Genetic diversity analysis among male and female Jojoba genotypes employing gene targeted molecular markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) markers.

    PubMed

    Heikrujam, Monika; Kumar, Jatin; Agrawal, Veena

    2015-09-01

    To detect genetic variations among different Simmondsia chinensis genotypes, two gene targeted markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) were employed in terms of their informativeness and efficiency in analyzing genetic relationships among different genotypes. A total of 15 SCoT and 17 CBDP primers detected genetic polymorphism among 39 Jojoba genotypes (22 females and 17 males). Comparatively, CBDP markers proved to be more effective than SCoT markers in terms of percentage polymorphism as the former detecting an average of 53.4% and the latter as 49.4%. The Polymorphic information content (PIC) value and marker index (MI) of CBPD were 0.43 and 1.10, respectively which were higher than those of SCoT where the respective values of PIC and MI were 0.38 and 1.09. While comparing male and female genotype populations, the former showed higher variation in respect of polymorphic percentage and PIC, MI and Rp values over female populations. Nei's diversity (h) and Shannon index (I) were calculated for each genotype and found that the genotype "MS F" (in both markers) was highly diverse and genotypes "Q104 F" (SCoT) and "82-18 F" (CBDP) were least diverse among the female genotype populations. Among male genotypes, "32 M" (CBDP) and "MS M" (SCoT) revealed highest h and I values while "58-5 M" (both markers) was the least diverse. Jaccard's similarity co-efficient of SCoT markers ranged from 0.733 to 0.922 in female genotypes and 0.941 to 0.746 in male genotype population. Likewise, CBDP data analysis also revealed similarity ranging from 0.751 to 0.958 within female genotypes and 0.754 to 0.976 within male genotype populations thereby, indicating genetically diverse Jojoba population. Employing the NTSYS (Numerical taxonomy and multivariate analysis system) Version 2.1 software, both the markers generated dendrograms which revealed that all the Jojoba genotypes were clustered into two major groups, one group consisting of

  17. Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map.

    PubMed

    N'Diaye, Amidou; Haile, Jemanesh K; Cory, Aron T; Clarke, Fran R; Clarke, John M; Knox, Ron E; Pozniak, Curtis J

    2017-01-01

    Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype

  18. Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map

    PubMed Central

    Haile, Jemanesh K.; Cory, Aron T.; Clarke, Fran R.; Clarke, John M.; Knox, Ron E.; Pozniak, Curtis J.

    2017-01-01

    Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype

  19. Application of ISSR markers to analyze molecular relationships in Iranian jasmine (Jasminum spp.) accessions.

    PubMed

    Ghasemi Ghehsareh, Masood; Salehi, Hassan; Khosh-Khui, Morteza; Niazi, Ali

    2015-01-01

    There are many species of jasmines in different regions of Iran in natural or cultivated form, and there is no information about their genetic status. Therefore, inter-simple sequence repeat (ISSR) analysis was used to evaluate genetic variations of the 53 accessions representing eight species of Jasminum collected from different regions of Iran. A total of 21 ISSR primers were used which generated 981 bands of different sizes. Mean percentage of polymorphic bands was 90.64 %. Maximum resolving power, polymorphic information content average, and marker index values were 21.55, 0.35, and 14.42 for primers of 3, 4, and 3 respectively. The unweighted pair group method with arithmetic mean dendrogram based on Jaccard's coefficients indicated that 53 accessions were divided into two major clusters. The first major cluster was divided into two subclusters; the subcluster A included Jasminum grandiflorum L., J. officinale L., and J. azoricum L. and the subcluster B consisted of three forms of J. sambac L. (single, semi-double, and double flowers). The second major cluster was divided into two subclusters; the first subcluster (C) included J. humile L., J. primulinum Hemsl., J. nudiflorum Lindl. and the second subcluster (D) consisted of J. fruticans L. At the species level, the highest percentage of polymorphism (34.05 %), numbers of effective alleles (1.16), Shannon index (0.151), and Nei's genetic diversity (0.098) were observed in J. officinale. The lowest values of percentage polymorphism (0.011), number of effective alleles (1.009), Shannon index (0.007), and Nei's genetic diversity (0.005) were obtained for J. nudiflorum. Based on pairwise population matrix of Nei's unbiased genetic identity, the highest identity (0.85) was found between J.officinale and J. azoricum and the lowest identity (0.69) was between J. grandiflorum and J. perimulinum. Based on analysis of molecular variance, the amount of genetic variations among the eight populations was 83 %. This study

  20. Identification of RAPD and SCAR markers associated with yield traits in the Indian tropical tasar silkworm Antheraea mylitta drury

    PubMed Central

    Dutta, Suhrid R.; Kar, Prasanta K.; Srivastava, Ashok K.; Sinha, Manoj K.; Shankar, Jai; Ghosh, Ananta K.

    2012-01-01

    The tropical tasar silkworm, Antheraea mylitta, is a semi-domesticated vanya silk-producing insect of high economic importance. To date, no molecular marker associated with cocoon and shell weights has been identified in this species. In this report, we identified a randomly amplified polymorphic DNA (RAPD) marker and examined its inheritance, and also developed a stable diagnostic sequence-characterized amplified region (SCAR) marker. Silkworms were divided into groups with high (HCSW) and low (LCSW) cocoon and shell weights, and the F2 progeny of a cross between these two groups were obtained. DNA from these silkworms was screened by PCR using 34 random primers and the resulting RAPD fragments were used for cluster analysis and discriminant function analysis (DFA). The clustering pattern in a UPGMA-based dendogram and DFA clearly distinguished the HCSW and LCSW groups. Multiple regression analysis identified five markers associated with cocoon and shell weights. The marker OPW16905 bp showed the most significant association with cocoon and shell weights, and its inheritance was confirmed in F2 progeny. Cloning and sequencing of this 905 bp fragment showed 88% identity between its 134 nucleotides and the Bmc-1/Yamato-like retroposon of A. mylitta. This marker was further converted into a diagnostic SCAR marker (SCOPW 16826 bp). The SCAR marker developed here may be useful in identifying the right parental stock of tasar silk-worms for high cocoon and shell weights in breeding programs designed to enhance the productivity of tasar silk. PMID:23271934

  1. 75 FR 59620 - Natchez Fireworks Safety Zone; Lower Mississippi River, Mile Marker 365.5 to Mile Marker 363...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ...-AA00 Natchez Fireworks Safety Zone; Lower Mississippi River, Mile Marker 365.5 to Mile Marker 363... establishing a temporary safety zone for all waters of the Lower Mississippi River from mile marker 365.5 to... from mile marker 365.5 to 363 extending the entire width [[Page 59621

  2. A Hot-Deck Multiple Imputation Procedure for Gaps in Longitudinal Recurrent Event Histories

    PubMed Central

    Wang, Chia-Ning; Little, Roderick; Nan, Bin; Harlow, Siobán D.

    2012-01-01

    Summary We propose a regression-based hot deck multiple imputation method for gaps of missing data in longitudinal studies, where subjects experience a recurrent event process and a terminal event. Examples are repeated asthma episodes and death, or menstrual periods and the menopause, as in our motivating application. Research interest concerns the onset time of a marker event, defined by the recurrent-event process, or the duration from this marker event to the final event. Gaps in the recorded event history make it difficult to determine the onset time of the marker event, and hence, the duration from onset to the final event. Simple approaches such as jumping gap times or dropping cases with gaps have obvious limitations. We propose a procedure for imputing information in the gaps by substituting information in the gap from a matched individual with a completely recorded history in the corresponding interval. Predictive Mean Matching is used to incorporate information on longitudinal characteristics of the repeated process and the final event time. Multiple imputation is used to propagate imputation uncertainty. The procedure is applied to an important data set for assessing the timing and duration of the menopausal transition. The performance of the proposed method is assessed by a simulation study. PMID:21361886

  3. Uniparental Markers of Contemporary Italian Population Reveals Details on Its Pre-Roman Heritage

    PubMed Central

    Álvarez-Iglesias, Vanesa; Fondevila, Manuel; Blanco-Verea, Alejandro; Carracedo, Ángel; Pascali, Vincenzo L.; Capelli, Cristian

    2012-01-01

    Background According to archaeological records and historical documentation, Italy has been a melting point for populations of different geographical and ethnic matrices. Although Italy has been a favorite subject for numerous population genetic studies, genetic patterns have never been analyzed comprehensively, including uniparental and autosomal markers throughout the country. Methods/Principal Findings A total of 583 individuals were sampled from across the Italian Peninsula, from ten distant (if homogeneous by language) ethnic communities — and from two linguistic isolates (Ladins, Grecani Salentini). All samples were first typed for the mitochondrial DNA (mtDNA) control region and selected coding region SNPs (mtSNPs). This data was pooled for analysis with 3,778 mtDNA control-region profiles collected from the literature. Secondly, a set of Y-chromosome SNPs and STRs were also analyzed in 479 individuals together with a panel of autosomal ancestry informative markers (AIMs) from 441 samples. The resulting genetic record reveals clines of genetic frequencies laid according to the latitude slant along continental Italy – probably generated by demographical events dating back to the Neolithic. The Ladins showed distinctive, if more recent structure. The Neolithic contribution was estimated for the Y-chromosome as 14.5% and for mtDNA as 10.5%. Y-chromosome data showed larger differentiation between North, Center and South than mtDNA. AIMs detected a minor sub-Saharan component; this is however higher than for other European non-Mediterranean populations. The same signal of sub-Saharan heritage was also evident in uniparental markers. Conclusions/Significance Italy shows patterns of molecular variation mirroring other European countries, although some heterogeneity exists based on different analysis and molecular markers. From North to South, Italy shows clinal patterns that were most likely modulated during Neolithic times. PMID:23251386

  4. Uniparental markers of contemporary Italian population reveals details on its pre-Roman heritage.

    PubMed

    Brisighelli, Francesca; Álvarez-Iglesias, Vanesa; Fondevila, Manuel; Blanco-Verea, Alejandro; Carracedo, Angel; Pascali, Vincenzo L; Capelli, Cristian; Salas, Antonio

    2012-01-01

    According to archaeological records and historical documentation, Italy has been a melting point for populations of different geographical and ethnic matrices. Although Italy has been a favorite subject for numerous population genetic studies, genetic patterns have never been analyzed comprehensively, including uniparental and autosomal markers throughout the country. A total of 583 individuals were sampled from across the Italian Peninsula, from ten distant (if homogeneous by language) ethnic communities--and from two linguistic isolates (Ladins, Grecani Salentini). All samples were first typed for the mitochondrial DNA (mtDNA) control region and selected coding region SNPs (mtSNPs). This data was pooled for analysis with 3,778 mtDNA control-region profiles collected from the literature. Secondly, a set of Y-chromosome SNPs and STRs were also analyzed in 479 individuals together with a panel of autosomal ancestry informative markers (AIMs) from 441 samples. The resulting genetic record reveals clines of genetic frequencies laid according to the latitude slant along continental Italy--probably generated by demographical events dating back to the Neolithic. The Ladins showed distinctive, if more recent structure. The Neolithic contribution was estimated for the Y-chromosome as 14.5% and for mtDNA as 10.5%. Y-chromosome data showed larger differentiation between North, Center and South than mtDNA. AIMs detected a minor sub-Saharan component; this is however higher than for other European non-Mediterranean populations. The same signal of sub-Saharan heritage was also evident in uniparental markers. Italy shows patterns of molecular variation mirroring other European countries, although some heterogeneity exists based on different analysis and molecular markers. From North to South, Italy shows clinal patterns that were most likely modulated during Neolithic times.

  5. Pleiotropy between genetic markers of obesity and risk of prostate cancer

    PubMed Central

    Edwards, Todd L.; Giri, Ayush; Motley, Saundra; Duong, Wynne; Fowke, Jay H.

    2013-01-01

    Background To address inconsistent findings of obesity and prostate cancer risk, we analyzed the association between prostate cancer (PC) and genetic markers of obesity and metabolism. Methods Analyses included 176,520 single nucleotide polymorphisms (SNPs) associated with 23 metabolic traits. We examined the association between SNPs and PC in 871 cases and 906 controls, including 427 high-grade cases with Gleason ≥7. Genetic risk scores (GRSs) for body mass index (BMI) and waist-to-hip ratio (WHR) were also created by summing alleles associated with increasing BMI or WHR. Results PC was associated with 5 loci, including cyclin M2, with p-values less than 1×10−4. In addition, the WHR GRS was associated with high-grade PC versus controls (OR: 1.05; 95% CI: 1.00 – 1.11, p-value = 0.048), and high-grade PC versus low-grade PC (OR: 1.07, 95% CI 1.01 – 1.13, p-value = 0.03). None of these findings exceed the threshold for significance after correction for multiple testing. Conclusions Variants in genes known to be associated with metabolism and obesity may be associated with PC. We show evidence for pleiotropy between WHR GRS and PC grade. This finding is consistent with the function of several WHR genes, and previously described relationships with cancer traits. Impact Limitations in standard obesity measures suggest alternative characterizations of obesity may be needed to understand the role of metabolic dysregulation in PC. The underlying genetics of WHR or other Metabochip SNPs, while not statistically significant beyond multiple testing thresholds within our sample size, support the metabolic hypothesis of prostate carcinogenesis and warrant further investigation in independent samples. PMID:23810916

  6. Application of microsatellite markers as potential tools for traceability of Girgentana goat breed dairy products.

    PubMed

    Sardina, Maria Teresa; Tortorici, Lina; Mastrangelo, Salvatore; Di Gerlando, Rosalia; Tolone, Marco; Portolano, Baldassare

    2015-08-01

    In livestock, breed assignment may play a key role in the certification of products linked to specific breeds. Traceability of farm animals and authentication of their products can contribute to improve breed profitability and sustainability of animal productions with significant impact on the rural economy of particular geographic areas and on breed and biodiversity conservation. With the goal of developing a breed genetic traceability system for Girgentana dairy products, the aim of this study was to identify specific microsatellite markers able to discriminate among the most important Sicilian dairy goat breeds, in order to detect possible adulteration in Girgentana dairy products. A total of 20 microsatellite markers were analyzed on 338 individual samples from Girgentana, Maltese, and Derivata di Siria goat breeds. Specific microsatellite markers useful for traceability of dairy products were identified. Eight microsatellite markers showed alleles present at the same time in Maltese and Derivata di Siria and absent in Girgentana and, therefore, they were tested on DNA pools of the three breeds. Considering the electropherograms' results, only FCB20, SRCRSP5, and TGLA122 markers were tested on DNA samples extracted from cheeses of Girgentana goat breed. These three microsatellite markers could be applied in a breed genetic traceability system of Girgentana dairy products in order to detect adulteration due to Maltese and Derivata di Siria goat breeds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Interordinal chimera formation between medaka and zebrafish for analyzing stem cell differentiation.

    PubMed

    Hong, Ni; Chen, Songlin; Ge, Ruowen; Song, Jianxing; Yi, Meisheng; Hong, Yunhan

    2012-08-10

    Chimera formation is a standard test for pluripotency of stem cells in vivo. Interspecific chimera formation between distantly related organisms offers also an attractive approach for propagating endangered species. Parameters influencing interspecies chimera formation have remained poorly elucidated. Here, we report interordinal chimera formation between medaka and zebrafish, which separated ∼320 million years ago and exhibit a more than 2-fold difference in developmental speed. We show that, on transplantation into zebrafish blastulae, both noncultivated blastomeres and long-term cultivated embryonic stem (ES) cells of medaka adopted the zebrafish developmental program and differentiated into physiologically functional cell types including pigment cells, blood cells, and cardiomyocytes. We also show that medaka ES cells express differentiation gene markers during chimeric embryogenesis. Therefore, the evolutionary distance and different embryogenesis speeds do not produce donor-host incompatibility to compromise chimera formation between medaka and zebrafish, and molecular markers are valuable for analyzing lineage commitment and cell differentiation in interspecific chimeric embryos.

  8. Interordinal Chimera Formation Between Medaka and Zebrafish for Analyzing Stem Cell Differentiation

    PubMed Central

    Hong, Ni; Chen, Songlin; Ge, Ruowen; Song, Jianxing

    2012-01-01

    Chimera formation is a standard test for pluripotency of stem cells in vivo. Interspecific chimera formation between distantly related organisms offers also an attractive approach for propagating endangered species. Parameters influencing interspecies chimera formation have remained poorly elucidated. Here, we report interordinal chimera formation between medaka and zebrafish, which separated ∼320 million years ago and exhibit a more than 2-fold difference in developmental speed. We show that, on transplantation into zebrafish blastulae, both noncultivated blastomeres and long-term cultivated embryonic stem (ES) cells of medaka adopted the zebrafish developmental program and differentiated into physiologically functional cell types including pigment cells, blood cells, and cardiomyocytes. We also show that medaka ES cells express differentiation gene markers during chimeric embryogenesis. Therefore, the evolutionary distance and different embryogenesis speeds do not produce donor-host incompatibility to compromise chimera formation between medaka and zebrafish, and molecular markers are valuable for analyzing lineage commitment and cell differentiation in interspecific chimeric embryos. PMID:22204449

  9. Fourteen-Genome Comparison Identifies DNA Markers for Severe-Disease-Associated Strains of Clostridium difficile▿†

    PubMed Central

    Forgetta, Vincenzo; Oughton, Matthew T.; Marquis, Pascale; Brukner, Ivan; Blanchette, Ruth; Haub, Kevin; Magrini, Vince; Mardis, Elaine R.; Gerding, Dale N.; Loo, Vivian G.; Miller, Mark A.; Mulvey, Michael R.; Rupnik, Maja; Dascal, Andre; Dewar, Ken

    2011-01-01

    Clostridium difficile is a common cause of infectious diarrhea in hospitalized patients. A severe and increased incidence of C. difficile infection (CDI) is associated predominantly with the NAP1 strain; however, the existence of other severe-disease-associated (SDA) strains and the extensive genetic diversity across C. difficile complicate reliable detection and diagnosis. Comparative genome analysis of 14 sequenced genomes, including those of a subset of NAP1 isolates, allowed the assessment of genetic diversity within and between strain types to identify DNA markers that are associated with severe disease. Comparative genome analysis of 14 isolates, including five publicly available strains, revealed that C. difficile has a core genome of 3.4 Mb, comprising ∼3,000 genes. Analysis of the core genome identified candidate DNA markers that were subsequently evaluated using a multistrain panel of 177 isolates, representing more than 50 pulsovars and 8 toxinotypes. A subset of 117 isolates from the panel had associated patient data that allowed assessment of an association between the DNA markers and severe CDI. We identified 20 candidate DNA markers for species-wide detection and 10,683 single nucleotide polymorphisms (SNPs) associated with the predominant SDA strain (NAP1). A species-wide detection candidate marker, the sspA gene, was found to be the same across 177 sequenced isolates and lacked significant similarity to those of other species. Candidate SNPs in genes CD1269 and CD1265 were found to associate more closely with disease severity than currently used diagnostic markers, as they were also present in the toxin A-negative and B-positive (A-B+) strain types. The genetic markers identified illustrate the potential of comparative genomics for the discovery of diagnostic DNA-based targets that are species specific or associated with multiple SDA strains. PMID:21508155

  10. Analysis of some polymorphic markers of the CFTR gene in cystic fibrosis patients and healthy donors from the Moscow region

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Amosenko, F.A.; Sazonova, M.A.; Kapranov, N.I.

    1995-04-01

    Allelic frequencies of three polymorphic markers in the CFTR gene were estimated on chromosomes derived from cystic fibrosis (CF) patients and healthy donors from Moscow and the Moscow region. These polymorphic markers are tetranucleotide tandem repeats GATT in intron 6B, M470V in exon 10, and T854T in exon 14 (fragment A). Frequencies at allele 1 of the M470V marker, along with allele 2 of GATT and T854T, are two times higher for CF patients without {Delta}F508 mutation than for healthy donors, and there is linkage disequilibrium of these alleles of the polymorphic markers analyzed with the CF gene. Allele 1more » of M470V and T854T markers, as well as allele 2 of the GATT marker (six repeats), are absolutely linked to mutation F508 of the CFTR gene. Using the polymorphic markers studied, family analysis of CF was carried out in two families. 10 refs., 1 fig., 1 tab.« less

  11. Identification of chemical markers in Cordyceps sinensis by HPLC-MS/MS.

    PubMed

    Hu, Hankun; Xiao, Ling; Zheng, Baogen; Wei, Xin; Ellis, Alexis; Liu, Yi-Ming

    2015-10-01

    Authentication and quality assessment of Cordyceps sinensis, a precious and pricey natural product that offers a variety of health benefits, is highly significant. To identify effective chemical markers, authentic C. sinensis was thoroughly screened by using HPLC-MS/MS. In addition to many previously reported ingredients, two glycosides, i.e., cyclo-Ala-Leu-rhamnose and Phe-o-glucose, were detected for the first time in this material. Six ingredients detected, including cordycepin, D-mannitol, Phe, Phe-o-glucose, cyclo-Gly-Pro, and cyclo-Ala-Leu-rhamnose, were selected as a collection of chemical markers. An HPLC-MS/MS method was developed to simultaneously quantify them with sensitivity and specificity. The method had limits of detection ranging from 0.008 μg mL(-1) for cordycepin to 0.75 μg mL(-1) for cyclo-Gly-Pro. Recovery was found between 96 and 103 % in all tests. To evaluate the effectiveness of the marker collection proposed, five authentic C. sinensis samples and five samples of its substitutes were analyzed. Cordycepin, D-mannitol, and Phe were found present in all samples. The contents ranged from 0.0076 to 0.029 % (w/w) for cordycepin, 0.33 to 18.9 % for mannitol, and 0.0013 to 0.642 % for Phe. Interestingly, the two glycosides, Phe-o-glucose and cyclo-Ala-Leu-rhamnose, were detected only in authentic C. sinensis samples. These results indicated that the proposed protocol based on HPLC-MS/MS quantification of the markers might have a great potential in authentication and quality assessment of C. sinensis. Graphical abstract Chemical markers of C. sinensis identified in this work.

  12. Preimplantation genetic diagnosis for Duchenne muscular dystrophy by multiple displacement amplification.

    PubMed

    Ren, Zi; Zeng, Hai-tao; Xu, Yan-wen; Zhuang, Guang-lun; Deng, Jie; Zhang, Cheng; Zhou, Can-quan

    2009-02-01

    To evaluate the use of multiple displacement amplification (MDA) in preimplantation genetic diagnosis (PGD) for female carriers with Duchenne muscular dystrophy (DMD). MDA was used to amplify a whole genome of single cells. Following the setup on single cells, the test was applied in two clinical cases of PGD. One mutant exon, six short tandem repeats (STR) markers within the dystrophin gene, and amelogenin were incorporated into singleplex polymerase chain reaction (PCR) assays on MDA products of single blastomeres. Center for reproductive medicine in First Affiliated Hospital, Sun Yat-sen University, China. Two female carriers with a duplication of exons 3-11 and a deletion of exons 47-50, respectively. The MDA of single cells and fluorescent PCR assays for PGD. The ability to analyze single blastomeres for DMD using MDA. The protocol setup previously allowed for the accurate diagnosis of each embryo. Two clinical cases resulted in a healthy girl, which was the first successful clinical application of MDA in PGD for DMD. We suggest that this protocol is reliable to increase the accuracy of the PGD for DMD.

  13. Multiple-strand displacement and identification of single nucleotide polymorphisms as markers of genotypic variation of Pasteuria penetrans biotypes infecting root-knot nematodes.

    PubMed

    Nong, Guang; Chow, Virginia; Schmidt, Liesbeth M; Dickson, Don W; Preston, James F

    2007-08-01

    Pasteuria species are endospore-forming obligate bacterial parasites of soil-inhabiting nematodes and water-inhabiting cladocerans, e.g. water fleas, and are closely related to Bacillus spp. by 16S rRNA gene sequence. As naturally occurring bacteria, biotypes of Pasteuria penetrans are attractive candidates for the biocontrol of various Meloidogyne spp. (root-knot nematodes). Failure to culture these bacteria outside their hosts has prevented isolation of genomic DNA in quantities sufficient for identification of genes associated with host recognition and virulence. We have applied multiple-strand displacement amplification (MDA) to generate DNA for comparative genomics of biotypes exhibiting different host preferences. Using the genome of Bacillus subtilis as a paradigm, MDA allowed quantitative detection and sequencing of 12 marker genes from 2000 cells. Meloidogyne spp. infected with P. penetrans P20 or B4 contained single nucleotide polymorphisms (SNPs) in the spoIIAB gene that did not change the amino acid sequence, or that substituted amino acids with similar chemical properties. Individual nematodes infected with P. penetrans P20 or B4 contained SNPs in the spoIIAB gene sequenced in MDA-generated products. Detection of SNPs in the spoIIAB gene in a nematode indicates infection by more than one genotype, supporting the need to sequence genomes of Pasteuria spp. derived from single spore isolates.

  14. Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

    PubMed Central

    Chin, Jun L.; Pavlides, Michael; Moolla, Ahmad; Ryan, John D.

    2016-01-01

    Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID:27378924

  15. MIDAS: software for analysis and visualisation of interallelic disequilibrium between multiallelic markers

    PubMed Central

    Gaunt, Tom R; Rodriguez, Santiago; Zapata, Carlos; Day, Ian NM

    2006-01-01

    Background Various software tools are available for the display of pairwise linkage disequilibrium across multiple single nucleotide polymorphisms. The HapMap project also presents these graphics within their website. However, these approaches are limited in their use of data from multiallelic markers and provide limited information in a graphical form. Results We have developed a software package (MIDAS – Multiallelic Interallelic Disequilibrium Analysis Software) for the estimation and graphical display of interallelic linkage disequilibrium. Linkage disequilibrium is analysed for each allelic combination (of one allele from each of two loci), between all pairwise combinations of any type of multiallelic loci in a contig (or any set) of many loci (including single nucleotide polymorphisms, microsatellites, minisatellites and haplotypes). Data are presented graphically in a novel and informative way, and can also be exported in tabular form for other analyses. This approach facilitates visualisation of patterns of linkage disequilibrium across genomic regions, analysis of the relationships between different alleles of multiallelic markers and inferences about patterns of evolution and selection. Conclusion MIDAS is a linkage disequilibrium analysis program with a comprehensive graphical user interface providing novel views of patterns of linkage disequilibrium between all types of multiallelic and biallelic markers. Availability Available from and PMID:16643648

  16. Use of Simple Sequence Repeat (SSR) markers for DNA fingerprinting and diversity analysis of sugarcane (Saccharum spp.) cultivars resistant and susceptible to red rot

    USDA-ARS?s Scientific Manuscript database

    In recent years SSR markers have been used widely for the genetic analysis. The objective of present research was to use SSR markers to develop DNA-based genetic identification and analyze genetic relationship of sugarcane cultivars grown in Pakistan either resistant or susceptible to red rot. Twent...

  17. Converging Intracranial Markers of Conscious Access

    PubMed Central

    Gaillard, Raphaël; Dehaene, Stanislas; Adam, Claude; Clémenceau, Stéphane; Hasboun, Dominique; Baulac, Michel; Cohen, Laurent; Naccache, Lionel

    2009-01-01

    We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms), accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access. PMID:19296722

  18. Integrative analysis for the discovery of lung cancer serological markers and validation by MRM-MS

    PubMed Central

    An, Byung Chull; Choi, Yoo-Duk; Yang, Eun Gyeong; Na, Kook-Joo; Lee, Seung-Taek; Park, Jae-Il; Kim, Seon-Young; Lee, Cheolju

    2017-01-01

    Non-small-cell lung cancer (NSCLC) constitutes approximately 80% of all diagnosed lung cancers, and diagnostic markers detectable in the plasma/serum of NSCLC patients are greatly needed. In this study, we established a pipeline for the discovery of markers using 9 transcriptome datasets from publicly available databases and profiling of six lung cancer cell secretomes. Thirty-one out of 312 proteins that overlapped between two-fold differentially expressed genes and identified cell secretome proteins were detected in the pooled plasma of lung cancer patients. To quantify the candidates in the serum of NSCLC patients, multiple-reaction-monitoring mass spectrometry (MRM-MS) was performed for five candidate biomarkers. Finally, two potential biomarkers (BCHE and GPx3; AUC = 0.713 and 0.673, respectively) and one two-marker panel generated by logistic regression (BCHE/GPx3; AUC = 0.773) were identified. A validation test was performed by ELISA to evaluate the reproducibility of GPx3 and BCHE expression in an independent set of samples (BCHE and GPx3; AUC = 0.630 and 0.759, respectively, BCHE/GPx3 panel; AUC = 0.788). Collectively, these results demonstrate the feasibility of using our pipeline for marker discovery and our MRM-MS platform for verifying potential biomarkers of human diseases. PMID:28837649

  19. Integrative analysis for the discovery of lung cancer serological markers and validation by MRM-MS.

    PubMed

    Shin, Jihye; Song, Sang-Yun; Ahn, Hee-Sung; An, Byung Chull; Choi, Yoo-Duk; Yang, Eun Gyeong; Na, Kook-Joo; Lee, Seung-Taek; Park, Jae-Il; Kim, Seon-Young; Lee, Cheolju; Lee, Seung-Won

    2017-01-01

    Non-small-cell lung cancer (NSCLC) constitutes approximately 80% of all diagnosed lung cancers, and diagnostic markers detectable in the plasma/serum of NSCLC patients are greatly needed. In this study, we established a pipeline for the discovery of markers using 9 transcriptome datasets from publicly available databases and profiling of six lung cancer cell secretomes. Thirty-one out of 312 proteins that overlapped between two-fold differentially expressed genes and identified cell secretome proteins were detected in the pooled plasma of lung cancer patients. To quantify the candidates in the serum of NSCLC patients, multiple-reaction-monitoring mass spectrometry (MRM-MS) was performed for five candidate biomarkers. Finally, two potential biomarkers (BCHE and GPx3; AUC = 0.713 and 0.673, respectively) and one two-marker panel generated by logistic regression (BCHE/GPx3; AUC = 0.773) were identified. A validation test was performed by ELISA to evaluate the reproducibility of GPx3 and BCHE expression in an independent set of samples (BCHE and GPx3; AUC = 0.630 and 0.759, respectively, BCHE/GPx3 panel; AUC = 0.788). Collectively, these results demonstrate the feasibility of using our pipeline for marker discovery and our MRM-MS platform for verifying potential biomarkers of human diseases.

  20. Evaluation of hippuric acid content in goat milk as a marker of feeding regimen.

    PubMed

    Carpio, A; Bonilla-Valverde, D; Arce, C; Rodríguez-Estévez, V; Sánchez-Rodríguez, M; Arce, L; Valcárcel, M

    2013-09-01

    Organic producers, traders, and consumers must address 2 issues related to milk: authentication of the production system and nutritional differentiation. The presence of hippuric acid (HA) in goat milk samples has been proposed as a possible marker to differentiate the feeding regimen of goats. The objective of this work is to check the hypothesis that HA could be a marker for the type of feeding regimen of goats by studying the influence of production system (conventional or organic) and feeding regimen (with or without grazing fodder). With this purpose, commercial cow and goat milk samples (n=27) and raw goat milk samples (n=185; collected from different breeds, localizations, and dates) were analyzed. Samples were grouped according to breed, feeding regimen, production system, and origin to compare HA content by ANOVA and honestly significant difference Tukey test at a confidence level of ≥95%. Hippuric acid content was obtained by analyzing milk samples with capillary electrophoresis. This method was validated by analyzing part of the samples with HPLC as a reference technique. Sixty-nine raw goat milk samples (of the total 158 samples analyzed in this work) were quantified by capillary electrophoresis. In these samples, the lowest average content for HA was 7±3 mg/L. This value corresponds to a group of conventional raw milk samples from goats fed with compound feed. The highest value of this group was 28±10 mg/L, corresponding to goats fed compound feed plus grass. Conversely, for organic raw goat milk samples, the highest concentration was 67±14 mg/L, which corresponds to goats fed grass. By contrast, the lowest value of this organic group was 26±10 mg/L, which belongs to goats fed organic compounds. Notice that the highest HA average content was found in samples from grazing animals corresponding to the organic group. This result suggests that HA is a good marker to determine the type of goats feeding regimen; a high content of HA represents a diet

  1. Uniparental genetic markers in South Amerindians

    PubMed Central

    Bisso-Machado, Rafael; Bortolini, Maria Cátira; Salzano, Francisco Mauro

    2012-01-01

    A comprehensive review of uniparental systems in South Amerindians was undertaken. Variability in the Y-chromosome haplogroups were assessed in 68 populations and 1,814 individuals whereas that of Y-STR markers was assessed in 29 populations and 590 subjects. Variability in the mitochondrial DNA (mtDNA) haplogroup was examined in 108 populations and 6,697 persons, and sequencing studies used either the complete mtDNA genome or the highly variable segments 1 and 2. The diversity of the markers made it difficult to establish a general picture of Y-chromosome variability in the populations studied. However, haplogroup Q1a3a* was almost always the most prevalent whereas Q1a3* occurred equally in all regions, which suggested its prevalence among the early colonizers. The STR allele frequencies were used to derive a possible ancient Native American Q-clade chromosome haplotype and five of six STR loci showed significant geographic variation. Geographic and linguistic factors moderately influenced the mtDNA distributions (6% and 7%, respectively) and mtDNA haplogroups A and D correlated positively and negatively, respectively, with latitude. The data analyzed here provide rich material for understanding the biological history of South Amerindians and can serve as a basis for comparative studies involving other types of data, such as cultural data. PMID:22888284

  2. Characterization and identification of ISSR markers associated with oil content in sea buckthorn berries.

    PubMed

    Ding, J; Ruan, C J; Guan, Y; Shan, J Y; Li, H; Bao, Y H

    2016-08-19

    Bioactive oils extracted from sea buckthorn (Hippophae rhamnoides) berries contain highly nutritional and medicinal compounds; however, the oil contents of sea buckthorn berries are very low. Thirteen inter-simple sequence repeat (ISSR) primers were used to identify markers associated with oil content of dry pulp in 51 cultivars and lines, which clustered into three major groups based on 137 polymorphic markers. Dry pulp oil contents in 45 cultivars and lines in Group I ranged from 6.6 to 33.1%; these accessions belonged to H. rhamnoides ssp mongolica and its hybrids with H. rhamnoides ssp sinensis. Three lines (H. rhamnoides ssp mongolica) in Group II had high dry pulp oil contents (33.7 to 37.5%), whereas three lines of hybrids in Group III had low dry pulp oil contents (10.9 to 17.5%). The dry pulp oil content of H. rhamnoides ssp mongolica (27.2 ± 0.9%) was higher than that of hybrids (12.0 ± 1.2%) (P < 0.01). Four ISSR markers (881 340 , 825 1000 , 817 380 , and 807 1100 ) had positive association with high dry pulp oil content (P < 0.01) using stepwise multiple regression analysis. The use of these ISSR markers is a potential strategy to select genotypes with high dry pulp oil content and suitable parental combinations for improvement of sea buckthorn berries.

  3. EST-derived SSR markers used as anchor loci for the construction of a consensus linkage map in ryegrass (Lolium spp.)

    PubMed Central

    2010-01-01

    Background Genetic markers and linkage mapping are basic prerequisites for marker-assisted selection and map-based cloning. In the case of the key grassland species Lolium spp., numerous mapping populations have been developed and characterised for various traits. Although some genetic linkage maps of these populations have been aligned with each other using publicly available DNA markers, the number of common markers among genetic maps is still low, limiting the ability to compare candidate gene and QTL locations across germplasm. Results A set of 204 expressed sequence tag (EST)-derived simple sequence repeat (SSR) markers has been assigned to map positions using eight different ryegrass mapping populations. Marker properties of a subset of 64 EST-SSRs were assessed in six to eight individuals of each mapping population and revealed 83% of the markers to be polymorphic in at least one population and an average number of alleles of 4.88. EST-SSR markers polymorphic in multiple populations served as anchor markers and allowed the construction of the first comprehensive consensus map for ryegrass. The integrated map was complemented with 97 SSRs from previously published linkage maps and finally contained 284 EST-derived and genomic SSR markers. The total map length was 742 centiMorgan (cM), ranging for individual chromosomes from 70 cM of linkage group (LG) 6 to 171 cM of LG 2. Conclusions The consensus linkage map for ryegrass based on eight mapping populations and constructed using a large set of publicly available Lolium EST-SSRs mapped for the first time together with previously mapped SSR markers will allow for consolidating existing mapping and QTL information in ryegrass. Map and markers presented here will prove to be an asset in the development for both molecular breeding of ryegrass as well as comparative genetics and genomics within grass species. PMID:20712870

  4. Left Ventricular Hypertrophy: An allometric comparative analysis of different ECG markers

    NASA Astrophysics Data System (ADS)

    Bonomini, M. P.; Ingallina, F.; Barone, V.; Valentinuzzi, M. E.; Arini, P. D.

    2011-12-01

    Allometry, in general biology, measures the relative growth of a part in relation to the whole living organism. Left ventricular hypertrophy (LVH) is the heart adaptation to excessive load (systolic or diastolic). The increase in left ventricular mass leads to an increase in the electrocardiographic voltages. Based on clinical data, we compared the allometric behavior of three different ECG markers of LVH. To do this, the allometric fit AECG = δ + β (VM) relating left ventricular mass (estimated from ecocardiographic data) and ECG amplitudes (expressed as the Cornell-Voltage, Sokolow and the ECG overall voltage indexes) were compared. Besides, sensitivity and specifity for each index were analyzed. The more sensitive the ECG criteria, the better the allometric fit. In conclusion: The allometric paradigm should be regarded as the way to design new and more sensitive ECG-based LVH markers.

  5. Molecular phylogeny of Gavilea (Chloraeinae: Orchidaceae) using plastid and nuclear markers.

    PubMed

    Chemisquy, M Amelia; Morrone, Osvaldo

    2012-03-01

    A phylogenetic analysis is provided for 70% of the representatives of genus Gavilea, as well as for several species of the remaining genera of subtribe Chloraeinae: Bipinnula, Chloraea and Geoblasta. Sequences from the plastid markers rpoC1, matK-trnK and atpB-rbcL and the nuclear marker ITS, were analyzed using Maximum Parsimony and Bayesian Inference. Monophyly of subtribe Chloraeinae was confirmed, as well as its position inside tribe Cranichideae. Neither Chloraea nor Bipinnula were recovered as monophyletic. Gavilea turned out polyphyletic, with Chloraeachica embedded in the genus while Gavilea supralabellata was related to Chloraea and might be a hybrid between both genera. None of the two sections of Gavilea were monophyletic, and the topologies obtained do not suggest a new division of the genus. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Lipid and other plasma markers are associated with anxiety, depression, and fatigue.

    PubMed

    Lieberman, Harris R; Kellogg, Mark D; Kramer, F Matthew; Bathalon, Gaston P; Lesher, Larry L

    2012-03-01

    Few peripheral metabolites have been shown to be associated with mood in healthy individuals or patients with central nervous system diseases. During military basic combat training (BCT), mood state, physical performance and body composition substantially improve, providing an opportunity to examine relationships between mood and nutritional and hormonal biomarkers. Thirty-five females enrolled in U.S. Marine BCT, an intense physically and mentally challenging 12-week course, were studied. Every 4 weeks, mood was assessed with the Profile of Mood States (POMS), as were nutritional, metabolic and hormonal plasma markers. Mood and fitness improved over BCT, and there were substantial changes in biochemical markers. Multiple regression demonstrated that, in combination, cholesterol (HDL, LDL), fructosamine, triglycerides, free fatty acids (FFA), dehydroepiandrosterone-sulfate (DHEA-S), ACTH, and substance P accounted for 44% of variation in anxiety, 40% confusion, 37% fatigue, 27% depression and 40% in total mood (p < .0001). Increased HDL, FFA, DHEA-S, and substance P were associated with degraded mood (p < .05). Increased LDL, triglycerides, fructosamine, and ACTH were associated with improved mood (p < .05). Other markers, including glucose, cortisol, and C-reactive protein were not associated with mood. Normal human mood state was associated with 8 plasma markers. Increased HDL and lower LDL, which are associated with improved cardiovascular status, were associated with negative affect. Fructosamine and substance P, not previously known to be related to mood, were associated with it. We are not aware of any biological parameters that in aggregate predict such a substantial proportion of variation in normal mood.

  7. Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-κB and STAT3.

    PubMed

    Ma, Jing; Gong, Wei; Liu, Su; Li, Qian; Guo, Mengzheng; Wang, Jinhan; Wang, Suying; Chen, Naiyao; Wang, Yafei; Liu, Qiang; Zhao, Hui

    2018-01-01

    The oncogenic microRNA-21 contributes to the pathogenesis of multiple myeloma. Ibrutinib (also referred to as PCI-32765), an inhibitor of Bruton's tyrosine kinase, while its effects on multiple myeloma have not been well described. Here, we show that microRNA-21 is an oncogenic marker closely linked with progression of multiple myeloma. Moreover, ibrutinib attenuates microRNA-21 expression in multiple myeloma cells by inhibiting nuclear factor-κB and signal transducer and activator of transcription 3 signaling pathways. Taken together, our results suggest that ibrutinib is a promising potential treatment for multiple myeloma. Further investigation of mechanisms of ibrutinib function in multiple myeloma will be necessary to evaluate its use as a novel multiple myeloma treatment.

  8. A Bayesian test for Hardy–Weinberg equilibrium of biallelic X-chromosomal markers

    PubMed Central

    Puig, X; Ginebra, J; Graffelman, J

    2017-01-01

    The X chromosome is a relatively large chromosome, harboring a lot of genetic information. Much of the statistical analysis of X-chromosomal information is complicated by the fact that males only have one copy. Recently, frequentist statistical tests for Hardy–Weinberg equilibrium have been proposed specifically for dealing with markers on the X chromosome. Bayesian test procedures for Hardy–Weinberg equilibrium for the autosomes have been described, but Bayesian work on the X chromosome in this context is lacking. This paper gives the first Bayesian approach for testing Hardy–Weinberg equilibrium with biallelic markers at the X chromosome. Marginal and joint posterior distributions for the inbreeding coefficient in females and the male to female allele frequency ratio are computed, and used for statistical inference. The paper gives a detailed account of the proposed Bayesian test, and illustrates it with data from the 1000 Genomes project. In that implementation, a novel approach to tackle multiple testing from a Bayesian perspective through posterior predictive checks is used. PMID:28900292

  9. Four-dimensional measurement of the displacement of internal fiducial and skin markers during 320-multislice computed tomography scanning of breast cancer.

    PubMed

    Yamashita, Hideomi; Okuma, Kae; Tada, Keiichiro; Shiraishi, Kenshiro; Takahashi, Wataru; Shibata-Mobayashi, Shino; Sakumi, Akira; Saotome, Naoya; Haga, Akihiro; Onoe, Tsuyoshi; Ino, Kenji; Akahane, Masaaki; Ohtomo, Kuni; Nakagawa, Keiichi

    2012-10-01

    To study the three-dimensional movement of internal tumor bed fiducial and breast skin markers, using 320-multislice computed tomography (CT); and to analyze intrafractional errors for breast cancer patients undergoing breast irradiation. This study examined 280 markers on the skin of the breast (200 markers) and on the primary tumor bed (80 markers) of 20 patients treated by external-beam photon radiotherapy. Motion assessment was analyzed in 41 respiratory phases during 20 s of cine CT in the radiotherapy position. To assess intrafractional errors resulting from respiratory motion, four-dimensional CT scans were acquired for 20 patients. Motion in the anterior-posterior (A/P) and superior-inferior (S/I) directions showed a strong correlation (|r| > 0.7) with the respiratory curve for most markers (79% and 70%, respectively). The average marker displacements between maximum and minimum value during 20 s for the 200 breast skin metal markers were 1.1 ± 0.3 mm, 2.1 ± 0.6 mm, and 1.6 ± 0.4 mm in the left-right, A/P, and S/I directions, respectively. For the 80 tumor bed clips, displacements were 0.9 ± 0.2 mm in left-right, 1.7 ± 0.5 mm in A/P, and 1.1 ± 0.3 mm in S/I. There was no significant difference in the motion between breast quadrant regions or between the primary site and the other regions. Motion in primary breast tumors was evaluated with 320-multislice CT. Very little change was detected during individual radiation treatment fractions. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Efficient anchoring of alien chromosome segments introgressed into bread wheat by new Leymus racemosus genome-based markers.

    PubMed

    Edet, Offiong Ukpong; Kim, June-Sik; Okamoto, Masanori; Hanada, Kousuke; Takeda, Tomoyuki; Kishii, Masahiro; Gorafi, Yasir Serag Alnor; Tsujimoto, Hisashi

    2018-03-27

    The tertiary gene pool of bread wheat, to which Leymus racemosus belongs, has remained underutilized due to the current limited genomic resources of the species that constitute it. Continuous enrichment of public databases with useful information regarding these species is, therefore, needed to provide insights on their genome structures and aid successful utilization of their genes to develop improved wheat cultivars for effective management of environmental stresses. We generated de novo DNA and mRNA sequence information of L. racemosus and developed 110 polymorphic PCR-based markers from the data, and to complement the PCR markers, DArT-seq genotyping was applied to develop additional 9990 SNP markers. Approximately 52% of all the markers enabled us to clearly genotype 22 wheat-L. racemosus chromosome introgression lines, and L. racemosus chromosome-specific markers were highly efficient in detailed characterization of the translocation and recombination lines analyzed. A further analysis revealed remarkable transferability of the PCR markers to three other important Triticeae perennial species: L. mollis, Psathyrostachys huashanica and Elymus ciliaris, indicating their suitability for characterizing wheat-alien chromosome introgressions carrying chromosomes of these genomes. The efficiency of the markers in characterizing wheat-L. racemosus chromosome introgression lines proves their reliability, and their high transferability further broadens their scope of application. This is the first report on sequencing and development of markers from L. racemosus genome and the application of DArT-seq to develop markers from a perennial wild relative of wheat, marking a paradigm shift from the seeming concentration of the technology on cultivated species. Integration of these markers with appropriate cytogenetic methods would accelerate development and characterization of wheat-alien chromosome introgression lines.

  11. Genome-wide generation and use of informative intron-spanning and intron-length polymorphism markers for high-throughput genetic analysis in rice

    PubMed Central

    Badoni, Saurabh; Das, Sweta; Sayal, Yogesh K.; Gopalakrishnan, S.; Singh, Ashok K.; Rao, Atmakuri R.; Agarwal, Pinky; Parida, Swarup K.; Tyagi, Akhilesh K.

    2016-01-01

    We developed genome-wide 84634 ISM (intron-spanning marker) and 16510 InDel-fragment length polymorphism-based ILP (intron-length polymorphism) markers from genes physically mapped on 12 rice chromosomes. These genic markers revealed much higher amplification-efficiency (80%) and polymorphic-potential (66%) among rice accessions even by a cost-effective agarose gel-based assay. A wider level of functional molecular diversity (17–79%) and well-defined precise admixed genetic structure was assayed by 3052 genome-wide markers in a structured population of indica, japonica, aromatic and wild rice. Six major grain weight QTLs (11.9–21.6% phenotypic variation explained) were mapped on five rice chromosomes of a high-density (inter-marker distance: 0.98 cM) genetic linkage map (IR 64 x Sonasal) anchored with 2785 known/candidate gene-derived ISM and ILP markers. The designing of multiple ISM and ILP markers (2 to 4 markers/gene) in an individual gene will broaden the user-preference to select suitable primer combination for efficient assaying of functional allelic variation/diversity and realistic estimation of differential gene expression profiles among rice accessions. The genomic information generated in our study is made publicly accessible through a user-friendly web-resource, “Oryza ISM-ILP marker” database. The known/candidate gene-derived ISM and ILP markers can be enormously deployed to identify functionally relevant trait-associated molecular tags by optimal-resource expenses, leading towards genomics-assisted crop improvement in rice. PMID:27032371

  12. Diversity and genetic stability in banana genotypes in a breeding program using inter simple sequence repeats (ISSR) markers.

    PubMed

    Silva, A V C; Nascimento, A L S; Vitória, M F; Rabbani, A R C; Soares, A N R; Lédo, A S

    2017-02-23

    Banana (Musa spp) is a fruit species frequently cultivated and consumed worldwide. Molecular markers are important for estimating genetic diversity in germplasm and between genotypes in breeding programs. The objective of this study was to analyze the genetic diversity of 21 banana genotypes (FHIA 23, PA42-44, Maçã, Pacovan Ken, Bucaneiro, YB42-47, Grand Naine, Tropical, FHIA 18, PA94-01, YB42-17, Enxerto, Japira, Pacovã, Prata-Anã, Maravilha, PV79-34, Caipira, Princesa, Garantida, and Thap Maeo), by using inter-simple sequence repeat (ISSR) markers. Material was generated from the banana breeding program of Embrapa Cassava & Fruits and evaluated at Embrapa Coastal Tablelands. The 12 primers used in this study generated 97.5% polymorphism. Four clusters were identified among the different genotypes studied, and the sum of the first two principal components was 48.91%. From the Unweighted Pair Group Method using Arithmetic averages (UPGMA) dendrogram, it was possible to identify two main clusters and subclusters. Two genotypes (Garantida and Thap Maeo) remained isolated from the others, both in the UPGMA clustering and in the principal cordinate analysis (PCoA). Using ISSR markers, we could analyze the genetic diversity of the studied material and state that these markers were efficient at detecting sufficient polymorphism to estimate the genetic variability in banana genotypes.

  13. The relationship of exposure to air pollutants in pregnancy with surrogate markers of endothelial dysfunction in umbilical cord.

    PubMed

    Poursafa, Parinaz; Baradaran-Mahdavi, Sadegh; Moradi, Bita; Haghjooy Javanmard, Shaghayegh; Tajadini, Mohammadhasan; Mehrabian, Ferdous; Kelishadi, Roya

    2016-04-01

    This study aims to investigate the association of exposure to ambient air pollution during pregnancy with cord blood concentrations of surrogate markers of endothelial dysfunction. This population-based cohort was conducted from March 2014 to March 2015 among 250 mother-neonate pairs in urban areas of Isfahan, the second large and air-polluted city in Iran. We analyzed the association between the ambient carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), particular matter 10 (PM10), and air quality index (AQI) with cord blood levels of endothelin-1, vascular adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM). Multiple regression analysis was conducted after adjustment for potential confounding factors and covariates. The regression coefficient (beta), standard error of the estimate (SE), and 95% confidence intervals for each regression coefficient (95% CI) are reported. Data of 233 mother-neonate pairs were complete, and included in the analysis. Multiple regression analyses showed that AQI, CO and O3 had significant correlation with cord blood ICAM-1 [Beta (SE), 95%CI: 2.93 (0.72), 1.33,5.54; 2.28(1.44), 1.56,5.12; and 2.02(0.01), 1.03,2.04, respectively] as well as with VCAM-1 [2.78(0.91), 1.69,4.57; 2.47(1.47), 1.43,5.37; and 2.01(0.01),1.07,2.04, respectively]. AQI, PM10, and SO2 were significantly associated with Endothelin-1 concentrations [Beta (SE), 95%CI: 10.16(5.08),7.61,14.28; 9.70(3.46), 2.88,16.52; and 1.07(0.02), 1.03,2.11, respectively]. The significant associations of air pollutants with markers of endothelial dysfunction during fetal period may provide another evidence on the adverse health effects of air pollutants on early stages of atherosclerosis from fetal period. Our findings underscore the importance of considering environmental factors in primordial prevention of chronic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Mirrored pyramidal wells for simultaneous multiple vantage point microscopy.

    PubMed

    Seale, K T; Reiserer, R S; Markov, D A; Ges, I A; Wright, C; Janetopoulos, C; Wikswo, J P

    2008-10-01

    We report a novel method for obtaining simultaneous images from multiple vantage points of a microscopic specimen using size-matched microscopic mirrors created from anisotropically etched silicon. The resulting pyramidal wells enable bright-field and fluorescent side-view images, and when combined with z-sectioning, provide additional information for 3D reconstructions of the specimen. We have demonstrated the 3D localization and tracking over time of the centrosome of a live Dictyostelium discoideum. The simultaneous acquisition of images from multiple perspectives also provides a five-fold increase in the theoretical collection efficiency of emitted photons, a property which may be useful for low-light imaging modalities such as bioluminescence, or low abundance surface-marker labelling.

  15. Mirrored pyramidal wells for simultaneous multiple vantage point microscopy

    PubMed Central

    Seale, K.T.; Reiserer, R.S.; Markov, D.A.; Ges, I.A.; Wright, C.; Janetopoulos, C.; Wikswo, J.P.

    2013-01-01

    Summary We report a novel method for obtaining simultaneous images from multiple vantage points of a microscopic specimen using size-matched microscopic mirrors created from anisotropically etched silicon. The resulting pyramidal wells enable bright-field and fluorescent side-view images, and when combined with z-sectioning, provide additional information for 3D reconstructions of the specimen. We have demonstrated the 3D localization and tracking over time of the centrosome of a live Dictyostelium discoideum. The simultaneous acquisition of images from multiple perspectives also provides a five-fold increase in the theoretical collection efficiency of emitted photons, a property which may be useful for low-light imaging modalities such as bioluminescence, or low abundance surface-marker labelling. PMID:19017196

  16. Recombination of mitochondrial DNA in skeletal muscle of individuals with multiple mitochondrial DNA heteroplasmy.

    PubMed

    Zsurka, Gábor; Kraytsberg, Yevgenia; Kudina, Tatiana; Kornblum, Cornelia; Elger, Christian E; Khrapko, Konstantin; Kunz, Wolfram S

    2005-08-01

    Experimental evidence for human mitochondrial DNA (mtDNA) recombination was recently obtained in an individual with paternal inheritance of mtDNA and in an in vitro cell culture system. Whether mtDNA recombination is a common event in humans remained to be determined. To detect mtDNA recombination in human skeletal muscle, we analyzed the distribution of alleles in individuals with multiple mtDNA heteroplasmy using single-cell PCR and allele-specific PCR. In all ten individuals who carried a heteroplasmic D-loop mutation and a distantly located tRNA point mutation or a large deletion, we observed a mixture of four allelic combinations (tetraplasmy), a hallmark of recombination. Twelve of 14 individuals with closely located heteroplasmic D-loop mutation pairs contained a mixture of only three types of mitochondrial genomes (triplasmy), consistent with the absence of recombination between adjacent markers. These findings indicate that mtDNA recombination is common in human skeletal muscle.

  17. Ideal, nonideal, and no-marker variables: The confirmatory factor analysis (CFA) marker technique works when it matters.

    PubMed

    Williams, Larry J; O'Boyle, Ernest H

    2015-09-01

    A persistent concern in the management and applied psychology literature is the effect of common method variance on observed relations among variables. Recent work (i.e., Richardson, Simmering, & Sturman, 2009) evaluated 3 analytical approaches to controlling for common method variance, including the confirmatory factor analysis (CFA) marker technique. Their findings indicated significant problems with this technique, especially with nonideal marker variables (those with theoretical relations with substantive variables). Based on their simulation results, Richardson et al. concluded that not correcting for method variance provides more accurate estimates than using the CFA marker technique. We reexamined the effects of using marker variables in a simulation study and found the degree of error in estimates of a substantive factor correlation was relatively small in most cases, and much smaller than error associated with making no correction. Further, in instances in which the error was large, the correlations between the marker and substantive scales were higher than that found in organizational research with marker variables. We conclude that in most practical settings, the CFA marker technique yields parameter estimates close to their true values, and the criticisms made by Richardson et al. are overstated. (c) 2015 APA, all rights reserved).

  18. Accuracy of an infrared marker-based patient positioning system (ExacTrac®) for stereotactic body radiotherapy in localizing the planned isocenter using fiducial markers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Montes-Rodríguez, María de los Ángeles, E-mail: angy24538@yahoo.com; Mitsoura, Eleni; Hernández-Bojórquez, Mariana

    2014-11-07

    Stereotactic Body Radiation Therapy (SBRT) requires a controlled immobilization and position monitoring of patient and target. The purpose of this work is to analyze the performance of the imaging system ExacTrac® (ETX) using infrared and fiducial markers. Materials and methods: In order to assure the accuracy of isocenter localization, a Quality Assurance procedure was applied using an infrared marker-based positioning system. Scans were acquired of an inhouse-agar gel and solid water phantom with infrared spheres. In the inner part of the phantom, three reference markers were delineated as reference and one pellet was place internally; which was assigned as themore » isocenter. The iPlan® RT Dose treatment planning system. Images were exported to the ETX console. Images were acquired with the ETX to check the correctness of the isocenter placement. Adjustments were made in 6D the reference markers were used to fuse the images. Couch shifts were registered. The procedure was repeated for verification purposes. Results: The data recorded of the verifications in translational and rotational movements showed averaged 3D spatial uncertainties of 0.31 ± 0.42 mm respectively 0.82° ± 0.46° in the phantom and the first correction of these uncertainties were of 1.51 ± 1.14 mm respectively and 1.37° ± 0.61°. Conclusions: This study shows a high accuracy and repeatability in positioning the selected isocenter. The ETX-system for verifying the treatment isocenter position has the ability to monitor the tracing position of interest, making it possible to be used for SBRT positioning within uncertainty ≤1mm.« less

  19. Fiducial marker for correlating images

    DOEpatents

    Miller, Lisa Marie [Rocky Point, NY; Smith, Randy J [Wading River, NY; Warren, John B [Port Jefferson, NY; Elliott, Donald [Hampton Bays, NY

    2011-06-21

    The invention relates to a fiducial marker having a marking grid that is used to correlate and view images produced by different imaging modalities or different imaging and viewing modalities. More specifically, the invention relates to the fiducial marking grid that has a grid pattern for producing either a viewing image and/or a first analytical image that can be overlaid with at least one other second analytical image in order to view a light path or to image different imaging modalities. Depending on the analysis, the grid pattern has a single layer of a certain thickness or at least two layers of certain thicknesses. In either case, the grid pattern is imageable by each imaging or viewing modality used in the analysis. Further, when viewing a light path, the light path of the analytical modality cannot be visualized by viewing modality (e.g., a light microscope objective). By correlating these images, the ability to analyze a thin sample that is, for example, biological in nature but yet contains trace metal ions is enhanced. Specifically, it is desired to analyze both the organic matter of the biological sample and the trace metal ions contained within the biological sample without adding or using extrinsic labels or stains.

  20. Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial.

    PubMed

    Khalili, Mohammad; Eghtesadi, Shahryar; Mirshafiey, Abbas; Eskandari, Ghazaleh; Sanoobar, Meisam; Sahraian, Mohamad Ali; Motevalian, Abbas; Norouzi, Abbas; Moftakhar, Shirin; Azimi, Amirreza

    2014-01-01

    Multiple sclerosis is a neurodegenerative and demyelinating disease of central nervous system. High levels of oxidative stress are associated with inflammation and play an important role in pathogenesis of multiple sclerosis. This double-blind, randomized controlled clinical study was carried out to determine the effect of daily consumption of lipoic acid on oxidative stress among multiple sclerosis patients. A total of 52 relapsing-remitting multiple sclerosis patients, aged 18-50 years with Expanded Disability Status Scale ≤5.5 were assigned to consume either lipoic acid (1200 mg/day) or placebo capsules for 12 weeks. Fasting blood samples were collected before the first dose taken and 12 hours after the last. Dietary intakes were obtained by using 3-day dietary records. Consumption of lipoic acid resulted in a significant improvement of total antioxidant capacity (TAC) in comparison to the placebo group (P = 0.004). Although a significant change of TAC (-1511 mmol/L, P = 0.001) was found within lipoic acid group, other markers of oxidative stress including superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde levels were not affected by lipoic acid consumption. These results suggest that 1200 mg of lipoic acid improves serum TAC among multiple sclerosis patients but does not affect other markers of oxidative stress.

  1. Genetic variation, population structure and linkage disequilibrium in Switchgrass with ISSR, SCoT and EST-SSR markers.

    PubMed

    Zhang, Yu; Yan, Haidong; Jiang, Xiaomei; Wang, Xiaoli; Huang, Linkai; Xu, Bin; Zhang, Xinquan; Zhang, Lexin

    2016-01-01

    To evaluate genetic variation, population structure, and the extent of linkage disequilibrium (LD), 134 switchgrass ( Panicum virgatum L.) samples were analyzed with 51 markers, including 16 ISSRs, 20 SCoTs, and 15 EST-SSRs. In this study, a high level of genetic variation was observed in the switchgrass samples and they had an average Nei's gene diversity index (H) of 0.311. A total of 793 bands were obtained, of which 708 (89.28 %) were polymorphic. Using a parameter marker index (MI), the efficiency of the three types of markers (ISSR, SCoT, and EST-SSR) in the study were compared and we found that SCoT had a higher marker efficiency than the other two markers. The 134 switchgrass samples could be divided into two sub-populations based on STRUCTURE, UPGMA clustering, and principal coordinate analyses (PCA), and upland and lowland ecotypes could be separated by UPGMA clustering and PCA analyses. Linkage disequilibrium analysis revealed an average r 2 of 0.035 across all 51 markers, indicating a trend of higher LD in sub-population 2 than that in sub-population 1 ( P  < 0.01). The population structure revealed in this study will guide the design of future association studies using these switchgrass samples.

  2. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition

    PubMed Central

    Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara Mª; Teixidó, Montserrat; Gimenez, Mª Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Bladé, Joan; de Larrea, Carlos Fernández

    2017-01-01

    The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1–4%, 5–20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6–9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×109/L vs. 214×109/L, P<0.0001) and higher bone marrow plasma cells (median 53% vs. 36%, P=0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia. PMID:28255016

  3. A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis.

    PubMed

    Sugii, Yuh; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Kumon, Kazuki; Mizutani, Akifumi; Seno, Akimasa; Tokutaka, Heizo; Kudoh, Takayuki; Seno, Masaharu

    2016-01-01

    To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer.

  4. The use of regression analysis in determining reference intervals for low hematocrit and thrombocyte count in multiple electrode aggregometry and platelet function analyzer 100 testing of platelet function.

    PubMed

    Kuiper, Gerhardus J A J M; Houben, Rik; Wetzels, Rick J H; Verhezen, Paul W M; Oerle, Rene van; Ten Cate, Hugo; Henskens, Yvonne M C; Lancé, Marcus D

    2017-11-01

    Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r 2 ≥ 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r 2 = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

  5. Improving selection of markers in nutrition research: evaluation of the criteria proposed by the ILSI Europe Marker Validation Initiative.

    PubMed

    Calder, Philip C; Boobis, Alan; Braun, Deborah; Champ, Claire L; Dye, Louise; Einöther, Suzanne; Greyling, Arno; Matthys, Christophe; Putz, Peter; Wopereis, Suzan; Woodside, Jayne V; Antoine, Jean-Michel

    2017-06-01

    The conduct of high-quality nutrition research requires the selection of appropriate markers as outcomes, for example as indicators of food or nutrient intake, nutritional status, health status or disease risk. Such selection requires detailed knowledge of the markers, and consideration of the factors that may influence their measurement, other than the effects of nutritional change. A framework to guide selection of markers within nutrition research studies would be a valuable tool for researchers. A multidisciplinary Expert Group set out to test criteria designed to aid the evaluation of candidate markers for their usefulness in nutrition research and subsequently to develop a scoring system for markers. The proposed criteria were tested using thirteen markers selected from a broad range of nutrition research fields. The result of this testing was a modified list of criteria and a template for evaluating a potential marker against the criteria. Subsequently, a semi-quantitative system for scoring a marker and an associated template were developed. This system will enable the evaluation and comparison of different candidate markers within the same field of nutrition research in order to identify their relative usefulness. The ranking criteria of proven, strong, medium or low are likely to vary according to research setting, research field and the type of tool used to assess the marker and therefore the considerations for scoring need to be determined in a setting-, field- and tool-specific manner. A database of such markers, their interpretation and range of possible values would be valuable to nutrition researchers.

  6. Using SCC8, SCF27 and VMC7f2 markers in grapevine breeding for seedlessness via marker assisted selection.

    PubMed

    Akkurt, M; Çakır, A; Shidfar, M; Çelikkol, B P; Söylemezoğlu, G

    2012-08-13

    We used molecular markers associated with seedlessness in grapes, namely SCC8, SCF27 and VMC7f2, to improve the efficiency of seedless grapevine breeding via marker assisted selection (MAS). DNA from 372 F₁ hybrid progeny from the cross between seeded "Alphonse Lavallée" and seedless "Sultani" was amplified by PCR using three markers. After digestion of SCC8 marker amplification products by restriction enzyme BgIII, 40 individuals showed homozygous SCC8+/SCC8+ alleles at the seed development inhibitor (SdI) locus. DNA from 80 of the progeny amplified with the SCF27 marker produced bands; 174 individuals had 198-bp alleles of the VMC7f2 marker associated with seedlessness. In the second year, based on MAS, 183 F₁ hybrids were designated as seedless grapevine candidates because they were positive for a minimum of one marker. Twenty individuals were selected as genetic resources for future studies on seedless grapevine breeding because they carried alleles for the three markers associated with seedlessness. The VMC7f2 SSR marker was identified as the marker most associated with seedlessness.

  7. Automatic cytometric device using multiple wavelength excitations

    NASA Astrophysics Data System (ADS)

    Rongeat, Nelly; Ledroit, Sylvain; Chauvet, Laurence; Cremien, Didier; Urankar, Alexandra; Couderc, Vincent; Nérin, Philippe

    2011-05-01

    Precise identification of eosinophils, basophils, and specific subpopulations of blood cells (B lymphocytes) in an unconventional automatic hematology analyzer is demonstrated. Our specific apparatus mixes two excitation radiations by means of an acousto-optics tunable filter to properly control fluorescence emission of phycoerythrin cyanin 5 (PC5) conjugated to antibodies (anti-CD20 or anti-CRTH2) and Thiazole Orange. This way our analyzer combining techniques of hematology analysis and flow cytometry based on multiple fluorescence detection, drastically improves the signal to noise ratio and decreases the spectral overlaps impact coming from multiple fluorescence emissions.

  8. Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors.

    PubMed

    Ansari, Sahar; Chen, Chider; Xu, Xingtian; Annabi, Nasim; Zadeh, Homayoun H; Wu, Benjamin M; Khademhosseini, Ali; Shi, Songtao; Moshaverinia, Alireza

    2016-06-01

    Repair and regeneration of muscle tissue following traumatic injuries or muscle diseases often presents a challenging clinical situation. If a significant amount of tissue is lost the native regenerative potential of skeletal muscle will not be able to grow to fill the defect site completely. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material, present an advantageous alternative therapeutic option for muscle tissue engineering in comparison to current treatment modalities available. To date, there has been no report on application of gingival mesenchymal stem cells (GMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of the current study were to develop an injectable 3D RGD-coupled alginate scaffold with multiple growth factor delivery capacity for encapsulating GMSCs, and to evaluate the capacity of encapsulated GMSCs to differentiate into myogenic tissue in vitro and in vivo where encapsulated GMSCs were transplanted subcutaneously into immunocompromised mice. The results demonstrate that after 4 weeks of differentiation in vitro, GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited muscle cell-like morphology with high levels of mRNA expression for gene markers related to muscle regeneration (MyoD, Myf5, and MyoG) via qPCR measurement. Our quantitative PCR analyzes revealed that the stiffness of the RGD-coupled alginate regulates the myogenic differentiation of encapsulated GMSCs. Histological and immunohistochemical/fluorescence staining for protein markers specific for myogenic tissue confirmed muscle regeneration in subcutaneous transplantation in our in vivo animal model. GMSCs showed significantly greater capacity for myogenic regeneration in comparison to hBMMSCs (p < 0.05). Altogether, our findings confirmed that GMSCs encapsulated in RGD-modified alginate hydrogel with multiple growth factor delivery capacity is a promising

  9. Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia.

    PubMed

    Hoover, D B; Isaacs, E R; Jacques, F; Hoard, J L; Pagé, P; Armour, J A

    2009-12-15

    Dysfunction of the intrinsic cardiac nervous system is implicated in the genesis of atrial and ventricular arrhythmias. While this system has been studied extensively in animal models, far less is known about the intrinsic cardiac nervous system of humans. This study was initiated to anatomically identify neurotransmitters associated with the right atrial ganglionated plexus (RAGP) of the human heart. Biopsies of epicardial fat containing a portion of the RAGP were collected from eight patients during cardiothoracic surgery and processed for immunofluorescent detection of specific neuronal markers. Colocalization of markers was evaluated by confocal microscopy. Most intrinsic cardiac neuronal somata displayed immunoreactivity for the cholinergic marker choline acetyltransferase and the nitrergic marker neuronal nitric oxide synthase. A subpopulation of intrinsic cardiac neurons also stained for noradrenergic markers. While most intrinsic cardiac neurons received cholinergic innervation evident as punctate immunostaining for the high affinity choline transporter, some lacked cholinergic inputs. Moreover, peptidergic, nitrergic, and noradrenergic nerves provided substantial innervation of intrinsic cardiac ganglia. These findings demonstrate that the human RAGP has a complex neurochemical anatomy, which includes the presence of a dual cholinergic/nitrergic phenotype for most of its neurons, the presence of noradrenergic markers in a subpopulation of neurons, and innervation by a host of neurochemically distinct nerves. The putative role of multiple neurotransmitters in controlling intrinsic cardiac neurons and mediating efferent signaling to the heart indicates the possibility of novel therapeutic targets for arrhythmia prevention.

  10. Mitochondrial Genome Sequencing and Development of Genetic Markers for the Detection of DNA of Invasive Bighead and Silver Carp (Hypophthalmichthys nobilis and H. molitrix) in Environmental Water Samples from the United States

    PubMed Central

    Farrington, Heather L.; Edwards, Christine E.; Guan, Xin; Carr, Matthew R.; Baerwaldt, Kelly; Lance, Richard F.

    2015-01-01

    Invasive Asian bighead and silver carp (Hypophthalmichthys nobilis and H. molitrix) pose a substantial threat to North American aquatic ecosystems. Recently, environmental DNA (eDNA), genetic material shed by organisms into their environment that can be detected by non-invasive sampling strategies and genetic assays, has gained recognition as a tool for tracking the invasion front of these species toward the Great Lakes. The goal of this study was to develop new species-specific conventional PCR (cPCR) and quantitative (qPCR) markers for detection of these species in North American surface waters. We first generated complete mitochondrial genome sequences from 33 bighead and 29 silver carp individuals collected throughout their introduced range. These sequences were aligned with those from other common and closely related fish species from the Illinois River watershed to identify and design new species-specific markers for the detection of bighead and silver carp DNA in environmental water samples. We then tested these genetic markers in the laboratory for species-specificity and sensitivity. Newly developed markers performed well in field trials, did not have any false positive detections, and many markers had much higher detection rates and sensitivity compared to the markers currently used in eDNA surveillance programs. We also explored the use of multiple genetic markers to determine whether it would improve detection rates, results of which showed that using multiple highly sensitive markers should maximize detection rates in environmental samples. The new markers developed in this study greatly expand the number of species-specific genetic markers available to track the invasion front of bighead and silver carp and will improve the resolution of these assays. Additionally, the use of the qPCR markers developed in this study may reduce sample processing time and cost of eDNA monitoring for these species. PMID:25706532

  11. Mitochondrial genome sequencing and development of genetic markers for the detection of DNA of invasive bighead and silver carp (Hypophthalmichthys nobilis and H. molitrix) in environmental water samples from the United States.

    PubMed

    Farrington, Heather L; Edwards, Christine E; Guan, Xin; Carr, Matthew R; Baerwaldt, Kelly; Lance, Richard F

    2015-01-01

    Invasive Asian bighead and silver carp (Hypophthalmichthys nobilis and H. molitrix) pose a substantial threat to North American aquatic ecosystems. Recently, environmental DNA (eDNA), genetic material shed by organisms into their environment that can be detected by non-invasive sampling strategies and genetic assays, has gained recognition as a tool for tracking the invasion front of these species toward the Great Lakes. The goal of this study was to develop new species-specific conventional PCR (cPCR) and quantitative (qPCR) markers for detection of these species in North American surface waters. We first generated complete mitochondrial genome sequences from 33 bighead and 29 silver carp individuals collected throughout their introduced range. These sequences were aligned with those from other common and closely related fish species from the Illinois River watershed to identify and design new species-specific markers for the detection of bighead and silver carp DNA in environmental water samples. We then tested these genetic markers in the laboratory for species-specificity and sensitivity. Newly developed markers performed well in field trials, did not have any false positive detections, and many markers had much higher detection rates and sensitivity compared to the markers currently used in eDNA surveillance programs. We also explored the use of multiple genetic markers to determine whether it would improve detection rates, results of which showed that using multiple highly sensitive markers should maximize detection rates in environmental samples. The new markers developed in this study greatly expand the number of species-specific genetic markers available to track the invasion front of bighead and silver carp and will improve the resolution of these assays. Additionally, the use of the qPCR markers developed in this study may reduce sample processing time and cost of eDNA monitoring for these species.

  12. 21 CFR 878.4660 - Skin marker.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Skin marker. 878.4660 Section 878.4660 Food and... GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4660 Skin marker. (a) Identification. A skin marker is a pen-like device intended to be used to write on the patient's skin, e.g., to outline surgical...

  13. Imaging markers for Alzheimer disease

    PubMed Central

    Bocchetta, Martina; Chételat, Gael; Rabinovici, Gil D.; de Leon, Mony J.; Kaye, Jeffrey; Reiman, Eric M.; Scheltens, Philip; Barkhof, Frederik; Black, Sandra E.; Brooks, David J.; Carrillo, Maria C.; Fox, Nick C.; Herholz, Karl; Nordberg, Agneta; Jack, Clifford R.; Jagust, William J.; Johnson, Keith A.; Rowe, Christopher C.; Sperling, Reisa A.; Thies, William; Wahlund, Lars-Olof; Weiner, Michael W.; Pasqualetti, Patrizio; DeCarli, Charles

    2013-01-01

    Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, 18F-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured (“metric”: visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR+ and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR+ and 16% and 24% of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR−. Within markers, the largest proportion of diagnostic LR+ and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials. PMID:23897875

  14. Vision and vision-related outcome measures in multiple sclerosis

    PubMed Central

    Balcer, Laura J.; Miller, David H.; Reingold, Stephen C.

    2015-01-01

    Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

  15. Biochemical Markers of Bone Turnover in Percutaneous Vertebroplasty for Osteoporotic Compression Fracture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Komemushi, Atsushi, E-mail: kome64@yo.rim.or.jp; Tanigawa, Noboru; Kariya, Shuji

    Purpose. To evaluate relationships between biochemical markers of bone turnover, bone mineral density, and new compression fractures following vertebroplasty. Methods. Initially, we enrolled 30 consecutive patients with vertebral compression fractures caused by osteoporosis. Twenty-three of the 30 patients visited our hospital for follow-up examinations for more than 4 weeks after vertebroplasty. The patients were divided into two groups: patients with new fractures (group F) and patients with no new fractures (group N). We analyzed differences in the following parameters between these two groups: serum bone alkaline phosphatase, urinary crosslinked N-telopeptide of type I collagen, urinary deoxypyridinoline, and bone mineral density.more » Next, the patients were divided into another two groups: patients with higher risk (group H: urinary crosslinked N-telopeptide of type I collagen >54.3 nmol BCE/mmol Cr or urinary deoxypyridinoline >7.6 nmol/mmol Cr, and serum bone alkaline phosphatase <29.0 U/l) and patients with lower risk (group L). We analyzed the difference in the rate of new fractures between these two groups. Results. We identified 9 new fractures in 7 patients. There were no significant differences between groups F and N. We identified 5 new fractures in 3 of the 4 patients in group H, and 4 new fractures in 4 of the 19 patients in group L. There was a significant difference in the rate of new fractures between groups H and L. Conclusions. A combination of high levels of bone resorption markers and normal levels of bone formation markers may be associated with increased risk of new recurrent fractures after percutaneous vertebroplasty.« less

  16. New Zealand supereruption provides time marker for the Last Glacial Maximum in Antarctica

    USGS Publications Warehouse

    Dunbar, Nelia W.; Iverson, Nels A.; Van Eaton, Alexa R.; Sigl, Michael; Alloway, Brent V.; Kurbatov, Andrei V.; Mastin, Larry G.; McConnell, Joseph R.; Wilson, Colin J. N.

    2017-01-01

    Multiple, independent time markers are essential to correlate sediment and ice cores from the terrestrial, marine and glacial realms. These records constrain global paleoclimate reconstructions and inform future climate change scenarios. In the Northern Hemisphere, sub-visible layers of volcanic ash (cryptotephra) are valuable time markers due to their widespread dispersal and unique geochemical fingerprints. However, cryptotephra are not as widely identified in the Southern Hemisphere, leaving a gap in the climate record, particularly during the Last Glacial Maximum (LGM). Here we report the first identification of New Zealand volcanic ash in Antarctic ice. The Oruanui supereruption from Taupo volcano (25,580  ±  258 cal. a BP) provides a key time marker for the LGM in the New Zealand sector of the SW Pacific. This finding provides a high-precision chronological link to mid-latitude terrestrial and marine sites, and sheds light on the long-distance transport of tephra in the Southern Hemisphere. As occurred after identification of the Alaskan White River Ash in northern Europe, recognition of ash from the Oruanui eruption in Antarctica dramatically increases the reach and value of tephrochronology, providing links among climate records in widely different geographic areas and depositional environments.

  17. [BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF): NEUROBIOLOGY AND MARKER VALUE IN NEUROPSYCHIATRY].

    PubMed

    Levada, O A; Cherednichenko, N V

    2015-01-01

    In this review current publications about neurobiology and marker value of brain derived neurotrophic factor (BDNF) in neuropsychiatry are analyzed. It is shown that BDNF is an important member of the family of neurotrophins which widely represented in various structures of the CNS. In prenatal period BDNF is involved in all stages of neuronal networks formation, and in the postnatal period its main role is maintaining the normal brain architectonics, involvement in the processes of neurogenesis and realization of neuroprotective functions. BDNF plays an important role in learning and memory organization, food and motor behavior. BDNF brain expression decreases with age, as well as in degenerative and vascular dementias, affective, anxiety, and behavioral disorders. The reducing of BDNF serum, level reflects the decreasing of its cerebral expression and could be used as a neurobiological marker of these pathological processes but the rising of its concentration could indicate the therapy effectiveness.

  18. Genomic relationships based on X chromosome markers and accuracy of genomic predictions with and without X chromosome markers

    PubMed Central

    2014-01-01

    Background Although the X chromosome is the second largest bovine chromosome, markers on the X chromosome are not used for genomic prediction in some countries and populations. In this study, we presented a method for computing genomic relationships using X chromosome markers, investigated the accuracy of imputation from a low density (7K) to the 54K SNP (single nucleotide polymorphism) panel, and compared the accuracy of genomic prediction with and without using X chromosome markers. Methods The impact of considering X chromosome markers on prediction accuracy was assessed using data from Nordic Holstein bulls and different sets of SNPs: (a) the 54K SNPs for reference and test animals, (b) SNPs imputed from the 7K to the 54K SNP panel for test animals, (c) SNPs imputed from the 7K to the 54K panel for half of the reference animals, and (d) the 7K SNP panel for all animals. Beagle and Findhap were used for imputation. GBLUP (genomic best linear unbiased prediction) models with or without X chromosome markers and with or without a residual polygenic effect were used to predict genomic breeding values for 15 traits. Results Averaged over the two imputation datasets, correlation coefficients between imputed and true genotypes for autosomal markers, pseudo-autosomal markers, and X-specific markers were 0.971, 0.831 and 0.935 when using Findhap, and 0.983, 0.856 and 0.937 when using Beagle. Estimated reliabilities of genomic predictions based on the imputed datasets using Findhap or Beagle were very close to those using the real 54K data. Genomic prediction using all markers gave slightly higher reliabilities than predictions without X chromosome markers. Based on our data which included only bulls, using a G matrix that accounted for sex-linked relationships did not improve prediction, compared with a G matrix that did not account for sex-linked relationships. A model that included a polygenic effect did not recover the loss of prediction accuracy from exclusion of X

  19. Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding

    PubMed Central

    Luo, Zhijing; Chen, Mingjiao; Zhao, Xiangxiang; Zhang, Dabing; Qi, Yiping; Yuan, Zheng

    2016-01-01

    Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection. PMID:26799713

  20. Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding.

    PubMed

    Fan, Wei; Zong, Jie; Luo, Zhijing; Chen, Mingjiao; Zhao, Xiangxiang; Zhang, Dabing; Qi, Yiping; Yuan, Zheng

    2016-01-01

    Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection.

  1. Stress-Related Immune Markers in Depression: Implications for Treatment

    PubMed Central

    Hughes, Martina M.; Connor, Thomas J.

    2016-01-01

    Major depression is a serious psychiatric disorder; however, the precise biological basis of depression still remains elusive. A large body of evidence implicates a dysregulated endocrine and inflammatory response system in the pathogenesis of depression. Despite this, given the heterogeneity of depression, not all depressed patients exhibit dysregulation of the inflammatory and endocrine systems. Evidence suggests that inflammation is associated with depression in certain subgroups of patients and that those who have experienced stressful life events such as childhood trauma or bereavement may be at greater risk of developing depression. Consequently, prolonged exposure to stress is thought to be a key trigger for the onset of a depressive episode. This review assesses the relationship between stress and the immune system, with a particular interest in the mechanisms by which stress impacts immune function, and how altered immune functioning, in turn, may lead to a feed forward cascade of multiple systems dysregulation and the subsequent manifestation of depressive symptomology. The identification of stress-related immune markers and potential avenues for advances in therapeutic intervention is vital. Changes in specific biological markers may be used to characterize or differentiate depressive subtypes or specific symptoms and may predict treatment response, in turn facilitating a more effective, targeted, and fast-acting approach to treatment. PMID:26775294

  2. TipMT: Identification of PCR-based taxon-specific markers.

    PubMed

    Rodrigues-Luiz, Gabriela F; Cardoso, Mariana S; Valdivia, Hugo O; Ayala, Edward V; Gontijo, Célia M F; Rodrigues, Thiago de S; Fujiwara, Ricardo T; Lopes, Robson S; Bartholomeu, Daniella C

    2017-02-11

    Molecular genetic markers are one of the most informative and widely used genome features in clinical and environmental diagnostic studies. A polymerase chain reaction (PCR)-based molecular marker is very attractive because it is suitable to high throughput automation and confers high specificity. However, the design of taxon-specific primers may be difficult and time consuming due to the need to identify appropriate genomic regions for annealing primers and to evaluate primer specificity. Here, we report the development of a Tool for Identification of Primers for Multiple Taxa (TipMT), which is a web application to search and design primers for genotyping based on genomic data. The tool identifies and targets single sequence repeats (SSR) or orthologous/taxa-specific genes for genotyping using Multiplex PCR. This pipeline was applied to the genomes of four species of Leishmania (L. amazonensis, L. braziliensis, L. infantum and L. major) and validated by PCR using artificial genomic DNA mixtures of the Leishmania species as templates. This experimental validation demonstrates the reliability of TipMT because amplification profiles showed discrimination of genomic DNA samples from Leishmania species. The TipMT web tool allows for large-scale identification and design of taxon-specific primers and is freely available to the scientific community at http://200.131.37.155/tipMT/ .

  3. Phylogenetic Relationships between Four Salix L. Species Based on DArT Markers

    PubMed Central

    Przyborowski, Jerzy A.; Sulima, Paweł; Kuszewska, Anna; Załuski, Dariusz; Kilian, Andrzej

    2013-01-01

    The objectives of this study were to evaluate the usefulness of DArT markers in genotypic identification of willow species and describe genetic relationships between four willow species: Salix viminalis, S. purpurea, S. alba and S. triandra. The experimental plant material comprised 53 willow genotypes of these four species, which are popularly grown in Poland. DArT markers seem to identify Salix species with a high degree of accuracy. As a result, the examined species were divided into four distinct groups which corresponded to the four analyzed species. In our study, we observed that S. triandra was very different genetically from the other species, including S. alba which is generally classified into the same subgenus of Salix. The above corroborates the findings of other authors who relied on molecular methods to reveal that the classification of S. triandra to the subgenus Salix was erroneous. The Principal Coordinate Analysis (PCoA) and the neighbor-joining dendrogram also confirmed the clear division of the studied willow genotypes into four clusters corresponding to individual species. This confirmed the usefulness of DArT markers in taxonomic analyses and identification of willow species. PMID:24336112

  4. Phylogenetic relationships between four Salix L. species based on DArT markers.

    PubMed

    Przyborowski, Jerzy A; Sulima, Paweł; Kuszewska, Anna; Załuski, Dariusz; Kilian, Andrzej

    2013-12-11

    The objectives of this study were to evaluate the usefulness of DArT markers in genotypic identification of willow species and describe genetic relationships between four willow species: Salix viminalis, S. purpurea, S. alba and S. triandra. The experimental plant material comprised 53 willow genotypes of these four species, which are popularly grown in Poland. DArT markers seem to identify Salix species with a high degree of accuracy. As a result, the examined species were divided into four distinct groups which corresponded to the four analyzed species. In our study, we observed that S. triandra was very different genetically from the other species, including S. alba which is generally classified into the same subgenus of Salix. The above corroborates the findings of other authors who relied on molecular methods to reveal that the classification of S. triandra to the subgenus Salix was erroneous. The Principal Coordinate Analysis (PCoA) and the neighbor-joining dendrogram also confirmed the clear division of the studied willow genotypes into four clusters corresponding to individual species. This confirmed the usefulness of DArT markers in taxonomic analyses and identification of willow species.

  5. Molecular markers in glioma.

    PubMed

    Ludwig, Kirsten; Kornblum, Harley I

    2017-09-01

    Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.

  6. Identification and validation of single nucleotide polymorphic markers linked to Ug99 stem rust resistance in spring wheat

    PubMed Central

    Chao, Shiaoman; Singh, Ravi P.; Sorrells, Mark E.

    2017-01-01

    Wheat stem rust (Puccinia graminis f. sp. tritici Eriks. and E. Henn.) is one of the most destructive diseases world-wide. Races belonging to Ug99 (or TTKSK) continue to cause crop losses in East Africa and threaten global wheat production. Developing and deploying wheat varieties with multiple race-specific genes or complex adult plant resistance is necessary to achieve durability. In the present study, we applied genome-wide association studies (GWAS) for identifying loci associated with the Ug99 stem rust resistance (SR) in a panel of wheat lines developed at the International Maize and Wheat Improvement Center (CIMMYT). Genotyping was carried out using the wheat 9K iSelect single nucleotide polymorphism (SNP) chip. Phenotyping was done in the field in Kenya by infection of Puccinia graminis f. sp. tritici race TTKST, the Sr24-virulent variant of Ug99. Marker-trait association identified 12 SNP markers significantly associated with resistance. Among them, 7 were mapped on five chromosomes. Markers located on chromosomes 4A and 4B overlapped with the location of the Ug99 resistance genes SrND643 and Sr37, respectively. Markers identified on 7DL were collocated with Sr25. Additional significant markers were located in the regions where no Sr gene has been reported. The chromosome location for five of the SNP markers was unknown. A BLASTN search of the NCBI database using the flanking sequences of the SNPs associated with Ug99 resistance revealed that several markers were linked to plant disease resistance analogues, while others were linked to regulatory factors or metabolic enzymes. A KASP (Kompetitive Allele Specific PCR) assay was used for validating six marker loci linked to genes with resistance to Ug99. Of those, four co-segregated with the Sr25-pathotypes while the rest identified unknown resistance genes. With further investigation, these markers can be used for marker-assisted selection in breeding for Ug99 stem rust resistance in wheat. PMID:28241006

  7. Biochemical markers assisted screening of Fusarium wilt resistant Musa paradisiaca (L.) cv. puttabale micropropagated clones.

    PubMed

    Venkatesh; Krishna, V; Kumar, K Girish; Pradeepa, K; Kumar, S R Santosh; Kumar, R Shashi

    2013-07-01

    An efficient protocol was standardized for screening of panama wilt resistant Musa paradisiaca cv. Puttabale clones, an endemic cultivar of Karnataka, India. The synergistic effect of 6-benzyleaminopurine (2 to 6 mg/L) and thidiazuron (0.1 to 0.5 mg/L) on MS medium provoked multiple shoot induction from the excised meristem. An average of 30.10 +/- 5.95 shoots was produced per propagule at 4 mg/L 6-benzyleaminopurine and 0.3 mg/L thidiazuron concentrations. Elongation of shoots observed on 5 mg/L BAP augmented medium with a mean length of 8.38 +/- 0.30 shoots per propagule. For screening of disease resistant clones, multiple shoot buds were mutated with 0.4% ethyl-methane-sulfonate and cultured on MS medium supplemented with Fusarium oxysporum f. sp. cubense (FOC) culture filtrate (5-15%). Two month old co-cultivated secondary hardened plants were used for screening of disease resistance against FOC by the determination of biochemical markers such as total phenol, phenylalanine ammonia lyase, oxidative enzymes like peroxidase, polyphenol oxidase, catalase and PR-proteins like chitinase, beta-1-3 glucanase activities. The mutated clones of M. paradisiaca cv. Puttabale cultured on FOC culture filtrate showed significant increase in the levels of biochemical markers as an indicative of acquiring disease resistant characteristics to FOC wilt.

  8. Quality transitivity and traceability system of herbal medicine products based on quality markers.

    PubMed

    Liu, Changxiao; Guo, De-An; Liu, Liang

    2018-05-15

    Due to a variety of factors to affect the herb quality, the existing quality management model is unable to evaluate the process control. The development of the concept of "quality marker" (Q-marker) lays basis for establishing an independent process quality control system for herbal products. To ensure the highest degree of safety, effectiveness and quality process control of herbal products, it is aimed to establish a quality transitivity and traceability system of quality and process control from raw materials to finished herbal products. Based on the key issues and challenges of quality assessment, the current status of quality and process controls from raw materials to herbal medicinal products listed in Pharmacopoeia were analyzed and the research models including discovery and identification of Q-markers, analysis and quality management of risk evaluation were designed. Authors introduced a few new technologies and methodologies, such as DNA barcoding, chromatographic technologies, fingerprint analysis, chemical markers, bio-responses, risk management and solution for quality process control. The quality and process control models for herbal medicinal products were proposed and the transitivity and traceability system from raw materials to the finished products was constructed to improve the herbal quality from the entire supply and production chain. The transitivity and traceability system has been established based on quality markers, especially on how to control the production process under Good Engineering Practices, as well as to implement the risk management for quality and process control in herbal medicine production. Copyright © 2018 Elsevier GmbH. All rights reserved.

  9. Polymorphic microsatellite markers for the rare and endangered cactus Uebelmannia pectinifera (Cactaceae) and its congeneric species.

    PubMed

    Moraes, E M; Cidade, F W; Silva, G A R; Machado, M C

    2014-12-04

    The cactus genus Uebelmannia includes 3 narrow endemic species associated with rocky savanna habitats in eastern South America. Because of their rarity and illegal over-collection, all of these species are endangered. Taxonomic uncertainties resulting from dramatic local variation in morphology within Uebelmannia species preclude effective conservation efforts, such as the reintroduction or translocation of plants, to restore declining populations. In this study, we developed and characterized 18 perfect, dinucleotide simple-sequence repeat markers for U. pectinifera, the most widely distributed species in the genus, and tested the cross-amplification of these markers in the remaining congeneric species and subspecies. All markers were polymorphic in a sample from 2 U. pectinifera populations. The effective number of alleles ranged from 1.6 to 8.7, with an average per population of 3.3 (SE ± 0.30) and 4.5 (SE ± 0.50). Expected heterozygosity ranged from 0.375 to 0.847 and 8-10 loci showed departures from Hardy- Weinberg equilibrium in the analyzed populations. Based on the observed polymorphism level of each marker, as well as the analysis of null allele presence and evidence of amplification of duplicate loci, a subset of 12 loci can be used as reliable markers to investigate the genetic structure, diversity, and species limits of the Uebelmannia genus.

  10. A sequence-based genetic map of Medicago truncatula and comparison of marker colinearity with M. sativa.

    PubMed Central

    Choi, Hong-Kyu; Kim, Dongjin; Uhm, Taesik; Limpens, Eric; Lim, Hyunju; Mun, Jeong-Hwan; Kalo, Peter; Penmetsa, R Varma; Seres, Andrea; Kulikova, Olga; Roe, Bruce A; Bisseling, Ton; Kiss, Gyorgy B; Cook, Douglas R

    2004-01-01

    A core genetic map of the legume Medicago truncatula has been established by analyzing the segregation of 288 sequence-characterized genetic markers in an F(2) population composed of 93 individuals. These molecular markers correspond to 141 ESTs, 80 BAC end sequence tags, and 67 resistance gene analogs, covering 513 cM. In the case of EST-based markers we used an intron-targeted marker strategy with primers designed to anneal in conserved exon regions and to amplify across intron regions. Polymorphisms were significantly more frequent in intron vs. exon regions, thus providing an efficient mechanism to map transcribed genes. Genetic and cytogenetic analysis produced eight well-resolved linkage groups, which have been previously correlated with eight chromosomes by means of FISH with mapped BAC clones. We anticipated that mapping of conserved coding regions would have utility for comparative mapping among legumes; thus 60 of the EST-based primer pairs were designed to amplify orthologous sequences across a range of legume species. As an initial test of this strategy, we used primers designed against M. truncatula exon sequences to rapidly map genes in M. sativa. The resulting comparative map, which includes 68 bridging markers, indicates that the two Medicago genomes are highly similar and establishes the basis for a Medicago composite map. PMID:15082563

  11. Use of DNA markers in forest tree improvement research

    Treesearch

    D.B. Neale; M.E. Devey; K.D. Jermstad; M.R. Ahuja; M.C. Alosi; K.A. Marshall

    1992-01-01

    DNA markers are rapidly being developed for forest trees. The most important markers are restriction fragment length polymorphisms (RFLPs), polymerase chain reaction- (PCR) based markers such as random amplified polymorphic DNA (RAPD), and fingerprinting markers. DNA markers can supplement isozyme markers for monitoring tree improvement activities such as; estimating...

  12. Population genetic analysis of a global collection of Fragaria vesca using microsatellite markers

    PubMed Central

    Hilmarsson, Hrannar Smári; Hytönen, Timo; Isobe, Sachiko; Göransson, Magnus; Toivainen, Tuomas

    2017-01-01

    The woodland strawberry, Fragaria vesca, holds great promise as a model organism. It not only represents the important Rosaceae family that includes economically important species such as apples, pears, peaches and roses, but it also complements the well-known model organism Arabidopsis thaliana in key areas such as perennial life cycle and the development of fleshy fruit. Analysis of wild populations of A. thaliana has shed light on several important developmental pathways controlling, for example, flowering time and plant growth, suggesting that a similar approach using F. vesca might add to our understanding on the development of rosaceous species and perennials in general. As a first step, 298 F. vesca plants were analyzed using microsatellite markers with the primary aim of analyzing population structure and distribution of genetic diversity. Of the 68 markers tested, 56 were polymorphic, with an average of 4.46 alleles per locus. Our analysis partly confirms previous classification of F. vesca subspecies in North America and suggests two groups within the subsp. bracteata. In addition, F. vesca subsp. vesca forms a single global population with evidence that the Icelandic group is a separate cluster from the main Eurasian population. PMID:28854285

  13. Population genetic analysis of a global collection of Fragaria vesca using microsatellite markers.

    PubMed

    Hilmarsson, Hrannar Smári; Hytönen, Timo; Isobe, Sachiko; Göransson, Magnus; Toivainen, Tuomas; Hallsson, Jón Hallsteinn

    2017-01-01

    The woodland strawberry, Fragaria vesca, holds great promise as a model organism. It not only represents the important Rosaceae family that includes economically important species such as apples, pears, peaches and roses, but it also complements the well-known model organism Arabidopsis thaliana in key areas such as perennial life cycle and the development of fleshy fruit. Analysis of wild populations of A. thaliana has shed light on several important developmental pathways controlling, for example, flowering time and plant growth, suggesting that a similar approach using F. vesca might add to our understanding on the development of rosaceous species and perennials in general. As a first step, 298 F. vesca plants were analyzed using microsatellite markers with the primary aim of analyzing population structure and distribution of genetic diversity. Of the 68 markers tested, 56 were polymorphic, with an average of 4.46 alleles per locus. Our analysis partly confirms previous classification of F. vesca subspecies in North America and suggests two groups within the subsp. bracteata. In addition, F. vesca subsp. vesca forms a single global population with evidence that the Icelandic group is a separate cluster from the main Eurasian population.

  14. Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival

    PubMed Central

    Balz, Ellen; Herzog, Susann; Plantera, Laura; Vogelgesang, Silke; Seifert, Carolin; Bialke, Angela; Venugopal, Chitra; Singh, Sheila K.; Hoffmann, Wolfgang; Schroeder, Henry W. S.

    2018-01-01

    Patients with glioblastoma multiforme (GBM) are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs) are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin) as well as differentiation and microglia markers (GFAP, Iba1, and Sparc) in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed. At mRNA level, ABCG2 and CD95 were reduced, GFAP was unchanged; all other investigated markers were increased in GBM. At protein level, CD44, ELF4, Nanog, Nestin, and Sparc were elevated in GBM, but only CD133 and Nestin were strongly associated with survival time. In addition, ABCG2 and GFAP expression was decreased in LN18 neurospheres whereas CD44, CD95, CD133, ELF4, Nanog, Nestin, and Sparc were upregulated. Altogether only CD133 and Nestin were associated with survival rates. This raises concerns regarding the suitability of the other target structures as prognostic markers, but makes both CD133 and Nestin candidates for GBM therapy. Nevertheless, a search for more specific marker proteins is urgently needed. PMID:29535786

  15. Use of DNA Markers for Investigating Sources of Bacteria in Contaminated Ground Water: Wooster Township, Wayne County, Ohio

    USGS Publications Warehouse

    Dumouchelle, Denise H.

    2006-01-01

    In 2004, a public-health nuisance was declared by the Wayne County Board of Health in the Scenic Heights Drive-Batdorf Road area of Wooster Township, Wayne County, Ohio, because of concerns about the safety of water from local wells. Repeated sampling had detected the presence of fecal-indicator bacteria and elevated nitrate concentrations. In June 2006, the U.S. Geological Survey (USGS), in cooperation with the Ohio Environmental Protection Agency (Ohio EPA), collected and analyzed samples from some of the affected wells to help investigate the possibility of human-origin bacterial contamination. Water samples from 12 wells and 5 home sewage-treatment systems (HSTS) were collected. Bromide concentrations were determined in samples from the 12 wells. Samples from 5 of the 12 wells were analyzed for wastewater compounds. Total coliform, enterococci and Escherichia coli (E. coli) bacteria concentrations were determined for samples from 8 of the 12 wells. In addition, two microbial source-tracking tools that employ DNA markers were used on samples from several wells and a composite sample of water from five septic tanks. The DNA markers from the Enterococcus faecium species and the order Bacteroidales are associated with specific sources, either human or ruminant sources. Bromide concentrations ranged from 0.04 to 0.18 milligrams per liter (mg/L). No wastewater compounds were detected at concentrations above the reporting limits. Samples from the 12 wells also were collected by Ohio EPA and analyzed for chloride and nitrate. Chloride concentrations ranged from 12.6 to 61.6 mg/L and nitrate concentrations ranged from 2.34 to 11.9 mg/L (as N). Total coliforms and enterococci were detected in samples from 8 wells, at concentrations from 2 to 200 colony-forming units per 100 milliliters (CFU/100 mL) and 0.5 to 17 CFU/100 mL, respectively. E. coli were detected in samples from three of the eight wells, at concentrations of 1 or 2 CFU/100 mL. Tests for the human

  16. Prediction of industrial tomato hybrids from agronomic traits and ISSR molecular markers.

    PubMed

    Figueiredo, A S T; Resende, J T V; Faria, M V; Da-Silva, P R; Fagundes, B S; Morales, R G F

    2016-05-13

    Heterosis is a highly relevant phenomenon in plant breeding. This condition is usually established in hybrids derived from crosses of highly divergent parents. The success of a breeder in obtaining heterosis is directly related to the correct identification of genetically contrasting parents. Currently, the diallel cross is the most commonly used methodology to detect contrasting parents; however, it is a time- and cost-consuming procedure. Therefore, new tools capable of performing this task quickly and accurately are required. Thus, the purpose of this study was to estimate the genetic divergence in industrial tomato lines, based on agronomic traits, and to compare with estimates obtained using inter-simple sequence repeat (ISSR) molecular markers. The genetic divergence among 10 industrial tomato lines, based on nine morphological characters and 12 ISSR primers was analyzed. For data analysis, Pearson and Spearman correlation coefficients were calculated between the genetic dissimilarity measures estimated by Mahalanobis distance and Jaccard's coefficient of genetic dissimilarity from the heterosis estimates, combining ability, and means of important traits of industrial tomato. The ISSR markers efficiently detected contrasting parents for hybrid production in tomato. Parent RVTD-08 was indicated as the most divergent, both by molecular and morphological markers, that positively contributed to increased heterosis and by the specific combining ability in the crosses in which it participated. The genetic dissimilarity estimated by ISSR molecular markers aided the identification of the best hybrids of the experiment in terms of total fruit yield, pulp yield, and soluble solids content.

  17. Current molecular markers for gastric progenitor cells and gastric cancer stem cells.

    PubMed

    Qiao, Xiaotan T; Gumucio, Deborah L

    2011-07-01

    Gastric stem and progenitor cells (GPC) play key roles in the homeostatic renewal of gastric glands and are instrumental in epithelial repair after injury. Until very recently, the existence of GPC could only be inferred by indirect labeling strategies. The last few years have seen significant progress in the identification of biomarkers that allow prospective identification of GPC. The analysis of these unique cell populations is providing new insights into the molecular underpinnings of gastric epithelial homeostasis and repair. Of closely related interest is the potential to identify so-called cancer stem cells, a rare subpopulation of tumor-initiating cells. Here, we review the current useful biomarkers for GPC, including: (a) those that have been demonstrated by lineage tracing to give rise to all gastric cell lineages (e.g., the villin-transgene marker as well as Lgr5); (b) those that give rise to a subset of gastric lineages (e.g., TFF2); (c) markers that recognize cryptic progenitors for metaplasia (e.g., MIST1), and (d) markers that have not yet been analyzed by lineage tracing (e.g., DCKL1/DCAMKL1, CD133/PROM1, and CD44). The study of these markers has been mostly limited to the mouse model, but the hope is that the rapid pace of recent breakthroughs in this animal model will soon lead to a greater understanding of human gastric stem cell biology and to new insights into gastric cancer, the second leading cause of cancer-related death worldwide.

  18. Identification of molecular markers associated with Verticillium wilt resistance in alfalfa (Medicago sativa L.) using high-resolution melting.

    PubMed

    Zhang, Tiejun; Yu, Long-Xi; McCord, Per; Miller, David; Bhamidimarri, Suresh; Johnson, David; Monteros, Maria J; Ho, Julie; Reisen, Peter; Samac, Deborah A

    2014-01-01

    Verticillium wilt, caused by the soilborne fungus, Verticillium alfalfae, is one of the most serious diseases of alfalfa (Medicago sativa L.) worldwide. To identify loci associated with resistance to Verticillium wilt, a bulk segregant analysis was conducted in susceptible or resistant pools constructed from 13 synthetic alfalfa populations, followed by association mapping in two F1 populations consisted of 352 individuals. Simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers were used for genotyping. Phenotyping was done by manual inoculation of the pathogen to replicated cloned plants of each individual and disease severity was scored using a standard scale. Marker-trait association was analyzed by TASSEL. Seventeen SNP markers significantly associated with Verticillium wilt resistance were identified and they were located on chromosomes 1, 2, 4, 7 and 8. SNP markers identified on chromosomes 2, 4 and 7 co-locate with regions of Verticillium wilt resistance loci reported in M. truncatula. Additional markers identified on chromosomes 1 and 8 located the regions where no Verticillium resistance locus has been reported. This study highlights the value of SNP genotyping by high resolution melting to identify the disease resistance loci in tetraploid alfalfa. With further validation, the markers identified in this study could be used for improving resistance to Verticillium wilt in alfalfa breeding programs.

  19. Evaluation of solar-powered raised pavement markers.

    DOT National Transportation Integrated Search

    2008-01-01

    An evaluation of a limited number of solar-powered raised pavement markers (SRPMs) was conducted to : determine if this type of marker would be more visible than retroreflective markers in some situations on : Oregon highways. SRPMs typically use Lig...

  20. Identification and characterization of gene-based SSR markers in date palm (Phoenix dactylifera L.).

    PubMed

    Zhao, Yongli; Williams, Roxanne; Prakash, C S; He, Guohao

    2012-12-15

    Date palm (Phoenix dactylifera L.) is an important tree in the Middle East and North Africa due to the nutritional value of its fruit. Molecular Breeding would accelerate genetic improvement of fruit tree through marker assisted selection. However, the lack of molecular markers in date palm restricts the application of molecular breeding. In this study, we analyzed 28,889 EST sequences from the date palm genome database to identify simple-sequence repeats (SSRs) and to develop gene-based markers, i.e. expressed sequence tag-SSRs (EST-SSRs). We identified 4,609 ESTs as containing SSRs, among which, trinucleotide motifs (69.7%) were the most common, followed by tetranucleotide (10.4%) and dinucleotide motifs (9.6%). The motif AG (85.7%) was most abundant in dinucleotides, while motifs AGG (26.8%), AAG (19.3%), and AGC (16.1%) were most common among trinucleotides. A total of 4,967 primer pairs were designed for EST-SSR markers from the computational data. In a follow up laboratory study, we tested a sample of 20 random selected primer pairs for amplification and polymorphism detection using genomic DNA from date palm cultivars. Nearly one-third of these primer pairs detected DNA polymorphism to differentiate the twelve date palm cultivars used. Functional categorization of EST sequences containing SSRs revealed that 3,108 (67.4%) of such ESTs had homology with known proteins. Date palm EST sequences exhibits a good resource for developing gene-based markers. These genic markers identified in our study may provide a valuable genetic and genomic tool for further genetic research and varietal development in date palm, such as diversity study, QTL mapping, and molecular breeding.

  1. The Pioneer 10 plasma analyzer results at Jupiter

    NASA Technical Reports Server (NTRS)

    Wolfe, J. H.

    1975-01-01

    Results are reported for the Pioneer 10 plasma-analyzer experiment at Jupiter. The analyzer system consisted of dual 90-deg quadrispherical electrostatic analyzers, multiple charged-particle detectors, and attendant electronics; it was capable of determining the incident plasma-distribution parameters over the energy range from 100 to 18,000 eV for protons and from approximately 1 to 500 eV for electrons. Data are presented on the interaction between the solar wind and the Jovian magnetosphere, the interplanetary ion flux, observations of the magnetosheath plasma, and traversals of the bow shock and magnetopause. Values are estimated for the proton isotropic temperature, number density, and bulk velocity within the magnetosheath flow field as well as for the beta parameter, ion number density, and magnetic-energy density of the magnetospheric plasma. It is argued that Jupiter has a reasonably thick magnetosphere somewhat similar to earth's except for the vastly different scale sizes involved.

  2. International scientific communications in the field of colorectal tumour markers.

    PubMed

    Ivanov, Krasimir; Donev, Ivan

    2017-05-27

    To analyze scientometrically the dynamic science internationalization on colorectal tumour markers as reflected in five information portals and to outline the significant journals, scientists and institutions. A retrospective problem-oriented search was performed in Web of Science Core Collection (WoS), MEDLINE, BIOSIS Citation Index (BIOSIS) and Scopus for 1986-2015 as well as in Dervent Innovations Index (Derwent) for 1995-2015. Several specific scientometric parameters of the publication output and citation activity were comparatively analyzed. The following scientometric parameters were analyzed: (1) annual dynamics of publications; (2) scientific institutions; (3) journals; (4) authors; (5) scientific forums; (6) patents - number of patents, names and countries of inventors, and (7) citations (number of citations to publications by single authors received in WoS, BIOSIS Citation Index and Scopus). There is a trend towards increasing publication output on colorectal tumour markers worldwide along with high citation rates. Authors from 70 countries have published their research results in journals and conference proceedings in 21 languages. There is considerable country stratification similar to that in most systematic investigations. The information provided to end users and scientometricians varies between these data-bases in terms of most parameters due to different journal coverage, indexing systems and editorial policy. The lists of the so-called "core" journals and most productive authors in WoS, BIOSIS, MEDLINE and Scopus along with the list of the most productive authors - inventors in Derwent present a particular interest to the beginners in the field, the institutional and national science managers and the journal editorial board members. The role of the purposeful assessment of scientific forums and patents is emphasized. Our results along with this problem-oriented collection containing the researchers' names, addresses and publications could

  3. Noise and analyzer-crystal angular position analysis for analyzer-based phase-contrast imaging

    NASA Astrophysics Data System (ADS)

    Majidi, Keivan; Li, Jun; Muehleman, Carol; Brankov, Jovan G.

    2014-04-01

    The analyzer-based phase-contrast x-ray imaging (ABI) method is emerging as a potential alternative to conventional radiography. Like many of the modern imaging techniques, ABI is a computed imaging method (meaning that images are calculated from raw data). ABI can simultaneously generate a number of planar parametric images containing information about absorption, refraction, and scattering properties of an object. These images are estimated from raw data acquired by measuring (sampling) the angular intensity profile of the x-ray beam passed through the object at different angular positions of the analyzer crystal. The noise in the estimated ABI parametric images depends upon imaging conditions like the source intensity (flux), measurements angular positions, object properties, and the estimation method. In this paper, we use the Cramér-Rao lower bound (CRLB) to quantify the noise properties in parametric images and to investigate the effect of source intensity, different analyzer-crystal angular positions and object properties on this bound, assuming a fixed radiation dose delivered to an object. The CRLB is the minimum bound for the variance of an unbiased estimator and defines the best noise performance that one can obtain regardless of which estimation method is used to estimate ABI parametric images. The main result of this paper is that the variance (hence the noise) in parametric images is directly proportional to the source intensity and only a limited number of analyzer-crystal angular measurements (eleven for uniform and three for optimal non-uniform) are required to get the best parametric images. The following angular measurements only spread the total dose to the measurements without improving or worsening CRLB, but the added measurements may improve parametric images by reducing estimation bias. Next, using CRLB we evaluate the multiple-image radiography, diffraction enhanced imaging and scatter diffraction enhanced imaging estimation techniques

  4. Noise and Analyzer-Crystal Angular Position Analysis for Analyzer-Based Phase-Contrast Imaging

    PubMed Central

    Majidi, Keivan; Li, Jun; Muehleman, Carol; Brankov, Jovan G.

    2014-01-01

    The analyzer-based phase-contrast X-ray imaging (ABI) method is emerging as a potential alternative to conventional radiography. Like many of the modern imaging techniques, ABI is a computed imaging method (meaning that images are calculated from raw data). ABI can simultaneously generate a number of planar parametric images containing information about absorption, refraction, and scattering properties of an object. These images are estimated from raw data acquired by measuring (sampling) the angular intensity profile (AIP) of the X-ray beam passed through the object at different angular positions of the analyzer crystal. The noise in the estimated ABI parametric images depends upon imaging conditions like the source intensity (flux), measurements angular positions, object properties, and the estimation method. In this paper, we use the Cramér-Rao lower bound (CRLB) to quantify the noise properties in parametric images and to investigate the effect of source intensity, different analyzer-crystal angular positions and object properties on this bound, assuming a fixed radiation dose delivered to an object. The CRLB is the minimum bound for the variance of an unbiased estimator and defines the best noise performance that one can obtain regardless of which estimation method is used to estimate ABI parametric images. The main result of this manuscript is that the variance (hence the noise) in parametric images is directly proportional to the source intensity and only a limited number of analyzer-crystal angular measurements (eleven for uniform and three for optimal non-uniform) are required to get the best parametric images. The following angular measurements only spread the total dose to the measurements without improving or worsening CRLB, but the added measurements may improve parametric images by reducing estimation bias. Next, using CRLB we evaluate the Multiple-Image Radiography (MIR), Diffraction Enhanced Imaging (DEI) and Scatter Diffraction Enhanced Imaging (S

  5. Development of next-generation mapping populations: Multi-parent Advanced Generation Inter-Cross (MAGIC) and Marker-Assisted Recurrent Selection (MARS) populations in peanut

    USDA-ARS?s Scientific Manuscript database

    Generation Inter-Cross (MAGIC) and Marker-Assisted Recurrent Selection (MARS) have been proposed and used in many crops to dissect complex traits or QTL. MAGIC allows for dissecting genomic structure, and for improving breeding populations by integrating multiple alleles from different parents. MAR...

  6. Fluorescent marker-based and marker-free discrimination between healthy and cancerous human tissues using hyper-spectral imaging

    NASA Astrophysics Data System (ADS)

    Arnold, Thomas; De Biasio, Martin; Leitner, Raimund

    2015-06-01

    Two problems are addressed in this paper (i) the fluorescent marker-based and the (ii) marker-free discrimination between healthy and cancerous human tissues. For both applications the performance of hyper-spectral methods are quantified. Fluorescent marker-based tissue classification uses a number of fluorescent markers to dye specific parts of a human cell. The challenge is that the emission spectra of the fluorescent dyes overlap considerably. They are, furthermore disturbed by the inherent auto-fluorescence of human tissue. This results in ambiguities and decreased image contrast causing difficulties for the treatment decision. The higher spectral resolution introduced by tunable-filter-based spectral imaging in combination with spectral unmixing techniques results in an improvement of the image contrast and therefore more reliable information for the physician to choose the treatment decision. Marker-free tissue classification is based solely on the subtle spectral features of human tissue without the use of artificial markers. The challenge in this case is that the spectral differences between healthy and cancerous tissues are subtle and embedded in intra- and inter-patient variations of these features. The contributions of this paper are (i) the evaluation of hyper-spectral imaging in combination with spectral unmixing techniques for fluorescence marker-based tissue classification, (ii) the evaluation of spectral imaging for marker-free intra surgery tissue classification. Within this paper, we consider real hyper-spectral fluorescence and endoscopy data sets to emphasize the practical capability of the proposed methods. It is shown that the combination of spectral imaging with multivariate statistical methods can improve the sensitivity and specificity of the detection and the staging of cancerous tissues compared to standard procedures.

  7. Using multiple markers to elucidate the ancient, historical and modern relationships among North American Arctic dog breeds

    PubMed Central

    Brown, S K; Darwent, C M; Wictum, E J; Sacks, B N

    2015-01-01

    Throughout most of the Americas, post-colonial dogs largely erased the genetic signatures of pre-historical dogs. However, the North American Arctic harbors dogs that are potentially descended from pre-historical ancestors, as well as those affected by post-colonial translocations and admixtures. In particular, Inuit dogs from Canada and Greenland are thought to descend from dogs associated with Thule peoples, who relied on them for transportation ca. 1000 years ago. Whether Thule dogs reflected an earlier colonization by Paleoeskimo dogs ca. 4500 years ago is unknown. During the Alaskan Gold Rush, additional sled dogs, possibly of post-colonial derivation, the Alaskan Husky, Malamute and Siberian Husky, were used in the Arctic. The genealogical relationships among and origins of these breeds are unknown. Here we use autosomal, paternal and maternal DNA markers to (1) test the hypothesis that Inuit dogs have retained their indigenous ancestry, (2) characterize their relationship to one another and to other Arctic breeds, and (3) estimate the age of North American indigenous matrilines and patrilines. On the basis of the agreement of all three markers we determined that Inuit dogs have maintained their indigenous nature, and that they likely derive from Thule dogs. In addition, we provide support for previous research that the Inuit dogs from Canada and Greenland dog should not be distinguished as two breeds. The Alaskan Husky displayed evidence of European introgression, in contrast to the Malamute and Siberian Husky, which appear to have maintained most of their ancient Siberian ancestry. PMID:26103948

  8. Using multiple markers to elucidate the ancient, historical and modern relationships among North American Arctic dog breeds.

    PubMed

    Brown, S K; Darwent, C M; Wictum, E J; Sacks, B N

    2015-12-01

    Throughout most of the Americas, post-colonial dogs largely erased the genetic signatures of pre-historical dogs. However, the North American Arctic harbors dogs that are potentially descended from pre-historical ancestors, as well as those affected by post-colonial translocations and admixtures. In particular, Inuit dogs from Canada and Greenland are thought to descend from dogs associated with Thule peoples, who relied on them for transportation ca. 1000 years ago. Whether Thule dogs reflected an earlier colonization by Paleoeskimo dogs ca. 4500 years ago is unknown. During the Alaskan Gold Rush, additional sled dogs, possibly of post-colonial derivation, the Alaskan Husky, Malamute and Siberian Husky, were used in the Arctic. The genealogical relationships among and origins of these breeds are unknown. Here we use autosomal, paternal and maternal DNA markers to (1) test the hypothesis that Inuit dogs have retained their indigenous ancestry, (2) characterize their relationship to one another and to other Arctic breeds, and (3) estimate the age of North American indigenous matrilines and patrilines. On the basis of the agreement of all three markers we determined that Inuit dogs have maintained their indigenous nature, and that they likely derive from Thule dogs. In addition, we provide support for previous research that the Inuit dogs from Canada and Greenland dog should not be distinguished as two breeds. The Alaskan Husky displayed evidence of European introgression, in contrast to the Malamute and Siberian Husky, which appear to have maintained most of their ancient Siberian ancestry.

  9. Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumor

    PubMed Central

    Mosqueda-Taylor, Adalberto; Molina-Frechero, Nelly; Mori-Estevez, Ana D.; Sánchez-Acuña, Guillermo

    2013-01-01

    Objectives: The aim of this study was to compare among PCNAand Ki-67 as the most reliable immunohistochemical marker for evaluating cell proliferation in ameloblastic tumors. Study Design: Observational, retrospective, and descriptive study of a large series of ameloblastic tumors, composed of 161 ameloblastomas and four ameloblastic carcinomas, to determine and compare PCNA and Ki-67 expression using immunohistochemistry techniques. Results: When analyzing Ki-67 positivity, the desmoplastic ameloblastoma demonstrated a significantly lower proliferation rate (1.9%) compared with the solid/multicystic and unicystic ameloblastomas and ameloblastic carcinomas (p<0.05), whereas the ameloblastic carcinomas displayed a significantly higher rate compared with all of the other ameloblastomas (48.7%) (p<0.05). When analyzing cell proliferation with PCNA, we found significant differences only between the ameloblastic carcinomas (93.3%) and the desmoplastic ameloblastomas (p<0.05). When differences between the immunopositivity for PCNA and Ki-67 were compared, the percentages were higher for PCNA in all types of ameloblastomas and ameloblastic carcinomas. In all cases, the percentages were greater than 80%, whereas the immunopositivity for Ki-67 was significantly lower; for example, the ameloblastic carcinoma expressed the highest positivity and only reached 48.7%, compared to 93.3% when we used PCNA. Conclusions: In the present study, when we used the proliferation cell marker Ki-67, the percentages of positivity were more specific and varied among the different types of ameloblastomas, suggesting that Ki-67 is a more specific marker for the proliferation of ameloblastic tumor cells. Key words:Ameloblastomas, ameloblastic carcinoma, PCNA, Ki-67, cell proliferation markers. PMID:23229269

  10. Epidemiological markers of Serratia marcescens isolates causing nosocomial infections in Spain (1981-1991).

    PubMed

    Boquete, T; Vindel, A; Martin-Bourgon, C; Azañedo, L; Sáez-Nieto, J A

    1996-12-01

    The distribution of epidemiological markers (serotyping and phage-typing) of Serratia marcescens isolates from nosocomial episodes (63 nosocomial cutbreaks with 475 isolates, and 1208 sporadic cases) received in our laboratory during the period 1981-1991 was studied. The records for 1683 isolates from Spanish hospitals have been analyzed. In relation with the sporadic cases, the predominant types were serotype O6 (13.4%) and serotype O14 (11.4%); polyagglutinable strains accounted for 15.6%; in outbreaks, type O14 is clearly predominant (27.4%). Phage-typing was a good secondary marker, with a 87.9% of typability; the number of lytic patterns was very high, extended patterns (six or more phages) being the most frequent. We have studied the characteristics of S. marcescens isolates causing infections in the nosocomial environment in Spain.

  11. Identification of the origin of faecal contamination in estuarine oysters using Bacteroidales and F-specific RNA bacteriophage markers.

    PubMed

    Mieszkin, S; Caprais, M P; Le Mennec, C; Le Goff, M; Edge, T A; Gourmelon, M

    2013-09-01

    The aim of this study was to identify the origin of faecal pollution impacting the Elorn estuary (Brittany, France) by applying microbial source tracking (MST) markers in both oysters and estuarine waters. The MST markers used were as follows: (i) human-, ruminant- and pig-associated Bacteroidales markers by real-time PCR and (ii) human genogroup II and animal genogroup I of F-specific RNA bacteriophages (FRNAPH) by culture/genotyping and by direct real-time reverse-transcriptase PCR. The higher occurrence of the human genogroup II of F-specific RNA bacteriophages using a culture/genotyping method, and human-associated Bacteroidales marker by real-time PCR, allowed the identification of human faecal contamination as the predominant source of contamination in oysters (total of 18 oyster batches tested) and waters (total of 24 water samples tested). The importance of using the intravalvular liquids instead of digestive tissues, when applying host-associated Bacteroidales markers in oysters, was also revealed. This study has shown that the application of a MST toolbox of diverse bacterial and viral methods can provide multiple lines of evidence to identify the predominant source of faecal contamination in shellfish from an estuarine environment. Application of this MST toolbox is a useful approach to understand the origin of faecal contamination in shellfish harvesting areas in an estuarine setting. © 2013 The Society for Applied Microbiology.

  12. Ecosystem service bundles for analyzing tradeoffs in diverse landscapes

    PubMed Central

    Raudsepp-Hearne, C.; Peterson, G. D.; Bennett, E. M.

    2010-01-01

    A key challenge of ecosystem management is determining how to manage multiple ecosystem services across landscapes. Enhancing important provisioning ecosystem services, such as food and timber, often leads to tradeoffs between regulating and cultural ecosystem services, such as nutrient cycling, flood protection, and tourism. We developed a framework for analyzing the provision of multiple ecosystem services across landscapes and present an empirical demonstration of ecosystem service bundles, sets of services that appear together repeatedly. Ecosystem service bundles were identified by analyzing the spatial patterns of 12 ecosystem services in a mixed-use landscape consisting of 137 municipalities in Quebec, Canada. We identified six types of ecosystem service bundles and were able to link these bundles to areas on the landscape characterized by distinct social–ecological dynamics. Our results show landscape-scale tradeoffs between provisioning and almost all regulating and cultural ecosystem services, and they show that a greater diversity of ecosystem services is positively correlated with the provision of regulating ecosystem services. Ecosystem service-bundle analysis can identify areas on a landscape where ecosystem management has produced exceptionally desirable or undesirable sets of ecosystem services. PMID:20194739

  13. Reflexions sur les marqueurs de structuration de la conversation (Considerations on the Structural Markers of Conversation).

    ERIC Educational Resources Information Center

    Auchlin, Antoine

    1981-01-01

    Examines morphemic markers that signal the opening and closing of discourse units, emphasizing their complexity and their central role for a descriptive model of conversation. Then proceeds to analyze their functions within the overall structure of conversation, classifying them according to their properties and uses. Societe Nouvelle Didier…

  14. A novel all-optical label processing for OPS networks based on multiple OOC sequences from multiple-groups OOC

    NASA Astrophysics Data System (ADS)

    Qiu, Kun; Zhang, Chongfu; Ling, Yun; Wang, Yibo

    2007-11-01

    This paper proposes an all-optical label processing scheme using multiple optical orthogonal codes sequences (MOOCS) for optical packet switching (OPS) (MOOCS-OPS) networks, for the first time to the best of our knowledge. In this scheme, the multiple optical orthogonal codes (MOOC) from multiple-groups optical orthogonal codes (MGOOC) are permuted and combined to obtain the MOOCS for the optical labels, which are used to effectively enlarge the capacity of available optical codes for optical labels. The optical label processing (OLP) schemes are reviewed and analyzed, the principles of MOOCS-based optical labels for OPS networks are given, and analyzed, then the MOOCS-OPS topology and the key realization units of the MOOCS-based optical label packets are studied in detail, respectively. The performances of this novel all-optical label processing technology are analyzed, the corresponding simulation is performed. These analysis and results show that the proposed scheme can overcome the lack of available optical orthogonal codes (OOC)-based optical labels due to the limited number of single OOC for optical label with the short code length, and indicate that the MOOCS-OPS scheme is feasible.

  15. What Is Wrong with ANOVA and Multiple Regression? Analyzing Sentence Reading Times with Hierarchical Linear Models

    ERIC Educational Resources Information Center

    Richter, Tobias

    2006-01-01

    Most reading time studies using naturalistic texts yield data sets characterized by a multilevel structure: Sentences (sentence level) are nested within persons (person level). In contrast to analysis of variance and multiple regression techniques, hierarchical linear models take the multilevel structure of reading time data into account. They…

  16. Transcriptome analysis of Capsicum annuum varieties Mandarin and Blackcluster: assembly, annotation and molecular marker discovery.

    PubMed

    Ahn, Yul-Kyun; Tripathi, Swati; Kim, Jeong-Ho; Cho, Young-Il; Lee, Hye-Eun; Kim, Do-Sun; Woo, Jong-Gyu; Cho, Myeong-Cheoul

    2014-01-10

    Next generation sequencing technologies have proven to be a rapid and cost-effective means to assemble and characterize gene content and identify molecular markers in various organisms. Pepper (Capsicum annuum L., Solanaceae) is a major staple vegetable crop, which is economically important and has worldwide distribution. High-throughput transcriptome profiling of two pepper cultivars, Mandarin and Blackcluster, using 454 GS-FLX pyrosequencing yielded 279,221 and 316,357 sequenced reads with a total 120.44 and 142.54Mb of sequence data (average read length of 431 and 450 nucleotides). These reads resulted from 17,525 and 16,341 'isogroups' and were assembled into 19,388 and 18,057 isotigs, and 22,217 and 13,153 singletons for both the cultivars, respectively. Assembled sequences were annotated functionally based on homology to genes in multiple public databases. Detailed sequence variant analysis identified a total of 9701 and 12,741 potential SNPs which eventually resulted in 1025 and 1059 genotype specific SNPs, for both the varieties, respectively, after examining SNP frequency distribution for each mapped unigenes. These markers for pepper will be highly valuable for marker-assisted breeding and other genetic studies. © 2013 Elsevier B.V. All rights reserved.

  17. Prevalence of hepatitis B virus markers among hospital personnel in Israel: correlation with some risk factors.

    PubMed

    Weiss, Y; Rabinovitch, M; Cahaner, Y; Noy, D; Siegman-Igra, Y

    1994-03-01

    During 1986-1987, 480 employees of the Tel-Aviv Medical Center were screened for hepatitis B virus (HBV) markers as a preliminary step in a vaccination campaign. One hundred and seventeen (24.4%) had evidence of previous infection, including nine (1.9%) carriers. The effect of potential risk factors on seropositivity was evaluated by multiple logistic regression analysis, which enabled assessment of the individual contribution of each risk factor under the specific environmental conditions. The following risk factors were found to influence seropositivity: origin from Third World countries as opposed to the Western World, employment as sanitary workers, age over 40 years, and history of accidental needle punctures. In the heterogeneous Israeli population, hospital workers had a relatively high prevalence of HBV markers, probably resulting from occupational exposure.

  18. A reductionist approach to extract robust molecular markers from microarray data series - Isolating markers to track osseointegration.

    PubMed

    Barik, Anwesha; Banerjee, Satarupa; Dhara, Santanu; Chakravorty, Nishant

    2017-04-01

    Complexities in the full genome expression studies hinder the extraction of tracker genes to analyze the course of biological events. In this study, we demonstrate the applications of supervised machine learning methods to reduce the irrelevance in microarray data series and thereby extract robust molecular markers to track biological processes. The methodology has been illustrated by analyzing whole genome expression studies on bone-implant integration (ossointegration). Being a biological process, osseointegration is known to leave a trail of genetic footprint during the course. In spite of existence of enormous amount of raw data in public repositories, researchers still do not have access to a panel of genes that can definitively track osseointegration. The results from our study revealed panels comprising of matrix metalloproteinases and collagen genes were able to track osseointegration on implant surfaces (MMP9 and COL1A2 on micro-textured; MMP12 and COL6A3 on superimposed nano-textured surfaces) with 100% classification accuracy, specificity and sensitivity. Further, our analysis showed the importance of the progression of the duration in establishment of the mechanical connection at bone-implant surface. The findings from this study are expected to be useful to researchers investigating osseointegration of novel implant materials especially at the early stage. The methodology demonstrated can be easily adapted by scientists in different fields to analyze large databases for other biological processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Sequencing consolidates molecular markers with plant breeding practice.

    PubMed

    Yang, Huaan; Li, Chengdao; Lam, Hon-Ming; Clements, Jonathan; Yan, Guijun; Zhao, Shancen

    2015-05-01

    Plenty of molecular markers have been developed by contemporary sequencing technologies, whereas few of them are successfully applied in breeding, thus we present a review on how sequencing can facilitate marker-assisted selection in plant breeding. The growing global population and shrinking arable land area require efficient plant breeding. Novel strategies assisted by certain markers have proven effective for genetic gains. Fortunately, cutting-edge sequencing technologies bring us a deluge of genomes and genetic variations, enlightening the potential of marker development. However, a large gap still exists between the potential of molecular markers and actual plant breeding practices. In this review, we discuss marker-assisted breeding from a historical perspective, describe the road from crop sequencing to breeding, and highlight how sequencing facilitates the application of markers in breeding practice.

  20. Simultaneous quantitative determination of multiple bioactive markers in Ocimum sanctum obtained from different locations and its marketed herbal formulations using UPLC-ESI-MS/MS combined with principal component analysis.

    PubMed

    Pandey, Renu; Chandra, Preeti; Srivastava, Mukesh; Mishra, D K; Kumar, Brijesh

    2015-01-01

    Ocimum sanctum L., with phenolic acids, flavonoids, propenyl phenols and terpenoids as active pharmacological constituents, is a popular medicinal herb and is present as an ingredient in many herbal formulations. Therefore, development of a reliable analytical method for simultaneous determination of the pharmacologically active constituents of O. sanctum is of high importance. To develop and validate a new, rapid, sensitive and selective UPLC-ESI/MS/MS method for simultaneous determination of 23 bioactive markers including phenolic acids, flavonoids, propenyl phenol and terpenoid in the leaf extract and marketed herbal formulations of O. sanctum. An UPLC-ESI/MS/MS method using negative electrospray ionisation (ESI) in multiple-reaction-monitoring (MRM) mode was used for simultaneous determination. Chromatographic separation was achieved on an Acquity UPLC BEH C18 -column using a gradient elution with 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Principal component analysis (PCA) was applied to correlate and discriminate eight geographical collections of O. sanctum based on quantitative data of the analytes. The developed method was validated as per International Conference on Harmonization guidelines and found to be accurate, with overall recovery in the range 95.09-104.84% (RSD ≤ 1.85%), precise (RSD ≤ 1.98%) and linear (r(2)  ≥ 0.9971) over the concentration range of 0.5-1000 ng/mL. Ursolic acid was found to be the most abundant marker in all the samples investigated, except for the marketed tablet. The method established is simple, rapid and sensitive, hence it can be reliably utilised for the quality control of O. sanctum and derived herbal formulations. Copyright © 2015 John Wiley & Sons, Ltd.