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Sample records for side population phenotype

  1. A side effect resource to capture phenotypic effects of drugs

    DEFF Research Database (Denmark)

    Kuhn, Michael; Campillos, Monica; Letunic, Ivica

    2010-01-01

    The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research...

  2. Cluster analysis in phenotyping a Portuguese population.

    Science.gov (United States)

    Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J

    2015-09-03

    Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.

  3. Phenotype heterogeneity in cancer cell populations

    International Nuclear Information System (INIS)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-01-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  4. Phenotype heterogeneity in cancer cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

    2016-06-08

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  5. Phenotype heterogeneity in cancer cell populations

    Science.gov (United States)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  6. The use of fluorescent indoline dyes for side population analysis.

    Science.gov (United States)

    Kohara, Hiroshi; Watanabe, Kohei; Shintou, Taichi; Nomoto, Tsuyoshi; Okano, Mie; Shirai, Tomoaki; Miyazaki, Takeshi; Tabata, Yasuhiko

    2013-01-01

    Dye efflux assay evaluated by flow cytometry is useful for stem cell studies. The side population (SP) cells, characterized by the capacity to efflux Hoechst 33342 dye, have been shown to be enriched for hematopoietic stem cells (HSCs) in bone marrow. In addition, SP cells are isolated from various tissues and cell lines, and are also potential candidates for cancer stem cells. However, ultra violet (UV) light, which is not common for every flow cytometer, is required to excite Hoechst 33342. Here we showed that a fluorescent indoline dye ZMB793 can be excited by 488-nm laser, equipped in almost all the modern flow cytometers, and ZMB793-excluding cells showed SP phenotype. HSCs were exclusively enriched in the ZMB793-excluding cells, while ZMB793 was localized in cytosol of bone marrow lineage cells. The efflux of ZMB793 dye was mediated by ATP binding cassette (ABC) transporter Abcg2. Moreover, staining properties were affected by the side-chain structure of the dyes. These data indicate that the fluorescent dye ZMB793 could be used for the SP cell analysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Population FBA predicts metabolic phenotypes in yeast.

    Directory of Open Access Journals (Sweden)

    Piyush Labhsetwar

    2017-09-01

    Full Text Available Using protein counts sampled from single cell proteomics distributions to constrain fluxes through a genome-scale model of metabolism, Population flux balance analysis (Population FBA successfully described metabolic heterogeneity in a population of independent Escherichia coli cells growing in a defined medium. We extend the methodology to account for correlations in protein expression arising from the co-regulation of genes and apply it to study the growth of independent Saccharomyces cerevisiae cells in two different growth media. We find the partitioning of flux between fermentation and respiration predicted by our model agrees with recent 13C fluxomics experiments, and that our model largely recovers the Crabtree effect (the experimentally known bias among certain yeast species toward fermentation with the production of ethanol even in the presence of oxygen, while FBA without proteomics constraints predicts respirative metabolism almost exclusively. The comparisons to the 13C study showed improvement upon inclusion of the correlations and motivated a technique to systematically identify inconsistent kinetic parameters in the literature. The minor secretion fluxes for glycerol and acetate are underestimated by our method, which indicate a need for further refinements to the metabolic model. For yeast cells grown in synthetic defined (SD medium, the calculated broad distribution of growth rates matches experimental observations from single cell studies, and we characterize several metabolic phenotypes within our modeled populations that make use of diverse pathways. Fast growing yeast cells are predicted to perform significant amount of respiration, use serine-glycine cycle and produce ethanol in mitochondria as opposed to slow growing cells. We use a genetic algorithm to determine the proteomics constraints necessary to reproduce the growth rate distributions seen experimentally. We find that a core set of 51 constraints are essential but

  8. Evolution of increased phenotypic diversity enhances population performance by reducing sexual harassment in damselflies.

    Science.gov (United States)

    Takahashi, Yuma; Kagawa, Kotaro; Svensson, Erik I; Kawata, Masakado

    2014-07-18

    The effect of evolutionary changes in traits and phenotypic/genetic diversity on ecological dynamics has received much theoretical attention; however, the mechanisms and ecological consequences are usually unknown. Female-limited colour polymorphism in damselflies is a counter-adaptation to male mating harassment, and thus, is expected to alter population dynamics through relaxing sexual conflict. Here we show the side effect of the evolution of female morph diversity on population performance (for example, population productivity and sustainability) in damselflies. Our theoretical model incorporating key features of the sexual interaction predicts that the evolution of increased phenotypic diversity will reduce overall fitness costs to females from sexual conflict, which in turn will increase productivity, density and stability of a population. Field data and mesocosm experiments support these model predictions. Our study suggests that increased phenotypic diversity can enhance population performance that can potentially reduce extinction rates and thereby influence macroevolutionary processes.

  9. Phenotypic equilibrium as probabilistic convergence in multi-phenotype cell population dynamics.

    Directory of Open Access Journals (Sweden)

    Da-Quan Jiang

    Full Text Available We consider the cell population dynamics with n different phenotypes. Both the Markovian branching process model (stochastic model and the ordinary differential equation (ODE system model (deterministic model are presented, and exploited to investigate the dynamics of the phenotypic proportions. We will prove that in both models, these proportions will tend to constants regardless of initial population states ("phenotypic equilibrium" under weak conditions, which explains the experimental phenomenon in Gupta et al.'s paper. We also prove that Gupta et al.'s explanation is the ODE model under a special assumption. As an application, we will give sufficient and necessary conditions under which the proportion of one phenotype tends to 0 (die out or 1 (dominate. We also extend our results to non-Markovian cases.

  10. Isolation and characterization of multidrug-resistant side population ...

    African Journals Online (AJOL)

    Results: SP cells in the prostate cancer samples constituted 2.8 %, but fell to 0.6 % after treatment with ... tumor. Keywords: Side population cells, ABC transporters, Cancer stem cells, Chemotherapy, Prostate treatment failure, Tumor recurrence, Drug resistance ..... Identification of human brain tumour initiating cells.

  11. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C

    2012-02-01

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using chi(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  12. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C

    2011-04-17

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using χ(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  13. Population and housing: A two-sided relationship

    Directory of Open Access Journals (Sweden)

    Clara H. Mulder

    2006-11-01

    Full Text Available In this paper I explore the relationship between population and housing. I argue that this relationship is two-sided. On the one hand, the size of a population, and particularly the number of households, determines the demand for housing. On the other hand, the availability of suitable and affordable housing may attract certain categories of migrants. It also influences young people's opportunities to leave the parental home, marry or cohabit, and have children. Furthermore, home-ownership hampers residential mobility and migration by binding people to a place.

  14. Phenotypic plasticity and population differentiation in an ongoing species invasion.

    Directory of Open Access Journals (Sweden)

    Silvia Matesanz

    Full Text Available The ability to succeed in diverse conditions is a key factor allowing introduced species to successfully invade and spread across new areas. Two non-exclusive factors have been suggested to promote this ability: adaptive phenotypic plasticity of individuals, and the evolution of locally adapted populations in the new range. We investigated these individual and population-level factors in Polygonum cespitosum, an Asian annual that has recently become invasive in northeastern North America. We characterized individual fitness, life-history, and functional plasticity in response to two contrasting glasshouse habitat treatments (full sun/dry soil and understory shade/moist soil in 165 genotypes sampled from nine geographically separate populations representing the range of light and soil moisture conditions the species inhabits in this region. Polygonum cespitosum genotypes from these introduced-range populations expressed broadly similar plasticity patterns. In response to full sun, dry conditions, genotypes from all populations increased photosynthetic rate, water use efficiency, and allocation to root tissues, dramatically increasing reproductive fitness compared to phenotypes expressed in simulated understory shade. Although there were subtle among-population differences in mean trait values as well as in the slope of plastic responses, these population differences did not reflect local adaptation to environmental conditions measured at the population sites of origin. Instead, certain populations expressed higher fitness in both glasshouse habitat treatments. We also compared the introduced-range populations to a single population from the native Asian range, and found that the native population had delayed phenology, limited functional plasticity, and lower fitness in both experimental environments compared with the introduced-range populations. Our results indicate that the future spread of P. cespitosum in its introduced range will likely be

  15. Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

    Science.gov (United States)

    Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

    2015-11-01

    Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

  16. Phenotypic switching of populations of cells in a stochastic environment

    Science.gov (United States)

    Hufton, Peter G.; Lin, Yen Ting; Galla, Tobias

    2018-02-01

    In biology phenotypic switching is a common bet-hedging strategy in the face of uncertain environmental conditions. Existing mathematical models often focus on periodically changing environments to determine the optimal phenotypic response. We focus on the case in which the environment switches randomly between discrete states. Starting from an individual-based model we derive stochastic differential equations to describe the dynamics, and obtain analytical expressions for the mean instantaneous growth rates based on the theory of piecewise-deterministic Markov processes. We show that optimal phenotypic responses are non-trivial for slow and intermediate environmental processes, and systematically compare the cases of periodic and random environments. The best response to random switching is more likely to be heterogeneity than in the case of deterministic periodic environments, net growth rates tend to be higher under stochastic environmental dynamics. The combined system of environment and population of cells can be interpreted as host-pathogen interaction, in which the host tries to choose environmental switching so as to minimise growth of the pathogen, and in which the pathogen employs a phenotypic switching optimised to increase its growth rate. We discuss the existence of Nash-like mutual best-response scenarios for such host-pathogen games.

  17. Comparative Analyses of Phenotypic Trait Covariation within and among Populations.

    Science.gov (United States)

    Peiman, Kathryn S; Robinson, Beren W

    2017-10-01

    Many morphological, behavioral, physiological, and life-history traits covary across the biological scales of individuals, populations, and species. However, the processes that cause traits to covary also change over these scales, challenging our ability to use patterns of trait covariance to infer process. Trait relationships are also widely assumed to have generic functional relationships with similar evolutionary potentials, and even though many different trait relationships are now identified, there is little appreciation that these may influence trait covariation and evolution in unique ways. We use a trait-performance-fitness framework to classify and organize trait relationships into three general classes, address which ones more likely generate trait covariation among individuals in a population, and review how selection shapes phenotypic covariation. We generate predictions about how trait covariance changes within and among populations as a result of trait relationships and in response to selection and consider how these can be tested with comparative data. Careful comparisons of covariation patterns can narrow the set of hypothesized processes that cause trait covariation when the form of the trait relationship and how it responds to selection yield clear predictions about patterns of trait covariation. We discuss the opportunities and limitations of comparative approaches to evaluate hypotheses about the evolutionary causes and consequences of trait covariation and highlight the importance of evaluating patterns within populations replicated in the same and in different selective environments. Explicit hypotheses about trait relationships are key to generating effective predictions about phenotype and its evolution using covariance data.

  18. A probabilistic model for cell population phenotyping using HCS data.

    Directory of Open Access Journals (Sweden)

    Edouard Pauwels

    Full Text Available High Content Screening (HCS platforms allow screening living cells under a wide range of experimental conditions and give access to a whole panel of cellular responses to a specific treatment. The outcome is a series of cell population images. Within these images, the heterogeneity of cellular response to the same treatment leads to a whole range of observed values for the recorded cellular features. Consequently, it is difficult to compare and interpret experiments. Moreover, the definition of phenotypic classes at a cell population level remains an open question, although this would ease experiments analyses. In the present work, we tackle these two questions. The input of the method is a series of cell population images for which segmentation and cellular phenotype classification has already been performed. We propose a probabilistic model to represent and later compare cell populations. The model is able to fully exploit the HCS-specific information: "dependence structure of population descriptors" and "within-population variability". The experiments we carried out illustrate how our model accounts for this specific information, as well as the fact that the model benefits from considering them. We underline that these features allow richer HCS data analysis than simpler methods based on single cellular feature values averaged over each well. We validate an HCS data analysis method based on control experiments. It accounts for HCS specificities that were not taken into account by previous methods but have a sound biological meaning. Biological validation of previously unknown outputs of the method constitutes a future line of work.

  19. Phenotype of normal spirometry in an aging population.

    Science.gov (United States)

    Vaz Fragoso, Carlos A; McAvay, Gail; Van Ness, Peter H; Casaburi, Richard; Jensen, Robert L; MacIntyre, Neil; Gill, Thomas M; Yaggi, H Klar; Concato, John

    2015-10-01

    In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]). To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories. Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm). Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories. GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the

  20. Functional heterogeneity of side population cells in skeletal muscle

    International Nuclear Information System (INIS)

    Uezumi, Akiyoshi; Ojima, Koichi; Fukada, So-ichiro; Ikemoto, Madoka; Masuda, Satoru; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

    2006-01-01

    Skeletal muscle regeneration has been exclusively attributed to myogenic precursors, satellite cells. A stem cell-rich fraction referred to as side population (SP) cells also resides in skeletal muscle, but its roles in muscle regeneration remain unclear. We found that muscle SP cells could be subdivided into three sub-fractions using CD31 and CD45 markers. The majority of SP cells in normal non-regenerating muscle expressed CD31 and had endothelial characteristics. However, CD31 - CD45 - SP cells, which are a minor subpopulation in normal muscle, actively proliferated upon muscle injury and expressed not only several regulatory genes for muscle regeneration but also some mesenchymal lineage markers. CD31 - CD45 - SP cells showed the greatest myogenic potential among three SP sub-fractions, but indeed revealed mesenchymal potentials in vitro. These SP cells preferentially differentiated into myofibers after intramuscular transplantation in vivo. Our results revealed the heterogeneity of muscle SP cells and suggest that CD31 - CD45 - SP cells participate in muscle regeneration

  1. Phenotypic selection in natural populations: what limits directional selection?

    Science.gov (United States)

    Kingsolver, Joel G; Diamond, Sarah E

    2011-03-01

    Studies of phenotypic selection document directional selection in many natural populations. What factors reduce total directional selection and the cumulative evolutionary responses to selection? We combine two data sets for phenotypic selection, representing more than 4,600 distinct estimates of selection from 143 studies, to evaluate the potential roles of fitness trade-offs, indirect (correlated) selection, temporally varying selection, and stabilizing selection for reducing net directional selection and cumulative responses to selection. We detected little evidence that trade-offs among different fitness components reduced total directional selection in most study systems. Comparisons of selection gradients and selection differentials suggest that correlated selection frequently reduced total selection on size but not on other types of traits. The direction of selection on a trait often changes over time in many temporally replicated studies, but these fluctuations have limited impact in reducing cumulative directional selection in most study systems. Analyses of quadratic selection gradients indicated stabilizing selection on body size in at least some studies but provided little evidence that stabilizing selection is more common than disruptive selection for most traits or study systems. Our analyses provide little evidence that fitness trade-offs, correlated selection, or stabilizing selection strongly constrains the directional selection reported for most quantitative traits.

  2. Flow Cytometry of the Side Population: Tips & Tricks

    Directory of Open Access Journals (Sweden)

    Irene Sales-Pardo

    2006-01-01

    Full Text Available Background: The Side Population (SP has become an important hallmark for the definition of the stem cell compartment, especially in the detection of these cells and in their physical isolation by fluorescence-activated cell sorting (FACS. SP cells are CD34neg and were discovered using ultraviolet excitation based on the efflux of Hoechst 33342 (Ho342. Although the method works as originally described, we believe that this method is difficult for most investigators. First, because the ability to discriminate SP cells is based on the differential retention of Ho342 during a functional assay; second, because of the difficulties in setting the right experimental and acquisition conditions; and third, because the analysis of the acquired data requires an extensive expertise on flow cytometry to accurately detect the SP events. Methods: First of all and mainly for the SP application, the laser beam paths were exhaustively checked to ensure the lowest coefficients of variation. Blood suspensions were prepared by erythrocyte lysis with ammonium chloride and hematopoietic cells were labeled with Ho342. Results: The Ho342 concentration and the staining procedure are critical for the optimal resolution of the SP cells. Although UV laser alignment is very important to resolve the dim tail that outlines the SP, the problem with Ho342 excitation is not the Hoechst Blue emission, but rather the Hoechst Red's (because of the weak emission. Conclusions: Each laboratory must establish its own expected ranges based on its instrument and results may vary slightly due to instrument differences such as the narrowness of the band pass filters, laser power, laser emission wavelength, nozzle type, differential of pressure, light collection system (cuvette versus jet-in-air and beam shaping optics.

  3. Phenotypic variability in a population of globe artichoke

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    Angélica Reolon da Costa

    2014-11-01

    Full Text Available The existence of variability is a prerequisite for genetic improvement in plants. Globe artichoke is a high nutritious vegetable with medical value, representing a profitable alternative for rural producers. This research was conducted with the aim of evaluating the phenotypic variability in a commercial cultivar of artichoke (Cynara cardunculus var. scolymus L established from seeds. Field plants were assessed when primary head reached commercial stage. An amount of 21 quantitative and 5 multicategoric characters were assessed. The quantitative data were submitted to multivariate analysis. For quantitative characters the distance between individuals varied from 3.0 to 50.9, revealing high intrapopulation variability. The greater relative contribution characters for genetic divergence were the primary head fresh mass (79.88% and bottom fresh mass (8.43%. This indicates the possibility of plant selection for head quality in this population. The clustering analysis through UPGMA method, based on quantitative characters, allowed the formation of five groups. For multicategoric traits, the similarity among individuals varied from 1.22% to 100%. Within the existing population variability, it was possible to select plants with superior quantitative traits desirable for in natura consumption, as primary head fresh weight and length, bottom fresh mass, bract basis length and width, as well as non-quantitative traits as round head shape, absence of thorn and presence of violet color in the head.

  4. Detection and characterization of side population in Ewing's sarcoma SK-ES-1 cells in vitro

    International Nuclear Information System (INIS)

    Yang, Min; Zhang, Rui; Yan, Ming; Ye, Zhengxu; Liang, Wei; Luo, Zhuojing

    2010-01-01

    Dye exclusion is a valuable technique to isolate cancer stem cells (CSCs) based on an ability of stem cell to efflux fluorescent DNA-binding dye, especially for tumors without unique surface markers. It has been proven that side population (SP) cells that exclude Hoechst 33342 dye are enriched with stem-like cells in several cancer cell lines. In this study, we isolated and characterized SP cells from human Ewing's sarcoma cell line SK-ES-1 in vitro. SP cells were detected in SK-ES-1 and comprised 1.2% of total cell population. Only SP cells had the capacity to regenerate both SP and non-SP cells. The proliferation rates were similar between SP and non-SP cells. However, the clonogenicity and invasiveness of SP cells were significantly higher than that of non-SP cells. Further characterization of this SP phenotype presented other properties. SP cells exhibited increased multi-drug resistance and the ATP binding cassette protein (ABC) transporters were up-regulated in SP population. These findings suggest that SP cells derived from Ewing's sarcoma play the critical role in tumor metastasis and recurrence and might be an ideal target for clinical therapy.

  5. A hierarchical anatomical classification schema for prediction of phenotypic side effects.

    Science.gov (United States)

    Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

    2018-01-01

    Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

  6. Multidimensional clinical phenotyping of an adult cystic fibrosis patient population.

    Directory of Open Access Journals (Sweden)

    Douglas J Conrad

    Full Text Available Cystic Fibrosis (CF is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease.The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier.Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1 a low lung health scores phenotype, 2 a younger, well-nourished, male-dominated class, 3 various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency.This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study.

  7. Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

    Directory of Open Access Journals (Sweden)

    Kazuyo Yasuda

    Full Text Available Cancer stem-like cells (CSCs/cancer-initiaiting cells (CICs are defined as a small population of cancer cells that have self-renewal capacity, differentiation potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have been isolated by side population (SP analysis, ALDEFLUOR assay and using cell surface markers. However, these approaches are not definitive markers for CSCs/CICs, and it is necessary to refine recent methods for identifying more highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde dehydrogenese bright (ALDH(Br cells from ovarian cancer cells. Both SP cells and ALDH(Br cells exhibited higher tumor-initiating ability and higher expression level of a stem cell marker, sex determining region Y-box 2 (SOX2, than those of main population (MP cells and ALDH(Low cells, respectively. We analyzed an SP and ALDH(Br overlapping population (SP/ALDH(Br, and the SP/ALDH(Br population exhibited higher tumor-initiating ability than that of SP cells or ALDH(Br cells, enabling initiation of tumor with as few as 10(2 cells. Furthermore, SP/ADLH(Br population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDH(Low, MP/ALDH(Br and MP/ALDH(Low cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDH(Br population was detected in several gynecological cancer cells with ratios of 0.1% for HEC-1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous adenocarcinoma cells. Taken together, use of the SP and ALDH(Br overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.

  8. SECONDARY POPULATION OF INTERSTELLAR NEUTRALS seems deflected to the side

    Science.gov (United States)

    Nakagawa, H.; Bzowski, M.; Yamazaki, A.; Fukunishi, H.; Watanabe, S.; Takahashi, Y.; Taguchi, M.

    Recently the neutral hydrogen flow in the inner heliosphere was found to be deflected relative to the helium flow by about 4 degrees Lallement et al 2005 The explanation of this delfection offered was a distortion of the heliosphere under the action of an ambient interstellar magnetic field In a separate study a number of data sets pertaining to interstellar neutral atoms obtained with various techniques were compiled and interpreted as due to an inflow of interstellar gas from an ecliptic longitude shifted by 10 - 40 degrees from the canonical upstream interstellar neutral flow direction at 254 degrees Collier et al 2004 The origin and properties of such a flow is still under debate We have performed a cross-experiment analysis of the heliospheric hydrogen and helium photometric observations performed simltaneously by the Nozomi spacecraft between the Earth and Mars orbit and explored possible deflection of hydrogen and helium flows with respect to the canonical upwind direction For the interpretation we used predictions of a state of the art 3D and fully time-dependent model of the neutral gas in the heliosphere with the boundary conditions ionization rates and radiation pressure taken from literature The model includes two populations of the thermal interstellar hydrogen predicted by the highly-reputed Moscow Monte Carlo model of the heliosphere The agreement between the data and simulations is not satifactory when one assumes that the upwind direction is the same for both populations and identical with the direction derived from inerstellar helium

  9. Intraspecies differenes in phenotypic plasticity: Invasive versus non-invasive populations of Ceratophyllum demersum

    DEFF Research Database (Denmark)

    Hyldgaard, Benita; Brix, Hans

    2012-01-01

    High phenotypic plasticity has been hypothesized to affect the invasiveness of plants, as high plasticity may enlarge the breath of environments in which the plants can survive and reproduce. Here we compare the phenotypic plasticity of invasive and non-invasive populations of the same species...... hypothesized that the phenotypic plasticity in fitness-related traits like growth and photosynthesis were higher in the invasive than in the non-invasive population. The invasive population acclimated to elevated temperatures through increased rates of photosynthesis (range: Pamb: 8–452 mol O2 g−1 DM h−1......-harvesting complex. Hence, the invasive population of C. demersum from New Zealand had higher phenotypic plasticity in response to temperature than the non-invasive Danish population. This might be the result of genetic evolution since its introduction to New Zealand five decades ago, but further studies are needed...

  10. Bypassing Evolutionary Roadblocks: Phenotypic Diversity in Isogenic Population Bridges Tradeoff in Evolution of a New Function

    Science.gov (United States)

    Petrie, K. L.; Meyer, J. R.

    2017-07-01

    A novel mechanism of innovation bridges fitness valleys by violating the one gene-one phenotype dogma. Protein products of a single gene partition into populations, some of which carry out a new function and some the old, avoiding tradeoffs.

  11. Phenotypic plasticity in the range-margin population of the lycaenid butterfly Zizeeria maha

    Directory of Open Access Journals (Sweden)

    Otaki Joji M

    2010-08-01

    Full Text Available Abstract Background Many butterfly species have been experiencing the northward range expansion and physiological adaptation, probably due to climate warming. Here, we document an extraordinary field case of a species of lycaenid butterfly, Zizeeria maha, for which plastic phenotypes of wing color-patterns were revealed at the population level in the course of range expansion. Furthermore, we examined whether this outbreak of phenotypic changes was able to be reproduced in a laboratory. Results In the recently expanded northern range margins of this species, more than 10% of the Z. maha population exhibited characteristic color-pattern modifications on the ventral wings for three years. We physiologically reproduced similar phenotypes by an artificial cold-shock treatment of a normal southern population, and furthermore, we genetically reproduced a similar phenotype after selective breeding of a normal population for ten generations, demonstrating that the cold-shock-induced phenotype was heritable and partially assimilated genetically in the breeding line. Similar genetic process might have occurred in the previous and recent range-margin populations as well. Relatively minor modifications expressed in the tenth generation of the breeding line together with other data suggest a role of founder effect in this field case. Conclusions Our results support the notion that the outbreak of the modified phenotypes in the recent range-margin population was primed by the revelation of plastic phenotypes in response to temperature stress and by the subsequent genetic process in the previous range-margin population, followed by migration and temporal establishment of genetically unstable founders in the recent range margins. This case presents not only an evolutionary role of phenotypic plasticity in the field but also a novel evolutionary aspect of range expansion at the species level.

  12. Cigarette smoke promotes drug resistance and expansion of cancer stem cell-like side population.

    Directory of Open Access Journals (Sweden)

    Yi An

    Full Text Available It is well known that many patients continue to smoke cigarettes after being diagnosed with cancer. Although smoking cessation has typically been presumed to possess little therapeutic value for cancer, a growing body of evidence suggests that continued smoking is associated with reduced efficacy of treatment and a higher incidence of recurrence. We therefore investigated the effect of cigarette smoke condensate (CSC on drug resistance in the lung cancer and head and neck cancer cell lines A549 and UMSCC-10B, respectively. Our results showed that CSC significantly increased the cellular efflux of doxorubicin and mitoxantrone. This was accompanied by membrane localization and increased expression of the multi-drug transporter ABCG2. The induced efflux of doxorubicin was reversed upon addition of the specific ABCG2 inhibitor Fumitremorgin C, confirming the role of ABCG2. Treatment with CSC increased the concentration of phosphorylated Akt, while addition of the PI3K inhibitor LY294002 blocked doxorubicin extrusion, suggesting that Akt activation is required for CSC-induced drug efflux. In addition, CSC was found to promote resistance to doxorubicin as determined by MTS assays. This CSC-induced doxurbicin-resistance was mitigated by mecamylamine, a nicotinic acetylcholine receptor inhibitor, suggesting that nicotine is at least partially responsible for the effect of CSC. Lastly, CSC increased the size of the side population (SP, which has been linked to a cancer stem cell-like phenotype. In summary, CSC promotes chemoresistance via Akt-mediated regulation of ABCG2 activity, and may also increase the proportion of cancer stem-like cells, contributing to tumor resilience. These findings underscore the importance of smoking cessation following a diagnosis of cancer, and elucidate the mechanisms of continued smoking that may be detrimental to treatment.

  13. Metabolomics to unveil and understand phenotypic diversity between pathogen populations.

    Directory of Open Access Journals (Sweden)

    Ruben t'Kindt

    Full Text Available Leishmaniasis is a debilitating disease caused by the parasite Leishmania. There is extensive clinical polymorphism, including variable responsiveness to treatment. We study Leishmania donovani parasites isolated from visceral leishmaniasis patients in Nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. Here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for L. donovani to characterize the global metabolic differences between antimonial-sensitive and antimonial-resistant L. donovani isolates. Clones of drug-sensitive and drug-resistant parasite isolates from clinical samples were cultured in vitro and harvested for metabolomics analysis. The relative abundance of 340 metabolites was determined by ZIC-HILIC chromatography coupled to LTQ-Orbitrap mass spectrometry. Our measurements cover approximately 20% of the predicted core metabolome of Leishmania and additionally detected a large number of lipids. Drug-sensitive and drug-resistant parasites showed distinct metabolic profiles, and unsupervised clustering and principal component analysis clearly distinguished the two phenotypes. For 100 metabolites, the detected intensity differed more than three-fold between the 2 phenotypes. Many of these were in specific areas of lipid metabolism, suggesting that the membrane composition of the drug-resistant parasites is extensively modified. Untargeted metabolomics has been applied on clinical Leishmania isolates to uncover major metabolic differences between drug-sensitive and drug-resistant isolates. The identified major differences provide novel insights into the mechanisms involved in resistance to antimonial drugs, and facilitate investigations using targeted approaches to unravel the key changes mediating drug resistance.

  14. Nonequilibrium population dynamics of phenotype conversion of cancer cells.

    Directory of Open Access Journals (Sweden)

    Joseph Xu Zhou

    Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

  15. Application of the asthma phenotype algorithm from the Severe Asthma Research Program to an urban population.

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    Paru Patrawalla

    Full Text Available Identification and characterization of asthma phenotypes are challenging due to disease complexity and heterogeneity. The Severe Asthma Research Program (SARP used unsupervised cluster analysis to define 5 phenotypically distinct asthma clusters that they replicated using 3 variables in a simplified algorithm. We evaluated whether this simplified SARP algorithm could be used in a separate and diverse urban asthma population to recreate these 5 phenotypic clusters.The SARP simplified algorithm was applied to adults with asthma recruited to the New York University/Bellevue Asthma Registry (NYUBAR to classify patients into five groups. The clinical phenotypes were summarized and compared.Asthma subjects in NYUBAR (n = 471 were predominantly women (70% and Hispanic (57%, which were demographically different from the SARP population. The clinical phenotypes of the five groups generated by the simplified SARP algorithm were distinct across groups and distributed similarly to those described for the SARP population. Groups 1 and 2 (6 and 63%, respectively had predominantly childhood onset atopic asthma. Groups 4 and 5 (20% were older, with the longest duration of asthma, increased symptoms and exacerbations. Group 4 subjects were the most atopic and had the highest peripheral eosinophils. Group 3 (10% had the least atopy, but included older obese women with adult-onset asthma, and increased exacerbations.Application of the simplified SARP algorithm to the NYUBAR yielded groups that were phenotypically distinct and useful to characterize disease heterogeneity. Differences across NYUBAR groups support phenotypic variation and support the use of the simplified SARP algorithm for classification of asthma phenotypes in future prospective studies to investigate treatment and outcome differences between these distinct groups.Clinicaltrials.gov NCT00212537.

  16. Directional selection effects on patterns of phenotypic (co)variation in wild populations.

    Science.gov (United States)

    Assis, A P A; Patton, J L; Hubbe, A; Marroig, G

    2016-11-30

    Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. © 2016 The Author(s).

  17. Phylogeography and population dynamics of the white-sided dolphin (Lagenorhynchus acutus) in the North Atlantic

    KAUST Repository

    Banguera-Hinestroza, E.; Evans, P. G H; Mirimin, L.; Reid, R. J.; Mikkelsen, B.; Couperus, A. S.; Deaville, R.; Rogan, E.; Hoelzel, A. R.

    2014-01-01

    Highly mobile species in the marine environment may be expected to show little differentiation at the population level, but this is often not the case. Instead cryptic population structure is common, and effective conservation will require an understanding of how these patterns evolve. Here we present an assessment from both sides of the North Atlantic of differentiation among populations of a dolphin species that inhabits mainly pelagic waters, the Atlantic white-sided dolphin. We compare eleven putative populations in the western and eastern North Atlantic at mtDNA and microsatellite DNA loci and find reduced nucleotide diversity and signals for historical bottlenecks and post-bottleneck expansions in all regions. We calculate expansion times to have occurred during the early Holocene, following the last glacial maximum (LGM). We find evidence for connectivity among populations from either side of the North Atlantic, and differentiation between putative populations in the far northeast compared with all other areas sampled. Some data suggest the possibility of separate refugia during the LGM explaining this pattern, although ongoing ecological processes may also be a factor. We discuss the implications for developing effective programs of conservation and management in the context of ongoing anthropogenic impact. © 2014 Springer Science+Business Media Dordrecht.

  18. Phylogeography and population dynamics of the white-sided dolphin (Lagenorhynchus acutus) in the North Atlantic

    KAUST Repository

    Banguera-Hinestroza, E.

    2014-02-27

    Highly mobile species in the marine environment may be expected to show little differentiation at the population level, but this is often not the case. Instead cryptic population structure is common, and effective conservation will require an understanding of how these patterns evolve. Here we present an assessment from both sides of the North Atlantic of differentiation among populations of a dolphin species that inhabits mainly pelagic waters, the Atlantic white-sided dolphin. We compare eleven putative populations in the western and eastern North Atlantic at mtDNA and microsatellite DNA loci and find reduced nucleotide diversity and signals for historical bottlenecks and post-bottleneck expansions in all regions. We calculate expansion times to have occurred during the early Holocene, following the last glacial maximum (LGM). We find evidence for connectivity among populations from either side of the North Atlantic, and differentiation between putative populations in the far northeast compared with all other areas sampled. Some data suggest the possibility of separate refugia during the LGM explaining this pattern, although ongoing ecological processes may also be a factor. We discuss the implications for developing effective programs of conservation and management in the context of ongoing anthropogenic impact. © 2014 Springer Science+Business Media Dordrecht.

  19. Non-cultured adipose-derived CD45(-) side population cells are enriched for progenitors that give rise to myofibres in vivo

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Schrøder, Henrik D; Jensen, Charlotte H

    2008-01-01

    Side population (SP) cells are highly able to exclude the Hoechst 33342 dye through membrane transporters, a feature associated with cell immaturity and therefore proposed as a marker of stem cells. Herein we demonstrate that the adipose tissue derived stromal vascular fraction (SVF) contains...... skeletal muscle repair mainly relies on the satellitecell, several reports have shown that vessel-associated cells may adopt a myogenic phenotype when exposed to a muscle environment. In accordance with these findings, we also observed invitro myogenic specification of SPCD45(-) cells when cocultured...... a novel population of non-haematopoietic "side population" (SPCD45(-)) cells. Simultaneous qRT-PCR of 64 genes revealed that the freshly isolated SPCD45(-) was highly enriched for cells expressing genes related to stem cells, the Notch pathway, and early vascular precursors. Notably, the expression...

  20. Distance from Africa, not climate, explains within-population phenotypic diversity in humans

    Science.gov (United States)

    Betti, Lia; Balloux, François; Amos, William; Hanihara, Tsunehiko; Manica, Andrea

    2008-01-01

    The relative importance of ancient demography and climate in determining worldwide patterns of human within-population phenotypic diversity is still open to debate. Several morphometric traits have been argued to be under selection by climatic factors, but it is unclear whether climate affects the global decline in morphological diversity with increasing geographical distance from sub-Saharan Africa. Using a large database of male and female skull measurements, we apply an explicit framework to quantify the relative role of climate and distance from Africa. We show that distance from sub-Saharan Africa is the sole determinant of human within-population phenotypic diversity, while climate plays no role. By selecting the most informative set of traits, it was possible to explain over half of the worldwide variation in phenotypic diversity. These results mirror those previously obtained for genetic markers and show that ‘bones and molecules’ are in perfect agreement for humans. PMID:19129123

  1. Landscape patterns of phenotypic variation and population structuring in a selfing grass, Elymus glaucus (blue wildrye).

    Science.gov (United States)

    Vicky J. Erickson; Nancy L. Mandel; Frank C. Sorensen

    2004-01-01

    Source-related phenotypic variance was investigated in a common garden study of populations of Elymus glaucus Buckley (blue wildrye) from the Blue Mountain Ecological Province of northeastern Oregon and adjoining Washington. The primary objective of this study was to assess geographic patterns of potentially adaptive differentiation in this self-...

  2. Genetic variation in variability: phenotypic variability of fledging weight and its evolution in a songbird population

    NARCIS (Netherlands)

    Mulder, H.A.; Gienapp, P; Visser, ME

    2016-01-01

    Variation in traits is essential for natural selection to operate and genetic and environmental effects can contribute to this phenotypic variation. From domesticated populations, we know that families can differ in their level of within-family variance, which leads to the intriguing situation that

  3. Use of genetic data to infer population-specific ecological and phenotypic traits from mixed aggregations.

    Directory of Open Access Journals (Sweden)

    Paul Moran

    Full Text Available Many applications in ecological genetics involve sampling individuals from a mixture of multiple biological populations and subsequently associating those individuals with the populations from which they arose. Analytical methods that assign individuals to their putative population of origin have utility in both basic and applied research, providing information about population-specific life history and habitat use, ecotoxins, pathogen and parasite loads, and many other non-genetic ecological, or phenotypic traits. Although the question is initially directed at the origin of individuals, in most cases the ultimate desire is to investigate the distribution of some trait among populations. Current practice is to assign individuals to a population of origin and study properties of the trait among individuals within population strata as if they constituted independent samples. It seemed that approach might bias population-specific trait inference. In this study we made trait inferences directly through modeling, bypassing individual assignment. We extended a Bayesian model for population mixture analysis to incorporate parameters for the phenotypic trait and compared its performance to that of individual assignment with a minimum probability threshold for assignment. The Bayesian mixture model outperformed individual assignment under some trait inference conditions. However, by discarding individuals whose origins are most uncertain, the individual assignment method provided a less complex analytical technique whose performance may be adequate for some common trait inference problems. Our results provide specific guidance for method selection under various genetic relationships among populations with different trait distributions.

  4. Use of genetic data to infer population-specific ecological and phenotypic traits from mixed aggregations

    Science.gov (United States)

    Moran, Paul; Bromaghin, Jeffrey F.; Masuda, Michele

    2014-01-01

    Many applications in ecological genetics involve sampling individuals from a mixture of multiple biological populations and subsequently associating those individuals with the populations from which they arose. Analytical methods that assign individuals to their putative population of origin have utility in both basic and applied research, providing information about population-specific life history and habitat use, ecotoxins, pathogen and parasite loads, and many other non-genetic ecological, or phenotypic traits. Although the question is initially directed at the origin of individuals, in most cases the ultimate desire is to investigate the distribution of some trait among populations. Current practice is to assign individuals to a population of origin and study properties of the trait among individuals within population strata as if they constituted independent samples. It seemed that approach might bias population-specific trait inference. In this study we made trait inferences directly through modeling, bypassing individual assignment. We extended a Bayesian model for population mixture analysis to incorporate parameters for the phenotypic trait and compared its performance to that of individual assignment with a minimum probability threshold for assignment. The Bayesian mixture model outperformed individual assignment under some trait inference conditions. However, by discarding individuals whose origins are most uncertain, the individual assignment method provided a less complex analytical technique whose performance may be adequate for some common trait inference problems. Our results provide specific guidance for method selection under various genetic relationships among populations with different trait distributions.

  5. Habitat Fragmentation Differentially Affects Genetic Variation, Phenotypic Plasticity and Survival in Populations of a Gypsum Endemic

    Directory of Open Access Journals (Sweden)

    Silvia Matesanz

    2017-05-01

    Full Text Available Habitat fragmentation, i.e., fragment size and isolation, can differentially alter patterns of neutral and quantitative genetic variation, fitness and phenotypic plasticity of plant populations, but their effects have rarely been tested simultaneously. We assessed the combined effects of size and connectivity on these aspects of genetic and phenotypic variation in populations of Centaurea hyssopifolia, a narrow endemic gypsophile that previously showed performance differences associated with fragmentation. We grew 111 maternal families sampled from 10 populations that differed in their fragment size and connectivity in a common garden, and characterized quantitative genetic variation, phenotypic plasticity to drought for key functional traits, and plant survival, as a measure of population fitness. We also assessed neutral genetic variation within and among populations using eight microsatellite markers. Although C. hyssopifolia is a narrow endemic gypsophile, we found substantial neutral genetic variation and quantitative variation for key functional traits. The partition of genetic variance indicated that a higher proportion of variation was found within populations, which is also consistent with low population differentiation in molecular markers, functional traits and their plasticity. This, combined with the generally small effect of habitat fragmentation suggests that gene flow among populations is not restricted, despite large differences in fragment size and isolation. Importantly, population’s similarities in genetic variation and plasticity did not reflect the lower survival observed in isolated populations. Overall, our results indicate that, although the species consists of genetically variable populations able to express functional plasticity, such aspects of adaptive potential may not always reflect populations’ survival. Given the differential effects of habitat connectivity on functional traits, genetic variation and fitness

  6. Experimental evolution reveals differences between phenotypic and evolutionary responses to population density.

    Science.gov (United States)

    McNamara, K B; Simmons, L W

    2017-09-01

    Group living can select for increased immunity, given the heightened risk of parasite transmission. Yet, it also may select for increased male reproductive investment, given the elevated risk of female multiple mating. Trade-offs between immunity and reproduction are well documented. Phenotypically, population density mediates both reproductive investment and immune function in the Indian meal moth, Plodia interpunctella. However, the evolutionary response of populations to these traits is unknown. We created two replicated populations of P. interpunctella, reared and mated for 14 generations under high or low population densities. These population densities cause plastic responses in immunity and reproduction: at higher numbers, both sexes invest more in one index of immunity [phenoloxidase (PO) activity] and males invest more in sperm. Interestingly, our data revealed divergence in PO and reproduction in a different direction to previously reported phenotypic responses. Males evolving at low population densities transferred more sperm, and both males and females displayed higher PO than individuals at high population densities. These positively correlated responses to selection suggest no apparent evolutionary trade-off between immunity and reproduction. We speculate that the reduced PO activity and sperm investment when evolving under high population density may be due to the reduced population fitness predicted under increased sexual conflict and/or to trade-offs between pre- and post-copulatory traits. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  7. Phenotypic heterogeneity in a bacteriophage population only appears as stress-induced mutagenesis.

    Science.gov (United States)

    Yosef, Ido; Edgar, Rotem; Qimron, Udi

    2016-11-01

    Stress-induced mutagenesis has been studied in cancer cells, yeast, bacteria, and archaea, but not in viruses. In a recent publication, we present a bacteriophage model showing an apparent stress-induced mutagenesis. We show that the stress does not drive the mutagenesis, but only selects the fittest mutants. The mechanism underlying the observed phenomenon is a phenotypic heterogeneity that resembles persistence of the viral population. The new findings, the background for the ongoing debate on stress-induced mutagenesis, and the phenotypic heterogeneity underlying a novel phage infection strategy are discussed in this short manuscript.

  8. Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population.

    Science.gov (United States)

    Auger, Julie; Baptiste, Amandine; Benabbad, Imane; Thierry, Gaëlle; Costa, Jean-Marc; Amouyal, Mélanie; Kottler, Marie-Laure; Leheup, Bruno; Touraine, Renaud; Schmitt, Sébastien; Lebrun, Marine; Cormier Daire, Valérie; Bonnefont, Jean-Paul; de Roux, Nicolas; Elie, Caroline; Rosilio, Myriam

    2016-01-01

    The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation. We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis. Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications. Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions. © 2016 S. Karger AG, Basel.

  9. What role does heritability play in transgenerational phenotypic responses to captivity? Implications for managing captive populations.

    Science.gov (United States)

    Courtney Jones, Stephanie K; Byrne, Phillip G

    2017-12-01

    Animals maintained in captivity exhibit rapid changes in phenotypic traits, which may be maladaptive for natural environments. The phenotype can shift away from the wild phenotype via transgenerational effects, with the environment experienced by parents influencing the phenotype and fitness of offspring. There is emerging evidence that controlling transgenerational effects could help mitigate the effects of captivity, improving the success of captively bred animals post release. However, controlling transgenerational effects requires knowledge of the mechanisms driving transgenerational changes. To better understand the genetic mechanisms that contribute to transgenerational effects in captivity we investigated the heritability of behavioral phenotypes using mid parent- and single parent-offspring regressions in a population of captive-reared house mouse (Mus musculus) that we had previously shown exhibit transgenerational changes in boldness and activity behavioral types. Slopes for boldness and activity were all positive, indicating a low to moderate degree of heritability. Though, none of the heritability estimates were statistically significant due to the large surrounding errors. However, the large error surrounding the heritability estimates may also indicate that there is variability in heritability between behavioral traits within the boldness and activity behavioral types. The implication of this finding is that the potential for heritable genetic changes in captivity varies considerably between traits. We conclude that continued investigation of the potential for traits to evolve in captivity is needed to better inform captive breeding and reintroduction programs. © 2017 Wiley Periodicals, Inc.

  10. Phenotypic variability of Rhodnius ecuadoriensis populations at the Ecuadorian central and southern Andean region.

    Science.gov (United States)

    Villacís, Anita G; Grijalva, Mario J; Catalá, Silvia S

    2010-11-01

    Rhodnius ecuadoriensis is an important vector of Chagas disease in Ecuador. Whereas only sylvatic and peridomestic populations are common in Manabi province, this species occupies domestic, peridomestic, and sylvatic habitats in Loja province where high reinfestation of houses was observed. To explore the existence of phenetic changes linked to the domiciliation of the species, this study set out to analyze the wing and antennal phenotypes of R. ecuadoriensis in these two provinces where the vector presents different affinity for domestic habitats. The antennal phenotype and the wing size and shape distinguish the two geographical populations of R. ecuadoriensis. In Manabí, sylvatic and peridomestic specimens were very similar. In Loja, sylvatic and nonsylvatic (domestic and peridomestic) populations showed distinctive characteristics. Remarkable sexual dimorphism of wing and antenna, exclusive of domestic specimens, and high metric disparity in the wing shape of the domestic females point out the existence of a particular situation in this habitat. The results of this phenotypic analysis and previous evidence of behavioral differences support the hypothesis of disruptive selection acting upon R. ecuadoriensis populations.

  11. Genotypic and phenotypic diversity in populations of plant-probiotic Pseudomonas spp. colonizing roots

    Science.gov (United States)

    Picard, Christine; Bosco, Marco

    2008-01-01

    Several soil microorganisms colonizing roots are known to naturally promote the health of plants by controlling a range of plant pathogens, including bacteria, fungi, and nematodes. The use of theses antagonistic microorganisms, recently named plant-probiotics, to control plant-pathogenic fungi is receiving increasing attention, as they may represent a sustainable alternative to chemical pesticides. Many years of research on plant-probiotic microorganisms (PPM) have indicated that fluorescent pseudomonads producing antimicrobial compounds are largely involved in the suppression of the most widespread soilborne pathogens. Phenotype and genotype analysis of plant-probiotic fluorescent pseudomonads (PFP) have shown considerable genetic variation among these types of strains. Such variability plays an important role in the rhizosphere competence and the biocontrol ability of PFP strains. Understanding the mechanisms by which genotypic and phenotypic diversity occurs in natural populations of PFP could be exploited to choose those agricultural practices which best exploit the indigenous PFP populations, or to isolate new plant-probiotic strains for using them as inoculants. A number of different methods have been used to study diversity within PFP populations. Because different resolutions of the existing microbial diversity can be revealed depending on the approach used, this review first describes the most important methods used for the assessment of fluorescent Pseudomonas diversity. Then, we focus on recent data relating how differences in genotypic and phenotypic diversity within PFP communities can be attributed to geographic location, climate, soil type, soil management regime, and interactions with other soil microorganisms and host plants. It becomes evident that plant-related parameters exert the strongest influence on the genotypic and phenotypic variations in PFP populations.

  12. Phenotypic selection on flowering phenology and pollination efficiency traits between Primula populations with different pollinator assemblages

    OpenAIRE

    Wu, Yun; Li, Qing‐Jun

    2017-01-01

    Abstract Floral traits have largely been attributed to phenotypic selection in plant–pollinator interactions. However, the strength of this link has rarely been ascertained with real pollinators. We conducted pollinator observations and estimated selection through female fitness on flowering phenology and floral traits between two Primula secundiflora populations. We quantified pollinator‐mediated selection by subtracting estimates of selection gradients of plants receiving supplemental hand ...

  13. Phenotypic plasticity despite source-sink population dynamics in a long-lived perennial plant.

    Science.gov (United States)

    Anderson, Jill T; Sparks, Jed P; Geber, Monica A

    2010-11-01

    • Species that exhibit adaptive plasticity alter their phenotypes in response to environmental conditions, thereby maximizing fitness in heterogeneous landscapes. However, under demographic source-sink dynamics, selection should favor traits that enhance fitness in the source habitat at the expense of fitness in the marginal habitat. Consistent with source-sink dynamics, the perennial blueberry, Vaccinium elliottii (Ericaceae), shows substantially higher fitness and population sizes in dry upland forests than in flood-prone bottomland forests, and asymmetrical gene flow occurs from upland populations into bottomland populations. Here, we examined whether this species expresses plasticity to these distinct environments despite source-sink dynamics. • We assessed phenotypic responses to a complex environmental gradient in the field and to water stress in the glasshouse. • Contrary to expectations, V. elliottii exhibited a high degree of plasticity in foliar and root traits (specific leaf area, carbon isotope ratios, foliar nitrogen content, root : shoot ratio, root porosity and root architecture). • We propose that plasticity can be maintained in source-sink systems if it is favored within the source habitat and/or a phylogenetic artifact that is not costly. Additionally, plasticity could be advantageous if habitat-based differences in fitness result from incipient niche expansion. Our results illuminate the importance of evaluating phenotypic traits and fitness components across heterogeneous landscapes. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

  14. Allelic Frequencies of 20 Visible Phenotype Variants in the Korean Population

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    Ji Eun Lim

    2013-06-01

    Full Text Available The prediction of externally visible characteristics from DNA has been studied for forensic genetics over the last few years. Externally visible characteristics include hair, skin, and eye color, height, and facial morphology, which have high heritability. Recent studies using genome-wide association analysis have identified genes and variations that correlate with human visible phenotypes and developed phenotype prediction programs. However, most prediction models were constructed and validated based on genotype and phenotype information on Europeans. Therefore, we need to validate prediction models in diverse ethnic populations. In this study, we selected potentially useful variations for forensic science that are associated with hair and eye color, iris pattern, and facial morphology, based on previous studies, and analyzed their frequencies in 1,920 Koreans. Among 20 single nucleotide polymorphisms (SNPs, 10 SNPs were polymorphic, 6 SNPs were very rare (minor allele frequency < 0.005, and 4 SNPs were monomorphic in the Korean population. Even though the usability of these SNPs should be verified by an association study in Koreans, this study provides 10 potential SNP markers for forensic science for externally visible characteristics in the Korean population.

  15. Identification and validation of asthma phenotypes in Chinese population using cluster analysis.

    Science.gov (United States)

    Wang, Lei; Liang, Rui; Zhou, Ting; Zheng, Jing; Liang, Bing Miao; Zhang, Hong Ping; Luo, Feng Ming; Gibson, Peter G; Wang, Gang

    2017-10-01

    Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. To identify and prospectively validate asthma clusters in a Chinese population. Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07-3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26-40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02-4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95-69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission (P clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Phenotypic and allelic distribution of the ABO and Rhesus (D) blood groups in the Cameroonian population.

    Science.gov (United States)

    Ndoula, S T; Noubiap, J J N; Nansseu, J R N; Wonkam, A

    2014-06-01

    Data on blood group phenotypes are important for blood transfusion programs, for disease association and population genetics studies. This study aimed at reporting the phenotypic and allelic distribution of ABO and Rhesus (Rh) groups in various ethnolinguistic groups in the Cameroonians. We obtained ABO and Rhesus blood groups and self-identified ethnicity from 14,546 Cameroonian students. Ethnicity was classified in seven major ethnolinguistic groups: Afro-Asiatic, Nilo-Saharan, Niger-Kordofanian/West Atlantic, Niger-Kordofanian/Adamawa-Ubangui, Niger-Kordofanian/Benue-Congo/Bantu/Grassfield, Niger-Kordofanian/Benue-Congo/Bantu/Mbam and Niger-Kordofanian/Benue-Congo/Bantu/Equatorial. ABO allelic frequencies were determined using the Bernstein method. Differences in phenotypic distribution of blood groups were assessed using the chi-square test; a P value blood groups O, A, B and AB were 48.62%, 25.07%, 21.86% and 4.45%, respectively. Rhesus-positive was 96.32%. The allelic frequencies of O, A and B genes were 0.6978, 0.1605 and 0.1416, respectively. Phenotypic frequencies of the blood groups in the general study population and in the different ethnolinguistic groups were in agreement with Hardy-Weinberg equilibrium expectations (P > 0.05). The frequencies of O, A, and B blood phenotypes were significantly lower, respectively, in the Nilo-Saharan group (P = 0.009), the Niger-Kordofanian/Benue-Congo/Bantu groups (P = 0.021) and the Niger-Kordofanian/West-Atlantic group. AB blood group was most frequent in the Niger-Kordofanian/Adamawa-Ubangui group (P = 0.024). Our study provides the first data on ethnic distribution of ABO and Rhesus blood groups in the Cameroonian population and suggests that its general profile is similar to those of several sub-Saharan African populations. We found some significant differences in phenotypic distribution amongst major ethnolinguistic groups. These data may be important for blood donor recruitment policy and blood transfusion

  17. Sex differences in correlates of intermediate phenotypes and prevalent cardiovascular disease in the general population

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    Renate B. Schnabel

    2015-04-01

    Full Text Available Background-There are marked sex differences in cardiovascular disease [CVD] manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences.Methods and Results-In 5000 individuals of the population-based Gutenberg Health Study, mean age 55±11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD (coronary artery disease, heart failure, stroke, myocardial infarction, lower extremity artery disease [LEAD] N=561.We observed differential distributions of CVD risk factors with a higher risk factor burden in men. Manifest coronary artery disease, stroke, myocardial infarction and LEAD were more frequent in men; the proportion of heart failure was higher in women. Intermediate phenotypes showed clear sex differences with more beneficial values in women. Fairly linear changes towards less beneficial values with age were observed in both sexes. In multivariable-adjusted regression analyses age, systolic blood pressure and body mass index were consistently associated with intermediate phenotypes in both sexes with different ranking according to random forests, maximum model R² 0.43. Risk factor-adjusted associations with prevalent CVD showed some differences by sex. No interactions by menopausal status were observed. Conclusions-In a population-based cohort we observed sex differences in risk factors and a broad range of intermediate phenotypes of noninvasive cardiovascular structure and function. Their relation to prevalent CVD differed markedly. Our results indicate the need of future investigations to understand sex differences in CVD manifestation.

  18. Dynamics of sexual populations structured by a space variable and a phenotypical trait

    KAUST Repository

    Mirrahimi, Sepideh

    2013-03-01

    We study sexual populations structured by a phenotypic trait and a space variable, in a non-homogeneous environment. Departing from an infinitesimal model, we perform an asymptotic limit to derive the system introduced in Kirkpatrick and Barton (1997). We then perform a further simplification to obtain a simple model. Thanks to this simpler equation, we can describe rigorously the dynamics of the population. In particular, we provide an explicit estimate of the invasion speed, or extinction speed of the species. Numerical computations show that this simple model provides a good approximation of the original infinitesimal model, and in particular describes quite well the evolution of the species\\' range. © 2013 Elsevier Inc.

  19. Dynamics of sexual populations structured by a space variable and a phenotypical trait

    KAUST Repository

    Mirrahimi, Sepideh; Raoul, Gaë l

    2013-01-01

    We study sexual populations structured by a phenotypic trait and a space variable, in a non-homogeneous environment. Departing from an infinitesimal model, we perform an asymptotic limit to derive the system introduced in Kirkpatrick and Barton (1997). We then perform a further simplification to obtain a simple model. Thanks to this simpler equation, we can describe rigorously the dynamics of the population. In particular, we provide an explicit estimate of the invasion speed, or extinction speed of the species. Numerical computations show that this simple model provides a good approximation of the original infinitesimal model, and in particular describes quite well the evolution of the species' range. © 2013 Elsevier Inc.

  20. Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.

    Directory of Open Access Journals (Sweden)

    Guilherme Suarez-Kurtz

    Full Text Available The influence of self-reported "race/color", geographical origin and genetic ancestry on the distribution of three functional CYP3A5 polymorphisms, their imputed haplotypes and inferred phenotypes was examined in 909 healthy, adult Brazilians, self-identified as White, Brown or Black ("race/color" categories of the Brazilian census. The cohort was genotyped for CYP3A5*3 (rs776746, CYP3A5*6 (rs10264272 and CYP3A5*7 (rs41303343, CYP3A5 haplotypes were imputed and CYP3A5 metabolizer phenotypes were inferred according to the number of defective CYP3A5 alleles. Estimates of the individual proportions of Amerindian, African and European ancestry were available for the entire cohort. Multinomial log-linear regression models were applied to infer the statistical association between the distribution of CYP3A5 alleles, haplotypes and phenotypes (response variables, and self-reported Color, geographical region and ancestry (explanatory variables. We found that Color per se or in combination with geographical region associates significantly with the distribution of CYP3A5 variant alleles and CYP3A5 metabolizer phenotypes, whereas geographical region per se influences the frequency distribution of CYP3A5 variant alleles. The odds of having the default CYP3A5*3 allele and the poor metabolizer phenotype increases continuously with the increase of European ancestry and decrease of African ancestry. The opposite trend is observed in relation to CYP3A5*6, CYP3A5*7, the default CYP3A5*1 allele, and both the extensive and intermediate phenotypes. No significant effect of Amerindian ancestry on the distribution of CYP3A5 alleles or phenotypes was observed. In conclusion, this study strongly supports the notion that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies, and dealt with as a continuous variable, rather than proportioned in arbitrary categories that do not capture the

  1. Population structure and genotype-phenotype associations in a collection of oat landraces and historic cultivars

    Directory of Open Access Journals (Sweden)

    Louisa Rosemarie Winkler

    2016-07-01

    Full Text Available Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L. remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a particular focus on identifying under-utilized areas. A diverse panel of cultivated oat accessions was assembled from the USDA National Small Grains Collection to represent a gene pool relatively unaffected by twentieth century breeding activity and unlikely to have been included in recent molecular studies. The panel was genotyped using an oat iSelect 6K beadchip SNP array. The final dataset included 759 unique individuals and 2,715 polymorphic markers. Some population structure was apparent; with the first three principal components accounting for 38.8% of variation and 73% of individuals belonging to one of three clusters. One cluster with high genetic distinctness appears to have been largely overlooked in twentieth century breeding. Classification and phenotype data provided by the Germplasm Resources Information Network were evaluated for their relationship to population structure. Of the structuring variables evaluated, improvement status (cultivar or landrace was relatively unimportant, indicating that landraces and cultivars included in the panel were all sampled from a similar underlying population. Instead, lemma color and region of origin showed the strongest explanatory power. An exploratory association mapping study of the panel using a subset of 2,588 mapped markers generated novel indications of genomic regions associated with awn frequency, kernels per spikelet, lemma color and panicle type. Further results supported previous findings of loci associated with barley yellow dwarf virus tolerance, crown rust (caused by Puccinia coronata f. sp. avenae resistance, days to anthesis and growth habit (winter/spring. In addition, two novel loci were

  2. The Hawk-Dove game in phenotypically homogeneous and heterogeneous populations of finite dimension

    Science.gov (United States)

    Laruelle, Annick; da Silva Rocha, André Barreira; Escobedo, Ramón

    2018-02-01

    The Hawk-Dove game played between individuals in populations of finite dimension is analyzed by means of a stochastic model. We take into account both cases when all individuals in the population are either phenotypically homogeneous or heterogeneous. A strategy in the model is a gene representing the probability of playing the Hawk strategy. Individual interactions at the microscopic level are described by a genetic algorithm where evolution results from the interplay among selection, mutation, drift and cross-over of genes. We show that the behavioral patterns observed at the macroscopic level can be reproduced as the emergent result of individual interactions governed by the rules of the Hawk-Dove game at the microscopic level. We study how the results of the genetic algorithm compare with those obtained in evolutionary game theory, finding that, although genes continuously change both their presence and frequency in the population over time, the population average behavior always achieves stationarity and, when this happens, the final average strategy played in the population oscillates around the evolutionarily stable strategy in the homogeneous population case or the neutrally stable set in the heterogeneous population case.

  3. DNA methylation profiling reveals the presence of population-specific signatures correlating with phenotypic characteristics.

    Science.gov (United States)

    Giri, Anil K; Bharadwaj, Soham; Banerjee, Priyanka; Chakraborty, Shraddha; Parekatt, Vaisak; Rajashekar, Donaka; Tomar, Abhishek; Ravindran, Aarthi; Basu, Analabha; Tandon, Nikhil; Bharadwaj, Dwaipayan

    2017-06-01

    Phenotypic characteristics are known to vary substantially among different ethnicities around the globe. These variations are mediated by number of stochastic events and cannot be attributed to genetic architecture alone. DNA methylation is a well-established mechanism that sculpts our epigenome influencing phenotypic variation including disease manifestation. Since DNA methylation is an important determinant for health issues of a population, it demands a thorough investigation of the natural differences in genome wide DNA methylation patterns across different ethnic groups. This study is based on comparative analyses of methylome from five different ethnicities with major focus on Indian subjects. The current study uses hierarchical clustering approaches, principal component analysis and locus specific differential methylation analysis on Illumina 450K methylation data to compare methylome of different ethnic subjects. Our data indicates that the variations in DNA methylation patterns of Indians are less among themselves compared to other global population. It empirically correlated with dietary, cultural and demographical divergences across different ethnic groups. Our work further suggests that Indians included in this study, despite their genetic similarity with the Caucasian population, are in close proximity with Japanese in terms of their methylation signatures.

  4. Emergence of cooperation in phenotypically heterogeneous populations: a replicator dynamics analysis

    International Nuclear Information System (INIS)

    Barreira da Silva Rocha, A; Escobedo, R; Laruelle, A

    2015-01-01

    The emergence of cooperation is analyzed in heterogeneous populations where two kinds of individuals exist according to their phenotypic appearance. Phenotype recognition is assumed for all individuals: individuals are able to identify the type of every other individual, but fail to recognize their own type. Individuals thus behave under partial information conditions. The interactions between individuals are described by the snowdrift game, where individuals can either cooperate or defect. The evolution of such populations is studied in the framework of evolutionary game theory by means of the replicator dynamics. Overlapping generations are considered, so the replicator equations are formulated in discrete-time form. The stability analysis of the dynamical system is carried out and a detailed description of the behavior of trajectories starting from the interior of the state-space is given. We find that the four monomorphic states are unstable and that a polymorphic state exists which is a global attractor for non-degenerate initial states of the population. The result for the discrete-time replicator coincides with the one of the continuous case. (paper)

  5. Induction of mutagenized tomato populations for investigation on agronomic traits and mutant phenotyping

    Directory of Open Access Journals (Sweden)

    Rafiul Amin Laskar

    2018-01-01

    Full Text Available Global demand for tomato production increased tremendously due to its diverse utility in raw, cooked and processed form of food. This necessitates the continued supply of highly nutritious and better yielding improved cultivars to the producers, considering the rapid changing agro-climatic condition. In this study, induced mutant tomato populations of widely recommended tomato genotype Arka Vikas (Sel-22 were generated using chemical mutagen ethyl methane sulfonate (EMS, hydrazine hydrates (HZ and their combined treatments. In the in vitro study, a gradual reduction in germination percentage and seedling height occurred with the increasing concentrations of mutagens. Combination of EMS and HZ caused maximum biological inhibition followed by EMS and HZ treatments alone in M1 generation. The rate of survival and fertility in M1 plants of tomato was found highly affected due to mutagenic treatment, in which sensitivity toward combined treatment was found highest followed by EMS and HZ. Inspection on induced phenotypic variations in individual plants of M2 population resulted in identification and isolation of wide range of mutants with altered phenotypes. Highest mutation frequency was resulted by combined mutagens followed by the EMS and HZ treatment. Agronomic trait analyses showed intra and inter treatment variations in three quantitative traits (Plant height, fertile branch per plant and fruits per plant of M2 mutagenized population. Assessment on rate of mutant recovery in M2 population showed highest mutant recovery is possible with combination treatments and then 0.02% HZ followed by 0.02% EMS. In the present study, phenotyping of the mutants revealed that vegetative organs (‘plant size’, ‘plant habit’ and ‘leaf morphology’ was the most sensitive category (69.33% to which most of the mutant belongs, followed by ‘fruit color and size’ (20.27% and ‘germination’ (9.79%. Comparative investigation on number of mutants and

  6. Noise-Driven Phenotypic Heterogeneity with Finite Correlation Time in Clonal Populations.

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    UnJin Lee

    Full Text Available There has been increasing awareness in the wider biological community of the role of clonal phenotypic heterogeneity in playing key roles in phenomena such as cellular bet-hedging and decision making, as in the case of the phage-λ lysis/lysogeny and B. Subtilis competence/vegetative pathways. Here, we report on the effect of stochasticity in growth rate, cellular memory/intermittency, and its relation to phenotypic heterogeneity. We first present a linear stochastic differential model with finite auto-correlation time, where a randomly fluctuating growth rate with a negative average is shown to result in exponential growth for sufficiently large fluctuations in growth rate. We then present a non-linear stochastic self-regulation model where the loss of coherent self-regulation and an increase in noise can induce a shift from bounded to unbounded growth. An important consequence of these models is that while the average change in phenotype may not differ for various parameter sets, the variance of the resulting distributions may considerably change. This demonstrates the necessity of understanding the influence of variance and heterogeneity within seemingly identical clonal populations, while providing a mechanism for varying functional consequences of such heterogeneity. Our results highlight the importance of a paradigm shift from a deterministic to a probabilistic view of clonality in understanding selection as an optimization problem on noise-driven processes, resulting in a wide range of biological implications, from robustness to environmental stress to the development of drug resistance.

  7. Phenotypic selection varies with pollination intensity across populations of Sabatia angularis.

    Science.gov (United States)

    Emel, Sarah L; Franks, Steven J; Spigler, Rachel B

    2017-07-01

    Pollinators are considered primary selective agents acting on plant traits, and thus variation in the strength of the plant-pollinator interaction might drive variation in the opportunity for selection and selection intensity across plant populations. Here, we examine whether these critical evolutionary parameters covary with pollination intensity across wild populations of the biennial Sabatia angularis. We quantified pollination intensity in each of nine S. angularis populations as mean stigmatic pollen load per population. For female fitness and three components, fruit number, fruit set (proportion of flowers setting fruit) and number of seeds per fruit, we evaluated whether the opportunity for selection varied with pollination intensity. We used phenotypic selection analyses to test for interactions between pollination intensity and selection gradients for five floral traits, including flowering phenology. The opportunity for selection via fruit set and seeds per fruit declined significantly with increasing pollen receipt, as expected. We demonstrated significant directional selection on multiple traits across populations. We also found that selection intensity for all traits depended on pollination intensity. Consistent with general theory about the relationship between biotic interaction strength and the intensity of selection, our study suggests that variation in pollination intensity drives variation in selection across S. angularis populations. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  8. Genetic and phenotypic variability of iris color in Buenos Aires population

    Directory of Open Access Journals (Sweden)

    Diana María Hohl

    Full Text Available Abstract The aim of this work was to describe the phenotypic and genotypic variability related to iris color for the population of Buenos Aires province (Argentina, and to assess the usefulness of current methods of analysis for this country. We studied five Single Nucleotide Polymorphisms (SNPs included in the IrisPlex kit, in 118 individuals, and we quantified eye color with Digital Iris Analysis Tool. The markers fit Hardy-Weinberg equilibrium for the whole sample, but not for rs12913832 within the group of brown eyes (LR=8.429; p=0.004. We found a remarkable association of HERC2 rs12913832 GG with blue color (p < 0.01 but the other markers did not show any association with iris color. The results for the Buenos Aires population differ from those of other populations of the world for these polymorphisms (p < 0,01. The differences we found might respond to the admixed ethnic composition of Argentina; therefore, methods of analysis used in European populations should be carefully applied when studying the population of Argentina. These findings reaffirm the importance of this investigation in the Argentinian population for people identification based on iris color.

  9. Phenotypic selection on flowering phenology and pollination efficiency traits between Primula populations with different pollinator assemblages.

    Science.gov (United States)

    Wu, Yun; Li, Qing-Jun

    2017-10-01

    Floral traits have largely been attributed to phenotypic selection in plant-pollinator interactions. However, the strength of this link has rarely been ascertained with real pollinators. We conducted pollinator observations and estimated selection through female fitness on flowering phenology and floral traits between two Primula secundiflora populations. We quantified pollinator-mediated selection by subtracting estimates of selection gradients of plants receiving supplemental hand pollination from those of plants receiving open pollination. There was net directional selection for an earlier flowering start date at populations where the dominant pollinators were syrphid flies, and flowering phenology was also subjected to stabilized quadratic selection. However, a later flowering start date was significantly selected at populations where the dominant pollinators were legitimate (normal pollination through the corolla tube entrance) and illegitimate bumblebees (abnormal pollination through nectar robbing hole which located at the corolla tube), and flowering phenology was subjected to disruptive quadratic selection. Wider corolla tube entrance diameter was selected at both populations. Furthermore, the strength of net directional selection on flowering start date and corolla tube entrance diameter was stronger at the population where the dominant pollinators were syrphid flies. Pollinator-mediated selection explained most of the between-population variations in the net directional selection on flowering phenology and corolla tube entrance diameter. Our results suggested the important influence of pollinator-mediated selection on floral evolution. Variations in pollinator assemblages not only resulted in variation in the direction of selection but also the strength of selection on floral traits.

  10. Developing visual images for communicating information aboutantiretroviral side effects to a low-literate population.

    Science.gov (United States)

    Dowse, Ros; Ramela, Thato; Barford, Kirsty-Lee; Browne, Sara

    2010-09-01

    The side effects of antiretroviral (ARV) therapy are linked to altered quality of life and adherence. Poor adherence has also been associated with low health-literacy skills, with an uninformed patient more likely to make ARV-related decisions that compromise the efficacy of the treatment. Low literacy skills disempower patients in interactions with healthcare providers and preclude the use of existing written patient information materials, which are generally written at a high reading level. Visual images or pictograms used as a counselling tool or included in patient information leaflets have been shown to improve patients' knowledge, particularly in low-literate groups. The objective of this study was to design visuals or pictograms illustrating various ARV side effects and to evaluate them in a low-literate South African Xhosa population. Core images were generated either from a design workshop or from posed photos or images from textbooks. The research team worked closely with a graphic artist. Initial versions of the images were discussed and assessed in group discussions, and then modified and eventually evaluated quantitatively in individual interviews with 40 participants who each had a maximum of 10 years of schooling. The familiarity of the human body, its facial expressions, postures and actions contextualised the information and contributed to the participants' understanding. Visuals that were simple, had a clear central focus and reflected familiar body experiences (e.g. vomiting) were highly successful. The introduction of abstract elements (e.g. fever) and metaphorical images (e.g. nightmares) presented problems for interpretation, particularly to those with the lowest educational levels. We recommend that such visual images should be designed in collaboration with the target population and a graphic artist, taking cognisance of the audience's literacy skills and culture, and should employ a multistage iterative process of modification and

  11. Perfluorocarbons and Gilbert syndrome (phenotype) in the C8 Health Study Population

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Hongmin [Cancer Center, School of Public Health, West Virginia University, Morgantown, WV 265050-9190 (United States); Department of Epidemiology and Statistics, School of Public Health, Hebei United University, Hebei 063000 (China); Ducatman, Alan [Department of Occupational and Environmental Health, School of Public Health, West Virginia University (United States); Department of Medicine, School of Medicine, West Virginia University (United States); Clinical Translational Science Institute, West Virginia University (United States); Zhang, Jianjun [Department of Biostatistics, School Public Health, West Virginia University (United States)

    2014-11-15

    Background: Gilbert syndrome (GS) is an inherited defect of bilirubin conjugation, most commonly caused by a gene mutation for the enzyme UGT1A. GS is known to affect the metabolism and excretion of drugs and xenobiotics. Perfluorocarbon compounds (PFCs) are bio-persistent environmental contaminants that affect metabolic regulation. In this study, we examined the associations of GS phenotype and serum PFCs in the C8 Health Study Population. Materials and methods: Using 2005–2006 data from a large PFC-exposure population survey, we compared serum PFCs concentrations between GS and non GS clinical phenotypes, in a cross sectional design, adjusting for standard risk factors, including age, BMI, smoking status, socioeconomic status and gender. Results: Among 10 PFC compounds considered, only perfluorohexanoic acid (PFHxA) was seen at a significantly higher concentration in GS men and women. Conclusion: PFHxA exposure may be associated with GS. Our findings do not support increased exposure in GS for other PFCs. - Highlights: • Most serum PFCs are not associated with clinically evident Gilbert syndrome. • However, serum perfluorohexanoic acid is positively associated. • The investigation addresses the clinical presentation, not the genetic mutation.

  12. Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR Variants in a Thai Population.

    Directory of Open Access Journals (Sweden)

    Rebekah van Bruggen

    Full Text Available Pyruvate kinase (PKLR is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41 is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.

  13. Population structure and strong divergent selection shape phenotypic diversification in maize landraces.

    Science.gov (United States)

    Pressoir, G; Berthaud, J

    2004-02-01

    To conserve the long-term selection potential of maize, it is necessary to investigate past and present evolutionary processes that have shaped quantitative trait variation. Understanding the dynamics of quantitative trait evolution is crucial to future crop breeding. We characterized population differentiation of maize landraces from the State of Oaxaca, Mexico for quantitative traits and molecular markers. Qst values were much higher than Fst values obtained for molecular markers. While low values of Fst (0.011 within-village and 0.003 among-villages) suggest that considerable gene flow occurred among the studied populations, high levels of population differentiation for quantitative traits were observed (ie an among-village Qst value of 0.535 for kernel weight). Our results suggest that although quantitative traits appear to be under strong divergent selection, a considerable amount of gene flow occurs among populations. Furthermore, we characterized nonproportional changes in the G matrix structure both within and among villages that are consequences of farmer selection. As a consequence of these differences in the G matrix structure, the response to multivariate selection will be different from one population to another. Large changes in the G matrix structure could indicate that farmers select for genes of major and pleiotropic effect. Farmers' decision and selection strategies have a great impact on phenotypic diversification in maize landraces.

  14. Identification and characterisation of side population cells in the canine pituitary gland.

    Science.gov (United States)

    van Rijn, Sarah J; Gremeaux, Lies; Riemers, Frank M; Brinkhof, Bas; Vankelecom, Hugo; Penning, Louis C; Meij, Björn P

    2012-06-01

    To date, stem/progenitor cells have not been identified in the canine pituitary gland. Cells that efficiently exclude the vital dye Hoechst 33342 can be visualised and identified using fluorescence activated cell sorting (FACS) as a 'side population' (SP), distinct from the main population (MP). Such SPs have been identified in several tissues and display stem/progenitor cell characteristics. In this study, a small SP (1.3%, n=6) was detected in the anterior pituitary glands of healthy dogs. Quantitative PCR indicated significantly higher expression of CD34 and Thy1 in this SP, but no differences in the expression of CD133, Bmi-1, Axin2 or Shh. Pro-opiomelanocortin (POMC) and Lhx3 expression were significantly higher in the MP than in the SP, but no differences in the expression of Tpit, GH or PRL were found. The study demonstrated the existence of an SP of cells in the normal canine pituitary gland, encompassing cells with stem cell characteristics and without POMC expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    International Nuclear Information System (INIS)

    Lushaj, Entela B.; Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi

    2012-01-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  16. Cigarette smoking in male patients with chronic schizophrenia in a Chinese population: prevalence and relationship to clinical phenotypes.

    Directory of Open Access Journals (Sweden)

    Xiang Yang Zhang

    Full Text Available The high prevalence of smoking in schizophrenia of European background may be related to smoking's reducing clinical symptoms and medication side effects. Because smoking prevalence and its associations with clinical phenotypes are less well characterized in Chinese than European patients with schizophrenia, we assessed these smoking behaviors using clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND in 776 Chinese male schizophrenia and 560 control subjects. Patients also were rated on the Positive and Negative Symptom Scale (PANSS, the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES, and the Abnormal Involuntary Movement Scale (AIMS. We found that the schizophrenia patients had a higher lifetime incidence of smoking (79% vs 63%, were more likely to be heavy smokers (61% vs 31%, and had lower smoking cessation rates (4% vs 9% (all p0.05 than the non-smoking patients. These results suggest that Chinese males with schizophrenia smoke more frequently than the general population. Further, smokers with schizophrenia may display fewer negative symptoms and possibly less parkinsonism than non-smokers with schizophrenia.

  17. Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

    Science.gov (United States)

    Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

    2015-04-01

    Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

  18. A robust new metric of phenotypic distance to estimate and compare multiple trait differences among populations

    Directory of Open Access Journals (Sweden)

    Rebecca SAFRAN, Samuel FLAXMAN, Michael KOPP, Darren E. IRWIN, Derek BRIGGS, Matthew R. EVANS, W. Chris FUNK, David A. GRAY, Eileen A. HEBE

    2012-06-01

    Full Text Available Whereas a rich literature exists for estimating population genetic divergence, metrics of phenotypic trait divergence are lacking, particularly for comparing multiple traits among three or more populations. Here, we review and analyze via simulation Hedges’ g, a widely used parametric estimate of effect size. Our analyses indicate that g is sensitive to a combination of unequal trait variances and unequal sample sizes among populations and to changes in the scale of measurement. We then go on to derive and explain a new, non-parametric distance measure, “Δp”, which is calculated based upon a joint cumulative distribution function (CDF from all populations under study. More precisely, distances are measured in terms of the percentiles in this CDF at which each population’s median lies. Δp combines many desirable features of other distance metrics into a single metric; namely, compared to other metrics, p is relatively insensitive to unequal variances and sample sizes among the populations sampled. Furthermore, a key feature of Δp—and our main motivation for developing it—is that it easily accommodates simultaneous comparisons of any number of traits across any number of populations. To exemplify its utility, we employ Δp to address a question related to the role of sexual selection in speciation: are sexual signals more divergent than ecological traits in closely related taxa? Using traits of known function in closely related populations, we show that traits predictive of reproductive performance are, indeed, more divergent and more sexually dimorphic than traits related to ecological adaptation [Current Zoology 58 (3: 423-436, 2012].

  19. Genotype-phenotype correlation of xeroderma pigmentosum in a Chinese Han population.

    Science.gov (United States)

    Sun, Z; Zhang, J; Guo, Y; Ni, C; Liang, J; Cheng, R; Li, M; Yao, Z

    2015-04-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to sunlight, freckle-like pigmentation and a greatly increased incidence of skin cancers. Genetic mutation detection and genotype-phenotype analysis of XP are rarely reported in the Chinese Han population. To investigate the mutational spectrum of XP in a Chinese Han population, to discover any genotype-phenotype correlation and, consequently, to propose a simple and effective tool for the molecular diagnosis of XP. This study was carried out on 12 unrelated Chinese families that included 13 patients with clinically suspected XP. Genomic DNA was extracted from peripheral blood samples. Mutation screening was performed by direct sequencing of exons and flanking intron-exon boundaries for the entire coding region of eight XP genes. In 12 patients, direct sequencing of the whole coding region of eight XP genes revealed pathogenic mutations, including seven compound heterozygous mutations, three homozygous mutations and a Japanese founder mutation. Thirteen mutations have not been previously identified. This cohort was composed of four patients with XP-C (XPC), two with XP-G (ERCC5), three with XP-A (XPA) and three with XP-V (POLH). This study identified 13 novel mutations and extended the mutation spectrum of XP in the Chinese Han population. In this cohort, we found that patients with XP-G have no neurological symptoms, and patients with XP-A and XP-V have a high incidence of malignancy. Furthermore, lack of stringent protection against sunlight, late diagnosis and long duration of disease play an important role. © 2014 British Association of Dermatologists.

  20. Stimulation of angiogenesis, neurogenesis and regeneration by side population cells from dental pulp.

    Science.gov (United States)

    Ishizaka, Ryo; Hayashi, Yuki; Iohara, Koichiro; Sugiyama, Masahiko; Murakami, Masashi; Yamamoto, Tsubasa; Fukuta, Osamu; Nakashima, Misako

    2013-03-01

    Mesenchymal stem cells (MSCs) have been used for cell therapy in various experimental disease models. However, the regenerative potential of MSCs from different tissue sources and the influence of the tissue niche have not been investigated. In this study, we compared the regenerative potential of dental pulp, bone marrow and adipose tissue-derived CD31(-) side population (SP) cells isolated from an individual porcine source. Pulp CD31(-) SP cells expressed the highest levels of angiogenic/neurotrophic factors and had the highest migration activity. Conditioned medium from pulp CD31(-) SP cells produced potent anti-apoptotic activity and neurite outgrowth, compared to those from bone marrow and adipose CD31(-) SP cells. Transplantation of pulp CD31(-) SP cells in a mouse hindlimb ischemia model produced higher blood flow and capillary density than transplantation of bone marrow and adipose CD31(-) SP cells. Motor function recovery and infarct size reduction were greater with pulp CD31(-) SP cells. Pulp CD31(-) SP cells induced maximal angiogenesis, neurogenesis and pulp regeneration in ectopic transplantation models compared to other tissue sources. These results demonstrate that pulp stem cells have higher angiogenic, neurogenic and regenerative potential and may therefore be superior to bone marrow and adipose stem cells for cell therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Differential factors associated with challenge-proven food allergy phenotypes in a population cohort of infants: a latent class analysis.

    Science.gov (United States)

    Peters, R L; Allen, K J; Dharmage, S C; Lodge, C J; Koplin, J J; Ponsonby, A-L; Wake, M; Lowe, A J; Tang, M L K; Matheson, M C; Gurrin, L C

    2015-05-01

    Food allergy, eczema and wheeze are early manifestations of allergic disease and commonly co-occur in infancy although their interrelationship is not well understood. Data from population studies are essential to determine whether there are differential drivers of multi-allergy phenotypes. We aimed to define phenotypes and risk factors of allergic disease using latent class analysis (LCA). The HealthNuts study is a prospective, population-based cohort of 5276 12-month-old infants in Melbourne, Australia. LCA was performed using the following baseline data collected at age 12 months: food sensitization (skin prick test ≥ 2 mm) and allergy (oral food challenge) to egg, peanut and sesame; early (food-sensitized eczema (16%), single egg allergy (9%), multiple food allergies (predominantly peanut) (3%) and multiple food allergies (predominantly egg) (2%). Compared to the baseline group of no allergic disease, shared risk factors for all allergic phenotypes were parents born overseas (particularly Asia), delayed introduction of egg, male gender (except for single egg allergy) and family history of allergic disease, whilst exposure to pet dogs was protective for all phenotypes. Other factors including filaggrin mutations, vitamin D and the presence of older siblings differed by phenotype. Multiple outcomes in infancy can be used to determine five distinct allergy phenotypes at the population level, which have both shared and separate risk factors suggesting differential mechanisms of disease. © 2014 John Wiley & Sons Ltd.

  2. The CAPN10 Gene Is Associated with Insulin Resistance Phenotypes in the Spanish Population

    Science.gov (United States)

    Sáez, María E.; González-Sánchez, José L.; Ramírez-Lorca, Reposo; Martínez-Larrad, María T.; Zabena, Carina; González, Alejandro; Morón, Francisco J.; Ruiz, Agustín; Serrano-Ríos, Manuel

    2008-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population. PMID:18698425

  3. The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

    Directory of Open Access Journals (Sweden)

    María E Sáez

    Full Text Available Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10 has been associated with type 2 diabetes (T2DM, a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS in T2DM and in polycystic ovary syndrome (PCOS. In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

  4. Phenotypic characterisation of cell populations in the brains of horses experimentally infected with West Nile virus.

    Science.gov (United States)

    Delcambre, G H; Liu, J; Streit, W J; Shaw, G P J; Vallario, K; Herrington, J; Wenzlow, N; Barr, K L; Long, M T

    2017-11-01

    West Nile virus (WNV), a mosquito borne member of the Flaviviridae, is one of the most commonly diagnosed agents of viral encephalitis in horses and people worldwide. A cassette of markers for formalin-fixed paraffin-embedded tissue and an archive of tissues from experimental infections in the horse were used to investigate the equine neuroimmune response to WNV meningoencephalomyelitis to phenotype the early response to WNV infection in the horse. Quantitative analysis using archived tissue from experimentally infected horses. The thalamus and hindbrain from 2 groups of 6 horses were compared and consisted of a culture positive tissues from WNV experimentally horses, in the other, normal horses. Formalin-fixed paraffin-embedded tissue from the thalamus and hindbrain were immunolabeled for microglia, astrocytes, B cells, macrophages/neutrophils, CD3 + T cells. Fresh frozen tissues were immunolabeled for CD4 + and CD8 + T lymphocyte cell markers. Cell counts were obtained using a computer software program. Differences, after meeting assumptions of abnormality, were computed using a general linear model with a Tukey test (Phorses, Iba-1 + microglia, CD3 + T lymphocyte and MAC387 + macrophage staining were significantly increased. The T cell response for the WNV-challenged horses was mixed, composed of CD4 + and CD8 + T lymphocytes. A limited astrocyte response was also observed in WNV-challenged horses, and MAC387 + and B cells were the least abundant cell populations. The results of this study were limited by a single collection time post-infection. Furthermore, a comprehensive analysis of cellular phenotypes is needed for naturally infected horses. Unfortunately, in clinical horses, there is high variability of sampling in terms of days post-infection and tissue handling. The data show that WNV-challenged horses recruit a mixed T cell population at the onset of neurologic disease. © 2017 EVJ Ltd.

  5. The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin

    DEFF Research Database (Denmark)

    Wassermann, Tina; Meinike Jørgensen, Karin; Ivanyshyn, Karolina

    2016-01-01

    Ciprofloxacin is a widely used antibiotic, in the class of quinolones, for treatment of Pseudomonas aeruginosa infections. The immediate response of P. aeruginosa to subinhibitory concentrations of ciprofloxacin has been investigated previously. However, the long-term phenotypic adaptation, which...... populations compared to unexposed populations. Three replicate populations of P. aeruginosa PAO1 and its hypermutable mutant ΔmutS were cultured aerobically for approximately 940 generations by daily passages in LB medium with and without subinhibitory concentration of ciprofloxacin and aliquots...

  6. Changes related to gender, geographic population and habitat in the antennal phenotype of Triatoma patagonica Del Ponte, 1929 (Hemiptera: Reduviidae).

    Science.gov (United States)

    Rodríguez, Claudia S; Crocco, Liliana; Altamirano, Alejandra; Catalá, Silvia

    2013-02-01

    Triatomines undergo morphological changes as an adaptive response to different habitats (wild, peridomestic, domestic, laboratory). The characterization of the antennal phenotype provides information on intraspecific variation caused by geographical origin and/or habitat. Triatoma patagonica Del Ponte, 1929 is known to occur in peridomiciles of rural areas in Argentina, where it also invades non-colonized dwellings. Here we describe and compare the antennal phenotype of T. patagonica in populations of different geographic origin, and explore possible modifications induced by laboratory rearing with the aim of investigating the range of phenotypic variation of the species for the first time. Sixty antennas of adult males and females of T. patagonica belonging to two peridomiciliary populations of different geographical origin were analyzed. Four types of sensilla were observed in three antennal segments, showing sexual dimorphism in the species. The multivariate analysis separated the populations of similar habitat (peridomicile) but different geographical origin, without showing differences between the peridomiciliary and laboratory populations of the same geographical origin. These results suggest phenotypic plasticity in T. patagonica, which would allow the species to adapt to a wide range of habitats without having a close association with a given host and its environment. The range of antennal phenotypic variation of T. patagonica would also be an indicator of its current stage of adaptation to the human environment. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells

    Science.gov (United States)

    ZHAO, LU; ZHAO, YUE; SCHWARZ, BETTINA; MYSLIWIETZ, JOSEF; HARTIG, ROLAND; CAMAJ, PETER; BAO, QI; JAUCH, KARL-WALTER; GUBA, MAKUS; ELLWART, JOACHIM WALTER; NELSON, PETER JON; BRUNS, CHRISTIANE JOSEPHINE

    2016-01-01

    Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multi-drug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst 33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density. PMID:27177126

  8. Genetic divergence in nuclear genomes between populations of Fagus crenata along the Japan Sea and Pacific sides of Japan.

    Science.gov (United States)

    Hiraoka, Koichi; Tomaru, Nobuhiro

    2009-05-01

    Genetic diversity and structure in Fagus crenata were studied by analyzing 14 nuclear microsatellite loci in 23 populations distributed throughout the species' range. Although population differentiation was very low (F (ST) = 0.027; R (ST) = 0.041), both neighbor-joining tree and Bayesian clustering analyses provided clear evidence of genetic divergence between populations along the Japan Sea (Japan Sea lineage) and Pacific (Pacific lineage) sides of Japan, indicating that physical barriers to migration and gene flow, notably the mountain ranges separating the populations along the Japan Sea and Pacific sides, have promoted genetic divergence between these populations. The two lineages of the nuclear genome are generally consistent with those of the chloroplast genome detected in a previous study, with several discrepancies between the two genomes. Within-population genetic diversity was generally very high (average H (E) = 0.839), but decreased in a clinal fashion from southwest to northeast, largely among populations of the Japan Sea lineage. This geographical gradient may have resulted from the late-glacial and postglacial recolonization to the northeast, which led to a loss of within-population genetic diversity due to cumulative founder effects.

  9. The outbreak fingolimod cardiovascular side effects in relapsing-remitting multiple sclerosis patient: A longitudinal study in an Iranian population

    Directory of Open Access Journals (Sweden)

    Morteza Abdar

    2017-03-01

    Full Text Available BACKGROUND: Fingolimod (FTY-720 has shown efficacy in relapsing multiple sclerosis (MS, while some side effects of this drug have been recognized that the most important is cardiovascular side effects. The aim of this study was to evaluate the cardiovascular side effects of FTY-720. However, the effect of fingolimod on cardiac has not been well recognized. This study was designed to evaluate the cardiovascular side effects of fingolimod in relapsing-remitting multiple sclerosis (RRMS patient in an Iranian population. METHODS: This prospective clinical trial study was performed on 200 RRMS patients. The patients received a single daily oral dose of fingolimod 0.5 mg. During the first 6 hours after the first fingolimod dose, the patients’ vital signs and electrocardiographic traces were continuously monitored. Moreover, the patients followed up over 6 months after receiving fingolimod. RESULTS: The results showed that pulse rate (P < 0.001, systolic blood pressure (BP (P < 0.001, and diastolic BP (P < 0.001 were decreased significantly during 6 hours after receiving the first dose of fingolimod. The most reduction in vital sign was observed in 3 hours. Arrhythmia, bradycardia, and dizziness were the other complications of fingolimod, which were detected in our study. CONCLUSION: All the side effects such as hypotension and bradycardia were happened in first 3 hours after receiving the fingolimod. Indeed, we advise clinicians to monitor the patients for first 6 hours after initiation of fingolimod to decrease worse side effects. 

  10. Success and failure in replication of genotype-phenotype associations: How does replication help in understanding the genetic basis of phenotypic variation in outbred populations?

    Science.gov (United States)

    Schielzeth, Holger; Rios Villamil, Alejandro; Burri, Reto

    2018-03-25

    Recent developments in sequencing technologies have facilitated genomewide mapping of phenotypic variation in natural populations. Such mapping efforts face a number of challenges potentially leading to low reproducibility. However, reproducible research forms the basis of scientific progress. We here discuss the options for replication and the reasons for potential nonreproducibility. We then review the evidence for reproducible quantitative trait loci (QTL) with a focus on natural animal populations. Existing case studies of replication fall into three categories: (i) traits that have been mapped to major effect loci (including chromosomal inversion and supergenes) by independent research teams; (ii) QTL fine-mapped in discovery populations; and (iii) attempts to replicate QTL across multiple populations. Major effect loci, in particular those associated with inversions, have been successfully replicated in several cases within and across populations. Beyond such major effect variants, replication has been more successful within than across populations, suggesting that QTL discovered in natural populations may often be population-specific. This suggests that biological causes (differences in linkage patterns, allele frequencies or context-dependencies of QTL) contribute to nonreproducibility. Evidence from other fields, notably animal breeding and QTL mapping in humans, suggests that a significant fraction of QTL is indeed reproducible in direction and magnitude at least within populations. However, there is also a large number of QTL that cannot be easily reproduced. We put forward that more studies should explicitly address the causes and context-dependencies of QTL signals, in particular to disentangle linkage differences, allele frequency differences and gene-by-environment interactions as biological causes of nonreproducibility of QTL, especially between populations. © 2018 John Wiley & Sons Ltd.

  11. Biologic characteristics of the side population of human small cell lung cancer cell line H446.

    Science.gov (United States)

    Wang, Bo; Yang, Huan; Huang, Yu-Zheng; Yan, Ru-Hong; Liu, Fen-Ju; Zhang, Jun-Ning

    2010-03-01

    Recently, the theory of cancer stem cells (CSCs) has presented new targets and orientations for tumor therapy. The major difficulties in researching CSCs include their isolation and purification. The aim of this study is to identify and characterize the side population (SP) cells in small cell lung cancer (SCLC) cell line H446, which lays the foundation for the isolation and purification of CSCs. Fluorescence-activated cell sorting (FACS) was used to sort SP and non-SP (NSP) cells from H446. Both subgroups were cultivated to survey the capacity to form into suspended tumor cell spheres. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR were used to evaluate the expression levels of the mRNA of CD133, ABCG2, and nucleostemin in both subgroups. The capacity of proliferation and the differences in drug resistance of both subgroups and unsorted cells were tested by the MTT method. The differentiation ability of both subgroups was determined by FACS. Proliferation was determined by subcutaneous tumor formation in nude mice. The percent of Hoechst 33342 negative cells was about (5.1 +/- 0.2)% in H446 by fluorescence microscopy. The percent of SP cells was (6.3 +/- 0.1)% by flow cytometry. SP cells had a stronger capability of forming into tumor spheres than NSP cells. The mRNA expression levels of ABCG2, CD133, and nucleostemin in SP cells were 21.60 +/- 0.26, 7.10 +/- 0.14, and 1.02 +/- 0.08 folds higher than that in NSP cells (P 0.05, respectively). In vivo, SP cells showed better proliferative ability and tougher viability when treated with drugs. SP cells can differentiate into NSP cells, but NSP cells cannot differentiate into SP cells. SP cells had a greater ability to form tumors. The H446 cell line contained some SP cells with stem cell properties. CD133 and ABCG2 may be cancer stem cell markers of SCLC.

  12. Using species distribution model to estimate the wintering population size of the endangered scaly-sided merganser in China.

    Directory of Open Access Journals (Sweden)

    Qing Zeng

    Full Text Available Scaly-sided Merganser is a globally endangered species restricted to eastern Asia. Estimating its population is difficult and considerable gap exists between populations at its breeding grounds and wintering sites. In this study, we built a species distribution model (SDM using Maxent with presence-only data to predict the potential wintering habitat for Scaly-sided Merganser in China. Area under the receiver operating characteristic curve (AUC method suggests high predictive power of the model (training and testing AUC were 0.97 and 0.96 respectively. The most significant environmental variables included annual mean temperature, mean temperature of coldest quarter, minimum temperature of coldest month and precipitation of driest quarter. Suitable conditions for Scaly-sided Merganser are predicted in the middle and lower reaches of the Yangtze River, especially in Jiangxi, Hunan and Hubei Provinces. The predicted suitable habitat embraces 6,984 km of river. Based on survey results from three consecutive winters (2010-2012 and previous studies, we estimated that the entire wintering population of Scaly-sided Merganser in China to be 3,561 ± 478 individuals, which is consistent with estimate in its breeding ground.

  13. Comparing the predictive abilities of phenotypic and marker-assisted selection methods in a biparental lettuce population

    Science.gov (United States)

    Breeding and selection for the traits with polygenic inheritance is a challenging task that can be done by phenotypic selection, by marker-assisted selection or by genome wide selection. We tested predictive ability of four selection models in a biparental population genotyped with 95 SNP markers an...

  14. Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population

    OpenAIRE

    Walsh Tom; Rayan Amal; Sa'ed Judeh; Shahin Hashem; Shepshelovich Jeanne; Lee Ming K; Hirschberg Koret; Tekin Mustafa; Salhab Wa'el; Avraham Karen B; King Mary-Claire; Kanaan Moien

    2006-01-01

    Abstract Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to characterise the genetics of inherited hearing loss in this population, we worked with West Bank schools for the deaf to identify children with prelingual, bilateral, severe to profound hearing loss not attributable to infection, trauma or other known environmental exposure. Of 156 fa...

  15. Wolbachia wSinvictaA infections in natural populations of the fire ant Solenopsis invicta: testing for phenotypic effects.

    Science.gov (United States)

    Bouwma, Andrew M; Shoemaker, Dewayne

    2011-01-01

    Wolbachia are intracellular bacteria that commonly infect many arthropods and some nematodes. In arthropods, these maternally transmitted bacteria often induce a variety of phenotypic effects to enhance their own spread within host populations. Wolbachia phenotypic effects generally either provide benefits to infected host females (cytoplasmic incompatibility, positive fitness effects) or bias host sex ratio in favor of females (male-killing, parthenogenesis, feminization), all of which increase the relative production of infected females in host populations. Wolbachia surveys have found infections to be exceedingly common in ants, but little is known at this juncture as to what phenotypic effects, if any, they induce in this group. Previous studies have demonstrated that individuals from native populations of the invasive fire ant Solenopsis invicta commonly harbor one or more of three Wolbachia variants. One of the variants, wSinvictaA, typically occurs at low prevalence in S. invicta populations, appears to have been transmitted horizontally into S. invicta three or more times, and has been lost repeatedly from host lineages over time. In order to determine the phenotypic effects and likely population dynamics of wSinvictaA infections in these ants, brood production patterns of newly mated fire ant queens were studied during simulated claustral founding and measured wSinvictaA transmission fidelity within mature single-queen families. No clear evidence was found for Wolbachia-induced cytoplasmic incompatibility, significant fitness effects, or male-killing. Maternal transmission was perfect to both virgin queens and males. Possible mechanisms for how this variant could be maintained in host populations are discussed.

  16. Concomitant targeting of multiple key transcription factors effectively disrupts cancer stem cells enriched in side population of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Xiyan Wang

    Full Text Available A major challenge in the treatment of pancreatic ductal adenocarcinoma is the failure of chemotherapy, which is likely due to the presence of the cancer stem cells (CSCs.To identify side population (SP cells and characterize s-like properties in human pancreatic cancer cell lines (h-PCCLs and to exploit the efficacy of concomitant targeting of multiple key transcription factors governing the stemness of pancreatic CSCs in suppressing CSC-like phenotypes.Flow cytometry and Hoechst 33342 DNA-binding dye efflux assay were used to sort SP and non-SP (NSP cells from three h-PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness, migration and drug resistance of SP cells were evaluated. Expression of CSC marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO designed to simultaneously targeting Sox2, Oct4 and c-Myc were assessed.CSCs were enriched in the side proportion (SP cells contained in the h-PCCLs and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with NSP cells. SP cells overexpressed stem cell markers CD133 and ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene ABCG2. Moreover, SP cells consistently demonstrated significantly greater tumorigenicity than NSP cells in xenograft model of nude mice. CdODN-SOC efficiently suppressed all CSC properties and phenotypes, and minimized the tumorigenic capability of the SP cells and the resistance to chemotherapy. By comparison, the negative control failed to do so.The findings indicate that targeting the key genes conferring the stemness of CSCs can efficiently eliminate CSC-like phenotypes, and thus may be considered a new approach for cancer therapy. Specifically, the present study establishes the combination of Sox2/Oct4/c-Myc targeting as a

  17. Phenotypic differences in leucocyte populations among healthy preterm and full-term newborns.

    Science.gov (United States)

    Quinello, C; Silveira-Lessa, A L; Ceccon, M E J R; Cianciarullo, M A; Carneiro-Sampaio, M; Palmeira, P

    2014-07-01

    The immune system of neonates has been considered functionally immature, and due to their high susceptibility to infections, the aim of this study was to analyse the phenotypic differences in leucocyte populations in healthy preterm and full-term newborns. We evaluated the absolute numbers and frequencies of dendritic cells (DCs) and DC subsets, monocytes and T and B lymphocytes and subsets in the cord blood of healthy moderate and very preterm (Group 1), late preterm (Group 2) and full-term (Group 3) newborns and in healthy adults, as controls, by flow cytometry. The analyses revealed statistically higher absolute cell numbers in neonates compared with adults due to the characteristic leucocytosis of neonates. We observed a lower frequency of CD80(+) myeloid and plasmacytoid DCs in Group 1 and reduced expression of TLR-4 on myeloid DCs in all neonates compared with adults. TLR-2(+) monocytes were reduced in Group 1 compared with Groups 2 and 3, and TLR-4(+) monocytes were reduced in Groups 1 and 2 compared with Group 3. The frequencies and numbers of naïve CD4(+) T and CD19(+) B cells were higher in the three groups of neonates compared with adults, while CD4(+) effector and effector memory T cells and CD19(+) memory B cells were elevated in adults compared with neonates, as expected. Our study provides reference values for leucocytes in cord blood from term and preterm newborns, which may facilitate the identification of immunological deficiencies in protection against extracellular pathogens. © 2014 John Wiley & Sons Ltd.

  18. Enhanced population of side band of {sup 155}Gd in heavy-ion Coulomb excitation

    Energy Technology Data Exchange (ETDEWEB)

    Oshima, Masumi; Hayakawa, Takehito; Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; and others

    1998-03-01

    In the Coulomb excitation of {sup 155}Gd with heavy projectiles, {sup 32}S, {sup 58}Ni and {sup 90}Zr, unexpectedly large enhancement of a positive-parity side band has been observed. This enhancement could not be reproduced by a Coulomb-excitation calculation taking into account the recommended upper limits of E1 or E3 transitions, which are compiled in the whole mass region, and is proportional to the electric field accomplished in the Coulomb-scattering process. (author)

  19. Gaucher disease types 1 and 3: Phenotypic characterization of large populations from the ICGG Gaucher Registry.

    Science.gov (United States)

    Grabowski, Gregory A; Zimran, Ari; Ida, Hiroyuki

    2015-07-01

    Study of the natural history of Gaucher disease has revealed marked phenotypic variation. Correlations to genotypes could provide insight into individual susceptibility to varying disease severity, which may impact whole-life medical care, reproductive decisions, and therapeutic choices for affected families. Importantly, pre-symptomatic or prospective interventions or the use of therapies with significant risk require accurate risk-benefit analyses based on the prognosis for individual patients. The body of international data held within the International Collaborative Gaucher Group (ICGG) Gaucher Registry provides an unprecedented opportunity to characterize the phenotypes of Gaucher disease types 1 and 3 and to appreciate demographic and ethnic factors that may influence phenotypes. The diversity of GBA gene mutations from patients with Gaucher disease represented in the ICGG Gaucher Registry database and in the literature provides the basis for initial genotype/phenotype correlations, the outcomes of which are summarized here. © 2015 Wiley Periodicals, Inc.

  20. Demographic perspectives on agrarian transformations and 'surplus populations': supply-side banalities versus redistributive imperatives

    NARCIS (Netherlands)

    A.M. Fischer (Andrew Martín)

    2011-01-01

    textabstractThis paper frames the discussion of agrarian transformations and 'surplus populations' in the Global South within a political economy and macro-structural consideration of the developmental challenges faced in the context of contemporary rapid population growth. The case is made that the

  1. The effects of stabilizing and directional selection on phenotypic and genotypic variation in a population of RNA enzymes.

    Science.gov (United States)

    Hayden, Eric J; Bratulic, Sinisa; Koenig, Iwo; Ferrada, Evandro; Wagner, Andreas

    2014-02-01

    The distribution of variation in a quantitative trait and its underlying distribution of genotypic diversity can both be shaped by stabilizing and directional selection. Understanding either distribution is important, because it determines a population's response to natural selection. Unfortunately, existing theory makes conflicting predictions about how selection shapes these distributions, and very little pertinent experimental evidence exists. Here we study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a combination of high throughput genotyping and measurement of a biochemical phenotype allow us to address this question. We show that directional selection, compared to stabilizing selection, increases the genotypic diversity of an evolving ribozyme population. In contrast, it leaves the variance in the phenotypic trait unchanged.

  2. Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

    Science.gov (United States)

    de Sá Rodrigues, L C; Holmes, K E; Thompson, V; Newton, M A; Stein, T J

    2017-03-01

    An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells. © 2015 John Wiley & Sons Ltd.

  3. Phenotypic expression of partial AZFc deletions is independent of the variations in DAZL and BOULE in a Han population.

    Science.gov (United States)

    Chen, Pu; Ma, Mingyi; Li, Lei; Zhang, Sizhong; Su, Dan; Ma, Yongxin; Liu, Yunqiang; Tao, Dachang; Lin, Li; Yang, Yuan

    2010-01-01

    DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population.

  4. Quantitative gene expression profiling of CD45(+) and CD45(-) skeletal muscle-derived side population cells

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline; Kristiansen, Gitte Qvistgaard; Jensen, Line

    2011-01-01

    transcripts associated with endothelial cells, Notch signaling and myogenic precursors. By comparing the mRNA signatures of mSPs with those of adipose tissue-derived SP populations, a common endothelial component seemed to reside in both muscle and fat-derived SPCD45(-) entities. However, each SP subset......The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we...... describe the isolation of adult mouse normal skeletal muscle residing SPCD45(+) and SPCD45(-) cells from a parent mononuclear muscle-derived cell (MDC) population. Relative quantitative real time PCR (RT-PCR) of 64 genes revealed that mSPCD45(-) compared with mSPCD45(+) was enriched for cells expressing...

  5. Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population

    Science.gov (United States)

    Arenas, I. A.; Tremblay, J.; Deslauriers, B.; Sandoval, J.; Šeda, O.; Gaudet, D.; Merlo, E.; Kotchen, T.; Cowley, A. W.

    2013-01-01

    Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation. PMID:23269701

  6. Linking individual phenotype to density-dependent population growth: the influence of body size on the population dynamics of malaria vectors

    Science.gov (United States)

    Russell, Tanya L.; Lwetoijera, Dickson W.; Knols, Bart G. J.; Takken, Willem; Killeen, Gerry F.; Ferguson, Heather M.

    2011-01-01

    Understanding the endogenous factors that drive the population dynamics of malaria mosquitoes will facilitate more accurate predictions about vector control effectiveness and our ability to destabilize the growth of either low- or high-density insect populations. We assessed whether variation in phenotypic traits predict the dynamics of Anopheles gambiae sensu lato mosquitoes, the most important vectors of human malaria. Anopheles gambiae dynamics were monitored over a six-month period of seasonal growth and decline. The population exhibited density-dependent feedback, with the carrying capacity being modified by rainfall (97% wAICc support). The individual phenotypic expression of the maternal (p = 0.0001) and current (p = 0.040) body size positively influenced population growth. Our field-based evidence uniquely demonstrates that individual fitness can have population-level impacts and, furthermore, can mitigate the impact of exogenous drivers (e.g. rainfall) in species whose reproduction depends upon it. Once frontline interventions have suppressed mosquito densities, attempts to eliminate malaria with supplementary vector control tools may be attenuated by increased population growth and individual fitness. PMID:21389034

  7. Quantitative gene expression profiling of CD45+ and CD45- skeletal muscle-derived side population cells

    DEFF Research Database (Denmark)

    Ditte Caroline Andersen, Ditte Caroline; Kristiansen, Gitte Qvist; Jensen, Line

    2012-01-01

    The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we desc...... a satellite cell subpopulation) remain in the mSPCD45(-) fraction, and we show that these cells express high levels of many of the known myogenic precursor/stem cell related markers, including Pax7 and Myf5.......The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we...... describe the isolation of adult mouse normal skeletal muscle residing SPCD45(+) and SPCD45(-) cells from a parent mononuclear muscle-derived cell (MDC) population. Relative quantitative real time PCR (RT-PCR) of 64 genes revealed that mSPCD45(-) compared with mSPCD45(+) was enriched for cells expressing...

  8. Autism phenotype versus registered diagnosis in Swedish children: prevalence trends over 10 years in general population samples.

    Science.gov (United States)

    Lundström, Sebastian; Reichenberg, Abraham; Anckarsäter, Henrik; Lichtenstein, Paul; Gillberg, Christopher

    2015-04-28

    To compare the annual prevalence of the autism symptom phenotype and of registered diagnoses for autism spectrum disorder during a 10 year period in children. Population based study. Child and Adolescent Twin Study and national patient register, Sweden. 19, 993 twins (190 with autism spectrum disorder) and all children (n=1,078,975; 4620 with autism spectrum disorder) born in Sweden over a 10 year period from 1993 to 2002. Annual prevalence of the autism symptom phenotype (that is, symptoms on which the diagnostic criteria are based) assessed by a validated parental telephone interview (the Autism-Tics, ADHD and other Comorbidities inventory), and annual prevalence of reported diagnoses of autism spectrum disorder in the national patient register. The annual prevalence of the autism symptom phenotype was stable during the 10 year period (P=0.87 for linear time trend). In contrast, there was a monotonic significant increase in prevalence of registered diagnoses of autism spectrum disorder in the national patient register (Pautism symptom phenotype has remained stable in children in Sweden while the official prevalence for registered, clinically diagnosed, autism spectrum disorder has increased substantially. This suggests that administrative changes, affecting the registered prevalence, rather than secular factors affecting the pathogenesis, are important for the increase in reported prevalence of autism spectrum disorder. © Lundström et al 2015.

  9. Dynamic Behaviour of a Population of Controlled-by-price Demand Side Resources

    DEFF Research Database (Denmark)

    Sossan, Fabrizio; Han, Xue; Bindner, Henrik W.

    2014-01-01

    It is described that controlling or shedding by price the power consumption of a population of thermostatic loads introduces in the aggregate consumption dynamic effects th at cannot be disregarded if electrical flexible demand is meant to supply power system services. It is shown that inducing...

  10. Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain.

    Science.gov (United States)

    Domingo, Laia; Salas, Dolores; Zubizarreta, Raquel; Baré, Marisa; Sarriugarte, Garbiñe; Barata, Teresa; Ibáñez, Josefa; Blanch, Jordi; Puig-Vives, Montserrat; Fernández, Ana; Castells, Xavier; Sala, Maria

    2014-01-10

    Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; cancers, extreme breast density being strongly associated with occult tumors (OR

  11. Short-range phenotypic divergence among genetically distinct parapatric populations of an Australian funnel-web spider.

    Science.gov (United States)

    Wong, Mark K L; Woodman, James D; Rowell, David M

    2017-07-01

    Speciation involves divergence at genetic and phenotypic levels. Where substantial genetic differentiation exists among populations, examining variation in multiple phenotypic characters may elucidate the mechanisms by which divergence and speciation unfold. Previous work on the Australian funnel-web spider Atrax sutherlandi Gray (2010; Records of the Australian Museum 62 , 285-392; Mygalomorphae: Hexathelidae: Atracinae) has revealed a marked genetic structure along a 110-kilometer transect, with six genetically distinct, parapatric populations attributable to past glacial cycles. In the present study, we explore variation in three classes of phenotypic characters (metabolic rate, water loss, and morphological traits) within the context of this phylogeographic structuring. Variation in metabolic and water loss rates shows no detectable association with genetic structure; the little variation observed in these rates may be due to the spiders' behavioral adaptations (i.e., burrowing), which buffer the effects of climatic gradients across the landscape. However, of 17 morphological traits measured, 10 show significant variation among genetic populations, in a disjunct manner that is clearly not latitudinal. Moreover, patterns of variation observed for morphological traits serving different organismic functions (e.g., prey capture, burrowing, and locomotion) are dissimilar. In contrast, a previous study of an ecologically similar sympatric spider with little genetic structure indicated a strong latitudinal response in 10 traits over the same range. The congruence of morphological variation with deep phylogeographic structure in Tallaganda's A. sutherlandi populations, as well as the inconsistent patterns of variation across separate functional traits, suggest that the spiders are likely in early stages of speciation, with parapatric populations independently responding to local selective forces.

  12. Why We Should Study the Broader Autism Phenotype in Typically Developing Populations

    Science.gov (United States)

    Landry, Oriane; Chouinard, Philippe A.

    2016-01-01

    The broader autism phenotype (BAP) is a term applied to individuals with personality and cognitive traits that are similar to but milder than those observed in autism spectrum disorder (ASD). Subtle autistic traits in the core diagnostic domains of social communication and rigid behavior were described in family members of people with an ASD even…

  13. Prevalence of weak RhD phenotype in the blood donor population ...

    African Journals Online (AJOL)

    Background: The weak RhD phenotype is a form of RhD antigen that, in routine RhD typing, does not react by agglutination with potent monoclonal anti-D serum, but requires addition of antiglobulin serum to demonstrate the presence of the antigen. However, the weak D antigen can cause immunization or sensitization ...

  14. Phenotypic assortment mediates the effect of social selection in a wild beetle population

    NARCIS (Netherlands)

    Formica, Vincent A.; McGlothlin, Joel W.; Wood, Corlett W.; Augat, Malcolm E.; Butterfield, Rebecca E.; Barnard, Mollie E.; Brodie, Edmund D.

    2011-01-01

    Social interactions often have major fitness consequences, but little is known about how specific interacting phenotypes affect the strength of natural selection. Social influences on the evolutionary process can be assessed using a multilevel selection approach that partitions the effects of social

  15. Phenotypic plasticity of Vaccinium meridionale (Ericaceae in wild populations of mountain forests in Colombia

    Directory of Open Access Journals (Sweden)

    Gustavo A Ligarreto

    2011-06-01

    Full Text Available Vaccinium meridionale is a promising crop for the Andean region of South America and is currently available only in the wild. Spontaneous populations of this plant are found across the Colombian mountains, but very few published records on this plant morphology are available. A zonification study of V. meridionale was conducted in four principal areas of a low mountain forest of Colombia (Provinces of Boyacá, Cundinamarca, Santander and Nariño in 2007. A total of 20 populations and 100 plants of V. meridionale were individually characterized and surveyed, using a list of 26 characters of morphological variables (9 quantitative and 17 qualitative characters. Our results indicated that natural populations of V. meridionale might be found in the tropical forest under a highly heterogeneous climate and microclimate conditions, at different mountain regions between 2 357 and 3 168masl. The shrubs of V. meridionale exhibited a high level of intra-population variation in several quantitative (plant height, stem diameter and qualitative (growth habit, ramification density, presence of anthocyanins in stems morphological characters, suggesting an environmentally induced phenotypic plasticity. Plant height, stem diameter and foliar density were the most variable morphological traits, with coefficients of variation higher than 50%. However, several quantitative characters of its reproductive potential, such as berry dimensions, rachis length and number of flowers per inflorescence, resulted with low plasticity with coefficients of variation lower than 30.2%, indicating that these characters were genetically determined. The highest correlation coefficients (pVaccinium meridionale es una planta promisoria para la región Andina de Sudamérica y está disponible actualmente sólo en forma silvestre. Las poblaciones espontáneas de esta planta se encuentran en las montañas colombianas y existen muy pocos reportes publicados respecto a su morfología. Se

  16. Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in Germany – Tattoos are not restricted to a specific social phenotype

    Science.gov (United States)

    Müller, Cornelia Sigrid Lissi; Oertel, Angela; Körner, Rebecca; Pföhler, Claudia; Vogt, Thomas

    2017-01-01

    ABSTRACT Background: More and more people of all age classes have a tattoo. Intriguingly, there are multiple prejudices in the general population and published data that concern tattooed persons, such as being criminals, having a low education, being alcohol or drug abusers, or more risky in their life style. Objective: To obtain and to evaluate sociodemographic data on tattooed persons, to investigate the incidence of tattoo-related cutaneous complications and to define personal risk factors and course of the persons after being tattooed concerning behavior of personal environment. Patients and Methods: We interviewed 426 participants with already existing tattoos and 20 participants just before getting a new tattoo by using an online questionnaire. The participators were asked about socio-epidemiologic aspects of tattoos in general and special aspects of their own tattoo(s) in particular. There were no exclusion criteria. Results: Tattoos are interesting for people seeking popular body art, esp. university graduates and financially-secure individuals. 446 persons participated in this study. Most of the persons were female with a mean age of 35. Local pruritus around the tattooed area was the most common cutaneous side effect among the participants. 93.5% of the participants did not want a tattoo removal. Intriguingly, most of the participants experienced no career problems related to the tattoo(s). Limitations: The study population is not representative as we included only persons being tattooed prior to or getting newly tattooed. Furthermore, there is a potential selection bias as the participation in this study was voluntary. Only persons that felt involved by the flyer did answer the questionnaire. Conclusion: The present data shows that common tattooed persons are not low educated criminals with any drug or alcohol abuse or with risky life style. Nowadays being tattooed encompasses a kind of body art and displays a certain kind of lifestyle habit. PMID

  17. Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in Germany - Tattoos are not restricted to a specific social phenotype.

    Science.gov (United States)

    Müller, Cornelia Sigrid Lissi; Oertel, Angela; Körner, Rebecca; Pföhler, Claudia; Vogt, Thomas

    2017-01-01

    Background : More and more people of all age classes have a tattoo. Intriguingly, there are multiple prejudices in the general population and published data that concern tattooed persons, such as being criminals, having a low education, being alcohol or drug abusers, or more risky in their life style. Objective : To obtain and to evaluate sociodemographic data on tattooed persons, to investigate the incidence of tattoo-related cutaneous complications and to define personal risk factors and course of the persons after being tattooed concerning behavior of personal environment. Patients and Methods : We interviewed 426 participants with already existing tattoos and 20 participants just before getting a new tattoo by using an online questionnaire. The participators were asked about socio-epidemiologic aspects of tattoos in general and special aspects of their own tattoo(s) in particular. There were no exclusion criteria. Results : Tattoos are interesting for people seeking popular body art, esp. university graduates and financially-secure individuals. 446 persons participated in this study. Most of the persons were female with a mean age of 35. Local pruritus around the tattooed area was the most common cutaneous side effect among the participants. 93.5% of the participants did not want a tattoo removal. Intriguingly, most of the participants experienced no career problems related to the tattoo(s). Limitations : The study population is not representative as we included only persons being tattooed prior to or getting newly tattooed. Furthermore, there is a potential selection bias as the participation in this study was voluntary. Only persons that felt involved by the flyer did answer the questionnaire. Conclusion : The present data shows that common tattooed persons are not low educated criminals with any drug or alcohol abuse or with risky life style. Nowadays being tattooed encompasses a kind of body art and displays a certain kind of lifestyle habit.

  18. A comparative study on genetic and environmental influences on metabolic phenotypes in Eastern (Chinese) and Western (Danish) populations

    DEFF Research Database (Denmark)

    Li, Shuxia

    2015-01-01

    the risk of clinic diseases e.g. diabetes, atherosclerosis, stroke and cardiovascular disease. Metabolic phenotypes, similar to most complex traits, can be influenced by both genetic and environmental factors as well as their interplay. Many family and twin studies have demonstrated both genetic...... and environmental factors play important role in the variation of metabolic phenotypes and intra-individual change over time. Although both genetic and environmental factors are involved the development of metabolic disorders, the role of environment should be emphasized as the expression or function of gene can...... be regulated to adapt to existing environmental circumstance. In other words, adaptive evolution in populations under distinct environmental and cultural circumstances could have resulted in varying genetic basis of metabolic factors and development of metabolic disorders or diseases. Thus, it can...

  19. Sange fra Vestkysten – en overset side af populærmusikken i Danmark

    Directory of Open Access Journals (Sweden)

    Niels Kayser Nielsen

    2011-06-01

    Full Text Available Det vestjyske musikmiljø, på kysten fra Grænsen til Skagen, henlever en stille tilværelse i den danske kulturelle offentlighed og er med enkelte markante undtagelser næsten ukendt på den populærkulturelle musikscene. Denne artikel er et forsøg på at give mæle til et populærkulturelt marginalområde af Danmark; ikke for at placere det i en offerrolle, men snarere for at komplettere billedet af dansk musikkultur ved at pege på en center/periferi-tilgang. Nærmere bestemt foretages der analyser af de tematikker – kærlighed, politik, arbejde, kristentro, hjemstedsfornemmelse – der er så fremtrædende i den vestjyske musikkultur. Det er en grundtanke, at en opmærksomhed på også denne del af dansk musikliv er ønskværdig i henseende til udformningen af et kulturelt demokrati med henblik på en ligeværdig anerkendelse. 

  20. Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1

    OpenAIRE

    Suri, Mohnish; Evers, Jochem M. G.; Laskowski, Roman A.; O'Brien, Sinead; Baker, Kate; Clayton‐Smith, Jill; Dabir, Tabib; Josifova, Dragana; Joss, Shelagh; Kerr, Bronwyn; Kraus, Alison; McEntagart, Meriel; Morton, Jenny; Smith, Audrey; Splitt, Miranda

    2017-01-01

    Abstract Background Syntaxin‐binding protein 1, encoded by STXBP1, is highly expressed in the brain and involved in fusing synaptic vesicles with the plasma membrane. Studies have shown that pathogenic loss‐of‐function variants in this gene result in various types of epilepsies, mostly beginning early in life. We were interested to model pathogenic missense variants on the protein structure to investigate the mechanism of pathogenicity and genotype–phenotype correlations. Methods We report 11...

  1. Geographically distinct Ceratophyllum demersum populations differ in growth, photosynthetic responses and phenotypic plasticity to nitrogen availability

    DEFF Research Database (Denmark)

    Hyldgaard, Benita; Sorrell, Brian Keith; Olesen, Birgit

    2012-01-01

    from New Zealand (NZ) and a noninvasive population from Denmark (DK). The populations were compared with a focus on both morphological and physiological traits. The NZ population had higher relative growth rates (RGRs) and photosynthesis rates (Pmax) (range: RGR, 0.06–0.08 per day; Pmax, 200–395 µmol O......2 g–1 dry mass (DM) h–1) compared with the Danish population (range: RGR, 0.02–0.05 per day; Pmax, 88–169 µmol O2 g–1 DM h–1). The larger, faster-growing NZ population also showed higher plasticity than the DK population in response to nitrogen in traits important for growth. Hence, the observed...... differences in growth behaviour between the two populations are a result of genetic differences and differences in their level of plasticity. Here, we show that two populations of the same species from similar climates but different geographical areas can differ in several ecophysiological traits after growth...

  2. Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population

    Directory of Open Access Journals (Sweden)

    Walsh Tom

    2006-01-01

    Full Text Available Abstract Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to characterise the genetics of inherited hearing loss in this population, we worked with West Bank schools for the deaf to identify children with prelingual, bilateral, severe to profound hearing loss not attributable to infection, trauma or other known environmental exposure. Of 156 families enrolled, hearing loss in 17 families (11 per cent was due to mutations in GJB2 (connexin 26, a smaller fraction of GJB2-associated deafness than in other populations. In order to estimate how many different genes might be responsible for hearing loss in this population, we evaluated ten families for linkage to all 36 known human autosomal deafness-related genes, fully sequencing hearing-related genes at any linked sites in informative relatives. Four families harboured four novel alleles of TMPRSS3 (988ΔA = 352stop, otoancorin (1067A >T = D356V and pendrin (716T > A = V239D and 1001G > T = 346stop. In each family, all affected individuals were homozygous for the critical mutation. Each allele was specific to one or a few families in the cohort; none were widespread. Since epidemiological tests of association of mutations with deafness were not feasible for such rare alleles, we used functional and bioinformatics approaches to evaluate their consequences. In six other families, hearing loss was not linked to any known gene, suggesting that these families harbour novel genes responsible for this phenotype. We conclude that inherited hearing loss is highly heterogeneous in this population, with most extended families acting as genetic isolates in this context. We also conclude that the same genes are responsible for hearing loss in this population as elsewhere, so that gene discovery in these families informs the genetics of hearing loss worldwide.

  3. Phenotypic plasticity and local adaptation in leaf ecophysiological traits of 13 contrasting cork oak populations under different water availabilities.

    Science.gov (United States)

    Ramírez-Valiente, Jose Alberto; Sánchez-Gómez, David; Aranda, Ismael; Valladares, Fernando

    2010-05-01

    Plants distributed across a wide range of environmental conditions are submitted to differential selective pressures. Long-term selection can lead to the development of adaptations to the local environment, generating ecotypic differentiation. Additionally, plant species can cope with this environmental variability by phenotypic plasticity. In this study, we examine the importance of both processes in coping with environmental heterogeneity in the Mediterranean sclerophyllous cork oak Quercus suber. For this purpose, we measured growth and key functional traits at the leaf level in 9-year-old plants across 2 years of contrasting precipitation (2005 and 2006) in a common garden. Plants were grown from acorns originated from 13 populations spanning a wide range of climates along the distribution range of the species. The traits measured were: leaf size (LS), specific leaf area (SLA), carbon isotope discrimination (Delta(13)C) and leaf nitrogen content per unit mass (N(mass)). Inter-population differences in LS, SLA and Delta(13)C were found. These differences were associated with rainfall and temperature at the sites of origin, suggesting local adaptation in response to diverging climates. Additionally, SLA and LS exhibited positive responses to the increase in annual rainfall. Year effect explained 28% of the total phenotypic variance in LS and 2.7% in SLA. There was a significant genotype x environment interaction for shoot growth and a phenotypic correlation between the difference in shoot growth among years and the annual mean temperature at origin. This suggests that populations originating from warm sites can benefit more from wet conditions than populations from cool sites. Finally, we investigated the relationships between functional traits and aboveground growth by several regression models. Our results showed that plants with lower SLA presented larger aboveground growth in a dry year and plants with larger leaf sizes displayed larger growth rates in both

  4. Phenotypic and genetic differentiation among yellow monkeyflower populations from thermal and non-thermal soils in Yellowstone National Park.

    Science.gov (United States)

    Lekberg, Ylva; Roskilly, Beth; Hendrick, Margaret F; Zabinski, Catherine A; Barr, Camille M; Fishman, Lila

    2012-09-01

    In flowering plants, soil heterogeneity can generate divergent natural selection over fine spatial scales, and thus promote local adaptation in the absence of geographic barriers to gene flow. Here, we investigate phenotypic and genetic differentiation in one of the few flowering plants that thrives in both geothermal and non-thermal soils in Yellowstone National Park (YNP). Yellow monkeyflowers (Mimulus guttatus) growing at two geothermal ("thermal") sites in YNP were distinct in growth form and phenology from paired populations growing nearby ( 0.34), which were only weakly differentiated from each other (all F (ST) geothermal gradient in Yellowstone.

  5. Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.

    Science.gov (United States)

    Welt, C K; Arason, G; Gudmundsson, J A; Adams, J; Palsdóttir, H; Gudlaugsdóttir, G; Ingadóttir, G; Crowley, W F

    2006-11-01

    The phenotype of women with polycystic ovary syndrome (PCOS) is variable, depending on the ethnic background. The phenotypes of women with PCOS in Iceland and Boston were compared. The study was observational with a parallel design. Subjects were studied in an outpatient setting. Women, aged 18-45 yr, with PCOS defined by hyperandrogenism and fewer than nine menses per year, were examined in Iceland (n = 105) and Boston (n = 262). PCOS subjects underwent a physical exam, fasting blood samples for androgens, gonadotropins, metabolic parameters, and a transvaginal ultrasound. The phenotype of women with PCOS was compared between Caucasian women in Iceland and Boston and among Caucasian, African-American, Hispanic, and Asian women in Boston. Androstenedione (4.0 +/- 1.3 vs. 3.5 +/- 1.2 ng/ml; P PCOS. There were no differences in fasting blood glucose, insulin, or homeostasis model assessment in body mass index-matched Caucasian subjects from Iceland or Boston or in different ethnic groups in Boston. Polycystic ovary morphology was demonstrated in 93-100% of women with PCOS in all ethnic groups. The data demonstrate differences in the reproductive features of PCOS without differences in glucose and insulin in body mass index-matched populations. These studies also suggest that measuring androstenedione is important for the documentation of hyperandrogenism in Icelandic women. Finally, polycystic ovary morphology by ultrasound is an almost universal finding in women with PCOS as defined by hyperandrogenism and irregular menses.

  6. Phenotypic and genotypic variations among three allopatric populations of Lutzomyia umbratilis, main vector of Leishmania guyanensis.

    Science.gov (United States)

    de Souza Freitas, Moises Thiago; Ríos-Velasquez, Claudia Maria; Costa, César Raimundo Lima; Figueirêdo, Carlos Alberto Santiago; Aragão, Nádia Consuelo; da Silva, Lidiane Gomes; de Aragão Batista, Marcus Vinicius; Balbino, Teresa Cristina Leal; Pessoa, Felipe Arley Costa; de Queiroz Balbino, Valdir

    2015-09-04

    In South America, Lutzomyia umbratilis is the main vector of Leishmania guyanensis, one of the species involved in the transmission of American tegumentary leishmaniasis. In Brazil, L. umbratilis has been recorded in the Amazon region, and in the state of Pernambuco, Northeastern region, where an isolated population has been identified. This study assessed the phylogeographic structure and size and shape differences of the wing of three Brazilian populations. Samples of L. umbratilis were collected from Rio Preto da Eva (north of the Amazon River, Amazonas), from Manacapuru (south of the Amazon River), and from the isolated population in Recife, Pernambuco state. These samples were processed to obtain sequences of the Cytochrome Oxidase I mitochondrial gene. Geometrics morphometry analysis of the right wing shape of the three populations was made using discriminate canonical analysis. Phylogenetic analysis revealed the presence of two distinct monophyletic clades: one clade comprised of the Recife and Rio Preto da Eva samples, and the other clade comprised of the Manacapuru samples. Comparing the Manacapuru population with the Recife and Rio Preto da Eva populations generated high indices of interpopulational divergence. Geometric morphometry analysis indicated two distinct groups between the studied populations. Canonical variate analysis of wing shape indicated that Rio Preto da Eva population is significantly closer to Recife population, and both populations were genetically distant from Manacapuru. The polymorphic sites and geometric morphometry analysis indicate that the distance, lack of continuity and environmental differences have not modified the ancestral relationship between Recife and Rio Preto da Eva populations. The genetic and morphological similarities shared by the Recife and Rio Preto da Eva populations suggest that these populations are more closely related evolutionarily. These results confirm the existence of an L. umbratilis species complex in

  7. Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences

    Energy Technology Data Exchange (ETDEWEB)

    Sachse, C.; Brockmoeller, J.; Bauer, S.; Roots, I. [Humboldt Univ., Berlin (Germany)

    1997-02-01

    Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles. Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine. For genotyping, nested PCR-RFLP tests from a PCR amplificate of the entire CYP2D6 gene were developed. The frequency of the CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was .364. The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity (intermediate metabolizer phenotype [IM]) showed frequencies of .324, .018, and .015, respectively. By use of novel PCR tests for discrimination, CYP2D6 gene duplication alleles were found with frequencies of.005 (*1 x 2), .013 (* 2 x 2), and .001 (*4 x 2). Frequencies of alleles with complete deficiency (poor metabolizer phenotype [PM]) were .207 (*4), .020 (*3 and *5), .009 (*6), and .001 (*7, *15, and *16). The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were not found. All 41 PMs (7.0%) in this sample were explained by five mutations detected by four PCR-RFLP tests, which may suffice, together with the gene duplication test, for clinical prediction of CYP2D6 capacity. Three novel variants of known CYP2D6 alleles were discovered: *1C (T{sub 1957}C), *2B (additional C{sub 2558}T), and *4E (additional C{sub 2938}T). Analysis of variance showed significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) between carriers of EN/PM (mean MR = .006) and IM/PM (mean MR = .014) alleles and between carriers of one (mean MR = .009) and two (mean MR = .003) functional alleles. The results of this study provide a solid basis for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment. 35 refs., 4 figs., 5 tabs.

  8. Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

    Directory of Open Access Journals (Sweden)

    Relu Cocoş

    Full Text Available Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1 ∶ 1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18 ± 1 years showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

  9. Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

    Science.gov (United States)

    Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

    2016-02-01

    Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

  10. Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain

    Science.gov (United States)

    2014-01-01

    Introduction Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. Methods We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Results Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; screening-detected cancers, extreme breast density

  11. Parallel Genetic and Phenotypic Evolution of DNA Superhelicity in Experimental Populations of Escherichia coli

    DEFF Research Database (Denmark)

    Crozat, Estelle; Winkworth, Cynthia; Gaffé, Joël

    2010-01-01

    , indicate that changes in DNA superhelicity have been important in the evolution of these populations. Surprisingly, however, most of the evolved alleles we tested had either no detectable or slightly deleterious effects on fitness, despite these signatures of positive selection.......DNA supercoiling is the master function that interconnects chromosome structure and global gene transcription. This function has recently been shown to be under strong selection in Escherichia coli. During the evolution of 12 initially identical populations propagated in a defined environment...

  12. An investigation of secondary anti-D immunisation among phenotypically RhD-negative individuals in the Chinese population.

    Science.gov (United States)

    Wang, Qing-Ping; Dong, Guang-Tao; Wang, Xue-Dong; Gu, Juan; Li, Zheng; Sun, An-Yuan; Shao, Chao-Peng; Pan, Zhao-Lin; Huang, Li-Hua; Xie, Wei-Xing; Sun, Guang-Ming; Chen, Jian-Jiang; Pei, Hao; Yang, Xiao-Juan; Shan, Ping-Nan

    2014-04-01

    Despite the introduction of anti-D prophylaxis into clinical practice, RhD alloimmunisation remains a problem, particularly in the context of transfusions and pregnancy-induced alloimmunisation. The incidence of RhD alloimmunisation among phenotypically RhD-negative individuals is unknown in most countries. We investigated RhD alloimmmunisation in RhD-negative pregnant women and transfusion recipients in south-east China in order to optimise the prevention of this phenomenon. We analysed the RhD alloimmunisation status of RhD-negative pregnant women and transfusion recipients in south-east China. The RhD blood types of the study population were identified by standard serological methods. The D antigen was further tested with the indirect antiglobulin test to exclude or confirm weak D or partial D types. RhC, c, E and e antigens were typed in all subjects. If anti-D antibody screening was positive, the specificity and titre of the antibody were determined. The Del phenotype was investigated by the polymerase chain reaction sequence-specific primer method. An anti-D antibody was found in 61 of 416 RhD-negative pregnant women (14.66%), and in 11 of 227 RhD-negative transfusion recipients (4.85%). None of the 72 RhD-negative pregnant women or transfusion recipients with anti-D had the Del phenotype. Anti-D antibodies were not detected among Del phenotype individuals and Del phenotypes were not found in anti-D antibody producing individuals. Our study suggests that the risk of alloimmunity-induced neonatal haemolysis increases in true RhD-negative multipara. Perinatal protection would be necessary in these patients, while antenatal anti-D testing and Rh immune globulin prophylaxis would be unnecessary for RhDel pregnant women. Pregnant women and transfusion recipients with the Del type seldom produce anti-D antibody. RhD-negative recipients are not at risk of alloimmunisation after transfusion with Del red blood cells.

  13. Phenotypic variation in California populations of valley oak (Quercus lobata Née) sampled along elevational gradients

    Science.gov (United States)

    Ana L. Albarrán-Lara; Jessica W. Wright; Paul F. Gugger; Annette Delfino-Mix; Juan Manuel Peñaloza-Ramírez; Victoria L. Sork

    2015-01-01

    California oaks exhibit tremendous phenotypic variation throughout their range. This variation reflects phenotypic plasticity in tree response to local environmental conditions as well as genetic differences underlying those phenotypes. In this study, we analyze phenotypic variation in leaf traits for valley oak adults sampled along three elevational transects and in...

  14. SALL4, a stem cell factor, affects the side population by regulation of the ATP-binding cassette drug transport genes.

    Directory of Open Access Journals (Sweden)

    Ha-Won Jeong

    2011-04-01

    Full Text Available Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with decreased SALL4 expression were more sensitive to drug treatments than the parental cells. This led to our investigation of the implication of SALL4 in drug resistance and its role in side population (SP cancer stem cells. SALL4 expression was higher in SP cells compared to non-SP cells by 2-4 fold in various malignant hematopoietic cell lines. Knocking down of SALL4 in isolated SP cells resulted in a reduction of SP cells, indicating that SALL4 is required for their self-renewal. The SP phenotype is known to be mediated by members of the ATP-binding cassette (ABC drug transport protein family, such as ABCG2 and ABCA3. Using chromatin-immunoprecipitation (ChIP, quantitative reverse transcription polymerase chain reaction (qRT-PCR and electrophoretic mobility shift assay(EMSA, we demonstrated that SALL4 was able to bind to the promoter region of ABCA3 and activate its expression while regulating the expression of ABCG2 indirectly. Furthermore, SALL4 expression was positively correlated to those of ABCG2 and ABCA3 in primary leukemic patient samples. Taken together, our results suggest a novel role for SALL4 in drug sensitivity, at least in part through the maintenance of SP cells, and therefore may be responsible for drug-resistance in leukemia. We are the first to demonstrate a direct link between stem cell factor SALL4, SP and drug resistance in leukemia.

  15. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis

    Energy Technology Data Exchange (ETDEWEB)

    Santamaria-Martinez, Albert [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat de Barcelona, Barcelona (Spain); Barquinero, Jordi [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Banc de Sang i Teixits, Barcelona (Spain); Barbosa-Desongles, Anna; Hurtado, Antoni; Pinos, Tomas [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Seoane, Joan [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Medical Oncology program, Vall d' Hebron Institute of Oncology, Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Poupon, Marie-France [Institut Curie, Paris (France); Morote, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Servei d' Urologia. Hospital Vall d' Hebron, Barcelona (Spain); Reventos, Jaume [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Munell, Francina, E-mail: fmunell@ir.vhebron.net [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain)

    2009-10-15

    Cancer stem cells are a distinct cellular population that is believed to be responsible for tumor initiation and maintenance. Recent data suggest that solid tumors also contain another type of stem cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs), which contribute to the formation of tumor-associated stroma. The Hoechst 33342 efflux assay has proved useful to identify a rare cellular fraction, named Side Population (SP), enriched in cells with stem-like properties. Using this assay, we identified SP cells in a prostate cancer xenograft containing human prostate cancer cells and mouse stromal cells. The SP isolation, subculture and sequential sorting allowed the generation of single-cell-derived clones of murine origin that were recognized as MSC by their morphology, plastic adherence, proliferative potential, adipogenic and osteogenic differentiation ability and immunophenotype (CD45{sup -}, CD81{sup +} and Sca-1{sup +}). We also demonstrated that SP clonal cells secrete transforming growth factor {beta}1 (TGF-{beta}1) and that their inhibition reduces proliferation and accelerates differentiation. These results reveal the existence of SP cells in the stroma of a cancer xenograft, and provide evidence supporting their MSC nature and the role of TGF-{beta}1 in maintaining their proliferation and undifferentiated status. Our data also reveal the usefulness of the SP assay to identify and isolate MSC cells from carcinomas.

  16. A stochastic algorithm for global optimization and for best populations: A test case of side chains in proteins

    Science.gov (United States)

    Glick, Meir; Rayan, Anwar; Goldblum, Amiram

    2002-01-01

    The problem of global optimization is pivotal in a variety of scientific fields. Here, we present a robust stochastic search method that is able to find the global minimum for a given cost function, as well as, in most cases, any number of best solutions for very large combinatorial “explosive” systems. The algorithm iteratively eliminates variable values that contribute consistently to the highest end of a cost function's spectrum of values for the full system. Values that have not been eliminated are retained for a full, exhaustive search, allowing the creation of an ordered population of best solutions, which includes the global minimum. We demonstrate the ability of the algorithm to explore the conformational space of side chains in eight proteins, with 54 to 263 residues, to reproduce a population of their low energy conformations. The 1,000 lowest energy solutions are identical in the stochastic (with two different seed numbers) and full, exhaustive searches for six of eight proteins. The others retain the lowest 141 and 213 (of 1,000) conformations, depending on the seed number, and the maximal difference between stochastic and exhaustive is only about 0.15 Kcal/mol. The energy gap between the lowest and highest of the 1,000 low-energy conformers in eight proteins is between 0.55 and 3.64 Kcal/mol. This algorithm offers real opportunities for solving problems of high complexity in structural biology and in other fields of science and technology. PMID:11792838

  17. Phenotypic characterization of aberrant stem and progenitor cell populations in myelodysplastic syndromes.

    Science.gov (United States)

    Ostendorf, Benjamin N; Flenner, Eva; Flörcken, Anne; Westermann, Jörg

    2018-01-01

    Recent reports have revealed myelodysplastic syndromes (MDS) to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and multiple surface markers are aberrantly expressed. These aberrant antigen expression patterns hold diagnostic and therapeutic promise. However, eradication of MDS requires targeting of early myelodysplasia propagating stem cells. This warrants an exact assessment of the differentiation stage at which aberrant expression occurs in transformed hematopoiesis. Here, we report results on the prospective and extensive dissection of the hematopoietic hierarchy in 20 patients with either low-risk MDS or MDS with excess blasts and compare it to hematopoiesis in patients with non-malignancy-associated cytopenia or B cell lymphoma without bone marrow infiltration. We found patients with MDS with excess blasts to exhibit characteristic expansions of specific immature progenitor compartments. We also identified the aberrant expression of several markers including ALDH, CLL-1, CD44, and CD47 to be specific features of hematopoiesis in MDS with excess blasts. We show that amongst these, aberrant CLL-1 expression manifested at the early uncommitted hematopoietic stem cell level, suggesting a potential role as a therapeutic target.

  18. Phenotypic characterization of aberrant stem and progenitor cell populations in myelodysplastic syndromes.

    Directory of Open Access Journals (Sweden)

    Benjamin N Ostendorf

    Full Text Available Recent reports have revealed myelodysplastic syndromes (MDS to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and multiple surface markers are aberrantly expressed. These aberrant antigen expression patterns hold diagnostic and therapeutic promise. However, eradication of MDS requires targeting of early myelodysplasia propagating stem cells. This warrants an exact assessment of the differentiation stage at which aberrant expression occurs in transformed hematopoiesis. Here, we report results on the prospective and extensive dissection of the hematopoietic hierarchy in 20 patients with either low-risk MDS or MDS with excess blasts and compare it to hematopoiesis in patients with non-malignancy-associated cytopenia or B cell lymphoma without bone marrow infiltration. We found patients with MDS with excess blasts to exhibit characteristic expansions of specific immature progenitor compartments. We also identified the aberrant expression of several markers including ALDH, CLL-1, CD44, and CD47 to be specific features of hematopoiesis in MDS with excess blasts. We show that amongst these, aberrant CLL-1 expression manifested at the early uncommitted hematopoietic stem cell level, suggesting a potential role as a therapeutic target.

  19. Phenotypic differentiation is associated with divergent sexual selection among closely related barn swallow populations

    Czech Academy of Sciences Publication Activity Database

    Wilkins, M. R.; Karaardic, H.; Vortman, Y.; Parchman, T. L.; Albrecht, Tomáš; Petrželková, Adéla; Özkan, L.; Pap, P. L.; Hubbard, J. K.; Hund, A. K.; Safran, R. J.

    2016-01-01

    Roč. 29, č. 12 (2016), s. 2410-2421 ISSN 1010-061X R&D Projects: GA MŠk(CZ) LH14045 Institutional support: RVO:68081766 Keywords : birds * natural selection * population genetics * sexual selection & conflicts * speciation Subject RIV: EG - Zoology Impact factor: 2.792, year: 2016

  20. Phenotyping asthma, rhinitis and eczema in MeDALL population-based birth cohorts

    DEFF Research Database (Denmark)

    Garcia-Aymerich, J; Benet, M; Saeys, Y

    2015-01-01

    at 4 years and 14 585 at 8 years from seven European population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms 'ever' and 'in the last 12 months', doctor diagnosis, age...

  1. Hybridization between ecotypes in a phenotypically and ecologically heterogeneous population of Iris savannarum (Iridaceae) in Florida.

    Science.gov (United States)

    Iris series Hexagonae is a small, monophyletic complex of 5 species and associated hybrid populations, popularly known as the “Louisiana irises.” The Hexagonae alliance of Iris have been recognized as a textbook case of introgressive hybridization based on numerous studies in Louisiana. We previou...

  2. Altered genotypic and phenotypic frequencies of aphid populations under enriched CO2 and O3 atmospheres

    Science.gov (United States)

    Edward B. Mondor; Michelle N. Tremblay; Caroline S. Awmack; Richard L. Lindroth

    2005-01-01

    Environmental change is anticipated to negatively affect both plant and animal populations. As abiotic factors rapidly change habitat suitability, projections range from altered genetic diversity to wide-spread species loss. Here, we assess the degree to which changes in atmospheric composition associated with environmental change will influence not only the abundance...

  3. Phenotypic selection on leaf WUE and related ecophysiological traits for natural populations of desert sunflowers

    NARCIS (Netherlands)

    Donovan, L.A.; Rosenthal, D.R.; Dudley, S.A.; Ludwig, F.

    2007-01-01

    Plant water-use efficiency (WUE) is expected to affect plant fitness and thus be under natural selection in arid habitats. Although many natural population studies have assessed plant WUE, only a few related WUE to fitness. The further determination of whether selection on WUE is direct or indirect

  4. Expansion of the genotypic and phenotypic spectrum of xeroderma pigmentosum in Chinese population.

    Science.gov (United States)

    Zhang, Jia; Cheng, Ruhong; Yu, Xia; Sun, Zhonghui; Li, Ming; Yao, Zhirong

    2017-01-01

    Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by exaggerated sunburn reactions, freckle-like pigmentation, and a high possibility of developing cutaneous tumors. XP comprised seven complementation groups (from XP-A to XP-G) and a variant form XP-V. This study was based on five unrelated Chinese families with six patients clinically suspected to be XP. Mutation screening was performed by direct sequencing of the entire coding region of eight XP genes. All of the pathogenic mutations were identified by mutational analysis, including four novel mutations. Our study successfully identified the pathogenic mutations in six XP patients (three XP-A, one XP-G, one XP-V, and a rare XP-D group in Chinese population). We reviewed the reported XP cases with mutations in the Chinese population and concluded that four complementation groups (XP-A, XP-C, XP-G, and XP-V) that occupy the major proportion should be considered as a first step in genetic detection (especially, XPA is the most common group, and unlike in other populations, XP-G is not rare in the Chinese population). Moreover, XP-D and XP-F, two rare subgroups, should also be added for further mutational analysis. Further, we provide some information for Chinese dermatologists that, when an early diagnosis is made, XP-C and XP-V patients can have relatively good prognoses. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil

    Science.gov (United States)

    2009-01-01

    In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers. PMID:21637504

  6. Flow cytometric monitoring of bacterioplankton phenotypic diversity predicts high population-specific feeding rates by invasive dreissenid mussels.

    Science.gov (United States)

    Props, Ruben; Schmidt, Marian L; Heyse, Jasmine; Vanderploeg, Henry A; Boon, Nico; Denef, Vincent J

    2018-02-01

    Species invasion is an important disturbance to ecosystems worldwide, yet knowledge about the impacts of invasive species on bacterial communities remains sparse. Using a novel approach, we simultaneously detected phenotypic and derived taxonomic change in a natural bacterioplankton community when subjected to feeding pressure by quagga mussels, a widespread aquatic invasive species. We detected a significant decrease in diversity within 1 h of feeding and a total diversity loss of 11.6 ± 4.1% after 3 h. This loss of microbial diversity was caused by the selective removal of high nucleic acid populations (29 ± 5% after 3 h). We were able to track the community diversity at high temporal resolution by calculating phenotypic diversity estimates from flow cytometry (FCM) data of minute amounts of sample. Through parallel FCM and 16S rRNA gene amplicon sequencing analysis of environments spanning a broad diversity range, we showed that the two approaches resulted in highly correlated diversity measures and captured the same seasonal and lake-specific patterns in community composition. Based on our results, we predict that selective feeding by invasive dreissenid mussels directly impacts the microbial component of the carbon cycle, as it may drive bacterioplankton communities toward less diverse and potentially less productive states. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  7. Phenotypes of individuals affected by airborne chemicals in the general population

    DEFF Research Database (Denmark)

    Berg, Nikolaj Drimer; Linneberg, A.; Dirksen, Asger

    2009-01-01

    to symptoms than less severely affected individuals, and the number of symptoms was more predictive for severity than the number of exposures. Most predictive for the severity of reported symptoms were CNS-symptoms other than headache (OR = 3.2, P ... (OR = 2.0, P = 0.001). CONCLUSION: CNS-symptoms except from headache were a main characteristic of individuals severely affected by common chemical exposures in a general population-based sample...

  8. Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort

    Science.gov (United States)

    Lovasz, Barbara Dorottya; Lakatos, Laszlo; Horvath, Agnes; Szita, Istvan; Pandur, Tunde; Mandel, Michael; Vegh, Zsuzsanna; Golovics, Petra Anna; Mester, Gabor; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos Sandor; Lakatos, Peter Laszlo

    2013-01-01

    AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn’s disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long

  9. A Multidisciplinary Phenotyping and Genotyping Analysis of a Mapping Population Enables Quality to Be Combined with Yield in Rice

    Directory of Open Access Journals (Sweden)

    Mariafe Calingacion

    2017-05-01

    Full Text Available In this study a mapping population (F8 of ca 200 progeny from a cross between the commercial rice varieties Apo and IR64 has been both genotyped and phenotyped. A genotyping-by-sequencing approach was first used to identify 2,681 polymorphic SNP markers which gave dense coverage of the genome with a good distribution across all 12 chromosomes. The coefficient of parentage was also low, at 0.13, confirming that the parents are genetically distant from each other. The progeny, together with both parents, were grown under irrigated and water restricted conditions in a randomised block design. All grain was harvested to determine variation in yield across the population. The grains were then polished following standard procedures prior to performing the phenotyping analyses. A Gas Chromatography—Mass Spectrometry approach was used to determine the volatile biochemical profiles of each line and after data curation and processing, discriminatory metabolites were putatively identified based on in-house and commercial spectral libraries. These data were used to predict the potential role of these metabolites in determining differences in aroma between genotypes. A number of QTLs for yield and for individual metabolites have been identified. Following these combined multi-disciplinary analyses, it proved possible to identify a number of lines which appeared to combine the favourable aroma attributes of IR64 with the favourable (higher yield potential of Apo. As such, these lines are excellent candidates to assess further as potential genotypes to work up into a new variety of rice which has both good yield and good quality, thus meeting the needs of both farmer and consumer alike.

  10. Optimizing the creation of base populations for aquaculture breeding programs using phenotypic and genomic data and its consequences on genetic progress.

    Science.gov (United States)

    Fernández, Jesús; Toro, Miguel Á; Sonesson, Anna K; Villanueva, Beatriz

    2014-01-01

    The success of an aquaculture breeding program critically depends on the way in which the base population of breeders is constructed since all the genetic variability for the traits included originally in the breeding goal as well as those to be included in the future is contained in the initial founders. Traditionally, base populations were created from a number of wild strains by sampling equal numbers from each strain. However, for some aquaculture species improved strains are already available and, therefore, mean phenotypic values for economically important traits can be used as a criterion to optimize the sampling when creating base populations. Also, the increasing availability of genome-wide genotype information in aquaculture species could help to refine the estimation of relationships within and between candidate strains and, thus, to optimize the percentage of individuals to be sampled from each strain. This study explores the advantages of using phenotypic and genome-wide information when constructing base populations for aquaculture breeding programs in terms of initial and subsequent trait performance and genetic diversity level. Results show that a compromise solution between diversity and performance can be found when creating base populations. Up to 6% higher levels of phenotypic performance can be achieved at the same level of global diversity in the base population by optimizing the selection of breeders instead of sampling equal numbers from each strain. The higher performance observed in the base population persisted during 10 generations of phenotypic selection applied in the subsequent breeding program.

  11. The Super-Seniors Study: Phenotypic characterization of a healthy 85+ population.

    Science.gov (United States)

    Halaschek-Wiener, Julius; Tindale, Lauren C; Collins, Jennifer A; Leach, Stephen; McManus, Bruce; Madden, Kenneth; Meneilly, Graydon; Le, Nhu D; Connors, Joseph M; Brooks-Wilson, Angela R

    2018-01-01

    To understand why some people live to advanced age in good health and others do not, it is important to study not only disease, but also long-term good health. The Super-Seniors Study aims to identify factors associated with healthy aging. 480 healthy oldest-old 'Super-Seniors' aged 85 to 105 years and never diagnosed with cancer, cardiovascular disease, diabetes, dementia, or major pulmonary disease, were compared to 545 mid-life controls aged 41-54, who represent a group that is unselected for survival from late-life diseases. Health and lifestyle information, personal and family medical history, and blood samples were collected from all participants. Super-Seniors also underwent four geriatric tests. Super-Seniors showed high cognitive (Mini-Mental State Exam mean = 28.3) and functional capacity (Instrumental Activities of Daily Living Scale mean = 21.4), as well as high physical function (Timed Up and Go mean = 12.3 seconds) and low levels of depression (Geriatric Depression Scale mean = 1.5). Super-Seniors were less likely to be current smokers than controls, but the frequency of drinking alcohol was the same in both groups. Super-Seniors were more likely to have 4 or more offspring; controls were more likely to have no children. Female Super-Seniors had a mean age of last fertility 1.9 years older than controls, and were 2.3 times more likely to have had a child at ≥ 40 years. The parents of Super-Seniors had mean ages of deaths of 79.3 years for mothers, and 74.5 years for fathers, each exceeding the life expectancy for their era by a decade. Super-Seniors are cognitively and physically high functioning individuals who have evaded major age-related chronic diseases into old age, representing the approximately top 1% for healthspan. The familiality of long lifespan of the parents of Super-Seniors supports the hypothesis that heritable factors contribute to this desirable phenotype.

  12. Phenotypic selection on leaf water use efficiency and related ecophysiological traits for natural populations of desert sunflowers.

    Science.gov (United States)

    Donovan, Lisa A; Dudley, Susan A; Rosenthal, David M; Ludwig, Fulco

    2007-05-01

    Plant water-use efficiency (WUE) is expected to affect plant fitness and thus be under natural selection in arid habitats. Although many natural population studies have assessed plant WUE, only a few related WUE to fitness. The further determination of whether selection on WUE is direct or indirect through functionally related traits has yielded no consistent results. For natural populations of two desert annual sunflowers, Helianthus anomalus and H. deserticola, we used phenotypic selection analysis with vegetative biomass as the proxy for fitness to test (1) whether there was direct and indirect selection on WUE (carbon isotope ratio) and related traits (leaf N, area, succulence) and (2) whether direct selection was consistent with hypothesized drought/dehydration escape and avoidance strategies. There was direct selection for lower WUE in mesic and dry H. anomalus populations, consistent with dehydration escape, even though it is the longer lived of the two species. For mesic H. anomalus, direct selection favored lower WUE and higher N, suggesting that plants may be "wasting water" to increase N delivery via the transpiration stream. For the shorter lived H. deserticola in the direr habitat, there was indirect selection for lower WUE, inconsistent with drought escape. There was also direct selection for higher leaf N, succulence and leaf size. There was no direct selection for higher WUE consistent with dehydration avoidance in either species. Thus, in these natural populations of two desert dune species higher fitness was associated with some combination direct and indirect selection for lower WUE, higher leaf N and larger leaf size. Our understanding of the adaptive value of plant ecophysiological traits will benefit from further consideration of related traits such as leaf nitrogen and more tests in natural populations.

  13. Population differences in host use by a seed-beetle: local adaptation, phenotypic plasticity and maternal effects.

    Science.gov (United States)

    Amarillo-Suárez, Angela R; Fox, Charles W

    2006-11-01

    For insects that develop inside discrete hosts, both host size and host quality constrain offspring growth, influencing the evolution of body size and life history traits. Using a two-generation common garden experiment, we quantified the contribution of maternal and rearing hosts to differences in growth and life history traits between populations of the seed-feeding beetle Stator limbatus that use a large-seeded host, Acacia greggii, and a small-seeded host, Pseudosamanea guachapele. Populations differed genetically for all traits when beetles were raised in a common garden. Contrary to expectations from the local adaptation hypothesis, beetles from all populations were larger, developed faster and had higher survivorship when reared on seeds of A. greggii (the larger host), irrespective of their native host. We observed two host plant-mediated maternal effects: offspring matured sooner, regardless of their rearing host, when their mothers were reared on P. guachapele (this was not caused by an effect of rearing host on egg size), and females laid larger eggs on P. guachapele. This is the first study to document plasticity by S. limbatus in response to P. guachapele, suggesting that plasticity is an ancestral trait in S. limbatus that likely plays an important role in diet expansion. Although differences between populations in growth and life history traits are likely adaptations to their host plants, host-associated maternal effects, partly mediated by maternal egg size plasticity, influence growth and life history traits and likely play an important role in the evolution of the breadth of S. limbatus' diet. More generally, phenotypic plasticity mediates the fitness consequences of using novel hosts, likely facilitating colonization of new hosts, but also buffering herbivores from selection post-colonization. Plasticity in response to novel versus normal hosts varied among our study populations such that disentangling the historical role of plasticity in

  14. Phenotypic differences in teeth dimensions among Chennai population: An aid in sex determination

    Directory of Open Access Journals (Sweden)

    Sreedevi Dharman

    2015-01-01

    Full Text Available Objective: To investigate the presence of sexual dimorphism by studying the size of the teeth among males and females in Chennai population, which aids in sex determination. Materials and Methods: Incisocervical length, mesiodistal and buccolingual diameters were measured in teeth of 60 subjects (30 males, 30 females in the age group of 18-22 years from Chennai population. The differences in the mean values of parameters in males and females were calculated using independent t-test. Discriminant functional analysis was performed to determine the accuracy of sex. Results: Significant differences were found in mean incisocervical length which were found to be larger in males with P < 0.05 in 11, 12, 14, 17, 21, 22, 24, 26, 27, 31, 32, 33, 34, 41, 43, and 45 and with P < 0.001 in 13, 23, 32, 42, 43, and 44, with the exception of 37 and 47 which were larger in females. Mean mesiodistal diameter was larger in males with P < 0.05 in 11, 12, and 21 and with P < 0.001 in 13, 23, 33, and 43. Mean buccolingual diameter was larger in males with P < 0.05 in 12, 21, 31, 33, and 41 and with P < 0.001 in 11, 13, 23, and 43. Accuracy rate of predicting sex based on incisocervical length (17, 23, 47 and mesiodistal diameter (13, 33 was 78.3% and based on buccolingual diameter (13 was 76.7%. Conclusion: Males showed greater sexual dimorphism than females. Application of incisocervical, mesiodistal, and buccolingual dimensional variability among males and females in the Chennai population can aid in sex determination in forensic odontology, as the results showed moderate extent of dimorphism with an overall accuracy rate of predicting sex to be 78%.

  15. Gene-environment and protein degradation signatures characterize genomic and phenotypic diversity in wild Caenorhabditis elegans populations

    NARCIS (Netherlands)

    Volkers, J.M.; Snoek, L.B.; Hellenberg Hubar, van C.J.; Coopman, R.; Chen, W.; Yang, Wentao; Sterken, M.G.; Schulenburg, H.; Braeckman, B.; Kammenga, J.E.

    2013-01-01

    Background: Analyzing and understanding the relationship between genotypes and phenotypes is at the heart of genetics. Research on the nematode Caenorhabditis elegans has been instrumental for unraveling genotype-phenotype relations, and has important implications for understanding the biology of

  16. Phenotypic and functional profiling of CD4 T cell compartment in distinct populations of healthy adults with different antigenic exposure.

    Directory of Open Access Journals (Sweden)

    Sophie Roetynck

    Full Text Available Multiparameter flow cytometry has revealed extensive phenotypic and functional heterogeneity of CD4 T cell responses in mice and humans, emphasizing the importance of assessing multiple aspects of the immune response in correlation with infection or vaccination outcome. The aim of this study was to establish and validate reliable and feasible flow cytometry assays, which will allow us to characterize CD4 T cell population in humans in field studies more fully.We developed polychromatic flow cytometry antibody panels for immunophenotyping the major CD4 T cell subsets as well as broadly characterizing the functional profiles of the CD4 T cells in peripheral blood. We then validated these assays by conducting a pilot study comparing CD4 T cell responses in distinct populations of healthy adults living in either rural or urban Kenya. This study revealed that the expression profile of CD4 T cell activation and memory markers differed significantly between African and European donors but was similar amongst African individuals from either rural or urban areas. Adults from rural Kenya had, however, higher frequencies and greater polyfunctionality among cytokine producing CD4 T cells compared to both urban populations, particularly for "Th1" type of response. Finally, endemic exposure to malaria in rural Kenya may have influenced the expansion of few discrete CD4 T cell populations with specific functional signatures.These findings suggest that environmentally driven T cell activation does not drive the dysfunction of CD4 T cells but is rather associated with greater magnitude and quality of CD4 T cell response, indicating that the level or type of microbial exposure and antigenic experience may influence and shape the functionality of CD4 T cell compartment. Our data confirm that it is possible and mandatory to assess multiple functional attributes of CD4 T cell response in the context of infection.

  17. Phenotypic divergence among west European populations of Reed Bunting Emberiza schoeniclus: the effects of migratory and foraging behaviours.

    Directory of Open Access Journals (Sweden)

    Júlio M Neto

    Full Text Available Divergent selection and local adaptation are responsible for many phenotypic differences between populations, potentially leading to speciation through the evolution of reproductive barriers. Here we evaluated the morphometric divergence among west European populations of Reed Bunting in order to determine the extent of local adaptation relative to two important selection pressures often associated with speciation in birds: migration and diet. We show that, as expected by theory, migratory E. s. schoeniclus had longer and more pointed wings and a slightly smaller body mass than the resident subspecies, with the exception of E. s. lusitanica, which despite having rounder wings was the smallest of all subspecies. Tail length, however, did not vary according to the expectation (shorter tails in migrants probably because it is strongly correlated with wing length and might take longer to evolve. E. s. witherbyi, which feed on insects hiding inside reed stems during the winter, had a very thick, stubby bill. In contrast, northern populations, which feed on seeds, had thinner bills. Despite being much smaller, the southern E. s. lusitanica had a significantly thicker, longer bill than migratory E. s. schoeniclus, whereas birds from the UK population had significantly shorter, thinner bills. Geometric morphometric analyses revealed that the southern subspecies have a more convex culmen than E. s. schoeniclus, and E. s. lusitanica differs from the nominate subspecies in bill shape to a greater extent than in linear bill measurements, especially in males. Birds with a more convex culmen are thought to exert a greater strength at the bill tip, which is in agreement with their feeding technique. Overall, the three subspecies occurring in Western Europe differ in a variety of traits following the patterns predicted from their migratory and foraging behaviours, strongly suggesting that these birds have became locally adapted through natural selection.

  18. Genetic Variation and Phenotypic Response of 15 Sweet Corn (Zea mays L. Hybrids to Population Density

    Directory of Open Access Journals (Sweden)

    William F. Tracy

    2013-06-01

    Full Text Available Planting sweet corn at higher densities may increase the canopy cover, reducing light transmission to the understory and suppressing weed growth. High planting densities can also negatively impact the crop, however, by decreasing ear size and overall yield. The objective of this study was to determine the potential for increased density tolerance of 15 sweet corn hybrids by estimating the general combining ability (GCA and specific combining ability (SCA for traits of interest. In 2010 and 2011, a half-diallel of six historic sweet corn inbreds was evaluated in a split-block randomized complete block design in four Wisconsin environments, with four replicates in each environment. Hybrids were planted at a low density of 29,936 plants ha−1, a medium density of 63,615 plants ha−1, and a high density of 97,293 plants ha−1. Significant differences between hybrids were found for phenomorphological traits and ear characteristics. Inbreds C68, C40 and Ia5125 produced the progeny most tolerant of the highest population density. Among these genotypes, tolerance to high density is a heritable trait, indicating the feasibility of breeding sweet corn for density tolerance and potential weed competitiveness.

  19. Refining clinical phenotypes by contrasting ethnically different populations with schizophrenia from Australia, India and Sarawak.

    Science.gov (United States)

    McLean, Duncan; John, Sujit; Barrett, Robert; McGrath, John; Loa, Peter; Thara, Rangaswamy; Mowry, Bryan

    2012-04-30

    We contrasted demographic and clinical characteristics in transethnic schizophrenia populations from Australia (n=821), India (n=520) and Sarawak, Malaysia (n=298) and proposed cultural explanations for identified site differences. From these we aimed to identify candidate variables free from significant cultural confounding that are hence suitable for inclusion in genetic analyses. We observed five phenomena: (1) more individuals were living alone in Australia than India or Sarawak; (2) drug use was lower in India than Australia or Sarawak; (3) duration of untreated psychosis (DUP) was longer in India than Australia or Sarawak; (4) the rate of schizoaffective disorder was lower in India than Australia or Sarawak; and (5) age at psychosis onset (AAO) was older in Sarawak than Australia or India. We suggest that site differences for living arrangements, drug use and DUP are culturally confounded. The schizoaffective site difference likely results from measurement bias. The AAO site difference, however, has no obvious cultural or measurement bias explanation. Therefore, this may be an ideal candidate for use in genetic studies, given that genetic variants affecting AAO have already been proposed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Growth hormone receptor deficiency in Ecuador: clinical and biochemical phenotype in two populations.

    Science.gov (United States)

    Guevara-Aguirre, J; Rosenbloom, A L; Fielder, P J; Diamond, F B; Rosenfeld, R G

    1993-02-01

    We have identified 56 patients with GH receptor deficiency (Laron syndrome) from two provinces in southern Ecuador, one group of 26 (Loja province) with a 4:1 female predominance and 30 patients from neighboring El Oro province with a normal sex ratio. There were no significant differences between the Loja and El Oro populations in stature (-5.3 to -11.5 standard deviation score), other auxologic measures, or in biochemical measures. GH binding protein, the circulating extracellular domain of the GH receptor, was measured by ligand immunofunction assay and found to be comparably low in children and adults. Levels of insulin-like growth factor (IGF)-I and -II and the GH-dependent IGF binding protein-3 (measured by RIA) were significantly greater, and GH and IGF binding protein-2 levels significantly lower in adults than children. Levels of IGF-I (adults) and IGF binding protein-3 (children and adults) correlated inversely with statural deviation from normal (P < 0.01). School performance was at an exceptionally high level, 41 out of 47 who had attended school being in the top 3 in classes of 15-50 persons.

  1. Phenotypic and genotypic characterization of antioxidant enzyme system in human population exposed to radiation from mobile towers.

    Science.gov (United States)

    Gulati, Sachin; Yadav, Anita; Kumar, Neeraj; Priya, Kanu; Aggarwal, Neeraj K; Gupta, Ranjan

    2018-03-01

    In the present era, cellular phones have changed the life style of human beings completely and have become an essential part of their lives. The number of cell phones and cell towers are increasing in spite of their disadvantages. These cell towers transmit radiation continuously without any interruption, so people living within 100s of meters from the tower receive 10,000 to 10,000,000 times stronger signal than required for mobile communication. In the present study, we have examined superoxide dismutase (SOD) enzyme activity, catalase (CAT) enzyme activity, lipid peroxidation assay, and effect of functional polymorphism of SOD and CAT antioxidant genes against mobile tower-induced oxidative stress in human population. From our results, we have found a significantly lower mean value of manganese superoxide dismutase (MnSOD) enzyme activity, catalase (CAT) enzyme activity, and a high value of lipid peroxidation assay in exposed as compared to control subjects. Polymorphisms in antioxidant MnSOD and CAT genes significantly contributed to its phenotype. In the current study, a significant association of genetic polymorphism of antioxidant genes with genetic damage has been observed in human population exposed to radiations emitted from mobile towers.

  2. Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population

    Directory of Open Access Journals (Sweden)

    Jaworek Thomas J

    2012-06-01

    Full Text Available Abstract Background Oculocutaneous albinism (OCA is caused by a group of genetically heterogeneous inherited defects that result in the loss of pigmentation in the eyes, skin and hair. Mutations in the TYR, OCA2, TYRP1 and SLC45A2 genes have been shown to cause isolated OCA. No comprehensive analysis has been conducted to study the spectrum of OCA alleles prevailing in Pakistani albino populations. Methods We enrolled 40 large Pakistani families and screened them for OCA genes and a candidate gene, SLC24A5. Protein function effects were evaluated using in silico prediction algorithms and ex vivo studies in human melanocytes. The effects of splice-site mutations were determined using an exon-trapping assay. Results Screening of the TYR gene revealed four known (p.Arg299His, p.Pro406Leu, p.Gly419Arg, p.Arg278* and three novel mutations (p.Pro21Leu, p.Cys35Arg, p.Tyr411His in ten families. Ex vivo studies revealed the retention of an EGFP-tagged mutant (p.Pro21Leu, p.Cys35Arg or p.Tyr411His tyrosinase in the endoplasmic reticulum (ER at 37°C, but a significant fraction of p.Cys35Arg and p.Tyr411His left the ER in cells grown at a permissive temperature (31°C. Three novel (p.Asp486Tyr, p.Leu527Arg, c.1045-15 T > G and two known mutations (p.Pro743Leu, p.Ala787Thr of OCA2 were found in fourteen families. Exon-trapping assays with a construct containing a novel c.1045-15 T > G mutation revealed an error in splicing. No mutation in TYRP1, SLC45A2, and SLC24A5 was found in the remaining 16 families. Clinical evaluation of the families segregating either TYR or OCA2 mutations showed nystagmus, photophobia, and loss of pigmentation in the skin or hair follicles. Most of the affected individuals had grayish-blue colored eyes. Conclusions Our results show that ten and fourteen families harbored mutations in the TYR and OCA2 genes, respectively. Our findings, along with the results of previous studies, indicate that the p.Cys35Arg, p.Arg278

  3. No association of CpG island methylator phenotype and colorectal cancer survival: population-based study.

    Science.gov (United States)

    Jia, Min; Jansen, Lina; Walter, Viola; Tagscherer, Katrin; Roth, Wilfried; Herpel, Esther; Kloor, Matthias; Bläker, Hendrik; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael

    2016-11-22

    Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment. The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010. Detailed information were obtained from standardised personal interviews and medical records. During follow-up (median: 4.9 years), we assessed vital status, cause of death and therapy details. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of survival after CRC. The CIMP-H occurred more frequently in patients with older age, female gender, cancer in the proximal colon, BRAF mutation and microsatellite instability-high (MSI-H). However, CIMP status was not associated with CRC prognosis in CRC patients (HR=1.00; 95% CI=0.72-1.40 for overall survival; HR=0.96; 95% CI=0.65-1.41 for disease-specific survival) or in any of the subgroups. Although CIMP status was associated with the presence of MSI-H and BRAF mutation, the prognostic effects of MSI-H (HR=0.49; 95% CI=0.27-0.90) and BRAF mutation (HR=1.78; 95% CI=1.10-2.84) were independent of CIMP status. Similar benefit of chemotherapy was found for CRC outcomes in both the CIMP-low/negative group and the CIMP-high group. CpG island methylator phenotype was not associated with CRC prognosis after adjusting for other important clinical factors and associated mutations.

  4. Psychosis as a transdiagnostic and extended phenotype in the general population

    Science.gov (United States)

    van Os, Jim; Reininghaus, Uli

    2016-01-01

    A large body of research indicates that weak expressions of positive psychotic symptoms (“psychotic experiences”) can be measured in the general population, and likely represent the behavioural manifestation of distributed multifactorial (genetic and non‐genetic) risk for psychosis. Psychotic experiences are a transdiagnostic phenomenon: the majority of individuals with these experiences have a diagnosis of non‐psychotic disorder, particularly common mental disorder, in which psychotic experiences predict greater illness severity and poorer treatment response. Some of the people with common mental disorder and psychotic experiences will present to mental health services meeting criteria for “clinical high risk”. Treatment of the transdiagnostic dimension of psychosis in individuals with common mental disorder who meet “clinical high risk” criteria thus may improve outcome (which cannot be interpreted as prevention of “schizophrenia”). Subthreshold psychotic experiences are transitory in about 80% of individuals, while around 20% go on to develop persistent psychotic experiences and 7% a psychotic disorder, with an annual transition rate of 0.5‐1%. Persistence is associated, on the one hand, with environmental exposures, particularly childhood trauma, and, on the other, with network‐type dynamic interactions between psychotic experiences themselves (e.g., interactions between hallucinatory experiences and delusional ideation) and between symptom dimensions (e.g., interactions between affective symptoms and psychotic experiences, or interactions between subthreshold negative symptoms and psychotic experiences). The study of psychotic experiences is helping to elucidate the mechanisms by which environmental and genetic influences shape the transdiagnostic expression of psychosis proneness, that is mostly transitory but may first become persistent over time and eventually give rise to transition to a psychotic disorder. PMID:27265696

  5. Identification of cancer stem-like side population cells in purified primary cultured human laryngeal squamous cell carcinoma epithelia.

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    Chun-Ping Wu

    Full Text Available Cancer stem-like side population (SP cells have been identified in many solid tumors; however, most of these investigations are performed using established cancer cell lines. Cancer cells in tumor tissue containing fibroblasts and many other types of cells are much more complex than any cancer cell line. Although SP cells were identified in the laryngeal squamous cell carcinoma (LSCC cell line Hep-2 in our pilot study, it is unknown whether the LSCC tissue contains SP cells. In this study, LSCC cells (LSCCs were primary cultured and purified from a surgically resected LSCC specimen derived from a well-differentiated epiglottic neoplasm of a Chinese male. This was followed by the verification of epithelium-specific characteristics, such as ultrastructure and biomarkers. A distinct SP subpopulation (4.45±1.07% was isolated by Hoechst 33342 efflux analysis from cultured LSCCs by using a flow cytometer. Cancer stem cell (CSC-associated assays, including expression of self-renewal and CSC marker genes, proliferation, differentiation, spheroid formation, chemotherapy resistance, and tumorigenicity were then conducted between SP and non-SP (NSP LSCCs. In vitro and in vivo assays revealed that SP cells manifested preferential expression of self-renewal and CSC marker genes, higher capacity for proliferation, differentiation, and spheroid formation; enhanced resistance to chemotherapy; and greater xenograft tumorigenicity in immunodeficient mice compared with NSP cells. These findings suggest that the primary cultured and purified LSCCs contain cancer stem-like SP cells, which may serve as a valuable model for CSC research in LSCC.

  6. The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk Prospective Population Study

    Science.gov (United States)

    Arsenault, Benoit J.; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J.; Kastelein, John J.P.; Khaw, Kay-Tee; Boekholdt, S. Matthijs

    2010-01-01

    Background Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals. Methods A total of 21 787 participants aged 45–79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women. Results Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic-waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02–2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20–4.62) compared with women who did not have the phenotype. Interpretation Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic-waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery disease. PMID:20643837

  7. Assessing the value of phenotypic information from non-genotyped animals for QTL mapping of complex traits in real and simulated populations.

    Science.gov (United States)

    Melo, Thaise P; Takada, Luciana; Baldi, Fernando; Oliveira, Henrique N; Dias, Marina M; Neves, Haroldo H R; Schenkel, Flavio S; Albuquerque, Lucia G; Carvalheiro, Roberto

    2016-06-21

    QTL mapping through genome-wide association studies (GWAS) is challenging, especially in the case of low heritability complex traits and when few animals possess genotypic and phenotypic information. When most of the phenotypic information is from non-genotyped animals, GWAS can be performed using the weighted single-step GBLUP (WssGBLUP) method, which permits to combine all available information, even that of non-genotyped animals. However, it is not clear to what extent phenotypic information from non-genotyped animals increases the power of QTL detection, and whether factors such as the extent of linkage disequilibrium (LD) in the population and weighting SNPs in WssGBLUP affect the importance of using information from non-genotyped animals in GWAS. These questions were investigated in this study using real and simulated data. Analysis of real data showed that the use of phenotypes of non-genotyped animals affected SNP effect estimates and, consequently, QTL mapping. Despite some coincidence, the most important genomic regions identified by the analyses, either using or ignoring phenotypes of non-genotyped animals, were not the same. The simulation results indicated that the inclusion of all available phenotypic information, even that of non-genotyped animals, tends to improve QTL detection for low heritability complex traits. For populations with low levels of LD, this trend of improvement was less pronounced. Stronger shrinkage on SNPs explaining lower variance was not necessarily associated with better QTL mapping. The use of phenotypic information from non-genotyped animals in GWAS may improve the ability to detect QTL for low heritability complex traits, especially in populations in which the level of LD is high.

  8. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer.

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    Singh, Sandeep; Trevino, Jose; Bora-Singhal, Namrata; Coppola, Domenico; Haura, Eric; Altiok, Soner; Chellappan, Srikumar P

    2012-09-25

    Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs), Hoechst 33342 dye effluxing side population (SP) cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549), as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of stem-like cells from NSCLC. Therefore, the outcome of the

  9. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer

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    Singh Sandeep

    2012-09-01

    Full Text Available Abstract Background Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs, Hoechst 33342 dye effluxing side population (SP cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. Results SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549, as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Conclusions Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of

  10. Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

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    Unwin, Nigel; Howitt, Christina; Rose, Angela Mc; Samuels, T Alafia; Hennis, Anselm Jm; Hambleton, Ian R

    2017-12-01

    Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. A representative population-based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population.

  11. Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study.

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    Sheehan, Rory; Horsfall, Laura; Strydom, André; Osborn, David; Walters, Kate; Hassiotis, Angela

    2017-08-03

    To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. Cohort study using data from The Health Improvement Network. UK primary care. Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, pmovement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Prevalence and clinical characteristics of metabolically healthy obese individuals and other obese/non-obese metabolic phenotypes in a working population: results from the Icaria study

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    Albert Goday

    2016-04-01

    Full Text Available Abstract Background Metabolically healthy obese (MHO phenotype may present with distinct characteristics compared with those with a metabolically unhealthy obese phenotype. Epidemiologic data on the distribution of these conditions in the working population are lacking. We aimed to evaluate the prevalence and clinical characteristics of MHO and other obese/non-obese metabolic phenotypes in a working population. Methods Cross-sectional analysis of all subjects who had undergone a medical examination with Ibermutuamur Prevention Society from May 2004 to December 2007. Participants were classified into 5 categories according to their body mass index (BMI; within each of these categories, participants were further classified as metabolically healthy (MH or metabolically unhealthy (MUH according to the modified NCEP-ATPIII criteria. A logistic regression analysis was performed to evaluate some clinically relevant factors associated with a MH status. Results In the overall population, the prevalence of the MHO phenotype was 8.6 %. The proportions of MH individuals in the overweight and obese categories were: 87.1 % (overweight and 55.5 % (obese I-III [58.8, 40.0, and 38.7 % of the obese I, II, and III categories, respectively]. When the overweight and obese categories were considered, compared with individuals who were MUH, those who were MH tended to be younger and more likely to be female or participate in physical exercise; they were also less likely to smoke, or to be a heavy drinker. In the underweight and normal weight categories, compared with individuals who were MH, those who were MUH were more likely to be older, male, manual (blue collar workers, smokers and heavy drinkers. Among participants in the MUH, normal weight group, the proportion of individuals with a sedentary lifestyle was higher relative to those in the MH, normal weight group. The factors more strongly associated with the MUH phenotype were BMI and age, followed by the

  13. Side Effects

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    Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

  14. Evolution and ecology meet molecular genetics: adaptive phenotypic plasticity in two isolated Negev desert populations of Acacia raddiana at either end of a rainfall gradient

    Science.gov (United States)

    Ward, David; Shrestha, Madan K.; Golan-Goldhirsh, Avi

    2012-01-01

    Background and Aims The ecological, evolutionary and genetic bases of population differentiation in a variable environment are often related to the selection pressures that plants experience. We compared differences in several growth- and defence-related traits in two isolated populations of Acacia raddiana trees from sites at either end of an extreme environmental gradient in the Negev desert. Methods We used random amplified polymorphic DNA (RAPD) to determine the molecular differences between populations. We grew plants under two levels of water, three levels of nutrients and three levels of herbivory to test for phenotypic plasticity and adaptive phenotypic plasticity. Key Results The RAPD analyses showed that these populations are highly genetically differentiated. Phenotypic plasticity in various morphological traits in A. raddiana was related to patterns of population genetic differentiation between the two study sites. Although we did not test for maternal effects in these long-lived trees, significant genotype × environment (G × E) interactions in some of these traits indicated that such plasticity may be adaptive. Conclusions The main selection pressure in this desert environment, perhaps unsurprisingly, is water. Increased water availability resulted in greater growth in the southern population, which normally receives far less rain than the northern population. Even under the conditions that we defined as low water and/or nutrients, the performance of the seedlings from the southern population was significantly better, perhaps reflecting selection for these traits. Consistent with previous studies of this genus, there was no evidence of trade-offs between physical and chemical defences and plant growth parameters in this study. Rather, there appeared to be positive correlations between plant size and defence parameters. The great variation in several traits in both populations may result in a diverse potential for responding to selection pressures in

  15. Haptoglobin phenotype, preeclampsia risk and the efficacy of vitamin C and E supplementation to prevent preeclampsia in a racially diverse population.

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    Tracey L Weissgerber

    Full Text Available Haptoglobin's (Hp antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH. This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393 and a case-control cohort (703 cases, 1,406 controls. The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01 in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia.

  16. Phenotypic evaluation of the resistance in F1 carnation populations to vascular wilt caused by Fusarium oxysporum f.sp. dianthi

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    Johana Carolina Soto-Sedano

    2012-08-01

    Full Text Available One of the most important phytosanitary problems of the carnation crops in Colombia and in the entire world is vascular wilting produced by Fusarium oxysporum f.sp. dianthi. Currently, an effective treatment against the pathogen does not exist; the search for resistant varieties has been the most successful method for control of this disease. Breeding programs are vital to solving the problem of the carnation fusariosis. The objective of this research was the phenotypic evaluation of carnation F1 populations, products of contrasting crossing, resistant per susceptible to F. oxysporum f.sp. dianthi, in order to determine if the resistance is inherited in the lines. This information will contribute to the selection of material and to the successful introduction of the resistant characteristic, whose expression is commercially acceptable, to the gene pool. The methodology adopted was a phenotypic evaluation of the response to the parasite in the population (450 individuals and in the parental. This evaluation estimated the area under the curve (AU DPC, using a scale of symptoms reported for carnation vascular wilt. Three different phenotypes were established with this evaluation. The moderately susceptible one is the predominant phenotype and an analysis of phenotypic frequencies was carried out on it. The results show that the individuals of the evaluated F1 population were distributed between two extreme ranges, resistant and susceptible; this shows that there is segregation for the trait resistant to F. oxysporum f.sp dianthi. We did not observe clearly differentiated classes, i.e. with complete absence or presence of the disease, indicating a possible control of the resistance in the evaluated carnation material, governed by more than one gene and with a possible additive genetic action

  17. Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population

    DEFF Research Database (Denmark)

    Nissen, Peter H; Christensen, Signe E; Heickendorff, Lene

    2007-01-01

    CONTEXT: The autosomal dominantly inherited condition familial hypocalciuric hypercalcemia (FHH) is characterized by elevated plasma calcium levels, relative or absolute hypocalciuria, and normal to moderately elevated plasma PTH. The condition is difficult to distinguish clinically from primary...... hyperparathyroidism and is caused by inactivating mutations in the calcium sensing receptor (CASR) gene. OBJECTIVE: We sought to define the mutation spectrum of the CASR gene in a Danish FHH population and to establish genotype-phenotype relationships regarding the different mutations. DESIGN AND PARTICIPANTS...

  18. The marine side of a terrestrial carnivore: intra-population variation in use of allochthonous resources by arctic foxes.

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    Arnaud Tarroux

    Full Text Available Inter-individual variation in diet within generalist animal populations is thought to be a widespread phenomenon but its potential causes are poorly known. Inter-individual variation can be amplified by the availability and use of allochthonous resources, i.e., resources coming from spatially distinct ecosystems. Using a wild population of arctic fox as a study model, we tested hypotheses that could explain variation in both population and individual isotopic niches, used here as proxy for the trophic niche. The arctic fox is an opportunistic forager, dwelling in terrestrial and marine environments characterized by strong spatial (arctic-nesting birds and temporal (cyclic lemmings fluctuations in resource abundance. First, we tested the hypothesis that generalist foraging habits, in association with temporal variation in prey accessibility, should induce temporal changes in isotopic niche width and diet. Second, we investigated whether within-population variation in the isotopic niche could be explained by individual characteristics (sex and breeding status and environmental factors (spatiotemporal variation in prey availability. We addressed these questions using isotopic analysis and bayesian mixing models in conjunction with linear mixed-effects models. We found that: i arctic fox populations can simultaneously undergo short-term (i.e., within a few months reduction in both isotopic niche width and inter-individual variability in isotopic ratios, ii individual isotopic ratios were higher and more representative of a marine-based diet for non-breeding than breeding foxes early in spring, and iii lemming population cycles did not appear to directly influence the diet of individual foxes after taking their breeding status into account. However, lemming abundance was correlated to proportion of breeding foxes, and could thus indirectly affect the diet at the population scale.

  19. Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey.

    Science.gov (United States)

    Li, Jiang; Xiao, Cheng; Yang, Hui; Zhou, Yun; Wang, Rui; Cao, Yongtong

    2017-12-09

    Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.

  20. Crickets are not a free lunch: protein capture from scalable organic side-streams via high-density populations of Acheta domesticus.

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    Mark E Lundy

    Full Text Available It has been suggested that the ecological impact of crickets as a source of dietary protein is less than conventional forms of livestock due to their comparatively efficient feed conversion and ability to consume organic side-streams. This study measured the biomass output and feed conversion ratios of house crickets (Acheta domesticus reared on diets that varied in quality, ranging from grain-based to highly cellulosic diets. The measurements were made at a much greater population scale and density than any previously reported in the scientific literature. The biomass accumulation was strongly influenced by the quality of the diet (p99% mortality without reaching a harvestable size. Therefore, the potential for A. domesticus to sustainably supplement the global protein supply, beyond what is currently produced via grain-fed chickens, will depend on capturing regionally scalable organic side-streams of relatively high-quality that are not currently being used for livestock production.

  1. Studying the Genetics of Complex Disease With Ancestry-Specific Human Phenotype Networks: The Case of Type 2 Diabetes in East Asian Populations.

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    Qiu, Jingya; Moore, Jason H; Darabos, Christian

    2016-05-01

    Genome-wide association studies (GWAS) have led to the discovery of over 200 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM). Additionally, East Asians develop T2DM at a higher rate, younger age, and lower body mass index than their European ancestry counterparts. The reason behind this occurrence remains elusive. With comprehensive searches through the National Human Genome Research Institute (NHGRI) GWAS catalog literature, we compiled a database of 2,800 ancestry-specific SNPs associated with T2DM and 70 other related traits. Manual data extraction was necessary because the GWAS catalog reports statistics such as odds ratio and P-value, but does not consistently include ancestry information. Currently, many statistics are derived by combining initial and replication samples from study populations of mixed ancestry. Analysis of all-inclusive data can be misleading, as not all SNPs are transferable across diverse populations. We used ancestry data to construct ancestry-specific human phenotype networks (HPN) centered on T2DM. Quantitative and visual analysis of network models reveal the genetic disparities between ancestry groups. Of the 27 phenotypes in the East Asian HPN, six phenotypes were unique to the network, revealing the underlying ancestry-specific nature of some SNPs associated with T2DM. We studied the relationship between T2DM and five phenotypes unique to the East Asian HPN to generate new interaction hypotheses in a clinical context. The genetic differences found in our ancestry-specific HPNs suggest different pathways are involved in the pathogenesis of T2DM among different populations. Our study underlines the importance of ancestry in the development of T2DM and its implications in pharmocogenetics and personalized medicine. © 2016 The Authors. *Genetic Epidemiology Published by Wiley Periodicals, Inc.

  2. Conventional and right-sided screening for subcutaneous ICD in a population with congenital heart disease at high risk of sudden cardiac death.

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    Alonso, Pau; Osca, Joaquín; Rueda, Joaquín; Cano, Oscar; Pimenta, Pedro; Andres, Ana; Sancho, María José; Martinez, Luis

    2017-11-01

    Information regarding suitability for subcutaneous defibrillator (sICD) implantation in tetralogy of Fallot (ToF) and systemic right ventricle is scarce and needs to be further explored. The main objective of our study was to determine the proportion of patients with ToF and systemic right ventricle eligible for sICD with both, standard and right-sided screening methods. Secondary objectives were: (i) to study sICD eligibility specifically in patients at high risk of sudden cardiac death, (ii) to identify independent predictors for sICD eligibility, and (iii) to compare the proportion of eligible patients in a nonselected ICD population. We recruited 102 patients with ToF, 33 with systemic right ventricle, and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left-arm and right-arm electrodes 1 cm right lateral of the xiphoid midline. The Boston Scientific ECG screening tool was utilized. In high-risk patients with ToF, eligibility was higher with right-sided screening in comparison with standard screening (61% vs. 44%; p = .018). Eligibility in high-risk right ventricle population was identical with both screening methods (77%, p = ns). The only independent predictor for sICD eligibility was QRS duration. In high-risk patients with ToF, right-sided implantation of the sICD could be an alternative to a conventional ICD. In patients with a systemic right ventricle, implantation of a sICD is an alternative to a conventional sICD. © 2017 Wiley Periodicals, Inc.

  3. Maintenance of phenotypic variation: repeatibility, heritability, and size-dependent processes in a wild brook trout population

    Science.gov (United States)

    Benjamin H. Letcher; Jason A Coombs; Keith H. Nislow

    2011-01-01

    Phenotypic variation in body size can result from within-cohort variation in birth dates, among-individual growth variation and size-selective processes. We explore the relative effects of these processes on the maintenance of wide observed body size variation in stream-dwelling brook trout (Salvelinus fontinalis). Based on the analyses of multiple...

  4. Endometrial Cancer Side-Population Cells Show Prominent Migration and Have a Potential to Differentiate into the Mesenchymal Cell Lineage

    Science.gov (United States)

    Kato, Kiyoko; Takao, Tomoka; Kuboyama, Ayumi; Tanaka, Yoshihiro; Ohgami, Tatsuhiro; Yamaguchi, Shinichiro; Adachi, Sawako; Yoneda, Tomoko; Ueoka, Yousuke; Kato, Keiji; Hayashi, Shinichi; Asanoma, Kazuo; Wake, Norio

    2010-01-01

    Cancer stem-like cell subpopulations, referred to as “side-population” (SP) cells, have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Although SP cells have been identified in the normal human endometrium and endometrial cancer, little is known about their characteristics. In this study, we isolated and characterized the SP cells in human endometrial cancer cells and in rat endometrial cells expressing oncogenic human K-Ras protein. These SP cells showed i) reduction in the expression levels of differentiation markers; ii) long-term proliferative capacity of the cell cultures; iii) self-renewal capacity in vitro; iv) enhancement of migration, lamellipodia, and, uropodia formation; and v) enhanced tumorigenicity. In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor cells and stromal-like cells with enriched extracellular matrix. The expression levels of vimentin, α-smooth muscle actin, and collagen III were enhanced in SP tumors compared with the levels in non-SP tumors. In addition, analysis of microdissected samples and fluorescence in situ hybridization of Hec1-SP-tumors showed that the stromal-like cells with enriched extracellular matrix contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. Moreober, in a Matrigel assay, SP cells differentiated into α-smooth muscle actin-expressing cells. These findings demonstrate that SP cells have cancer stem-like cell features, including the potential to differentiate into the mesenchymal cell lineage. PMID:20008133

  5. Interleukin-6 Receptor rs7529229 T/C Polymorphism Is Associated with Left Main Coronary Artery Disease Phenotype in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Feng He

    2014-04-01

    Full Text Available Left main coronary artery disease (LMCAD is a particular severe phenotype of coronary artery disease (CAD and heritability. Interleukin (IL may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD. In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS and ligation detection reaction (LDR method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR = 1.46, 95% confidence interval (CI = 1.02–2.11, p = 0.042; CC + TC vs. TT, adjusted OR = 1.31, 95% CI = 1.02–1.69, p = 0.037. None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed.

  6. Do recognizable lifetime eating disorder phenotypes naturally occur in a culturally asian population? A combined latent profile and taxometric approach.

    Science.gov (United States)

    Thomas, Jennifer J; Eddy, Kamryn T; Ruscio, John; Ng, King Lam; Casale, Kristen E; Becker, Anne E; Lee, Sing

    2015-05-01

    We examined whether empirically derived eating disorder (ED) categories in Hong Kong Chinese patients (N = 454) would be consistent with recognizable lifetime ED phenotypes derived from latent structure models of European and American samples. We performed latent profile analysis (LPA) using indicator variables from data collected during routine assessment, and then applied taxometric analysis to determine whether latent classes were qualitatively versus quantitatively distinct. Latent profile analysis identified four classes: (i) binge/purge (47%); (ii) non-fat-phobic low-weight (34%); (iii) fat-phobic low-weight (12%); and (iv) overweight disordered eating (6%). Taxometric analysis identified qualitative (categorical) distinctions between the binge/purge and non-fat-phobic low-weight classes, and also between the fat-phobic and non-fat-phobic low-weight classes. Distinctions between the fat-phobic low-weight and binge/purge classes were indeterminate. Empirically derived categories in Hong Kong showed recognizable correspondence with recognizable lifetime ED phenotypes. Although taxometric findings support two distinct classes of low weight EDs, LPA findings also support heterogeneity among non-fat-phobic individuals. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  7. Biochemical fingerprinting of water coliform bacteria, a new method for measuring phenotypic diversity and for comparing different bacterial populations.

    Science.gov (United States)

    Kühn, I; Allestam, G; Stenström, T A; Möllby, R

    1991-01-01

    A simple, automated microplate system for biochemical characterization of water isolates can be used to obtain fingerprints of the bacterial flora from various water samples. Mathematical models for calculating the diversities and similarities between bacterial populations are described for such fingerprints. The diversity may give information on whether an indigenous or allochthonous flora is present, and the similarities between bacterial populations, as calculated by using a population similarity coefficient (Sp), may indicate contaminations between different water samples. The system was demonstrated on coliform bacterial populations from various water samples, with or without suspected intercontamination. For unrelated water samples, the Sps were close to 0, whereas repeated samples of the same source showed Sps of 0.64 to 0.74. The Sp values from several water samples were also clustered to form a dendrogram, thus indicating the relative similarities between the bacterial populations to confirm suspected common sources of pollution. PMID:1781680

  8. Positive health effects of the natural outdoor environment in typical populations in different regions in Europe (PHENOTYPE): a study programme protocol.

    Science.gov (United States)

    Nieuwenhuijsen, Mark J; Kruize, Hanneke; Gidlow, Christopher; Andrusaityte, Sandra; Antó, Josep Maria; Basagaña, Xavier; Cirach, Marta; Dadvand, Payam; Danileviciute, Asta; Donaire-Gonzalez, David; Garcia, Judith; Jerrett, Michael; Jones, Marc; Julvez, Jordi; van Kempen, Elise; van Kamp, Irene; Maas, Jolanda; Seto, Edmund; Smith, Graham; Triguero, Margarita; Wendel-Vos, Wanda; Wright, John; Zufferey, Joris; van den Hazel, Peter Jan; Lawrence, Roderick; Grazuleviciene, Regina

    2014-04-16

    Growing evidence suggests that close contact with nature brings benefits to human health and well-being, but the proposed mechanisms are still not well understood and the associations with health remain uncertain. The Positive Health Effects of the Natural Outdoor environment in Typical Populations in different regions in Europe (PHENOTYPE) project investigates the interconnections between natural outdoor environments and better human health and well-being. The PHENOTYPE project explores the proposed underlying mechanisms at work (stress reduction/restorative function, physical activity, social interaction, exposure to environmental hazards) and examines the associations with health outcomes for different population groups. It implements conventional and new innovative high-tech methods to characterise the natural environment in terms of quality and quantity. Preventive as well as therapeutic effects of contact with the natural environment are being covered. PHENOTYPE further addresses implications for land-use planning and green space management. The main innovative part of the study is the evaluation of possible short-term and long-term associations of green space and health and the possible underlying mechanisms in four different countries (each with quite a different type of green space and a different use), using the same methodology, in one research programme. This type of holistic approach has not been undertaken before. Furthermore there are technological innovations such as the use of remote sensing and smartphones in the assessment of green space. The project will produce a more robust evidence base on links between exposure to natural outdoor environment and human health and well-being, in addition to a better integration of human health needs into land-use planning and green space management in rural as well as urban areas.

  9. Cognitive-behavioral phenotypes of Williams syndrome are associated with genetic variation in the GTF2I gene, in a healthy population.

    Science.gov (United States)

    Crespi, Bernard J; Hurd, Peter L

    2014-11-28

    Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated. We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies. These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.

  10. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K., E-mail: mishima-k@dent.showa-u.ac.jp

    2013-05-01

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.

  11. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K.

    2013-01-01

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities

  12. Neutral Evolution in a Biological Population as Diffusion in Phenotype Space: Reproduction with Local Mutation but without Selection

    Science.gov (United States)

    Lawson, Daniel John; Jensen, Henrik Jeldtoft

    2007-03-01

    The process of “evolutionary diffusion,” i.e., reproduction with local mutation but without selection in a biological population, resembles standard diffusion in many ways. However, evolutionary diffusion allows the formation of localized peaks that undergo drift, even in the infinite population limit. We relate a microscopic evolution model to a stochastic model which we solve fully. This allows us to understand the large population limit, relates evolution to diffusion, and shows that independent local mutations act as a diffusion of interacting particles taking larger steps.

  13. Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations.

    Science.gov (United States)

    DeStefano, A L; Cupples, L A; Arnos, K S; Asher, J H; Baldwin, C T; Blanton, S; Carey, M L; da Silva, E O; Friedman, T B; Greenberg, J; Lalwani, A K; Milunsky, A; Nance, W E; Pandya, A; Ramesar, R S; Read, A P; Tassabejhi, M; Wilcox, E R; Farrer, L A

    1998-05-01

    Waardenburg syndrome (WS) type 1 is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary abnormalities of the eye, hair, and skin, and dystopia canthorum. The phenotype is variable and affected individuals may exhibit only one or a combination of several of the associated features. To assess the relationship between phenotype and gene defect, clinical and genotype data on 48 families (271 WS individuals) collected by members of the Waardenburg Consortium were pooled. Forty-two unique mutations in the PAX3 gene, previously identified in these families, were grouped in five mutation categories: amino acid (AA) substitution in the paired domain, AA substitution in the homeodomain, deletion of the Ser-Thr-Pro-rich region, deletion of the homeodomain and the Ser-Thr-Pro-rich region, and deletion of the entire gene. These mutation classes are based on the structure of the PAX3 gene and were chosen to group mutations predicted to have similar defects in the gene product. Association between mutation class and the presence of hearing loss, eye pigment abnormality, skin hypopigmentation, or white forelock was evaluated using generalized estimating equations, which allowed for incorporation of a correlation structure that accounts for potential similarity among members of the same family. Odds for the presence of eye pigment abnormality, white forelock, and skin hypopigmentation were 2, 8, and 5 times greater, respectively, for individuals with deletions of the homeodomain and the Pro-Ser-Thr-rich region compared to individuals with an AA substitution in the homeodomain. Odds ratios that differ significantly from 1.0 for these traits may indicate that the gene products resulting from different classes of mutations act differently in the expression of WS. Although a suggestive association was detected for hearing loss with an odds ratio of 2.6 for AA substitution in the paired domain compared with AA substitution in the homeodomain, this odds

  14. Analysis of the genetic relationships and diversity among 11 populations of Xanthoceras sorbifolia using phenotypic and microsatellite marker data

    Directory of Open Access Journals (Sweden)

    Zhan Shen

    2017-03-01

    Conclusions: Microsatellite markers can be used to efficiently distinguish X. sorbifolia populations and assess their genetic diversity. The information we have provided will contribute to the conservation and management of this important plant genetic resource.

  15. Linking individual phenotype to density-dependent population growth: the influence of body size on the population dynamics of malaria vectors

    NARCIS (Netherlands)

    Russell, T.L.; Lwetoijera, D.W.; Knols, B.G.J.; Takken, W.; Killeen, G.F.; Ferguson, H.M.

    2011-01-01

    Understanding the endogenous factors that drive the population dynamics of malaria mosquitoes will facilitate more accurate predictions about vector control effectiveness and our ability to destabilize the growth of either low- or high-density insect populations. We assessed whether variation in

  16. Linking individual phenotype to density-dependent population growth: the influence of body size on the population dynamics of malaria vectors

    NARCIS (Netherlands)

    Russell, T.L.; Lwetoijera, D.W.; Knols, B.G.J.; Takken, W.; Killeen, G.F.; Ferguson, H.M.

    2011-01-01

    Understanding the endogenous factors that drive the population dynamics of malaria mosquitoes will facilitate more accurate predictions about vector control effectiveness and our ability to destabilize the growth of either low-or high-density insect populations. We assessed whether variation in

  17. Genetic Diversity and Phenotypic Variation in an Introgression Line Population Derived from an Interspecific Cross between Oryza glaberrima and Oryza sativa.

    Directory of Open Access Journals (Sweden)

    Caijin Chen

    Full Text Available The introduction of closely related species genomic fragments is an effective way to enrich genetic diversity and creates new germplasms in crops. Here, we studied the genetic diversity of an introgression line (IL population composed of 106 ILs derived from an interspecific tetra cross between O. glaberrima and O. sativa (RAM3/Jin23B//Jin23B///YuetaiB. The proportion of O. glaberrima genome (PGG in the ILs ranged from 0.3% to 36.7%, with an average value of 12.32% which is close to the theoretically expected proportion. A total of 250 polymorphic alleles were amplified by 21 AFLP primer combinations with an average of 12 alleles per primer. Population structure analysis revealed that the IL population can be divided into four genetically distinct subpopulations. Both principal component analysis and neighbor-joining tree analysis showed that ILs with a higher PGG displayed greater genetic diversity. Canonical discriminant analysis identified six phenotypic traits (plant height, yield per plant, filled grain percentage, panicle length, panicle number and days to flowering as the main discriminatory traits among the ILs and between the subpopulations and showed significant phenotypic distances between subpopulations. The effects of PGG on phenotypic traits in the ILs were estimated using a linear admixed model, which showed a significant positive effect on grain yield per plant (0.286±0.117, plant height (0.418 ± 0.132, panicle length (0.663 ± 0.107, and spikelet number per panicle (0.339 ± 0.128, and a significant negative effect on filled grain percentage (-0.267 ± 0.123 and days to flowering (-0.324 ± 0.075. We found that an intermediate range (10% - 20% of PGG was more effective for producing ILs with favorable integrated agronomic traits. Our results confirm that construction of IL population carrying O. glaberrima genomic fragments could be an effective approach to increase the genetic diversity of O. sativa genome and an appropriate

  18. Assessment of host-associated genetic differentiation among phenotypically divergent populations of a coral-eating gastropod across the Caribbean.

    Directory of Open Access Journals (Sweden)

    Lyza Johnston

    Full Text Available Host-associated adaptation is emerging as a potential driver of population differentiation and speciation for marine organisms with major implications for ecosystem structure and function. Coralliophila abbreviata are corallivorous gastropods that live and feed on most of the reef-building corals in the tropical western Atlantic and Caribbean. Populations of C. abbreviata associated with the threatened acroporid corals, Acropora palmata and A. cervicornis, display different behavioral, morphological, demographic, and life-history characteristics than those that inhabit other coral host taxa, indicating that host-specific selective forces may be acting on C. abbreviata. Here, we used newly developed polymorphic microsatellite loci and mitochondrial cytochrome b sequence data to assess the population genetic structure, connectivity, and demographic history of C. abbreviata populations from three coral host taxa (A. palmata, Montastraea spp., Mycetophyllia spp. and six geographic locations across the Caribbean. Analysis of molecular variance provided some evidence of weak and possibly geographically variable host-associated differentiation but no evidence of differentiation among sampling locations or major oceanographic regions, suggesting high gene flow across the Caribbean. Phylogenetic network and bayesian clustering analyses supported a hypothesis of a single panmictic population as individuals failed to cluster by host or sampling location. Demographic analyses consistently supported a scenario of population expansion during the Pleistocene, a time of major carbonate reef development in the region. Although further study is needed to fully elucidate the interactive effects of host-associated selection and high gene flow in this system, our results have implications for local and regional community interactions and impact of predation on declining coral populations.

  19. Assessment of host-associated genetic differentiation among phenotypically divergent populations of a coral-eating gastropod across the Caribbean.

    Science.gov (United States)

    Johnston, Lyza; Miller, Margaret W; Baums, Iliana B

    2012-01-01

    Host-associated adaptation is emerging as a potential driver of population differentiation and speciation for marine organisms with major implications for ecosystem structure and function. Coralliophila abbreviata are corallivorous gastropods that live and feed on most of the reef-building corals in the tropical western Atlantic and Caribbean. Populations of C. abbreviata associated with the threatened acroporid corals, Acropora palmata and A. cervicornis, display different behavioral, morphological, demographic, and life-history characteristics than those that inhabit other coral host taxa, indicating that host-specific selective forces may be acting on C. abbreviata. Here, we used newly developed polymorphic microsatellite loci and mitochondrial cytochrome b sequence data to assess the population genetic structure, connectivity, and demographic history of C. abbreviata populations from three coral host taxa (A. palmata, Montastraea spp., Mycetophyllia spp.) and six geographic locations across the Caribbean. Analysis of molecular variance provided some evidence of weak and possibly geographically variable host-associated differentiation but no evidence of differentiation among sampling locations or major oceanographic regions, suggesting high gene flow across the Caribbean. Phylogenetic network and bayesian clustering analyses supported a hypothesis of a single panmictic population as individuals failed to cluster by host or sampling location. Demographic analyses consistently supported a scenario of population expansion during the Pleistocene, a time of major carbonate reef development in the region. Although further study is needed to fully elucidate the interactive effects of host-associated selection and high gene flow in this system, our results have implications for local and regional community interactions and impact of predation on declining coral populations.

  20. Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay.

    Directory of Open Access Journals (Sweden)

    Kaoru Miyazaki

    Full Text Available Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP, but not endometrial main population cells (EMP, exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay.ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom, a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells.We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo endometrial tissue reconstitution. Using this assay, we demonstrated that ESP

  1. Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample.

    Directory of Open Access Journals (Sweden)

    Katsuhiko Nosho

    Full Text Available The CpG island methylator phenotype (CIMP is a distinct phenotype associated with microsatellite instability (MSI and BRAF mutation in colon cancer. Recent investigations have selected 5 promoters (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 as surrogate markers for CIMP-high. However, no study has comprehensively evaluated an expanded set of methylation markers (including these 5 markers using a large number of tumors, or deciphered the complex clinical and molecular associations with CIMP-high determined by the validated marker panel. METHOLODOLOGY/PRINCIPAL FINDINGS: DNA methylation at 16 CpG islands [the above 5 plus CDKN2A (p16, CHFR, CRABP1, HIC1, IGFBP3, MGMT, MINT1, MINT31, MLH1, p14 (CDKN2A/ARF and WRN] was quantified in 904 colorectal cancers by real-time PCR (MethyLight. In unsupervised hierarchical clustering analysis, the 5 markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1, CDKN2A, CRABP1, MINT31, MLH1, p14 and WRN were generally clustered with each other and with MSI and BRAF mutation. KRAS mutation was not clustered with any methylation marker, suggesting its association with a random methylation pattern in CIMP-low tumors. Utilizing the validated CIMP marker panel (including the 5 markers, multivariate logistic regression demonstrated that CIMP-high was independently associated with older age, proximal location, poor differentiation, MSI-high, BRAF mutation, and inversely with LINE-1 hypomethylation and beta-catenin (CTNNB1 activation. Mucinous feature, signet ring cells, and p53-negativity were associated with CIMP-high in only univariate analysis. In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status.Our study provides valuable data for standardization of the use of CIMP-high-specific methylation markers. CIMP-high is independently associated with clinical and key molecular features in colorectal cancer. Our data also

  2. Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China

    OpenAIRE

    Jin, Tianbo; Yang, Hua; Zhang, Jiayi; Yunus, Zulfiya; Sun, Qiang; Geng, Tingting; Chen, Chao; Yang, Jie

    2015-01-01

    Purpose: Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions. Methods: The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5’UTR, promoters, exons, introns, and 3’UTR region of the whole CYP3A4 gene in 100 unrelated, healthy. Results: Twenty-one genetic polymorphisms ...

  3. The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

    DEFF Research Database (Denmark)

    Hansen, Pia Skov; van der Deure, Wendy M; Peeters, Robin P

    2007-01-01

    OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size...... between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84.......9%; Asp/Glu 14.5% and Glu/Glu 0.6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l, P = 0.04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0.007). The polymorphism accounted...

  4. Polymorphisms and phenotypic analysis of cytochrome P450 3A4 in the Uygur population in northwest China.

    Science.gov (United States)

    Jin, Tianbo; Yang, Hua; Zhang, Jiayi; Yunus, Zulfiya; Sun, Qiang; Geng, Tingting; Chen, Chao; Yang, Jie

    2015-01-01

    Genetic polymorphisms in CYP3A4 can change its activity to a certain degree, thus leading to differences among different populations in drug efficacy or adverse drug reactions. The study was intended to validate the genetic polymorphisms in CYP3A4 in Uygur Chinese population, we sequenced and screened for genetic variants including 5'UTR, promoters, exons, introns, and 3'UTR region of the whole CYP3A4 gene in 100 unrelated, healthy. Twenty-one genetic polymorphisms in CYP3A4, and nine of them were novel. We detected CYP3A4*8, a putative poor-metabolizer allele, with the frequency of 0.5% in Uygur population. Tfsitescan revealed that the density of transcription factor varied in the different promoter regions, among which some were key regions for transcription factor binding. our results provide basic information about CPY3A4 alleles in Uygur and suggest that the enzymatic activities of CPY3A4 may differ among the diverse ethnic populations of China.

  5. Regulation of voltage-gated potassium channels attenuates resistance of side-population cells to gefitinib in the human lung cancer cell line NCI-H460.

    Science.gov (United States)

    Choi, Seon Young; Kim, Hang-Rae; Ryu, Pan Dong; Lee, So Yeong

    2017-02-21

    Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux. In the present study, we found that mRNA expression of Kv channels in SP cells was different compared to Non-SP cells, and the resistance of SP cells to gefitinib was weakened with a combination treatment of gefitinib and Kv channel blockers or a Kv7 opener, compared to single-treatment gefitinib, through inhibition of the Ras-Raf signaling pathway. The findings indicate that Kv channels in SP cells could be new targets for reducing the resistance to gefitinib.

  6. The Impact of Marine Protected Areas on Reef-Wide Population Structure and Fishing-Induced Phenotypes in Coral-Reef Fishes

    Science.gov (United States)

    Fidler, Robert Young, III

    Overfishing and destructive fishing practices threaten the sustainability of fisheries worldwide. In addition to reducing population sizes, anthropogenic fishing effort is highly size-selective, preferentially removing the largest individuals from harvested stocks. Intensive, size-selective mortality induces widespread phenotypic shifts toward the predominance of smaller and earlier-maturing individuals. Fish that reach sexual maturity at smaller size and younger age produce fewer, smaller, and less viable larvae, severely reducing the reproductive capacity of exploited populations. These directional phenotypic alterations, collectively known as "fisheries-induced evolution" (FIE) are among the primary causes of the loss of harvestable fish biomass. Marine protected areas (MPAs) are one of the most widely utilized components of fisheries management programs around the world, and have been proposed as a potential mechanism by which the impacts of FIE may be mitigated. The ability of MPAs to buffer exploited populations against fishing pressure, however, remains debated due to inconsistent results across studies. Additionally, empirical evidence of phenotypic shifts in fishes within MPAs is lacking. This investigation addresses both of these issues by: (1) using a categorical meta-analysis of MPAs to standardize and quantify the magnitude of MPA impacts across studies; and (2) conducting a direct comparison of life-history phenotypes known to be influenced by FIE in six reef-fish species inside and outside of MPAs. The Philippines was used as a model system for analyses due to the country's significance in global marine biodiversity and reliance on MPAs as a fishery management tool. The quantitative impact of Philippine MPAs was assessed using a "reef-wide" meta-analysis. This analysis used pooled visual census data from 39 matched pairs of MPAs and fished reefs surveyed twice over a mean period of 3 years. In 17 of these MPAs, two additional surveys were conducted

  7. A population of human brain cells expressing phenotypic markers of more than one lineage can be induced in vitro to differentiate into mesenchymal cells

    International Nuclear Information System (INIS)

    Rieske, Piotr; Augelli, Brian J.; Stawski, Robert; Gaughan, John; Azizi, S. Ausim; Krynska, Barbara

    2009-01-01

    Proliferating astrocytic cells from germinal, as well as mature areas of brain parenchyma, have the characteristics of neural stem/progenitor cells and are capable of generating both neurons and glia. We previously reported that primary fetal human brain cells, designated as Normal Human Astrocytes (NHA), expressed, in addition to GFAP, Vimentin and Nestin, low levels of βIII-Tubulin, an early neuronal marker, and differentiated into neurons and astrocytes in vitro. Here, we showed that primary NHA cells co-express low levels of mesenchymal markers Fibronectin and Collagen-1 in culture. These cells transitioned into mesenchymal-like cells when cultured in adherent conditions in serum containing media. The mesenchymal-like derivatives of these cells were characterized based on their morphological changes, high expression of Vimentin and extracellular matrix (ECM) proteins, Collagen-1 and Fibronectin, and decline of neural markers. When incubated in osteogenic and adipogenic induction media, the mesenchymal-like cells differentiated into osteoblasts and adipocytes. Furthermore, NHA cells express markers of neural crest cells, SOX-10 and p75. These data support the idea of ectoderm-derived mesenchymal lineages. These findings suggest that a population of primitive fetal brain cells with neural/neural crest/mesenchymal phenotype, resembles the remarkable phenotypic plasticity of neural crest cells, and differentiates into adipocytes and osteocytes under the influence of environmental factors

  8. Mixed Phenotype Acute Leukemia with Two Immunophenotypically Distinct B and T Blasts Populations, Double Chromosome and Complex Karyotype: Report of an Unusual Case

    Directory of Open Access Journals (Sweden)

    Samah A. Kohla

    2015-01-01

    Full Text Available Mixed phenotype acute leukemia (MPAL is considered as a rare type of leukemia with an incidence of less than 4% of all acute leukemia based on the most recent 2008 WHO classification. Common subtypes are the B/myeloid and T/myeloid; B/T and trilineage MPAL being extremely rare. We present a case of a male in his 20s, whose peripheral blood smears showed 34% blast cells and bone marrow with 70% blasts. Immunophenotyping by multiparametric flow cytometry showed two populations of blasts, the major one with B-lineage and the minor one with T-lineage. Conventional karyotyping revealed complex karyotype with the presence of double Philadelphia chromosome ( Ph + . BCR/ABL1 rearrangement was confirmed by fluorescent in situ hybridization (FISH analysis. The BCR/ABL1 ES probe on interphase cells indicated pl90 minor m-BCR/ABL fusion in 46% and a second abnormal clone with double Ph + in 16% of the cells analyzed confirmed by reverse transcription-PCR (RT-PCR. The case was diagnosed as MPAL with double Philadelphia chromosome Ph + . The patient was treated with dasatinib, four cycle hyper CVAD/methotrexate cytarabin protocol, and allogeneic transplant. He is still alive in complete hematological, cytogenetic, and molecular remission. Mixed phenotype B/T acute leukemia is an extremely rare disease, particularly those with double Philadelphia chromosomes and clinically presents challenges in diagnosis and treatment.

  9. Phenotypic Plasticity of HSP70s Gene Expression during Diapause: Signs of Evolutionary Responses to Cold Stress among Soybean Pod Borer Populations (Leguminivora glycinivorella) in Northeast of China

    Science.gov (United States)

    Han, Lanlan; Fan, Dong; Zhao, Kuijun

    2014-01-01

    The soybean pod borer (Leguminivora glycinivorella Matsumura) successfully survives the winter because of its high expression of 70-kDa heat shock proteins (HSP70s) during its overwintering diapause. The amount of HSP70s is different under different environmental stresses. In this study, inducible heat shock protein 70 and its constitutive heat shock cognate 70 were cloned by RT-PCR and RACE. These genes were named Lg-hsp70 and Lg-hsc70, respectively. Gene transcription and protein expression after cold stress treatment (5°C to −5°C) were analyzed by western blotting and by qRT-PCR for four populations that were sampled in the northeast region of China, including Shenyang, Gongzhuling, Harbin and Heihe, when the soybean pod borer was in diapause. As the cold shock temperature decreased, the levels of Lg-HSP70s were significantly up-regulated. The amount of cold-induced Lg-HSP70s was highest in the southernmost population (Shenyang, 41°50′N) and lowest in the northernmost population (Heihe, 50°22′N). These results support the hypothesis that the soybean pod borer in the northeast region of China displays phenotypic plasticity, and the accumulation of Lg-HSP70s is a strategy for overcoming environmental stress. These results also suggest that the induction of HSP70 synthesis, which is a complex physiological adaptation, can evolve quickly and inherit stability. PMID:25330365

  10. The impact of herbicide-resistant rice technology on phenotypic diversity and population structure of United States weedy rice.

    Science.gov (United States)

    Burgos, Nilda Roma; Singh, Vijay; Tseng, Te Ming; Black, Howard; Young, Nelson D; Huang, Zhongyun; Hyma, Katie E; Gealy, David R; Caicedo, Ana L

    2014-11-01

    The use of herbicide-resistant (HR) Clearfield rice (Oryza sativa) to control weedy rice has increased in the past 12 years to constitute about 60% of rice acreage in Arkansas, where most U.S. rice is grown. To assess the impact of HR cultivated rice on the herbicide resistance and population structure of weedy rice, weedy samples were collected from commercial fields with a history of Clearfield rice. Panicles from each weedy type were harvested and tested for resistance to imazethapyr. The majority of plants sampled had at least 20% resistant offspring. These resistant weeds were 97 to 199 cm tall and initiated flowering from 78 to 128 d, generally later than recorded for accessions collected prior to the widespread use of Clearfield rice (i.e. historical accessions). Whereas the majority (70%) of historical accessions had straw-colored hulls, only 30% of contemporary HR weedy rice had straw-colored hulls. Analysis of genotyping-by-sequencing data showed that HR weeds were not genetically structured according to hull color, whereas historical weedy rice was separated into straw-hull and black-hull populations. A significant portion of the local rice crop genome was introgressed into HR weedy rice, which was rare in historical weedy accessions. Admixture analyses showed that HR weeds tend to possess crop haplotypes in the portion of chromosome 2 containing the ACETOLACTATE SYNTHASE gene, which confers herbicide resistance to Clearfield rice. Thus, U.S. HR weedy rice is a distinct population relative to historical weedy rice and shows modifications in morphology and phenology that are relevant to weed management. © 2014 American Society of Plant Biologists. All Rights Reserved.

  11. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

    Science.gov (United States)

    Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Campbell, Laura; Teague, Jessica E.; Schlapbach, Christoph; Elco, Christopher; Huang, Victor; Matos, Tiago R.; Kupper, Thomas S.; Clark, Rachael A.

    2015-01-01

    The skin of an adult human contains approximately 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All non-recirculating resident memory T cells (TRM) expressed CD69, but the majority were CD4+, CD103− and located in the dermis, in contrast to studies in mice. Both CD4+ and CD8+ CD103+ TRM were enriched in the epidermis, had potent effector functions and had a limited proliferative capacity compared to CD103− TRM. TRM of both types had more potent effector functions than recirculating T cells. Induction of CD103 on human T cells was enhanced by keratinocyte contact, depended on TGFβ and was independent of T cell keratinocyte adhesive interactions. We observed two distinct populations of recirculating T cells, CCR7+/L-selectin+ central memory T cells (TCM) and CCR7+/L-selectin− T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions and TMM were depleted more slowly from skin after alemtuzumab, suggesting TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities. PMID:25787765

  12. Phenotypic and molecular characterization of a tomato (Solanum lycopersicum L.) F2 population segregation for improving shelf life.

    Science.gov (United States)

    Yogendra, K N; Ramanjini Gowda, P H

    2013-02-27

    Breeding for better quality fruits is a major focus for tomatoes, which are continuously subjected to post-harvest losses. Several methods have been used to improve the fruit shelf life of tomatoes, including the use of ripening gene mutants of Solanum lycopersicum. We developed extended shelf-life tomato hybrids with better quality fruits using ripening mutants. Nine tomato crosses were developed using 3 fruit ripening gene mutants of S. lycopersicum [alcobaca (alc), non-ripening, and ripening inhibitor] and 3 agronomically superior Indian cultivars ('Sankranti', 'Vaibhav', and 'Pusaruby') with short shelf life. The hybrid progenies developed from alc x 'Vaibhav' had the highest extended shelf life (up to 40 days) compared with that of other varieties and hybrids. Further, the F(2) progenies of alc x 'Vaibhav' were evaluated for fruit quality traits and yield parameters. A wide range of genetic variability was observed in shelf life (5-106 days) and fruit firmness (0.55-10.65 lbs/cm(2)). The potential polymorphic simple sequence repeat markers underlying shelf life traits were identified in an F(2) mapping population. The marker association with fruit quality traits and yield was confirmed with single-marker analysis and composite interval mapping. The genetic parameters analyzed in the parents and F(1) and F(2) populations indicated that the cross between the cultivar 'Vaibhav' and ripening gene mutant alc yielded fruit with long shelf life and good quality.

  13. The accuracy of warfarin dosage based on VKORC1 and CYP2C9 phenotypes in a Chinese population

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    Agustinus Wijaya

    2012-05-01

    Full Text Available Background: The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9 genotype in Chinese population.Methods: Blood samples were taken from 37 patients. We compared the warfarin dosage obtained from genotype (according to www.warfarindosing.org and treatment dosage with international normalized ratio (INR value within 2.0-3.0.Results: The majority of Chinese people in our study are VKORC1 homozygous AA (89.2%, rarely VKORC1 heterozygous AG and we cannot find a patient with homozygous GG. For CYP2C9 genotype, most patients have the wildtype variants (CYP2C9*2 CC and CYP2C9*3 AA. The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than for patients with other genotype variants.Conclusion: There is no significant difference between pharmacogenetic algorithm (www.warfarindosing.org and our treatment dosage. Our conclusion is that the pharmacogenetic algorithm is accurate to predict the warfarin dose. (Med J Indones. 2012;21:108-12Keywords: CYP2C9, pharmacogenetic algorithm, VKORC1, warfarin

  14. Temperature Effects on Development and Phenotype in a Free-Living Population of Western Pond Turtles (Emys marmorata).

    Science.gov (United States)

    Christie, Nicole E; Geist, Nicholas R

    Changes in temperature regimes are occurring globally due to climate change as well as habitat alterations. Temperatures are expected to continue to rise in the future, along with a greater degree of climatic instability. Such changes could have potentially serious consequences for oviparous ectotherms, especially those with temperature-dependent sex determination. To investigate the effects of temperature on a range of developmental phenomena in a population of western pond turtles (Emys marmorata), we placed temperature sensors on top of each layer of eggs within nests and recorded temperatures hourly through the first 2-3 mo of incubation. These methods allowed us to look at in situ nest temperatures with high resolution. We found that mean incubation temperatures were similar between different nests and at different levels within nests but that incubation temperature fluctuations and maximum incubation temperatures differed greatly in both cases. The hatchling turtles were more likely to be female if they spent 30% or more of their sex-determining period of incubation above 29°C. Hatching success was best predicted by the maximum incubation temperature. We also found that incubation duration tended to be shorter as the mean temperature increased. However, exposure to either extremely high or low temperatures extended incubation times.

  15. [Phenotypic plasticity and its regulation of tillers prolonged reproductive growth of Puccinellia tenuiflora population on alkalized meadow in Songnen Plains of China].

    Science.gov (United States)

    Sun, Ju; Yang, Yun-Fei

    2007-04-01

    Puccinellia tenuiflora is a salt-tolerant plant of grass family. By the method of random sampling, big samples of reproductive tillers of P. tenuiflora population on the alkalized meadow in the Songnen Plains of China were collected at early heading, heading, flowering, and milky stages, respectively, and the plasticity of their quantitative characters was analyzed. The results showed that except some fluctuations at flowering stage, the tiller height, tiller biomass, spike length and spike biomass of the reproductive tillers at other three growth stages increased significantly every five days with the increasing time of reproductive growth. At each growth stage, tiller height had a significant positive correlation with spike biomass, but a negative correlation with reproductive allocation. With the time of reproductive growth prolonged, the increasing rate of spike biomass at early heading, flowering and milky stages increased in power function with the increase of tiller height. The reproductive allocation decreased linearly by 43.2% and 44.31% at early heading and heading stages, respectively when the reproductive growth time increased ten days, and by 130% at milky stage when the time increased five days. The regulation of the tiller phenotypic plasticity of P. tenuiflora population at its reproductive growth stage followed definite patterns.

  16. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

    Directory of Open Access Journals (Sweden)

    Specht Günther

    2010-03-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle, security aspects (by using database technology and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs. It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  17. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

    Science.gov (United States)

    Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

    2010-03-09

    Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  18. Recovery of native genetic background in admixed populations using haplotypes, phenotypes, and pedigree information--using Cika cattle as a case breed.

    Directory of Open Access Journals (Sweden)

    Mojca Simčič

    Full Text Available The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which

  19. Berberine diminishes side population and down-regulates stem cell-associated genes in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2.

    Science.gov (United States)

    Park, S H; Sung, J H; Chung, N

    2014-09-01

    Cancer stem cells play an important role in metastasis and the relapse of drug resistant cancers. Side-population (SP) cells are capable of effluxing Hoechst 33342 dye and are referred to as cancer stem cells. We investigated the effect of berberine on pancreatic cancer stem cells of PANC-1 and MIA PaCa-2. For both cell lines, the proportions of SP cells in the presence of berberine were investigated and compared to the proportions in the presence of gemcitabine, a standard pancreatic anti-cancer drug. The proportions of SP cells in the PANC-1 and MIA PaCa-2 cell lines were about 9 and PANC-1 decreased to 5.7 ± 2.0 and 6.8 ± 0.8%, respectively, which compares to the control proportion of (9.7 ± 1.7). After berberine and gemcitabine treatment of PANC-1, of the four stem cell-associated genes (SOX2, POU5F1, NANOG, and NOTCH1), all but NOTCH1 were down-regulated. Unfortunately, the effect of berberine and gemcitabine treatments on MIA PaCa-2 SP cells could not be clearly observed because SP cells represented only a very small proportion of MIA PaCa-2 cells. However, SOX2, POU5F1, and NANOG genes were shown to be effectively down-regulated in the MIA PaCa-2 cell line as a whole. Taken together, these results indicate that berberine is as effective at targeting pancreatic cancer cell lines as gemcitabine. Therefore, we believe that POU5F1, SOX2, and NANOG can serve as potential markers, and berberine may be an effective anti-cancer agent when targeting human pancreatic cancer cells and/or their cancer stem cells.

  20. BTG2 Is Down-Regulated and Inhibits Cancer Stem Cell-Like Features of Side Population Cells in Hepatocellular Carcinoma.

    Science.gov (United States)

    Huang, Chen-Song; Zhai, Jing-Ming; Zhu, Xiao-Xu; Cai, Jian-Peng; Chen, Wei; Li, Jian-Hui; Yin, Xiao-Yu

    2017-12-01

    Our previous study found that B cell translocation gene 2 (BTG2) was hyper-methylated and down-regulated in side population (SP) cells of hepatocellular carcinoma (HCC) cell line. However, its clinical significances and biological impacts on HCC SP cells remained unclear. To investigate the prognostic value of BTG2 gene in HCC and its influences on cancer stem cells (CSCs)-like traits of HCC cell line SP cells. BTG2 expression in human HCC and adjacent non-cancerous tissues was detected by immunohistochemical staining and quantitative real-time PCR, and also obtained from GEO and TCGA data. Its prognostic values were assessed. Its biological influences on HCC cell line SP cells were evaluated using cell viability, cell cycle, plate clone-forming assay, and chemoresistance in vitro and tumorigenicity in vivo. BTG2 expression was significantly suppressed in human HCC compared to adjacent non-cancerous tissues. BTG2 expression was correlated with TNM stage, tumor size and vascular invasion. Lower expression of BTG2 was associated with poorer overall survival and disease-free survival. In vitro, overexpression of BTG2 substantially suppressed cell proliferation and accumulation of HCC cell line SP cells in G0/G1 phase. Colony formation ability was markedly suppressed by BTG2 overexpression. Moreover, sensitivity of HCC cell line SP cells to 5-fluorouracil was substantially increased by overexpression of BTG2. Furthermore, tumorigenicity of HCC cell line SP cells transfected with BTG2 plasmids was significantly reduced in vivo. BTG2 gene could regulate the CSC-like traits of HCC cell line SP cells, and it represented as a molecular prognostic marker for HCC.

  1. Honokiol inhibits sphere formation and xenograft growth of oral cancer side population cells accompanied with JAK/STAT signaling pathway suppression and apoptosis induction

    International Nuclear Information System (INIS)

    Huang, Jhy-Shrian; Yao, Chih-Jung; Chuang, Shuang-En; Yeh, Chi-Tai; Lee, Liang-Ming; Chen, Ruei-Ming; Chao, Wan-Ju; Whang-Peng, Jacqueline; Lai, Gi-Ming

    2016-01-01

    Eliminating cancer stem cells (CSCs) has been suggested for prevention of tumor recurrence and metastasis. Honokiol, an active compound of Magnolia officinalis, had been proposed to be a potential candidate drug for cancer treatment. We explored its effects on the elimination of oral CSCs both in vitro and in vivo. By using the Hoechst side population (SP) technique, CSCs-like SP cells were isolated from human oral squamous cell carcinoma (OSCC) cell lines, SAS and OECM-1. Effects of honokiol on the apoptosis and signaling pathways of SP-derived spheres were examined by Annexin V/Propidium iodide staining and Western blotting, respectively. The in vivo effectiveness was examined by xenograft mouse model and immunohistochemical tissue staining. The SP cells possessed higher stemness marker expression (ABCG2, Ep-CAM, Oct-4 and Nestin), clonogenicity, sphere formation capacity as well as tumorigenicity when compared to the parental cells. Treatment of these SP-derived spheres with honokiol resulted in apoptosis induction via Bax/Bcl-2 and caspase-3-dependent pathway. This apoptosis induction was associated with marked suppression of JAK2/STAT3, Akt and Erk signaling pathways in honokiol-treated SAS spheres. Consistent with its effect on JAK2/STAT3 suppression, honokiol also markedly inhibited IL-6-mediated migration of SAS cells. Accordingly, honokiol dose-dependently inhibited the growth of SAS SP xenograft and markedly reduced the immunohistochemical staining of PCNA and endothelial marker CD31 in the xenograft tumor. Honokiol suppressed the sphere formation and xenograft growth of oral CSC-like cells in association with apoptosis induction and inhibition of survival/proliferation signaling pathways as well as angiogenesis. These results suggest its potential as an integrative medicine for combating oral cancer through targeting on CSCs. The online version of this article (doi:10.1186/s12885-016-2265-6) contains supplementary material, which is available to

  2. Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Juan; Xin, Beibei; Wang, Hui; He, Xiaodan [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China); Wei, Wei; Zhang, Ti [Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Tianjin 300060 (China); Shen, Xiaohong, E-mail: zebal2014@163.com [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China)

    2016-08-01

    Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues. Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer. - Highlights: • Gastrin induces ABCG2 expression mediated by NF-κB activation. • Gastrin regulates NF-κB's function that binds to the ABCG2 promoter in BxPC-3 cells. • Gastrin promotes the SP proportion in BxPC-3 cells by modulating ABCG2 expression via activation of NF-κB molecule. • Gastrin induces an increase in migration and invasion potential in pancreatic cancer cell by regulating NF-κB/ABCG2 signaling.

  3. [Index screening and comprehensive evaluation of phenotypic traits of low nitrogen tolerance using BILs population derived from Dongxiang wild rice (Oryza rufipogon Griff)].

    Science.gov (United States)

    Hu, Biao-lin; Li, Xia; Wan, Yong; Qiu, Zai-hui; Nie, Yuan-yuan; Xie, Jian-kun

    2015-08-01

    To identify the low nitrogen tolerance of Dongxiang wild rice (DXWR) and its progenies, ten phenotypic traits including plant height (PH), heading day (HD), panicle length (PL), number of effective tillers per plant (NETP), number of filled grains per panicle (NFGP), number of grains per panicle (NGP), grain density (GD), spikelet fertility (SF), 1000-grain mass (TGM) and grain yield per plant (GYP) were studied under normal and low nitrogen treatments, using backcross inbred lines (BILs) of Xieqingzao B//DXWR/Xieqingzao B in BC1 F12. Comprehensive evaluation on the low nitrogen tolerance of the BILs population was conducted using principal component analysis and the subordinate function. The evaluation results indicated that the low nitrogen tolerance of the line 116, 143 and 157 was the strongest, which could be served as the intermediate materials for genetic studies on the low nitrogen tolerance of DXWR and breeding for the low nitrogen tolerance in rice. The optimal regression equation of the low nitrogen tolerance in rice was established using stepwise regression analysis. The relative values of five traits including PH, NGP, SF, TGM and GYP were screened out and could be used as comprehensive evaluation indices for the low nitrogen tolerance in the whole growth stage. Therefore, more attention should be paid to the relative values of these five traits, especially for NGP and GYP, in the genetic improvement of the low nitrogen tolerance in rice.

  4. Genetic variants of 17q21 are associated with childhood-onset asthma and related phenotypes in a northeastern Han Chinese population: a case-control study.

    Science.gov (United States)

    Yu, X; Yu, C; Ren, Z; Deng, Y; Song, J; Zhang, H; Zhou, H

    2014-05-01

    A genome-wide association study (GWAS) suggested that variants on chromosome 17q21 were associated with childhood-onset asthma in white populations. Two replication studies had been conducted in southern Han Chinese population in 2009 and 2012. However, these two Chinese replication results were inconsistent. To further confirm the role of 17q21 common variants, an association study of 17q21 single nucleotide polymorphisms (SNPs) with the risk of childhood-onset asthma was performed in a Han population from northeastern China. In this study, rs3894194, rs12603332 and rs11650680 were genotyped in 435 asthmatic children and 601 healthy controls by using a SNaPshot method. Our data showed that the allelic frequency of rs12603332 and rs11650680 showed significant differences between asthmatic cases and healthy controls, with an odds ratio (OR) of 1.36 [95% confidence interval (CI) 1.12-1.65, P=0.002] and an OR of 1.36 (95% CI 1.07-1.74, P=0.01). Genotype distribution analysis also showed the significant associations of the above two loci with childhood asthma under dominant, recessive and additive model (dominant OR=1.57, 95% CI 1.04-2.36, P=0.032; recessive OR=1.41, 95% CI 1.09-1.83, P=0.009; additive OR=1.97, 95% CI 1.24-3.14, P=0.004; recessive OR=1.50, 95% CI 1.13-1.98, P=0.005). Besides, linear regression analysis showed that rs3894194 and rs12603332 were also significantly associated with asthma phenotypes such as log10 -transformed immunoglobulin E (IgE) level (IU/ml) and log10 -transformed eosinophil percentage (dominant, P=0.04; additive, P=0.01; recessive, P=0.04; recessive, P=0.03; additive, P=0.02). Collectively, our findings suggest that orosomucoid 1-like 3 (ORMDL3) locus on chromosome 17q21 is a risk factor for childhood-onset asthma in northeastern Han Chinese population. Further studies will be needed to elucidate the pathogenesis that ORMDL3 locus predisposes to childhood-onset asthma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Phenotypically heterogeneous podoplanin-expressing cell populations are associated with the lymphatic vessel growth and fibrogenic responses in the acutely and chronically infarcted myocardium.

    Science.gov (United States)

    Cimini, Maria; Cannatá, Antonio; Pasquinelli, Gianandrea; Rota, Marcello; Goichberg, Polina

    2017-01-01

    Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of LYVE-1-negative cells dispersed between myocytes, predominantly in the vicinity of the infarcted region. Podoplanin-carrying populations displayed a mesenchymal progenitor marker PDGFRα, and intermittently expressed Prox-1, a master regulator of the lymphatic endothelial fate. At the stages of scar formation and maturation, concomitantly with the enlargement of lymphatic network in the injured myocardium, the podoplanin-rich LYVE-1-negative multicellular assemblies were apparent in the fibrotic area, aligned with extracellular matrix deposits, or located in immediate proximity to activated blood vessels with high VEGFR-2 content. Of note, these podoplanin-containing cells acquired the expression of PDGFRβ or a hematoendothelial epitope CD34. Although Prox-1 labeling was abundant in the area affected by MI, the podoplanin-presenting cells were not consistently Prox-1-positive. The concordance of podoplanin with VEGFR-3 similarly varied. Thus, our data reveal previously unknown phenotypic and structural heterogeneity within the podoplanin-positive cell compartment in the infarcted heart, and suggest an alternate ability of podoplanin-presenting cardiac cells to generate lymphatic endothelium and pro

  6. Phenotypically heterogeneous podoplanin-expressing cell populations are associated with the lymphatic vessel growth and fibrogenic responses in the acutely and chronically infarcted myocardium.

    Directory of Open Access Journals (Sweden)

    Maria Cimini

    Full Text Available Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI. However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of LYVE-1-negative cells dispersed between myocytes, predominantly in the vicinity of the infarcted region. Podoplanin-carrying populations displayed a mesenchymal progenitor marker PDGFRα, and intermittently expressed Prox-1, a master regulator of the lymphatic endothelial fate. At the stages of scar formation and maturation, concomitantly with the enlargement of lymphatic network in the injured myocardium, the podoplanin-rich LYVE-1-negative multicellular assemblies were apparent in the fibrotic area, aligned with extracellular matrix deposits, or located in immediate proximity to activated blood vessels with high VEGFR-2 content. Of note, these podoplanin-containing cells acquired the expression of PDGFRβ or a hematoendothelial epitope CD34. Although Prox-1 labeling was abundant in the area affected by MI, the podoplanin-presenting cells were not consistently Prox-1-positive. The concordance of podoplanin with VEGFR-3 similarly varied. Thus, our data reveal previously unknown phenotypic and structural heterogeneity within the podoplanin-positive cell compartment in the infarcted heart, and suggest an alternate ability of podoplanin-presenting cardiac cells to generate lymphatic endothelium

  7. Direct stamp of technology or origin on the genotypic and phenotypic variation of indigenous Saccharomyces cerevisiae population in a natural model of boiled grape juice fermentation into traditional Msalais wine in China.

    Science.gov (United States)

    Zhu, Li-Xia; Wang, Guan-Qiong; Xue, Ju-Lan; Gou, Dong-Qi; Duan, Chang-Qing

    2017-08-01

    Saccharomyces cerevisiae strains worldwide show genetic and phenotypic diversity and their population substructures are greatly affected by their technological application or geographical origins. Msalais is a traditional wine obtained via a unique method of spontaneous fermentation of local boiled grape juice in Southern Xinjiang. We analyzed 436 indigenous S. cerevisiae strains associated with Msalais fermentation. These strains were highly diverse with respect to the interdelta region and 24 phenotypic traits, with apparent differentiation according to strain origins and technologies used to produce Msalais. The genetic and phenotypic diversity of strains from traditional workshops was higher than in strains from modern plants. These local strains had different origin- or technology-specific fermentative characteristics. Strains growing in large-scale fermentation tanks tolerated high temperature, whereas strains from traditional workshops tolerated high alcohol content (16%) and low temperature (13°C). Almost all the strains were characterized by the highest fermenting vigor, with weak H2S production and no histamine, cadaverine, phenethylamine and tryptamine production. Majority of strains had pronounced autolytic activity with high β-glucosidase and polygalacturonase activity and alcohol production. Our study reveals a direct stamp of technology or origin on genotypic and phenotypic variation of an indigenous S. cerevisiae population. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. [The influence of STAT4 rs7574865 (G/T) polymorphism on the risk of clinical and immunological phenotypes of systemic sclerosis in a Russian patient population: Results of a pilot study].

    Science.gov (United States)

    Krylov, M Yu; Ananyeva, L P; Koneva, О А; Starovoytova, M N; Desinova, O V; Ovsyannikova, O B; Aleksandrova, E N; Novikov, A A; Guseva, I A; Konovalova, N V; Varlamov, D A

    To examine the association of signal transducer and activator transcription 4 (STAT4) rs7574865 G/T polymorphism with a predisposition to systemic sclerosis (SSC) and associated clinical and autoimmune phenotypes in a Russian population. A total of 102 patients with SSC and 103 healthy individuals as controls were examined. STAT4 rs7574865 polymorphism was investigated by real-time polymerase chain reaction. The carriers of the T allele showed a statistically significant association with SSC, a diffuse form (DF), the presence of interstitial lung disease (ILD), cardiac injury (CI), and seropositivity for anti-topoisomerase I antibodies (ATA). The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.

  9. Functional characterizations of venom phenotypes in the eastern diamondback rattlesnake (Crotalus adamanteus) and evidence for expression-driven divergence in toxic activities among populations

    Science.gov (United States)

    Margres, Mark J.; Walls, Robert; Suntravat, Montamas; Lucena, Sara; Sánchez, Elda E.; Rokyta, Darin R.

    2016-01-01

    Phenotypes frequently vary across and within species. The connection between specific phenotypic effects and function, however, is less understood despite being essential to our understanding of the adaptive process. Snake venoms are ideal for identifying functionally important phenotypic variation because venom variation is common, and venoms can be functionally characterized through simple assays and toxicity measurements. Previous work with the eastern diamondback rattlesnake (Crotalus adamanteus) used multivariate statistical approaches to identify six unique venom phenotypes. We functionally characterized hemolytic, gelatinase, fibrinogenolytic, and coagulant activity for all six phenotypes, as well as one additional venom, to determine if the statistically significant differences in toxin expression levels previously documented corresponded to differences in venom activity. In general, statistical differences in toxin expression predicted the identified functional differences, or lack thereof, in toxic activity, demonstrating that the statistical approach used to characterize C. adamanteus venoms was a fair representation of biologically meaningful differences. Minor differences in activity not accounted for by the statistical model may be the result of amino-acid differences and/or post-translational modifications, but overall we were able to link variation in protein expression levels to variation in function as predicted by multivariate statistical approaches. PMID:27179420

  10. Population and colony structure and morphometrics in the queen dimorphic little black ant, Monomorium sp. AZ-02, with a review of queen phenotypes in the genus Monomorium.

    Directory of Open Access Journals (Sweden)

    Robert A Johnson

    Full Text Available The North American little black ant, Monomorium sp. AZ-02 (subfamily Myrmicinae, displays a dimorphism that consists of alate (winged and ergatoid (wingless queens. Surveys at our field site in southcentral Arizona, USA, demonstrated that only one queen phenotype (alate or ergatoid occurred in each colony during the season in which reproductive sexuals were produced. A morphometric analysis demonstrated that ergatoid queens retained all specialized anatomical features of alate queens (except for wings, and that they were significantly smaller and had a lower mass than alate queens. Using eight morphological characters, a discriminant analysis correctly categorized all queens (40 of 40 of both phenotypes. A molecular phylogeny using 420 base pairs of the mitochondrial gene cytochrome oxidase I demonstrated that alate and ergatoid queens are two alternative phenotypes within the species; both phenotypes were intermixed on our phylogeny, and both phenotypes often displayed the same haplotype. A survey of the genus Monomorium (358 species found that wingless queens (ergatoid queens, brachypterous queens occur in 42 of 137 species (30.6% in which the queen has been described. These wingless queen species are geographically and taxonomically widespread as they occur on several continents and in eight species groups, suggesting that winglessness probably arose independently on many occasions in the genus.

  11. PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics.

    Science.gov (United States)

    Chantreau, Maxime; Grec, Sébastien; Gutierrez, Laurent; Dalmais, Marion; Pineau, Christophe; Demailly, Hervé; Paysant-Leroux, Christine; Tavernier, Reynald; Trouvé, Jean-Paul; Chatterjee, Manash; Guillot, Xavier; Brunaud, Véronique; Chabbert, Brigitte; van Wuytswinkel, Olivier; Bendahmane, Abdelhafid; Thomasset, Brigitte; Hawkins, Simon

    2013-10-15

    Flax (Linum usitatissimum L.) is an economically important fiber and oil crop that has been grown for thousands of years. The genome has been recently sequenced and transcriptomics are providing information on candidate genes potentially related to agronomically-important traits. In order to accelerate functional characterization of these genes we have generated a flax EMS mutant population that can be used as a TILLinG (Targeting Induced Local Lesions in Genomes) platform for forward and reverse genetics. A population of 4,894 M2 mutant seed families was generated using 3 different EMS concentrations (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and 1,552 families (38.5%) showed a visual developmental phenotype (stem size and diameter, plant architecture, flower-related). The majority of these families showed more than one phenotype. Mutant phenotype data are organised in a database and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb). Preliminary screens were also performed for atypical fiber and seed phenotypes. Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to validate the collection for reverse genetics, DNA pools were screened for two genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations in the C3H and CAD genes, respectively. The average mutation rate was calculated as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five out of the 52 flax cad mutant families containing missense or codon stop mutations showed the typical orange-brown xylem phenotype observed in CAD down-regulated/mutant plants in other species. We have developed a flax mutant population that can be used as an efficient

  12. Genetic and environmental dissections of sub-phenotypes of metabolic syndrome in the chinese population: a twin-based heritability study

    DEFF Research Database (Denmark)

    Duan, Haiping; Pang, Zengchang; Zhang, Dongfeng

    2011-01-01

    contains 654 twins collected in the Qingdao municipality. A total of 10 phenotypes covering anthropometric measurements, plasma glucose levels, lipids, blood pressures etc. were examined. Univariate and bivariate structural equation models were fitted for assessing the genetic and environmental...... contributions. Results: The AE model combining additive genetic (A) and unique environmental (E) factors produced the best fit for all phenotypes except for triglyceride. Modest to high heritability estimates were obtained in univariate analysis ranging from 0.5 for total cholesterol to 0.78 for weight...

  13. History, haldanes and health inequities: exploring phenotypic changes in body size by generation and income level in the US-born White and Black non-Hispanic populations 1959-1962 to 2005-2008.

    Science.gov (United States)

    Krieger, Nancy; Chen, Jarvis T; Waterman, Pamela D; Kosheleva, Anna; Beckfield, Jason

    2013-02-01

    Most public health literature on trends in population health and health inequities pertains to observed or targeted changes in rates or proportions per year or decade. We explore, in novel analyses, whether additional insight can be gained by using the 'haldane', a metric developed by evolutionary biologists to measure change in traits in standard deviations per generation, thereby enabling meaningful comparisons across species and time periods. We analysed the phenotypic embodied traits of body height, weight and body mass index of US-born White and Black non-Hispanic adults ages 20 to 44 as measured in six large nationally representative population samples spanning from the 1959-1962 National Health Examination Survey I to the 2005-2008 National Health and Nutrition Examination Survey. Setting the former as baseline, we computed the haldane for each outcome for each racial/ethnic group for each survey, overall and stratified by family income quintile. For height, high rates of phenotypic change (haldane ≥ 0.3) occurred chiefly between 1960 and 1980, especially for the Black population in the higher income quintiles. By contrast, for weight, high rates of phenotypic change became evident for both the White and Black populations in the late 1980s and increased thereafter; for body mass index, the shift to high rates of change started in both groups in the late 1990s, especially in the middle income quintiles. Our results support use of the haldane as a supplemental metric to place changes in population health and health inequities in a larger biological and historical context.

  14. Genetic and Phenotype [Phenotypic] Catalog of Native Resident Trout of the interior Columbia River Basin : FY-99 Report : Populations of the Pend Oreille, Kettle, and Sanpoil River Basins of Colville National Forest.

    Energy Technology Data Exchange (ETDEWEB)

    Trotter, Patrick C.

    2001-05-01

    The 1994 Fish and Wildlife Program of the Northwest Power Planning Council specifies the recovery and preservation of population health of native resident fishes of the Columbia River Basin. Among the native resident species of concern are interior rainbow trout of the Columbia River redband subspecies Oncorhynchus mykiss gairdneri 1 and westslope cutthroat trout O. clarki lewisi. The westslope cutthroat trout has been petitioned for listing under the U. S. Endangered Species Act (American Wildlands et al. 1997). Before at-risk populations can be protected, their presence and status must be established. Where introgression from introduced species is a concern, as in the case of both westslope cutthroat trout and redband rainbow trout, genetic issues must be addressed as well. As is true with native trout elsewhere in the western United States (Behnke 1992), most of the remaining pure populations of these species in the Columbia River Basin are in relatively remote headwater reaches. The objective of this project is to photo-document upper Columbia Basin native resident trout populations in Washington, and to ascertain their species or subspecies identity and relative genetic purity using a nonlethal DNA technique. FY-99 was year two of a five-year project in which we conducted field visits to remote locations to seek out and catalog these populations. In FY-99 we worked in collaboration with the Colville National Forest and Kalispel Indian Tribe to catalog populations in the northeastern corner of Washington State.

  15. Phenotypic variation among trees in a population of a Pistacia atlantica X P. integerrima cross sold as UCB-1 rootstock for grafting P. vera (pistachio) cultivars

    Science.gov (United States)

    UCB-1 is widely used in California as a pistachio rootstock because of its Verticillium resistance, salt and cold tolerance, and vigor. It can grow in most locations in California. However, significant variation exists in the phenotypic performance of trees grafted to seedling UCB-1 rootstocks. In J...

  16. Phenotypic and genotypic variation of Phragmites australis: Comparison of populations in two human-made lakes of different age and history

    Czech Academy of Sciences Publication Activity Database

    Čurn, V.; Kubátová, B.; Vávřová, P.; Křiváčková; Suchá, O.; Čížková, Hana

    2007-01-01

    Roč. 86, - (2007), s. 321-330 ISSN 0304-3770 R&D Projects: GA ČR(CZ) GA526/06/0276 Institutional research plan: CEZ:AV0Z60870520 Keywords : Phragmites * Phenotypic variation * Genotypic variation * Lake * Clone Subject RIV: EF - Botanics Impact factor: 1.497, year: 2007

  17. Impact of polymorphisms in WFS1 on prediabetic phenotypes in a population-based sample of middle-aged people with normal and abnormal glucose regulation

    DEFF Research Database (Denmark)

    Sparsø, T; Andersen, G; Albrechtsen, Anders

    2008-01-01

    AIM/HYPOTHESIS: Recently, variants in WFS1 have been shown to be associated with type 2 diabetes. We aimed to examine metabolic risk phenotypes of WFS1 variants in glucose-tolerant people and in individuals with abnormal glucose regulation. METHODS: The type 2 diabetes-associated WFS1 variant rs7...

  18. Phenotypically and functionally distinct CD8+ lymphocyte populations in long-term drug-free tolerance and chronic rejection in human kidney graft recipients

    NARCIS (Netherlands)

    Baeten, Dominique; Louis, Stéphanie; Braud, Christophe; Braudeau, Cécile; Ballet, Caroline; Moizant, Frédéric; Pallier, Annaik; Giral, Magali; Brouard, Sophie; Soulillou, Jean-Paul

    2006-01-01

    A substantial proportion of long-term kidney graft recipients, including those with a stable renal function in the absence of immunosuppressive therapy, present a skewed T cell receptor (TCR) Vbeta chain usage, essentially in the CD8+ subset. This study analyzed in more detail phenotypical and

  19. The spatial patterns of directional phenotypic selection

    KAUST Repository

    Siepielski, Adam M.; Gotanda, Kiyoko M.; Morrissey, Michael B.; Diamond, Sarah E.; DiBattista, Joseph; Carlson, Stephanie Marie

    2013-01-01

    the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data

  20. Medications and Side Effects

    Science.gov (United States)

    ... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

  1. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample.

    Science.gov (United States)

    Ogino, Shuji; Kawasaki, Takako; Kirkner, Gregory J; Kraft, Peter; Loda, Massimo; Fuchs, Charles S

    2007-07-01

    The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation is a distinct phenotype in colorectal cancer. However, a choice of markers for CIMP has been controversial. A recent extensive investigation has selected five methylation markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1) as surrogate markers for epigenomic aberrations in tumor. The use of these markers as a CIMP-specific panel needs to be validated by an independent, large dataset. Using MethyLight assays on 920 colorectal cancers from two large prospective cohort studies, we quantified DNA methylation in eight CIMP-specific markers [the above five plus CDKN2A (p16), CRABP1, and MLH1]. A CIMP-high cutoff was set at > or = 6/8 or > or = 5/8 methylated promoters, based on tumor distribution and BRAF/KRAS mutation frequencies. All but two very specific markers [MLH1 (98% specific) and SOCS1 (93% specific)] demonstrated > or = 85% sensitivity and > or = 80% specificity, indicating overall good concordance in methylation patterns and good performance of these markers. Based on sensitivity, specificity, and false positives and negatives, the eight markers were ranked in order as: RUNX3, CACNA1G, IGF2, MLH1, NEUROG1, CRABP1, SOCS1, and CDKN2A. In conclusion, a panel of markers including at least RUNX3, CACNA1G, IGF2, and MLH1 can serve as a sensitive and specific marker panel for CIMP-high.

  2. Phenotypic and functional characterization of earthworm coelomocyte subsets: Linking light scatter-based cell typing and imaging of the sorted populations.

    Science.gov (United States)

    Engelmann, Péter; Hayashi, Yuya; Bodó, Kornélia; Ernszt, Dávid; Somogyi, Ildikó; Steib, Anita; Orbán, József; Pollák, Edit; Nyitrai, Miklós; Németh, Péter; Molnár, László

    2016-12-01

    Flow cytometry is a common approach to study invertebrate immune cells including earthworm coelomocytes. However, the link between light-scatter- and microscopy-based phenotyping remains obscured. Here we show, by means of light scatter-based cell sorting, both subpopulations (amoebocytes and eleocytes) can be physically isolated with good sort efficiency and purity confirmed by downstream morphological and cytochemical applications. Immunocytochemical analysis using anti-EFCC monoclonal antibodies combined with phalloidin staining has revealed antigenically distinct, sorted subsets. Screening of lectin binding capacity indicated wheat germ agglutinin (WGA) as the strongest reactor to amoebocytes. This is further evidenced by WGA inhibition assays that suggest high abundance of N-acetyl-d-glucosamine in amoebocytes. Post-sort phagocytosis assays confirmed the functional differences between amoebocytes and eleocytes, with the former being in favor of bacterial engulfment. This study has proved successful in linking flow cytometry and microscopy analysis and provides further experimental evidence of phenotypic and functional heterogeneity in earthworm coelomocyte subsets. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Effect of GBA Mutations on Phenotype of Parkinson’s Disease: A Study on Chinese Population and a Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2015-01-01

    Full Text Available GBA has been identified as a genetic risk factor for PD. Whether the clinical manifestations of PD patients with or without GBA mutations are different has still not reached a consensus. We firstly detected the GBA mutation L444P in 1147 Chinese PD patients and simultaneously evaluated their corresponding clinical data. Then we compared the phenotypes between 646 PD patients with GBA mutations and 10344 PD patients without GBA mutations worldwide through meta-analysis. Through the method of meta-analysis, there was significant difference in age at onset (MD = −3.10 [95% CI: −4.88, −1.32], bradykinesia as an initial symptom (OR = 1.49 [95% CI: 1.15, 1.94], having family history (OR = 1.50 [95% CI: 1.18, 1.91], and dementia (OR = 3.21 [95% CI: 1.97, 5.24] during the comparison between PD patients with and without GBA mutations. While, in the aspect of tremor as an initial symptom (OR = 0.81 [95% CI: 0.64, 1.03], the severity of motor symptoms such as H-Y (MD = 0.06 [95% CI: −0.06, 0.17] and UPDRS-III (MD = 1.61 [95% CI: −0.65, 3.87] and having dyskinesia (OR = 1.60 [95% CI: 0.90, 2.84] during the comparison between the two groups revealed no statistical differences. Our results suggested that the phenotypes of PD patients with GBA mutations are different from GBA noncarriers.

  4. Phenotypic covariance at species' borders.

    Science.gov (United States)

    Caley, M Julian; Cripps, Edward; Game, Edward T

    2013-05-28

    Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species' borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species' borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future.

  5. Phenotypic Diversities of Four Populations of Clarias Gariepinus (Siluriformes, Clariidae Obtained from Ogun and Ondo State Waterbodies in South-Western Nigeria

    Directory of Open Access Journals (Sweden)

    Ola-Oladimeji F. A.

    2017-08-01

    Full Text Available The study determined the variation in the morphological and meristic features among four populations of Clarias gariepinus Burchell, 1822 obtained from Owena Dam and River Oluwa in Ondo State and Rivers Omo and Ogbere in Ogun State, both in Nigeria. A total of ninety five (95 and one hundred and twenty (120 fish specimens collected from Ondo and Ogun states respectively were measured using standard procedures and the results were analysed using Analysis of variance and multivariate analyses. The results obtained from the ANOVA and Principal Component Analyses of Clarias gariepinus from the four populations revealed heterogeneity for most of their characters. Therefore, the morphological differences between the wild African catfish found in Ondo and Ogun state populations could be linked to genetic differences or environmental factors or a combination of both factors. Hence, this study concluded that the populations are different which could imply high genetic diversity if molecular marker techniques are employed in further studies.

  6. Genetic and Phenotypic Catalog of Native Resident Trout of the Interior Columbia River Basin; Populations of the Upper Yakima Basin, 1997-1998 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Trotter, Patrick C. (Fishery Science Consultant, Seattle, WA); McMillan, Bill; Gayeski, Nick (Washington Trout, Duvall, WA)

    1999-10-01

    The objective of this project is to photo-document upper Columbia Basin native resident trout populations in Washington, and to ascertain their species or subspecies identity and relative genetic purity using a nonlethal DNA technique.

  7. Genetic and Phenotypic Catalog of Native Resident Trout of the interior Columbia River Basin : FY-2001 Report : Populations in the Wenatchee, Entiat, Lake Chelan and Methow River Drainages.

    Energy Technology Data Exchange (ETDEWEB)

    Trotter, Patrick C.

    2001-10-01

    The 1994 Fish and Wildlife Program of the Northwest Power Planning Council specifies the recovery and preservation of population health of native resident fishes of the Columbia River Basin. Among the native resident species of concern are interior rainbow trout of the Columbia River redband subspecies Oncorhynchus mykiss gairdneri 1 and westslope cutthroat trout O. clarki lewisi. The westslope cutthroat trout has been petitioned for listing under the U. S. Endangered Species Act (American Wildlands et al. 1997). Before at-risk populations can be protected, their presence and status must be established. Where introgression from introduced species is a concern, as in the case of both westslope cutthroat trout and redband rainbow trout, genetic issues must be addressed as well. As is true with native trout elsewhere in the western United States (Behnke 1992), most of the remaining pure populations of these species in the Columbia River Basin are in relatively remote headwater reaches. The objective of this project was to photo-document upper Columbia Basin native resident trout populations in Washington, and to ascertain their species or subspecies identity and relative genetic purity using a nonlethal DNA technique. FY-2001 was year three (and final year) of a project in which we conducted field visits to remote locations to seek out and catalog these populations. In FY-2001 we worked in collaboration with the Wenatchee National Forest to catalog populations in the Wenatchee, Entiat, Lake Chelan, and Methow River drainages of Washington State.

  8. Genetic differentiation in natural populations of Lutzomyia longipalpis (Lutz & Neiva) (Diptera: Psychodidae) with different phenotypic spot patterns on tergites in males.

    Science.gov (United States)

    Silva, M H; Nascimento, M D S B; Leonardo, F S; Rebêlo, J M M; Pereira, S R F

    2011-01-01

    Entomological surveys in the state of Maranhão have recorded morphologically distinct populations of Lutzomyia longipalpis (Lutz & Neiva). Some populations have one pair of spots (1S) on the fourth tergite, while others have two pairs (2S) on the third and fourth tergites of males. In the present study we investigated the degree of genetic polymorphism among four populations in the municipalities of Caxias, Codó and Raposa, in the state of Maranhão, Brazil, by using RAPD (Random Amplified Polymorphic DNA) markers. A total of 35 loci were identified, of which 30 were polymorphic. The highest polymorphism was observed with primer OPA 4, which produced 11 different profiles. Genetic diversity was assessed using grouping methods that produced a dendrogram in which the genotypes could be clearly separated into two main clades according to the number of spots on the male abdominal tergites. One cluster contained the populations from Caxias and Codó, and the other was formed by the populations from Raposa and Codó. The results of our RAPD analysis showed a clear separation between the populations with one and two pairs of spots. The epidemiologic significance of this genetic differentiation should be investigated in future studies.

  9. Heterogeneity of functional properties of Clone 66 murine breast cancer cells expressing various stem cell phenotypes.

    Science.gov (United States)

    Mukhopadhyay, Partha; Farrell, Tracy; Sharma, Gayatri; McGuire, Timothy R; O'Kane, Barbara; Sharp, J Graham

    2013-01-01

    Breast cancer grows, metastasizes and relapses from rare, therapy resistant cells with a stem cell phenotype (cancer stem cells/CSCs). However, there is a lack of studies comparing the functions of CSCs isolated using different phenotypes in order to determine if CSCs are homogeneous or heterogeneous. Cells with various stem cell phenotypes were isolated by sorting from Clone 66 murine breast cancer cells that grow orthotopically in immune intact syngeneic mice. These populations were compared by in vitro functional assays for proliferation, growth, sphere and colony formation; and in vivo limiting dilution analysis of tumorigenesis. The proportion of cells expressing CD44(high)CD24(low/neg), side population (SP) cells, ALDH1(+), CD49f(high), CD133(high), and CD34(high) differed, suggesting heterogeneity. Differences in frequency and size of tumor spheres from these populations were observed. Higher rates of proliferation of non-SP, ALDH1(+), CD34(low), and CD49f(high) suggested properties of transit amplifying cells. Colony formation was higher from ALDH1(-) and non-SP cells than ALDH1(+) and SP cells suggesting a progenitor phenotype. The frequency of clonal colonies that grew in agar varied and was differentially altered by the presence of Matrigel™. In vivo, fewer cells with a stem cell phenotype were needed for tumor formation than "non-stem" cells. Fewer SP cells were needed to form tumors than ALDH1(+) cells suggesting further heterogeneities of cells with stem phenotypes. Different levels of cytokines/chemokines were produced by Clone 66 with RANTES being the highest. Whether the heterogeneity reflects soluble factor production remains to be determined. These data demonstrate that Clone 66 murine breast cancer cells that express stem cell phenotypes are heterogeneous and exhibit different functional properties, and this may also be the case for human breast cancer stem cells.

  10. Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a Northern European family population.

    Science.gov (United States)

    Zhang, Yi; Kent, Jack W; Lee, Adam; Cerjak, Diana; Ali, Omar; Diasio, Robert; Olivier, Michael; Blangero, John; Carless, Melanie A; Kissebah, Ahmed H

    2013-03-19

    Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated with the MetS leading components. However, evidence supporting the functions of FABPs in humans using genetic approaches has been scarce, suggesting FABPs may be under epigenetic regulation. The objective of this study was to test the hypothesis that CpG methylation status of a key regulator of lipid homeostasis, FABP3, is a quantitative trait associated with status of MetS phenotypes in humans. We used a mass-spec based quantitative method, EpiTYPER®, to profile a CpG island that extends from the promoter to the first exon of the FABP3 gene in our family-based cohort of Northern European descent (n=517). We then conducted statistical analysis of the quantitative relationship of CpG methylation and MetS measures following the variance-component association model. Heritability of each methylation and the effect of age and sex on CpG methylation were also assessed in our families. We find that methylation levels of individual CpG units and the regional average are heritable and significantly influenced by age and sex. Regional methylation was strongly associated with plasma total cholesterol (p=0.00028) and suggestively associated with LDL-cholesterol (p=0.00495). Methylation at individual units was significantly associated with insulin sensitivity, lipid particle sizing and diastolic blood pressure (pmetabolism (βWHR=-0.72; βLDL-c=-0.53) while positively correlated with plasma adiponectin (β=0.24). Further, we show that differential methylation of FABP3 affects binding activity with

  11. Side Effects (Management)

    Science.gov (United States)

    ... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

  12. Adaptive evolution of molecular phenotypes

    International Nuclear Information System (INIS)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-01-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak. (paper)

  13. Predicting Flowering Behavior and Exploring Its Genetic Determinism in an Apple Multi-family Population Based on Statistical Indices and Simplified Phenotyping

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Durand

    2017-06-01

    Full Text Available Irregular flowering over years is commonly observed in fruit trees. The early prediction of tree behavior is highly desirable in breeding programmes. This study aims at performing such predictions, combining simplified phenotyping and statistics methods. Sequences of vegetative vs. floral annual shoots (AS were observed along axes in trees belonging to five apple related full-sib families. Sequences were analyzed using Markovian and linear mixed models including year and site effects. Indices of flowering irregularity, periodicity and synchronicity were estimated, at tree and axis scales. They were used to predict tree behavior and detect QTL with a Bayesian pedigree-based analysis, using an integrated genetic map containing 6,849 SNPs. The combination of a Biennial Bearing Index (BBI with an autoregressive coefficient (γg efficiently predicted and classified the genotype behaviors, despite few misclassifications. Four QTLs common to BBIs and γg and one for synchronicity were highlighted and revealed the complex genetic architecture of the traits. Irregularity resulted from high AS synchronism, whereas regularity resulted from either asynchronous locally alternating or continual regular AS flowering. A relevant and time-saving method, based on a posteriori sampling of axes and statistical indices is proposed, which is efficient to evaluate the tree breeding values for flowering regularity and could be transferred to other species.

  14. Predicting Flowering Behavior and Exploring Its Genetic Determinism in an Apple Multi-family Population Based on Statistical Indices and Simplified Phenotyping.

    Science.gov (United States)

    Durand, Jean-Baptiste; Allard, Alix; Guitton, Baptiste; van de Weg, Eric; Bink, Marco C A M; Costes, Evelyne

    2017-01-01

    Irregular flowering over years is commonly observed in fruit trees. The early prediction of tree behavior is highly desirable in breeding programmes. This study aims at performing such predictions, combining simplified phenotyping and statistics methods. Sequences of vegetative vs. floral annual shoots (AS) were observed along axes in trees belonging to five apple related full-sib families. Sequences were analyzed using Markovian and linear mixed models including year and site effects. Indices of flowering irregularity, periodicity and synchronicity were estimated, at tree and axis scales. They were used to predict tree behavior and detect QTL with a Bayesian pedigree-based analysis, using an integrated genetic map containing 6,849 SNPs. The combination of a Biennial Bearing Index (BBI) with an autoregressive coefficient (γ g ) efficiently predicted and classified the genotype behaviors, despite few misclassifications. Four QTLs common to BBIs and γ g and one for synchronicity were highlighted and revealed the complex genetic architecture of the traits. Irregularity resulted from high AS synchronism, whereas regularity resulted from either asynchronous locally alternating or continual regular AS flowering. A relevant and time-saving method, based on a posteriori sampling of axes and statistical indices is proposed, which is efficient to evaluate the tree breeding values for flowering regularity and could be transferred to other species.

  15. Radiation Therapy Side Effects

    Science.gov (United States)

    Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

  16. CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the Impact of CYP2D6∗10 on Interindividual Variation in a Chinese Population

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    Pei Hu

    2017-05-01

    Full Text Available Purpose: Asian populations have around 40–60% frequency of reduced function allele CYP2D6∗10 compared to 1–2% in Caucasian populations. The wide range of CYP2D6 enzyme activities in subjects with the CYP2D6∗10 variant is a big concern for clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzyme activity as a result of one CYP2D6∗10 allele or two CYP2D6∗10 alleles has not been reported in large Asian populations.Methods: A total of 421 healthy Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and direct DNA sequencing. A total of 235 subjects with CYP2D6∗1/∗1 (n = 22, CYP2D6∗1/∗10 (n = 93, CYP2D6∗10/∗10 (n = 85, and CYP2D6∗5/∗10 (n = 35 were phenotyped for CYP2D6 using dextromethorphan as the probe drug. Metabolic ratios (MR were calculated as the ratio of parent drug to metabolite in 0–3 h urine, 3 h plasma, and 3 h saliva for each sample type.Results: The urinary, plasma, or salivary MRs increased successively in subjects with CYP2D6∗1/∗1, ∗1/∗10, ∗10/∗10, and ∗5/∗10 (all P < 0.001. In the normal metabolizer group, homozygous CYP2D6∗10/∗10 decreased the CYP2D6 enzyme activity further than heterozygous CYP2D6∗1/∗10. Urinary, plasma, and salivary MRs were highly correlated.Conclusion: The normal metabolizer group calls for a more detailed classification. The activity score system could more accurately predict enzyme activity than by grouping a number of genotypes into a single phenotype group. Single-point plasma samples and saliva samples could be used as alternative phenotyping methods for clinical convenience.

  17. Evaluation of the phenotypic performance of a Red Maasai and Dorper double backcross resource population: indoor trickle challenge with Haemonchus contortus.

    Science.gov (United States)

    Mugambi, J M; Audho, J O; Njomo, S; Baker, R L

    2005-02-28

    Six F(1) Dorper (D) x Red Maasai (R) rams were mated to both D and R ewes to produce backcross lambs. These six double backcross resource families are being analysed to identify quantitative trait loci that may be controlling resistance to gastro-intestinal (GI) nematode parasites, mainly Haemonchus contortus. After assessing the phenotypic performance of the lambs following exposure to natural infections, the surviving lambs were drenched and moved indoors for an artificial challenge with H. contortus along with straightbred D and R lambs. A total of 1317 lambs were included in the analyses consisting of 523 3/4D, 580 3/4R, 87 D and 127 R. The D lambs were significantly and consistently heavier than R lambs and 3/4D were significantly heavier than the 3/4R lambs. The difference between the backcrosses was about half of that between the straightbreds. Resistance was assessed in terms of faecal egg counts (FEC) and total worm counts (TWC) at necropsy while packed cell volume (PCV) was used to assess resilience to weekly oral doses of 2500 infective larvae of H. contortus. No significant breed differences were observed for log transformed FEC (LFEC). A significant breed difference in PCV was recorded. The backcrosses had the higher values and while no differences were observed between the straightbreds, 3/4D had significantly higher PCV than the 3/4R. Despite the absence of breed differences in FEC the R and the 3/4R had significantly fewer worms than the D and the 3/4D. The D had significantly longer worms than the R and the 3/4D had significantly longer worms than the 3/4R. Worms recovered from D had more eggs than those recovered from R. Similarly worms from 3/4D contained more eggs than those from 3/4R. Thus, on a breed basis the breed with more worms had longer worms. In contrast, when, in a small part of the experiment two doses of larvae were used to check for any breed by dose interactions, worms from the low dose (and hence fewer worms) animals were longer

  18. The phenotypic and genotypic characteristics of antibiotic resistance in Escherichia coli populations isolated from farm animals with different exposure to antimicrobial agents.

    Science.gov (United States)

    Mazurek, Justyna; Pusz, Paweł; Bok, Ewa; Stosik, Michał; Baldy-Chudzik, Katarzyna

    2013-01-01

    The aim of the study was to determine the influence of the presence or the absence of antibiotic input on the emergence and maintenance of resistance in commensal bacteria from food producing animals. The research material constituted E. coli isolates from two animal species: swine at different age from one conventional pig farm with antibiotic input in young pigs and from beef and dairy cattle originated from organic breeding farm. The sensitivity to 16 antimicrobial agents was tested, and the presence of 15 resistance genes was examined. In E. coli from swine, the most prevalent resistance was resistance to streptomycin (88.3%), co-trimoxazole (78.8%), tetracycline (57.3%) ampicillin (49.3%) and doxycycline (44.9%) with multiple resistance in the majority. The most commonly observed resistance genes were: bla(TEM) (45.2%), tetA (35.8%), aadA1 (35.0%), sul3 (29.5%), dfrA1 (20.4%). Differences in phenotypes and genotypes of E. coli between young swine undergoing prevention program and the older ones without the antibiotic pressure occurred. A disparate resistance was found in E. coli from cattle: cephalothin (36.9%), cefuroxime (18.9%), doxycycline (8.2%), nitrofurantoin (7.7%), and concerned mainly dairy cows. Among isolates from cattle, multidrug resistance was outnumbered by resistance to one or two antibiotics and the only found gene markers were: bla(SHV), (3.4%), tetA (1.29%), bla(TEM) (0.43%) and tetC (0.43%). The presented outcomes provide evidence that antimicrobial pressure contributes to resistance development, and enteric microflora constitutes an essential reservoir of resistance genes.

  19. Anthropological research on the urban population inhabiting the city of Iaşi during the medieval period. The 17th century necropolis located on the eastern side of ’’Curtea Domneasca’’

    Directory of Open Access Journals (Sweden)

    Vasilica-Monica Groza

    2013-10-01

    Full Text Available This article contains anthropological data regarding a series of 111 human skeletons (discovered in 60 inhumation tombs unearthed from the medieval necropolis (17th century located on the eastern side of ’’Curtea Domnească’’ of Iaşi. By analysing each skeleton according to the methodology used in paleoanthropological research, we distinguished a set of biometric and morphological features which signalized in the end the common anthropological features of the group inhumed in this medieval necropolis. We point out that the anthropological research conducted upon 96 adult skeletons (70 males and 26 females indicates, on average, a population of over-medium height in the case of males and tall in the case of females, with a wide, high and moderately long neurocranium, a brachycephalic cranial index, hypsicranic and metriocranic skullcap, oval metriometope forehead, with intermediate crests and medium-sized occipital bone. The faces are mesoprosope and mesene with mesoconch orbits and mesorrhine noses. The mandibular robustness is moderate in the case of males and reduced in the case of females, while the shaping of the cranial bone is more accentuated at the former. Analyzing the main biometric and morphological indicators, we established that the primary background for this population group can be defined as dinarico-mediteranido, with secondary Alpinoid, Nordoid and East-Europoid influences.

  20. Determination of urine caffeine and its metabolites by use of high-performance liquid chromatography-tandem mass spectrometry: estimating dietary caffeine exposure and metabolic phenotyping in population studies.

    Science.gov (United States)

    Rybak, Michael E; Pao, Ching-I; Pfeiffer, Christine M

    2014-01-01

    We have developed and validated a high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determining urine caffeine and 14 caffeine metabolites suitable for estimating caffeine exposure and metabolic phenotyping in population studies. Sample preparation consisted solely of a series of simple reagent treatments at room temperature. Stable isotope-labeled analogs were used as internal standards for all analytes. We developed rapid LC-MS/MS separations for both positive and negative ion mode electrospray ionizations to maximize measurement sensitivity. Limits of detection were 0.05-0.1 μmol/L depending on the analytes. Method imprecision, based on total coefficients of variation, was generally 1 μmol/L. Analyte recoveries were typically within 10 % of being quantitative (100 %), and good agreement was observed among analytes measured across different MS/MS transitions. We applied this method to the analysis of a convenience set of human urine samples (n = 115) and were able to detect a majority of the analytes in ≥99 % of samples as well as calculate caffeine metabolite phenotyping ratios for cytochrome P450 1A2 and N-acetyltransferase 2. Whereas existing LC-MS/MS methods are limited in number of caffeine metabolites for which they are validated, or are designed for studies in which purposely elevated caffeine levels are expected, our method is the first of its kind designed specifically for the rapid, sensitive, accurate, and precise measurement of urine caffeine and caffeine metabolites at concentrations relevant to population studies.

  1. Relationship between Lipid Phenotypes, Overweight, Lipid Lowering Drug Response and KIF6 and HMG-CoA Genotypes in a Subset of the Brisighella Heart Study Population

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    Sabrina Angelini

    2017-12-01

    Full Text Available The existence of genetic traits might explain the susceptibility to develop hypercholesterolemia and the inter-individual differences in statin response. This study was performed to evaluate whether individuals’ polymorphisms in HMG-CoA and KIF6 genes are independently associated with hypercholesterolemia, other lipid-associated traits, and statin response in unselected individuals enrolled in the Brisighella heart study (Survey 2012. A total of 1622 individuals, of which 183 under statin medication, were genotyped for a total of five polymorphisms (KIF6 rs20455, rs9471077, rs9462535; HMG-CoA rs3761740, rs3846662. The relationships between the five loci and clinical characteristics were analyzed. The principal basic parameters calculated on 12 h fasting blood included total cholesterol (TC, High Density Lipoprotein Cholesterol (HDL-C, Low-Density Lipoprotein Cholesterol (LDL-C, and triglycerides (TG. Hypercholesterolemia was defined as a TC >200 mg/dL or use of lipid-lowering medication. 965 individuals were characterized by hypercholesterolemia; these subjects were significantly older (p < 0.001, with body mass index (BMI and waist circumference significantly higher (p < 0.001 compared to the others. HMG-CoA rs3846662 GG genotype was significantly over-represented in the hypercholesterolemic group (p = 0.030. HMG-CoA rs3846662 genotype was associated with the level of TC and LDL-C. Furthermore, in the same subset of untreated subjects, we observed a significant correlation between the KIF6 rs20455 and HDL-C. KIF6 variants were associated with a significantly lower (rs20455 or higher (rs9471077 and rs9462535 risk of obesity, in males only. No association between responsiveness to statins and the polymorphisms under investigation were observed. Our results showed associations between HMG-CoA rs3846662 and KIF6 rs20455 and lipid phenotypes, which may have an influence on dyslipidemia-related events. Moreover, this represents the first study

  2. Further phenotypic characterization of the primitive lineage− CD34+CD38−CD90+CD45RA− hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patients with chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    Wisniewski, D; Affer, M; Willshire, J; Clarkson, B

    2011-01-01

    The most primitive hematopoietic stem cell (HSC)/progenitor cell (PC) population reported to date is characterized as being Lin−CD34+CD38−CD90+CD45R. We have a long-standing interest in comparing the characteristics of hematopoietic progenitor cell populations enriched from normal subjects and patients with chronic myelogenous leukemia (CML). In order to investigate further purification of HSCs and for potential targetable differences between the very primitive normal and CML stem/PCs, we have phenotypically compared the normal and CML Lin−CD34+CD38−CD90+CD45RA− HSC/PC populations. The additional antigens analyzed were HLA-DR, the receptor tyrosine kinases c-kit and Tie2, the interleukin-3 cytokine receptor, CD33 and the activation antigen CD69, the latter of which was recently reported to be selectively elevated in cell lines expressing the Bcr-Abl tyrosine kinase. Notably, we found a strikingly low percentage of cells from the HSC/PC sub-population isolated from CML patients that were found to express the c-kit receptor (<1%) compared with the percentages of HSC/PCs expressing the c-kitR isolated from umbilical cord blood (50%) and mobilized peripheral blood (10%). Surprisingly, Tie2 receptor expression within the HSC/PC subset was extremely low from both normal and CML samples. Using in vivo transplantation studies, we provide evidence that HLA-DR, c-kitR, Tie2 and IL-3R may not be suitable markers for further partitioning of HSCs from the Lin−CD34+CD38−CD90+CD45RA− sub-population

  3. The Impact of Herbicide-Resistant Rice Technology on Phenotypic Diversity and Population Structure of United States Weedy Rice1[W][OPEN

    Science.gov (United States)

    Burgos, Nilda Roma; Singh, Vijay; Tseng, Te Ming; Black, Howard; Young, Nelson D.; Huang, Zhongyun; Hyma, Katie E.; Gealy, David R.; Caicedo, Ana L.

    2014-01-01

    The use of herbicide-resistant (HR) Clearfield rice (Oryza sativa) to control weedy rice has increased in the past 12 years to constitute about 60% of rice acreage in Arkansas, where most U.S. rice is grown. To assess the impact of HR cultivated rice on the herbicide resistance and population structure of weedy rice, weedy samples were collected from commercial fields with a history of Clearfield rice. Panicles from each weedy type were harvested and tested for resistance to imazethapyr. The majority of plants sampled had at least 20% resistant offspring. These resistant weeds were 97 to 199 cm tall and initiated flowering from 78 to 128 d, generally later than recorded for accessions collected prior to the widespread use of Clearfield rice (i.e. historical accessions). Whereas the majority (70%) of historical accessions had straw-colored hulls, only 30% of contemporary HR weedy rice had straw-colored hulls. Analysis of genotyping-by-sequencing data showed that HR weeds were not genetically structured according to hull color, whereas historical weedy rice was separated into straw-hull and black-hull populations. A significant portion of the local rice crop genome was introgressed into HR weedy rice, which was rare in historical weedy accessions. Admixture analyses showed that HR weeds tend to possess crop haplotypes in the portion of chromosome 2 containing the ACETOLACTATE SYNTHASE gene, which confers herbicide resistance to Clearfield rice. Thus, U.S. HR weedy rice is a distinct population relative to historical weedy rice and shows modifications in morphology and phenology that are relevant to weed management. PMID:25122473

  4. Environmental and phenotype-related risk factors for owner-reported allergic/atopic skin symptoms and for canine atopic dermatitis verified by veterinarian in a Finnish dog population.

    Science.gov (United States)

    Anturaniemi, Johanna; Uusitalo, Liisa; Hielm-Björkman, Anna

    2017-01-01

    The aim of this cross-sectional study was to observe whether environmental factors and phenotypic traits are associated with owner-reported skin problems and with veterinary diagnosed canine atopic dermatitis (CAD). Data were collected using the validated online DOGRISK questionnaire. Out of the data that the questionnaire provides for analysis, focus was first turned towards addressing questions regarding 'Atopy/allergy (skin symptoms)' using a total of 8643 dogs: 1585 dogs with owner-reported allergic/atopic skin symptoms and 7058 dogs without. A subsequent analysis compared dogs with veterinary-verified CAD (n = 322) as a case group against the 7058 dogs without owner-reported skin symptoms. The association between 21 factors related to the environment, canine phenotypes and breed groups within both populations were analysed using univariable and multivariable logistic regression. The environmental factors that showed a significant inverse association with the risk of owner-reported allergic/atopic skin symptoms were as following: whether the dog was living in a detached house, whether there were other dogs in the household, and whether the dog was born in the current household. Having over 50% white colour in the coat and living in an extremely clean household were significantly associated with an increased risk of owner-reported allergic/atopic skin symptoms. The five breeds demonstrating the highest proportion of owner-reported allergic/atopic skin symptoms were West Highland white terrier, Boxer, English bulldog, Dalmatian and French bulldog. The Fédération Cynologique Internationale dog breed groups 3 (Terriers) and 6 (Scent hounds and related breeds) showed a significantly higher risk for owner-reported allergic/atopic skin symptoms than mixed breed dogs. In the second population, the inverse association was observed between the risk of CAD and the presence of other dogs in the household, and whether the dog had been born in the current household. The

  5. Environmental and phenotype-related risk factors for owner-reported allergic/atopic skin symptoms and for canine atopic dermatitis verified by veterinarian in a Finnish dog population.

    Directory of Open Access Journals (Sweden)

    Johanna Anturaniemi

    Full Text Available The aim of this cross-sectional study was to observe whether environmental factors and phenotypic traits are associated with owner-reported skin problems and with veterinary diagnosed canine atopic dermatitis (CAD. Data were collected using the validated online DOGRISK questionnaire. Out of the data that the questionnaire provides for analysis, focus was first turned towards addressing questions regarding 'Atopy/allergy (skin symptoms' using a total of 8643 dogs: 1585 dogs with owner-reported allergic/atopic skin symptoms and 7058 dogs without. A subsequent analysis compared dogs with veterinary-verified CAD (n = 322 as a case group against the 7058 dogs without owner-reported skin symptoms. The association between 21 factors related to the environment, canine phenotypes and breed groups within both populations were analysed using univariable and multivariable logistic regression. The environmental factors that showed a significant inverse association with the risk of owner-reported allergic/atopic skin symptoms were as following: whether the dog was living in a detached house, whether there were other dogs in the household, and whether the dog was born in the current household. Having over 50% white colour in the coat and living in an extremely clean household were significantly associated with an increased risk of owner-reported allergic/atopic skin symptoms. The five breeds demonstrating the highest proportion of owner-reported allergic/atopic skin symptoms were West Highland white terrier, Boxer, English bulldog, Dalmatian and French bulldog. The Fédération Cynologique Internationale dog breed groups 3 (Terriers and 6 (Scent hounds and related breeds showed a significantly higher risk for owner-reported allergic/atopic skin symptoms than mixed breed dogs. In the second population, the inverse association was observed between the risk of CAD and the presence of other dogs in the household, and whether the dog had been born in the current

  6. Evolution of molecular phenotypes under stabilizing selection

    International Nuclear Information System (INIS)

    Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

    2013-01-01

    Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes. (paper)

  7. Comportamento fenotípico e genotípico de populações de manjericão Phenotypic and genotypic behavior of basil populations

    Directory of Open Access Journals (Sweden)

    Arie F Blank

    2010-09-01

    Full Text Available Genótipos de manjericão (Ocimum basilicum L. apresentam diferentes teores, rendimentos e composições químicas de óleos essenciais. Fatores influenciam na produção do óleo essencial de manjericão, como a cultivar plantada e o método de cultivo. O estudo dos parâmetros genéticos tem sido ferramenta útil na identificação de genótipos superiores. Este trabalho teve o objetivo de estimar alguns parâmetros genéticos associados ao comportamento produtivo de seis populações de manjericão nos anos agrícola 2004/05 e 2005/06. As características massa seca de folha + inflorescência e rendimento de óleo essencial apresentaram grande variabilidade por forte influência dos anos estudados. Já o teor de linalol manteve sua produtividade estável ao longo dos dois anos. Teor e rendimento de óleo essencial e teor de linalol no óleo essencial apresentaram herdabilidades altas na análise conjunta, indicando controle genético e grande possibilidade de serem transmitidas para as gerações futuras. Na análise conjunta as populações PI 197442-S3-bulk 3, PI 197442-S3-bulk 5 e PI 197442-S3-bulk 8 apresentaram os maiores teores e rendimentos de óleo essencial. Quanto ao constituinte químico majoritário do óleo essencial, o linalol, todas as populações apresentaram teores semelhantes, diferindo apenas na presença de alguns constituintes químicos minoritários.Basil (Ocimum basilicum L. genotypes present different contents, yields and chemical constituents in its essential oils. Factors influence the essential oil production of basil, such as cultivar and cultivation method. The study of genetic parameters is a useful tool to identify superior genotypes. In this work we estimated some genetic parameters associated to the production behavior of six basil populations cultivated in 2004/05 and 2005/06. The variables dry weight of leaves + inflorescences and essential oil yield presented high variability because of strong influence of

  8. Single-sided NMR

    CERN Document Server

    Casanova, Federico; Blümich, Bernhard

    2011-01-01

    Single-Sided NMR describes the design of the first functioning single-sided tomograph, the related measurement methods, and a number of applications. One of the key advantages to this method is the speed at which the images are obtained.

  9. Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis.

    Directory of Open Access Journals (Sweden)

    Xue-bin Wang

    Full Text Available Homocysteine (Hcy is a potential risk factor for age-related cataract (ARC. Methylenetetrahydrofolate reductase (MTHFR is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs in MTHFR gene were genotyped using the high-resolution melting (HRM method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male. The plasma MTHFR activity, folic acid (FA, vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA. The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003. Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003. Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118 on ARC risk (OR = 1.55, P = 0.003. Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001 was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC

  10. Federated Tensor Factorization for Computational Phenotyping

    Science.gov (United States)

    Kim, Yejin; Sun, Jimeng; Yu, Hwanjo; Jiang, Xiaoqian

    2017-01-01

    Tensor factorization models offer an effective approach to convert massive electronic health records into meaningful clinical concepts (phenotypes) for data analysis. These models need a large amount of diverse samples to avoid population bias. An open challenge is how to derive phenotypes jointly across multiple hospitals, in which direct patient-level data sharing is not possible (e.g., due to institutional policies). In this paper, we developed a novel solution to enable federated tensor factorization for computational phenotyping without sharing patient-level data. We developed secure data harmonization and federated computation procedures based on alternating direction method of multipliers (ADMM). Using this method, the multiple hospitals iteratively update tensors and transfer secure summarized information to a central server, and the server aggregates the information to generate phenotypes. We demonstrated with real medical datasets that our method resembles the centralized training model (based on combined datasets) in terms of accuracy and phenotypes discovery while respecting privacy. PMID:29071165

  11. Side Effects: Sleep Problems

    Science.gov (United States)

    Sleep problems are a common side effect during cancer treatment. Learn how a polysomnogram can assess sleep problems. Learn about the benefits of managing sleep disorders in men and women with cancer.

  12. Side Effects: Fatigue

    Science.gov (United States)

    Fatigue is a common side effect of many cancer treatments such as chemotherapy, radiation therapy, immunotherapy, and surgery. Anemia and pain can also cause fatigue. Learn about symptoms and way to manage fatigue.

  13. Side Effects: Diarrhea

    Science.gov (United States)

    Diarrhea, a side effect of cancer treatment, may cause symptoms such as loose, watery stools. Diarrhea can lead to dehydration and malnutrition in cancer patients. Learn about ways to treat and manage diarrhea during cancer treatment.

  14. Side Effects: Appetite Loss

    Science.gov (United States)

    Cancer treatments may lower your appetite. Side effects such as nausea, fatigue, or mouth sores can also making eating difficult. Learn how to eat well to avoid losing weight or becoming dehydrated, so you stay strong during treatment.

  15. Side Effects: Pain

    Science.gov (United States)

    Controlling pain is an important part of your cancer treatment plan. Learn how to track levels of pain. Find out how pain, a side effect of cancer treatment, is treated using acupuncture, biofeedback, and physical therapy.

  16. Side Effects: Anemia

    Science.gov (United States)

    Anemia is a side effect of cancer treatments, including chemotherapy and radiation therapy. It can make women and men feel fatigued, dizzy, and short of breath. Learn how to manage fatigue caused by anemia during cancer treatment.

  17. Side core lifter

    Energy Technology Data Exchange (ETDEWEB)

    Edelman, Ya A

    1982-01-01

    A side core lifter is proposed which contains a housing with guide slits and a removable core lifter with side projections on the support section connected to the core receiver. In order to preserve the structure of the rock in the core sample by means of guaranteeing rectilinear movement of the core lifter in the rock, the support and core receiver sections are hinged. The device is equipped with a spring for angular shift in the core-reception part.

  18. Asthma phenotypes in childhood.

    Science.gov (United States)

    Reddy, Monica B; Covar, Ronina A

    2016-04-01

    This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

  19. [Psychoanalysis and Side Effect].

    Science.gov (United States)

    Shirahase, Joichiro

    2015-01-01

    A study of psychoanalysis from the perspective of side effects reveals that its history was a succession of measures to deal with its own side effects. This, however, does not merely suggest that, as a treatment method, psychoanalysis is incomplete and weak: rather, its history is a record of the growth and development of psychoanalysis that discovered therapeutic significance from phenomena that were initially regarded as side effects, made use of these discoveries, and elaborated them as a treatment method. The approach of research seen during the course of these developments is linked to the basic therapeutic approach of psychoanalysis. A therapist therefore does not draw conclusions about a patient's words and behaviors from a single aspect, but continues to make efforts to actively discover a variety of meanings and values from them, and to make the patient's life richer and more productive. This therapeutic approach is undoubtedly one of the unique aspects of psychoanalysis. I discuss the issue of psychoanalysis and side effects with the aim of clarifying this unique characteristic of psychoanalysis. The phenomenon called resistance inevitably emerges during the process of psychoanalytic treatment. Resistance can not only obstruct the progress of therapy; it also carries the risk of causing a variety of disadvantages to the patient. It can therefore be seen as an adverse effect. However, if we re-examine this phenomenon from the perspective of transference, we find that resistance is in fact a crucial tool in psychoanalysis, and included in its main effect, rather than a side effect. From the perspective of minimizing the character of resistance as a side effect and maximizing its character as a main effect, I have reviewed logical organization, dynamic evaluation, the structuring of treatment, the therapist's attitudes, and the training of therapists. I conclude by stating that psychoanalysis has aspects that do not match the perspective known as a side

  20. Brain nuclei in actively courting red-sided garter snakes: a paradigm of neural trimorphism.

    Science.gov (United States)

    Krohmer, Randolph W; DeMarchi, Geno A; Baleckaitis, Daniel D; Lutterschmidt, Deborah I; Mason, Robert T

    2011-03-28

    During the breeding season, two distinct male phenotypes are exhibited by red-sided garter snakes (Thamnophis sirtalis parietalis), with courtship behavior being directed not only toward females, but also toward a sub-population of males called she-males. She-males are morphologically identical to other males except for a circulating androgen level three times that of normal males and their ability to produce a female-like pheromone. As in other vertebrates, limbic nuclei in the red-sided garter snake brain are involved in the control of sexual behaviors. For example, an intact anterior hypothalamus pre-optic area (AHPOA) is essential for the initiation and maintenance of reproduction. To determine if brain morphology varies among the three behavioral phenotypes (i.e., males, she-males, and females) during the breeding season, we examined the volume, cell size and cell density of the AHPOA as well as a control region, the external nucleus of the optic tract (ENOT). We used Luxol Fast Blue and Ziehl's Fuchsin to visualize neurons and glial cells, respectively. No significant differences were observed among the three behavioral phenotypes in the volume, cell size or density in the control region. In contrast, the volume, cell size and density of the AHPOA of she-males were significantly greater than those of both male and female snakes. While the volume of the AHPOA was significantly greater in females compared to males, no differences were observed in cell size or density. These differences in brain morphology suggest a possible underlying mechanism for phenotypic-specific behavioral patterns. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Working the Dark Side

    DEFF Research Database (Denmark)

    Bjering, Jens Christian Borrebye

    A few days after the terror attacks of 9/11, then Vice President Dick Cheney appeared on television with a call for “working the dark side.” While still unclear what this expression entailed at the time, Cheney's comment appears in retrospect to almost have been prophetic for the years to come....... By analyzing official reports and testimonies from soldiers partaking in the War On Terror, the dissertation's second part—dark arts—focuses on the transformation of the dark side into a productive space in which “information” and the hunt for said information overshadowed all legal, ethical, or political...

  2. Clinical phenotypes of asthma

    NARCIS (Netherlands)

    Bel, Elisabeth H.

    2004-01-01

    PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

  3. Forskningens personlige side

    DEFF Research Database (Denmark)

    Hansen, Finn Thorbjørn

    2008-01-01

    Artiklen omhandler den ontologiske vending inden for universitetspædagogisk forskning, og redegør for hvorfor en mere personlig og eksistentiel side ved forskningen må medtænkes i universitetspædagogikken og -vejledningen. Udgivelsesdato: 24.11.08...

  4. Side loading filter apparatus

    International Nuclear Information System (INIS)

    Reynolds, K.E.

    1981-01-01

    A side loading filter chamber for use with radioactive gases is described. The equipment incorporates an inexpensive, manually operated, mechanism for aligning filter units with a number of laterally spaced wall openings and for removing the units from the chamber. (U.K.)

  5. Side insertable spacer

    International Nuclear Information System (INIS)

    Patterson, J.F.; Ewing, R.H.

    1992-01-01

    This patent describes a spacer for restraining the fuel rods of a nuclear fuel assembly, the assembly being formed of a plurality of parallel, elongated fuel rods so arranged that the assembly is bounded by a polygon having an even number of sides, the rods being so arranged as to lie in a plurality of sets of parallel rows, the rows of each set being perpendicular to one of the sides of the polygon. It comprises a number of spacer combs equal to at least half the number of the sides of the polygon, the spacer combs being superposed on each other, each of the spacer combs comprising: a single base strip having a length equal to that of one of the sides of the polygon and grid strips equal in number to the spaces between rows in one of the sets, and at least a majority of the grid strips being of a length sufficient to extend substantially the full length of the rows; the grid strips being provided with spring members positioned to engage each of the rods; the grid strips being provided with spring members positioned to engage each of the rods; the grid strips being secured to and extending at right angles to the base strip; the grid strips of different combs being positioned at angles to each other, so as to occupy the spaces between rows in different sets

  6. T- and NK-cell populations with regulatory phenotype and markers of apoptosis in circulating lymphocytes of patients with CIN3 or microcarcinoma of the cervix: evidence for potential mechanisms of immune suppression.

    Science.gov (United States)

    Kurmyshkina, Olga V; Kovchur, Pavel I; Schegoleva, Ludmila V; Volkova, Tatyana O

    2017-01-01

    expression, confirming that this change likely has different functional significance for these two subsets. A search for correlations between the phenotypic parameters analyzed in this study was performed to demonstrate that women with early neoplastic lesions of the cervix, such as carcinoma in situ and microinvasive carcinoma, displayed a coordinated increase in expression of Treg markers in circulating lymphocytes, along with more pronounced cross-relationships between Treg numbers, CD95 expression on T cells, and apoptosis, compared to the control group. The results of this study suggest that a diversity of immune regulatory mechanisms that provide support for initial stages of invasive growth in cervical cancer patients includes systemic changes in the ratios between the principal regulatory and effector lymphocyte populations both within adaptive and innate immunity.

  7. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  8. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  9. Systematic identification of proteins that elicit drug side effects

    DEFF Research Database (Denmark)

    Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica

    2013-01-01

    Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins...... that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug-target relations to identify overrepresented protein-side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause......) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations....

  10. Phenotypic characterisation and molecular polymorphism of ...

    African Journals Online (AJOL)

    The study of the phenotypic characterisation and molecular polymorphism of local chicken populations was carried out in Benin on 326 chickens of the Forest ecological area and 316 of the Savannah ecological area, all were 7 months old at least. The collection of blood for the molecular typing was achieved on 121 ...

  11. Genotype-Phenotype Aspects of Type 2 Long QT Syndrome

    NARCIS (Netherlands)

    Shimizu, Wataru; Moss, Arthur J.; Wilde, Arthur A. M.; Towbin, Jeffrey A.; Ackerman, Michael J.; January, Craig T.; Tester, David J.; Zareba, Wojciech; Robinson, Jennifer L.; Qi, Ming; Vincent, G. Michael; Kaufman, Elizabeth S.; Hofman, Nynke; Noda, Takashi; Kamakura, Shiro; Miyamoto, Yoshihiro; Shah, Samit; Amin, Vinit; Goldenberg, Ilan; Andrews, Mark L.; McNitt, Scott

    2009-01-01

    Objectives The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS). Background Previous studies were limited by population size in their ability to examine phenotypic effect of

  12. Genetic Regulation of Phenotypic Plasticity and Canalisation in Yeast Growth.

    Directory of Open Access Journals (Sweden)

    Anupama Yadav

    Full Text Available The ability of a genotype to show diverse phenotypes in different environments is called phenotypic plasticity. Phenotypic plasticity helps populations to evade extinctions in novel environments, facilitates adaptation and fuels evolution. However, most studies focus on understanding the genetic basis of phenotypic regulation in specific environments. As a result, while it's evolutionary relevance is well established, genetic mechanisms regulating phenotypic plasticity and their overlap with the environment specific regulators is not well understood. Saccharomyces cerevisiae is highly sensitive to the environment, which acts as not just external stimulus but also as signalling cue for this unicellular, sessile organism. We used a previously published dataset of a biparental yeast population grown in 34 diverse environments and mapped genetic loci regulating variation in phenotypic plasticity, plasticity QTL, and compared them with environment-specific QTL. Plasticity QTL is one whose one allele exhibits high plasticity whereas the other shows a relatively canalised behaviour. We mapped phenotypic plasticity using two parameters-environmental variance, an environmental order-independent parameter and reaction norm (slope, an environmental order-dependent parameter. Our results show a partial overlap between pleiotropic QTL and plasticity QTL such that while some plasticity QTL are also pleiotropic, others have a significant effect on phenotypic plasticity without being significant in any environment independently. Furthermore, while some plasticity QTL are revealed only in specific environmental orders, we identify large effect plasticity QTL, which are order-independent such that whatever the order of the environments, one allele is always plastic and the other is canalised. Finally, we show that the environments can be divided into two categories based on the phenotypic diversity of the population within them and the two categories have

  13. HIV Medicines and Side Effects

    Science.gov (United States)

    ... medicines, talk to your health care provider about possible side effects. Tell your health care provider about your lifestyle and point out any possible side effects that would be especially hard for you to ...

  14. Probiotics: Safety and Side Effects

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Probiotics Safety and Side Effects Past Issues / Winter 2016 ... Says About the Safety and Side Effects of Probiotics Whether probiotics are likely to be safe for ...

  15. Side-View Face Recognition

    NARCIS (Netherlands)

    Santemiz, P.; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.

    2010-01-01

    Side-view face recognition is a challenging problem with many applications. Especially in real-life scenarios where the environment is uncontrolled, coping with pose variations up to side-view positions is an important task for face recognition. In this paper we discuss the use of side view face

  16. Adaptation to different climates results in divergent phenotypic ...

    Indian Academy of Sciences (India)

    The phenotypic plasticity of wing size and wing shape of Zaprionus indianus was ... C) in two natural populations living under different climates, equatorial and ... size and shape in an invasive drosophilid. J. Genet. 87, 209–217]. Introduction.

  17. Differential Impact of Lactose/Lactase Phenotype on Colonic Microflora

    Directory of Open Access Journals (Sweden)

    Andrew Szilagyi

    2010-01-01

    Full Text Available BACKGROUND: The ability to digest lactose divides the world’s population into two phenotypes that may be risk variability markers for several diseases. Prebiotic effects likely favour lactose maldigesters who experience lactose spilling into their colon.

  18. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  19. Phenotypic Resistance to Antibiotics

    Directory of Open Access Journals (Sweden)

    Jose L. Martinez

    2013-04-01

    Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  20. Invasion strategies in clonal aquatic plants: Are phenotypic differences caused by phenotypic plasticity or local adaptation?

    DEFF Research Database (Denmark)

    Riis, Tenna; Lambertini, Carla; Olesen, Birgit

    2010-01-01

    conditions and plant morphological characteristics. Conclusions: The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between......Background and Aims: The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important....... Methods: Field populations with a large phenotypic variety were sampled in a range of lakes and streams with different chemical and physical properties. The phenotypic plasticity of the species before and after cultivation was studied in a common garden growth experiment, and the genetic diversity...

  1. Age is associated with asthma phenotypes.

    Science.gov (United States)

    Ponte, Eduardo V; Lima, Aline; Almeida, Paula C A; de Jesus, Juliana P V; Lima, Valmar B; Scichilone, Nicola; Souza-Machado, Adelmir; Cruz, Álvaro A

    2017-11-01

    The relationship between age and asthma phenotypes is important as population is ageing, asthma is becoming common in older ages and recently developed treatments for asthma are guided by phenotypes. The aim of this study is to evaluate whether age is associated with specific asthma phenotypes. This is a cross-sectional study. We included subjects with asthma of varied degrees of severity. Subjects underwent spirometry, skin prick test to aeroallergens, answered the Asthma Control Questionnaire and had blood samples collected. We performed binary logistic regression analysis to evaluate whether age is associated with asthma phenotypes. We enrolled 868 subjects. In comparison with subjects ≤ 40 years, older subjects had high odds of irreversible airway obstruction (from 41 to 64 years, OR: 1.83 (95% CI: 1.32-2.54); ≥65 years, OR: 3.45 (2.12-5.60)) and severe asthma phenotypes (from 41 to 64 years, OR: 3.23 (2.26-4.62); ≥65 years, OR: 4.55 (2.39-8.67)). Older subjects had low odds of atopic (from 41 to 64 years, OR: 0.56 (0.39-0.79); ≥65 years, OR: 0.47 (0.27-0.84)) and eosinophilic phenotypes (from 41 to 64 years, OR: 0.63 (0.46-0.84); ≥65 years, OR: 0.39 (0.24-0.64)). Older subjects with asthma have low odds of atopic and eosinophilic phenotypes, whereas they present high odds of irreversible airway obstruction and severe asthma. © 2017 Asian Pacific Society of Respirology.

  2. The Mass-Dimension Relationships in the Mussels Mytilus Galloprovincialis (Mollusca, Bivalvia from Different Phenotypical Groups in Periphyton Populations near Odessa Coast, the North-Western Part of Black Sea

    Directory of Open Access Journals (Sweden)

    Govorin I. A.

    2016-06-01

    Full Text Available The data of the size-mass indices in the mussels Mytilus galloprovincialis (Lamarck, 1819 from three phenotypic groups - brown, dark violet (black and “zebra” (brown with radial black stripes shells in the periphyton settlements on the concrete traverses near Odessa coast, the North-western part of Black Sea (Ukraine, in March-November 2014-2015 are presented. A comparative evaluation has been made on the relationships of total mass of the mollusks, wet and dry mass of their soft body and mass of the shells on the one hand, and the size of animals (length of its shells on the other hand, in the each of phenotypical groups from the five marine beach areas. It is shown, that in the marine areas with different degrees of isolation from the open sea by coast-protection engineering constructions, the mussels from different phenotypes have almost the same size-mass characteristics. Only the dry weight of soft animal body, which indicated to fatness of mollusk and therefore demonstrated his biological prosperity in specific hydrological conditions, can serve as a reliable criterion which can mark the shellfish habitats with different gradients of environmental factors.

  3. Drug target identification using side-effect similarity

    DEFF Research Database (Denmark)

    Campillos, Monica; Kuhn, Michael; Gavin, Anne-Claude

    2008-01-01

    Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed...... drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro...... binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs....

  4. Invasion strategies in clonal aquatic plants: are phenotypic differences caused by phenotypic plasticity or local adaptation?

    Science.gov (United States)

    Riis, Tenna; Lambertini, Carla; Olesen, Birgit; Clayton, John S.; Brix, Hans; Sorrell, Brian K.

    2010-01-01

    Background and Aims The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important. Here the primary adaptive strategy in three non-native, clonally reproducing macrophytes (Egeria densa, Elodea canadensis and Lagarosiphon major) in New Zealand freshwaters were examined and an attempt was made to link observed differences in plant morphology to local variation in habitat conditions. Methods Field populations with a large phenotypic variety were sampled in a range of lakes and streams with different chemical and physical properties. The phenotypic plasticity of the species before and after cultivation was studied in a common garden growth experiment, and the genetic diversity of these same populations was also quantified. Key Results For all three species, greater variation in plant characteristics was found before they were grown in standardized conditions. Moreover, field populations displayed remarkably little genetic variation and there was little interaction between habitat conditions and plant morphological characteristics. Conclusions The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between populations may facilitate ecotypic differentiation in the future cannot be excluded. These results thus indicate that invasive clonal aquatic plants adapt to new introduced areas by phenotypic plasticity. Inorganic carbon, nitrogen and phosphorous were important in controlling plant size of E. canadensis and L. major, but no other relationships between plant characteristics and habitat conditions were apparent. This implies that within-species differences in plant size can be explained

  5. Advanced phenotyping and phenotype data analysis for the plant growth and development study

    Directory of Open Access Journals (Sweden)

    Md. Matiur eRahaman

    2015-08-01

    Full Text Available Due to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis.

  6. ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

    Science.gov (United States)

    Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

    2017-11-01

    A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. How accurate is the phenotype? – An analysis of developmental noise in a cotton aphid clone

    Directory of Open Access Journals (Sweden)

    Babbitt Gregory A

    2008-02-01

    Full Text Available Abstract Background The accuracy by which phenotype can be reproduced by genotype potentially is important in determining the stability, environmental sensitivity, and evolvability of morphology and other phenotypic traits. Because two sides of an individual represent independent development of the phenotype under identical genetic and environmental conditions, average body asymmetry (or "fluctuating asymmetry" can estimate the developmental instability of the population. The component of developmental instability not explained by intrapopulational differences in gene or environment (or their interaction can be further defined as internal developmental noise. Surprisingly, developmental noise remains largely unexplored despite its potential influence on our interpretations of developmental stability, canalization, and evolvability. Proponents of fluctuating asymmetry as a bioindicator of environmental or genetic stress, often make the assumption that developmental noise is minimal and, therefore, that phenotype can respond sensitively to the environment. However, biologists still have not measured whether developmental noise actually comprises a significant fraction of the overall environmental response of fluctuating asymmetry observed within a population. Results In a morphometric study designed to partition developmental noise from fluctuating asymmetry in the wing morphology of a monoclonal culture of cotton aphid, Aphis gossipyii, it was discovered that fluctuating asymmetry in the aphid wing was nearly four times higher than in other insect species. Also, developmental noise comprised a surprisingly large fraction (≈ 50% of the overall response of fluctuating asymmetry to a controlled graded temperature environment. Fluctuating asymmetry also correlated negatively with temperature, indicating that environmentally-stimulated changes in developmental instability are mediated mostly by changes in the development time of individuals

  8. Refined Phenotyping of Modic Changes

    Science.gov (United States)

    Määttä, Juhani H.; Karppinen, Jaro; Paananen, Markus; Bow, Cora; Luk, Keith D.K.; Cheung, Kenneth M.C.; Samartzis, Dino

    2016-01-01

    Abstract Low back pain (LBP) is the world's most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese. We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting ≥30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors. In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P disability. The strength of the associations increased with the number of MC. This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP. PMID:27258491

  9. Comparing Demand Side Management approaches

    NARCIS (Netherlands)

    Molderink, Albert; Bakker, Vincent; Hurink, Johann L.; Smit, Gerardus Johannes Maria

    2012-01-01

    Due to increasing energy prices and the greenhouse effect, a more efficient energy supply is desirable, preferably based on renewable sources. To cope with the decrease of flexibility due to the introduction of renewables in production side of the supply chain, a more flexible consumer side is

  10. Environmental change, phenotypic plasticity, and genetic compensation.

    Science.gov (United States)

    Grether, Gregory F

    2005-10-01

    When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.

  11. The phenotypic diversity and fruit characterization of winter squash ...

    African Journals Online (AJOL)

    PRECIOUS

    2010-01-11

    Jan 11, 2010 ... collected from different provinces of the Black Sea region in 2006 and 2007 and phenotypic ... Picture of the diversity fruit size, shape and color for Cucurbita maxima ... Fruit traits used winter squash (C. maxima Duch) population characterization. S/N ..... Group J: There were a total of 18 populations in this.

  12. The spatial patterns of directional phenotypic selection.

    Science.gov (United States)

    Siepielski, Adam M; Gotanda, Kiyoko M; Morrissey, Michael B; Diamond, Sarah E; DiBattista, Joseph D; Carlson, Stephanie M

    2013-11-01

    Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

  13. The spatial patterns of directional phenotypic selection

    KAUST Repository

    Siepielski, Adam M.

    2013-09-12

    Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

  14. Genetic and phenotype catalog of native resident trout of the interior Columbia River Basin: FY-99 report: populations of the Pend Oreille, Kettle, and Sanpoil River Basins of Colville National Forest/ fiscal year 1999 report; ANNUAL

    International Nuclear Information System (INIS)

    Trotter, Patrick C.

    2001-01-01

    The 1994 Fish and Wildlife Program of the Northwest Power Planning Council specifies the recovery and preservation of population health of native resident fishes of the Columbia River Basin. Among the native resident species of concern are interior rainbow trout of the Columbia River redband subspecies Oncorhynchus mykiss gairdneri 1 and westslope cutthroat trout O. clarki lewisi. The westslope cutthroat trout has been petitioned for listing under the U. S. Endangered Species Act (American Wildlands et al. 1997). Before at-risk populations can be protected, their presence and status must be established. Where introgression from introduced species is a concern, as in the case of both westslope cutthroat trout and redband rainbow trout, genetic issues must be addressed as well. As is true with native trout elsewhere in the western United States (Behnke 1992), most of the remaining pure populations of these species in the Columbia River Basin are in relatively remote headwater reaches. The objective of this project is to photo-document upper Columbia Basin native resident trout populations in Washington, and to ascertain their species or subspecies identity and relative genetic purity using a nonlethal DNA technique. FY-99 was year two of a five-year project in which we conducted field visits to remote locations to seek out and catalog these populations. In FY-99 we worked in collaboration with the Colville National Forest and Kalispel Indian Tribe to catalog populations in the northeastern corner of Washington State

  15. From metabolome to phenotype

    DEFF Research Database (Denmark)

    Khakimov, Bekzod; Rasmussen, Morten Arendt; Kannangara, Rubini Maya

    2017-01-01

    for ideal vegetable protein production and for augmented β-glucan production. Seeds from three barley lines (Bomi, lys3.a and lys5.f) were sampled eight times during grain filling and analysed for metabolites using gas chromatography-mass spectrometry (GC-MS). The lys3.a mutation disrupts a regulator gene...... their successful application to link genetic and environmental factors with the seed phenotype of unique and agro-economically important barley models for optimal vegetable protein and dietary fibre production......., causing an increase in proteins rich in the essential amino acid lysine, while lys5.f carries a mutation in an ADP-glucose transporter gene leading to a significant increase in production of mixed-linkage β-glucan at the expense of α-glucan. Unique metabolic patterns associated with the tricarboxylic acid...

  16. Side Effects and Their Management

    Science.gov (United States)

    ... tumors. Donate Now Subscribe for e-updates Please leave this field empty ... tumors and their treatments bring an array of possible side effects in to a patient’s life. Fatigue, cognitive changes, and mood changes are ...

  17. Side Effects: Hair Loss (Alopecia)

    Science.gov (United States)

    Hair loss, also called alopecia, is a side effect of cancer treatments, such as chemotherapy and radiation therapy. Learn how to cope with and manage hair loss. Listen to tips from others who have experienced hair loss.

  18. Coping – Late Side Effects

    Science.gov (United States)

    Cancer treatment can cause late side effects that may not show up for months or years after treatment. These late effects may include heart and lung problems, bone loss, eye and hearing changes, lymphedema, and other problems

  19. Side Effects: Nausea and Vomiting

    Science.gov (United States)

    Types of nausea and vomiting caused by cancer treatment include: anticipatory, acute, and delayed. Controlling these side effects will help to prevent serious problems such as malnutrition and dehydration in people with cancer.

  20. Natural variation of model mutant phenotypes in Ciona intestinalis.

    Directory of Open Access Journals (Sweden)

    Paolo Sordino

    Full Text Available BACKGROUND: The study of ascidians (Chordata, Tunicata has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. CONCLUSIONS/SIGNIFICANCE: Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity.

  1. Natural Variation of Model Mutant Phenotypes in Ciona intestinalis

    Science.gov (United States)

    Brown, Euan R.; Leccia, Nicola I.; Squarzoni, Paola; Tarallo, Raffaella; Alfano, Christian; Caputi, Luigi; D'Ambrosio, Palmira; Daniele, Paola; D'Aniello, Enrico; D'Aniello, Salvatore; Maiella, Sylvie; Miraglia, Valentina; Russo, Monia Teresa; Sorrenti, Gerarda; Branno, Margherita; Cariello, Lucio; Cirino, Paola; Locascio, Annamaria; Spagnuolo, Antonietta; Zanetti, Laura; Ristoratore, Filomena

    2008-01-01

    Background The study of ascidians (Chordata, Tunicata) has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. Methodology/Principal Findings Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. Conclusions/Significance Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity. PMID:18523552

  2. Deep Learning for Plant Phenotyping

    OpenAIRE

    Mori, Matteo

    2016-01-01

    Plant Phenotyping is an emerging science which provides us the knowledge to better understand plants. Indeed, the study of the link between genetic background and environment in which plants develop can help us to determine cures for plants’ sicknesses and new ways to improve yields using limited resources. In this regard, one of the main aspects of Plant Phenotyping that were studied in the past, was Root Phenotyping, which is based on the study of the root architectures. In particular, toda...

  3. Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting.

    Science.gov (United States)

    Howe, B J; Cooper, M E; Vieira, A R; Weinberg, S M; Resick, J M; Nidey, N L; Wehby, G L; Marazita, M L; Moreno Uribe, L M

    2015-07-01

    Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ(2) statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10(-8)) and permanent dentitions (51% vs. 8%, P = 4 × 10(-62)) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the

  4. The Influence of Second-Hand Cigarette Smoke Exposure during Childhood and Active Cigarette Smoking on Crohn's Disease Phenotype Defined by the Montreal Classification Scheme in a Western Cape Population, South Africa.

    Directory of Open Access Journals (Sweden)

    Tawanda Chivese

    Full Text Available Smoking may worsen the disease outcomes in patients with Crohn's disease (CD, however the effect of exposure to second-hand cigarette smoke during childhood is unclear. In South Africa, no such literature exists. The aim of this study was to investigate whether disease phenotype, at time of diagnosis of CD, was associated with exposure to second-hand cigarette during childhood and active cigarette smoking habits.A cross sectional examination of all consecutive CD patients seen during the period September 2011-January 2013 at 2 large inflammatory bowel disease centers in the Western Cape, South Africa was performed. Data were collected via review of patient case notes, interviewer-administered questionnaire and clinical examination by the attending gastroenterologist. Disease phenotype (behavior and location was evaluated at time of diagnosis, according to the Montreal Classification scheme. In addition, disease behavior was stratified as 'complicated' or 'uncomplicated', using predefined definitions. Passive cigarette smoke exposure was evaluated during 3 age intervals: 0-5, 6-10, and 11-18 years.One hundred and ninety four CD patients were identified. Cigarette smoking during the 6 months prior to, or at time of diagnosis was significantly associated with ileo-colonic (L3 disease (RRR = 3.63; 95% CI, 1.32-9.98, p = 0.012 and ileal (L1 disease (RRR = 3.54; 95% CI, 1.06-11.83, p = 0.040 compared with colonic disease. In smokers, childhood passive cigarette smoke exposure during the 0-5 years age interval was significantly associated with ileo-colonic CD location (RRR = 21.3; 95% CI, 1.16-391.55, p = 0.040. No significant association between smoking habits and disease behavior at diagnosis, whether defined by the Montreal scheme, or stratified as 'complicated' vs 'uncomplicated', was observed.Smoking habits were associated with ileo-colonic (L3 and ileal (L1 disease at time of diagnosis in a South African cohort.

  5. Animal biometrics: quantifying and detecting phenotypic appearance.

    Science.gov (United States)

    Kühl, Hjalmar S; Burghardt, Tilo

    2013-07-01

    Animal biometrics is an emerging field that develops quantified approaches for representing and detecting the phenotypic appearance of species, individuals, behaviors, and morphological traits. It operates at the intersection between pattern recognition, ecology, and information sciences, producing computerized systems for phenotypic measurement and interpretation. Animal biometrics can benefit a wide range of disciplines, including biogeography, population ecology, and behavioral research. Currently, real-world applications are gaining momentum, augmenting the quantity and quality of ecological data collection and processing. However, to advance animal biometrics will require integration of methodologies among the scientific disciplines involved. Such efforts will be worthwhile because the great potential of this approach rests with the formal abstraction of phenomics, to create tractable interfaces between different organizational levels of life. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. The Moon's near side megabasin and far side bulge

    CERN Document Server

    Byrne, Charles

    2013-01-01

    Since Luna and Lunar Orbiter photographed the far side of the Moon, the mysterious dichotomy between the face of the Moon as we see it from Earth and the side of the Moon that is hidden has puzzled lunar scientists. As we learned more from the Apollo sample return missions and later robotic satellites, the puzzle literally deepened, showing asymmetry of the crust and mantle, all the way to the core of the Moon. This book summarizes the author’s successful search for an ancient impact feature, the Near Side Megabasin of the Moon and the extensions to impact theory needed to find it. The implications of this ancient event are developed to answer many of the questions about the history of the Moon.

  7. Distinct genetic architectures for phenotype means and plasticities in Zea mays.

    Science.gov (United States)

    Kusmec, Aaron; Srinivasan, Srikant; Nettleton, Dan; Schnable, Patrick S

    2017-09-01

    Phenotypic plasticity describes the phenotypic variation of a trait when a genotype is exposed to different environments. Understanding the genetic control of phenotypic plasticity in crops such as maize is of paramount importance for maintaining and increasing yields in a world experiencing climate change. Here, we report the results of genome-wide association analyses of multiple phenotypes and two measures of phenotypic plasticity in a maize nested association mapping (US-NAM) population grown in multiple environments and genotyped with ~2.5 million single-nucleotide polymorphisms. We show that across all traits the candidate genes for mean phenotype values and plasticity measures form structurally and functionally distinct groups. Such independent genetic control suggests that breeders will be able to select semi-independently for mean phenotype values and plasticity, thereby generating varieties with both high mean phenotype values and levels of plasticity that are appropriate for the target performance environments.

  8. Holistic and component plant phenotyping using temporal image sequence.

    Science.gov (United States)

    Das Choudhury, Sruti; Bashyam, Srinidhi; Qiu, Yumou; Samal, Ashok; Awada, Tala

    2018-01-01

    Image-based plant phenotyping facilitates the extraction of traits noninvasively by analyzing large number of plants in a relatively short period of time. It has the potential to compute advanced phenotypes by considering the whole plant as a single object (holistic phenotypes) or as individual components, i.e., leaves and the stem (component phenotypes), to investigate the biophysical characteristics of the plants. The emergence timing, total number of leaves present at any point of time and the growth of individual leaves during vegetative stage life cycle of the maize plants are significant phenotypic expressions that best contribute to assess the plant vigor. However, image-based automated solution to this novel problem is yet to be explored. A set of new holistic and component phenotypes are introduced in this paper. To compute the component phenotypes, it is essential to detect the individual leaves and the stem. Thus, the paper introduces a novel method to reliably detect the leaves and the stem of the maize plants by analyzing 2-dimensional visible light image sequences captured from the side using a graph based approach. The total number of leaves are counted and the length of each leaf is measured for all images in the sequence to monitor leaf growth. To evaluate the performance of the proposed algorithm, we introduce University of Nebraska-Lincoln Component Plant Phenotyping Dataset (UNL-CPPD) and provide ground truth to facilitate new algorithm development and uniform comparison. The temporal variation of the component phenotypes regulated by genotypes and environment (i.e., greenhouse) are experimentally demonstrated for the maize plants on UNL-CPPD. Statistical models are applied to analyze the greenhouse environment impact and demonstrate the genetic regulation of the temporal variation of the holistic phenotypes on the public dataset called Panicoid Phenomap-1. The central contribution of the paper is a novel computer vision based algorithm for

  9. Rethinking the evolution of specialization: A model for the evolution of phenotypic heterogeneity.

    Science.gov (United States)

    Rubin, Ilan N; Doebeli, Michael

    2017-12-21

    Phenotypic heterogeneity refers to genetically identical individuals that express different phenotypes, even when in the same environment. Traditionally, "bet-hedging" in fluctuating environments is offered as the explanation for the evolution of phenotypic heterogeneity. However, there are an increasing number of examples of microbial populations that display phenotypic heterogeneity in stable environments. Here we present an evolutionary model of phenotypic heterogeneity of microbial metabolism and a resultant theory for the evolution of phenotypic versus genetic specialization. We use two-dimensional adaptive dynamics to track the evolution of the population phenotype distribution of the expression of two metabolic processes with a concave trade-off. Rather than assume a Gaussian phenotype distribution, we use a Beta distribution that is capable of describing genotypes that manifest as individuals with two distinct phenotypes. Doing so, we find that environmental variation is not a necessary condition for the evolution of phenotypic heterogeneity, which can evolve as a form of specialization in a stable environment. There are two competing pressures driving the evolution of specialization: directional selection toward the evolution of phenotypic heterogeneity and disruptive selection toward genetically determined specialists. Because of the lack of a singular point in the two-dimensional adaptive dynamics and the fact that directional selection is a first order process, while disruptive selection is of second order, the evolution of phenotypic heterogeneity dominates and often precludes speciation. We find that branching, and therefore genetic specialization, occurs mainly under two conditions: the presence of a cost to maintaining a high phenotypic variance or when the effect of mutations is large. A cost to high phenotypic variance dampens the strength of selection toward phenotypic heterogeneity and, when sufficiently large, introduces a singular point into

  10. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  11. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  12. Social identity performance : Extending the strategic side of SIDE

    NARCIS (Netherlands)

    Klein, Olivier; Spears, Russell; Reicher, Stephen

    This article extends the social identity model of deindividuation effects (SIDE) by considering the various ways in which relations of visibility to an audience can affect the public expression of identity-relevant norms (identity performance). It is suggested that social identity performance can

  13. Dark Side of the Universe

    CERN Document Server

    2016-01-01

    The Dark Side of the Universe (DSU) workshops bring together a wide range of theorists and experimentalists to discuss current ideas on models of the dark side, and relate them to current and future experiments. This year's DSU will take place in the colorful Norwegian city of Bergen. Topics include dark matter, dark energy, cosmology, and physics beyond the standard model. One of the goals of the workshop is to expose in particular students and young researchers to the fascinating topics of dark matter and dark energy, and to provide them with the opportunity to meet some of the best researchers in these areas .

  14. Running away from side effects

    DEFF Research Database (Denmark)

    Casla, S; Hojman, P; Márquez-Rodas, I

    2015-01-01

    The number of breast cancer survivors increases every year, thanks to the development of new treatments and screening techniques. However, patients present with numerous side effects that may affect their quality of life. Exercise has been demonstrated to reduce some of these side effects...... be an integrative complementary intervention to improve physiological, physical and psychological factors that affect survival and quality of life of these patients. For that reason, the main objective of this review is to provide a general overview of exercise benefits in breast cancer patients and recommendations...

  15. Age at onset and Parkinson disease phenotype

    Science.gov (United States)

    Pagano, Gennaro; Ferrara, Nicola; Brooks, David J.

    2016-01-01

    Objective: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD. Methods: We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50–59 years, 60–69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers. Results: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups. Conclusions: Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials. PMID:26865518

  16. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  17. The DarkSide Program

    Directory of Open Access Journals (Sweden)

    Rossi B.

    2016-01-01

    Full Text Available DarkSide-50 at Gran Sasso underground laboratory (LNGS, Italy, is a direct dark matter search experiment based on a liquid argon TPC. DS-50 has completed its first dark matter run using atmospheric argon as target. The detector performances and the results of the first physics run are presented in this proceeding.

  18. [Side Effects of Smoking Cessation].

    Science.gov (United States)

    Braun, Raffael; Huwiler, Bernhard

    2018-06-01

    Side Effects of Smoking Cessation Abstract. We present the case of a clozapine intoxication associated with aspiration pneumonia due to smoking cessation. Clozapine is mainly metabolized by CYP1A2. CYP1A2 is induced by cigarette smoking, which may change the plasma level of clozapine, especially if consuming habits change.

  19. Managing Chemotherapy Side Effects: Constipation

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods such as: ● ● Whole-grain breads and cereals ● ● Fruits and vegetables ● ● Nuts and seeds Turn this ...

  20. Side-View Face Recognition

    NARCIS (Netherlands)

    Santemiz, P.; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.; van den Biggelaar, Olivier

    As a widely used biometrics, face recognition has many advantages such as being non-intrusive, natural and passive. On the other hand, in real-life scenarios with uncontrolled environment, pose variation up to side-view positions makes face recognition a challenging work. In this paper we discuss

  1. The Human Side of Libraries.

    Science.gov (United States)

    Surace, Cecily J.

    This paper discusses current trends in personnel management, with emphasis on performance standards and employee evaluation. Advances in personnel management from the scientific management theory to the application of the "human side of enterprise" approach should be reflected in how library managers review personnel and operate their libraries.…

  2. The DarkSide experiment

    International Nuclear Information System (INIS)

    Bottino, B.; Aalseth, C.E.; Acconcia, G.

    2017-01-01

    DarkSide is a dark matter direct search experiment at Laboratori Nazionali del Gran Sasso (LNGS). DarkSide is based on the detection of rare nuclear recoils possibly induced by hypothetical dark matter particles, which are supposed to be neutral, massive (m > 10 GeV) and weakly interactive (Wimp). The dark matter detector is a two-phase time projection chamber (TPC) filled with ultra-pure liquid argon. The TPC is placed inside a muon and a neutron active vetoes to suppress the background. Using argon as active target has many advantages, the key features are the strong discriminant power between nuclear and electron recoils, the spatial reconstruction and easy scalability to multi-tons size. At the moment DarkSide-50 is filled with ultra-pure argon, extracted from underground sources, and from April 2015 it is taking data in its final configuration. When combined with the preceding search with an atmospheric argon target, it is possible to set a 90% CL upper limit on the WIMP-nucleon spin-independent cross section of 2.0×10"−"44 cm"2 for a WIMP mass of 100 GeV/c"2. The next phase of the experiment, DarkSide-20k, will be the construction of a new detector with an active mass of ∼ 20 tons.

  3. Finasteride and sexual side effects

    Directory of Open Access Journals (Sweden)

    Venkataram Mysore

    2012-01-01

    Full Text Available Finasteride, a 5-alpha reductase inhibitor, widely used in the medical management of male pattern hairloss, has been reported to cause sexual side effects. This article critically examines the evidence available and makes recommendations as to how a physician should counsel a patient while prescribing the drug.

  4. Truck side guard specifications : recommended standard

    Science.gov (United States)

    2016-09-01

    This document is intended to be used by (1) public or private medium/heavy-duty truck fleets considering adding side guards; (2) jurisdictions or customers that require side guards through policy or procurement; (3) manufacturers of side guards; and ...

  5. Warfarin Side Effects: Watch for Interactions

    Science.gov (United States)

    Warfarin side effects: Watch for interactions Although commonly used to treat blood clots, warfarin (Coumadin, Jantoven) can have dangerous side effects or ... bleeding. Here are precautions to take to avoid warfarin side effects. By Mayo Clinic Staff If you' ...

  6. FeNO as biomarker for asthma phenotyping and management.

    Science.gov (United States)

    Ricciardolo, Fabio L M; Sorbello, Valentina; Ciprandi, Giorgio

    2015-01-01

    The current review aims to revisit literature on exhaled nitric oxide (FeNO) in asthma phenotyping and management to clarify the utility of this test in clinical practice. It is increasingly evident that multiple profiles characterize asthma as a complex disease for which is necessary to find tools able to discriminate among these phenotypes to achieve the best therapeutic strategy for all asthmatic patients. Current findings indicate that FeNO, a noninvasive and easy-to-obtain biomarker, can be considered a useful tool in predicting asthma developing and exacerbation, in identifying specific asthma phenotypes, in improving asthma diagnosis and management in a selected population, and in monitoring efficacy of standard corticosteroid and biologic therapy. Based on this evidence, FeNO might become an appropriate tool for physicians to better define specific asthma phenotypes and to better deal with asthma worsening.

  7. Deep Phenotyping: Deep Learning For Temporal Phenotype/Genotype Classification

    OpenAIRE

    Najafi, Mohammad; Namin, Sarah; Esmaeilzadeh, Mohammad; Brown, Tim; Borevitz, Justin

    2017-01-01

    High resolution and high throughput, genotype to phenotype studies in plants are underway to accelerate breeding of climate ready crops. Complex developmental phenotypes are observed by imaging a variety of accessions in different environment conditions, however extracting the genetically heritable traits is challenging. In the recent years, deep learning techniques and in particular Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs) and Long-Short Term Memories (LSTMs), h...

  8. Isolation and characterization of multidrug-resistant side population ...

    African Journals Online (AJOL)

    The SP cells showed high resistance to drugs such as 5-fluorouracil, cisplatin, paclitaxel (2 μmol/L) and oxaliplatin. The survival rate of SP cells after treatment with these drugs was significantly higher (p < 0.01) than that of non-SP cells. Furthermore, the number of spheres generated in serumfree medium was significantly ...

  9. Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data.

    Directory of Open Access Journals (Sweden)

    Jonathan D Mosley

    Full Text Available A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1 non-synonymous SNPs (nsSNPs associated with "mechanistic phenotypes", comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1 thrombosis, evaluated in a population of 1,655 African Americans; and (2 four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs, and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03, driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10-5, FDR p = 0.03 (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L while the additive model showed enrichment related to chromatid segregation (p = 4×10-6, FDR p = 0.005 (KIF25, PINX1. We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.

  10. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-12-01

    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  11. Características fenotípicas da hipertensão arterial resistente na população brasileira Phenotypic characteristics of resistant hypertension in the Brazilian population

    Directory of Open Access Journals (Sweden)

    Ana Paula Cabral de Faria

    2013-01-01

    definition may be useful in terms of categorizing a larger group of resistant hypertensive individuals, as these two subgroups share high cardiovascular risk, some important clinical and pathophysiologic particularities need to be better evaluated, before considering resistant controlled and uncontrolled patients as part of the same group. We compared cardiovascular characteristics of these two subgroups with resistant hypertension. In spite of some similar features, the UCRH subgroup has cardiovascular phenotypes with worse prognosis, such as increased vascular stiffness and left ventricular hypertrophy, as well as more impaired endothelial function and lower nocturnal blood pressure dipping, among others. Considering these differences, the UCRH subgroup is associated with greater cardiovascular risk and may be considered as more resistant to antihypertensive treatment. In addition to the importance of better prevention and treatment of resistant hypertension by identifying early risk factors and optimizing drug therapy, some clinical implications must be considered when managing controlled and uncontrolled patients as similar to the resistant hypertension group.

  12. PHENOTYPIC CORRELATIONS AND BODY WEIGHTS ...

    African Journals Online (AJOL)

    Dr Osondu

    Ethiopian Journal of Environmental Studies and Management Vol. 4 No.3 2011. PHENOTYPIC ... because of its high meat quality and acceptance by her populace. The meat is ... commands high price in the restaurants and markets than other ...

  13. Testing evolutionary hypotheses for phenotypic divergence using landscape genetics.

    Science.gov (United States)

    Funk, W Chris; Murphy, Melanie A

    2010-02-01

    Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.

  14. Reported Sildenafil Side Effects in Pediatric Pulmonary Hypertension Patients

    Directory of Open Access Journals (Sweden)

    Stephanie Leigh Siehr

    2015-03-01

    Full Text Available Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH in adults, and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil (alone or in combination with other PH therapies completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic and hematologic side effects. Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys on monotherapy, and 43 patients (118 surveys on sildenafil plus an endothelin receptor antagonist (bosentan or ambrisentan and/or a prostacyclin (epoprostenol or treprostinil. Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal and neurologic side effect in pediatric patients on sildenafil therapy for pulmonary arterial hypertension was 30%. Side effects were more common in patients on combination therapy with an endothelin receptor antagonist and/or prostacyclin than in patients on sildenafil monotherapy.

  15. Study of selected phenotype switching strategies in time varying environment

    Energy Technology Data Exchange (ETDEWEB)

    Horvath, Denis, E-mail: horvath.denis@gmail.com [Centre of Interdisciplinary Biosciences, Institute of Physics, Faculty of Science, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia); Brutovsky, Branislav, E-mail: branislav.brutovsky@upjs.sk [Department of Biophysics, Institute of Physics, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia)

    2016-03-22

    Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback–Leibler functional distances and the Hamming distance. - Highlights: • Relation between phenotype switching and environment is studied. • The Markov chain Monte Carlo based model is developed. • Stochastic and deterministic strategies of phenotype switching are utilized. • Statistical measures of the dynamic heterogeneity reveal universal properties. • The results extend to higher lattice dimensions.

  16. Study of selected phenotype switching strategies in time varying environment

    International Nuclear Information System (INIS)

    Horvath, Denis; Brutovsky, Branislav

    2016-01-01

    Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback–Leibler functional distances and the Hamming distance. - Highlights: • Relation between phenotype switching and environment is studied. • The Markov chain Monte Carlo based model is developed. • Stochastic and deterministic strategies of phenotype switching are utilized. • Statistical measures of the dynamic heterogeneity reveal universal properties. • The results extend to higher lattice dimensions.

  17. The Dark Side of Management

    DEFF Research Database (Denmark)

    Hanlon, Gerard; Dunne, Stephen; Johnsen, Christian Garmann

    2017-01-01

    Towards the end of 2015, the ephemera collective organised, chaired and participated within two separate Q+A panels celebrating the launch of Gerard Hanlon’s The dark side of management: A secret history of management theory. The events took place in The University of Leicester’s School of Manage...... of Management and Copenhagen Business School’s Management, Politics and Philosophy Department. Each of the events were recorded, transcribed, edited and amalgamated into the following feature....

  18. Development of Side Coupled Cavities

    International Nuclear Information System (INIS)

    Conto, J.M. de; Carretta, J.M.; Gomez-Martinez, Y.; Micoud, R.

    2008-01-01

    Side coupled Cavities are good candidates for proton accelerations in the 90-180 MeV range, as it has been first proposed for the CERN LINAC4 project. A side coupled Linac is made of a lump chain of resonant cavities, alternatively accelerating and coupling. A side coupled cavity has been designed in a CERN-LPSC collaboration to achieve LINAC4 requirements. After RF studies, a complete thermal study has been done, showing that 10-15% is the absolute maximum duty-cycle achievable by such a cavity. Error studies have been developed. They have shown that a tuning ring is mandatory and that a K equals 3% coupling factor is a good choice. A prototype has been built and each cell has been measured and tuned. A simple and accurate method has been used to get both the resonant frequency and the coupling factor, with a movable tuner and a linear fit. A similar method has been used to get the second order coupling factor. A large dispersion is observed on K. This is mainly due to the shape of the coupling apertures, which are very sensitive to mechanical errors. A future and realistic design must be very careful to guarantee a constant aperture (the important parameter is more the dispersion of k than its exact value). Finally, we analyse how to tune the cavity. This has to checked carefully and probably improved or corrected. Results are expected for mid-2008

  19. Metabolic Side Effects of Lithium

    Directory of Open Access Journals (Sweden)

    M. Cagdas Eker

    2010-04-01

    Full Text Available Lithium is an alkaline ion being used since 19th century. After its widespread use in psychiatric disorders, observed side effects caused skepticism about its therapeutic efficacy. Despite several disadvantages, lithium is one of the indispensible drugs used in affective disorders, especially in bipolar disorder. It became a necessity for physicians to recognize its side effects since lithium is still accepted as a gold standard in the treatment of bipolar disorder. Adverse effects of chronic administration of lithium on several organ systems are widely known. In this article metabolic effects of lithium on thyroid and parathyroid glands, body mass index and kidneys will be discussed along with their mechanisms, clinical findings, possible risk factors and treatment. One of the most common side effect of lithium is hypothyroidism. It has the same clinical and biochemical properties as primary hypothyroidism and observed as subclinical hypothyroidism in the first place. Hypothyroidism, even its subclinical form, may be associated with non-response or inadequate response and is indicated as a risk factor for development of rapid cycling bipolar disorder. Therefore, hypothyroidism should be screened no matter how severe it is and should be treated with thyroid hormone in the presence of clinical hypothyroidism. Weight gain due to lithium administration disturbs the compliance to treatment and negatively affects the course of the illness. Increased risk for diabetes, hypertension, ischemic heart disease and stroke because of weight gain constitute other centers of problem. Indeed, it is of importance to determine the risk factors before treatment, to follow up the weight, to re-organize nutritional habits and to schedule exercises. Another frequent problematic side effect of lithium treatment is renal dysfunction which clinically present as nephrogenic diabetes insipidus with the common symptoms of polyuria and polydipsia. Nephrogenic diabetes

  20. Phenotypic heterogeneity of peripheral monocytes in healthy dogs.

    Science.gov (United States)

    Gibbons, Natalie; Goulart, Michelle R; Chang, Yu-Mei; Efstathiou, Konstantinos; Purcell, Robert; Wu, Ying; Peters, Laureen M; Turmaine, Mark; Szladovits, Balazs; Garden, Oliver A

    2017-08-01

    Monocytes are key cells of the innate immune system. Their phenotypic and functional roles have been investigated in humans, mice and other animals, such as the rat, pig and cow. To date, detailed phenotypic analysis of monocytes has not been undertaken in dogs. Two important surface markers in human monocytes are CD14 and MHC class II (MHC II). By flow cytometry, we demonstrated that canine monocytes can be subdivided into three separate populations: CD14 pos MHC II neg , CD14 pos MHC II pos and CD14 neg MHC II pos . Both light and transmission electron microscopy confirmed the monocytic identity of all three populations. The CD14 pos MHC II neg population could be distinguished on an ultrastructural level by their smaller size, the presence of more numerous, larger granules, and more pseudopodia than both of the other populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Side of Onset in Parkinson’s Disease and Alterations in Religiosity: Novel Behavioral Phenotypes

    Directory of Open Access Journals (Sweden)

    Paul M. Butler

    2011-01-01

    Full Text Available Behavioral neurologists have long been interested in changes in religiosity following circumscribed brain lesions. Advances in neuroimaging and cognitive experimental techniques have been added to these classical lesion-correlational approaches in attempt to understand changes in religiosity due to brain damage. In this paper we assess processing dynamics of religious cognition in patients with Parkinson’s disease (PD. We administered a four-condition story-based priming procedure, and then covertly probed for changes in religious belief. Story-based priming emphasized mortality salience, religious ritual, and beauty in nature (Aesthetic. In neurologically intact controls, religious belief-scores significantly increased following the Aesthetic prime condition. When comparing effects of right (RO versus left onset (LO in PD patients, a double-dissociation in religious belief-scores emerged based on prime condition. RO patients exhibited a significant increase in belief following the Aesthetic prime condition and LO patients significantly increased belief in the religious ritual prime condition. Results covaried with executive function measures. This suggests lateral cerebral specialization for ritual-based (left frontal versus aesthetic-based (right frontal religious cognition. Patient-centered individualized treatment plans should take religiosity into consideration as a complex disease-associated phenomenon connected to other clinical variables and health outcomes.

  2. 49 CFR 229.69 - Side bearings.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Side bearings. 229.69 Section 229.69....69 Side bearings. (a) Friction side bearings with springs designed to carry weight may not have more than 25 percent of the springs in any one nest broken. (b) Friction side bearings may not be run in...

  3. Side-to-side sutureless vascular anastomosis with magnets.

    Science.gov (United States)

    Erdmann, Detlev; Sweis, Ranya; Heitmann, Christoph; Yasui, Koji; Olbrich, Kevin C; Levin, L Scott; Sharkawy, A Adam; Klitzman, Bruce

    2004-09-01

    Abbe and Payr introduced vascular techniques and devices to facilitate vessel anastomosis over a century ago. Obora published the idea of a sutureless vascular anastomosis with use of magnetic rings in 1978. The purpose of this study was to assess the performance of a new magnetic device to perform a side-to-side arteriovenous anastomosis in a dog model. Male fox hounds (25 kg) were treated preoperatively and daily postoperatively with clopidogrel bisulfate (Plavix) and aspirin. The femoral artery and vein were exposed unilaterally in 3 dogs and bilaterally in 4 dogs (n = 11 anastomoses). A 4-mm arteriotomy was performed, and 1 oval magnet 0.5 mm thick was inserted into the lumen of the artery and a second magnet was applied external to the artery, compressing and stabilizing the arterial wall to create a magnetic port. An identical venous magnetic port was created with another pair of oval magnets. When the 2 ports were allowed to approach each other, they self-aligned and magnetically coupled to complete the arteriovenous anastomosis. Patency was assessed for the first hour with direct observation, again after 9 weeks with duplex ultrasound scanning, and at 10 weeks under direct open observation. The anastomoses were explanted after 10 weeks. Hydrodynamic resistance was measured ex vivo on the final 8 anastomoses by measuring the pressure drop across an anastomosis with a known flow rate. After implantation, very high flow created visible turbulence and palpable vibration. All 11 anastomoses were patent under direct observation and palpation. Ten of 11 anastomoses were clearly patent on duplex scans, and patency of 1 anastomosis was questionable. Hydrodynamic resistance averaged 0.73 +/- 0.33 mm Hg min/mL (mean +/- SEM). Vascular anastomoses performed with magnets demonstrated feasibility; exhibited 100% patency after 10 weeks in a dog arteriovenous shunt model; lacked apparent aneurysm or other potentially catastrophic failure; demonstrated remodeling of the

  4. The quantitative genetics of phenotypic variation in animals

    NARCIS (Netherlands)

    Hill, W.G.; Mulder, H.A.; Zhang, X.S.

    2007-01-01

    Considerable attention has been paid to estimating genetic variability in quantitative traits and to how it is maintained and changed by selection in natural and domesticated populations, but rather little attention has been paid to how levels of environmental and phenotypic variance are influenced.

  5. Maternal Vitamin D Levels and the Autism Phenotype among Offspring

    Science.gov (United States)

    Whitehouse, Andrew J. O.; Holt, Barbara J.; Serralha, Michael; Holt, Patrick G.; Hart, Prue H.; Kusel, Merci M. H.

    2013-01-01

    We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean.…

  6. Predictable Phenotypes of Antibiotic Resistance Mutations.

    Science.gov (United States)

    Knopp, M; Andersson, D I

    2018-05-15

    Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations. IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain

  7. Flapping propulsion with side-by-side pitching foils

    Science.gov (United States)

    Huera-Huarte, Francisco

    2016-11-01

    Fish schools are one of the most common types of collective behaviour observed in nature. One of the reasons why fish swim in groups, is to reduce the cost of transport of the school. In this work we explore the propulsive performance of two foils flapping in a symmetric configuration, i.e. with an out-of-phase flapping motion. Direct thrust measurements and Particle Image Velocimetry (PIV) allowed a detailed examination of the forces and the wake generated by the system, for different kinematics (swept angles and frequencies) and shaft separations. For certain specific cases, volumetric PIV shows major differences on how the different structures in the wake of the system evolve, depending on the imposed kinematics and the side-by-side separation between the foils. Results obtained will be compared against data produced with isolated flapping foils with similar imposed kinematics, with the aim to better understand the interactions between both and the performance of the system as a whole. The author would like to acknowledge the financial support provided by the Spanish Ministerio de Economia y competitividad (MINECO) through Grant DPI2015-71645-P.

  8. Red hair is the null phenotype of MC1R.

    Science.gov (United States)

    Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

    2008-08-01

    The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

  9. Musculoskeletal phenotype through the life course: the role of nutrition.

    Science.gov (United States)

    Ward, Kate

    2012-02-01

    This review considers the definition of a healthy bone phenotype through the life course and the modulating effects of muscle function and nutrition. In particular, it will emphasise that optimal bone strength (and how that is regulated) is more important than simple measures of bone mass. The forces imposed on bone by muscle loading are the primary determinants of musculoskeletal health. Any factor that changes muscle loading on the bone, or the response of bone to loading results in alterations of bone strength. Advances in technology have enhanced the understanding of a healthy bone phenotype in different skeletal compartments. Multiple components of muscle strength can also be quantified. The critical evaluation of emerging technologies for assessment of bone and muscle phenotype is vital. Populations with low and moderate/high daily Ca intakes and/or different vitamin D status illustrate the importance of nutrition in determining musculoskeletal phenotype. Changes in mass and architecture maintain strength despite low Ca intake or vitamin D status. There is a complex interaction between body fat and bone which, in addition to protein intake, is emerging as a key area of research. Muscle and bone should be considered as an integrative unit; the role of body fat requires definition. There remains a lack of longitudinal evidence to understand how nutrition and lifestyle define musculoskeletal health. In conclusion, a life-course approach is required to understand the definition of healthy skeletal phenotype in different populations and at different stages of life.

  10. Childhood asthma-predictive phenotype.

    Science.gov (United States)

    Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

    2014-01-01

    Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Phenotypic and Functional Changes Induced in Hematopoietic Stem/Progenitor Cells After Gamma-Ray Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Simonnet, A.J.; Nehme, J.; Leboulch, Ph.; Tronik-Le Roux, D. [Institute of Emerging Diseases and Innovative Therapies, Functional Bioengineering Laboratory, Commissariat a l' Energie Atomique (CEA), Evry (France); Simonnet, A.J.; Nehme, J.; Leboulch, Ph.; Tronik-Le Roux, D. [Institut National de la Sante et de la Recherche Medicale (INSERM) U733 (Unite Mixte de Recherche) - UMR INSERM CEA Paris XI (France); Vaigot, P. [Institute of Cellular and Molecular Radiation Biology, Department of Genetic Instability, Recombination and Repair, Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France); Vaigot, P. [UMR 217, UMR-CEA-Centre National de la Recherche Scientifique (France); Barroca, V. [Laboratory of Gametogenesis, Apoptosis, Genotoxicity, Institute of Cellular and Molecular Radiation Biology, Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France); Barroca, V. [Institut National de la Sante et de la Recherche Medicale U566 - UMR INSERM-CEA-PARIS VII (France); Leboulch, Ph. [Genetics Division, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (US)

    2009-07-01

    Ionizing radiation (IR) exposure causes rapid and acute bone marrow (BM) suppression that is reversible for nonlethal doses. Evidence is accumulating that IR can also provoke long-lasting residual hematopoietic injury. To better understand these effects, we analyzed phenotypic and functional changes in the stem/progenitor compartment of irradiated mice over a 10-week period. We found that hematopoietic stem cells (HSCs) identified by their repopulating ability continued to segregate within the Hoechst dye excluding 'side population (SP)' early after IR exposure. However, transient phenotypic changes were observed within this cell population: Sca-1 (S) and c-Kit (K) expression levels were increased and severely reduced, respectively, with a concurrent increase in the proportion of SPSK cells positive for established indicators of the presence of HSCs: CD150 and CD105. Ten weeks after IR exposure, expression of Sca-1 and c-Kit at the SP cell surface returned to control levels, and BM cellularity of irradiated mice was restored. However, the c-Kit{sup +}Sca-1{sup +}Lin{sup -/low} (KSL) stem/progenitor compartment displayed major phenotypic modifications, including an increase and a severe decrease in the frequencies of CD150{sup +}Flk2{sup -} and CD150{sup -}Flk2{sup +} cells, respectively. CD150{sup +} KSL cells also showed impaired reconstituting ability, an increased tendency to apoptosis, and accrued DNA damage. Finally, 15 weeks after exposure, irradiated mice, but not age matched controls, allowed engraftment and significant hematopoietic contribution from transplanted con-genic HSCs without additional host conditioning. These results provide novel insight in our understanding of immediate and delayed IR-induced hematopoietic injury and highlight similarities between HSCs of young irradiated and old mice. (authors)

  12. Phenotypic and Functional Changes Induced in Hematopoietic Stem/Progenitor Cells After Gamma-Ray Radiation Exposure

    International Nuclear Information System (INIS)

    Simonnet, A.J.; Nehme, J.; Leboulch, Ph.; Tronik-Le Roux, D.; Simonnet, A.J.; Nehme, J.; Leboulch, Ph.; Tronik-Le Roux, D.; Vaigot, P.; Vaigot, P.; Barroca, V.; Barroca, V.; Leboulch, Ph.

    2009-01-01

    Ionizing radiation (IR) exposure causes rapid and acute bone marrow (BM) suppression that is reversible for nonlethal doses. Evidence is accumulating that IR can also provoke long-lasting residual hematopoietic injury. To better understand these effects, we analyzed phenotypic and functional changes in the stem/progenitor compartment of irradiated mice over a 10-week period. We found that hematopoietic stem cells (HSCs) identified by their repopulating ability continued to segregate within the Hoechst dye excluding 'side population (SP)' early after IR exposure. However, transient phenotypic changes were observed within this cell population: Sca-1 (S) and c-Kit (K) expression levels were increased and severely reduced, respectively, with a concurrent increase in the proportion of SPSK cells positive for established indicators of the presence of HSCs: CD150 and CD105. Ten weeks after IR exposure, expression of Sca-1 and c-Kit at the SP cell surface returned to control levels, and BM cellularity of irradiated mice was restored. However, the c-Kit + Sca-1 + Lin -/low (KSL) stem/progenitor compartment displayed major phenotypic modifications, including an increase and a severe decrease in the frequencies of CD150 + Flk2 - and CD150 - Flk2 + cells, respectively. CD150 + KSL cells also showed impaired reconstituting ability, an increased tendency to apoptosis, and accrued DNA damage. Finally, 15 weeks after exposure, irradiated mice, but not age matched controls, allowed engraftment and significant hematopoietic contribution from transplanted con-genic HSCs without additional host conditioning. These results provide novel insight in our understanding of immediate and delayed IR-induced hematopoietic injury and highlight similarities between HSCs of young irradiated and old mice. (authors)

  13. NPP Krsko secondary side analysis

    International Nuclear Information System (INIS)

    Fabijan, Lj.

    1987-01-01

    The purpose of this work is to analyze secondary side thermohydraulics response on steam generator tube plugging in order to ensure nominal NPP power. We had established that the additional opening of the governing valve No. 3 and 4 can compensate pressure drop caused by steam generator tube plugging. Two main steam flows with four governing valves were simulated. Steam expansion in turbine and feed water system was modeled separately. All important process point and steam moisture changes impact on nominal NPP power were analysed. (author)

  14. Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease

    DEFF Research Database (Denmark)

    Jakobsen, Christian; Bartek, Jiri; Wewer, Anne Vibeke

    2011-01-01

    Background Few studies have compared phenotype and disease course in children and adults with inflammatory bowel disease (IBD). Aim To compare phenotype, treatment and disease course in children (<15 years) and adults (=18 years) with IBD. Methods Two population-based cohorts comprising paediatri...

  15. Longitudinal Investigation into Genetics in the Conservation of Metabolic Phenotypes in Danish and Chinese Twins

    DEFF Research Database (Denmark)

    Li, Shuxia; Kyvik, Kirsten Ohm; Duan, Haiping

    2016-01-01

    twin study on long-term stability of metabolic phenotypes in Danish and Chinese twins identified a common pattern of high genetic control over phenotype conservation, and at the same time revealed population-specific patterns of genetic and common environmental regulation on the variance as well...

  16. Genetic architecture and phenotypic plasticity of thermally-regulated traits in an eruptive species, Dendroctonus ponderosae

    Science.gov (United States)

    Barbara J. Bentz; Ryan B. Bracewell; Karen E. Mock; Michael E. Pfrender

    2011-01-01

    Phenotypic plasticity in thermally-regulated traits enables close tracking of changing environmental conditions, and can thereby enhance the potential for rapid population increase, a hallmark of outbreak insect species. In a changing climate, exposure to conditions that exceed the capacity of existing phenotypic plasticity may occur. Combining information on genetic...

  17. Fire coral clones demonstrate phenotypic plasticity among reef habitats.

    Science.gov (United States)

    Dubé, Caroline E; Boissin, Emilie; Maynard, Jeffrey A; Planes, Serge

    2017-08-01

    Clonal populations are often characterized by reduced levels of genotypic diversity, which can translate into lower numbers of functional phenotypes, both of which impede adaptation. Study of partially clonal animals enables examination of the environmental settings under which clonal reproduction is favoured. Here, we gathered genotypic and phenotypic information from 3,651 georeferenced colonies of the fire coral Millepora platyphylla in five habitats with different hydrodynamic regimes in Moorea, French Polynesia. In the upper slope where waves break, most colonies grew as vertical sheets ("sheet tree") making them more vulnerable to fragmentation. Nearly all fire corals in the other habitats are encrusting or massive. The M. platyphylla population is highly clonal (80% of the colonies are clones), while characterized by the highest genotype diversity ever documented for terrestrial or marine populations (1,064 genotypes). The proportion of clones varies greatly among habitats (≥58%-97%) and clones (328 clonal lineages) are distributed perpendicularly from the reef crest, perfectly aligned with wave energy. There are six clonal lineages with clones dispersed in at least two adjacent habitats that strongly demonstrate phenotypic plasticity. Eighty per cent of the colonies in these lineages are "sheet tree" on the upper slope, while 80%-100% are encrusting or massive on the mid slope and back reef. This is a unique example of phenotypic plasticity among reef-building coral clones as corals typically have wave-tolerant growth forms in high-energy reef areas. © 2017 John Wiley & Sons Ltd.

  18. Phenotypic and functional characterization of human mammary stem/progenitor cells in long term culture.

    Directory of Open Access Journals (Sweden)

    Devaveena Dey

    Full Text Available BACKGROUND: Cancer stem cells exhibit close resemblance to normal stem cells in phenotype as well as function. Hence, studying normal stem cell behavior is important in understanding cancer pathogenesis. It has recently been shown that human breast stem cells can be enriched in suspension cultures as mammospheres. However, little is known about the behavior of these cells in long-term cultures. Since extensive self-renewal potential is the hallmark of stem cells, we undertook a detailed phenotypic and functional characterization of human mammospheres over long-term passages. METHODOLOGY: Single cell suspensions derived from human breast 'organoids' were seeded in ultra low attachment plates in serum free media. Resulting primary mammospheres after a week (termed T1 mammospheres were subjected to passaging every 7th day leading to the generation of T2, T3, and T4 mammospheres. PRINCIPAL FINDINGS: We show that primary mammospheres contain a distinct side-population (SP that displays a CD24(low/CD44(low phenotype, but fails to generate mammospheres. Instead, the mammosphere-initiating potential rests within the CD44(high/CD24(low cells, in keeping with the phenotype of breast cancer-initiating cells. In serial sphere formation assays we find that even though primary (T1 mammospheres show telomerase activity and fourth passage T4 spheres contain label-retaining cells, they fail to initiate new mammospheres beyond T5. With increasing passages, mammospheres showed an increase in smaller sized spheres, reduction in proliferation potential and sphere forming efficiency, and increased differentiation towards the myoepithelial lineage. Significantly, staining for senescence-associated beta-galactosidase activity revealed a dramatic increase in the number of senescent cells with passage, which might in part explain the inability to continuously generate mammospheres in culture. CONCLUSIONS: Thus, the self-renewal potential of human breast stem cells is

  19. Side effects during subcutaneous immunotherapy in children with allergic diseases.

    Science.gov (United States)

    Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

    2018-05-01

    Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  20. Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

    DEFF Research Database (Denmark)

    Song, Yong; Schwager, Michelle J; Backer, Vibeke

    2017-01-01

    The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically...... separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit......-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases....

  1. Starvation induces phenotypic diversification and convergent evolution in Vibrio vulnificus.

    Directory of Open Access Journals (Sweden)

    Hwajiun Chen

    Full Text Available Starvation is a common stress experienced by bacteria living in natural environments and the ability to adapt to and survive intense stress is of paramount importance for any bacterial population. A series of starvation experiments were conducted using V. vulnificus 93U204 in phosphate-buffered saline and seawater. The starved population entered the death phase during the first week and approximately 1% of cells survived. After that the population entered a long-term stationary phase, and could survive for years. Starvation-induced diversification (SID of phenotypes was observed in starved populations and phenotypic variants (PVs appeared in less than 8 days. The cell density, rather than the population size, had a major effect on the extent of SID. SID was also observed in strain YJ016, where it evolved at a faster pace. PVs appeared to emerge in a fixed order: PV with reduced motility, PV with reduced proteolytic activity, and PV with reduced hemolytic activity. All of the tested PVs had growth advantages in the stationary phase phenotypes and increased fitness compared with 93U204 cells in co-culture competition experiments, which indicates that they had adapted to starvation. We also found that SID occurred in natural seawater with a salinity of 1%-3%, so this mechanism may facilitate bacterial adaptation in natural environments.

  2. Comparisons of phenotype and immunomodulatory capacity among rhesus bone-marrow-derived mesenchymal stem/stromal cells, multipotent adult progenitor cells, and dermal fibroblasts

    Science.gov (United States)

    Wang, Qi; Clarkson, Christina; Graham, Melanie; Donahue, Robert; Hering, Bernhard J.; Verfaillie, Catherine M.; Bansal-Pakala, Pratima; O'Brien, Timothy D.

    2015-01-01

    Background Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4+ and CD8+ lymphocyte populations have not been reported. Methods We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT-PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type. Results and Conclusions Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable. PMID:24825538

  3. Phenotypic heterogeneity in modeling cancer evolution.

    Directory of Open Access Journals (Sweden)

    Ali Mahdipour-Shirayeh

    Full Text Available The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous population of stem cells (SCs and their associated progenitors. The fate of a malignant mutation is determined not only by overall stem cell and non-stem cell growth rates but also differentiation and dedifferentiation rates. We investigate the effect of such a complex population structure on the evolution of malignant mutations. We derive exactly calculated results for the fixation probability of a mutant arising in each of the subpopulations. The exactly calculated results are in almost perfect agreement with the numerical simulations. Moreover, a condition for evolutionary advantage of a mutant cell versus the wild type population is given in the present study. We also show that microenvironment-induced plasticity in invading mutants leads to more aggressive mutants with higher fixation probability. Our model predicts that decreasing polarity between stem and non-stem cells' turnover would raise the survivability of non-plastic mutants; while it would suppress the development of malignancy for plastic mutants. The derived results are novel and general with potential applications in nature; we discuss our model in the context of colorectal/intestinal cancer (at the epithelium. However, the model clearly needs to be validated through appropriate experimental data. This novel mathematical framework can be applied more generally to a variety of problems concerning selection in heterogeneous populations, in other contexts such as population genetics, and ecology.

  4. The importance of environment on respiratory genotype/phenotype relationships in the Inuit

    DEFF Research Database (Denmark)

    Candelaria, P V; Backer, Vibeke; Khoo, S-K

    2010-01-01

    Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry....

  5. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona

    2016-01-01

    OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analy...

  6. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape

  7. Delineating SPTAN1 associated phenotypes

    DEFF Research Database (Denmark)

    Syrbe, Steffen; Harms, Frederike L; Parrini, Elena

    2017-01-01

    De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutati...

  8. The dark side of technology

    CERN Document Server

    Townsend, Peter

    2016-01-01

    Technological progress comes with a dark side where good ideas and intentions produce undesirable results (extreme downsides include atomic and biological weapons). The many and various unexpected outcomes of technology span humorous to bizarre, to situations that threaten human survival. Development can be positive for some, but negative and isolating for others (e.g. older or poorer people). Progress is often transient, as faster electronics and computers dramatically shorten retention time of data, knowledge, and information loss (e.g. even photos may be unreadable within a generation). Progress and globalization are also destroying past languages and cultures. Advances cut across all areas of science and life, and the scope is vast from biology, medicine, agriculture, transport, electronics, computers, long-range communications, to a global economy. Reliance on technology causes unexpected technology-driven vulnerability to natural events (e.g. intense sunspot activity) that could annihilate advanced soci...

  9. Ocean acidification challenges copepod phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    A. Vehmaa

    2016-11-01

    Full Text Available Ocean acidification is challenging phenotypic plasticity of individuals and populations. Calanoid copepods (zooplankton are shown to be fairly plastic against altered pH conditions, and laboratory studies indicate that transgenerational effects are one mechanism behind this plasticity. We studied phenotypic plasticity of the copepod Acartia sp. in the course of a pelagic, large-volume mesocosm study that was conducted to investigate ecosystem and biogeochemical responses to ocean acidification. We measured copepod egg production rate, egg-hatching success, adult female size and adult female antioxidant capacity (ORAC as a function of acidification (fCO2  ∼  365–1231 µatm and as a function of quantity and quality of their diet. We used an egg transplant experiment to reveal whether transgenerational effects can alleviate the possible negative effects of ocean acidification on offspring development. We found significant negative effects of ocean acidification on adult female size. In addition, we found signs of a possible threshold at high fCO2, above which adaptive maternal effects cannot alleviate the negative effects of acidification on egg-hatching and nauplii development. We did not find support for the hypothesis that insufficient food quantity (total particulate carbon < 55 µm or quality (C : N weakens the transgenerational effects. However, females with high-ORAC-produced eggs with high hatching success. Overall, these results indicate that Acartia sp. could be affected by projected near-future CO2 levels.

  10. Ocean acidification challenges copepod phenotypic plasticity

    Science.gov (United States)

    Vehmaa, Anu; Almén, Anna-Karin; Brutemark, Andreas; Paul, Allanah; Riebesell, Ulf; Furuhagen, Sara; Engström-Öst, Jonna

    2016-11-01

    Ocean acidification is challenging phenotypic plasticity of individuals and populations. Calanoid copepods (zooplankton) are shown to be fairly plastic against altered pH conditions, and laboratory studies indicate that transgenerational effects are one mechanism behind this plasticity. We studied phenotypic plasticity of the copepod Acartia sp. in the course of a pelagic, large-volume mesocosm study that was conducted to investigate ecosystem and biogeochemical responses to ocean acidification. We measured copepod egg production rate, egg-hatching success, adult female size and adult female antioxidant capacity (ORAC) as a function of acidification (fCO2 ˜ 365-1231 µatm) and as a function of quantity and quality of their diet. We used an egg transplant experiment to reveal whether transgenerational effects can alleviate the possible negative effects of ocean acidification on offspring development. We found significant negative effects of ocean acidification on adult female size. In addition, we found signs of a possible threshold at high fCO2, above which adaptive maternal effects cannot alleviate the negative effects of acidification on egg-hatching and nauplii development. We did not find support for the hypothesis that insufficient food quantity (total particulate carbon < 55 µm) or quality (C : N) weakens the transgenerational effects. However, females with high-ORAC-produced eggs with high hatching success. Overall, these results indicate that Acartia sp. could be affected by projected near-future CO2 levels.

  11. Partial phenotyping in voluntary blood donors of Gujarat State

    Directory of Open Access Journals (Sweden)

    Maitrey Gajjar

    2016-01-01

    Full Text Available Introduction: Partial phenotyping of voluntary blood donors has vital role in transfusion practice, population genetic study and in resolving legal issues.The Rh blood group is one of the most complex and highly immunogenic blood group known in humans. The Kell system, discovered in 1946, is the third most potent system at triggering hemolytic transfusion reactions and consists of 25 highly immunogenic antigens. Knowledge of Rh & Kell phenotypes in given population is relevant for better planning and management of blood bank; the main goal is to find compatible blood for patients needing multiple blood transfusions. The aim of this study was to evaluate the frequency of Rh & Kell phenotype of voluntary donors in Gujarat state. Materials and Methods: The present study was conducted by taking 5670 samples from random voluntary blood donors coming in blood donation camp. Written consent was taken for donor phenotyping. The antigen typing of donors was performed by Qwalys-3(manufacturer: Diagast by using electromagnetic technology on Duolys plates. Results: Out of 5670 donors, the most common Rh antigen observed in the study population was e (99.07% followed by D (95.40%, C (88.77%, c (55.89% and E (17.88%. The frequency of the Kell antigen (K was 1.78 %. Discussion: The antigen frequencies among blood donors from Gujarat were compared with those published for other Indian populations. The frequency of D antigen in our study (95.4% and north Indian donors (93.6 was significantly higher than in the Caucasians (85% and lower than in the Chinese (99%. The frequencies of C, c and E antigens were dissimilar to other ethnic groups while the ′e′ antigen was present in high frequency in our study as also in the other ethnic groups. Kell antigen (K was found in only 101 (1.78 % donors out of 5670. Frequency of Kell antigen in Caucasian and Black populations is 9% & 2% respectively. The most common Kell phenotype was K-k+, not just in Indians (96.5% but

  12. Interoperability between phenotype and anatomy ontologies.

    Science.gov (United States)

    Hoehndorf, Robert; Oellrich, Anika; Rebholz-Schuhmann, Dietrich

    2010-12-15

    Phenotypic information is important for the analysis of the molecular mechanisms underlying disease. A formal ontological representation of phenotypic information can help to identify, interpret and infer phenotypic traits based on experimental findings. The methods that are currently used to represent data and information about phenotypes fail to make the semantics of the phenotypic trait explicit and do not interoperate with ontologies of anatomy and other domains. Therefore, valuable resources for the analysis of phenotype studies remain unconnected and inaccessible to automated analysis and reasoning. We provide a framework to formalize phenotypic descriptions and make their semantics explicit. Based on this formalization, we provide the means to integrate phenotypic descriptions with ontologies of other domains, in particular anatomy and physiology. We demonstrate how our framework leads to the capability to represent disease phenotypes, perform powerful queries that were not possible before and infer additional knowledge. http://bioonto.de/pmwiki.php/Main/PheneOntology.

  13. Genetic versus rearing-environment effects on phenotype: hatchery and natural rearing effects on hatchery- and wild-born coho salmon.

    Directory of Open Access Journals (Sweden)

    Cedar M Chittenden

    Full Text Available With the current trends in climate and fisheries, well-designed mitigative strategies for conserving fish stocks may become increasingly necessary. The poor post-release survival of hatchery-reared Pacific salmon indicates that salmon enhancement programs require assessment. The objective of this study was to determine the relative roles that genotype and rearing environment play in the phenotypic expression of young salmon, including their survival, growth, physiology, swimming endurance, predator avoidance and migratory behaviour. Wild- and hatchery-born coho salmon adults (Oncorhynchus kisutch returning to the Chehalis River in British Columbia, Canada, were crossed to create pure hatchery, pure wild, and hybrid offspring. A proportion of the progeny from each cross was reared in a traditional hatchery environment, whereas the remaining fry were reared naturally in a contained side channel. The resulting phenotypic differences between replicates, between rearing environments, and between cross types were compared. While there were few phenotypic differences noted between genetic groups reared in the same habitat, rearing environment played a significant role in smolt size, survival, swimming endurance, predator avoidance and migratory behaviour. The lack of any observed genetic differences between wild- and hatchery-born salmon may be due to the long-term mixing of these genotypes from hatchery introgression into wild populations, or conversely, due to strong selection in nature--capable of maintaining highly fit genotypes whether or not fish have experienced part of their life history under cultured conditions.

  14. The importance of environment on respiratory genotype/phenotype relationships in the Inuit

    DEFF Research Database (Denmark)

    Candelaria, P V; Backer, V; Khoo, S-K

    2010-01-01

    Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry.......Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry....

  15. Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daniel [Iowa State University; Phan, Ngoc [Iowa State University; Isely, Christopher [Iowa State University; Bruene, Lucas [Iowa State University; Bratlie, Kaitlin M [Ames Laboratory

    2014-11-10

    Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (~600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

  16. Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins

    DEFF Research Database (Denmark)

    Li, Shuxia; Kyvik, Kirsten Ohm; Pang, Zengchang

    2016-01-01

    OBJECTIVE: The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic...... pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23-64). The classical twin models were fitted to the longitudinal change in each phenotypephenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype. RESULTS: Moderate to high...... contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated...

  17. 49 CFR 238.217 - Side structure.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Side structure. 238.217 Section 238.217 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Equipment § 238.217 Side structure. Each passenger car shall comply with the following: (a) Side posts and...

  18. Distributed video coding with multiple side information

    DEFF Research Database (Denmark)

    Huang, Xin; Brites, C.; Ascenso, J.

    2009-01-01

    Distributed Video Coding (DVC) is a new video coding paradigm which mainly exploits the source statistics at the decoder based on the availability of some decoder side information. The quality of the side information has a major impact on the DVC rate-distortion (RD) performance in the same way...... the quality of the predictions had a major impact in predictive video coding. In this paper, a DVC solution exploiting multiple side information is proposed; the multiple side information is generated by frame interpolation and frame extrapolation targeting to improve the side information of a single...

  19. The Lighter Side of Gravity

    Science.gov (United States)

    Narlikar, Jayant Vishnu

    1996-10-01

    From the drop of an apple to the stately dance of the galaxies, gravity is omnipresent in the Cosmos. Even with its high profile, gravity is the most enigmatic of all the known basic forces in nature. The Lighter Side of Gravity presents a beautifully clear and completely nontechnical introduction to the phenomenon of this force in all its manifestations. Astrophysicist Jayant Narlikar begins with an historical background to the discovery of the law of gravitation by Isaac Newton in the seventeenth century. Using familiar analogies, interesting anecdotes, and numerous illustrations to get across subtle effects and difficult points to readers, he goes on to describe the general theory of relativity and some of its strange and unfamiliar ideas such as curved spacetime, the bending of light, and black holes. Since first publication in 1982 (W.H. Freeman), Dr. Narlikar has brought his book completely up to date and expanded it to include the discovery of gigantic gravitational lenses in space, the findings of the Cosmic Background Explorer (COBE) satellite, the detection of dark matter in galaxies, the investigation of the very early Universe, and other new ideas in cosmology. This lucid and stimulating book presents a clear approach to the intriguing phenomenon of gravity for everyone who has ever felt caught in its grip. Jayant Narlikar is the winner of many astronomical prizes and the author of Introduction to Cosmology (Cambridge University Press, 1993).

  20. A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens

    NARCIS (Netherlands)

    Guo, Ying; Gu, Xiaorong; Sheng, Zheya; Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P.M.A.; Carlborg, Örjan; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2016-01-01

    Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA)

  1. The GP problem: quantifying gene-to-phenotype relationships.

    Science.gov (United States)

    Cooper, Mark; Chapman, Scott C; Podlich, Dean W; Hammer, Graeme L

    2002-01-01

    In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

  2. Body composition and bone density during and after childhood cancer therapy : The flip side of therapy

    NARCIS (Netherlands)

    den Hoed, M.A.H.

    2017-01-01

    In the Netherlands, there are approximately 8000 childhood cancer survivors, and this population of survivors is expanding due to improved therapy. However, therapy has a consequent flip side, namely their inherent side effects. Approximately 75% of the CCS will develop one or more severe chronic

  3. Automated phenotyping of permanent crops

    Science.gov (United States)

    McPeek, K. Thomas; Steddom, Karl; Zamudio, Joseph; Pant, Paras; Mullenbach, Tyler

    2017-05-01

    AGERpoint is defining a new technology space for the growers' industry by introducing novel applications for sensor technology and data analysis to growers of permanent crops. Serving data to a state-of-the-art analytics engine from a cutting edge sensor platform, a new paradigm in precision agriculture is being developed that allows growers to understand the unique needs of each tree, bush or vine in their operation. Autonomous aerial and terrestrial vehicles equipped with multiple varieties of remote sensing technologies give AGERpoint the ability to measure key morphological and spectral features of permanent crops. This work demonstrates how such phenotypic measurements combined with machine learning algorithms can be used to determine the variety of crops (e.g., almond and pecan trees). This phenotypic and varietal information represents the first step in enabling growers with the ability to tailor their management practices to individual plants and maximize their economic productivity.

  4. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  5. Phenotypic deconstruction of gene circuitry

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  6. From plant genomes to phenotypes

    OpenAIRE

    Bolger, Marie; Gundlach, Heidrun; Scholz, Uwe; Mayer, Klaus; Usadel, Björn; Schwacke, Rainer; Schmutzer, Thomas; Chen, Jinbo; Arend, Daniel; Oppermann, Markus; Weise, Stephan; Lange, Matthias; Fiorani, Fabio; Spannagl, Manuel

    2017-01-01

    Recent advances in sequencing technologies have greatly accelerated the rate of plant genome and applied breeding research. Despite this advancing trend, plant genomes continue to present numerous difficulties to the standard tools and pipelines not only for genome assembly but also gene annotation and downstream analysis.Here we give a perspective on tools, resources and services necessary to assemble and analyze plant genomes and link them to plant phenotypes.

  7. A matter of identity — Phenotype and differentiation potential of human somatic stem cells

    Directory of Open Access Journals (Sweden)

    S.E.P. New

    2015-07-01

    Full Text Available Human somatic stem cells with neural differentiation potential can be valuable for developing cell-based therapies, including treatment of birth-related defects, while avoiding issues associated with cell reprogramming. Precisely defining the “identity” and differentiation potential of somatic stem cells from different sources, has proven difficult, given differences in sets of specific markers, protocols used and lack of side-by-side characterization of these cells in different studies. Therefore, we set to compare expression of mesenchymal and neural markers in human umbilical cord-derived mesenchymal stem cells (UC-MSCs, pediatric adipose-derived stem cells (p-ADSCs in parallel with human neural stem cells (NSCs. We show that UC-MSCs at a basal level express mesenchymal and so-called “neural” markers, similar to that we previously reported for the p-ADSCs. All somatic stem cell populations studied, independently from tissue and patient of origin, displayed a remarkably similar expression of surface markers, with the main difference being the restricted expression of CD133 and CD34 to NSCs. Expression of certain surface and neural markers was affected by the expansion medium used. As predicted, UC-MSCs and p-ADSCs demonstrated tri-mesenchymal lineage differentiation potential, though p-ADSCs display superior chondrogenic differentiation capability. UC-MSCs and p-ADSCs responded also to neurogenic induction by up-regulating neuronal markers, but crucially they appeared morphologically immature when compared with differentiated NSCs. This highlights the need for further investigation into the use of these cells for neural therapies. Crucially, this study demonstrates the lack of simple means to distinguish between different cell types and the effect of culture conditions on their phenotype, and indicates that a more extensive set of markers should be used for somatic stem cell characterization, especially when developing therapeutic

  8. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  9. NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping.

    Science.gov (United States)

    Laughlin, Maren R; Lloyd, K C Kent; Cline, Gary W; Wasserman, David H

    2012-10-01

    The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community's needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses.

  10. Physiological and skill demands of 'on-side' and 'off-side' games.

    Science.gov (United States)

    Gabbett, Tim J; Jenkins, David G; Abernethy, Bruce

    2010-11-01

    This study investigated the physiological and skill demands of 'on-side' and 'off-side' games in elite rugby league players. Sixteen male rugby league players participated in 'on-side' and 'off-side' games. Both small-sided games were played in a 40- × 40-m playing area. The 'off-side' game permitted players to have 3 'plays' while in possession of the ball. Players were permitted to pass backward or forward (to an 'off-side' player). The 'on-side' game also permitted players to have 3 'plays' while in possession of the ball. However, players were only permitted to pass backward to players in an 'on-side' position. Heart rate and movement patterns (via global positioning system) were recorded continuously throughout both games. Data were collected on the distance covered, number of high-acceleration and velocity efforts, and recovery between efforts. Video footage was also taken to track the performance of the players. Post hoc inspection of the footage was undertaken to count the number of possessions and the number and quality of disposals. In comparison to 'on-side' games, 'off-side' games had a greater number of involvements ("touches"), passes, and effective passes. However, the cognitive demands of 'on-side' games were greater than 'off-side' games. 'Off-side' games resulted in a greater total distance covered, greater distance covered in mild and moderate accelerations, and greater distance covered in low, moderate, and high-velocity efforts. There were also a greater number of short duration recovery periods between efforts in 'off-side' games. The results of this study demonstrate that 'off-side' games provide greater physiological and skill demands than 'on-side' games. 'Off-side' games may provide a practical alternative to 'on-side' games for the development of skill and fitness in elite rugby league players.

  11. The Human Phenotype Ontology in 2017

    International Nuclear Information System (INIS)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

    2016-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

  12. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids

    2002-01-01

    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  13. Phenotypic variability in Meesmann's dystrophy

    DEFF Research Database (Denmark)

    Ehlers, Niels; Hjortdal, Jesper; Nielsen, Kim

    2008-01-01

    symptoms often include blurred vision and ocular irritation. Typical cases may be entirely free of complaints. Intermittent pain episodes, such as occur in recurrent erosion syndrome, are not the rule. Genetic sequencing indicated a familial relationship with the originally described Meesmann family......'s dystrophy occurs worldwide. The largest family described is the original German one, now supplemented with a Danish branch. Despite the presence of an identical genetic defect, the clinical phenotype varies. This suggests that non-KRT12-related mechanisms are responsible for the variation....

  14. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...... of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the 45 known type 2...

  15. A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects.

    Directory of Open Access Journals (Sweden)

    Jeanette Prinz

    2016-09-01

    Full Text Available The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments.

  16. ACE phenotyping in Gaucher disease.

    Science.gov (United States)

    Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

    2018-04-01

    Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Lethal mutagenesis: targeting the mutator phenotype in cancer.

    Science.gov (United States)

    Fox, Edward J; Loeb, Lawrence A

    2010-10-01

    The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Single side Emitting Transparent OLED lamp

    NARCIS (Netherlands)

    Lifka, H.; Verschuren, C.A.; Bruls, D.M.; Tanase, C.

    2011-01-01

    Transparent OLEDs offer great potential for novel applications. Preferably, the light should be emitted from one side only. This can bedone to some extent by modifying electrode thicknesses, but at the cost of reduced transparency. Here, we demonstrate a new approach tomake single side emissive

  19. Side-emitting fiber optic position sensor

    Science.gov (United States)

    Weiss, Jonathan D [Albuquerque, NM

    2008-02-12

    A side-emitting fiber optic position sensor and method of determining an unknown position of an object by using the sensor. In one embodiment, a concentrated beam of light source illuminates the side of a side-emitting fiber optic at an unknown axial position along the fiber's length. Some of this side-illuminated light is in-scattered into the fiber and captured. As the captured light is guided down the fiber, its intensity decreases due to loss from side-emission away from the fiber and from bulk absorption within the fiber. By measuring the intensity of light emitted from one (or both) ends of the fiber with a photodetector(s), the axial position of the light source is determined by comparing the photodetector's signal to a calibrated response curve, look-up table, or by using a mathematical model. Alternatively, the side-emitting fiber is illuminated at one end, while a photodetector measures the intensity of light emitted from the side of the fiber, at an unknown position. As the photodetector moves further away from the illuminated end, the detector's signal strength decreases due to loss from side-emission and/or bulk absorption. As before, the detector's signal is correlated to a unique position along the fiber.

  20. Macrophage Phenotype and Function in Different Stages of Atherosclerosis

    Science.gov (United States)

    Tabas, Ira; Bornfeldt, Karin E.

    2016-01-01

    The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for more than 50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to HDL; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and pro-resolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge. PMID:26892964

  1. Left-sided congenital heart lesions in mosaic Turner syndrome.

    Science.gov (United States)

    Bouayed Abdelmoula, Nouha; Abdelmoula, Balkiss; Smaoui, Walid; Trabelsi, Imen; Louati, Rim; Aloulou, Samir; Aloulou, Wafa; Abid, Fatma; Kammoun, Senda; Trigui, Khaled; Bedoui, Olfa; Denguir, Hichem; Mallek, Souad; Ben Aziza, Mustapha; Dammak, Jamila; Kaabi, Oldez; Abdellaoui, Nawel; Turki, Fatma; Kaabi, Asma; Kamoun, Wafa; Jabeur, Jihen; Ltaif, Wided; Chaker, Kays; Fourati, Haytham; M'rabet, Samir; Ben Ameur, Hedi; Gouia, Naourez; Mhiri, Mohamed Nabil; Rebai, Tarek

    2018-04-01

    In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-β-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.

  2. Environmental, phenotypic and genetic variation of wild barley (Hordeum spontaneum) from Israel

    NARCIS (Netherlands)

    Vanhala, T.; Rijn, C.P.E.; Buntjer, J.; Stam, P.; Nevo, E.; Poorter, H.; Eeuwijk, van F.A.

    2004-01-01

    Wild relatives of crop plants offer an attractive gene pool for cultivar improvement. We evaluated genetic and phenotypic variation for a set of 72 Israeli accessions of wild barley from 21 populations. These populations were grouped further into four ecotypes. In addition, environmental variables

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

    African Journals Online (AJOL)

    A single nucleotide polymorphism (SNP) assay for population stratification test ... phenotypes and unlinked candidate loci in case-control and cohort studies of ... Key words: Chinese, Japanese, population stratification, ancestry informative ...

  4. Epigenetic population differentiation in field- and common garden-grown Scabiosa columbaria plants

    NARCIS (Netherlands)

    Groot, Maartje P; Wagemaker, Niels CAM; Ouborg, N Joop; Verhoeven, Koen J F; Vergeer, Philippine

    Populations often differ in phenotype and these differences can be caused by adaptation by natural selection, random neutral processes, and environmental responses. The most straightforward way to divide mechanisms that influence phenotypic variation is heritable variation and environmental-induced

  5. Population Heterogeneity of Lactobacillus plantarum WCFS1 Microcolonies in Response to and Recovery from Acid Stress

    NARCIS (Netherlands)

    Ingham, C.J.; Beerthuyzen, M.; Vlieg, J.E.T.V.H.

    2008-01-01

    Within an isogenic microbial population in a homogenous environment, individual bacteria can still exhibit differences in phenotype. Phenotypic heterogeneity can facilitate the survival of subpopulations under stress. As the gram-positive bacterium Lactobacillus plantarum grows, it acidifies the

  6. Sediment sorting at a side channel bifurcation

    Science.gov (United States)

    van Denderen, Pepijn; Schielen, Ralph; Hulscher, Suzanne

    2017-04-01

    Side channels have been constructed to reduce the flood risk and to increase the ecological value of the river. In various Dutch side channels large aggradation in these channels occurred after construction. Measurements show that the grain size of the deposited sediment in the side channel is smaller than the grain size found on the bed of the main channel. This suggest that sorting occurs at the bifurcation of the side channel. The objective is to reproduce with a 2D morphological model the fining of the bed in the side channel and to study the effect of the sediment sorting on morphodynamic development of the side channel. We use a 2D Delft3D model with two sediment fractions. The first fraction corresponds with the grain size that can be found on the bed of the main channel and the second fraction corresponds with the grain size found in the side channel. With the numerical model we compute several side channel configurations in which we vary the length and the width of the side channel, and the curvature of the upstream channel. From these computations we can derive the equilibrium state and the time scale of the morphodynamic development of the side channel. Preliminary results show that even when a simple sediment transport relation is used, like Engelund & Hansen, more fine sediment enters the side channel than coarse sediment. This is as expected, and is probably related to the bed slope effects which are a function of the Shields parameter. It is expected that by adding a sill at the entrance of the side channel the slope effect increases. This might reduce the amount of coarse sediment which enters the side channel even more. It is unclear whether the model used is able to reproduce the effect of such a sill correctly as modelling a sill and reproducing the correct hydrodynamic and morphodynamic behaviour is not straightforward in a 2D model. Acknowledgements: This research is funded by STW, part of the Dutch Organization for Scientific Research under

  7. A Study of Clinicopathological Differences Between Right-sided and Left-sided Colon Cancers

    OpenAIRE

    芳賀, 駿介; 遠藤, 俊吾; 加藤, 博之; 高橋, 直樹; 吉松, 和彦; 橋本, 雅彦; 石橋, 敬一郎; 梅原, 有弘; 横溝, 肇; 梶原, 哲郎; Shunsuke, HAGA; Shungo, ENDO; Hiroyuki, KATO; Naoki, TAKAHASHI; Kazuhiko, YOSHIMATSU

    1996-01-01

    The present study was aimed to determine the clinicopathological features of cancers of the right-sided colon (cecum, ascending colon, transverse colon) and left-sided colon (descending colon, sigmoid colon) in order to help improve the efficacy of their treatment. Excluding multiple cancer cases, 364 patients with primary colon cancer underwent surgey at our department between 1974 and 1994; they comprised 171 individuals with right-sided colon cancer and 193 with left-sided colon cancer. A ...

  8. Digest: Plants adapt under attack: genotypic selection and phenotypic plasticity under herbivore pressure.

    Science.gov (United States)

    Hawkins, Nichola J

    2018-03-31

    Plant species adapt to changing environmental conditions through phenotypic plasticity and natural selection. Agrawal et al. (2018) found that dandelions responded to the presence of insect pests by producing higher levels of defensive compounds. This defensive response resulted both from phenotypic plasticity, with individual plants' defenses triggered by insect attack, and from evolution by natural selection acting on genetic variation in the plant population. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  9. Phenotypic Changes in Different Spinach Varieties Grown and Selected under Organic Conditions

    Directory of Open Access Journals (Sweden)

    Nicolas Schermann

    2011-09-01

    Full Text Available Organic and low-input agriculture needs flexible varieties that can buffer environmental stress and adapt to the needs of farmers. We implemented an experiment to investigate the evolutionary capacities of a sample of spinach (Spinacia oleracea L. population varieties for a number of phenotypic traits. Three farmers cultivated, selected and multiplied one or several populations over two years on their farms. The third year, the versions of the varieties cultivated and selected by the different farmers were compared to the original seed lots they had been given. After two cycles of cultivation and on-farm mass selection, all the observed varieties showed significant phenotypic changes (differences between the original version and the version cultivated by farmers for morphological and phenological traits. When the divergence among versions within varieties was studied, the results show that the varieties conserved their identity, except for one variety, which evolved in such a way that it may now be considered two different varieties. The heterogeneity of the population varieties was assessed in comparison with a commercial F1 hybrid used as control, and we found no specific differences in phenotypic diversity between the hybrid and population varieties. The phenotypic changes shown by the population varieties in response to on-farm cultivation and selection could be useful for the development of specific adaptation. These results call into question the current European seed legislation and the requirements of phenotypic stability for conservation varieties.

  10. Global change and the evolution of phenotypic plasticity in plants.

    Science.gov (United States)

    Matesanz, Silvia; Gianoli, Ernesto; Valladares, Fernando

    2010-09-01

    Global change drivers create new environmental scenarios and selective pressures, affecting plant species in various interacting ways. Plants respond with changes in phenology, physiology, and reproduction, with consequences for biotic interactions and community composition. We review information on phenotypic plasticity, a primary means by which plants cope with global change scenarios, recommending promising approaches for investigating the evolution of plasticity and describing constraints to its evolution. We discuss the important but largely ignored role of phenotypic plasticity in range shifts and review the extensive literature on invasive species as models of evolutionary change in novel environments. Plasticity can play a role both in the short-term response of plant populations to global change as well as in their long-term fate through the maintenance of genetic variation. In new environmental conditions, plasticity of certain functional traits may be beneficial (i.e., the plastic response is accompanied by a fitness advantage) and thus selected for. Plasticity can also be relevant in the establishment and persistence of plants in novel environments that are crucial for populations at the colonizing edge in range shifts induced by climate change. Experimental studies show taxonomically widespread plastic responses to global change drivers in many functional traits, though there is a lack of empirical support for many theoretical models on the evolution of phenotypic plasticity. Future studies should assess the adaptive value and evolutionary potential of plasticity under complex, realistic global change scenarios. Promising tools include resurrection protocols and artificial selection experiments. © 2010 New York Academy of Sciences.

  11. Morphological analysis and DNA methylation in Conyza bonariensis L. cronquist (Asteraceae phenotypes

    Directory of Open Access Journals (Sweden)

    Juliana Maria de Paula

    2017-08-01

    Full Text Available ABSTRACT The species Conyza bonariensis (L. cause losses in agriculture due to their invasive capacity and resistance to herbicides like glyphosate. The species of this genus exhibit phenotypic plasticity, which complicates their identification and characterization. Thus, experiments were performed with 2 extreme C. bonariensis phenotypes (called broad leaf and narrow leaf in greenhouse conditions and in the laboratory, in order to verify if the morphological differences among these phenotypes are a genetic character or result from environmental effects. In addition to the comparative morphological analysis, assessment of DNA methylation profile was performed to detect the occurrence, or not, of differences in the epigenetic level. The morphological characteristics evaluated were length, width, shape, margin and leaves indument; plant height and stem indument; the number of capitula, flowers and seeds. The Methylation Sensitive Amplified Polymorphism technique was used to investigate the methylation levels. The morphological differences of phenotypes supposed to be C. bonariensis are probably genetic in origin and not the result of environmental effects, since, after 6 crop cycles in a greenhouse under the same environmental conditions, these phenotypes remained with the same morphological characteristics and seed production in relation to the original phenotypes found in the collection site. The different phenotypes did not show differences corresponding to DNA methylation patterns that could indicate an epigenetic effect as the cause of the differences between the 2 phenotypes. The results of morphological analysis and methylation probably indicate that maybe they are individuals of populations from different taxa not registered yet in the literature.

  12. The phenotypic equilibrium of cancer cells: From average-level stability to path-wise convergence.

    Science.gov (United States)

    Niu, Yuanling; Wang, Yue; Zhou, Da

    2015-12-07

    The phenotypic equilibrium, i.e. heterogeneous population of cancer cells tending to a fixed equilibrium of phenotypic proportions, has received much attention in cancer biology very recently. In the previous literature, some theoretical models were used to predict the experimental phenomena of the phenotypic equilibrium, which were often explained by different concepts of stabilities of the models. Here we present a stochastic multi-phenotype branching model by integrating conventional cellular hierarchy with phenotypic plasticity mechanisms of cancer cells. Based on our model, it is shown that: (i) our model can serve as a framework to unify the previous models for the phenotypic equilibrium, and then harmonizes the different kinds of average-level stabilities proposed in these models; and (ii) path-wise convergence of our model provides a deeper understanding to the phenotypic equilibrium from stochastic point of view. That is, the emergence of the phenotypic equilibrium is rooted in the stochastic nature of (almost) every sample path, the average-level stability just follows from it by averaging stochastic samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Mechanisms by Which Phenotypic Plasticity Affects Adaptive Divergence and Ecological Speciation.

    Science.gov (United States)

    Nonaka, Etsuko; Svanbäck, Richard; Thibert-Plante, Xavier; Englund, Göran; Brännström, Åke

    2015-11-01

    Phenotypic plasticity is the ability of one genotype to produce different phenotypes depending on environmental conditions. Several conceptual models emphasize the role of plasticity in promoting reproductive isolation and, ultimately, speciation in populations that forage on two or more resources. These models predict that plasticity plays a critical role in the early stages of speciation, prior to genetic divergence, by facilitating fast phenotypic divergence. The ability to plastically express alternative phenotypes may, however, interfere with the early phase of the formation of reproductive barriers, especially in the absence of geographic barriers. Here, we quantitatively investigate mechanisms under which plasticity can influence progress toward adaptive genetic diversification and ecological speciation. We use a stochastic, individual-based model of a predator-prey system incorporating sexual reproduction and mate choice in the predator. Our results show that evolving plasticity promotes the evolution of reproductive isolation under diversifying environments when individuals are able to correctly select a more profitable habitat with respect to their phenotypes (i.e., adaptive habitat choice) and to assortatively mate with relatively similar phenotypes. On the other hand, plasticity facilitates the evolution of plastic generalists when individuals have a limited capacity for adaptive habitat choice. We conclude that plasticity can accelerate the evolution of a reproductive barrier toward adaptive diversification and ecological speciation through enhanced phenotypic differentiation between diverging phenotypes.

  14. The phenotypic variance gradient - a novel concept.

    Science.gov (United States)

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  15. The DarkSide Program at LNGS

    OpenAIRE

    Wright, Alex; Collaboration, for the DarkSide

    2011-01-01

    DarkSide is a direct detection dark matter program based on two phase time projection chambers with depleted argon targets. The DarkSide detectors are designed, using novel low background techniques and active shielding, to be capable of demonstrating in situ a very low level of residual background. This means that each detector in the DarkSide program should have the ability to make a convincing claim of dark matter detection based on the observation of a few nuclear recoil events. The colla...

  16. The far-side solar magnetic index

    International Nuclear Information System (INIS)

    Hernandez, Irene Gonzalez; Jain, Kiran; Hill, Frank; Tobiska, W Kent

    2011-01-01

    Several magnetic indices are used to model the solar irradiance and ultimately to forecast it. However, the observation of such indices are generally limited to the Earth-facing hemisphere of the Sun. Seismic maps of the far side of the Sun have proven their capability to locate and track medium-large active regions at the non-visible hemisphere. We present here the possibility of using the average signal from these seismic far-side maps as a proxy to the non-visible solar activity which can complement the current front-side solar activity indices.

  17. The Microenvironment in Gliomas: Phenotypic Expressions

    Directory of Open Access Journals (Sweden)

    Davide Schiffer

    2015-12-01

    Full Text Available The microenvironment of malignant gliomas is described according to its definition in the literature. Beside tumor cells, a series of stromal cells (microglia/macrophages, pericytes, fibroblasts, endothelial cells, normal and reactive astrocytes represents the cell component, whereas a complex network of molecular signaling represents the functional component. Its most evident expressions are perivascular and perinecrotic niches that are believed to be the site of tumor stem cells or progenitors in the tumor. Phenotypically, both niches are not easily recognizable; here, they are described together with a critical revision of their concept. As for perinecrotic niches, an alternative interpretation is given about their origin that regards the tumor stem cells as the residue of those that populated hyperproliferating areas in which necroses develop. This is based on the concept that the stem-like is a status and not a cell type, depending on the microenvironment that regulates a conversion of tumor non-stem cells and tumor stem cells through a cell reprogramming.

  18. HFE genotype affects exosome phenotype in cancer.

    Science.gov (United States)

    Mrowczynski, Oliver D; Madhankumar, A B; Slagle-Webb, Becky; Lee, Sang Y; Zacharia, Brad E; Connor, James R

    2017-08-01

    Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. Tumor progression and recurrence is common with little understanding of mechanisms. A major recent focus in cancer biology is the impact of exosomes on metastatic behavior and the tumor microenvironment. Exosomes have been demonstrated to contribute to the oncogenic effect on the surrounding tumor environment and also mediate resistance to therapy. The effect of genotype on exosomal phenotype has not yet been explored. We interrogated exosomes from human neuroblastoma cells that express wild-type or mutant forms of the HFE gene. HFE, one of the most common autosomal recessive polymorphisms in the Caucasian population, originally associated with hemochromatosis, has also been associated with increased tumor burden, therapeutic resistance boost, and negative impact on patient survival. Herein, we demonstrate that changes in genotype cause major differences in the molecular and functional properties of exosomes; specifically, HFE mutant derived exosomes have increased expression of proteins relating to invasion, angiogenesis, and cancer therapeutic resistance. HFE mutant derived exosomes were also shown to transfer this cargo to recipient cells and cause an increased oncogenic functionality in those recipient cells. Copyright © 2017. Published by Elsevier B.V.

  19. Phenotypic assays for Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Song, Ok-Ryul; Deboosere, Nathalie; Delorme, Vincent; Queval, Christophe J; Deloison, Gaspard; Werkmeister, Elisabeth; Lafont, Frank; Baulard, Alain; Iantomasi, Raffaella; Brodin, Priscille

    2017-10-01

    Tuberculosis (TB) is still a major global threat, killing more than one million persons each year. With the constant increase of Mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of TB. Although screenings of small molecules on axenic M. tuberculosis cultures were successful for the identification of novel putative anti-TB drugs, new drugs in the development pipeline remains scarce. Host-directed therapy may represent an alternative for drug development against TB. Indeed, M. tuberculosis has multiple specific interactions within host phagocytes, which may be targeted by small molecules. In order to enable drug discovery strategies against microbes residing within host macrophages, we developed multiple fluorescence-based HT/CS phenotypic assays monitoring the intracellular replication of M. tuberculosis as well as its intracellular trafficking. What we propose here is a population-based, multi-parametric analysis pipeline that can be used to monitor the intracellular fate of M. tuberculosis and the dynamics of cellular events such as phagosomal maturation (acidification and permeabilization), zinc poisoning system or lipid body accumulation. Such analysis allows the quantification of biological events considering the host-pathogen interplay and may thus be derived to other intracellular pathogens. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  20. Identification of extreme motor phenotypes in Huntington's disease.

    Science.gov (United States)

    Braisch, Ulrike; Hay, Birgit; Muche, Rainer; Rothenbacher, Dietrich; Landwehrmeyer, G Bernhard; Long, Jeffrey D; Orth, Michael

    2017-04-01

    The manifestation of motor signs in Huntington's disease (HD) has a well-known inverse relationship with HTT CAG repeat length, but the prediction is far from perfect. The probability of finding disease modifiers is enhanced in individuals with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes conditional on CAG and age, such as patients with very early or very late onset of motor manifestation. Retrospective data were available from 1,218 healthy controls and 9,743 HD participants with CAG repeats ≥40, and a total of about 30,000 visits. Boundaries (2.5% and 97.5% quantiles) for extreme motor phenotypes (UHDRS total motor score (TMS) and motor age-at-onset) were estimated using quantile regression for longitudinal data. More than 15% of HD participants had an extreme TMS phenotype for at least one visit. In contrast, only about 4% of participants were consistent TMS extremes at two or more visits. Data from healthy controls revealed an upper cut-off of 13 for the TMS representing the extreme of motor ratings for a normal aging population. In HD, boundaries of motor age-at-onset based on diagnostic confidence or derived from the TMS data cut-off in controls were similar. In summary, a UHDRS TMS of more than 13 in an individual carrying the HD mutation indicates a high likelihood of motor manifestations of HD irrespective of CAG repeat length or age. The identification of motor phenotype extremes can be useful in the search for disease modifiers, for example, genetic or environmental such as medication. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Integrating Evolutionary Game Theory into Mechanistic Genotype-Phenotype Mapping.

    Science.gov (United States)

    Zhu, Xuli; Jiang, Libo; Ye, Meixia; Sun, Lidan; Gragnoli, Claudia; Wu, Rongling

    2016-05-01

    Natural selection has shaped the evolution of organisms toward optimizing their structural and functional design. However, how this universal principle can enhance genotype-phenotype mapping of quantitative traits has remained unexplored. Here we show that the integration of this principle and functional mapping through evolutionary game theory gains new insight into the genetic architecture of complex traits. By viewing phenotype formation as an evolutionary system, we formulate mathematical equations to model the ecological mechanisms that drive the interaction and coordination of its constituent components toward population dynamics and stability. Functional mapping provides a procedure for estimating the genetic parameters that specify the dynamic relationship of competition and cooperation and predicting how genes mediate the evolution of this relationship during trait formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Cattle phenotypes can disguise their maternal ancestry.

    Science.gov (United States)

    Srirattana, Kanokwan; McCosker, Kieren; Schatz, Tim; St John, Justin C

    2017-06-26

    Cattle are bred for, amongst other factors, specific traits, including parasite resistance and adaptation to climate. However, the influence and inheritance of mitochondrial DNA (mtDNA) are not usually considered in breeding programmes. In this study, we analysed the mtDNA profiles of cattle from Victoria (VIC), southern Australia, which is a temperate climate, and the Northern Territory (NT), the northern part of Australia, which has a tropical climate, to determine if the mtDNA profiles of these cattle are indicative of breed and phenotype, and whether these profiles are appropriate for their environments. A phylogenetic tree of the full mtDNA sequences of different breeds of cattle, which were obtained from the NCBI database, showed that the mtDNA profiles of cattle do not always reflect their phenotype as some cattle with Bos taurus phenotypes had Bos indicus mtDNA, whilst some cattle with Bos indicus phenotypes had Bos taurus mtDNA. Using D-loop sequencing, we were able to contrast the phenotypes and mtDNA profiles from different species of cattle from the 2 distinct cattle breeding regions of Australia. We found that 67 of the 121 cattle with Bos indicus phenotypes from NT (55.4%) had Bos taurus mtDNA. In VIC, 92 of the 225 cattle with Bos taurus phenotypes (40.9%) possessed Bos indicus mtDNA. When focusing on oocytes from cattle with the Bos taurus phenotype in VIC, their respective oocytes with Bos indicus mtDNA had significantly lower levels of mtDNA copy number compared with oocytes possessing Bos taurus mtDNA (P cattle with a Bos taurus phenotype. The phenotype of cattle is not always related to their mtDNA profiles. MtDNA profiles should be considered for breeding programmes as they also influence phenotypic traits and reproductive capacity in terms of oocyte quality.

  3. Lymphedema as a Cancer Treatment Side Effect

    Science.gov (United States)

    ... Considerations How Cancer is Treated Side Effects Dating, Sex, and Reproduction Advanced Cancer For Children For Teens For Young Adults For Older Adults Prevention and Healthy Living Cancer.Net Videos Coping With Cancer Research and Advocacy Survivorship Blog ...

  4. Managing Chemotherapy Side Effects: Bleeding Problems

    Science.gov (United States)

    ... C ancer I nstitute Managing Chemotherapy Side Effects Bleeding Problems “My nurse said that chemotherapy could make ... with a clean cloth. Keep pressing until the bleeding stops. If you bruise: Put ice on the ...

  5. Managing Chemotherapy Side Effects: Hair Loss (Alopecia)

    Science.gov (United States)

    ... C ancer I nstitute Managing Chemotherapy Side Effects Hair Loss (Alopecia) “Losing my hair was hard at first. ... and anywhere on your body may fall out. Hair loss is called alopecia. When will my hair start ...

  6. Managing Chemotherapy Side Effects: Nausea and Vomiting

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Nausea and Vomiting “I take medicine so I won’t feel sick ...

  7. Managing Chemotherapy Side Effects: Swelling (Fluid Retention)

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Swelling (Fluid retention) “My hands and feet were swollen and puffy. My nurse helped me understand why I had to stop eating salty ...

  8. Side- ja turvanguamet / Indrek Süld

    Index Scriptorium Estoniae

    Süld, Indrek

    2004-01-01

    Ilmunud ka: 2003 : annual report : [Eesti Raudtee]. - Tallinn, 2004, lk. 34-35; 2003 : godovoi ottshjot : [Eesti Raudtee]. - Tallinn, 2004, lk. 34-35. Ülevaade AS-i Eesti Raudtee side- ja turvanguameti tegevusest 2003. aastal. Skeem

  9. SIDES - Segment Interconnect Diagnostic Expert System

    International Nuclear Information System (INIS)

    Booth, A.W.; Forster, R.; Gustafsson, L.; Ho, N.

    1989-01-01

    It is well known that the FASTBUS Segment Interconnect (SI) provides a communication path between two otherwise independent, asynchronous bus segments. The SI is probably the most important module in any FASTBUS data acquisition network since it's failure to function can cause whole segments of the network to be inaccessible and sometimes inoperable. This paper describes SIDES, an intelligent program designed to diagnose SI's both in situ as they operate in a data acquisition network, and in the laboratory in an acceptance/repair environment. The paper discusses important issues such as knowledge acquisition; extracting knowledge from human experts and other knowledge sources. SIDES can benefit high energy physics experiments, where SI problems can be diagnosed and solved more quickly. Equipment pool technicians can also benefit from SIDES, first by decreasing the number of SI's erroneously turned in for repair, and secondly as SIDES acts as an intelligent assistant to the technician in the diagnosis and repair process

  10. Phenotypic and metabolic traits of commercial Saccharomyces cerevisiae yeasts.

    Science.gov (United States)

    Barbosa, Catarina; Lage, Patrícia; Vilela, Alice; Mendes-Faia, Arlete; Mendes-Ferreira, Ana

    2014-01-01

    Currently, pursuing yeast strains that display both a high potential fitness for alcoholic fermentation and a favorable impact on quality is a major goal in the alcoholic beverage industry. This considerable industrial interest has led to many studies characterizing the phenotypic and metabolic traits of commercial yeast populations. In this study, 20 Saccharomyces cerevisiae strains from different geographical origins exhibited high phenotypic diversity when their response to nine biotechnologically relevant conditions was examined. Next, the fermentation fitness and metabolic traits of eight selected strains with a unique phenotypic profile were evaluated in a high-sugar synthetic medium under two nitrogen regimes. Although the strains exhibited significant differences in nitrogen requirements and utilization rates, a direct relationship between nitrogen consumption, specific growth rate, cell biomass, cell viability, acetic acid and glycerol formation was only observed under high-nitrogen conditions. In contrast, the strains produced more succinic acid under the low-nitrogen regime, and a direct relationship with the final cell biomass was established. Glucose and fructose utilization patterns depended on both yeast strain and nitrogen availability. For low-nitrogen fermentation, three strains did not fully degrade the fructose. This study validates phenotypic and metabolic diversity among commercial wine yeasts and contributes new findings on the relationship between nitrogen availability, yeast cell growth and sugar utilization. We suggest that measuring nitrogen during the stationary growth phase is important because yeast cells fermentative activity is not exclusively related to population size, as previously assumed, but it is also related to the quantity of nitrogen consumed during this growth phase.

  11. Homogenizing bacterial cell factories: Analysis and engineering of phenotypic heterogeneity.

    Science.gov (United States)

    Binder, Dennis; Drepper, Thomas; Jaeger, Karl-Erich; Delvigne, Frank; Wiechert, Wolfgang; Kohlheyer, Dietrich; Grünberger, Alexander

    2017-07-01

    In natural habitats, microbes form multispecies communities that commonly face rapidly changing and highly competitive environments. Thus, phenotypic heterogeneity has evolved as an innate and important survival strategy to gain an overall fitness advantage over cohabiting competitors. However, in defined artificial environments such as monocultures in small- to large-scale bioreactors, cell-to-cell variations are presumed to cause reduced production yields as well as process instability. Hence, engineering microbial production toward phenotypic homogeneity is a highly promising approach for synthetic biology and bioprocess optimization. In this review, we discuss recent studies that have unraveled the cell-to-cell heterogeneity observed during bacterial gene expression and metabolite production as well as the molecular mechanisms involved. In addition, current single-cell technologies are briefly reviewed with respect to their applicability in exploring cell-to-cell variations. We highlight emerging strategies and tools to reduce phenotypic heterogeneity in biotechnological expression setups. Here, strain or inducer modifications are combined with cell physiology manipulations to achieve the ultimate goal of equalizing bacterial populations. In this way, the majority of cells can be forced into high productivity, thus reducing less productive subpopulations that tend to consume valuable resources during production. Modifications in uptake systems, inducer molecules or nutrients represent valuable tools for diminishing heterogeneity. Finally, we address the challenge of transferring homogeneously responding cells into large-scale bioprocesses. Environmental heterogeneity originating from extrinsic factors such as stirring speed and pH, oxygen, temperature or nutrient distribution can significantly influence cellular physiology. We conclude that engineering microbial populations toward phenotypic homogeneity is an increasingly important task to take biotechnological

  12. Side Stream Filtration for Cooling Towers

    Energy Technology Data Exchange (ETDEWEB)

    None

    2012-10-20

    This technology evaluation assesses side stream filtration options for cooling towers, with an objective to assess key attributes that optimize energy and water savings along with providing information on specific technology and implementation options. This information can be used to assist Federal sites to determine which options may be most appropriate for their applications. This evaluation provides an overview of the characterization of side stream filtration technology, describes typical applications, and details specific types of filtration technology.

  13. Embryonic left-right separation mechanism allows confinement of mutation-induced phenotypes to one lateral body half of bilaterians.

    Science.gov (United States)

    Ma, Kun

    2013-12-01

    A fundamental question in developmental biology is how a chimeric animal such as a bilateral gynandromorphic animal can have different phenotypes confined to different lateral body halves, and how mutation-induced phenotypes, such as genetic diseases, can be confined to one lateral body half in patients. Here, I propose that embryos of many, if not all, bilaterian animals are divided into left and right halves at a very early stage (which may vary among different types of animals), after which the descendants of the left-sided and right-sided cells will almost exclusively remain on their original sides, respectively, throughout the remaining development. This embryonic left-right separation mechanism allows (1) mutations and the mutation-induced phenotypes to be strictly confined to one lateral body half in animals and humans; (2) mothers with bilateral hereditary primary breast cancer to transmit their disease to their offspring at twofold of the rate compared to mothers with unilateral hereditary breast cancer; and (3) a mosaic embryo carrying genetic or epigenetic mutations to develop into either an individual with the mutation-induced phenotype confined unilaterally, or a pair of twins displaying complete, partial, or mirror-image discordance for the phenotype. Further, this left-right separation mechanism predicts that the two lateral halves of a patient carrying a unilateral genetic disease can each serve as a case and an internal control, respectively, for genetic and epigenetic comparative studies to identify the disease causations. © 2013 Wiley Periodicals, Inc.

  14. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have

  15. Population genetics without intraspecific data

    DEFF Research Database (Denmark)

    Thorne, Jeffrey L; Choi, Sang Chul; Yu, Jiaye

    2007-01-01

    A central goal of computational biology is the prediction of phenotype from DNA and protein sequence data. Recent models of sequence change use in silico prediction systems to incorporate the effects of phenotype on evolutionary rates. These models have been designed for analyzing sequence data...... populations, and parameters of interspecific models should have population genetic interpretations. We show, with two examples, how population genetic interpretations can be assigned to evolutionary models. The first example considers the impact of RNA secondary structure on sequence change, and the second...... reflects the tendency for protein tertiary structure to influence nonsynonymous substitution rates. We argue that statistical fit to data should not be the sole criterion for assessing models of sequence change. A good interspecific model should also yield a clear and biologically plausible population...

  16. MicroCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system.

    Science.gov (United States)

    Hur, Matthew; Gistelinck, Charlotte A; Huber, Philippe; Lee, Jane; Thompson, Marjorie H; Monstad-Rios, Adrian T; Watson, Claire J; McMenamin, Sarah K; Willaert, Andy; Parichy, David M; Coucke, Paul; Kwon, Ronald Y

    2017-09-08

    Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of phenotypic measures comprised of morphological and densitometric traits at a large number of sites within the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ system. Analyzing phenotypic patterns may increase productivity in genetic screens, and facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.

  17. Daddy issues: paternal effects on phenotype.

    Science.gov (United States)

    Rando, Oliver J

    2012-11-09

    The once popular and then heretical idea that ancestral environment can affect the phenotype of future generations is coming back into vogue due to advances in the field of epigenetic inheritance. How paternal environmental conditions influence the phenotype of progeny is now a tractable question, and researchers are exploring potential mechanisms underlying such effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Phenotypes of organ involvement in sarcoidosis

    NARCIS (Netherlands)

    Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena; Mihailović-Vučinić, Violeta; Rottoli, Paola; Grubanovic, Aleksandar; Müller, Annegret; Jochens, Arne; Tittmann, Lukas; Schnerch, Jasmin; Olivieri, Carmela; Fischer, Annegret; Jovanovic, Dragana; Filipovic, Snežana; Videnovic-Ivanovic, Jelica; Bresser, Paul; Jonkers, René; O'Reilly, Kate; Ho, Ling-Pei; Gaede, Karoline I.; Zabel, Peter; Dubaniewicz, Anna; Marshall, Ben; Kieszko, Robert; Milanowski, Janusz; Günther, Andreas; Weihrich, Anette; Petrek, Martin; Kolek, Vitezslav; Keane, Michael P.; O'Beirne, Sarah; Donnelly, Seamas; Haraldsdottir, Sigridur Olina; Jorundsdottir, Kristin B.; Costabel, Ulrich; Bonella, Francesco; Wallaert, Benoît; Grah, Christian; Peroš-Golubičić, Tatjana; Luisetti, Mauritio; Kadija, Zamir; Pabst, Stefan; Grohé, Christian; Strausz, János; Vašáková, Martina; Sterclova, Martina; Millar, Ann; Homolka, Jiří; Slováková, Alena; Kendrick, Yvonne; Crawshaw, Anjali; Wuyts, Wim; Spencer, Lisa; Pfeifer, Michael; Valeyre, Dominique; Poletti, Venerino; Wirtz, Hubertus; Prasse, Antje; Schreiber, Stefan; Krawczak, Michael; Müller-Quernheim, Joachim

    2018-01-01

    Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis. The baseline

  19. Emerging semantics to link phenotype and environment

    Directory of Open Access Journals (Sweden)

    Anne E. Thessen

    2015-12-01

    Full Text Available Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1 use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2 two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3 two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE and the Biological Collections Ontology (BCO; these provide a starting point for the development of a data model linking phenotypes and environments.

  20. Haptoglobin Phenotypes and Hypertension in Indigenous Zambians ...

    African Journals Online (AJOL)

    Haptoglobin Phenotypes and Hypertension in Indigenous Zambians at the University Teaching Hospital, Lusaka, Zambia. MM Phiri, T Kaile, FM Goma. Abstract. Objectives: The aim of the study was to investigate the association between presence of haptoglobin phenotypes and hypertension in indigenous Zambian patients ...

  1. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-01

    a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology

  2. The Neuroanatomy of the Autistic Phenotype

    Science.gov (United States)

    Fahim, Cherine; Meguid, Nagwa A.; Nashaat, Neveen H.; Yoon, Uicheul; Mancini-Marie, Adham; Evans, Alan C.

    2012-01-01

    The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X…

  3. Phenotypic plasticity as an adaptive response to predictable and unpredictable environmental changes

    DEFF Research Database (Denmark)

    Manenti, Tommaso

    Phenotypic plasticity is the ability of a genotype to modify its phenotype in response to environmental changes as a consequence of an interaction between genes and environment (Bradshaw, 1965). Plasticity contributes to the vast phenotypic variation observed in natural populations. Many examples...... of a plastic response are expected to depend on the environmental conditions experienced by organisms. Thus, in populations exposed to a non-changing environment, the plastic machinery might be a waste of resources. Contrary, in populations experiencing varying environmental conditions, plasticity is expected...... such as anti-predator behaviours or the activation of mechanisms to prevent thermal stress injuries suggest that plasticity is an adaptive response, favoured by natural selection. At the same time, organisms do show limited plastic responses, indicating that this ability is not for free. Costs and benefits...

  4. Evolving phenotypic networks in silico.

    Science.gov (United States)

    François, Paul

    2014-11-01

    Evolved gene networks are constrained by natural selection. Their structures and functions are consequently far from being random, as exemplified by the multiple instances of parallel/convergent evolution. One can thus ask if features of actual gene networks can be recovered from evolutionary first principles. I review a method for in silico evolution of small models of gene networks aiming at performing predefined biological functions. I summarize the current implementation of the algorithm, insisting on the construction of a proper "fitness" function. I illustrate the approach on three examples: biochemical adaptation, ligand discrimination and vertebrate segmentation (somitogenesis). While the structure of the evolved networks is variable, dynamics of our evolved networks are usually constrained and present many similar features to actual gene networks, including properties that were not explicitly selected for. In silico evolution can thus be used to predict biological behaviours without a detailed knowledge of the mapping between genotype and phenotype. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  5. Adjusting phenotypes by noise control.

    Directory of Open Access Journals (Sweden)

    Kyung H Kim

    2012-01-01

    Full Text Available Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

  6. Nordic research infrastructures for plant phenotyping

    Directory of Open Access Journals (Sweden)

    Kristiina Himanen

    2018-03-01

    Full Text Available Plant phenomics refers to the systematic study of plant phenotypes. Together with closely monitored, controlled climates, it provides an essential component for the integrated analysis of genotype-phenotype-environment interactions. Currently, several plant growth and phenotyping facilities are under establishment globally, and numerous facilities are already in use. Alongside the development of the research infrastructures, several national and international networks have been established to support shared use of the new methodology. In this review, an overview is given of the Nordic plant phenotyping and climate control facilities. Since many areas of phenomics such as sensor-based phenotyping, image analysis and data standards are still developing, promotion of educational and networking activities is especially important. These facilities and networks will be instrumental in tackling plant breeding and plant protection challenges. They will also provide possibilities to study wild species and their ecological interactions under changing Nordic climate conditions.

  7. Incidence of Important Hemobilia Following Transhepatic Biliary Drainage: Left-Sided Versus Right-Sided Approaches

    International Nuclear Information System (INIS)

    Rivera-Sanfeliz, G. M.; Assar, O. S. A.; LaBerge, J. M.; Wilson, M. W.; Gordon, R. L.; Ring, E. J.; Kerlan, R. K. Jr.

    2004-01-01

    Our purpose here is to describe our experience with important hemobilia following PTBD and to determine whether left-sided percutaneous transhepatic biliary drainage (PTBD) is associated with an increased incidence of important hemobilia compared to right-sided drainages. We reviewed 346 transhepatic biliary drainages over a four-year period and identified eight patients (2.3%) with important hemobilia requiring transcatheter embolization. The charts and radiographic files of these patients were reviewed. The side of the PTBD (left versus right), and the order of the biliary ductal branch entered (first, second, or third) were recorded. Of the 346 PTBDs, 269 were right-sided and 77 were left-sided. Of the eight cases of important hemobilia requiring transcatheter embolization, four followed right-sided and four followed left-sided PTBD, corresponding to a bleeding incidence of 1.5% (4/269) for right PTBD and 5.2% (4/77) for left PTBD. The higher incidence of hemobilia associated with left-sided PTBD approached, but did not reach the threshold of statistical significance (p = 0.077). In six of the eight patients requiring transcatheter embolization, first or second order biliary branches were accessed by catheter for PTBD. All patients with left-sided bleeding had first or proximal second order branches accessed by biliary drainage catheters. In conclusion, a higher incidence of hemobilia followed left- versus right-sided PTBD in this study, but the increased incidence did not reach statistical significance

  8. The Nature of Stable Insomnia Phenotypes

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L.

    2015-01-01

    Study Objectives: We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Design: Longitudinal. Setting: Urban, community-based. Participants: Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). Interventions: None. Measurements and results: At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the “neither criterion” phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. Conclusions: By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With

  9. Lamin A/C mutation affecting primarily the right side of the heart

    Directory of Open Access Journals (Sweden)

    Laura Ollila

    2013-04-01

    Full Text Available LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories.

  10. Biomechanics of side impact: Injury criteria, aging occupants, and airbag technology

    OpenAIRE

    Yoganandan, Narayan; Pintar, Frank A.; Stemper, Brian D.; Gennarelli, Thomas A.; Weigelt, John A.

    2006-01-01

    This paper presents a survey of side impact trauma-related biomedical investigations with specific reference to certain aspects of epidemiology relating to the growing elderly population, improvements in technology such as side airbags geared toward occupant safety, and development of injury criteria. The first part is devoted to the involvement of the elderly by identifying variables contributing to injury including impact severity, human factors, and national and international field data. T...

  11. Temporomandibular Disorders: The Habitual Chewing Side Syndrome

    Science.gov (United States)

    Santana-Mora, Urbano; López-Cedrún, José; Mora, María J.; Otero, Xosé L.; Santana-Penín, Urbano

    2013-01-01

    Background Temporomandibular disorders are the most common cause of chronic orofacial pain, but, except where they occur subsequent to trauma, their cause remains unknown. This cross-sectional study assessed chewing function (habitual chewing side) and the differences of the chewing side and condylar path and lateral anterior guidance angles in participants with chronic unilateral temporomandibular disorder. This is the preliminary report of a randomized trial that aimed to test the effect of a new occlusal adjustment therapy. Methods The masticatory function of 21 randomly selected completely dentate participants with chronic temporomandibular disorders (all but one with unilateral symptoms) was assessed by observing them eat almonds, inspecting the lateral horizontal movement of the jaw, with kinesiography, and by means of interview. The condylar path in the sagittal plane and the lateral anterior guidance angles with respect to the Frankfort horizontal plane in the frontal plane were measured on both sides in each individual. Results Sixteen of 20 participants with unilateral symptoms chewed on the affected side; the concordance (Fisher’s exact test, P = .003) and the concordance-symmetry level (Kappa coefficient κ = 0.689; 95% confidence interval [CI], 0.38 to 0.99; P = .002) were significant. The mean condylar path angle was steeper (53.47(10.88) degrees versus 46.16(7.25) degrees; P = .001), and the mean lateral anterior guidance angle was flatter (41.63(13.35) degrees versus 48.32(9.53) degrees P = .036) on the symptomatic side. Discussion The results of this study support the use of a new term based on etiology, “habitual chewing side syndrome”, instead of the nonspecific symptom-based “temporomandibular joint disorders”; this denomination is characterized in adults by a steeper condylar path, flatter lateral anterior guidance, and habitual chewing on the symptomatic side. PMID:23593156

  12. Endomorphisms on half-sided modular inclusions

    International Nuclear Information System (INIS)

    Svegstrup, Rolf Dyre

    2006-01-01

    In algebraic quantum field theory we consider nets of von Neumann algebras indexed over regions of the space time. Wiesbrock [''Conformal quantum field theory and half-sided modular inclusions of von Neumann algebras,'' Commun. Math. Phys. 158, 537-543 (1993)] has shown that strongly additive nets of von Neumann algebras on the circle are in correspondence with standard half-sided modular inclusions. We show that a finite index endomorphism on a half-sided modular inclusion extends to a finite index endomorphism on the corresponding net of von Neumann algebras on the circle. Moreover, we present another approach to encoding endomorphisms on nets of von Neumann algebras on the circle into half-sided modular inclusions. There is a natural way to associate a weight to a Moebius covariant endomorphism. The properties of this weight have been studied by Bertozzini et al. [''Covariant sectors with infinite dimension and positivity of the energy,'' Commun. Math. Phys. 193, 471-492 (1998)]. In this paper we show the converse, namely, how to associate a Moebius covariant endomorphism to a given weight under certain assumptions, thus obtaining a correspondence between a class of weights on a half-sided modular inclusion and a subclass of the Moebius covariant endomorphisms on the associated net of von Neumann algebras. This allows us to treat Moebius covariant endomorphisms in terms of weights on half-sided modular inclusions. As our aim is to provide a framework for treating endomorphisms on nets of von Neumann algebras in terms of the apparently simpler objects of weights on half-sided modular inclusions, we lastly give some basic results for manipulations with such weights

  13. Temporomandibular disorders: the habitual chewing side syndrome.

    Directory of Open Access Journals (Sweden)

    Urbano Santana-Mora

    Full Text Available BACKGROUND: Temporomandibular disorders are the most common cause of chronic orofacial pain, but, except where they occur subsequent to trauma, their cause remains unknown. This cross-sectional study assessed chewing function (habitual chewing side and the differences of the chewing side and condylar path and lateral anterior guidance angles in participants with chronic unilateral temporomandibular disorder. This is the preliminary report of a randomized trial that aimed to test the effect of a new occlusal adjustment therapy. METHODS: The masticatory function of 21 randomly selected completely dentate participants with chronic temporomandibular disorders (all but one with unilateral symptoms was assessed by observing them eat almonds, inspecting the lateral horizontal movement of the jaw, with kinesiography, and by means of interview. The condylar path in the sagittal plane and the lateral anterior guidance angles with respect to the Frankfort horizontal plane in the frontal plane were measured on both sides in each individual. RESULTS: Sixteen of 20 participants with unilateral symptoms chewed on the affected side; the concordance (Fisher's exact test, P = .003 and the concordance-symmetry level (Kappa coefficient κ = 0.689; 95% confidence interval [CI], 0.38 to 0.99; P = .002 were significant. The mean condylar path angle was steeper (53.47(10.88 degrees versus 46.16(7.25 degrees; P = .001, and the mean lateral anterior guidance angle was flatter (41.63(13.35 degrees versus 48.32(9.53 degrees P = .036 on the symptomatic side. DISCUSSION: The results of this study support the use of a new term based on etiology, "habitual chewing side syndrome", instead of the nonspecific symptom-based "temporomandibular joint disorders"; this denomination is characterized in adults by a steeper condylar path, flatter lateral anterior guidance, and habitual chewing on the symptomatic side.

  14. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    AlShahrani, Mona; Hoehndorf, Robert

    2018-01-01

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  15. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    Alshahrani, Mona

    2018-04-30

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  16. Laparoscopic side-to-side pancreaticojejunostomy for chronic pancreatitis in children

    Directory of Open Access Journals (Sweden)

    Kyoichi Deie

    2016-01-01

    Full Text Available Surgical pancreatic duct (PD drainage for chronic pancreatitis in children is relatively rare. It is indicated in cases of recurrent pancreatitis and PD dilatation that have not responded to medical therapy and therapeutic endoscopy. We performed laparoscopic side-to-side pancreaticojejunostomy for two paediatric patients with chronic pancreatitis. The main PD was opened easily by electrocautery after locating the dilated PD by intraoperative ultrasonography. The dilated PD was split longitudinally from the pancreatic tail to the pancreatic head by laparoscopic coagulation shears or electrocautery after pancreatography. A laparoscopic side-to-side pancreaticojejunostomy was performed by a one-layered technique using continuous 4-0 polydioxanone (PDS sutures from the pancreatic tail to the pancreatic head. There were no intraoperative or postoperative complications or recurrences. This procedure has cosmetic advantages compared with open surgery for chronic pancreatitis. Laparoscopic side-to-side pancreaticojejunostomy in children is feasible and effective for the treatment of chronic pancreatitis.

  17. Modeling occupants in far-side impacts.

    Science.gov (United States)

    Douglas, Clay; Fildes, Brian; Gibson, Tom

    2011-10-01

    Far-side impacts are not part of any regulated NCAP, FMVSS, or similar test regime despite accounting for 43 percent of the seriously injured persons and 30 percent of the harm in U.S. side impact crashes. Furthermore, injuries to the head and thorax account for over half of the serious injuries sustained by occupants in far-side crashes. Despite this, there is no regulated or well-accepted anthropomorphic test device (ATD) or computer model available to investigate far-side impacts. As such, this presents an opportunity to assess a computer model that can be used to measure the effect of varying restraint parameters on occupant biomechanics in far-side impacts. This study sets out to demonstrate the modified TASS human facet model's (MOTHMO) capabilities in modeling whole-body response in far-side impacts. MOTHMO's dynamic response was compared to that of postmortem human subjects (PMHS), WorldSID, and Thor-NT in a series of far-side sled tests. The advantages, disadvantages, and differences of using MOTHMO compared to ATDs were highlighted and described in terms of model design and instrumentation. Potential applications and improvements for MOTHMO were also recommended. The results showed that MOTHMO is capable of replicating the seat belt-to-shoulder complex interaction, pelvis impacts, head displacement, neck and shoulder belt loading from inboard mounted belts, and impacts from multiple directions. Overall, the model performed better than Thor-NT and at least as well as WorldSID when compared to PMHS results. Though WorldSID and Thor-NT ATDs were capable of reproducing many of these impact loads, measuring the seat belt-to-shoulder complex interaction and thoracic deflection at multiple sites and directions was less accurately handled. This study demonstrated that MOTHMO is capable of modeling whole-body response in far-side impacts. Furthermore, MOTHMO can be used as a virtual design tool to explore the effect of varying restraint parameters on occupant

  18. Mitochondrial genome and epigenome: two sides of the same coin.

    Science.gov (United States)

    D'Aquila, Patrizia; Montesanto, Alberto; Guarasci, Francesco; Passarino, Giuseppe; Bellizzi, Dina

    2017-01-01

    The involvement of mitochondrial content, structure and function as well as of the mitochondrial genome (mtDNA) in cell biology, by participating in the main processes occurring in the cells, has been a topic of intense interest for many years. More specifically, the progressive accumulation of variations in mtDNA of post-mitotic tissues represents a major contributing factor to both physiological and pathological phenotypes. Recently, an epigenetic overlay on mtDNA genetics is emerging, as demonstrated by the implication of the mitochondrial genome in the regulation of the intracellular epigenetic landscape being itself object of epigenetic modifications. Indeed, in vitro and population studies strongly suggest that, similarly to nuclear DNA, also mtDNA is subject to methylation and hydroxymethylation. It follows that the mitochondrial-nucleus cross talk and mitochondrial retrograde signaling in cellular properties require a concerted functional cooperation between genetic and epigenetic changes. The present paper aims to review the current advances in mitochondrial epigenetics studies and the increasing indication of mtDNA methylation status as an attractive biomarker for peculiar pathological phenotypes and environmental exposure.

  19. Algebraic Side-Channel Attack on Twofish

    Directory of Open Access Journals (Sweden)

    Chujiao Ma

    2017-05-01

    Full Text Available While algebraic side-channel attack (ASCA has been successful in breaking simple cryptographic algorithms, it has never been done on larger or more complex algorithms such as Twofish. Compared to other algorithms that ASCA has been used on, Twofish is more difficult to attack due to the key-dependent S-boxes as well as the complex key scheduling. In this paper, we propose the first algebraic side-channel attack on Twofish, and examine the importance of side-channel information in getting past the key-dependent S-boxes and the complex key scheduling. The cryptographic algorithm and side-channel information are both expressed as boolean equations and a SAT solver is used to recover the key. While algebraic attack by itself is not sufficient to break the algorithm, with the help of side-channel information such as Hamming weights, we are able to correctly solve for 96 bits of the 128 bits key in under 2 hours with known plaintext/ciphertext.

  20. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  1. Emergent properties of gene evolution: Species as attractors in phenotypic space

    Science.gov (United States)

    Reuveni, Eli; Giuliani, Alessandro

    2012-02-01

    The question how the observed discrete character of the phenotype emerges from a continuous genetic distance metrics is the core argument of two contrasted evolutionary theories: punctuated equilibrium (stable evolution scattered with saltations in the phenotype) and phyletic gradualism (smooth and linear evolution of the phenotype). Identifying phenotypic saltation on the molecular levels is critical to support the first model of evolution. We have used DNA sequences of ∼1300 genes from 6 isolated populations of the budding yeast Saccharomyces cerevisiae. We demonstrate that while the equivalent measure of the genetic distance show a continuum between lineage distance with no evidence of discrete states, the phenotypic space illustrates only two (discrete) possible states that can be associated with a saltation of the species phenotype. The fact that such saltation spans large fraction of the genome and follows by continuous genetic distance is a proof of the concept that the genotype-phenotype relation is not univocal and may have severe implication when looking for disease related genes and mutations. We used this finding with analogy to attractor-like dynamics and show that punctuated equilibrium could be explained in the framework of non-linear dynamics systems.

  2. Macrophage heterogeneity in tissues: phenotypic diversity and functions

    Science.gov (United States)

    Gordon, Siamon; Plüddemann, Annette; Martinez Estrada, Fernando

    2014-01-01

    During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults. We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment. In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation. PMID:25319326

  3. Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice

    OpenAIRE

    Rakov, Helena; Engels, Kathrin; H?nes, Georg Sebastian; Strucksberg, Karl-Heinz; Moeller, Lars Christian; K?hrle, Josef; Zwanziger, Denise; F?hrer, Dagmar

    2016-01-01

    Background Thyroid dysfunction is more common in the female population, however, the impact of sex on disease characteristics has rarely been addressed. Using a murine model, we asked whether sex has an influence on phenotypes, thyroid hormone status, and thyroid hormone tissue response in hyper- and hypothyroidism. Methods Hypo- and hyperthyroidism were induced in 5-month-old female and male wildtype C57BL/6N mice, by LoI/MMI/ClO4 ? or T4 i.p. treatment over 7?weeks, and control animals unde...

  4. Integrating phenotype ontologies with PhenomeNET

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel

    2017-12-19

    Background Integration and analysis of phenotype data from humans and model organisms is a key challenge in building our understanding of normal biology and pathophysiology. However, the range of phenotypes and anatomical details being captured in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization that includes as one of its components an ontology designed to integrate phenotype ontologies. While not applicable to matching arbitrary ontologies, PhenomeNET can be used to identify related phenotypes in different species, including human, mouse, zebrafish, nematode worm, fruit fly, and yeast. Results Here, we apply the PhenomeNET to identify related classes from two phenotype and two disease ontologies using automated reasoning. We demonstrate that we can identify a large number of mappings, some of which require automated reasoning and cannot easily be identified through lexical approaches alone. Combining automated reasoning with lexical matching further improves results in aligning ontologies. Conclusions PhenomeNET can be used to align and integrate phenotype ontologies. The results can be utilized for biomedical analyses in which phenomena observed in model organisms are used to identify causative genes and mutations underlying human disease.

  5. Redefining Aging in HIV Infection Using Phenotypes.

    Science.gov (United States)

    Stoff, David M; Goodkin, Karl; Jeste, Dilip; Marquine, Maria

    2017-10-01

    This article critically reviews the utility of "phenotypes" as behavioral descriptors in aging/HIV research that inform biological underpinnings and treatment development. We adopt a phenotypic redefinition of aging conceptualized within a broader context of HIV infection and of aging. Phenotypes are defined as dimensions of behavior, closely related to fundamental mechanisms, and, thus, may be more informative than chronological age. Primary emphasis in this review is given to comorbid aging and cognitive aging, though other phenotypes (i.e., disability, frailty, accelerated aging, successful aging) are also discussed in relation to comorbid aging and cognitive aging. The main findings that emerged from this review are as follows: (1) the phenotypes, comorbid aging and cognitive aging, are distinct from each other, yet overlapping; (2) associative relationships are the rule in HIV for comorbid and cognitive aging phenotypes; and (3) HIV behavioral interventions for both comorbid aging and cognitive aging have been limited. Three paths for research progress are identified for phenotype-defined aging/HIV research (i.e., clinical and behavioral specification, biological mechanisms, intervention targets), and some important research questions are suggested within each of these research paths.

  6. Phenotypic differentiation is associated with gender plasticity and its responsive delay to environmental changes in Alternanthera philoxeroides--phenotypic differentiation in alligator weed.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    Full Text Available Phenotypic plasticity is common in many taxa, and it may increase an organism's fitness in heterogeneous environments. However, in some cases, the frequency of environmental changes can be faster than the ability of the individual to produce new adaptive phenotypes. The importance of such a time delay in terms of individual fitness and species adaptability has not been well studied. Here, we studied gender plasticity of Alternanthera philoxeroides to address this issue through a reciprocal transplant experiment. We observed that the genders of A. philoxeroides were plastic and reversible between monoclinous and pistillody depending on habitats, the offspring maintained the maternal genders in the first year but changed from year 2 to 5, and there was a cubic relationship between the rate of population gender changes and environmental variations. This relationship indicates that the species must overcome a threshold of environmental variations to switch its developmental path ways between the two genders. This threshold and the maternal gender stability cause a significant delay of gender changes in new environments. At the same time, they result in and maintain the two distinct habitat dependent gender phenotypes. We also observed that there was a significant and adaptive life-history differentiation between monoclinous and pistillody individuals and the gender phenotypes were developmentally linked with the life-history traits. Therefore, the gender phenotypes are adaptive. Low seed production, seed germination failure and matching phenotypes to habitats by gender plasticity indicate that the adaptive phenotypic diversity in A. philoxeroides may not be the result of ecological selection, but of gender plasticity. The delay of the adaptive gender phenotype realization in changing environments can maintain the differentiation between gender systems and their associated life-history traits, which may be an important component in evolution of novel

  7. The nature of stable insomnia phenotypes.

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L

    2015-01-01

    We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impair