Linear and Nonlinear Thinking: A Multidimensional Model and Measure

ERIC Educational Resources Information Center

Groves, Kevin S.; Vance, Charles M.

2015-01-01

Building upon previously developed and more general dual-process models, this paper provides empirical support for a multidimensional thinking style construct comprised of linear thinking and multiple dimensions of nonlinear thinking. A self-report assessment instrument (Linear/Nonlinear Thinking Style Profile; LNTSP) is presented and…

The Somatic Genomic Landscape of Glioblastoma

PubMed Central

Brennan, Cameron W.; Verhaak, Roel G.W.; McKenna, Aaron; Campos, Benito; Noushmehr, Houtan; Salama, Sofie R.; Zheng, Siyuan; Chakravarty, Debyani; Sanborn, J. Zachary; Berman, Samuel H.; Beroukhim, Rameen; Bernard, Brady; Wu, Chang-Jiun; Genovese, Giannicola; Shmulevich, Ilya; Barnholtz-Sloan, Jill; Zou, Lihua; Vegesna, Rahulsimham; Shukla, Sachet A.; Ciriello, Giovanni; Yung, WK; Zhang, Wei; Sougnez, Carrie; Mikkelsen, Tom; Aldape, Kenneth; Bigner, Darell D.; Van Meir, Erwin G.; Prados, Michael; Sloan, Andrew; Black, Keith L.; Eschbacher, Jennifer; Finocchiaro, Gaetano; Friedman, William; Andrews, David W.; Guha, Abhijit; Iacocca, Mary; O’Neill, Brian P.; Foltz, Greg; Myers, Jerome; Weisenberger, Daniel J.; Penny, Robert; Kucherlapati, Raju; Perou, Charles M.; Hayes, D. Neil; Gibbs, Richard; Marra, Marco; Mills, Gordon B.; Lander, Eric; Spellman, Paul; Wilson, Richard; Sander, Chris; Weinstein, John; Meyerson, Matthew; Gabriel, Stacey; Laird, Peter W.; Haussler, David; Getz, Gad; Chin, Lynda

2013-01-01

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer. PMID:24120142

The somatic genomic landscape of glioblastoma.

PubMed

Brennan, Cameron W; Verhaak, Roel G W; McKenna, Aaron; Campos, Benito; Noushmehr, Houtan; Salama, Sofie R; Zheng, Siyuan; Chakravarty, Debyani; Sanborn, J Zachary; Berman, Samuel H; Beroukhim, Rameen; Bernard, Brady; Wu, Chang-Jiun; Genovese, Giannicola; Shmulevich, Ilya; Barnholtz-Sloan, Jill; Zou, Lihua; Vegesna, Rahulsimham; Shukla, Sachet A; Ciriello, Giovanni; Yung, W K; Zhang, Wei; Sougnez, Carrie; Mikkelsen, Tom; Aldape, Kenneth; Bigner, Darell D; Van Meir, Erwin G; Prados, Michael; Sloan, Andrew; Black, Keith L; Eschbacher, Jennifer; Finocchiaro, Gaetano; Friedman, William; Andrews, David W; Guha, Abhijit; Iacocca, Mary; O'Neill, Brian P; Foltz, Greg; Myers, Jerome; Weisenberger, Daniel J; Penny, Robert; Kucherlapati, Raju; Perou, Charles M; Hayes, D Neil; Gibbs, Richard; Marra, Marco; Mills, Gordon B; Lander, Eric; Spellman, Paul; Wilson, Richard; Sander, Chris; Weinstein, John; Meyerson, Matthew; Gabriel, Stacey; Laird, Peter W; Haussler, David; Getz, Gad; Chin, Lynda

2013-10-10

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Recycling Behavior: A Multidimensional Approach

ERIC Educational Resources Information Center

Meneses, Gonzalo Diaz; Palacio, Asuncion Beerli

2005-01-01

This work centers on the study of consumer recycling roles to examine the sociodemographic and psychographic profile of the distribution of recycling tasks and roles within the household. With this aim in mind, an empirical work was carried out, the results of which suggest that recycling behavior is multidimensional and comprises the undertaking…

A Mathematical Model for the Exhaust Gas Temperature Profile of a Diesel Engine

NASA Astrophysics Data System (ADS)

Brito, C. H. G.; Maia, C. B.; Sodré, J. R.

2015-09-01

This work presents a heat transfer model for the exhaust gas of a diesel power generator to determine the gas temperature profile in the exhaust pipe. The numerical methodology to solve the mathematical model was developed using a finite difference method approach for energy equation resolution and determination of temperature profiles considering turbulent fluid flow and variable fluid properties. The simulation was carried out for engine operation under loads from 0 kW to 40 kW. The model was compared with results obtained using the multidimensional Ansys CFX software, which was applied to solve the governor equations of turbulent fluid flow. The results for the temperature profiles in the exhaust pipe show a good proximity between the mathematical model developed and the multidimensional software.

Frailty and the prediction of dependence and mortality in low- and middle-income countries: a 10/66 population-based cohort study.

PubMed

At, Jotheeswaran; Bryce, Renata; Prina, Matthew; Acosta, Daisy; Ferri, Cleusa P; Guerra, Mariella; Huang, Yueqin; Rodriguez, Juan J Llibre; Salas, Aquiles; Sosa, Ana Luisa; Williams, Joseph D; Dewey, Michael E; Acosta, Isaac; Liu, Zhaorui; Beard, John; Prince, Martin

2015-06-10

In countries with high incomes, frailty indicators predict adverse outcomes in older people, despite a lack of consensus on definition or measurement. We tested the predictive validity of physical and multidimensional frailty phenotypes in settings in Latin America, India, and China. Population-based cohort studies were conducted in catchment area sites in Cuba, Dominican Republic, Venezuela, Mexico, Peru, India, and China. Seven frailty indicators, namely gait speed, self-reported exhaustion, weight loss, low energy expenditure, undernutrition, cognitive, and sensory impairment were assessed to estimate frailty phenotypes. Mortality and onset of dependence were ascertained after a median of 3.9 years. Overall, 13,924 older people were assessed at baseline, with 47,438 person-years follow-up for mortality and 30,689 for dependence. Both frailty phenotypes predicted the onset of dependence and mortality, even adjusting for chronic diseases and disability, with little heterogeneity of effect among sites. However, population attributable fractions (PAF) summarising etiologic force were highest for the aggregate effect of the individual indicators, as opposed to either the number of indicators or the dichotomised frailty phenotypes. The aggregate of all seven indicators provided the best overall prediction (weighted mean PAF 41.8 % for dependence and 38.3 % for mortality). While weight loss, underactivity, slow walking speed, and cognitive impairment predicted both outcomes, whereas undernutrition predicted only mortality and sensory impairment only dependence. Exhaustion predicted neither outcome. Simply assessed frailty indicators identify older people at risk of dependence and mortality, beyond information provided by chronic disease diagnoses and disability. Frailty is likely to be multidimensional. A better understanding of the construct and pathways to adverse outcomes could inform multidimensional assessment and intervention to prevent or manage dependence in frail older people, with potential to add life to years, and years to life.

Deriving Stopping Rules for Multidimensional Computerized Adaptive Testing

ERIC Educational Resources Information Center

Wang, Chun; Chang, Hua-Hua; Boughton, Keith A.

2013-01-01

Multidimensional computerized adaptive testing (MCAT) is able to provide a vector of ability estimates for each examinee, which could be used to provide a more informative profile of an examinee's performance. The current literature on MCAT focuses on the fixed-length tests, which can generate less accurate results for those examinees whose…

Physical Self-Perceptions in Adolescence: Generalizability of a Hierarchical Multidimensional Model across Three Cultures.

ERIC Educational Resources Information Center

Hagger, Martin S.; Biddle, Stuart J. H.; Chow, Edward W.; Stambulova, Natalia; Kavussanu, Maria

2003-01-01

Examined the generalizability of the form, structural parameters, and latent means of a hierarchical multidimensional model of physical self-perceptions in adolescents from three cultures. A children's version of the physical self-perception profile was administered to British, Hong Kong, and Russian students. Tests of cross-cultural…

Quantitative Analysis of Cotton Canopy Size in Field Conditions Using a Consumer-Grade RGB-D Camera.

PubMed

Jiang, Yu; Li, Changying; Paterson, Andrew H; Sun, Shangpeng; Xu, Rui; Robertson, Jon

2017-01-01

Plant canopy structure can strongly affect crop functions such as yield and stress tolerance, and canopy size is an important aspect of canopy structure. Manual assessment of canopy size is laborious and imprecise, and cannot measure multi-dimensional traits such as projected leaf area and canopy volume. Field-based high throughput phenotyping systems with imaging capabilities can rapidly acquire data about plants in field conditions, making it possible to quantify and monitor plant canopy development. The goal of this study was to develop a 3D imaging approach to quantitatively analyze cotton canopy development in field conditions. A cotton field was planted with 128 plots, including four genotypes of 32 plots each. The field was scanned by GPhenoVision (a customized field-based high throughput phenotyping system) to acquire color and depth images with GPS information in 2016 covering two growth stages: canopy development, and flowering and boll development. A data processing pipeline was developed, consisting of three steps: plot point cloud reconstruction, plant canopy segmentation, and trait extraction. Plot point clouds were reconstructed using color and depth images with GPS information. In colorized point clouds, vegetation was segmented from the background using an excess-green (ExG) color filter, and cotton canopies were further separated from weeds based on height, size, and position information. Static morphological traits were extracted on each day, including univariate traits (maximum and mean canopy height and width, projected canopy area, and concave and convex volumes) and a multivariate trait (cumulative height profile). Growth rates were calculated for univariate static traits, quantifying canopy growth and development. Linear regressions were performed between the traits and fiber yield to identify the best traits and measurement time for yield prediction. The results showed that fiber yield was correlated with static traits after the canopy development stage ( R 2 = 0.35-0.71) and growth rates in early canopy development stages ( R 2 = 0.29-0.52). Multi-dimensional traits (e.g., projected canopy area and volume) outperformed one-dimensional traits, and the multivariate trait (cumulative height profile) outperformed univariate traits. The proposed approach would be useful for identification of quantitative trait loci (QTLs) controlling canopy size in genetics/genomics studies or for fiber yield prediction in breeding programs and production environments.

Cumulative area of peaks in a multidimensional high performance liquid chromatogram.

PubMed

Stevenson, Paul G; Guiochon, Georges

2013-09-20

An algorithm was developed to recognize peaks in a multidimensional separation and calculate their cumulative peak area. To find the retention times of peaks in a one dimensional chromatogram, the Savitzky-Golay smoothing filter was used to smooth and find the first through third derivatives of the experimental profiles. Close examination of the shape of these curves informs on the number of peaks that are present and provides starting values for fitting theoretical profiles. Due to the nature of comprehensive multidimensional HPLC, adjacent cut fractions may contain compounds common to more than one cut fraction. The algorithm determines which components were common in adjacent cuts and subsequently calculates the area of a two-dimensional peak profile by interpolating the surface of the 2D peaks between adjacent peaks. This algorithm was tested by calculating the cumulative peak area of a series of 2D-HPLC separations of alkylbenzenes, phenol and caffeine with varied concentrations. A good relationship was found between the concentration and the cumulative peak area. Copyright © 2013 Elsevier B.V. All rights reserved.

Physical Self-Concept in Adolescence: Generalizability of a Multidimensional, Hierarchical Model Across Gender and Grade

ERIC Educational Resources Information Center

Hagger, Martin S.; Biddle, Stuart J. H.; John Wang, C. K.

2005-01-01

This study tests the generalizability of the factor pattern, structural parameters, and latent mean structure of a multidimensional, hierarchical model of physical self-concept in adolescents across gender and grade. A children's version of the Physical Self-Perception Profile (C-PSPP) was administered to seventh-, eighth- and ninth-grade high…

Multidimensional proteomics for cell biology.

PubMed

Larance, Mark; Lamond, Angus I

2015-05-01

The proteome is a dynamic system in which each protein has interconnected properties - dimensions - that together contribute to the phenotype of a cell. Measuring these properties has proved challenging owing to their diversity and dynamic nature. Advances in mass spectrometry-based proteomics now enable the measurement of multiple properties for thousands of proteins, including their abundance, isoform expression, turnover rate, subcellular localization, post-translational modifications and interactions. Complementing these experimental developments are new data analysis, integration and visualization tools as well as data-sharing resources. Together, these advances in the multidimensional analysis of the proteome are transforming our understanding of various cellular and physiological processes.

Coping as Part of Motivational Resilience in School: A Multidimensional Measure of Families, Allocations, and Profiles of Academic Coping

ERIC Educational Resources Information Center

Skinner, Ellen; Pitzer, Jennifer; Steele, Joel

2013-01-01

A study was designed to examine a multidimensional measure of children's coping in the academic domain as part of a larger model of motivational resilience. Using items tapping multiple ways of dealing with academic problems, including five adaptive ways (strategizing, help-seeking, comfort-seeking, self-encouragement, and commitment) and six…

Chemometric Strategies for Peak Detection and Profiling from Multidimensional Chromatography.

PubMed

Navarro-Reig, Meritxell; Bedia, Carmen; Tauler, Romà; Jaumot, Joaquim

2018-04-03

The increasing complexity of omics research has encouraged the development of new instrumental technologies able to deal with these challenging samples. In this way, the rise of multidimensional separations should be highlighted due to the massive amounts of information that provide with an enhanced analyte determination. Both proteomics and metabolomics benefit from this higher separation capacity achieved when different chromatographic dimensions are combined, either in LC or GC. However, this vast quantity of experimental information requires the application of chemometric data analysis strategies to retrieve this hidden knowledge, especially in the case of nontargeted studies. In this work, the most common chemometric tools and approaches for the analysis of this multidimensional chromatographic data are reviewed. First, different options for data preprocessing and enhancement of the instrumental signal are introduced. Next, the most used chemometric methods for the detection of chromatographic peaks and the resolution of chromatographic and spectral contributions (profiling) are presented. The description of these data analysis approaches is complemented with enlightening examples from omics fields that demonstrate the exceptional potential of the combination of multidimensional separation techniques and chemometric tools of data analysis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Person-Centered Perspective on Multidimensional Perfectionism in Canadian and Chinese University Students: A Multigroup Latent Profile Analysis

ERIC Educational Resources Information Center

Smith, Martin M.; Saklofske, Donald H.; Yan, Gonggu; Sherry, Simon B.

2016-01-01

This study investigated the generalizability of the tripartite model of perfectionism across Canadian and Chinese university students. Using latent profile analysis and indicators of perfectionistic strivings, perfectionistic concerns, and neuroticism in both groups, the authors derived a 3-profile solution: adaptive perfectionists, maladaptive…

Feature theory and the two-step hypothesis of Müllerian mimicry evolution.

PubMed

Balogh, Alexandra Catherine Victoria; Gamberale-Stille, Gabriella; Tullberg, Birgitta Sillén; Leimar, Olof

2010-03-01

The two-step hypothesis of Müllerian mimicry evolution states that mimicry starts with a major mutational leap between adaptive peaks, followed by gradual fine-tuning. The hypothesis was suggested to solve the problem of apostatic selection producing a valley between adaptive peaks, and appears reasonable for a one-dimensional phenotype. Extending the hypothesis to the realistic scenario of multidimensional phenotypes controlled by multiple genetic loci can be problematic, because it is unlikely that major mutational leaps occur simultaneously in several traits. Here we consider the implications of predator psychology on the evolutionary process. According to feature theory, single prey traits may be used by predators as features to classify prey into discrete categories. A mutational leap in such a trait could initiate mimicry evolution. We conducted individual-based evolutionary simulations in which virtual predators both categorize prey according to features and generalize over total appearances. We found that an initial mutational leap toward feature similarity in one dimension facilitates mimicry evolution of multidimensional traits. We suggest that feature-based predator categorization together with predator generalization over total appearances solves the problem of applying the two-step hypothesis to complex phenotypes, and provides a basis for a theory of the evolution of mimicry rings.

Framework for analyzing ecological trait-based models in multidimensional niche spaces

NASA Astrophysics Data System (ADS)

Biancalani, Tommaso; DeVille, Lee; Goldenfeld, Nigel

2015-05-01

We develop a theoretical framework for analyzing ecological models with a multidimensional niche space. Our approach relies on the fact that ecological niches are described by sequences of symbols, which allows us to include multiple phenotypic traits. Ecological drivers, such as competitive exclusion, are modeled by introducing the Hamming distance between two sequences. We show that a suitable transform diagonalizes the community interaction matrix of these models, making it possible to predict the conditions for niche differentiation and, close to the instability onset, the asymptotically long time population distributions of niches. We exemplify our method using the Lotka-Volterra equations with an exponential competition kernel.

Pathomechanisms of polycystic ovary syndrome: Multidimensional approaches.

PubMed

Sagvekar, Pooja; Dadachanji, Roshan; Patil, Krutika; Mukherjee, Srabani

2018-03-01

Polycystic ovary syndrome is a complex endocrine disorder affecting numerous women of reproductive age across the globe. Characterized mainly by irregular menses, hirsutism, skewed LH: FSH ratios and bulky polycystic ovaries, this multifactorial endocrinopathy results in unfavorable reproductive and metabolic sequelae, including anovulatory infertility, type 2 diabetes, metabolic syndrome and cardiovascular disease in later years. Increasing evidence has shown that the manifestation of polycystic ovary syndrome (PCOS) is attributable to a cumulative impact of altered genetic, epigenetic and protein profiles which bring about a systemic dysfunction. While genetic approaches help ascertain role of causal variants in its etiology, tissue-specific epigenetic patterns help in deciphering the auxiliary role of environmental, nutritional and behavioral factors. Proteomics is advantageous, linking both genotype and phenotype and contributing to biomarker discovery. Investigating molecular mechanism underlying PCOS is imperative in order to gain insight into the pathophysiology of PCOS and formulate novel diagnostic and treatment strategies. In this review we have summarized these three aspects, which have been successfully utilized to delineate the pathomechanisms of PCOS.

Phenotypes of organ involvement in sarcoidosis.

PubMed

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 phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies. Copyright ©ERS 2018.

Multi-parameter phenotypic profiling: using cellular effects to characterize small-molecule compounds.

PubMed

Feng, Yan; Mitchison, Timothy J; Bender, Andreas; Young, Daniel W; Tallarico, John A

2009-07-01

Multi-parameter phenotypic profiling of small molecules provides important insights into their mechanisms of action, as well as a systems level understanding of biological pathways and their responses to small molecule treatments. It therefore deserves more attention at an early step in the drug discovery pipeline. Here, we summarize the technologies that are currently in use for phenotypic profiling--including mRNA-, protein- and imaging-based multi-parameter profiling--in the drug discovery context. We think that an earlier integration of phenotypic profiling technologies, combined with effective experimental and in silico target identification approaches, can improve success rates of lead selection and optimization in the drug discovery process.

Using ToxCast data to reconstruct dynamic cell state ...

EPA Pesticide Factsheets

AbstractBackground. High-throughput in vitro screening is an important tool for evaluating the potential biological activity of the thousands of existing chemicals in commerce and the hundreds more introduced each year. Among the assay technologies available, high-content imaging (HCI) allows multiplexed measurements of cellular phenotypic changes induced by chemical exposures. For a large chemical inventory having limited concentration-time series data, the deconvolution of cellular response profiles into transitive or irrevocable state trajectories is an important consideration. Objectives. Our goal was to analyze temporal and concentration-related cellular changes measured using HCI to identify the “tipping point” at which the cells did not show recovery towards a normal phenotypic state. Methods. The effects of 976 chemicals (ToxCast Phase I and II) were evaluated using HCI as a function of concentration and time in HepG2 cells over a 72-hr exposure period to concentrations ranging from 0.4- to 200 µM. The cellular endpoints included nuclear p53 accumulation, JNK, markers of oxidative stress, cytoskeletal changes, mitochondrial energization and density, cell viability and cell cycle progression. A novel computational model was developed to interpret dynamic multidimensional system responses as cell-state trajectories. Results. Analysis of cell-state trajectories showed that HepG2 cells were resilient to the effects of 178 chemicals up to the highest co

Cattle phenotypes can disguise their maternal ancestry.

PubMed

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 < 0.01). However, embryos derived from oocytes with Bos indicus mtDNA had the same ability to develop to the blastocyst stage and the levels of mtDNA copy number in their blastocysts were similar to blastocysts derived from oocytes harbouring Bos taurus mtDNA. Nevertheless, oocytes originating from the Bos indicus phenotype exhibited lower developmental potential due to low mtDNA copy number when compared with oocytes from 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.

A cluster analysis of perfectionism among competitive athletes.

PubMed

Martinent, Guillaume; Ferrand, Claude

2006-12-01

In the present study, the ways in which athletes may experience perfectionism in a sport context were examined. The question of interest was whether self-confidence, intensity, and direction of cognitive and somatic precompetitive anxiety would differ across identifiable profiles of perfectionism. Competitive athletes (N= 166) completed the Sport-Multidimensional Perfectionism Scale, the French-Canadian Hewitt Multidimensional Perfectionism Scale, and the Competitive State Anxiety Inventory-2 Revised, including a Direction scale. Results of the cluster analysis indicated that athletes could be classified into three groups labelled Nonperfectionists, Adaptive perfectionists, and Maladaptive perfectionists. Perfectionism profiles differed significantly on Cognitive and Somatic Anxiety Intensity and on Cognitive Anxiety Direction. The importance of considering all dimensions of perfectionism simultaneously when examining the functional nature of this construct in sport is discussed.

Performance analysis of deciduous morphology for detecting biological siblings.

PubMed

Paul, Kathleen S; Stojanowski, Christopher M

2015-08-01

Family-centered burial practices influence cemetery structure and can represent social group composition in both modern and ancient contexts. In ancient sites dental phenotypic data are often used as proxies for underlying genotypes to identify potential biological relatives. Here, we test the performance of deciduous dental morphological traits for differentiating sibling pairs from unrelated individuals from the same population. We collected 46 deciduous morphological traits for 69 sibling pairs from the Burlington Growth Centre's long term Family Study. Deciduous crown features were recorded following published standards. After variable winnowing, inter-individual Euclidean distances were generated using 20 morphological traits. To determine whether sibling pairs are more phenotypically similar than expected by chance we used bootstrap resampling of distances to generate P values. Multidimensional scaling (MDS) plots were used to evaluate the degree of clustering among sibling pairs. Results indicate an average distance between siblings of 0.252, which is significantly less than 9,999 replicated averages of 69 resampled pseudo-distances generated from: 1) a sample of non-relative pairs (P < 0.001), and 2) a sample of relative and non-relative pairs (P < 0.001). MDS plots indicate moderate to strong clustering among siblings; families occupied 3.83% of the multidimensional space on average (versus 63.10% for the total sample). Deciduous crown morphology performed well in identifying related sibling pairs. However, there was considerable variation in the extent to which different families exhibited similarly low levels of phenotypic divergence. © 2015 Wiley Periodicals, Inc.

A Tool for Comparative Collection Analysis: Conducting a Shelflist Sample to Construct a Collection Profile.

ERIC Educational Resources Information Center

Paskoff, Beth M.; Perrault, Anna H.

1990-01-01

Describes a project that examined a random sample of 5 percent of a shelflist to provide detailed information about the distribution of imprints according to age and language, percentage of duplication, and distribution of serial and monographic formats. It is concluded that the resulting collection profile provides a multidimensional, quantified…

Improved Representation of the Self-Perception Profile for Children through Bifactor Exploratory Structural Equation Modeling

ERIC Educational Resources Information Center

Arens, A. Katrin; Morin, Alexandre J. S.

2017-01-01

This study illustrates an integrative psychometric framework to investigate two sources of construct-relevant multidimensionality in answers to the Self-Perception Profile for Children (SPPC). Using a sample of 2,353 German students attending Grades 3 to 6, we contrasted: (a) first-order versus hierarchical and bifactor models to investigate…

The Social Profile of Students in Basic General Education in Ecuador: A Data Analysis

ERIC Educational Resources Information Center

Buri, Olga Elizabeth Minchala; Stefos, Efstathios

2017-01-01

The objective of this study is to examine the social profile of students who are enrolled in Basic General Education in Ecuador. Both a descriptive and multidimensional statistical analysis was carried out based on the data provided by the National Survey of Employment, Unemployment and Underemployment in 2015. The descriptive analysis shows the…

Adaptive and Challenged Parenting among African American Mothers: Parenting Profiles Relate to Head Start Children's Aggression and Hyperactivity

ERIC Educational Resources Information Center

Carpenter, Johanna L.; Mendez, Julia

2013-01-01

Research Findings: This study used a within-group research design and person-centered analytic methods to identify multidimensional profiles of parenting styles, parenting practices, and related emotional factors in a sample of 274 African American mothers recruited from Head Start programs in the northeastern and southeastern United States.…

Predictive Validity of Career Decision-Making Profiles over Time among Chinese College Students

ERIC Educational Resources Information Center

Tian, Lin; Guan, Yanjun; Chen, Sylvia Xiaohua; Levin, Nimrod; Cai, Zijun; Chen, Pei; Zhu, Chengfeng; Fu, Ruchunyi; Wang, Yang; Zhang, Shu

2014-01-01

Two studies were conducted to validate the Chinese version of the Career Decision-Making Profiles (CDMP) questionnaire, a multidimensional measure of the way individuals make career decisions. Results of Study 1 showed that after dropping 1 item from the original CDMP scale, the 11-factor structure was supported among Chinese college students (N =…

The multidimensional perturbation value: a single metric to measure similarity and activity of treatments in high-throughput multidimensional screens.

PubMed

Hutz, Janna E; Nelson, Thomas; Wu, Hua; McAllister, Gregory; Moutsatsos, Ioannis; Jaeger, Savina A; Bandyopadhyay, Somnath; Nigsch, Florian; Cornett, Ben; Jenkins, Jeremy L; Selinger, Douglas W

2013-04-01

Screens using high-throughput, information-rich technologies such as microarrays, high-content screening (HCS), and next-generation sequencing (NGS) have become increasingly widespread. Compared with single-readout assays, these methods produce a more comprehensive picture of the effects of screened treatments. However, interpreting such multidimensional readouts is challenging. Univariate statistics such as t-tests and Z-factors cannot easily be applied to multidimensional profiles, leaving no obvious way to answer common screening questions such as "Is treatment X active in this assay?" and "Is treatment X different from (or equivalent to) treatment Y?" We have developed a simple, straightforward metric, the multidimensional perturbation value (mp-value), which can be used to answer these questions. Here, we demonstrate application of the mp-value to three data sets: a multiplexed gene expression screen of compounds and genomic reagents, a microarray-based gene expression screen of compounds, and an HCS compound screen. In all data sets, active treatments were successfully identified using the mp-value, and simulations and follow-up analyses supported the mp-value's statistical and biological validity. We believe the mp-value represents a promising way to simplify the analysis of multidimensional data while taking full advantage of its richness.

A quick aphasia battery for efficient, reliable, and multidimensional assessment of language function.

PubMed

Wilson, Stephen M; Eriksson, Dana K; Schneck, Sarah M; Lucanie, Jillian M

2018-01-01

This paper describes a quick aphasia battery (QAB) that aims to provide a reliable and multidimensional assessment of language function in about a quarter of an hour, bridging the gap between comprehensive batteries that are time-consuming to administer, and rapid screening instruments that provide limited detail regarding individual profiles of deficits. The QAB is made up of eight subtests, each comprising sets of items that probe different language domains, vary in difficulty, and are scored with a graded system to maximize the informativeness of each item. From the eight subtests, eight summary measures are derived, which constitute a multidimensional profile of language function, quantifying strengths and weaknesses across core language domains. The QAB was administered to 28 individuals with acute stroke and aphasia, 25 individuals with acute stroke but no aphasia, 16 individuals with chronic post-stroke aphasia, and 14 healthy controls. The patients with chronic post-stroke aphasia were tested 3 times each and scored independently by 2 raters to establish test-retest and inter-rater reliability. The Western Aphasia Battery (WAB) was also administered to these patients to assess concurrent validity. We found that all QAB summary measures were sensitive to aphasic deficits in the two groups with aphasia. All measures showed good or excellent test-retest reliability (overall summary measure: intraclass correlation coefficient (ICC) = 0.98), and excellent inter-rater reliability (overall summary measure: ICC = 0.99). Sensitivity and specificity for diagnosis of aphasia (relative to clinical impression) were 0.91 and 0.95 respectively. All QAB measures were highly correlated with corresponding WAB measures where available. Individual patients showed distinct profiles of spared and impaired function across different language domains. In sum, the QAB efficiently and reliably characterized individual profiles of language deficits.

A quick aphasia battery for efficient, reliable, and multidimensional assessment of language function

PubMed Central

Eriksson, Dana K.; Schneck, Sarah M.; Lucanie, Jillian M.

2018-01-01

This paper describes a quick aphasia battery (QAB) that aims to provide a reliable and multidimensional assessment of language function in about a quarter of an hour, bridging the gap between comprehensive batteries that are time-consuming to administer, and rapid screening instruments that provide limited detail regarding individual profiles of deficits. The QAB is made up of eight subtests, each comprising sets of items that probe different language domains, vary in difficulty, and are scored with a graded system to maximize the informativeness of each item. From the eight subtests, eight summary measures are derived, which constitute a multidimensional profile of language function, quantifying strengths and weaknesses across core language domains. The QAB was administered to 28 individuals with acute stroke and aphasia, 25 individuals with acute stroke but no aphasia, 16 individuals with chronic post-stroke aphasia, and 14 healthy controls. The patients with chronic post-stroke aphasia were tested 3 times each and scored independently by 2 raters to establish test-retest and inter-rater reliability. The Western Aphasia Battery (WAB) was also administered to these patients to assess concurrent validity. We found that all QAB summary measures were sensitive to aphasic deficits in the two groups with aphasia. All measures showed good or excellent test-retest reliability (overall summary measure: intraclass correlation coefficient (ICC) = 0.98), and excellent inter-rater reliability (overall summary measure: ICC = 0.99). Sensitivity and specificity for diagnosis of aphasia (relative to clinical impression) were 0.91 and 0.95 respectively. All QAB measures were highly correlated with corresponding WAB measures where available. Individual patients showed distinct profiles of spared and impaired function across different language domains. In sum, the QAB efficiently and reliably characterized individual profiles of language deficits. PMID:29425241

Tuberculosis patients co-infected with Mycobacterium bovis and Mycobacterium tuberculosis in an urban area of Brazil.

PubMed

Silva, Marcio Roberto; Rocha, Adalgiza da Silva; da Costa, Ronaldo Rodrigues; de Alencar, Andrea Padilha; de Oliveira, Vania Maria; Fonseca Júnior, Antônio Augusto; Sales, Mariana Lázaro; Issa, Marina de Azevedo; Filho, Paulo Martins Soares; Pereira, Omara Tereza Vianello; dos Santos, Eduardo Calazans; Mendes, Rejane Silva; Ferreira, Angela Maria de Jesus; Mota, Pedro Moacyr Pinto Coelho; Suffys, Philip Noel; Guimarães, Mark Drew Crosland

2013-05-01

In this cross-sectional study, mycobacteria specimens from 189 tuberculosis (TB) patients living in an urban area in Brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pncA gene and oxyR pseudogene analysis). Of these samples, 174 isolates simultaneously grew on Löwenstein-Jensen (LJ) and Stonebrink (SB)-containing media and presented phenotypic and molecular profiles of Mycobacterium tuberculosis, whereas 12 had molecular profiles of M. tuberculosis based on the DNA analysis of formalin-fixed paraffin wax-embedded tissue samples (paraffin blocks). One patient produced two sputum isolates, the first of which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, and the second of which only grew on SB media and presented phenotypic profiles of Mycobacterium bovis. One patient provided a bronchial lavage isolate, which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, but had molecular profiles of M. bovis from paraffin block DNA analysis, and one sample had molecular profiles of M. tuberculosis and M. bovis identified from two distinct paraffin blocks. Moreover, we found a low prevalence (1.6%) of M. bovis among these isolates, which suggests that local health service procedures likely underestimate its real frequency and that it deserves more attention from public health officials.

Gender Ideologies in Europe: A Multidimensional Framework.

PubMed

Grunow, Daniela; Begall, Katia; Buchler, Sandra

2018-02-01

The authors argue, in line with recent research, that operationalizing gender ideology as a unidimensional construct ranging from traditional to egalitarian is problematic and propose an alternative framework that takes the multidimensionality of gender ideologies into account. Using latent class analysis, they operationalize their gender ideology framework based on data from the 2008 European Values Study, of which eight European countries reflecting the spectrum of current work-family policies were selected. The authors examine the form in which gender ideologies cluster in the various countries. Five ideology profiles were identified: egalitarian, egalitarian essentialism, intensive parenting, moderate traditional, and traditional. The five ideology profiles were found in all countries, but with pronounced variation in size. Ideologies mixing gender essentialist and egalitarian views appear to have replaced traditional ideologies, even in countries offering some institutional support for gendered separate spheres.

Gender Ideologies in Europe: A Multidimensional Framework

PubMed Central

Begall, Katia; Buchler, Sandra

2018-01-01

The authors argue, in line with recent research, that operationalizing gender ideology as a unidimensional construct ranging from traditional to egalitarian is problematic and propose an alternative framework that takes the multidimensionality of gender ideologies into account. Using latent class analysis, they operationalize their gender ideology framework based on data from the 2008 European Values Study, of which eight European countries reflecting the spectrum of current work–family policies were selected. The authors examine the form in which gender ideologies cluster in the various countries. Five ideology profiles were identified: egalitarian, egalitarian essentialism, intensive parenting, moderate traditional, and traditional. The five ideology profiles were found in all countries, but with pronounced variation in size. Ideologies mixing gender essentialist and egalitarian views appear to have replaced traditional ideologies, even in countries offering some institutional support for gendered separate spheres. PMID:29491532

Multiple pathways to identification: exploring the multidimensionality of academic identity formation in ethnic minority males.

PubMed

Matthews, Jamaal S

2014-04-01

Empirical trends denote the academic underachievement of ethnic minority males across various academic domains. Identity-based explanations for this persistent phenomenon describe ethnic minority males as disidentified with academics, alienated, and oppositional. The present work interrogates these theoretical explanations and empirically substantiates a multidimensional lens for discussing academic identity formation within 330 African American and Latino early-adolescent males. Both hierarchical and iterative person-centered methods were utilized and reveal 5 distinct profiles derived from 6 dimensions of academic identity. These profiles predict self-reported classroom grades, mastery orientation, and self-handicapping in meaningful and varied ways. The results demonstrate multiple pathways to motivation and achievement, challenging previous oversimplified stereotypes of marginalized males. This exploratory study triangulates unique interpersonal and intrapersonal attributes for promoting healthy identity development and academic achievement among ethnic minority adolescent males.

On Visualizing Mixed-Type Data: A Joint Metric Approach to Profile Construction and Outlier Detection

ERIC Educational Resources Information Center

Grané, Aurea; Romera, Rosario

2018-01-01

Survey data are usually of mixed type (quantitative, multistate categorical, and/or binary variables). Multidimensional scaling (MDS) is one of the most extended methodologies to visualize the profile structure of the data. Since the past 60s, MDS methods have been introduced in the literature, initially in publications in the psychometrics area.…

Commitment Profiles: The Configural Effect of the Forms and Foci of Commitment on Work Outcomes

ERIC Educational Resources Information Center

Tsoumbris, Petros; Xenikou, Athena

2010-01-01

This study is based upon the conceptual linking of the multidimensional and multi-focal nature of work-related commitment. The main aims of our study were to create, through K-means cluster analysis, commitment profiles based on the three components of organizational and occupational commitment, and to examine their joint effect on key work…

Computational Typologies of Multidimensional End-of-Primary-School Performance Profiles from an Educational Perspective of Large-Scale TIMSS and PIRLS Surveys

ERIC Educational Resources Information Center

Unlu, Ali; Schurig, Michael

2015-01-01

Recently, performance profiles in reading, mathematics and science were created using the data collectively available in the Trends in International Mathematics and Science Study (TIMSS) and the Progress in International Reading Literacy Study (PIRLS) 2011. In addition, a classification of children to the end of their primary school years was…

Adolescent Risk Behaviors: Studying Typical and Atypical Individuals via Multidimensional Scaling Profile Analysis

ERIC Educational Resources Information Center

Dong, Yang; Ding, Cody

2012-01-01

Within the framework of problem behavior theory, the purpose of this study was to examine risk behavior profiles of typical and atypical adolescents and the differential outcomes of well-beings for these individuals in the United States. Based on the data from the survey of Health Behavior of School-Aged Children by World Health Organization,…

Java implementation of Class Association Rule algorithms

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

Tamura, Makio

2007-08-30

Java implementation of three Class Association Rule mining algorithms, NETCAR, CARapriori, and clustering based rule mining. NETCAR algorithm is a novel algorithm developed by Makio Tamura. The algorithm is discussed in a paper: UCRL-JRNL-232466-DRAFT, and would be published in a peer review scientific journal. The software is used to extract combinations of genes relevant with a phenotype from a phylogenetic profile and a phenotype profile. The phylogenetic profiles is represented by a binary matrix and a phenotype profile is represented by a binary vector. The present application of this software will be in genome analysis, however, it could be appliedmore » more generally.« less

Development of a 3D Tissue Culture-Based High-Content Screening Platform That Uses Phenotypic Profiling to Discriminate Selective Inhibitors of Receptor Tyrosine Kinases.

PubMed

Booij, Tijmen H; Klop, Maarten J D; Yan, Kuan; Szántai-Kis, Csaba; Szokol, Balint; Orfi, Laszlo; van de Water, Bob; Keri, Gyorgy; Price, Leo S

2016-10-01

3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses invasive human prostate cancer cells cultured in 3D in standard 384-well assay plates to study the activity of potential therapeutic small molecules and antibody biologics. Image analysis tools were developed to process 3D image data to measure over 800 phenotypic parameters. Multiparametric analysis was used to evaluate the effect of compounds on tissue morphology. We applied this screening platform to measure the activity and selectivity of inhibitors of the c-Met and epidermal growth factor (EGF) receptor (EGFR) tyrosine kinases in 3D cultured prostate carcinoma cells. c-Met and EGFR activity was quantified based on the phenotypic profiles induced by their respective ligands, hepatocyte growth factor and EGF. The screening method was applied to a novel collection of 80 putative inhibitors of c-Met and EGFR. Compounds were identified that induced phenotypic profiles indicative of selective inhibition of c-Met, EGFR, or bispecific inhibition of both targets. In conclusion, we describe a fully scalable high-content screening platform that uses phenotypic profiling to discriminate selective and nonselective (off-target) inhibitors in a physiologically relevant 3D cell culture setting. © 2016 Society for Laboratory Automation and Screening.

Phenotypic Plasticity of Cuticular Hydrocarbon Profiles in Insects.

PubMed

Otte, Tobias; Hilker, Monika; Geiselhardt, Sven

2018-03-01

The insect integument is covered by cuticular hydrocarbons (CHCs) which provide protection against environmental stresses, but are also used for communication. Here we review current knowledge on environmental and insect-internal factors which shape phenotypic plasticity of solitary living insects, especially herbivorous ones. We address the dynamics of changes which may occur within minutes, but may also last weeks, depending on the species and conditions. Two different modes of changes are suggested, i.e. stepwise and gradual. A switch between two distinct environments (e.g. host plant switch by phytophagous insects) results in stepwise formation of two distinct adaptive phenotypes, while a gradual environmental change (e.g. temperature gradients) induces a gradual change of numerous adaptive CHC phenotypes. We further discuss the ecological and evolutionary consequences of phenotypic plasticity of insect CHC profiles by addressing the question at which conditions is CHC phenotypic plasticity beneficial. The high plasticity of CHC profiles might be a trade-off for insects using CHCs for communication. We discuss how insects cope with the challenge to produce and "understand" a highly plastic, environmentally dependent CHC pattern that conveys reliable and comprehensible information. Finally, we outline how phenotypic plasticity of CHC profiles may promote speciation in insects that rely on CHCs for mate recognition.

Towards recommendations for metadata and data handling in plant phenotyping.

PubMed

Krajewski, Paweł; Chen, Dijun; Ćwiek, Hanna; van Dijk, Aalt D J; Fiorani, Fabio; Kersey, Paul; Klukas, Christian; Lange, Matthias; Markiewicz, Augustyn; Nap, Jan Peter; van Oeveren, Jan; Pommier, Cyril; Scholz, Uwe; van Schriek, Marco; Usadel, Björn; Weise, Stephan

2015-09-01

Recent methodological developments in plant phenotyping, as well as the growing importance of its applications in plant science and breeding, are resulting in a fast accumulation of multidimensional data. There is great potential for expediting both discovery and application if these data are made publicly available for analysis. However, collection and storage of phenotypic observations is not yet sufficiently governed by standards that would ensure interoperability among data providers and precisely link specific phenotypes and associated genomic sequence information. This lack of standards is mainly a result of a large variability of phenotyping protocols, the multitude of phenotypic traits that are measured, and the dependence of these traits on the environment. This paper discusses the current situation of standardization in the area of phenomics, points out the problems and shortages, and presents the areas that would benefit from improvement in this field. In addition, the foundations of the work that could revise the situation are proposed, and practical solutions developed by the authors are introduced. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The 'PhenoBox', a flexible, automated, open-source plant phenotyping solution.

PubMed

Czedik-Eysenberg, Angelika; Seitner, Sebastian; Güldener, Ulrich; Koemeda, Stefanie; Jez, Jakub; Colombini, Martin; Djamei, Armin

2018-04-05

There is a need for flexible and affordable plant phenotyping solutions for basic research and plant breeding. We demonstrate our open source plant imaging and processing solution ('PhenoBox'/'PhenoPipe') and provide construction plans, source code and documentation to rebuild the system. Use of the PhenoBox is exemplified by studying infection of the model grass Brachypodium distachyon by the head smut fungus Ustilago bromivora, comparing phenotypic responses of maize to infection with a solopathogenic Ustilago maydis (corn smut) strain and effector deletion strains, and studying salt stress response in Nicotiana benthamiana. In U. bromivora-infected grass, phenotypic differences between infected and uninfected plants were detectable weeks before qualitative head smut symptoms. Based on this, we could predict the infection outcome for individual plants with high accuracy. Using a PhenoPipe module for calculation of multi-dimensional distances from phenotyping data, we observe a time after infection-dependent impact of U. maydis effector deletion strains on phenotypic response in maize. The PhenoBox/PhenoPipe system is able to detect established salt stress responses in N. benthamiana. We have developed an affordable, automated, open source imaging and data processing solution that can be adapted to various phenotyping applications in plant biology and beyond. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders: Interpretation in the Light of the DSM-5

ERIC Educational Resources Information Center

Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

2013-01-01

This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to…

RASopathies are associated with a distinct personality profile.

PubMed

Bizaoui, Varoona; Gage, Jessica; Brar, Rita; Rauen, Katherine A; Weiss, Lauren A

2018-06-01

Personality is a complex, yet partially heritable, trait. Although some Mendelian diseases like Williams-Beuren syndrome are associated with a particular personality profile, studies have failed to assign the personality features to a single gene or pathway. As a family of monogenic disorders caused by mutations in the Ras/MAPK pathway known to influence social behavior, RASopathies are likely to provide insight into the genetic basis of personality. Eighty subjects diagnosed with cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Noonan syndrome were assessed using a parent-report BFQ-C (Big Five Questionnaire for Children) evaluating agreeableness, extraversion, conscientiousness, intellect/openness, and neuroticism, along with 55 unaffected sibling controls. A short questionnaire was added to assess sense of humor. RASopathy subjects and sibling controls were compared for individual components of personality, multidimensional personality profiles, and individual questions using Student tests, analysis of variance, and principal component analysis. RASopathy subjects were given lower scores on average compared to sibling controls in agreeableness, extraversion, conscientiousness, openness, and sense of humor, and similar scores in neuroticism. When comparing the multidimensional personality profile between groups, RASopathies showed a distinct profile from unaffected siblings, but no difference in this global profile was found within RASopathies, revealing a common profile for the Ras/MAPK-related disorders. In addition, several syndrome-specific strengths or weaknesses were observed in individual domains. We describe for the first time an association between a single pathway and a specific personality profile, providing a better understanding of the genetics underlying personality, and new tools for tailoring educational and behavioral approaches for individuals with RASopathies. © 2018 Wiley Periodicals, Inc.

The Stability and Structure of Career Decision-Making Profiles: A 1-Year Follow-Up

ERIC Educational Resources Information Center

Gati, Itamar; Levin, Nimrod

2012-01-01

The Career Decision-Making Profile (CDMP) questionnaire is a multidimensional measure of the way individuals make career decisions, developed as an alternative to the single, most-dominant trait approach. Using a sample of freshmen students, the 2-week reliability (N = 273) and 1-year stability (N = 182) of the CDMP was tested for each of the 12…

Joint mapping of genes and conditions via multidimensional unfolding analysis

PubMed Central

Van Deun, Katrijn; Marchal, Kathleen; Heiser, Willem J; Engelen, Kristof; Van Mechelen, Iven

2007-01-01

Background Microarray compendia profile the expression of genes in a number of experimental conditions. Such data compendia are useful not only to group genes and conditions based on their similarity in overall expression over profiles but also to gain information on more subtle relations between genes and conditions. Getting a clear visual overview of all these patterns in a single easy-to-grasp representation is a useful preliminary analysis step: We propose to use for this purpose an advanced exploratory method, called multidimensional unfolding. Results We present a novel algorithm for multidimensional unfolding that overcomes both general problems and problems that are specific for the analysis of gene expression data sets. Applying the algorithm to two publicly available microarray compendia illustrates its power as a tool for exploratory data analysis: The unfolding analysis of a first data set resulted in a two-dimensional representation which clearly reveals temporal regulation patterns for the genes and a meaningful structure for the time points, while the analysis of a second data set showed the algorithm's ability to go beyond a mere identification of those genes that discriminate between different patient or tissue types. Conclusion Multidimensional unfolding offers a useful tool for preliminary explorations of microarray data: By relying on an easy-to-grasp low-dimensional geometric framework, relations among genes, among conditions and between genes and conditions are simultaneously represented in an accessible way which may reveal interesting patterns in the data. An additional advantage of the method is that it can be applied to the raw data without necessitating the choice of suitable genewise transformations of the data. PMID:17550582

The nature of stable insomnia phenotypes.

PubMed

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 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. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes. © 2014 Associated Professional Sleep Societies, LLC.

Measuring geographic segregation: a graph-based approach

NASA Astrophysics Data System (ADS)

Hong, Seong-Yun; Sadahiro, Yukio

2014-04-01

Residential segregation is a multidimensional phenomenon that encompasses several conceptually distinct aspects of geographical separation between populations. While various indices have been developed as a response to different definitions of segregation, the reliance on such single-figure indices could oversimplify the complex, multidimensional phenomena. In this regard, this paper suggests an alternative graph-based approach that provides more detailed information than simple indices: The concentration profile graphically conveys information about how evenly a population group is distributed over the study region, and the spatial proximity profile depicts the degree of clustering across different threshold levels. These graphs can also be summarized into single numbers for comparative purposes, but the interpretation can be more accurate by inspecting the additional information. To demonstrate the use of these methods, the residential patterns of three major ethnic groups in Auckland, namely Māori, Pacific peoples, and Asians, are examined using the 2006 census data.

A second-order cell-centered Lagrangian ADER-MOOD finite volume scheme on multidimensional unstructured meshes for hydrodynamics

NASA Astrophysics Data System (ADS)

Boscheri, Walter; Dumbser, Michael; Loubère, Raphaël; Maire, Pierre-Henri

2018-04-01

In this paper we develop a conservative cell-centered Lagrangian finite volume scheme for the solution of the hydrodynamics equations on unstructured multidimensional grids. The method is derived from the Eucclhyd scheme discussed in [47,43,45]. It is second-order accurate in space and is combined with the a posteriori Multidimensional Optimal Order Detection (MOOD) limiting strategy to ensure robustness and stability at shock waves. Second-order of accuracy in time is achieved via the ADER (Arbitrary high order schemes using DERivatives) approach. A large set of numerical test cases is proposed to assess the ability of the method to achieve effective second order of accuracy on smooth flows, maintaining an essentially non-oscillatory behavior on discontinuous profiles, general robustness ensuring physical admissibility of the numerical solution, and precision where appropriate.

Multidimensional and comprehensive two-dimensional gas chromatography of dichloromethane soluble products from a high sulfur Jordanian oil shale.

PubMed

Amer, Mohammad W; Mitrevski, Blagoj; Jackson, W Roy; Chaffee, Alan L; Marriott, Philip J

2014-03-01

A high sulfur Jordanian oil shale was converted into liquid hydrocarbons by reaction at 390 °C under N2, and the dichloromethane soluble fraction of the products was isolated then analyzed by using gas chromatography (GC). Comprehensive two-dimensional GC (GC×GC) and multidimensional GC (MDGC) were applied for component separation on a polar - non-polar column set. Flame-ionization detection (FID) was used with GC×GC for general sample profiling, and mass spectrometry (MS) for component identification in MDGC. Multidimensional GC revealed a range of thiophenes (th), benzothiophenes (bth) and small amounts of dibenzothiophenes (dbth) and benzonaphthothiophenes (bnth). In addition, a range of aliphatic alkanes and cycloalkanes, ethers, polar single ring aromatic compounds and small amounts of polycyclic aromatics were also identified. Some of these compound classes were not uniquely observable by conventional 1D GC, and certainly this is true for many of their minor constituent members. The total number of distinct compounds was very large (ca.>1000). GC×GC was shown to be appropriate for general sample profiling, and MDGC-MS proved to be a powerful technique for the separation and identification of sulfur-containing components and other polar compounds. © 2013 Published by Elsevier B.V.

A Multidimensional B-Spline Correction for Accurate Modeling Sugar Puckering in QM/MM Simulations.

PubMed

Huang, Ming; Dissanayake, Thakshila; Kuechler, Erich; Radak, Brian K; Lee, Tai-Sung; Giese, Timothy J; York, Darrin M

2017-09-12

The computational efficiency of approximate quantum mechanical methods allows their use for the construction of multidimensional reaction free energy profiles. It has recently been demonstrated that quantum models based on the neglect of diatomic differential overlap (NNDO) approximation have difficulty modeling deoxyribose and ribose sugar ring puckers and thus limit their predictive value in the study of RNA and DNA systems. A method has been introduced in our previous work to improve the description of the sugar puckering conformational landscape that uses a multidimensional B-spline correction map (BMAP correction) for systems involving intrinsically coupled torsion angles. This method greatly improved the adiabatic potential energy surface profiles of DNA and RNA sugar rings relative to high-level ab initio methods even for highly problematic NDDO-based models. In the present work, a BMAP correction is developed, implemented, and tested in molecular dynamics simulations using the AM1/d-PhoT semiempirical Hamiltonian for biological phosphoryl transfer reactions. Results are presented for gas-phase adiabatic potential energy surfaces of RNA transesterification model reactions and condensed-phase QM/MM free energy surfaces for nonenzymatic and RNase A-catalyzed transesterification reactions. The results show that the BMAP correction is stable, efficient, and leads to improvement in both the potential energy and free energy profiles for the reactions studied, as compared with ab initio and experimental reference data. Exploration of the effect of the size of the quantum mechanical region indicates the best agreement with experimental reaction barriers occurs when the full CpA dinucleotide substrate is treated quantum mechanically with the sugar pucker correction.

A Multidimensional Model of Mothers’ Perceptions of Parent Alcohol Socialization and Adolescent Alcohol Misuse

PubMed Central

Ennett, Susan T.; Jackson, Christine; Cole, Veronica T.; Haws, Susan; Foshee, Vangie A.; Reyes, Heathe Luz McNaughton; Burns, Alison Reimuller; Cox, Melissa J.; Cai, Li

2015-01-01

We assessed a multidimensional model of parent alcohol socialization in which key socialization factors were considered simultaneously to identify combinations of factors that increase or decrease risk for development of adolescent alcohol misuse. Of interest was the interplay between putative risk and protective factors, such as whether the typically detrimental effects on youth drinking of parenting practices tolerant of some adolescent alcohol use are mitigated by an effective overall approach to parenting and parental modeling of modest alcohol use. The sample included 1,530 adolescents and their mothers; adolescents’ mean age was 13.0 (SD = .99) at the initial assessment. Latent profile analysis was conducted of mothers’ reports of their attitude toward teen drinking, alcohol-specific parenting practices, parental alcohol use and problem use, and overall approach to parenting. The profiles were used to predict trajectories of adolescent alcohol misuse from early to middle adolescence. Four profiles were identified: two profiles reflected conservative alcohol-specific parenting practices and two reflected alcohol-tolerant practices, all in the context of other attributes. Alcohol misuse accelerated more rapidly from grade 6 through 10 in the two alcohol-tolerant compared with conservative profiles. Results suggest that maternal tolerance of some youth alcohol use, even in the presence of dimensions of an effective parenting style and low parental alcohol use and problem use, is not an effective strategy for reducing risky adolescent alcohol use. PMID:26415053

Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated With Early Childhood Diarrhea in Rural Egypt

DTIC Science & Technology

2004-12-01

2004, American Society for Microbiology. All Rights Reserved. Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated with Early Childhood...Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We...expressed both toxins. The most common CF phenotypes were colonization factor antigen I (CFA/I) (10%), coli surface antigen 6 (CS6) (9%), CS14 (6%), and

Nonlinear Conservation Laws and Finite Volume Methods

NASA Astrophysics Data System (ADS)

Leveque, Randall J.

Introduction Software Notation Classification of Differential Equations Derivation of Conservation Laws The Euler Equations of Gas Dynamics Dissipative Fluxes Source Terms Radiative Transfer and Isothermal Equations Multi-dimensional Conservation Laws The Shock Tube Problem Mathematical Theory of Hyperbolic Systems Scalar Equations Linear Hyperbolic Systems Nonlinear Systems The Riemann Problem for the Euler Equations Numerical Methods in One Dimension Finite Difference Theory Finite Volume Methods Importance of Conservation Form - Incorrect Shock Speeds Numerical Flux Functions Godunov's Method Approximate Riemann Solvers High-Resolution Methods Other Approaches Boundary Conditions Source Terms and Fractional Steps Unsplit Methods Fractional Step Methods General Formulation of Fractional Step Methods Stiff Source Terms Quasi-stationary Flow and Gravity Multi-dimensional Problems Dimensional Splitting Multi-dimensional Finite Volume Methods Grids and Adaptive Refinement Computational Difficulties Low-Density Flows Discrete Shocks and Viscous Profiles Start-Up Errors Wall Heating Slow-Moving Shocks Grid Orientation Effects Grid-Aligned Shocks Magnetohydrodynamics The MHD Equations One-Dimensional MHD Solving the Riemann Problem Nonstrict Hyperbolicity Stiffness The Divergence of B Riemann Problems in Multi-dimensional MHD Staggered Grids The 8-Wave Riemann Solver Relativistic Hydrodynamics Conservation Laws in Spacetime The Continuity Equation The 4-Momentum of a Particle The Stress-Energy Tensor Finite Volume Methods Multi-dimensional Relativistic Flow Gravitation and General Relativity References

Identity Profiles in Lesbian, Gay, and Bisexual Youth: The Role of Family Influences

PubMed Central

Bregman, Hallie R.; Malik, Neena M.; Page, Matthew J. L.; Makynen, Emily; Lindahl, Kristin M.

2012-01-01

Sexual identity development is a central task of adolescence and young adulthood and can be especially challenging for sexual minority youth. Recent research has moved from a stage model of identity development in lesbian, gay, and bisexual (LGB) youth to examining identity in a non-linear, multidimensional manner. In addition, although families have been identified as important to youth's identity development, limited research has examined the influence of parental responses to youth's disclosure of their LGB sexual orientation on LGB identity. The current study examined a multidimensional model of LGB identity and its links with parental support and rejection. One hundred and sixty-nine LGB adolescents and young adults (ages 14–24, 56% male, 48% gay, 31% lesbian, 21% bisexual) described themselves on dimensions of LGB identity and reported on parental rejection, sexuality-specific social support, and non-sexuality-specific social support. Using latent profile analysis (LPA), two profiles were identified, indicating that youth experience both affirmed and struggling identities. Results indicated that parental rejection and sexuality-specific social support from families were salient links to LGB identity profile classification, while non-sexuality specific social support was unrelated. Parental rejection and sexuality-specific social support may be important to target in interventions for families to foster affirmed LGB identity development in youth. PMID:22847752

Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data.

PubMed

Mosley, Jonathan D; van Driest, Sara L; Wells, Quinn S; Shaffer, Christian M; Edwards, Todd L; Bastarache, Lisa; McCarty, Catherine A; Thompson, Will; Chute, Christopher G; Jarvik, Gail P; Crosslin, David R; Larson, Eric B; Kullo, Iftikhar J; Pacheco, Jennifer A; Peissig, Peggy L; Brilliant, Murray H; Linneman, James G; Denny, Josh C; Roden, Dan M

2016-12-01

Continued reductions in morbidity and mortality attributable to ischemic heart disease (IHD) require an understanding of the changing epidemiology of this disease. We hypothesized that we could use genetic correlations, which quantify the shared genetic architectures of phenotype pairs and extant risk factors from a historical prospective study to define the risk profile of a contemporary IHD phenotype. We used 37 phenotypes measured in the ARIC study (Atherosclerosis Risk in Communities; n=7716, European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19 093). All subjects had genome-wide single-nucleotide polymorphism genotyping. We measured pairwise genetic correlations (rG) between the ARIC and EHR phenotypes using linear mixed models. The genetic correlation estimates between the ARIC risk factors and the EHR IHD were modestly linearly correlated with hazards ratio estimates for incident IHD in ARIC (Pearson correlation [r]=0.62), indicating that the 2 IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes mellitus phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes, including total:high-density lipoprotein cholesterol ratio (rG=-0.44, P=0.005), high-density lipoprotein (rG=-0.48, P=0.005), systolic blood pressure (rG=0.44, P=0.02), and triglycerides (rG=0.38, P=0.02). EHR phenotypes related to type 2 diabetes mellitus, atherosclerotic, and hypertensive diseases were also genetically correlated with these ARIC risk factors. The EHR IHD risk profile differed from ARIC and indicates that treatment and prevention efforts in this population should target hypertensive and metabolic disease. © 2016 American Heart Association, Inc.

The Nature of Stable Insomnia Phenotypes

PubMed Central

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 the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes. Citation: Pillai V, Roth T, Drake CL. The nature of stable insomnia phenotypes. SLEEP 2015;38(1):127–138. PMID:25325468

Towards systems genetic analyses in barley: Integration of phenotypic, expression and genotype data into GeneNetwork.

PubMed

Druka, Arnis; Druka, Ilze; Centeno, Arthur G; Li, Hongqiang; Sun, Zhaohui; Thomas, William T B; Bonar, Nicola; Steffenson, Brian J; Ullrich, Steven E; Kleinhofs, Andris; Wise, Roger P; Close, Timothy J; Potokina, Elena; Luo, Zewei; Wagner, Carola; Schweizer, Günther F; Marshall, David F; Kearsey, Michael J; Williams, Robert W; Waugh, Robbie

2008-11-18

A typical genetical genomics experiment results in four separate data sets; genotype, gene expression, higher-order phenotypic data and metadata that describe the protocols, processing and the array platform. Used in concert, these data sets provide the opportunity to perform genetic analysis at a systems level. Their predictive power is largely determined by the gene expression dataset where tens of millions of data points can be generated using currently available mRNA profiling technologies. Such large, multidimensional data sets often have value beyond that extracted during their initial analysis and interpretation, particularly if conducted on widely distributed reference genetic materials. Besides quality and scale, access to the data is of primary importance as accessibility potentially allows the extraction of considerable added value from the same primary dataset by the wider research community. Although the number of genetical genomics experiments in different plant species is rapidly increasing, none to date has been presented in a form that allows quick and efficient on-line testing for possible associations between genes, loci and traits of interest by an entire research community. Using a reference population of 150 recombinant doubled haploid barley lines we generated novel phenotypic, mRNA abundance and SNP-based genotyping data sets, added them to a considerable volume of legacy trait data and entered them into the GeneNetwork http://www.genenetwork.org. GeneNetwork is a unified on-line analytical environment that enables the user to test genetic hypotheses about how component traits, such as mRNA abundance, may interact to condition more complex biological phenotypes (higher-order traits). Here we describe these barley data sets and demonstrate some of the functionalities GeneNetwork provides as an easily accessible and integrated analytical environment for exploring them. By integrating barley genotypic, phenotypic and mRNA abundance data sets directly within GeneNetwork's analytical environment we provide simple web access to the data for the research community. In this environment, a combination of correlation analysis and linkage mapping provides the potential to identify and substantiate gene targets for saturation mapping and positional cloning. By integrating datasets from an unsequenced crop plant (barley) in a database that has been designed for an animal model species (mouse) with a well established genome sequence, we prove the importance of the concept and practice of modular development and interoperability of software engineering for biological data sets.

Large-scale image-based profiling of single-cell phenotypes in arrayed CRISPR-Cas9 gene perturbation screens.

PubMed

de Groot, Reinoud; Lüthi, Joel; Lindsay, Helen; Holtackers, René; Pelkmans, Lucas

2018-01-23

High-content imaging using automated microscopy and computer vision allows multivariate profiling of single-cell phenotypes. Here, we present methods for the application of the CISPR-Cas9 system in large-scale, image-based, gene perturbation experiments. We show that CRISPR-Cas9-mediated gene perturbation can be achieved in human tissue culture cells in a timeframe that is compatible with image-based phenotyping. We developed a pipeline to construct a large-scale arrayed library of 2,281 sequence-verified CRISPR-Cas9 targeting plasmids and profiled this library for genes affecting cellular morphology and the subcellular localization of components of the nuclear pore complex (NPC). We conceived a machine-learning method that harnesses genetic heterogeneity to score gene perturbations and identify phenotypically perturbed cells for in-depth characterization of gene perturbation effects. This approach enables genome-scale image-based multivariate gene perturbation profiling using CRISPR-Cas9. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Shade avoidance components and pathways in adult plants revealed by phenotypic profiling.

PubMed

Nozue, Kazunari; Tat, An V; Kumar Devisetty, Upendra; Robinson, Matthew; Mumbach, Maxwell R; Ichihashi, Yasunori; Lekkala, Saradadevi; Maloof, Julin N

2015-04-01

Shade from neighboring plants limits light for photosynthesis; as a consequence, plants have a variety of strategies to avoid canopy shade and compete with their neighbors for light. Collectively the response to foliar shade is called the shade avoidance syndrome (SAS). The SAS includes elongation of a variety of organs, acceleration of flowering time, and additional physiological responses, which are seen throughout the plant life cycle. However, current mechanistic knowledge is mainly limited to shade-induced elongation of seedlings. Here we use phenotypic profiling of seedling, leaf, and flowering time traits to untangle complex SAS networks. We used over-representation analysis (ORA) of shade-responsive genes, combined with previous annotation, to logically select 59 known and candidate novel mutants for phenotyping. Our analysis reveals shared and separate pathways for each shade avoidance response. In particular, auxin pathway components were required for shade avoidance responses in hypocotyl, petiole, and flowering time, whereas jasmonic acid pathway components were only required for petiole and flowering time responses. Our phenotypic profiling allowed discovery of seventeen novel shade avoidance mutants. Our results demonstrate that logical selection of mutants increased success of phenotypic profiling to dissect complex traits and discover novel components.

Hypertriglyceridemic waist-to-height ratio phenotype: association with atherogenic lipid profile in Han adolescents.

PubMed

Ma, Chun-ming; Liu, Xiao-li; Yin, Fu-Zai; Gao, Guo-qin; Wang, Rui; Lu, Qiang

2015-09-01

Hypertriglyceridemic waist (HW) phenotype was associated with an atherogenic lipid profile in adolescents. But unlike adults, the cutoffs of waist circumference are age- and gender-specific standards and are less feasible for non-professional use. The present study tested the hypothesis that simple variables, such as waist-to-height ratio (WHtR) and serum triacylglycerol (TG) concentrations, could be used as screening tools for the identification of adolescents characterized by atherogenic lipid profile. In 2006, anthropometric and biochemical measurements were assessed in a cross-sectional population-based study of 3136 Han adolescents, aged 13-17 years. The hypertriglyceridemic waist-to-height ratio (HWHtR) phenotype was defined as serum TG concentrations ≥1.47 mmol/L and WHtR ≥0.48 for boys and ≥0.46 for girls. Hypercholesterolemia (total cholesterol ≥5.18 mmol/L), high low-density lipoprotein cholesterol (LDL-C ≥3.37 mmol/L), low high-density lipoprotein cholesterol (HDL-C <1.03 mmol/L), and high non-HDL-C (≥3.76 mmol/L) were considered as atherogenic lipid profiles. After control for age and sex, adolescents with the HWHtR phenotype were more likely to have hypercholesterolemia (odds ratio (OR) = 7.8, 95 % confidence interval (CI) = 3.5-17.3, P < 0.001), high LDL-C (OR = 9.4, 95 % CI = 2.8-31.2, P < 0.001), low HDL-C (OR = 10.8, 95 % CI = 6.9-17.0, P < 0.001), and high non-HDL-C (OR = 22.9, 95 % CI = 10.0-52.2, P < 0.001) than those adolescents with normal WHtR and normal serum TG concentrations. The present study demonstrates that HWHtR phenotype is a simple marker for identifying adolescents with atherogenic lipid profile. Compared with HW phenotype, HWHtR phenotype is a non-age-dependent index with higher applicability to screen for cardiovascular risk factors in adolescents. • The hypertriglyceridemic waist phenotype is represented by the simultaneous presence of elevated serum triacylglycerol and increased waist circumference. Hypertriglyceridemic waist phenotype can identify adolescents with metabolic syndrome. But the cutoffs of waist circumference are age- and gender-specific standards and are less feasible for non-professional use. • The present study demonstrates that hypertriglyceridemic waist-to-height ratio phenotype is a simple marker for identifying adolescents with atherogenic lipid profile. Compared with hypertriglyceridemic waist phenotype, hypertriglyceridemic waist-to-height ratio phenotype is a non-age-dependent index with higher applicability to screen for cardiovascular risk factors in adolescents.

In Vitro Assays for Mouse Müller Cell Phenotyping Through microRNA Profiling in the Damaged Retina.

PubMed

Reyes-Aguirre, Luis I; Quintero, Heberto; Estrada-Leyva, Brenda; Lamas, Mónica

2018-01-01

microRNA profiling has identified cell-specific expression patterns that could represent molecular signatures triggering the acquisition of a specific phenotype; in other words, of cellular identity and its associated function. Several groups have hypothesized that retinal cell phenotyping could be achieved through the determination of the global pattern of miRNA expression across specific cell types in the adult retina. This is especially relevant for Müller glia in the context of retinal damage, as these cells undergo dramatic changes of gene expression in response to injury, that render them susceptible to acquire a progenitor-like phenotype and be a source of new neurons.We describe a method that combines an experimental protocol for excitotoxic-induced retinal damage through N-methyl-D-aspartate subretinal injection with magnetic-activated cell sorting (MACS) of Müller cells and RNA isolation for microRNA profiling. Comparison of microRNA patterns of expression should allow Müller cell phenotyping under different experimental conditions.

Turbine blade profile design method based on Bezier curves

NASA Astrophysics Data System (ADS)

Alexeev, R. A.; Tishchenko, V. A.; Gribin, V. G.; Gavrilov, I. Yu.

2017-11-01

In this paper, the technique of two-dimensional parametric blade profile design is presented. Bezier curves are used to create the profile geometry. The main feature of the proposed method is an adaptive approach of curve fitting to given geometric conditions. Calculation of the profile shape is produced by multi-dimensional minimization method with a number of restrictions imposed on the blade geometry.The proposed method has been used to describe parametric geometry of known blade profile. Then the baseline geometry was modified by varying some parameters of the blade. The numerical calculation of obtained designs has been carried out. The results of calculations have shown the efficiency of chosen approach.

Development and Validation of Triarchic Psychopathy Scales from the Multidimensional Personality Questionnaire

PubMed Central

Brislin, Sarah J.; Drislane, Laura E.; Smith, Shannon Toney; Edens, John F.; Patrick, Christopher J.

2015-01-01

Psychopathy is conceptualized by the triarchic model as encompassing three distinct phenotypic constructs: boldness, meanness, and disinhibition. In the current study, the Multidimensional Personality Questionnaire (MPQ), a normal-range personality measure, was evaluated for representation of these three constructs. Consensus ratings were used to identify MPQ items most related to each triarchic (Tri) construct. Scale measures were developed from items indicative of each construct, and scores for these scales were evaluated for convergent and discriminant validity in community (N = 176) and incarcerated samples (N = 240). A cross the two samples, MPQ-Tri scale scores demonstrated good internal consistencies and relationships with criterion measures of various types consistent with predictions based on the triarchic model. Findings are discussed in terms of their implications for further investigation of the triarchic model constructs in preexisting datasets that include the MPQ, in particular longitudinal and genetically informative datasets. PMID:25642934

Are Multidimensional Pain Inventory Coping Strategy Profiles Associated with Long-Term Spinal Cord Stimulation Effectiveness?

PubMed

Paroli, Mery; Bernini, Olivia; De Carolis, Giuliano; Tollapi, Lara; Bondi, Franca; Martini, Antonella; Dario, Alessandro; Paolicchi, Adriana

2018-05-01

It is acknowledged that the way patients cope with pain may influence treatment outcome. In particular, psychological factors are deemed important when considering patients for suitability for spinal cord stimulation (SCS). The aim of the study is to observe how pre-implantation psychological characteristics impact the effectiveness of SCS for chronic pain. The analysis comprised data from 137 patients who underwent an SCS implant. Screening evaluation included a coping strategies profile (Multidimensional Pain Inventory) and psychiatric disorders (Mini-International Neuropsychiatric Interview). Based on SCS implant outcome collected during follow-up visits, patients were divided into three groups: subjects with long-term pain relief (long-term group), subjects who failed the SCS treatment and decided to explant trial device (trial explanter group [TE]), and those who chose a permanent device (permanent explanter group [PE]). Results showed that most of the patients who failed with the SCS (TE and PE groups) demonstrated a dysfunctional coping profile and showed a higher presence of psychiatric disorders, which significantly influenced the experience and perception of pain. The findings of this study support the value of a multidisciplinary screening. Addressing psychological issues before SCS implantation can reduce the failure rate of SCS.

Chromatographic peak deconvolution of constitutional isomers by multiple-reaction-monitoring mass spectrometry.

PubMed

Trapp, Oliver

2010-02-12

Highly efficient and sophisticated separation techniques are available to analyze complex compound mixtures with superior sensitivities and selectivities often enhanced by a 2nd dimension, e.g. a separation technique or spectroscopic and spectrometric techniques. For enantioselective separations numerous chiral stationary phases (CSPs) exist to cover a broad range of chiral compounds. Despite these advances enantioselective separations can become very challenging for mixtures of stereolabile constitutional isomers, because the on-column interconversion can lead to completely overlapping peak profiles. Typically, multidimensional separation techniques, e.g. multidimensional GC (MDGC), using an achiral 1st separation dimension and transferring selected analytes to a chiral 2nd separation are the method of choice to approach such problems. However, this procedure is very time consuming and only predefined sections of peaks can be transferred by column switching to the second dimension. Here we demonstrate for stereolabile 1,2-dialkylated diaziridines a technique to experimentally deconvolute overlapping gas chromatographic elution profiles of constitutional isomers based on multiple-reaction-monitoring MS (MRM-MS). The here presented technique takes advantage of different fragmentation probabilities and pathways to isolate the elution profile of configurational isomers. Copyright 2009 Elsevier B.V. All rights reserved.

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis

PubMed Central

Twarog, Nathaniel R.; Low, Jonathan A.; Currier, Duane G.; Miller, Greg; Chen, Taosheng; Shelat, Anang A.

2016-01-01

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2’-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used. PMID:26886014

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis.

PubMed

Twarog, Nathaniel R; Low, Jonathan A; Currier, Duane G; Miller, Greg; Chen, Taosheng; Shelat, Anang A

2016-01-01

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2'-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used.

Quantitative NMR Metabolite Profiling of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Discriminates between Biofilm and Planktonic Phenotypes

PubMed Central

2015-01-01

Wound bioburden in the form of colonizing biofilms is a major contributor to nonhealing wounds. Staphylococcus aureus is a Gram-positive, facultative anaerobe commonly found in chronic wounds; however, much remains unknown about the basic physiology of this opportunistic pathogen, especially with regard to the biofilm phenotype. Transcriptomic and proteomic analysis of S. aureus biofilms have suggested that S. aureus biofilms exhibit an altered metabolic state relative to the planktonic phenotype. Herein, comparisons of extracellular and intracellular metabolite profiles detected by 1H NMR were conducted for methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus strains grown as biofilm and planktonic cultures. Principal component analysis distinguished the biofilm phenotype from the planktonic phenotype, and factor loadings analysis identified metabolites that contributed to the statistical separation of the biofilm from the planktonic phenotype, suggesting that key features distinguishing biofilm from planktonic growth include selective amino acid uptake, lipid catabolism, butanediol fermentation, and a shift in metabolism from energy production to assembly of cell-wall components and matrix deposition. These metabolite profiles provide a basis for the development of metabolite biomarkers that distinguish between biofilm and planktonic phenotypes in S. aureus and have the potential for improved diagnostic and therapeutic use in chronic wounds. PMID:24809402

Classification of Marital Relationships: An Empirical Approach.

ERIC Educational Resources Information Center

Snyder, Douglas K.; Smith, Gregory T.

1986-01-01

Derives an empirically based classification system of marital relationships, employing a multidimensional self-report measure of marital interaction. Spouses' profiles on the Marital Satisfaction Inventory for samples of clinic and nonclinic couples were subjected to cluster analysis, resulting in separate five-group typologies for husbands and…

Multidimensional profiling platforms reveal metabolic dysregulation caused by organophosphorus pesticides.

PubMed

Medina-Cleghorn, Daniel; Heslin, Ann; Morris, Patrick J; Mulvihill, Melinda M; Nomura, Daniel K

2014-02-21

We are environmentally exposed to countless synthetic chemicals on a daily basis, with an increasing number of these chemical exposures linked to adverse health effects. However, our understanding of the (patho)physiological effects of these chemicals remains poorly understood, due in part to a general lack of effort to systematically and comprehensively identify the direct interactions of environmental chemicals with biological macromolecules in mammalian systems in vivo. Here, we have used functional chemoproteomic and metabolomic platforms to broadly identify direct enzyme targets that are inhibited by widely used organophosphorus (OP) pesticides in vivo in mice and to determine metabolic alterations that are caused by these chemicals. We find that these pesticides directly inhibit over 20 serine hydrolases in vivo leading to widespread disruptions in lipid metabolism. Through identifying direct biological targets of OP pesticides, we show heretofore unrecognized modes of toxicity that may be associated with these agents and underscore the utility of using multidimensional profiling approaches to obtain a more complete understanding of toxicities associated with environmental chemicals.

Phenotypic and ionome profiling of Triticum aestivum x Aegilops tauschii introgression lines

USDA-ARS?s Scientific Manuscript database

Eighty-four single homozygous introgressions of the Aegilops tauschii D-genome in the ‘Chinese Spring’ genetic background were used to study phenotypic and ionome profiles during two years of field experiments. An augmented design was used with a repeated check of a local bread wheat cultivar was im...

Using multidimensional topological data analysis to identify traits of hip osteoarthritis.

PubMed

Rossi-deVries, Jasmine; Pedoia, Valentina; Samaan, Michael A; Ferguson, Adam R; Souza, Richard B; Majumdar, Sharmila

2018-05-07

Osteoarthritis (OA) is a multifaceted disease with many variables affecting diagnosis and progression. Topological data analysis (TDA) is a state-of-the-art big data analytics tool that can combine all variables into multidimensional space. TDA is used to simultaneously analyze imaging and gait analysis techniques. To identify biochemical and biomechanical biomarkers able to classify different disease progression phenotypes in subjects with and without radiographic signs of hip OA. Longitudinal study for comparison of progressive and nonprogressive subjects. In all, 102 subjects with and without radiographic signs of hip osteoarthritis. 3T, SPGR 3D MAPSS T 1ρ /T 2 , intermediate-weighted fat-suppressed fast spin-echo (FSE). Multidimensional data analysis including cartilage composition, bone shape, Kellgren-Lawrence (KL) classification of osteoarthritis, scoring hip osteoarthritis with MRI (SHOMRI), hip disability and osteoarthritis outcome score (HOOS). Analysis done using TDA, Kolmogorov-Smirnov (KS) testing, and Benjamini-Hochberg to rank P-value results to correct for multiple comparisons. Subjects in the later stages of the disease had an increased SHOMRI score (P < 0.0001), increased KL (P = 0.0012), and older age (P < 0.0001). Subjects in the healthier group showed intact cartilage and less pain. Subjects found between these two groups had a range of symptoms. Analysis of this subgroup identified knee biomechanics (P < 0.0001) as an initial marker of the disease that is noticeable before the morphological progression and degeneration. Further analysis of an OA subgroup with femoroacetabular impingement (FAI) showed anterior labral tears to be the most significant marker (P = 0.0017) between those FAI subjects with and without OA symptoms. The data-driven analysis obtained with TDA proposes new phenotypes of these subjects that partially overlap with the radiographic-based classical disease status classification and also shows the potential for further examination of an early onset biomechanical intervention. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Medically unexplained dyspnoea and panic.

PubMed

Hauzer, Rose; Verheul, Willeke; Griez, Eric; Wesseling, Geertjan; van Duinen, Marlies

2015-07-01

Medically unexplained dyspnoea in the pulmonary setting is often accompanied by considerable levels of anxiety, suggestive of psychopathology, in particular panic disorder (PD). This pilot study investigates the value of the Multidimensional Dyspnea Profile as a tool to facilitate identification of a specific dyspnoea profile suggestive of comorbid PD. The verbal descriptors, feeling depressed, air hunger and concentrating on breathing, significantly differentiated between the two groups of patients with pulmonary disease with and without PD. © 2015 Asian Pacific Society of Respirology.

A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.

PubMed

Jiang, Li; Edwards, Stefan M; Thomsen, Bo; Workman, Christopher T; Guldbrandtsen, Bernt; Sørensen, Peter

2014-09-24

Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data from genome-wide association studies, and will help in the understanding of how the associated genetic variants influence disease or quantitative phenotypes.

Target identification of small molecules based on chemical biology approaches.

PubMed

Futamura, Yushi; Muroi, Makoto; Osada, Hiroyuki

2013-05-01

Recently, a phenotypic approach-screens that assess the effects of compounds on cells, tissues, or whole organisms-has been reconsidered and reintroduced as a complementary strategy of a target-based approach for drug discovery. Although the finding of novel bioactive compounds from large chemical libraries has become routine, the identification of their molecular targets is still a time-consuming and difficult process, making this step rate-limiting in drug development. In the last decade, we and other researchers have amassed a large amount of phenotypic data through progress in omics research and advances in instrumentation. Accordingly, the profiling methodologies using these datasets expertly have emerged to identify and validate specific molecular targets of drug candidates, attaining some progress in current drug discovery (e.g., eribulin). In the case of a compound that shows an unprecedented phenotype likely by inhibiting a first-in-class target, however, such phenotypic profiling is invalid. Under the circumstances, a photo-crosslinking affinity approach should be beneficial. In this review, we describe and summarize recent progress in both affinity-based (direct) and phenotypic profiling (indirect) approaches for chemical biology target identification.

Autism Spectrum and Obsessive–Compulsive Disorders: OC Behaviors, Phenotypes and Genetics

PubMed Central

Jacob, Suma; Landeros-Weisenberger, Angeli; Leckman, James F.

2014-01-01

Autism spectrum disorders (ASDs) are a phenotypically and etiologically heterogeneous set of disorders that include obsessive–compulsive behaviors (OCB) that partially overlap with symptoms associated with obsessive–compulsive disorder (OCD). The OCB seen in ASD vary depending on the individual’s mental and chronological age as well as the etiology of their ASD. Although progress has been made in the measurement of the OCB associated with ASD, more work is needed including the potential identification of heritable endophenotypes. Likewise, important progress toward the understanding of genetic influences in ASD has been made by greater refinement of relevant phenotypes using a broad range of study designs, including twin and family-genetic studies, parametric and nonparametric linkage analyses, as well as candidate gene studies and the study of rare genetic variants. These genetic analyses could lead to the refinement of the OCB phenotypes as larger samples are studied and specific associations are replicated. Like ASD, OCB are likely to prove to be multidimensional and polygenic. Some of the vulnerability genes may prove to be generalist genes influencing the phenotypic expression of both ASD and OCD while others will be specific to subcomponents of the ASD phenotype. In order to discover molecular and genetic mechanisms, collaborative approaches need to generate shared samples, resources, novel genomic technologies, as well as more refined phenotypes and innovative statistical approaches. There is a growing need to identify the range of molecular pathways involved in OCB related to ASD in order to develop novel treatment interventions. PMID:20029829

Microbial genotype-phenotype mapping by class association rule mining.

PubMed

Tamura, Makio; D'haeseleer, Patrik

2008-07-01

Microbial phenotypes are typically due to the concerted action of multiple gene functions, yet the presence of each gene may have only a weak correlation with the observed phenotype. Hence, it may be more appropriate to examine co-occurrence between sets of genes and a phenotype (multiple-to-one) instead of pairwise relations between a single gene and the phenotype. Here, we propose an efficient class association rule mining algorithm, netCAR, in order to extract sets of COGs (clusters of orthologous groups of proteins) associated with a phenotype from COG phylogenetic profiles and a phenotype profile. netCAR takes into account the phylogenetic co-occurrence graph between COGs to restrict hypothesis space, and uses mutual information to evaluate the biconditional relation. We examined the mining capability of pairwise and multiple-to-one association by using netCAR to extract COGs relevant to six microbial phenotypes (aerobic, anaerobic, facultative, endospore, motility and Gram negative) from 11,969 unique COG profiles across 155 prokaryotic organisms. With the same level of false discovery rate, multiple-to-one association can extract about 10 times more relevant COGs than one-to-one association. We also reveal various topologies of association networks among COGs (modules) from extracted multiple-to-one correlation rules relevant with the six phenotypes; including a well-connected network for motility, a star-shaped network for aerobic and intermediate topologies for the other phenotypes. netCAR outperforms a standard CAR mining algorithm, CARapriori, while requiring several orders of magnitude less computational time for extracting 3-COG sets. Source code of the Java implementation is available as Supplementary Material at the Bioinformatics online website, or upon request to the author. Supplementary data are available at Bioinformatics online.

Quantitative trait loci mapping and gene network analysis implicate protocadherin-15 as a determinant of brain serotonin transporter expression.

PubMed

Ye, R; Carneiro, A M D; Han, Q; Airey, D; Sanders-Bush, E; Zhang, B; Lu, L; Williams, R; Blakely, R D

2014-03-01

Presynaptic serotonin (5-hydroxytryptamine, 5-HT) transporters (SERT) regulate 5-HT signaling via antidepressant-sensitive clearance of released neurotransmitter. Polymorphisms in the human SERT gene (SLC6A4) have been linked to risk for multiple neuropsychiatric disorders, including depression, obsessive-compulsive disorder and autism. Using BXD recombinant inbred mice, a genetic reference population that can support the discovery of novel determinants of complex traits, merging collective trait assessments with bioinformatics approaches, we examine phenotypic and molecular networks associated with SERT gene and protein expression. Correlational analyses revealed a network of genes that significantly associated with SERT mRNA levels. We quantified SERT protein expression levels and identified region- and gender-specific quantitative trait loci (QTLs), one of which associated with male midbrain SERT protein expression, centered on the protocadherin-15 gene (Pcdh15), overlapped with a QTL for midbrain 5-HT levels. Pcdh15 was also the only QTL-associated gene whose midbrain mRNA expression significantly associated with both SERT protein and 5-HT traits, suggesting an unrecognized role of the cell adhesion protein in the development or function of 5-HT neurons. To test this hypothesis, we assessed SERT protein and 5-HT traits in the Pcdh15 functional null line (Pcdh15(av-) (3J) ), studies that revealed a strong, negative influence of Pcdh15 on these phenotypes. Together, our findings illustrate the power of multidimensional profiling of recombinant inbred lines in the analysis of molecular networks that support synaptic signaling, and that, as in the case of Pcdh15, can reveal novel relationships that may underlie risk for mental illness. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Machine learning and computer vision approaches for phenotypic profiling.

PubMed

Grys, Ben T; Lo, Dara S; Sahin, Nil; Kraus, Oren Z; Morris, Quaid; Boone, Charles; Andrews, Brenda J

2017-01-02

With recent advances in high-throughput, automated microscopy, there has been an increased demand for effective computational strategies to analyze large-scale, image-based data. To this end, computer vision approaches have been applied to cell segmentation and feature extraction, whereas machine-learning approaches have been developed to aid in phenotypic classification and clustering of data acquired from biological images. Here, we provide an overview of the commonly used computer vision and machine-learning methods for generating and categorizing phenotypic profiles, highlighting the general biological utility of each approach. © 2017 Grys et al.

Machine learning and computer vision approaches for phenotypic profiling

PubMed Central

Morris, Quaid

2017-01-01

With recent advances in high-throughput, automated microscopy, there has been an increased demand for effective computational strategies to analyze large-scale, image-based data. To this end, computer vision approaches have been applied to cell segmentation and feature extraction, whereas machine-learning approaches have been developed to aid in phenotypic classification and clustering of data acquired from biological images. Here, we provide an overview of the commonly used computer vision and machine-learning methods for generating and categorizing phenotypic profiles, highlighting the general biological utility of each approach. PMID:27940887

Toward a deeper characterization of the social phenotype of Williams syndrome: the association between personality and social drive

PubMed Central

Ng, Rowena; Järvinen, Anna; Bellugi, Ursula

2014-01-01

Previous research has robustly established a Williams syndrome (WS) specific personality profile, predominantly characterized a gregarious, people-oriented, and tense predisposition. Extending this work, the aims of the current, cross-sectional study were two-fold: (1) to elucidate the stability of personality characteristics in individuals with WS and typically developing (TD) comparisons across development, and (2) to explore the personality attributes that may be related to the respective profiles of social functioning characterizing the two groups, which is currently poorly understood. The sample comprised of participants with WS and TD matched on chronological age. The test battery included the Multidimensional Personality Questionnaire (MPQ) and the Salk Institute Sociability Questionnaire (SISQ), an index of real-life social behavior. The main results showed that compared to the TD individuals, the WS group were consistently rated higher in Social Closeness, and this trait remained stable across development. Interpersonal behaviors were best predicted by Social Closeness in WS and by Social Potency in TD. Regression analysis highlighted that while a central motive underlying the increased drive toward social interaction in individuals with WS pertains to a desire to form affectionate relationships, TD individuals by contrast are motivated by a desire to exert social influence over others (leadership, social-dominance) and Well-Being (positive emotional disposition). In conclusion, these findings provide novel insight into social motivational factors underpinning the WS social behavior in real life, and contribute toward a deeper characterization of the WS affiliative drive. We suggest potential areas for behavioral intervention targeting improved social adjustment in individuals with WS. PMID:24794322

Multidimensional Learner Model In Intelligent Learning System

NASA Astrophysics Data System (ADS)

Deliyska, B.; Rozeva, A.

2009-11-01

The learner model in an intelligent learning system (ILS) has to ensure the personalization (individualization) and the adaptability of e-learning in an online learner-centered environment. ILS is a distributed e-learning system whose modules can be independent and located in different nodes (servers) on the Web. This kind of e-learning is achieved through the resources of the Semantic Web and is designed and developed around a course, group of courses or specialty. An essential part of ILS is learner model database which contains structured data about learner profile and temporal status in the learning process of one or more courses. In the paper a learner model position in ILS is considered and a relational database is designed from learner's domain ontology. Multidimensional modeling agent for the source database is designed and resultant learner data cube is presented. Agent's modules are proposed with corresponding algorithms and procedures. Multidimensional (OLAP) analysis guidelines on the resultant learner module for designing dynamic learning strategy have been highlighted.

Reconceptualising manual therapy skills in contemporary practice.

PubMed

Rabey, Martin; Hall, Toby; Hebron, Clair; Palsson, Thorvaldur Skuli; Christensen, Steffan Wittrup; Moloney, Niamh

2017-06-01

With conflicting evidence regarding the effectiveness of manual therapy calls have arisen within some quarters of the physiotherapy profession challenging the continued use of manual skills for assessment and treatment. A reconceptualisation of the importance of manual examination findings is put forward, based upon a contemporary understanding of pain science, rather than considering these skills only in terms of how they should "guide" manual therapy interventions. The place for manual examination findings within complex, multidimensional presentations is considered using vignettes describing the presentations of five people with low back pain. As part of multidimensional, individualised management, the balance of evidence relating to the effectiveness, mechanisms of action and rationale for manual skills is discussed. It is concluded that if manual examination and therapeutic skills are used in a manner consistent with a contemporary understanding of pain science, multidimensional patient profiles and a person-centred approach, their selective and judicious use still has an important role. Copyright © 2017 Elsevier Ltd. All rights reserved.

The scheme and research of TV series multidimensional comprehensive evaluation on cross-platform

NASA Astrophysics Data System (ADS)

Chai, Jianping; Bai, Xuesong; Zhou, Hongjun; Yin, Fulian

2016-10-01

As for shortcomings of the comprehensive evaluation system on traditional TV programs such as single data source, ignorance of new media as well as the high time cost and difficulty of making surveys, a new evaluation of TV series is proposed in this paper, which has a perspective in cross-platform multidimensional evaluation after broadcasting. This scheme considers the data directly collected from cable television and the Internet as research objects. It's based on TOPSIS principle, after preprocessing and calculation of the data, they become primary indicators that reflect different profiles of the viewing of TV series. Then after the process of reasonable empowerment and summation by the six methods(PCA, AHP, etc.), the primary indicators form the composite indices on different channels or websites. The scheme avoids the inefficiency and difficulty of survey and marking; At the same time, it not only reflects different dimensions of viewing, but also combines TV media and new media, completing the multidimensional comprehensive evaluation of TV series on cross-platform.

Chronic Low Back Pain: Toward an Integrated Psychosocial Assessment Model.

ERIC Educational Resources Information Center

Strong, Jenny; And Others

1994-01-01

Integrated six dimensions of chronic low back pain (pain intensity, functional disability, attitudes toward pain, pain coping strategies, depression, illness behavior) to provide multidimensional patient profile. Data from 100 patients revealed presence of three distinct patient groups: patients who were in control, patients who were depressed and…

Assessment of Language and Literacy: A Process of Hypothesis Testing for Individual Differences

ERIC Educational Resources Information Center

Scott, Cheryl M.

2011-01-01

Purpose: Older school-aged children and adolescents with persistent language and literacy impairments vary in their individual profiles of linguistic strengths and weaknesses. Given the multidimensional nature and complexity of language, designing an assessment protocol capable of uncovering linguistic variation is challenging. A process of…

Internalizing and Externalizing Subtypes in Female Sexual Assault Survivors: Implications for the Understanding of Complex PTSD

ERIC Educational Resources Information Center

Miller, Mark W.; Resick, Patricia A.

2007-01-01

This study replicated and extended findings of internalizing and externalizing subtypes of posttraumatic psychopathology (Miller, M. W., Greif, J. L., & Smith, A. A. (2003). Multidimensional Personality Questionnaire profiles of veterans with traumatic combat exposure: Internalizing and externalizing subtypes. "Psychological Assessment, 15",…

Epistemological and Reading Beliefs Profiles and Their Role in Multiple Text Comprehension

ERIC Educational Resources Information Center

Mateos, Mar; Solé, Isabel; Martín, Elena; Castells, Nuria; Cuevas, Isabel; González-Lamas, Jara

2016-01-01

Introduction: The aim of this study was to analyse the role of epistemological beliefs and reading beliefs in the comprehension of multiple texts which presented conflicting positions about a controversial topic (nuclear energy). More specifically, we investigated the influence of the multidimensional configuration of epistemological and reading…

A latent modeling approach to genotype-phenotype relationships: maternal problem behavior clusters, prenatal smoking, and MAOA genotype.

PubMed

McGrath, L M; Mustanski, B; Metzger, A; Pine, D S; Kistner-Griffin, E; Cook, E; Wakschlag, L S

2012-08-01

This study illustrates the application of a latent modeling approach to genotype-phenotype relationships and gene × environment interactions, using a novel, multidimensional model of adult female problem behavior, including maternal prenatal smoking. The gene of interest is the monoamine oxidase A (MAOA) gene which has been well studied in relation to antisocial behavior. Participants were adult women (N = 192) who were sampled from a prospective pregnancy cohort of non-Hispanic, white individuals recruited from a neighborhood health clinic. Structural equation modeling was used to model a female problem behavior phenotype, which included conduct problems, substance use, impulsive-sensation seeking, interpersonal aggression, and prenatal smoking. All of the female problem behavior dimensions clustered together strongly, with the exception of prenatal smoking. A main effect of MAOA genotype and a MAOA × physical maltreatment interaction were detected with the Conduct Problems factor. Our phenotypic model showed that prenatal smoking is not simply a marker of other maternal problem behaviors. The risk variant in the MAOA main effect and interaction analyses was the high activity MAOA genotype, which is discrepant from consensus findings in male samples. This result contributes to an emerging literature on sex-specific interaction effects for MAOA.

Recapitulation of Ayurveda constitution types by machine learning of phenotypic traits.

PubMed

Tiwari, Pradeep; Kutum, Rintu; Sethi, Tavpritesh; Shrivastava, Ankita; Girase, Bhushan; Aggarwal, Shilpi; Patil, Rutuja; Agarwal, Dhiraj; Gautam, Pramod; Agrawal, Anurag; Dash, Debasis; Ghosh, Saurabh; Juvekar, Sanjay; Mukerji, Mitali; Prasher, Bhavana

2017-01-01

In Ayurveda system of medicine individuals are classified into seven constitution types, "Prakriti", for assessing disease susceptibility and drug responsiveness. Prakriti evaluation involves clinical examination including questions about physiological and behavioural traits. A need was felt to develop models for accurately predicting Prakriti classes that have been shown to exhibit molecular differences. The present study was carried out on data of phenotypic attributes in 147 healthy individuals of three extreme Prakriti types, from a genetically homogeneous population of Western India. Unsupervised and supervised machine learning approaches were used to infer inherent structure of the data, and for feature selection and building classification models for Prakriti respectively. These models were validated in a North Indian population. Unsupervised clustering led to emergence of three natural clusters corresponding to three extreme Prakriti classes. The supervised modelling approaches could classify individuals, with distinct Prakriti types, in the training and validation sets. This study is the first to demonstrate that Prakriti types are distinct verifiable clusters within a multidimensional space of multiple interrelated phenotypic traits. It also provides a computational framework for predicting Prakriti classes from phenotypic attributes. This approach may be useful in precision medicine for stratification of endophenotypes in healthy and diseased populations.

Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis.

PubMed

Lee, Jessica J Y; Gottlieb, Michael M; Lever, Jake; Jones, Steven J M; Blau, Nenad; van Karnebeek, Clara D M; Wasserman, Wyeth W

2018-05-01

Phenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze phenotypes. Such methods have allowed phenotypic data to be widely used in medical applications, from assisting clinical diagnoses to prioritizing genomic diagnoses. To channel the benefits of phenomics into the field of inborn errors of metabolism (IEM), we have recently launched IEMbase, an expert-curated knowledgebase of IEM and their disease-characterizing phenotypes. While our efforts with IEMbase have realized benefits, taking full advantage of phenomics requires a comprehensive curation of IEM phenotypes in core phenomics projects, which is dependent upon contributions from the IEM clinical and research community. Here, we assess the inclusion of IEM biochemical phenotypes in a core phenomics project, the Human Phenotype Ontology. We then demonstrate the utility of biochemical phenotypes using a text-based phenomics method to predict gene-disease relationships, showing that the prediction of IEM genes is significantly better using biochemical rather than clinical profiles. The findings herein provide a motivating goal for the IEM community to expand the computationally accessible descriptions of biochemical phenotypes associated with IEM in phenomics resources.

Active Learning Strategies for Phenotypic Profiling of High-Content Screens.

PubMed

Smith, Kevin; Horvath, Peter

2014-06-01

High-content screening is a powerful method to discover new drugs and carry out basic biological research. Increasingly, high-content screens have come to rely on supervised machine learning (SML) to perform automatic phenotypic classification as an essential step of the analysis. However, this comes at a cost, namely, the labeled examples required to train the predictive model. Classification performance increases with the number of labeled examples, and because labeling examples demands time from an expert, the training process represents a significant time investment. Active learning strategies attempt to overcome this bottleneck by presenting the most relevant examples to the annotator, thereby achieving high accuracy while minimizing the cost of obtaining labeled data. In this article, we investigate the impact of active learning on single-cell-based phenotype recognition, using data from three large-scale RNA interference high-content screens representing diverse phenotypic profiling problems. We consider several combinations of active learning strategies and popular SML methods. Our results show that active learning significantly reduces the time cost and can be used to reveal the same phenotypic targets identified using SML. We also identify combinations of active learning strategies and SML methods which perform better than others on the phenotypic profiling problems we studied. © 2014 Society for Laboratory Automation and Screening.

Examining the relationship between sex and motivation in triathletes.

PubMed

López-Fernández, Iván; Merino-Marbán, Rafael; Fernández-Rodríguez, Emilio

2014-08-01

The present paper assesses the relationship between sex and motivation in triathletes utilising a multidimensional measurement of motivation in sports. Data were collected from 138 triathlon participants (age range 17-72 years): 95 men (M = 36.7 yr., SD = 10.7) and 43 women (M = 34.6 yr., SD = 9.9). Measures included the Sport Motivation Scale, a multi-dimensional measure to assess different types of athletes' motivations for practising their sport. Results showed a significant sex difference in amotivation, with women displaying lower scores; but amotivation scores were very low. The results were not dependent on competition level or age. Men and women competing at the international level in triathlon have similar motivational profiles.

An Environmentally Sensitive Fluorescent Dye as a Multidimensional Probe of Amyloid Formation

PubMed Central

2016-01-01

We have explored amyloid formation using poly(amino acid) model systems in which differences in peptide secondary structure and hydrophobicity can be introduced in a controlled manner. We show that an environmentally sensitive fluorescent dye, dapoxyl, is able to identify β-sheet structure and hydrophobic surfaces, structural features likely to be related to toxicity, as a result of changes in its excitation and emission profiles and its relative quantum yield. These results show that dapoxyl is a multidimensional probe of the time dependence of amyloid aggregation, which provides information about the presence and nature of metastable aggregation intermediates that is inaccessible to the conventional probes that rely on changes in quantum yield alone. PMID:26865546

Tissue-Specific Profiling Reveals Transcriptome Alterations in Arabidopsis Mutants Lacking Morphological Phenotypes[C][W

PubMed Central

Simon, Marissa; Bruex, Angela; Kainkaryam, Raghunandan M.; Zheng, Xiaohua; Huang, Ling; Woolf, Peter J.; Schiefelbein, John

2013-01-01

Traditional genetic analysis relies on mutants with observable phenotypes. Mutants lacking visible abnormalities may nevertheless exhibit molecular differences useful for defining gene function. To examine this, we analyzed tissue-specific transcript profiles from Arabidopsis thaliana transcription factor gene mutants with known roles in root epidermis development, but lacking a single-gene mutant phenotype due to genetic redundancy. We discovered substantial transcriptional changes in each mutant, preferentially affecting root epidermal genes in a manner consistent with the known double mutant effects. Furthermore, comparing transcript profiles of single and double mutants, we observed remarkable variation in the sensitivity of target genes to the loss of one or both paralogous genes, including preferential effects on specific branches of the epidermal gene network, likely reflecting the pathways of paralog subfunctionalization during evolution. In addition, we analyzed the root epidermal transcriptome of the transparent testa glabra2 mutant to clarify its role in the network. These findings provide insight into the molecular basis of genetic redundancy and duplicate gene diversification at the level of a specific gene regulatory network, and they demonstrate the usefulness of tissue-specific transcript profiling to define gene function in mutants lacking informative visible changes in phenotype. PMID:24014549

Probing the Reproducibility of Leaf Growth and Molecular Phenotypes: A Comparison of Three Arabidopsis Accessions Cultivated in Ten Laboratories1[W

PubMed Central

Massonnet, Catherine; Vile, Denis; Fabre, Juliette; Hannah, Matthew A.; Caldana, Camila; Lisec, Jan; Beemster, Gerrit T.S.; Meyer, Rhonda C.; Messerli, Gaëlle; Gronlund, Jesper T.; Perkovic, Josip; Wigmore, Emma; May, Sean; Bevan, Michael W.; Meyer, Christian; Rubio-Díaz, Silvia; Weigel, Detlef; Micol, José Luis; Buchanan-Wollaston, Vicky; Fiorani, Fabio; Walsh, Sean; Rinn, Bernd; Gruissem, Wilhelm; Hilson, Pierre; Hennig, Lars; Willmitzer, Lothar; Granier, Christine

2010-01-01

A major goal of the life sciences is to understand how molecular processes control phenotypes. Because understanding biological systems relies on the work of multiple laboratories, biologists implicitly assume that organisms with the same genotype will display similar phenotypes when grown in comparable conditions. We investigated to what extent this holds true for leaf growth variables and metabolite and transcriptome profiles of three Arabidopsis (Arabidopsis thaliana) genotypes grown in 10 laboratories using a standardized and detailed protocol. A core group of four laboratories generated similar leaf growth phenotypes, demonstrating that standardization is possible. But some laboratories presented significant differences in some leaf growth variables, sometimes changing the genotype ranking. Metabolite profiles derived from the same leaf displayed a strong genotype × environment (laboratory) component. Genotypes could be separated on the basis of their metabolic signature, but only when the analysis was limited to samples derived from one laboratory. Transcriptome data revealed considerable plant-to-plant variation, but the standardization ensured that interlaboratory variation was not considerably larger than intralaboratory variation. The different impacts of the standardization on phenotypes and molecular profiles could result from differences of temporal scale between processes involved at these organizational levels. Our findings underscore the challenge of describing, monitoring, and precisely controlling environmental conditions but also demonstrate that dedicated efforts can result in reproducible data across multiple laboratories. Finally, our comparative analysis revealed that small variations in growing conditions (light quality principally) and handling of plants can account for significant differences in phenotypes and molecular profiles obtained in independent laboratories. PMID:20200072

Distribution of phenotypes among Bacillus thuringiensis strains

USDA-ARS?s Scientific Manuscript database

An extensive collection of Bacillus thuringiensis isolates from around the world were phenotypically profiled using standard biochemical tests. Six phenotypic traits occurred in 20-86% of the isolates and were useful in distinguishing isolates: production of urease (U; 20.5% of isolates), hydrolysis...

Behavioral Hypervolumes of Predator Groups and Predator-Predator Interactions Shape Prey Survival Rates and Selection on Prey Behavior

PubMed Central

Pruitt, Jonathan N.; Howell, Kimberly A.; Gladney, Shaniqua J.; Yang, Yusan; Lichtenstein, James L. L.; Spicer, Michelle Elise; Echeverri, Sebastian A.; Pinter-Wollman, Noa

2017-01-01

Predator-prey interactions often vary on the basis of the traits of the individual predators and prey involved. Here we examine whether the multidimensional behavioral diversity of predator groups shapes prey mortality rates and selection on prey behavior. We ran individual sea stars (Pisaster ochraceus) through three behavioral assays to characterize individuals’ behavioral phenotype along three axes. We then created groups that varied in the volume of behavioral space that they occupied. We further manipulated the ability of predators to interact with one another physically via the addition of barriers. Prey snails (Chlorostome funebralis) were also run through an assay to evaluate their predator avoidance behavior before their use in mesocosm experiments. We then subjected pools of prey to predator groups and recorded the number of prey consumed and their behavioral phenotypes. We found that predator-predator interactions changed survival selection on prey traits: when predators were prevented from interacting, more fearful snails had higher survival rates, whereas prey fearfulness had no effect on survival when predators were free to interact. We also found that groups of predators that occupied a larger volume in behavioral trait space consumed 35% more prey snails than homogeneous predator groups. Finally, we found that behavioral hypervolumes were better predictors of prey survival rates than single behavioral traits or other multivariate statistics (i.e., principal component analysis). Taken together, predator-predator interactions and multidimensional behavioral diversity determine prey survival rates and selection on prey traits in this system. PMID:28221831

Behavioral Hypervolumes of Predator Groups and Predator-Predator Interactions Shape Prey Survival Rates and Selection on Prey Behavior.

PubMed

Pruitt, Jonathan N; Howell, Kimberly A; Gladney, Shaniqua J; Yang, Yusan; Lichtenstein, James L L; Spicer, Michelle Elise; Echeverri, Sebastian A; Pinter-Wollman, Noa

2017-03-01

Predator-prey interactions often vary on the basis of the traits of the individual predators and prey involved. Here we examine whether the multidimensional behavioral diversity of predator groups shapes prey mortality rates and selection on prey behavior. We ran individual sea stars (Pisaster ochraceus) through three behavioral assays to characterize individuals' behavioral phenotype along three axes. We then created groups that varied in the volume of behavioral space that they occupied. We further manipulated the ability of predators to interact with one another physically via the addition of barriers. Prey snails (Chlorostome funebralis) were also run through an assay to evaluate their predator avoidance behavior before their use in mesocosm experiments. We then subjected pools of prey to predator groups and recorded the number of prey consumed and their behavioral phenotypes. We found that predator-predator interactions changed survival selection on prey traits: when predators were prevented from interacting, more fearful snails had higher survival rates, whereas prey fearfulness had no effect on survival when predators were free to interact. We also found that groups of predators that occupied a larger volume in behavioral trait space consumed 35% more prey snails than homogeneous predator groups. Finally, we found that behavioral hypervolumes were better predictors of prey survival rates than single behavioral traits or other multivariate statistics (i.e., principal component analysis). Taken together, predator-predator interactions and multidimensional behavioral diversity determine prey survival rates and selection on prey traits in this system.

A Kernel Machine Method for Detecting Effects of Interaction Between Multidimensional Variable Sets: An Imaging Genetics Application

PubMed Central

Ge, Tian; Nichols, Thomas E.; Ghosh, Debashis; Mormino, Elizabeth C.

2015-01-01

Measurements derived from neuroimaging data can serve as markers of disease and/or healthy development, are largely heritable, and have been increasingly utilized as (intermediate) phenotypes in genetic association studies. To date, imaging genetic studies have mostly focused on discovering isolated genetic effects, typically ignoring potential interactions with non-genetic variables such as disease risk factors, environmental exposures, and epigenetic markers. However, identifying significant interaction effects is critical for revealing the true relationship between genetic and phenotypic variables, and shedding light on disease mechanisms. In this paper, we present a general kernel machine based method for detecting effects of interaction between multidimensional variable sets. This method can model the joint and epistatic effect of a collection of single nucleotide polymorphisms (SNPs), accommodate multiple factors that potentially moderate genetic influences, and test for nonlinear interactions between sets of variables in a flexible framework. As a demonstration of application, we applied the method to data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to detect the effects of the interactions between candidate Alzheimer's disease (AD) risk genes and a collection of cardiovascular disease (CVD) risk factors, on hippocampal volume measurements derived from structural brain magnetic resonance imaging (MRI) scans. Our method identified that two genes, CR1 and EPHA1, demonstrate significant interactions with CVD risk factors on hippocampal volume, suggesting that CR1 and EPHA1 may play a role in influencing AD-related neurodegeneration in the presence of CVD risks. PMID:25600633

Towards systems genetic analyses in barley: Integration of phenotypic, expression and genotype data into GeneNetwork

PubMed Central

Druka, Arnis; Druka, Ilze; Centeno, Arthur G; Li, Hongqiang; Sun, Zhaohui; Thomas, William TB; Bonar, Nicola; Steffenson, Brian J; Ullrich, Steven E; Kleinhofs, Andris; Wise, Roger P; Close, Timothy J; Potokina, Elena; Luo, Zewei; Wagner, Carola; Schweizer, Günther F; Marshall, David F; Kearsey, Michael J; Williams, Robert W; Waugh, Robbie

2008-01-01

Background A typical genetical genomics experiment results in four separate data sets; genotype, gene expression, higher-order phenotypic data and metadata that describe the protocols, processing and the array platform. Used in concert, these data sets provide the opportunity to perform genetic analysis at a systems level. Their predictive power is largely determined by the gene expression dataset where tens of millions of data points can be generated using currently available mRNA profiling technologies. Such large, multidimensional data sets often have value beyond that extracted during their initial analysis and interpretation, particularly if conducted on widely distributed reference genetic materials. Besides quality and scale, access to the data is of primary importance as accessibility potentially allows the extraction of considerable added value from the same primary dataset by the wider research community. Although the number of genetical genomics experiments in different plant species is rapidly increasing, none to date has been presented in a form that allows quick and efficient on-line testing for possible associations between genes, loci and traits of interest by an entire research community. Description Using a reference population of 150 recombinant doubled haploid barley lines we generated novel phenotypic, mRNA abundance and SNP-based genotyping data sets, added them to a considerable volume of legacy trait data and entered them into the GeneNetwork . GeneNetwork is a unified on-line analytical environment that enables the user to test genetic hypotheses about how component traits, such as mRNA abundance, may interact to condition more complex biological phenotypes (higher-order traits). Here we describe these barley data sets and demonstrate some of the functionalities GeneNetwork provides as an easily accessible and integrated analytical environment for exploring them. Conclusion By integrating barley genotypic, phenotypic and mRNA abundance data sets directly within GeneNetwork's analytical environment we provide simple web access to the data for the research community. In this environment, a combination of correlation analysis and linkage mapping provides the potential to identify and substantiate gene targets for saturation mapping and positional cloning. By integrating datasets from an unsequenced crop plant (barley) in a database that has been designed for an animal model species (mouse) with a well established genome sequence, we prove the importance of the concept and practice of modular development and interoperability of software engineering for biological data sets. PMID:19017390

Characterization of Multidrug Resistant E. faecalis Strains from Pigs of Local Origin by ADSRRS-Fingerprinting and MALDI -TOF MS; Evaluation of the Compatibility of Methods Employed for Multidrug Resistance Analysis

PubMed Central

Nowakiewicz, Aneta; Ziółkowska, Grażyna; Zięba, Przemysław; Gnat, Sebastian; Trościańczyk, Aleksandra; Adaszek, Łukasz

2017-01-01

The aim of this study was to characterize multidrug resistant E. faecalis strains from pigs of local origin and to analyse the relationship between resistance and genotypic and proteomic profiles by amplification of DNA fragments surrounding rare restriction sites (ADSRRS-fingerprinting) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI -TOF MS). From the total pool of Enterococcus spp. isolated from 90 pigs, we selected 36 multidrug resistant E. faecalis strains, which represented three different phenotypic resistance profiles. Phenotypic resistance to tetracycline, macrolides, phenicols, and lincomycin and high-level resistance to aminoglycosides were confirmed by the occurrence of at least one corresponding resistance gene in each strain. Based on the analysis of the genotypic and phenotypic resistance of the strains tested, five distinct resistance profiles were generated. As a complement of this analysis, profiles of virulence genes were determined and these profiles corresponded to the phenotypic resistance profiles. The demonstration of resistance to a wide panel of antimicrobials by the strains tested in this study indicates the need of typing to determine the spread of resistance also at the local level. It seems that in the case of E. faecalis, type and scope of resistance strongly determines the genotypic pattern obtained with the ADSRRS-fingerprinting method. The ADSRRS-fingerprinting analysis showed consistency of the genetic profiles with the resistance profiles, while analysis of data with the use of the MALDI- TOF MS method did not demonstrate direct reproduction of the clustering pattern obtained with this method. Our observations were confirmed by statistical analysis (Simpson’s index of diversity, Rand and Wallace coefficients). Even though the MALDI -TOF MS method showed slightly higher discrimination power than ADSRRS-fingerprinting, only the latter method allowed reproduction of the clustering pattern of isolates based on phenotypic resistance and analysis of resistance and virulence genes (Wallace coefficient 1.0). This feature seems to be the most useful for epidemiological purposes and short-term analysis. PMID:28135327

Constraints on trait combinations explain climatic drivers of biodiversity: the importance of trait covariance in community assembly.

PubMed

Dwyer, John M; Laughlin, Daniel C

2017-07-01

Trade-offs maintain diversity and structure communities along environmental gradients. Theory indicates that if covariance among functional traits sets a limit on the number of viable trait combinations in a given environment, then communities with strong multidimensional trait constraints should exhibit low species diversity. We tested this prediction in winter annual plant assemblages along an aridity gradient using multilevel structural equation modelling. Univariate and multivariate functional diversity measures were poorly explained by aridity, and were surprisingly poor predictors of community richness. By contrast, the covariance between maximum height and seed mass strengthened along the aridity gradient, and was strongly associated with richness declines. Community richness had a positive effect on local neighbourhood richness, indicating that climate effects on trait covariance indirectly influence diversity at local scales. We present clear empirical evidence that declines in species richness along gradients of environmental stress can be due to increasing constraints on multidimensional phenotypes. © 2017 John Wiley & Sons Ltd/CNRS.

Changes in Domain Specific Self-Perception amongst Young People with Intellectual Disability: A Longitudinal Study

ERIC Educational Resources Information Center

O'Byrne, Clara; Muldoon, Orla T.

2018-01-01

This study examines the changes that occur in multidimensional self-concept of adolescents with a diagnosis of intellectual disabilities, across gender and category of intellectual disability (borderline, mild, moderate) groups. A sample of 54 young people completed the Harter Self-Perception Profile. Using a three-wave longitudinal study…

From Career Decision-Making Styles to Career Decision-Making Profiles: A Multidimensional Approach

ERIC Educational Resources Information Center

Gati, Itamar; Landman, Shiri; Davidovitch, Shlomit; Asulin-Peretz, Lisa; Gadassi, Reuma

2010-01-01

Previous research on individual differences in career decision-making processes has often focused on classifying individuals into a few types of decision-making "styles" based on the most dominant trait or characteristic of their approach to the decision process (e.g., rational, intuitive, dependent; Harren, 1979). In this research, an…

Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration.

PubMed

Arneson, Douglas; Bhattacharya, Anindya; Shu, Le; Mäkinen, Ville-Petteri; Yang, Xia

2016-09-09

Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development. To make the Mergeomics pipeline available to a wider research community, we have implemented an online, user-friendly web server ( http://mergeomics. idre.ucla.edu/ ). The web server features a modular implementation of the Mergeomics pipeline with detailed tutorials. Additionally, it provides curated genomic resources including tissue-specific expression quantitative trait loci, ENCODE functional annotations, biological pathways, and molecular networks, and offers interactive visualization of analytical results. Multiple computational tools including Marker Dependency Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted Key Driver Analysis (wKDA) can be used separately or in flexible combinations. User-defined summary-level genomic association datasets (e.g., genetic, transcriptomic, epigenomic) related to a particular disease or phenotype can be uploaded and computed real-time to yield biologically interpretable results, which can be viewed online and downloaded for later use. Our Mergeomics web server offers researchers flexible and user-friendly tools to facilitate integration of multidimensional data into holistic views of disease mechanisms in the form of tissue-specific key regulators, biological pathways, and gene networks.

Characterising the latent structure and organisation of self-reported thoughts, feelings and behaviours in adolescents and young adults

PubMed Central

Neufeld, Sharon; Jones, Peter B.; Fonagy, Peter; Bullmore, Edward T.; Dolan, Raymond J.; Moutoussis, Michael; Toseeb, Umar; Goodyer, Ian M.

2017-01-01

Little is known about the underlying relationships between self-reported mental health items measuring both positive and negative emotional and behavioural symptoms at the population level in young people. Improved measurement of the full range of mental well-being and mental illness may aid in understanding the aetiological substrates underlying the development of both mental wellness as well as specific psychiatric diagnoses. A general population sample aged 14 to 24 years completed self-report questionnaires on anxiety, depression, psychotic-like symptoms, obsessionality and well-being. Exploratory and confirmatory factor models for categorical data and latent profile analyses were used to evaluate the structure of both mental wellness and illness items. First order, second order and bifactor structures were evaluated on 118 self-reported items obtained from 2228 participants. A bifactor solution was the best fitting latent variable model with one general latent factor termed ‘distress’ and five ‘distress independent’ specific factors defined as self-confidence, antisocial behaviour, worry, aberrant thinking, and mood. Next, six distinct subgroups were derived from a person-centred latent profile analysis of the factor scores. Finally, concurrent validity was assessed using information on hazardous behaviours (alcohol use, substance misuse, self-harm) and treatment for mental ill health: both discriminated between the latent traits and latent profile subgroups. The findings suggest a complex, multidimensional mental health structure in the youth population rather than the previously assumed first or second order factor structure. Additionally, the analysis revealed a low hazardous behaviour/low mental illness risk subgroup not previously described. Population sub-groups show greater validity over single variable factors in revealing mental illness risks. In conclusion, our findings indicate that the structure of self reported mental health is multidimensional in nature and uniquely finds improved prediction to mental illness risk within person-centred subgroups derived from the multidimensional latent traits. PMID:28403164

Characterising the latent structure and organisation of self-reported thoughts, feelings and behaviours in adolescents and young adults.

PubMed

St Clair, Michelle C; Neufeld, Sharon; Jones, Peter B; Fonagy, Peter; Bullmore, Edward T; Dolan, Raymond J; Moutoussis, Michael; Toseeb, Umar; Goodyer, Ian M

2017-01-01

Little is known about the underlying relationships between self-reported mental health items measuring both positive and negative emotional and behavioural symptoms at the population level in young people. Improved measurement of the full range of mental well-being and mental illness may aid in understanding the aetiological substrates underlying the development of both mental wellness as well as specific psychiatric diagnoses. A general population sample aged 14 to 24 years completed self-report questionnaires on anxiety, depression, psychotic-like symptoms, obsessionality and well-being. Exploratory and confirmatory factor models for categorical data and latent profile analyses were used to evaluate the structure of both mental wellness and illness items. First order, second order and bifactor structures were evaluated on 118 self-reported items obtained from 2228 participants. A bifactor solution was the best fitting latent variable model with one general latent factor termed 'distress' and five 'distress independent' specific factors defined as self-confidence, antisocial behaviour, worry, aberrant thinking, and mood. Next, six distinct subgroups were derived from a person-centred latent profile analysis of the factor scores. Finally, concurrent validity was assessed using information on hazardous behaviours (alcohol use, substance misuse, self-harm) and treatment for mental ill health: both discriminated between the latent traits and latent profile subgroups. The findings suggest a complex, multidimensional mental health structure in the youth population rather than the previously assumed first or second order factor structure. Additionally, the analysis revealed a low hazardous behaviour/low mental illness risk subgroup not previously described. Population sub-groups show greater validity over single variable factors in revealing mental illness risks. In conclusion, our findings indicate that the structure of self reported mental health is multidimensional in nature and uniquely finds improved prediction to mental illness risk within person-centred subgroups derived from the multidimensional latent traits.

Density Large Deviations for Multidimensional Stochastic Hyperbolic Conservation Laws

NASA Astrophysics Data System (ADS)

Barré, J.; Bernardin, C.; Chetrite, R.

2018-02-01

We investigate the density large deviation function for a multidimensional conservation law in the vanishing viscosity limit, when the probability concentrates on weak solutions of a hyperbolic conservation law. When the mobility and diffusivity matrices are proportional, i.e. an Einstein-like relation is satisfied, the problem has been solved in Bellettini and Mariani (Bull Greek Math Soc 57:31-45, 2010). When this proportionality does not hold, we compute explicitly the large deviation function for a step-like density profile, and we show that the associated optimal current has a non trivial structure. We also derive a lower bound for the large deviation function, valid for a more general weak solution, and leave the general large deviation function upper bound as a conjecture.

Metabolic syndrome and metabolic risk profile according to polycystic ovary syndrome phenotype.

PubMed

Bil, Enes; Dilbaz, Berna; Cirik, Derya Akdag; Ozelci, Runa; Ozkaya, Enis; Dilbaz, Serdar

2016-07-01

It is unknown which phenotype of polycystic ovary syndrome (PCOS) has a greater metabolic risk and how to detect this risk. The aim of this study was therefore to compare the incidence of metabolic syndrome (MetS) and metabolic risk profile (MRP) for different phenotypes. A total of 100 consecutive newly diagnosed PCOS women in a tertiary referral hospital were recruited. Patients were classified into four phenotypes according to the Rotterdam criteria, on the presence of at least two of the three criteria hyperandrogenism (H), oligo/anovulation (O) and PCO appearance (P): phenotype A, H + O + P; phenotype B, H + O; phenotype C, H + P; phenotype D, O + P. Prevalence of MetS and MRP were compared among the four groups. Based on Natural Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, MetS prevalence was higher in phenotypes A and B (29.6% and 34.5%) compared with the other phenotypes (10.0% and 8.3%; P < 0.001). Although the prevalence of obesity was similar, the number of patients with homeostatic model assessment insulin resistance index (HOMA-IR) >3.8 was significantly higher in androgenic PCOS phenotypes. After logistic regression analysis, visceral adiposity index (VAI) was the only independent predictor of MetS in PCOS (P = 0.002). VAI was also significantly higher in phenotype B, when compared with the others (P < 0.01). Phenotypes A and B had the highest risk of MetS among the four phenotypes, and VAI may be a predictor of metabolic risk in PCOS women. © 2016 Japan Society of Obstetrics and Gynecology.

Racial Identity, Phenotype, and Self-Esteem among Biracial Polynesian/White Individuals

ERIC Educational Resources Information Center

Allen, G. E. Kawika; Garriott, Patton O.; Reyes, Carla J.; Hsieh, Catherine

2013-01-01

This study examined racial identity, self-esteem, and phenotype among biracial Polynesian/White adults. Eighty-four Polynesian/White persons completed the Biracial Identity Attitude Scale, the Rosenberg Self-Esteem Inventory, and a Polynesian phenotype scale. Profile analyses showed participants identified more with their Polynesian parent. A…

Platform for combined analysis of functional and biomolecular phenotypes of the same cell.

PubMed

Kelbauskas, L; Ashili, S; Zeng, J; Rezaie, A; Lee, K; Derkach, D; Ueberroth, B; Gao, W; Paulson, T; Wang, H; Tian, Y; Smith, D; Reid, B; Meldrum, Deirdre R

2017-03-16

Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression.

Classification and prediction of toxicity of chemicals using an automated phenotypic profiling of Caenorhabditis elegans.

PubMed

Gao, Shan; Chen, Weiyang; Zeng, Yingxin; Jing, Haiming; Zhang, Nan; Flavel, Matthew; Jois, Markandeya; Han, Jing-Dong J; Xian, Bo; Li, Guojun

2018-04-18

Traditional toxicological studies have relied heavily on various animal models to understand the effect of various compounds in a biological context. Considering the great cost, complexity and time involved in experiments using higher order organisms. Researchers have been exploring alternative models that avoid these disadvantages. One example of such a model is the nematode Caenorhabditis elegans. There are some advantages of C. elegans, such as small size, short life cycle, well defined genome, ease of maintenance and efficient reproduction. As these benefits allow large scale studies to be initiated with relative ease, the problem of how to efficiently capture, organize and analyze the resulting large volumes of data must be addressed. We have developed a new method for quantitative screening of chemicals using C. elegans. 33 features were identified for each chemical treatment. The compounds with different toxicities were shown to alter the phenotypes of C. elegans in distinct and detectable patterns. We found that phenotypic profiling revealed conserved functions to classify and predict the toxicity of different chemicals. Our results demonstrate the power of phenotypic profiling in C. elegans under different chemical environments.

Cardiovascular and metabolic profiles amongst different polycystic ovary syndrome phenotypes: who is really at risk?

PubMed

Daan, Nadine M P; Louwers, Yvonne V; Koster, Maria P H; Eijkemans, Marinus J C; de Rijke, Yolanda B; Lentjes, Eef W G; Fauser, Bart C J M; Laven, Joop S E

2014-11-01

To study the cardiometabolic profile characteristics and compare the prevalence of cardiovascular (CV) risk factors between women with different polycystic ovary syndrome (PCOS) phenotypes. A cross-sectional multicenter study analyzing 2,288 well phenotyped women with PCOS. Specialized reproductive outpatient clinic. Women of reproductive age (18-45 years) diagnosed with PCOS. Women suspected of oligo- or anovulation underwent a standardized screening consisting of a systematic medical and reproductive history taking, anthropometric measurements, and transvaginal ultrasonography followed by an extensive endocrinologic/metabolic evaluation. Differences in cardiometabolic profile characteristics and CV risk factor prevalence between women with different PCOS phenotypes, i.e., obesity/overweight, hypertension, insulin resistance, dyslipidemia, and metabolic syndrome. Women with hyperandrogenic PCOS (n=1,219; 53.3% of total) presented with a worse cardiometabolic profile and a higher prevalence of CV risk factors, such as obesity and overweight, insulin resistance, and metabolic syndrome, compared with women with nonhyperandrogenic PCOS. In women with nonhyperandrogenic PCOS overweight/obesity (28.5%) and dyslipidemia (low-density lipoprotein cholesterol≥3.0 mmol/L; 52.2%) were highly prevalent. Women with hyperandrogenic PCOS have a worse cardiometabolic profile and higher prevalence of CV risk factors compared with women with nonhyperandrogenic PCOS. However, all women with PCOS should be screened for the presence of CV risk factors, since the frequently found derangements at a young age imply an elevated risk for the development of CV disease later in life. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Prioritization of candidate disease genes by topological similarity between disease and protein diffusion profiles.

PubMed

Zhu, Jie; Qin, Yufang; Liu, Taigang; Wang, Jun; Zheng, Xiaoqi

2013-01-01

Identification of gene-phenotype relationships is a fundamental challenge in human health clinic. Based on the observation that genes causing the same or similar phenotypes tend to correlate with each other in the protein-protein interaction network, a lot of network-based approaches were proposed based on different underlying models. A recent comparative study showed that diffusion-based methods achieve the state-of-the-art predictive performance. In this paper, a new diffusion-based method was proposed to prioritize candidate disease genes. Diffusion profile of a disease was defined as the stationary distribution of candidate genes given a random walk with restart where similarities between phenotypes are incorporated. Then, candidate disease genes are prioritized by comparing their diffusion profiles with that of the disease. Finally, the effectiveness of our method was demonstrated through the leave-one-out cross-validation against control genes from artificial linkage intervals and randomly chosen genes. Comparative study showed that our method achieves improved performance compared to some classical diffusion-based methods. To further illustrate our method, we used our algorithm to predict new causing genes of 16 multifactorial diseases including Prostate cancer and Alzheimer's disease, and the top predictions were in good consistent with literature reports. Our study indicates that integration of multiple information sources, especially the phenotype similarity profile data, and introduction of global similarity measure between disease and gene diffusion profiles are helpful for prioritizing candidate disease genes. Programs and data are available upon request.

Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

PubMed Central

Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

2014-01-01

This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving.

PubMed

Han, Qing; Bradshaw, Elizabeth M; Nilsson, Björn; Hafler, David A; Love, J Christopher

2010-06-07

The large diversity of cells that comprise the human immune system requires methods that can resolve the individual contributions of specific subsets to an immunological response. Microengraving is process that uses a dense, elastomeric array of microwells to generate microarrays of proteins secreted from large numbers of individual live cells (approximately 10(4)-10(5) cells/assay). In this paper, we describe an approach based on this technology to quantify the rates of secretion from single immune cells. Numerical simulations of the microengraving process indicated an operating regime between 30 min-4 h that permits quantitative analysis of the rates of secretion. Through experimental validation, we demonstrate that microengraving can provide quantitative measurements of both the frequencies and the distribution in rates of secretion for up to four cytokines simultaneously released from individual viable primary immune cells. The experimental limits of detection ranged from 0.5 to 4 molecules/s for IL-6, IL-17, IFNgamma, IL-2, and TNFalpha. These multidimensional measures resolve the number and intensities of responses by cells exposed to stimuli with greater sensitivity than single-parameter assays for cytokine release. We show that cells from different donors exhibit distinct responses based on both the frequency and magnitude of cytokine secretion when stimulated under different activating conditions. Primary T cells with specific profiles of secretion can also be recovered after microengraving for subsequent expansion in vitro. These examples demonstrate the utility of quantitative, multidimensional profiles of single cells for analyzing the diversity and dynamics of immune responses in vitro and for identifying rare cells from clinical samples.

A latent modeling approach to genotype–phenotype relationships: maternal problem behavior clusters, prenatal smoking, and MAOA genotype

PubMed Central

Mustanski, B.; Metzger, A.; Pine, D. S.; Kistner-Griffin, E.; Cook, E.; Wakschlag, L. S.

2013-01-01

This study illustrates the application of a latent modeling approach to genotype–phenotype relationships and gene×environment interactions, using a novel, multidimensional model of adult female problem behavior, including maternal prenatal smoking. The gene of interest is the mono-amine oxidase A (MAOA) gene which has been well studied in relation to antisocial behavior. Participants were adult women (N=192) who were sampled from a prospective pregnancy cohort of non-Hispanic, white individuals recruited from a neighborhood health clinic. Structural equation modeling was used to model a female problem behavior phenotype, which included conduct problems, substance use, impulsive-sensation seeking, interpersonal aggression, and prenatal smoking. All of the female problem behavior dimensions clustered together strongly, with the exception of prenatal smoking. A main effect of MAOA genotype and a MAOA× physical maltreatment interaction were detected with the Conduct Problems factor. Our phenotypic model showed that prenatal smoking is not simply a marker of other maternal problem behaviors. The risk variant in the MAOA main effect and interaction analyses was the high activity MAOA genotype, which is discrepant from consensus findings in male samples. This result contributes to an emerging literature on sex-specific interaction effects for MAOA. PMID:22610759

Reliability of Automated Biochemical Identification of Burkholderia pseudomallei Is Regionally Dependent

PubMed Central

Podin, Yuwana; Kaestli, Mirjam; McMahon, Nicole; Hennessy, Jann; Ngian, Hie Ung; Wong, Jin Shyan; Mohana, Anand; Wong, See Chang; William, Timothy; Mayo, Mark; Baird, Robert W.

2013-01-01

Misidentifications of Burkholderia pseudomallei as Burkholderia cepacia by Vitek 2 have occurred. Multidimensional scaling ordination of biochemical profiles of 217 Malaysian and Australian B. pseudomallei isolates found clustering of misidentified B. pseudomallei isolates from Malaysian Borneo. Specificity of B. pseudomallei identification in Vitek 2 and potentially other automated identification systems is regionally dependent. PMID:23784129

Reliability of automated biochemical identification of Burkholderia pseudomallei is regionally dependent.

PubMed

Podin, Yuwana; Kaestli, Mirjam; McMahon, Nicole; Hennessy, Jann; Ngian, Hie Ung; Wong, Jin Shyan; Mohana, Anand; Wong, See Chang; William, Timothy; Mayo, Mark; Baird, Robert W; Currie, Bart J

2013-09-01

Misidentifications of Burkholderia pseudomallei as Burkholderia cepacia by Vitek 2 have occurred. Multidimensional scaling ordination of biochemical profiles of 217 Malaysian and Australian B. pseudomallei isolates found clustering of misidentified B. pseudomallei isolates from Malaysian Borneo. Specificity of B. pseudomallei identification in Vitek 2 and potentially other automated identification systems is regionally dependent.

A Practical Illustration of Multidimensional Diagnostic Skills Profiling: Comparing Results from Confirmatory Factor Analysis and Diagnostic Classification Models

ERIC Educational Resources Information Center

Kunina-Habenicht, Olga; Rupp, Andre A.; Wilhelm, Oliver

2009-01-01

In recent years there has been an increasing international interest in fine-grained diagnostic inferences on multiple skills for formative purposes. A successful provision of such inferences that support meaningful instructional decision-making requires (a) careful diagnostic assessment design coupled with (b) empirical support for the structure…

Identity Profiles in Lesbian, Gay, and Bisexual Youth: The Role of Family Influences

ERIC Educational Resources Information Center

Bregman, Hallie R.; Malik, Neena M.; Page, Matthew J. L.; Makynen, Emily; Lindahl, Kristin M.

2013-01-01

Sexual identity development is a central task of adolescence and young adulthood and can be especially challenging for sexual minority youth. Recent research has moved from a stage model of identity development in lesbian, gay, and bisexual (LGB) youth to examining identity in a non-linear, multidimensional manner. In addition, although families…

Insights into the Diversity of Attitudes Concerning Evolution and Creation: A Multidimensional Approach

ERIC Educational Resources Information Center

Konneman, Christiane; Asshoff, Roman; Hammann, Marcus

2016-01-01

The main aim of this paper is to describe high school students' attitudes concerning evolution and creation, with a focus on (1) attitudes toward evolutionary theory, (2) attitudes toward the Biblical accounts of creation, (3) creationist beliefs, and (4) scientistic beliefs. Latent class analyses revealed seven attitude profiles in a sample of…

Evolutionary branching under multi-dimensional evolutionary constraints.

PubMed

Ito, Hiroshi; Sasaki, Akira

2016-10-21

The fitness of an existing phenotype and of a potential mutant should generally depend on the frequencies of other existing phenotypes. Adaptive evolution driven by such frequency-dependent fitness functions can be analyzed effectively using adaptive dynamics theory, assuming rare mutation and asexual reproduction. When possible mutations are restricted to certain directions due to developmental, physiological, or physical constraints, the resulting adaptive evolution may be restricted to subspaces (constraint surfaces) with fewer dimensionalities than the original trait spaces. To analyze such dynamics along constraint surfaces efficiently, we develop a Lagrange multiplier method in the framework of adaptive dynamics theory. On constraint surfaces of arbitrary dimensionalities described with equality constraints, our method efficiently finds local evolutionarily stable strategies, convergence stable points, and evolutionary branching points. We also derive the conditions for the existence of evolutionary branching points on constraint surfaces when the shapes of the surfaces can be chosen freely. Copyright © 2016 Elsevier Ltd. All rights reserved.

Demographic, genetic and phenotypic characteristics of centenarians in Italy: Focus on gender differences.

PubMed

Montesanto, Alberto; De Rango, Francesco; Pirazzini, Chiara; Guidarelli, Giulia; Domma, Filippo; Franceschi, Claudio; Passarino, Giuseppe

2017-07-01

An impressive and coherent series of epidemiological data from different populations (New England Americans, Mormons, Ashkenazi Jewish, Icelandic, Okinawan Japanese, Italians) suggests that long-lived subjects able to reach the extreme limits of human life, such as centenarians and supercentenarians, represent an extraordinary and informative model to identify the mechanisms responsible for healthy aging and human longevity. In most studies, genetic, demographic and phenotypic characteristics of longevity are discussed separately. However, longevity is a very complex trait due to the complicated interactions of numerous genetic and environmental factors. It is therefore necessary to analyse centenarians with a multidimensional approach, trying to consider different aspects simultaneously. In this review we will focus on Italian centenarians, who have been extensively studied for many years with different approaches, in order to show their peculiarities and the emerging data from the studies carried out on this exceptional population. Copyright © 2017 Elsevier B.V. All rights reserved.

High throughput gene expression profiling: a molecular approach to integrative physiology

PubMed Central

Liang, Mingyu; Cowley, Allen W; Greene, Andrew S

2004-01-01

Integrative physiology emphasizes the importance of understanding multiple pathways with overlapping, complementary, or opposing effects and their interactions in the context of intact organisms. The DNA microarray technology, the most commonly used method for high-throughput gene expression profiling, has been touted as an integrative tool that provides insights into regulatory pathways. However, the physiology community has been slow in acceptance of these techniques because of early failure in generating useful data and the lack of a cohesive theoretical framework in which experiments can be analysed. With recent advances in both technology and analysis, we propose a concept of multidimensional integration of physiology that incorporates data generated by DNA microarray and other functional, genomic, and proteomic approaches to achieve a truly integrative understanding of physiology. Analysis of several studies performed in simpler organisms or in mammalian model animals supports the feasibility of such multidimensional integration and demonstrates the power of DNA microarray as an indispensable molecular tool for such integration. Evaluation of DNA microarray techniques indicates that these techniques, despite limitations, have advanced to a point where the question-driven profiling research has become a feasible complement to the conventional, hypothesis-driven research. With a keen sense of homeostasis, global regulation, and quantitative analysis, integrative physiologists are uniquely positioned to apply these techniques to enhance the understanding of complex physiological functions. PMID:14678487

Transcriptomic and phenotypic profiling in developing zebrafish exposed to thyroid hormone receptor agonists

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

Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.

There is a need to develop novel, high-throughput screening and prioritization methods to identify chemicals with adverse estrogen, androgen, and thyroid activity to protect human health and the environment and is of interest to the Endocrine Disruptor Screening Program. The current aim is to explore the utility of zebrafish as a testing paradigm to classify endocrine activity using phenotypically anchored transcriptome profiling. Transcriptome analysis was conducted on embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at a concentration that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of the animals exposed. Analysis of the top 1000more » significant differentially expressed transcripts across all treatments identified a unique transcriptional and phenotypic profile for thyroid hormone receptor agonists, which can be used as a biomarker screen for potential thyroid hormone agonists.« less

Toward a deeper characterization of the social phenotype of Williams syndrome: The association between personality and social drive.

PubMed

Ng, Rowena; Järvinen, Anna; Bellugi, Ursula

2014-08-01

Previous research has robustly established a Williams syndrome (WS) specific personality profile, predominantly characterized a gregarious, people-oriented, and tense predisposition. Extending this work, the aims of the current, cross-sectional study were two-fold: (1) to elucidate the stability of personality characteristics in individuals with WS and typically developing (TD) comparisons across development, and (2) to explore the personality attributes that may be related to the respective profiles of social functioning characterizing the two groups, which is currently poorly understood. The sample comprised of participants with WS and TD matched on chronological age. The test battery included the Multidimensional Personality Questionnaire (MPQ) and the Salk Institute Sociability Questionnaire (SISQ), an index of real-life social behavior. The main results showed that compared to the TD individuals, the WS group were consistently rated higher in Social Closeness, and this trait remained stable across development. Interpersonal behaviors were best predicted by Social Closeness in WS and by Social Potency in TD. Regression analysis highlighted that while a central motive underlying the increased drive toward social interaction in individuals with WS pertains to a desire to form affectionate relationships, TD individuals by contrast are motivated by a desire to exert social influence over others (leadership, social-dominance) and Well-Being (positive emotional disposition). In conclusion, these findings provide novel insight into social motivational factors underpinning the WS social behavior in real life, and contribute toward a deeper characterization of the WS affiliative drive. We suggest potential areas for behavioral intervention targeting improved social adjustment in individuals with WS. Copyright © 2014 Elsevier Ltd. All rights reserved.

ICM: a web server for integrated clustering of multi-dimensional biomedical data.

PubMed

He, Song; He, Haochen; Xu, Wenjian; Huang, Xin; Jiang, Shuai; Li, Fei; He, Fuchu; Bo, Xiaochen

2016-07-08

Large-scale efforts for parallel acquisition of multi-omics profiling continue to generate extensive amounts of multi-dimensional biomedical data. Thus, integrated clustering of multiple types of omics data is essential for developing individual-based treatments and precision medicine. However, while rapid progress has been made, methods for integrated clustering are lacking an intuitive web interface that facilitates the biomedical researchers without sufficient programming skills. Here, we present a web tool, named Integrated Clustering of Multi-dimensional biomedical data (ICM), that provides an interface from which to fuse, cluster and visualize multi-dimensional biomedical data and knowledge. With ICM, users can explore the heterogeneity of a disease or a biological process by identifying subgroups of patients. The results obtained can then be interactively modified by using an intuitive user interface. Researchers can also exchange the results from ICM with collaborators via a web link containing a Project ID number that will directly pull up the analysis results being shared. ICM also support incremental clustering that allows users to add new sample data into the data of a previous study to obtain a clustering result. Currently, the ICM web server is available with no login requirement and at no cost at http://biotech.bmi.ac.cn/icm/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Platform for combined analysis of functional and biomolecular phenotypes of the same cell

PubMed Central

Kelbauskas, L.; Ashili, S.; Zeng, J.; Rezaie, A.; Lee, K.; Derkach, D.; Ueberroth, B.; Gao, W.; Paulson, T.; Wang, H.; Tian, Y.; Smith, D.; Reid, B.; Meldrum, Deirdre R.

2017-01-01

Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression. PMID:28300162

Dietary glycemic index is associated with less favorable anthropometric and metabolic profiles in polycystic ovary syndrome women with different phenotypes.

PubMed

Graff, Scheila Karen; Mário, Fernanda Missio; Alves, Bruna Cherubini; Spritzer, Poli Mara

2013-10-01

To compare glycemic index (GI) in the usual diet of polycystic ovary syndrome (PCOS) and control women and to investigate whether dietary GI is associated with body composition and anthropometric and metabolic variables across PCOS phenotypes. Cross-sectional study. University hospital outpatient clinic. Sixty-one women with PCOS and 44 nonhirsute women with ovulatory cycles. Metabolic work-up, biochemical and hormonal assays, assessment of body composition and rest metabolic rate, physical activity (pedometer), and food consumption (food frequency questionnaire). GI, glycemic load, dietary intake, and hormone and metabolic profile in PCOS versus control and in PCOS women stratified by tertiles of GI and PCOS phenotype. Mean age was 23.7 ± 6.3 years. Participants with PCOS had higher body fat percentage, fasting insulin, insulin resistance, lipid accumulation product, and androgen levels compared with control women. PCOS and control women in the highest tertile of GI had higher body mass index and waist circumference than those in the lowest tertile. Dietary GI was higher in the classic PCOS group. Obesity and this more severe PCOS phenotype explained 28.3% of variance in dietary GI. Dietary GI is increased in the classic PCOS phenotype and associated with a less favorable anthropometric and metabolic profile. Obesity and classic PCOS phenotype are age-independent predictors of higher dietary GI. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Serum Biochemical Phenotypes in the Domestic Dog

PubMed Central

Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A.

2016-01-01

The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

Computational Models for Prediction of Yeast Strain Potential for Winemaking from Phenotypic Profiles

PubMed Central

Umek, Lan; Fonseca, Elza; Drumonde-Neves, João; Dequin, Sylvie; Zupan, Blaz; Schuller, Dorit

2013-01-01

Saccharomyces cerevisiae strains from diverse natural habitats harbour a vast amount of phenotypic diversity, driven by interactions between yeast and the respective environment. In grape juice fermentations, strains are exposed to a wide array of biotic and abiotic stressors, which may lead to strain selection and generate naturally arising strain diversity. Certain phenotypes are of particular interest for the winemaking industry and could be identified by screening of large number of different strains. The objective of the present work was to use data mining approaches to identify those phenotypic tests that are most useful to predict a strain's potential for winemaking. We have constituted a S. cerevisiae collection comprising 172 strains of worldwide geographical origins or technological applications. Their phenotype was screened by considering 30 physiological traits that are important from an oenological point of view. Growth in the presence of potassium bisulphite, growth at 40°C, and resistance to ethanol were mostly contributing to strain variability, as shown by the principal component analysis. In the hierarchical clustering of phenotypic profiles the strains isolated from the same wines and vineyards were scattered throughout all clusters, whereas commercial winemaking strains tended to co-cluster. Mann-Whitney test revealed significant associations between phenotypic results and strain's technological application or origin. Naïve Bayesian classifier identified 3 of the 30 phenotypic tests of growth in iprodion (0.05 mg/mL), cycloheximide (0.1 µg/mL) and potassium bisulphite (150 mg/mL) that provided most information for the assignment of a strain to the group of commercial strains. The probability of a strain to be assigned to this group was 27% using the entire phenotypic profile and increased to 95%, when only results from the three tests were considered. Results show the usefulness of computational approaches to simplify strain selection procedures. PMID:23874393

A kernel machine method for detecting effects of interaction between multidimensional variable sets: an imaging genetics application.

PubMed

Ge, Tian; Nichols, Thomas E; Ghosh, Debashis; Mormino, Elizabeth C; Smoller, Jordan W; Sabuncu, Mert R

2015-04-01

Measurements derived from neuroimaging data can serve as markers of disease and/or healthy development, are largely heritable, and have been increasingly utilized as (intermediate) phenotypes in genetic association studies. To date, imaging genetic studies have mostly focused on discovering isolated genetic effects, typically ignoring potential interactions with non-genetic variables such as disease risk factors, environmental exposures, and epigenetic markers. However, identifying significant interaction effects is critical for revealing the true relationship between genetic and phenotypic variables, and shedding light on disease mechanisms. In this paper, we present a general kernel machine based method for detecting effects of the interaction between multidimensional variable sets. This method can model the joint and epistatic effect of a collection of single nucleotide polymorphisms (SNPs), accommodate multiple factors that potentially moderate genetic influences, and test for nonlinear interactions between sets of variables in a flexible framework. As a demonstration of application, we applied the method to the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to detect the effects of the interactions between candidate Alzheimer's disease (AD) risk genes and a collection of cardiovascular disease (CVD) risk factors, on hippocampal volume measurements derived from structural brain magnetic resonance imaging (MRI) scans. Our method identified that two genes, CR1 and EPHA1, demonstrate significant interactions with CVD risk factors on hippocampal volume, suggesting that CR1 and EPHA1 may play a role in influencing AD-related neurodegeneration in the presence of CVD risks. Copyright © 2015 Elsevier Inc. All rights reserved.

Psychometric analysis of the Multidimensional Fatigue Inventory in a sample of persons treated for myocardial infarction.

PubMed

Fredriksson-Larsson, Ulla; Brink, Eva; Alsén, Pia; Falk, Kristin; Lundgren-Nilsson, Åsa

2015-01-01

Fatigue after myocardial infarction is a frequent and distressing symptom in the early recovery phase. The purpose of this study is to psychometrically evaluate the Multidimensional Fatigue Inventory (MFI-20). The MFI-20 was evaluated using Rasch analysis. The result showed that the MFI-20 can be used to obtain a global score reflecting an underlying unidimensional trait of fatigue; a transformation of the summarized raw scale scores into interval scale scores could be made. Also, 4 of the 5 original dimensions separately fitted the Rasch model. Calculation of a global score increases the possibility of identifying persons experiencing fatigue after myocardial infarction, and using the MFI-20 dimension scores increases the possibility of determining each person's specific fatigue profile.

Korean Early Childhood Educators' Multi-Dimensional Teacher Self-Efficacy and ECE Center Climate and Depression Severity in Teachers as Contributing Factors

ERIC Educational Resources Information Center

Kim, Yeon Ha; Kim, Yang Eun

2010-01-01

This study investigated profiles of South Korean early childhood educators' teacher self-efficacy and contributing factors to teacher self-efficacy. The contributing factors were examined with a focus on early childhood education (ECE) center climate and depression severity in teachers as well as teacher and classroom characteristics. The results…

Trait Emotional Intelligence and University Graduation Outcomes: Using Latent Profile Analysis to Identify Students at Risk for Degree Noncompletion

ERIC Educational Resources Information Center

Keefer, Kateryna V.; Parker, James D. A.; Wood, Laura M.

2012-01-01

This study explored the utility of trait emotional intelligence (EI) for predicting students' university graduation outcomes six years after enrolment in university. At the start of the program, 1,015 newly registered students completed a brief multidimensional self-report EI assessment and provided consent to track their subsequent degree…

Assignment Choice, Effort, and Assignment Completion: Does Work Ethic Predict Those Who Choose Higher-Effort Assignments?

ERIC Educational Resources Information Center

Parkhurst, John T.; Fleisher, Matthew S.; Skinner, Christopher H.; Woehr, David J.; Hawthorn-Embree, Meredith L.

2011-01-01

After completing the Multidimensional Work-Ethic Profile (MWEP), 98 college students were given a 20-problem math computation assignment and instructed to stop working on the assignment after completing 10 problems. Next, they were allowed to choose to finish either the partially completed assignment that had 10 problems remaining or a new…

Multidimensional protein identification technology (MudPIT): technical overview of a profiling method optimized for the comprehensive proteomic investigation of normal and diseased heart tissue.

PubMed

Kislinger, Thomas; Gramolini, Anthony O; MacLennan, David H; Emili, Andrew

2005-08-01

An optimized analytical expression profiling strategy based on gel-free multidimensional protein identification technology (MudPIT) is reported for the systematic investigation of biochemical (mal)-adaptations associated with healthy and diseased heart tissue. Enhanced shotgun proteomic detection coverage and improved biological inference is achieved by pre-fractionation of excised mouse cardiac muscle into subcellular components, with each organellar fraction investigated exhaustively using multiple repeat MudPIT analyses. Functional-enrichment, high-confidence identification, and relative quantification of hundreds of organelle- and tissue-specific proteins are achieved readily, including detection of low abundance transcriptional regulators, signaling factors, and proteins linked to cardiac disease. Important technical issues relating to data validation, including minimization of artifacts stemming from biased under-sampling and spurious false discovery, together with suggestions for further fine-tuning of sample preparation, are discussed. A framework for follow-up bioinformatic examination, pattern recognition, and data mining is also presented in the context of a stringent application of MudPIT for probing fundamental aspects of heart muscle physiology as well as the discovery of perturbations associated with heart failure.

Longitudinal Patterns of Glycemic Control and Blood Pressure in Pregnant Women with Type 1 Diabetes Mellitus: Phenotypes from Functional Data Analysis.

PubMed

Szczesniak, Rhonda D; Li, Dan; Duan, Leo L; Altaye, Mekibib; Miodovnik, Menachem; Khoury, Jane C

2016-11-01

Objective  To identify phenotypes of type 1 diabetes control and associations with maternal/neonatal characteristics based on blood pressure (BP), glucose, and insulin curves during gestation, using a novel functional data analysis approach that accounts for sparse longitudinal patterns of medical monitoring during pregnancy. Methods  We performed a retrospective longitudinal cohort study of women with type 1 diabetes whose BP, glucose, and insulin requirements were monitored throughout gestation as part of a program-project grant. Scores from sparse functional principal component analysis (fPCA) were used to classify gestational profiles according to the degree of control for each monitored measure. Phenotypes created using fPCA were compared with respect to maternal and neonatal characteristics and outcome. Results  Most of the gestational profile variation in the monitored measures was explained by the first principal component (82-94%). Profiles clustered into three subgroups of high, moderate, or low heterogeneity, relative to the overall mean response. Phenotypes were associated with baseline characteristics, longitudinal changes in glycohemoglobin A1 and weight, and to pregnancy-related outcomes. Conclusion  Three distinct longitudinal patterns of glucose, insulin, and BP control were found. By identifying these phenotypes, interventions can be targeted for subgroups at highest risk for compromised outcome, to optimize diabetes management during pregnancy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Characterizing associations and dissociations between anxiety, social, and cognitive phenotypes of Williams syndrome

PubMed Central

Ng, Rowena; Järvinen, Anna; Bellugi, Ursula

2014-01-01

Williams syndrome (WS) is a neurogenetic disorder known for its “hypersocial” phenotype and a complex profile of anxieties. The anxieties are poorly understood specifically in relation to the social-emotional and cognitive profiles. To address this gap, we employed a Wechsler intelligence test, the Brief Symptom Inventory, Beck Anxiety Inventory, and Salk Institute Sociability Questionnaire, to (1) examine how anxiety symptoms distinguish individuals with WS from typically developing (TD) individuals; and (2) assess the associations between three key phenotypic features of WS: intellectual impairment, social-emotional functioning, and anxiety. The results highlighted intensified neurophysiological symptoms and subjective experiences of anxiety in WS. Moreover, whereas higher cognitive ability was positively associated with anxiety in WS, the opposite pattern characterized the TD individuals. This study provides novel insight into how the three core phenotypic features associate/dissociate in WS, specifically in terms of the contribution of cognitive and emotional functioning to anxiety symptoms. PMID:24973548

Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach.

PubMed

Hayden, Kathleen M; Kuchibhatla, Maragatha; Romero, Heather R; Plassman, Brenda L; Burke, James R; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A

2014-11-01

Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline. To evaluate patterns of cognitive performance in cognitively normal individuals to derive latent profiles associated with later onset of disease using a combination of factor analysis and latent profile analysis. The National Alzheimer Coordinating Centers collect data, including a battery of neuropsychological tests, from participants at 29 National Institute on Aging-funded Alzheimer Disease Centers across the United States. Prior factor analyses of this battery demonstrated a four-factor structure comprising memory, attention, language, and executive function. Factor scores from these analyses were used in a latent profile approach to characterize cognition among a group of cognitively normal participants (N = 3,911). Associations between latent profiles and disease outcomes an average of 3 years later were evaluated with multinomial regression models. Similar analyses were used to determine predictors of profile membership. Four groups were identified; each with distinct characteristics and significantly associated with later disease outcomes. Two groups were significantly associated with development of cognitive impairment. In post hoc analyses, both the Trail Making Test Part B, and a contrast score (Delayed Recall - Trails B), significantly predicted group membership and later cognitive impairment. Latent profile analysis is a useful method to evaluate patterns of cognition in large samples for the identification of preclinical AD phenotypes; comparable results, however, can be achieved with very sensitive tests and contrast scores. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Profiles of Adolescent Religiousness using Latent Profile Analysis: Implications for Psychopathology

PubMed Central

Longo, Gregory S.; Bray, Bethany; Kim-Spoon, Jungmeen

2017-01-01

Prior research has documented robust associations between adolescent religiousness/spirituality (R/S) and psychopathology outcomes including externalizing and internalizing symptomatology, yet no previous studies have examined these associations with adolescent R/S profiles using a person-centered approach. We examined if there are identifiable subgroups characterized by unique multidimensional patterns of R/S experiences and how these experiences may be related to externalizing and internalizing symptomatology. The sample consisted of 220 Appalachian adolescents between 12 and 18 years old who were primarily White and primarily Christian. Latent profile analysis revealed three profiles of adolescent R/S; high religiousness (28.4%), introjectors (47.6%), and low religiousness (24.0%). These profiles were differentially related to internalizing and externalizing symptomatology such that the high religiousness group was significantly lower than the introjectors with respect to internalizing and externalizing symptomatology and lower than the low religiousness group in externalizing symptomatology. Implications and suggestions for future research using person-centered approaches to better understand differential developmental trajectories of religious development are provided. PMID:28220955

Justification of Fuzzy Declustering Vector Quantization Modeling in Classification of Genotype-Image Phenotypes

NASA Astrophysics Data System (ADS)

Ng, Theam Foo; Pham, Tuan D.; Zhou, Xiaobo

2010-01-01

With the fast development of multi-dimensional data compression and pattern classification techniques, vector quantization (VQ) has become a system that allows large reduction of data storage and computational effort. One of the most recent VQ techniques that handle the poor estimation of vector centroids due to biased data from undersampling is to use fuzzy declustering-based vector quantization (FDVQ) technique. Therefore, in this paper, we are motivated to propose a justification of FDVQ based hidden Markov model (HMM) for investigating its effectiveness and efficiency in classification of genotype-image phenotypes. The performance evaluation and comparison of the recognition accuracy between a proposed FDVQ based HMM (FDVQ-HMM) and a well-known LBG (Linde, Buzo, Gray) vector quantization based HMM (LBG-HMM) will be carried out. The experimental results show that the performances of both FDVQ-HMM and LBG-HMM are almost similar. Finally, we have justified the competitiveness of FDVQ-HMM in classification of cellular phenotype image database by using hypotheses t-test. As a result, we have validated that the FDVQ algorithm is a robust and an efficient classification technique in the application of RNAi genome-wide screening image data.

Repint of "Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity".

PubMed

Tordjman, S; Cohen, D; Anderson, G M; Botbol, M; Canitano, R; Coulon, N; Roubertoux, P L

2018-06-01

Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism. Copyright © 2018. Published by Elsevier Ltd.

Customized Molecular Phenotyping by Quantitative Gene Expression and Pattern Recognition Analysis

PubMed Central

Akilesh, Shreeram; Shaffer, Daniel J.; Roopenian, Derry

2003-01-01

Description of the molecular phenotypes of pathobiological processes in vivo is a pressing need in genomic biology. We have implemented a high-throughput real-time PCR strategy to establish quantitative expression profiles of a customized set of target genes. It enables rapid, reproducible data acquisition from limited quantities of RNA, permitting serial sampling of mouse blood during disease progression. We developed an easy to use statistical algorithm—Global Pattern Recognition—to readily identify genes whose expression has changed significantly from healthy baseline profiles. This approach provides unique molecular signatures for rheumatoid arthritis, systemic lupus erythematosus, and graft versus host disease, and can also be applied to defining the molecular phenotype of a variety of other normal and pathological processes. PMID:12840047

Stirring the motivational soup: within-person latent profiles of motivation in exercise.

PubMed

Lindwall, Magnus; Ivarsson, Andreas; Weman-Josefsson, Karin; Jonsson, Linus; Ntoumanis, Nikos; Patrick, Heather; Thøgersen-Ntoumani, Cecilie; Markland, David; Teixeira, Pedro

2017-01-14

The purpose of the present study was to use a person-oriented analytical approach to identify latent motivational profiles, based on the different behavioural regulations for exercise, and to examine differences in satisfaction of basic psychological needs (competence, autonomy and relatedness) and exercise behaviour across these motivational profiles. Two samples, consisting of 1084 and 511 adults respectively, completed exercise-related measures of behavioural regulation and psychological need satisfaction as well as exercise behaviour. Latent profile analyses were used to identify motivational profiles. Six profiles, representing different combinations of regulations for exercise, were found to best represent data in both samples. Some profiles were found in both samples (e.g., low motivation profile, self-determined motivation profile and self-determined with high introjected regulation profile), whereas others were unique to each sample. In line with the Self-Determination Theory, individuals belonging to more self-determined profiles demonstrated higher scores on need satisfaction. The results support the notions of motivation being a multidimensional construct and that people have different, sometimes competing, reasons for engaging in exercise. The benefits of using person-oriented analyses to examine within-person interactions of motivation and different regulations are discussed.

NMR-based metabolic study of fruits of Physalis peruviana L. grown in eight different Peruvian ecosystems.

PubMed

Maruenda, Helena; Cabrera, Rodrigo; Cañari-Chumpitaz, Cristhian; Lopez, Juan M; Toubiana, David

2018-10-01

The berry of Physalis peruviana L. (Solanaceae) represents an important socio-economical commodity for Latin America. The absence of a clear phenotype renders it difficult to trace its place of origin. In this study, Cape gooseberries from eight different regions within the Peruvian Andes were profiled for their metabolism implementing a NMR platform. Twenty-four compounds could be unequivocally identified and sixteen quantified. One-way ANOVA and post-hoc Tukey test revealed that all of the quantified metabolites changed significantly among regions: Bambamarca I showed the most accumulated significant differences. The coefficient of variation demonstrated high phenotypic plasticity for amino acids, while sugars displayed low phenotypic plasticity. Correlation analysis highlighted the closely coordinated behavior of the amino acid profile. Finally, PLS-DA revealed a clear separation among the regions based on their metabolic profiles, accentuating the discriminatory capacity of NMR in establishing significant phytochemical differences between producing regions of the fruit of P. peruviana L. Copyright © 2018 Elsevier Ltd. All rights reserved.

Validity of the Multidimensional Fatigue Symptom Inventory-Short Form in an African American Community-Based Sample

PubMed Central

Asvat, Yasmin; Malcarne, Vanessa L.; Sadler, Georgia R.; Jacobsen, Paul B.

2014-01-01

Objectives This study examined the psychometric properties of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) in a community-based sample of African Americans. Design. A sample of 340 African Americans (116 men, 224 women) ranging in age from 18–81 years were recruited from the community (e.g., churches, health fairs, beauty salons). Participants completed a brief demographic survey, the MFSI-SF and the Positive and Negative Affect Schedule. Results The structural validity of the MFSI-SF for a community-based sample of African Americans was not supported. The five dimensions of fatigue (General, Emotional, Physical, Mental, Vigor) found for Whites in prior research were not found for African Americans in this study. Instead, fatigue, while multidimensional for African Americans, was best represented by a unique four-four profile in which general and emotional fatigue are collapsed into a single dimension and physical fatigue, mental fatigue, and vigor are relatively distinct. Hence, in the absence of modifications, the MFSI-SF cannot be considered to be structurally invariant across ethnic groups. A modified four-factor version of the MFSI-SF exhibited excellent internal consistency reliability and evidence supports its convergent validity. Using the modified four-factor version, gender and age were not meaningfully associated with MFSI-SF scores. Conclusion Future research should further examine whether modifications to the MFSI-SF would, as the findings suggest, improve its validity as a measure of multidimensional fatigue in African Americans. PMID:24527980

How Turbulence Enables Core-collapse Supernova Explosions

NASA Astrophysics Data System (ADS)

Mabanta, Quintin A.; Murphy, Jeremiah W.

2018-03-01

An important result in core-collapse supernova (CCSN) theory is that spherically symmetric, one-dimensional simulations routinely fail to explode, yet multidimensional simulations often explode. Numerical investigations suggest that turbulence eases the condition for explosion, but how it does it is not fully understood. We develop a turbulence model for neutrino-driven convection, and show that this turbulence model reduces the condition for explosions by about 30%, in concordance with multidimensional simulations. In addition, we identify which turbulent terms enable explosions. Contrary to prior suggestions, turbulent ram pressure is not the dominant factor in reducing the condition for explosion. Instead, there are many contributing factors, with ram pressure being only one of them, but the dominant factor is turbulent dissipation (TD). Primarily, TD provides extra heating, adding significant thermal pressure and reducing the condition for explosion. The source of this TD power is turbulent kinetic energy, which ultimately derives its energy from the higher potential of an unstable convective profile. Investigating a turbulence model in conjunction with an explosion condition enables insight that is difficult to glean from merely analyzing complex multidimensional simulations. An explosion condition presents a clear diagnostic to explain why stars explode, and the turbulence model allows us to explore how turbulence enables explosion. Although we find that TD is a significant contributor to successful supernova explosions, it is important to note that this work is to some extent qualitative. Therefore, we suggest ways to further verify and validate our predictions with multidimensional simulations.

Modeling lineage and phenotypic diversification in the New World monkey (Platyrrhini, Primates) radiation.

PubMed

Aristide, Leandro; Rosenberger, Alfred L; Tejedor, Marcelo F; Perez, S Ivan

2015-01-01

Adaptive radiations that have taken place in the distant past can now be more thoroughly studied with the availability of large molecular phylogenies and comparative data drawn from extant and fossil species. Platyrrhines are a good example of a major mammalian evolutionary radiation confined to a single continent, involving a relatively large temporal scale and documented by a relatively small but informative fossil record. Here, we present comparative evidence using data on extant and fossil species to explore alternative evolutionary models in an effort to better understand the process of platyrrhine lineage and phenotypic diversification. Specifically, we compare the likelihood of null models of lineage and phenotypic diversification versus various models of adaptive evolution. Moreover, we statistically explore the main ecological dimension behind the platyrrhine diversification. Contrary to the previous proposals, our study did not find evidence of a rapid lineage accumulation in the phylogenetic tree of extant platyrrhine species. However, the fossil-based diversity curve seems to show a slowdown in diversification rates toward present times. This also suggests an early high rate of extinction among lineages within crown Platyrrhini. Finally, our analyses support the hypothesis that the platyrrhine phenotypic diversification appears to be characterized by an early and profound differentiation in body size related to a multidimensional niche model, followed by little subsequent change (i.e., stasis). Copyright © 2013 Elsevier Inc. All rights reserved.

Autism spectrum disorder profile in neurofibromatosis type I.

PubMed

Garg, Shruti; Plasschaert, Ellen; Descheemaeker, Mie-Jef; Huson, Susan; Borghgraef, Martine; Vogels, Annick; Evans, D Gareth; Legius, Eric; Green, Jonathan

2015-06-01

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant single-gene disorder, in which the co-occurrence of autism spectrum disorder (ASD) has attracted considerable research interest recently with prevalence estimates of 21-40%. However, detailed characterization of the ASD behavioral phenotype in NF1 is still lacking. This study characterized the phenotypic profile of ASD symptomatology presenting in 4-16 year old children with NF1 (n = 36) using evidence from parent-rated Social Responsiveness Scale and researcher autism diagnostic observation Scale-2. Compared to IQ-matched reference groups of children with autism and ASD, the NF1 profile shows overall similarity but improved eye contact, less repetitive behaviors and better language skills.

MONET: multidimensional radiative cloud scene model

NASA Astrophysics Data System (ADS)

Chervet, Patrick

1999-12-01

All cloud fields exhibit variable structures (bulge) and heterogeneities in water distributions. With the development of multidimensional radiative models by the atmospheric community, it is now possible to describe horizontal heterogeneities of the cloud medium, to study these influences on radiative quantities. We have developed a complete radiative cloud scene generator, called MONET (French acronym for: MOdelisation des Nuages En Tridim.) to compute radiative cloud scene from visible to infrared wavelengths for various viewing and solar conditions, different spatial scales, and various locations on the Earth. MONET is composed of two parts: a cloud medium generator (CSSM -- Cloud Scene Simulation Model) developed by the Air Force Research Laboratory, and a multidimensional radiative code (SHDOM -- Spherical Harmonic Discrete Ordinate Method) developed at the University of Colorado by Evans. MONET computes images for several scenario defined by user inputs: date, location, viewing angles, wavelength, spatial resolution, meteorological conditions (atmospheric profiles, cloud types)... For the same cloud scene, we can output different viewing conditions, or/and various wavelengths. Shadowing effects on clouds or grounds are taken into account. This code is useful to study heterogeneity effects on satellite data for various cloud types and spatial resolutions, and to determine specifications of new imaging sensor.

Development of the life impact burn recovery evaluation (LIBRE) profile: assessing burn survivors' social participation.

PubMed

Kazis, Lewis E; Marino, Molly; Ni, Pengsheng; Soley Bori, Marina; Amaya, Flor; Dore, Emily; Ryan, Colleen M; Schneider, Jeff C; Shie, Vivian; Acton, Amy; Jette, Alan M

2017-10-01

Measuring the impact burn injuries have on social participation is integral to understanding and improving survivors' quality of life, yet there are no existing instruments that comprehensively measure the social participation of burn survivors. This project aimed to develop the Life Impact Burn Recovery Evaluation Profile (LIBRE), a patient-reported multidimensional assessment for understanding the social participation after burn injuries. 192 questions representing multiple social participation areas were administered to a convenience sample of 601 burn survivors. Exploratory factor analysis and confirmatory factor analysis (CFA) were used to identify the underlying structure of the data. Using item response theory methods, a Graded Response Model was applied for each identified sub-domain. The resultant multidimensional LIBRE Profile can be administered via Computerized Adaptive Testing (CAT) or fixed short forms. The study sample included 54.7% women with a mean age of 44.6 (SD 15.9) years. The average time since burn injury was 15.4 years (0-74 years) and the average total body surface area burned was 40% (1-97%). The CFA indicated acceptable fit statistics (CFI range 0.913-0.977, TLI range 0.904-0.974, RMSEA range 0.06-0.096). The six unidimensional scales were named: relationships with family and friends, social interactions, social activities, work and employment, romantic relationships, and sexual relationships. The marginal reliability of the full item bank and CATs ranged from 0.84 to 0.93, with ceiling effects less than 15% for all scales. The LIBRE Profile is a promising new measure of social participation following a burn injury that enables burn survivors and their care providers to measure social participation.

A systems biology approach to defining regulatory mechanisms for cartilage and tendon cell phenotypes.

PubMed

Mueller, A J; Tew, S R; Vasieva, O; Clegg, P D; Canty-Laird, E G

2016-09-27

Phenotypic plasticity of adult somatic cells has provided emerging avenues for the development of regenerative therapeutics. In musculoskeletal biology the mechanistic regulatory networks of genes governing the phenotypic plasticity of cartilage and tendon cells has not been considered systematically. Additionally, a lack of strategies to effectively reproduce in vitro functional models of cartilage and tendon is retarding progress in this field. De- and redifferentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and redifferentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion of cartilage and tendon cells, and the expression of key developmental markers, challenges the physiological relevance of this culture system. The study also suggests that oxidative stress and PI3K signalling pathways are key modulators of in vitro phenotypes for cells of musculoskeletal origin.

Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome.

PubMed

Huang, Rong; Zheng, Jun; Li, Shengxian; Tao, Tao; Ma, Jing; Liu, Wei

2015-05-01

To investigate the different characteristics in Chinese Han women with polycystic ovary syndrome, and to analyze the significance of hyperandrogenism in insulin resistance and other metabolic profiles. A cross-sectional study. Medical university hospital. A total of 229 women with polycystic ovary syndrome aged 18-45 years. Women with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided into four groups according to the quartile intervals of free androgen index levels. Comparisons between groups were performed using one-way analysis of variance. Stepwise logistic regression analysis was performed to investigate the association between homeostasis model assessment-insulin resistance and independent variables. Within the four phenotypes, women with phenotype 1 (hyperandrogenism, oligo/anovulation, and polycystic ovaries) exhibited higher total testosterone, free androgen index, androstenedione, low-density lipoprotein, and lower quantitative insulin sensitivity check index (p < 0.05); women with phenotype 4 (oligo/anovulation and polycystic ovaries) showed lower total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance, but higher high-density lipoprotein (p < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance significantly increased, but high-density lipoprotein and quantitative insulin sensitivity check index decreased with the elevation of free androgen index intervals. After adjustment for lipid profiles, free androgen index was significantly associated with homeostasis model assessment-insulin resistance in both lean and overweight/obese women (odds ratio 1.302, p = 0.039 in lean vs. odds ratio 1.132, p = 0.036 in overweight/obese). Phenotypes 1 and 4 represent groups with the most and least severe metabolic profiles, respectively. Hyperandrogenism, particularly with elevated free androgen index, is likely a key contributing factor for insulin resistance and for the aggravation of other metabolic profiles. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

The PCOS Patients differ in Lipid Profile According to their Phenotypes.

PubMed

Spałkowska, Magdalena; Mrozińska, Sandra; Gałuszka-Bednarczyk, Anna; Gosztyła, Katarzyna; Przywara, Agnieszka; Guzik, Justyna; Janeczko, Marek; Milewicz, Tomasz; Wojas-Pelc, Anna

2018-01-31

Polycystic ovary syndrome (PCOS) affects 4-18% of women of reproductive age. The number of reports exploring the lipid profiles among PCOS patients and number of studied patients are limited. The aim of our study was to assess the lipid profile separately in lean and non-lean women with polycystic ovary syndrome divided according to hyperandrogenemia, defined as free androgen index (FAI)≥5. The second aim was to compare the lipid profiles among lean and non-lean PCOS patients with respect to hyperandrogenemia and regularity of menstruation cycles. We evaluated 232 patients from Department of Endocrinological Gynecology, Jagiellonian University Medical College in Krakow diagnosed with PCOS. The population consisted of 166 lean and 66 non-lean women. We observed higher levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C) in lean patients with FAI<5 than in lean patients with FAI≥5. There were no differences in lipid profile between non-lean patients with FAI≥5 and non-lean patients with FAI<5. Among lean patients higher total cholesterol levels were observed in those with irregular menstruation cycles and FAI<5 than in patients with FAI≥5 and regular cycles. There were no differences in lipid profiles between four phenotypes among non-lean PCOS patients. The results of our study showed differences in lipid profile between lean PCOS patients according to their phenotype based on androgens' level. This effect was abandoned by fat tissue mass in non-lean ones. Further studies should be conducted to explore these associations. © Georg Thieme Verlag KG Stuttgart · New York.

VIP impairs acquisition of the macrophage proinflammatory polarization profile.

PubMed

Carrión, Mar; Pérez-García, Selene; Martínez, Carmen; Juarranz, Yasmina; Estrada-Capetillo, Lizbeth; Puig-Kröger, Amaya; Gomariz, Rosa P; Gutiérrez-Cañas, Irene

2016-12-01

This study tested the hypothesis that vasoactive intestinal peptide (VIP) is able to modify the macrophage inflammatory profile, thus supporting its therapeutic role in autoimmune diseases. Macrophages are innate immune cells that display a variety of functions and inflammatory profiles in response to the environment that critically controls their polarization. Deregulation between the pro- and anti-inflammatory phenotypes has been involved in different pathologies. Rheumatoid arthritis (RA) is an autoimmune disease, in which macrophages are considered central effectors of synovial inflammation, displaying a proinflammatory profile. VIP is a pleiotropic neuropeptide with proven anti-inflammatory actions. As modulation of the macrophage phenotype has been implicated in the resolution of inflammatory diseases, we evaluated whether VIP is able to modulate human macrophage polarization. In vitro-polarized macrophages by GM-CSF (GM-MØ), with a proinflammatory profile, expressed higher levels of VIP receptors, vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2, respectively), than macrophages polarized by M-CSF (M-MØ) with anti-inflammatory activities. RA synovial macrophages, according to their GM-CSF-like polarization state, expressed both VPAC1 and VPAC2. In vitro-generated GM-MØ exposed to VIP exhibited an up-regulation of M-MØ gene marker expression, whereas their proinflammatory cytokine profile was reduced in favor of an anti-inflammatory function. Likewise, in GM-MØ, generated in the presence of VIP, VIP somehow changes the macrophages physiology profile to a less-damaging phenotype. Therefore, these results add new value to VIP as an immunomodulatory agent on inflammatory diseases. © Society for Leukocyte Biology.

Global gene expression profiling related to temperature-sensitive growth abnormalities in interspecific crosses between tetraploid wheat and Aegilops tauschii

PubMed Central

Sakaguchi, Kouhei; Ohno, Ryoko; Yoshida, Kentaro

2017-01-01

Triploid wheat hybrids between tetraploid wheat and Aegilops tauschii sometimes show abnormal growth phenotypes, and the growth abnormalities inhibit generation of wheat synthetic hexaploids. In type II necrosis, one of the growth abnormalities, necrotic cell death accompanied by marked growth repression occurs only under low temperature conditions. At normal temperature, the type II necrosis lines show grass-clump dwarfism with no necrotic symptoms, excess tillers, severe dwarfism and delayed flowering. Here, we report comparative expression analyses to elucidate the molecular mechanisms of the temperature-dependent phenotypic plasticity in the triploid wheat hybrids. We compared gene and small RNA expression profiles in crown tissues to characterize the temperature-dependent phenotypic plasticity. No up-regulation of defense-related genes was observed under the normal temperature, and down-regulation of wheat APETALA1-like MADS-box genes, considered to act as flowering promoters, was found in the grass-clump dwarf lines. Some microRNAs, including miR156, were up-regulated, whereas the levels of transcripts of the miR156 target genes SPLs, known to inhibit tiller and branch number, were reduced in crown tissues of the grass-clump dwarf lines at the normal temperature. Unusual expression of the miR156/SPLs module could explain the grass-clump dwarf phenotype. Dramatic alteration of gene expression profiles, including miRNA levels, in crown tissues is associated with the temperature-dependent phenotypic plasticity in type II necrosis/grass-clump dwarf wheat hybrids. PMID:28463975

Childhood CBCL Bipolar Profile and Adolescent/Young Adult Personality Disorders: A 9-year Follow-up

PubMed Central

Halperin, Jeffrey M.; Rucklidge, Julia J.; Powers, Robyn L.; Miller, Carlin J.; Newcorn, Jeffrey H.

2010-01-01

Background To assess the late adolescent psychiatric outcomes associated with a positive Child Behavior Checklist – Juvenile Bipolar Disorder Phenotype (CBCL-JBD) in children diagnosed with ADHD and followed over a 9-year period. Methods Parents of 152 children diagnosed as ADHD (ages 7–11 years) completed the CBCL. Ninety of these parents completed it again 9 years later as part of a comprehensive evaluation of Axis I and II diagnoses as assessed using semi-structured interviews. As previously proposed, the CBCL-JBD phenotype was defined as T-scores of 70 or greater on the Attention Problems, Aggression, and Anxiety/Depression subscales. Results The CBCL-JBD phenotype was found in 31% of those followed but only 4.9% of the sample continued to meet the phenotype criteria at follow up. Only two of the sample developed Bipolar Disorder by late adolescence and only one of those had the CBCL-JBD profile in childhood. The proxy did not predict any Axis I disorders. However, the CBCL-JBD proxy was highly predictive of later personality disorders. Limitations Only a subgroup of the original childhood sample was followed. Given this sample was confined to children with ADHD, it is not known whether the prediction of personality disorders from CBCL scores would generalize to a wider community or clinical population Conclusions A positive CBCL-JBD phenotype profile in childhood does not predict Axis I Disorders in late adolescence; however, it may be prognostic of the emergence of personality disorders. PMID:21056910

Forensic DNA Phenotyping: Predicting human appearance from crime scene material for investigative purposes.

PubMed

Kayser, Manfred

2015-09-01

Forensic DNA Phenotyping refers to the prediction of appearance traits of unknown sample donors, or unknown deceased (missing) persons, directly from biological materials found at the scene. "Biological witness" outcomes of Forensic DNA Phenotyping can provide investigative leads to trace unknown persons, who are unidentifiable with current comparative DNA profiling. This intelligence application of DNA marks a substantially different forensic use of genetic material rather than that of current DNA profiling presented in the courtroom. Currently, group-specific pigmentation traits are already predictable from DNA with reasonably high accuracies, while several other externally visible characteristics are under genetic investigation. Until individual-specific appearance becomes accurately predictable from DNA, conventional DNA profiling needs to be performed subsequent to appearance DNA prediction. Notably, and where Forensic DNA Phenotyping shows great promise, this is on a (much) smaller group of potential suspects, who match the appearance characteristics DNA-predicted from the crime scene stain or from the deceased person's remains. Provided sufficient funding being made available, future research to better understand the genetic basis of human appearance will expectedly lead to a substantially more detailed description of an unknown person's appearance from DNA, delivering increased value for police investigations in criminal and missing person cases involving unknowns. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Psychological profiling of offender characteristics from crime behaviors in serial rape offences.

PubMed

Kocsis, Richard N; Cooksey, Ray W; Irwin, Harvey J

2002-04-01

Criminal psychological profiling has progressively been incorporated into police procedures despite a dearth of empirical research. Indeed, in the study of serial violent crimes for the purpose of psychological profiling, very few original, quantitative, academically reviewed studies actually exist. This article reports on the analysis of 62 incidents of serial sexual assault. The statistical procedure of multidimensional scaling was employed in the analysis of this data, which in turn produced a five-cluster model of serial rapist behavior. First, a central cluster of behaviors were identified that represent common behaviors to all patterns of serial rape. Second, four distinct outlying patterns were identified as demonstrating distinct offence styles, these being assigned the following descriptive labels brutality, intercourse, chaotic, and ritual. Furthermore, analysis of these patterns also identified distinct offender characteristics that allow for the use of empirically robust offender profiles in future serial rape investigations.

Multidimensional Characterization of Sexual Minority Adolescents’ Sexual Safety Strategies

PubMed Central

Masters, N. Tatiana; Beadnell, Blair; Morrison, Diane M.; Hoppe, Marilyn J.; Wells, Elizabeth A.

2013-01-01

Young adults have high rates of sexually transmitted infections (STIs). Sexual minority youths’ risk for STIs, including HIV, is as high as or higher than sexual majority peers’. Sexual safety, while often treated as a single behavior such as condom use, can be best conceptualized as the result of multiple factors. We used latent class analysis to identify profiles based on ever-used sexual safety strategies and lifetime number of partners among 425 self-identified LGBTQ youth aged 14-19. Data collection took place anonymously online. We identified four specific subgroup profiles for males and three for females, with each subgroup representing a different level and type of sexual safety. Profiles differed from each other in terms of age and outness for males, and in outness, personal homonegativity, and amount of education received about sexual/romantic relationships for females. Youths’ sexual safety profiles have practice implications for sexuality educators, health care professionals, and parents. PMID:24011111

Phenotypic and microRNA transcriptomic profiling of the MDA-MB-231 spheroid-enriched CSCs with comparison of MCF-7 microRNA profiling dataset.

PubMed

Boo, Lily; Ho, Wan Yong; Mohd Ali, Norlaily; Yeap, Swee Keong; Ky, Huynh; Chan, Kok Gan; Yin, Wai Fong; Satharasinghe, Dilan Amila; Liew, Woan Charn; Tan, Sheau Wei; Cheong, Soon Keng; Ong, Han Kiat

2017-01-01

Breast cancer spheroids have been widely used as in vitro models of cancer stem cells (CSCs), yet little is known about their phenotypic characteristics and microRNAs (miRNAs) expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.

Peruvian Maca (Lepidium peruvianum): (I) Phytochemical and Genetic Differences in Three Maca Phenotypes.

PubMed

Meissner, Henry O; Mscisz, Alina; Mrozikiewicz, Mieczyslaw; Baraniak, Marek; Mielcarek, Sebastian; Kedzia, Bogdan; Piatkowska, Ewa; Jólkowska, Justyna; Pisulewski, Pawel

2015-09-01

Glucosinolates were previously reported as physiologically-important constituents present in Peruvian Maca (Lepidium peruvianum Chacon) and linked to various therapeutic functions of differently-colored Peruvian Maca hypocotyls. In two separate Trials, three colours of Maca hypocotyls "Black", "Red" and "Yellow" (termed "Maca phenotypes"), were selected from mixed crops of Peruvian Maca for laboratory studies as fresh and after being dried. Individual Maca phenotypes were cultivated in the highlands of the Peruvian Andes at 4,200m a.s.l. (Junin and Ninacaca). Glucosinolate levels, chromatographic HPLC profiles and DNA variability in the investigated Maca phenotypes are presented. Genotypic profiles were determined by the ISSR-PCR and RAPD techniques. Compared to the Black and Red phenotypes, the Yellow phenotype contained much lower Glucosinolate levels measured against Glucotropaeolin and m-methoxy-glucotropaeolin standards, and exhibited different RAPD and ISSR-PCR reactions. The Red Maca phenotype showed the highest concentrations of Glucosinolates as compared to the Black and Yellow Maca. It appears that the traditional system used by natives of the Peruvian Andean highlands in preparing Maca as a vegetable dish (boiling dried Maca after soaking in water), to supplement their daily meals, is as effective as laboratory methods - for extracting Glucosinolates, which are considered to be one of the key bioactive constituents responsible for therapeutic functions of Peruvian Maca phenotypes. It is reasonable to assume that the HPLC and DNA techniques combined, or separately, may assist in determining ID and "Fingerprints" identifying individual Peruvian Maca phenotypes, hence confirming the authenticity of marketable Maca products. The above assumptions warrant further laboratory testing.

Bistability in a Metabolic Network Underpins the De Novo Evolution of Colony Switching in Pseudomonas fluorescens

PubMed Central

Gallie, Jenna; Libby, Eric; Bertels, Frederic; Remigi, Philippe; Jendresen, Christian B.; Ferguson, Gayle C.; Desprat, Nicolas; Buffing, Marieke F.; Sauer, Uwe; Beaumont, Hubertus J. E.; Martinussen, Jan; Kilstrup, Mogens; Rainey, Paul B.

2015-01-01

Phenotype switching is commonly observed in nature. This prevalence has allowed the elucidation of a number of underlying molecular mechanisms. However, little is known about how phenotypic switches arise and function in their early evolutionary stages. The first opportunity to provide empirical insight was delivered by an experiment in which populations of the bacterium Pseudomonas fluorescens SBW25 evolved, de novo, the ability to switch between two colony phenotypes. Here we unravel the molecular mechanism behind colony switching, revealing how a single nucleotide change in a gene enmeshed in central metabolism (carB) generates such a striking phenotype. We show that colony switching is underpinned by ON/OFF expression of capsules consisting of a colanic acid-like polymer. We use molecular genetics, biochemical analyses, and experimental evolution to establish that capsule switching results from perturbation of the pyrimidine biosynthetic pathway. Of central importance is a bifurcation point at which uracil triphosphate is partitioned towards either nucleotide metabolism or polymer production. This bifurcation marks a cell-fate decision point whereby cells with relatively high pyrimidine levels favour nucleotide metabolism (capsule OFF), while cells with lower pyrimidine levels divert resources towards polymer biosynthesis (capsule ON). This decision point is present and functional in the wild-type strain. Finally, we present a simple mathematical model demonstrating that the molecular components of the decision point are capable of producing switching. Despite its simple mutational cause, the connection between genotype and phenotype is complex and multidimensional, offering a rare glimpse of how noise in regulatory networks can provide opportunity for evolution. PMID:25763575

In situ calibration of an infrared imaging video bolometer in the Large Helical Device

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

Mukai, K., E-mail: mukai.kiyofumi@LHD.nifs.ac.jp; Peterson, B. J.; Pandya, S. N.

The InfraRed imaging Video Bolometer (IRVB) is a powerful diagnostic to measure multi-dimensional radiation profiles in plasma fusion devices. In the Large Helical Device (LHD), four IRVBs have been installed with different fields of view to reconstruct three-dimensional profiles using a tomography technique. For the application of the measurement to plasma experiments using deuterium gas in LHD in the near future, the long-term effect of the neutron irradiation on the heat characteristics of an IRVB foil should be taken into account by regular in situ calibration measurements. Therefore, in this study, an in situ calibration system was designed.

Testing the adaptive radiation hypothesis for the lemurs of Madagascar.

PubMed

Herrera, James P

2017-01-01

Lemurs, the diverse, endemic primates of Madagascar, are thought to represent a classic example of adaptive radiation. Based on the most complete phylogeny of living and extinct lemurs yet assembled, I tested predictions of adaptive radiation theory by estimating rates of speciation, extinction and adaptive phenotypic evolution. As predicted, lemur speciation rate exceeded that of their sister clade by nearly twofold, indicating the diversification dynamics of lemurs and mainland relatives may have been decoupled. Lemur diversification rates did not decline over time, however, as predicted by adaptive radiation theory. Optimal body masses diverged among dietary and activity pattern niches as lineages diversified into unique multidimensional ecospace. Based on these results, lemurs only partially fulfil the predictions of adaptive radiation theory, with phenotypic evolution corresponding to an 'early burst' of adaptive differentiation. The results must be interpreted with caution, however, because over the long evolutionary history of lemurs (approx. 50 million years), the 'early burst' signal of adaptive radiation may have been eroded by extinction.

Testing the adaptive radiation hypothesis for the lemurs of Madagascar

PubMed Central

2017-01-01

Lemurs, the diverse, endemic primates of Madagascar, are thought to represent a classic example of adaptive radiation. Based on the most complete phylogeny of living and extinct lemurs yet assembled, I tested predictions of adaptive radiation theory by estimating rates of speciation, extinction and adaptive phenotypic evolution. As predicted, lemur speciation rate exceeded that of their sister clade by nearly twofold, indicating the diversification dynamics of lemurs and mainland relatives may have been decoupled. Lemur diversification rates did not decline over time, however, as predicted by adaptive radiation theory. Optimal body masses diverged among dietary and activity pattern niches as lineages diversified into unique multidimensional ecospace. Based on these results, lemurs only partially fulfil the predictions of adaptive radiation theory, with phenotypic evolution corresponding to an ‘early burst’ of adaptive differentiation. The results must be interpreted with caution, however, because over the long evolutionary history of lemurs (approx. 50 million years), the ‘early burst’ signal of adaptive radiation may have been eroded by extinction. PMID:28280597

Supergenes and their role in evolution.

PubMed

Thompson, M J; Jiggins, C D

2014-07-01

Adaptation is commonly a multidimensional problem, with changes in multiple traits required to match a complex environment. This is epitomized by balanced polymorphisms in which multiple phenotypes co-exist and are maintained in a population by a balance of selective forces. Consideration of such polymorphisms led to the concept of the supergene, where alternative phenotypes in a balanced polymorphism segregate as if controlled by a single genetic locus, resulting from tight genetic linkage between multiple functional loci. Recently, the molecular basis for several supergenes has been resolved. Thus, major chromosomal inversions have been shown to be associated with polymorphisms in butterflies, ants and birds, offering a mechanism for localised reduction in recombination. In several examples of plant self-incompatibility, the functional role of multiple elements within the supergene architecture has been demonstrated, conclusively showing that balanced polymorphism can be maintained at multiple coadapted and tightly linked elements. Despite recent criticism, we argue that the supergene concept remains relevant and is more testable than ever with modern molecular methods.

Genetic and environmental structure of DSM-IV criteria for Antisocial Personality Disorder: a twin study

PubMed Central

Rosenström, Tom; Ystrom, Eivind; Torvik, Fartein Ask; Czajkowski, Nikolai Olavi; Gillespie, Nathan A.; Aggen, Steven H.; Krueger, Robert F.; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

2017-01-01

Results from previous studies on DSM-IV and DSM-5 Antisocial Personality Disorder (ASPD) have suggested that the construct is etiologically multidimensional. To our knowledge, however, the structure of genetic and environmental influences in ASPD has not been examined using an appropriate range of biometric models and diagnostic interviews. The 7 ASPD criteria (section A) were assessed in a population-based sample of 2794 Norwegian twins by a structured interview for DSM-IV personality disorders. Exploratory analyses were conducted at the phenotypic level. Multivariate biometric models, including both independent and common pathways, were compared. A single phenotypic factor was found, and the best-fitting biometric model was a single-factor common pathway model, with common-factor heritability of 51% (95% CI = 40–67%). In other words, both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable. The findings support the validity of ASPD as a unidimensional diagnostic construct. PMID:28108863

Genetic and Environmental Structure of DSM-IV Criteria for Antisocial Personality Disorder: A Twin Study.

PubMed

Rosenström, Tom; Ystrom, Eivind; Torvik, Fartein Ask; Czajkowski, Nikolai Olavi; Gillespie, Nathan A; Aggen, Steven H; Krueger, Robert F; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

2017-05-01

Results from previous studies on DSM-IV and DSM-5 Antisocial Personality Disorder (ASPD) have suggested that the construct is etiologically multidimensional. To our knowledge, however, the structure of genetic and environmental influences in ASPD has not been examined using an appropriate range of biometric models and diagnostic interviews. The 7 ASPD criteria (section A) were assessed in a population-based sample of 2794 Norwegian twins by a structured interview for DSM-IV personality disorders. Exploratory analyses were conducted at the phenotypic level. Multivariate biometric models, including both independent and common pathways, were compared. A single phenotypic factor was found, and the best-fitting biometric model was a single-factor common pathway model, with common-factor heritability of 51% (95% CI 40-67%). In other words, both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable. The findings support the validity of ASPD as a unidimensional diagnostic construct.

An overview of animal models of pain: disease models and outcome measures

PubMed Central

Gregory, N; Harris, AL; Robinson, CR; Dougherty, PM; Fuchs, PN; Sluka, KA

2013-01-01

Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience including reflexive hyperalgesia measures, sensory and affective dimensions of pain and impact of pain on function and quality of life. In this review we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes, as well as the main behavioral tests for assessing pain in each model. PMID:24035349

Precision phenotyping of epicuticular waxes associated with insect resistance

USDA-ARS?s Scientific Manuscript database

Accurate phenotyping is imperative for linkage mapping and association genetics. Amounts and types of epicuticular waxes on the leaf surface are important for plant-insect interactions. In onion, specific wax profiles are associated with resistance to the insect pest Thrips tabaci. Epicuticular wax ...

Genome-enabled prediction models for yield related traits in chickpea

USDA-ARS?s Scientific Manuscript database

Genomic selection (GS) unlike marker-assisted backcrossing (MABC) predicts breeding values of lines using genome-wide marker profiling and allows selection of lines prior to field-phenotyping, thereby shortening the breeding cycle. A collection of 320 elite breeding lines was selected and phenotyped...

Prospective Characterization of Cognitive Function in Typical and 'Brainstem Predominant'Progressive Supranuclear Palsy Phenotypes.

PubMed

Lee, Young-Eun C; Williams, David R; Anderson, Jacqueline F I

2018-05-01

Clinicopathological studies over the last decade have broadened the clinical spectrum of progressive supranuclear palsy (PSP) to include several distinct clinical syndromes. We examined the cognitive profiles of patients with PSP-Richardson's syndrome (PSP-RS) and two atypical 'brainstem predominant' PSP phenotypes (PSP-parkinsonism, PSP-P; and PSP-pure akinesia with gait freezing, PSP-PAGF) using a comprehensive neuropsychological battery. Fourteen patients diagnosed as PSP-RS, three patients with PSP-P and four patients with PSP-PAGF were assessed using a comprehensive battery of neuropsychological tests. The typical PSP-RS subgroup demonstrated greater impairments in processing speed [t(19) = -4.10, p = 0.001 (d =1.66)] and executive function [t(19) = -2.63, p = 0.02 (d = 1.20)] compared to the 'brainstem predominant' PSP phenotype. This is the first prospective study to demonstrate that PSP-RS and 'brainstem predominant' PSP phenotypes can be differentiated on cognitive grounds. These differences correspond with variations in pathological profiles reported in the literature.

Evolution of cooperation in a multidimensional phenotype space.

PubMed

Kroumi, Dhaker; Lessard, Sabin

2015-06-01

The emergence of cooperation in populations of selfish individuals is a fascinating topic that has inspired much theoretical work. An important model to study cooperation is the phenotypic model, where individuals are characterized by phenotypic properties that are visible to others. The phenotype of an individual can be represented for instance by a vector x = (x1,…,xn), where x1,…,xn are integers. The population can be well mixed in the sense that everyone is equally likely to interact with everyone else, but the behavioral strategies of the individuals can depend on their distance in the phenotype space. A cooperator can choose to help other individuals exhibiting the same phenotype and defects otherwise. Cooperation is said to be favored by selection if it is more abundant than defection in the stationary state. This means that the average frequency of cooperators in the stationary state strictly exceeds 1/2. Antal et al. (2009c) found conditions that ensure that cooperation is more abundant than defection in a one-dimensional (i.e. n = 1) and an infinite-dimensional (i.e. n = ∞) phenotype space in the case of the Prisoner's Dilemma under weak selection. However, reality lies between these two limit cases. In this paper, we derive the corresponding condition in the case of a phenotype space of any finite dimension. This is done by applying a perturbation method to study a mutation-selection equilibrium under weak selection. This condition is obtained in the limit of a large population size by using the ancestral process. The best scenario for cooperation to be more likely to evolve is found to be a high population-scaled phenotype mutation rate, a low population-scaled strategy mutation rate and a high phenotype space dimension. The biological intuition is that a high population-scaled phenotype mutation rate reduces the quantity of interactions between cooperators and defectors, while a high population-scaled strategy mutation rate introduces newly mutated defectors that invade groups of cooperators. Finally it is easier for cooperation to evolve in a phenotype space of higher dimension because it becomes more difficult for a defector to migrate to a group of cooperators. The difference is significant from n = 1 to n = 2 and from n = 2 to n = 3, but becomes small as soon as n ≥ 3. Copyright © 2015 Elsevier Inc. All rights reserved.

Adaptation of the Biolog Phenotype MicroArrayTM Technology to Profile the Obligate Anaerobe Geobacter metallireducens

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

Joyner, Dominique; Fortney, Julian; Chakraborty, Romy

2010-05-17

The Biolog OmniLog? Phenotype MicroArray (PM) plate technology was successfully adapted to generate a select phenotypic profile of the strict anaerobe Geobacter metallireducens (G.m.). The profile generated for G.m. provides insight into the chemical sensitivity of the organism as well as some of its metabolic capabilities when grown with a basal medium containing acetate and Fe(III). The PM technology was developed for aerobic organisms. The reduction of a tetrazolium dye by the test organism represents metabolic activity on the array which is detected and measured by the OmniLog(R) system. We have previously adapted the technology for the anaerobic sulfate reducingmore » bacterium Desulfovibrio vulgaris. In this work, we have taken the technology a step further by adapting it for the iron reducing obligate anaerobe Geobacter metallireducens. In an osmotic stress microarray it was determined that the organism has higher sensitivity to impermeable solutes 3-6percent KCl and 2-5percent NaNO3 that result in osmotic stress by osmosis to the cell than to permeable non-ionic solutes represented by 5-20percent ethylene glycol and 2-3percent urea. The osmotic stress microarray also includes an array of osmoprotectants and precursor molecules that were screened to identify substrates that would provide osmotic protection to NaCl stress. None of the substrates tested conferred resistance to elevated concentrations of salt. Verification studies in which G.m. was grown in defined medium amended with 100mM NaCl (MIC) and the common osmoprotectants betaine, glycine and proline supported the PM findings. Further verification was done by analysis of transcriptomic profiles of G.m. grown under 100mM NaCl stress that revealed up-regulation of genes related to degradation rather than accumulation of the above-mentioned osmoprotectants. The phenotypic profile, supported by additional analysis indicates that the accumulation of these osmoprotectants as a response to salt stress does not occur in G.m. and response to stress must occur by other mechanisms. The Phenotype MicroArray technology can be reliably used as a rapid screening tool for characterization in anaerobic microbial ecology.« less

[Epidemiology of ageing in Northeastern Brazil: results of a household survey].

PubMed

Coelho Filho, J M; Ramos, L R

1999-10-01

The population of Brazil is ageing very rapidly, and the care of the elderly is an emerging priority. Up to this date, there is no comprehensive study addressing the profile of the elderly in Northeastern Brazil. The objective is to compile the multidimensional profile of the elderly residents in a metropolitan area of Northeastern Brazil. Six hundred sixty-seven elderly (60 years and over), residents in the city of Fortaleza, Ceará, Brazil, constituting a multistage random sample stratified by socioeconomic status. The data was gathered by household survey using a multidimensional functional assessment questionnaire. The majority of the elderly were living in multigenerational households (75,3%). More than half (51,9%) lived without the spouse; 92,4% mentioned at least one disease; 26,4% were considered psychiatric cases; 47,7% showed loss of autonomy; 6,6% were hospitalized, and 61,4% used health services within the twelve and six months preceding the interview, respectively. The prevalence of multigenerational households, loss of autonomy and psychiatric morbidity were higher in the poorest areas. The elderly population in the city of Fortaleza lives mainly in multigenerational households, with physical and mental morbidity rates particularly high in poor areas, they represent special concern in terms of burden for the social and health services in the next decades

Cell Painting, a high-content image-based assay for morphological profiling using multiplexed fluorescent dyes

PubMed Central

Bray, Mark-Anthony; Singh, Shantanu; Han, Han; Davis, Chadwick T.; Borgeson, Blake; Hartland, Cathy; Kost-Alimova, Maria; Gustafsdottir, Sigrun M.; Gibson, Christopher C.; Carpenter, Anne E.

2016-01-01

In morphological profiling, quantitative data are extracted from microscopy images of cells to identify biologically relevant similarities and differences among samples based on these profiles. This protocol describes the design and execution of experiments using Cell Painting, a morphological profiling assay multiplexing six fluorescent dyes imaged in five channels, to reveal eight broadly relevant cellular components or organelles. Cells are plated in multi-well plates, perturbed with the treatments to be tested, stained, fixed, and imaged on a high-throughput microscope. Then, automated image analysis software identifies individual cells and measures ~1,500 morphological features (various measures of size, shape, texture, intensity, etc.) to produce a rich profile suitable for detecting subtle phenotypes. Profiles of cell populations treated with different experimental perturbations can be compared to suit many goals, such as identifying the phenotypic impact of chemical or genetic perturbations, grouping compounds and/or genes into functional pathways, and identifying signatures of disease. Cell culture and image acquisition takes two weeks; feature extraction and data analysis take an additional 1-2 weeks. PMID:27560178

Stem cell media culture of melanoma results in the induction of a nonrepresentative neural expression profile.

PubMed

Anaka, Matthew; Freyer, Claudia; Gedye, Craig; Caballero, Otavia; Davis, Ian D; Behren, Andreas; Cebon, Jonathan

2012-02-01

The ability of cell lines to accurately represent cancer is a major concern in preclinical research. Culture of glioma cells as neurospheres in stem cell media (SCM) has been shown to better represent the genotype and phenotype of primary glioblastoma in comparison to serum cell lines. Despite the use of neurosphere-like models of many malignancies, there has been no robust analysis of whether other cancers benefit from a more representative phenotype and genotype when cultured in SCM. We analyzed the growth properties, transcriptional profile, and genotype of melanoma cells grown de novo in SCM, as while melanocytes share a common precursor with neural cells, melanoma frequently demonstrates divergent behavior in cancer stem cell assays. SCM culture of melanoma cells induced a neural lineage gene expression profile that was not representative of matched patient tissue samples and which could be induced in serum cell lines by switching them into SCM. There was no enrichment for expression of putative melanoma stem cell markers, but the SCM expression profile did overlap significantly with that of SCM cultures of glioma, suggesting that the observed phenotype is media-specific rather than melanoma-specific. Xenografts derived from either culture condition provided the best representation of melanoma in situ. Finally, SCM culture of melanoma did not prevent ongoing acquisition of DNA copy number abnormalities. In conclusion, SCM culture of melanoma does not provide a better representation of the phenotype or genotype of metastatic melanoma, and the resulting neural bias could potentially confound therapeutic target identification. Copyright © 2011 AlphaMed Press.

Phenotypes, serotypes and antibiotic susceptibility of Swedish Porphyromonas gingivalis isolates from periodontitis and periodontal abscesses.

PubMed

Dahlén, G; Gmür, R; Yoshino, T

2007-04-01

This study was conducted to reveal phenotypic, serological subtypes and antibiotic susceptibility among fresh isolates of Porphyromonas gingivalis in a Swedish population with periodontitis and periodontal abscess. Fifty-five subgingival strains were isolated and tentatively designated as P. gingivalis from 55 consecutive paper-point samples taken from 51 patients with periodontitis (at least one site with >6-mm pocket depth) in Sweden and were sent in for microbiological evaluation. Eight P. gingivalis strains from periodontal abscesses were also included. Four P. gingivalis strains served as reference and another four type strains were included. The strains were characterized by colony morphology, biochemical tests, enzyme profile, gas-liquid chromatography and antibiotic susceptibility. The strains were further characterized for whole cell protein profiles using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and were identified to serotype by specific monoclonal antibodies. Among the 55 P. gingivalis strains 35 had smooth (S), 13 rough (R) and seven semi-rough colony morphologies. All strains were phenotypically homogeneous in biochemical tests, enzyme profile and antibiotic susceptibility. All strains produced phenylacetic acid and alpha-fucosidase. Almost all (96%) of the subgingival strains, but relatively fewer (62%) of the abscess strains, belonged to serotype A. Two subgingival and three abscess strains were classified as serotype B. No specific SDS-PAGE protein profiles were recorded for the two serotypes. The P. gingivalis strains from Swedish periodontitis cases showed homogeneity in terms of biochemical phenotypes and antibiotic susceptibility patterns. The strains fell into two serotypes, of which serotype A predominated in the periodontitis cases and serotype B was overrepresented in periodontal abscesses.

Metabolic parameters linked by Phenotype MicroArray to acid resistance profiles of poultry-associated Salmonella enterica.

USDA-ARS?s Scientific Manuscript database

Phenotype microarrays were analyzed for 51 datasets derived from Salmonella enterica. The top 4 serovars associated with poultry products and one associated with turkey, respectively Typhimurium, Enteritidis, Heidelberg, Infantis and Senftenberg, were represented. Datasets were clustered into two ...

Settling the score: variant prioritization and Mendelian disease

PubMed Central

Eilbeck, Karen; Quinlan, Aaron; Yandell, Mark

2018-01-01

When investigating Mendelian disease using exome or genome sequencing, distinguishing disease-causing genetic variants from the multitude of candidate variants is a complex, multidimensional task. Many prioritization tools and online interpretation resources exist, and professional organizations have offered clinical guidelines for review and return of prioritization results. In this Review, we describe the strengths and weaknesses of widely used computational approaches, explain their roles in the diagnostic and discovery process and discuss how they can inform (and misinform) expert reviewers. We place variant prioritization in the wider context of gene prioritization, burden testing and genotype–phenotype association, and we discuss opportunities and challenges introduced by whole-genome sequencing. PMID:28804138

Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study.

PubMed

Moglia, Cristina; Calvo, Andrea; Canosa, Antonio; Bertuzzo, Davide; Cugnasco, Paolo; Solero, Luca; Grassano, Maurizio; Bersano, Enrica; Cammarosano, Stefania; Manera, Umberto; Pisano, Fabrizio; Mazzini, Letizia; Dalla Vecchia, Laura A; Mora, Gabriele; Chiò, Adriano

2017-11-01

To assess the prognostic influence of pre-morbid type 2 diabetes mellitus, arterial hypertension and cardiovascular (CV) risk profile on ALS phenotype and outcome in a population-based cohort of Italian patients. A total of 650 ALS patients from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid presence of type 2 diabetes mellitus, arterial hypertension was collected at the time of diagnosis. Patients' CV risk profile was calculated according to the Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice (JBS2). At the univariate analysis, the presence of pre-morbid arterial hypertension was associated with a higher age at onset of ALS and a shorter survival, and patients with a high CV risk profile had a worse prognosis than those with a low CV risk profile. The Cox multivariable analysis did not confirm such findings. Type 2 diabetes mellitus did not modify either the phenotype or the prognosis of ALS patients. This study performed on a large population-based cohort of ALS patients has demonstrated that arterial hypertension, type 2 diabetes and CV risk factors, calculated using the Framingham equation, do not influence ALS phenotype and prognosis.

Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown mice

PubMed Central

De Souza, Angus T.; Dai, Xudong; Spencer, Andrew G.; Reppen, Tom; Menzie, Ann; Roesch, Paula L.; He, Yudong; Caguyong, Michelle J.; Bloomer, Sherri; Herweijer, Hans; Wolff, Jon A.; Hagstrom, James E.; Lewis, David L.; Linsley, Peter S.; Ulrich, Roger G.

2006-01-01

RNA interference (RNAi) has great potential as a tool for studying gene function in mammals. However, the specificity and magnitude of the in vivo response to RNAi remains to be fully characterized. A molecular and phenotypic comparison of a genetic knockout mouse and the corresponding knockdown version would help clarify the utility of the RNAi approach. Here, we used hydrodynamic delivery of small interfering RNA (siRNA) to knockdown peroxisome proliferator activated receptor alpha (Ppara), a gene that is central to the regulation of fatty acid metabolism. We found that Ppara knockdown in the liver results in a transcript profile and metabolic phenotype that is comparable to those of Ppara−/− mice. Combining the profiles from mice treated with the PPARα agonist fenofibrate, we confirmed the specificity of the RNAi response and identified candidate genes proximal to PPARα regulation. Ppara knockdown animals developed hypoglycemia and hypertriglyceridemia, phenotypes observed in Ppara−/− mice. In contrast to Ppara−/− mice, fasting was not required to uncover these phenotypes. Together, these data validate the utility of the RNAi approach and suggest that siRNA can be used as a complement to classical knockout technology in gene function studies. PMID:16945951

Analysis of the miRNA Profiles of Melanoma Exosomes Derived Under Normoxic and Hypoxic Culture Conditions.

PubMed

Wozniak, Michal; Peczek, Lukasz; Czernek, Liliana; Düchler, Markus

2017-12-01

MicroRNAs (miRNAs) transported in melanoma-derived exosomes function as intercellular messengers supporting tumor survival and progression. Hypoxia increases melanoma phenotypic plasticity, drug resistance, and metastasis. We determined the miRNA profiles in exosomes derived from melanoma cells grown under hypoxic and normoxic conditions by microarray analyses and reverse transcription-polymerase chain reaction (RT-PCR) in order to analyze the potential influence of vesicle-transported miRNAs on cancer-related pathways and transcriptional programs. Despite phenotypical differences of the four cell lines used, their exosomes shared the majority of miRNAs. The levels of three miRNAs were higher in normoxic exosomes, whereas 15 miRNAs were significantly more abundant under hypoxic conditions. Pathway analysis pointed at several cellular processes contributing to proliferation, drug resistance, and modification of the tumor microenvironment, including immunosuppression. The miRNA-expression profiles of exosomes from patient-derived melanoma cells are modified by oxygen concentration and reflect the phenotypic changes of melanoma cells under different growth conditions. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Long-term outcomes of youth who manifested the CBCL-Pediatric Bipolar Disorder phenotype during childhood and/or adolescence.

PubMed

Meyer, Stephanie E; Carlson, Gabrielle A; Youngstrom, Eric; Ronsaville, Donna S; Martinez, Pedro E; Gold, Philip W; Hakak, Rashelle; Radke-Yarrow, Marian

2009-03-01

Recent studies have identified a Child Behavior Checklist (CBCL) profile that characterizes children with severe aggression, inattention, and mood instability. This profile has been coined the CBCL-Pediatric Bipolar Disorder (PBD) phenotype, because it is commonly seen among children with bipolar disorder. However, mounting evidence suggests that the CBCL-PBD may be a better tool for identifying children with severe functional impairment and broad-ranging psychiatric comorbidities rather than bipolar disorder itself. No studies have followed individuals with the CBCL-PBD profile through adulthood, so its long-term implications remain unclear. The present authors examined diagnostic and functional trajectories of individuals with the CBCL-PBD profile from early childhood through young adulthood using data from a longitudinal high-risk study. Participants (n=101) are part of a 23-year study of youth at risk for major mood disorder who have completed diagnostic and functional assessments at regular intervals. Across development, participants with the CBCL-PBD phenotype exhibited marked psychosocial impairment, increased rates of suicidal thoughts and behaviors and heightened risk for comorbid anxiety, bipolar disorder, cluster B personality disorders and ADHD in young adulthood, compared to participants without this presentation. However, diagnostic accuracy for any one particular disorder was found to be low. Children with the CBCL-PBD profile are at risk for ongoing, severe, psychiatric symptomatology including behavior and emotional comorbidities in general, and bipolar disorder, anxiety, ADHD, cluster B personality disorders in particular. However, the value of this profile may be in predicting ongoing comorbidity and impairment, rather than any one specific DSM-IV diagnosis.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

PubMed

Bukowski, Radek; Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M; Andrews, William; Saade, George R; Ilekis, John V; Reddy, Uma M; Baldwin, Donald A

2017-01-01

Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment ( n  = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL ( n  = 8), PNL ( n  = 10), TL ( n  = 7) and TNL ( n  = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

PubMed Central

Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R.; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M.; Andrews, William; Saade, George R.; Ilekis, John V.; Reddy, Uma M.; Baldwin, Donald A.

2017-01-01

Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5′and 3′ UTR regions. Conclusions The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. PMID:28879060

Epigenetic rather than genetic factors may explain phenotypic divergence between coastal populations of diploid and tetraploid Limonium spp. (Plumbaginaceae) in Portugal

PubMed Central

2013-01-01

Background The genus Limonium Miller comprises annual and perennial halophytes that can produce sexual and/or asexual seeds (apomixis). Genetic and epigenetic (DNA methylation) variation patterns were investigated in populations of three phenotypically similar putative sexual diploid species (L. nydeggeri, L. ovalifolium, L. lanceolatum), one sexual tetraploid species (L. vulgare) and two apomict tetraploid species thought to be related (L. dodartii, L. multiflorum). The extent of morphological differentiation between these species was assessed using ten diagnostic morphometric characters. Results A discriminant analysis using the morphometric variables reliably assigns individuals into their respective species groups. We found that only modest genetic and epigenetic differentiation was revealed between species by Methylation Sensitive Amplification Polymorphism (MSAP). However, whilst there was little separation possible between ploidy levels on the basis of genetic profiles, there was clear and pronounced interploidy discrimination on the basis of epigenetic profiles. Here we investigate the relative contribution of genetic and epigenetic factors in explaining the complex phenotypic variability seen in problematic taxonomic groups such as Limonium that operate both apomixis and sexual modes of reproduction. Conclusions Our results suggest that epigenetic variation might be one of the drivers of the phenotypic divergence between diploid and tetraploid taxa and discuss that intergenome silencing offers a plausible mechanistic explanation for the observed phenotypic divergence between these microspecies. These results also suggest that epigenetic profiling offer an additional tool to infer ploidy level in stored specimens and that stable epigenetic change may play an important role in apomict evolution and species recognition. PMID:24314092

Diversity analysis of cotton (Gossypium hirsutum L.) germplasm using the CottonSNP63K Array

USDA-ARS?s Scientific Manuscript database

Cotton germplasm resources contain beneficial alleles that can be exploited to develop germplasm adapting to emerging environmental and climate conditions, and this germplasm has commonly been characterized based on phenotypes. However, phenotypic profiles are limited by what can be observed and me...

Phylogenetic distribution of phenotypic traits in bacillus thuringiensis analyzed by multilocus sequence typing

USDA-ARS?s Scientific Manuscript database

Strains from a collection of 3,639 diverse Bacillus thuringiensis isolates were classified based on phenotypic profiles resulting from six biochemical tests, including production of amylase (T), lecithinase (L), urease (U), acid from sucrose (S) and salicin (A), and the hydrolysis of esculin (E). St...

Peruvian Maca (Lepidium peruvianum): (II) Phytochemical Profiles of Four Prime Maca Phenotypes Grown in Two Geographically-Distant Locations

PubMed Central

O. Meissner, Henry; Mscisz, Alina; Piatkowska, Ewa; Baraniak, Marek; Mielcarek, Sebastian; Kedzia, Bogdan; Holderna-Kedzia, Elzbieta; Pisulewski, Pawel

2016-01-01

Peruvian Maca crops (Lepidium peruvianum), grown in two geographically-distant cultivation sites located at similar altitudes in the highlands of the Peruvian Andes (Junin at 4,200 m a.s.l. and Ancash 4,150 m a.s.l.), were used in the study. Four prime Maca phenotypes, distinguished by hypocotyl colours labelled as “Yellow”, “Purple”, “Red” and “Black” were selected to determine distribution in levels and corresponding ratios between individual Glucosinolates (Glucotropaeolin and m-methylglucotropaeolin) in an attempt to identify four Peruvian Maca phenotypes from analyses of powdered hypocotyls. There were highly significant differences (P<0.01) in hypocotyl weight/size of four Maca phenotypes harvested in two locations. The Junin crop represented a mostly “large” class (13.3 g) with “small” size hypocotyls (7.2 g), while a “small” class was predominant in Ancash (3.5 g). Powdered Yellow Maca showed significantly higher (P<0.001) microbial contamination than the other three, with Black Maca being the least infected. Only minor, statistically-confirmed differences were detected in nutritive characteristics between the four Maca phenotypes grown in Junin, however highly significant differences (P<0.01) in Glucosinolates existed between the Red and Black Maca grown in Junin and Ancash. Irrespective of the cultivation location, Red phenotypes showed the highest content of Total Glucosinolates, followed by Black and Purple, with the Yellow phenotype showing consistently lower levels. Highly significant P<0.01) differences determined in ratios of individual Glucosinolates between four Maca phenotypes grown in two locations, confirms an earlier assumption that sums of individual Glucosinolates, their ratios and profiles, may be feasible to explore in analytically identifying individual Maca phenotypes in pulverised marketed Maca products. PMID:27127450

Peruvian Maca (Lepidium peruvianum): (II) Phytochemical Profiles of Four Prime Maca Phenotypes Grown in Two Geographically-Distant Locations.

PubMed

O Meissner, Henry; Mscisz, Alina; Piatkowska, Ewa; Baraniak, Marek; Mielcarek, Sebastian; Kedzia, Bogdan; Holderna-Kedzia, Elzbieta; Pisulewski, Pawel

2016-03-01

Peruvian Maca crops (Lepidium peruvianum), grown in two geographically-distant cultivation sites located at similar altitudes in the highlands of the Peruvian Andes (Junin at 4,200 m a.s.l. and Ancash 4,150 m a.s.l.), were used in the study. Four prime Maca phenotypes, distinguished by hypocotyl colours labelled as "Yellow", "Purple", "Red" and "Black" were selected to determine distribution in levels and corresponding ratios between individual Glucosinolates (Glucotropaeolin and m-methylglucotropaeolin) in an attempt to identify four Peruvian Maca phenotypes from analyses of powdered hypocotyls. There were highly significant differences (P<0.01) in hypocotyl weight/size of four Maca phenotypes harvested in two locations. The Junin crop represented a mostly "large" class (13.3 g) with "small" size hypocotyls (7.2 g), while a "small" class was predominant in Ancash (3.5 g). Powdered Yellow Maca showed significantly higher (P<0.001) microbial contamination than the other three, with Black Maca being the least infected. Only minor, statistically-confirmed differences were detected in nutritive characteristics between the four Maca phenotypes grown in Junin, however highly significant differences (P<0.01) in Glucosinolates existed between the Red and Black Maca grown in Junin and Ancash. Irrespective of the cultivation location, Red phenotypes showed the highest content of Total Glucosinolates, followed by Black and Purple, with the Yellow phenotype showing consistently lower levels. Highly significant P<0.01) differences determined in ratios of individual Glucosinolates between four Maca phenotypes grown in two locations, confirms an earlier assumption that sums of individual Glucosinolates, their ratios and profiles, may be feasible to explore in analytically identifying individual Maca phenotypes in pulverised marketed Maca products.

Peruvian Maca (Lepidium peruvianum): (I) Phytochemical and Genetic Differences in Three Maca Phenotypes

PubMed Central

Meissner, Henry O.; Mscisz, Alina; Mrozikiewicz, Mieczyslaw; Baraniak, Marek; Mielcarek, Sebastian; Kedzia, Bogdan; Piatkowska, Ewa; Jólkowska, Justyna; Pisulewski, Pawel

2015-01-01

Glucosinolates were previously reported as physiologically-important constituents present in Peruvian Maca (Lepidium peruvianum Chacon) and linked to various therapeutic functions of differently-colored Peruvian Maca hypocotyls. In two separate Trials, three colours of Maca hypocotyls “Black”, “Red” and “Yellow” (termed “Maca phenotypes”), were selected from mixed crops of Peruvian Maca for laboratory studies as fresh and after being dried. Individual Maca phenotypes were cultivated in the highlands of the Peruvian Andes at 4,200m a.s.l. (Junin and Ninacaca). Glucosinolate levels, chromatographic HPLC profiles and DNA variability in the investigated Maca phenotypes are presented. Genotypic profiles were determined by the ISSR-PCR and RAPD techniques. Compared to the Black and Red phenotypes, the Yellow phenotype contained much lower Glucosinolate levels measured against Glucotropaeolin and m-methoxy-glucotropaeolin standards, and exhibited different RAPD and ISSR-PCR reactions. The Red Maca phenotype showed the highest concentrations of Glucosinolates as compared to the Black and Yellow Maca. It appears that the traditional system used by natives of the Peruvian Andean highlands in preparing Maca as a vegetable dish (boiling dried Maca after soaking in water), to supplement their daily meals, is as effective as laboratory methods - for extracting Glucosinolates, which are considered to be one of the key bioactive constituents responsible for therapeutic functions of Peruvian Maca phenotypes. It is reasonable to assume that the HPLC and DNA techniques combined, or separately, may assist in determining ID and “Fingerprints” identifying individual Peruvian Maca phenotypes, hence confirming the authenticity of marketable Maca products. The above assumptions warrant further laboratory testing. PMID:26508907

A novel framework to alleviate the sparsity problem in context-aware recommender systems

NASA Astrophysics Data System (ADS)

Yu, Penghua; Lin, Lanfen; Wang, Jing

2017-04-01

Recommender systems have become indispensable for services in the era of big data. To improve accuracy and satisfaction, context-aware recommender systems (CARSs) attempt to incorporate contextual information into recommendations. Typically, valid and influential contexts are determined in advance by domain experts or feature selection approaches. Most studies have focused on utilizing the unitary context due to the differences between various contexts. Meanwhile, multi-dimensional contexts will aggravate the sparsity problem, which means that the user preference matrix would become extremely sparse. Consequently, there are not enough or even no preferences in most multi-dimensional conditions. In this paper, we propose a novel framework to alleviate the sparsity issue for CARSs, especially when multi-dimensional contextual variables are adopted. Motivated by the intuition that the overall preferences tend to show similarities among specific groups of users and conditions, we first explore to construct one contextual profile for each contextual condition. In order to further identify those user and context subgroups automatically and simultaneously, we apply a co-clustering algorithm. Furthermore, we expand user preferences in a given contextual condition with the identified user and context clusters. Finally, we perform recommendations based on expanded preferences. Extensive experiments demonstrate the effectiveness of the proposed framework.

Multi-dimensional Upwind Fluctuation Splitting Scheme with Mesh Adaption for Hypersonic Viscous Flow. Degree awarded by Virginia Polytechnic Inst. and State Univ., 9 Nov. 2001

NASA Technical Reports Server (NTRS)

Wood, William A., III

2002-01-01

A multi-dimensional upwind fluctuation splitting scheme is developed and implemented for two-dimensional and axisymmetric formulations of the Navier-Stokes equations on unstructured meshes. Key features of the scheme are the compact stencil, full upwinding, and non-linear discretization which allow for second-order accuracy with enforced positivity. Throughout, the fluctuation splitting scheme is compared to a current state-of-the-art finite volume approach, a second-order, dual mesh upwind flux difference splitting scheme (DMFDSFV), and is shown to produce more accurate results using fewer computer resources for a wide range of test cases. A Blasius flat plate viscous validation case reveals a more accurate upsilon-velocity profile for fluctuation splitting, and the reduced artificial dissipation production is shown relative to DMFDSFV. Remarkably, the fluctuation splitting scheme shows grid converged skin friction coefficients with only five points in the boundary layer for this case. The second half of the report develops a local, compact, anisotropic unstructured mesh adaptation scheme in conjunction with the multi-dimensional upwind solver, exhibiting a characteristic alignment behavior for scalar problems. The adaptation strategy is extended to the two-dimensional and axisymmetric Navier-Stokes equations of motion through the concept of fluctuation minimization.

Species diversity driven by morphological and ecological disparity: a case study of comparative seed morphology and anatomy across a large monocot order

PubMed Central

Benedict, John C.; Smith, Selena Y.; Specht, Chelsea D.; Collinson, Margaret E.; Leong-Škorničková, Jana; Parkinson, Dilworth Y.; Marone, Federica

2016-01-01

Phenotypic variation can be attributed to genetic heritability as well as biotic and abiotic factors. Across Zingiberales, there is a high variation in the number of species per clade and in phenotypic diversity. Factors contributing to this phenotypic variation have never been studied in a phylogenetic or ecological context. Seeds of 166 species from all eight families in Zingiberales were analyzed for 51 characters using synchrotron based 3D X-ray tomographic microscopy to determine phylogenetically informative characters and to understand the distribution of morphological disparity within the order. All families are distinguishable based on seed characters. Non-metric multidimensional scaling analyses show Zingiberaceae occupy the largest seed morphospace relative to the other families, and environmental analyses demonstrate that Zingiberaceae inhabit both temperate and tropical regions, while other Zingiberales are almost exclusively tropical. Temperate species do not cluster in morphospace nor do they share a common suite of character states. This suggests that the diversity seen is not driven by adaptation to temperate niches; rather, the morphological disparity seen likely reflects an underlying genetic plasticity that allowed Zingiberaceae to repeatedly colonize temperate environments. The notable morphoanatomical variety in Zingiberaceae seeds may account for their extraordinary ecological success and high species diversity as compared to other Zingiberales. PMID:27594701

Tensor decomposition-based and principal-component-analysis-based unsupervised feature extraction applied to the gene expression and methylation profiles in the brains of social insects with multiple castes.

PubMed

Taguchi, Y-H

2018-05-08

Even though coexistence of multiple phenotypes sharing the same genomic background is interesting, it remains incompletely understood. Epigenomic profiles may represent key factors, with unknown contributions to the development of multiple phenotypes, and social-insect castes are a good model for elucidation of the underlying mechanisms. Nonetheless, previous studies have failed to identify genes associated with aberrant gene expression and methylation profiles because of the lack of suitable methodology that can address this problem properly. A recently proposed principal component analysis (PCA)-based and tensor decomposition (TD)-based unsupervised feature extraction (FE) can solve this problem because these two approaches can deal with gene expression and methylation profiles even when a small number of samples is available. PCA-based and TD-based unsupervised FE methods were applied to the analysis of gene expression and methylation profiles in the brains of two social insects, Polistes canadensis and Dinoponera quadriceps. Genes associated with differential expression and methylation between castes were identified, and analysis of enrichment of Gene Ontology terms confirmed reliability of the obtained sets of genes from the biological standpoint. Biologically relevant genes, shown to be associated with significant differential gene expression and methylation between castes, were identified here for the first time. The identification of these genes may help understand the mechanisms underlying epigenetic control of development of multiple phenotypes under the same genomic conditions.

Discovery of a “White-Gray-Opaque” Tristable Phenotypic Switching System in Candida albicans: Roles of Non-genetic Diversity in Host Adaptation

PubMed Central

Guan, Guobo; Dai, Yu; Nobile, Clarissa J.; Liang, Weihong; Cao, Chengjun; Zhang, Qiuyu; Zhong, Jin; Huang, Guanghua

2014-01-01

Non-genetic phenotypic variations play a critical role in the adaption to environmental changes in microbial organisms. Candida albicans, a major human fungal pathogen, can switch between several morphological phenotypes. This ability is critical for its commensal lifestyle and for its ability to cause infections. Here, we report the discovery of a novel morphological form in C. albicans, referred to as the “gray” phenotype, which forms a tristable phenotypic switching system with the previously reported white and opaque phenotypes. White, gray, and opaque cell types differ in a number of aspects including cellular and colony appearances, mating competency, secreted aspartyl proteinase (Sap) activities, and virulence. Of the three cell types, gray cells exhibit the highest Sap activity and the highest ability to cause cutaneous infections. The three phenotypes form a tristable phenotypic switching system, which is independent of the regulation of the mating type locus (MTL). Gray cells mate over 1,000 times more efficiently than do white cells, but less efficiently than do opaque cells. We further demonstrate that the master regulator of white-opaque switching, Wor1, is essential for opaque cell formation, but is not required for white-gray transitions. The Efg1 regulator is required for maintenance of the white phenotype, but is not required for gray-opaque transitions. Interestingly, the wor1/wor1 efg1/efg1 double mutant is locked in the gray phenotype, suggesting that Wor1 and Efg1 could function coordinately and play a central role in the regulation of gray cell formation. Global transcriptional analysis indicates that white, gray, and opaque cells exhibit distinct gene expression profiles, which partly explain their differences in causing infections, adaptation ability to diverse host niches, metabolic profiles, and stress responses. Therefore, the white-gray-opaque tristable phenotypic switching system in C. albicans may play a significant role in a wide range of biological aspects in this common commensal and pathogenic fungus. PMID:24691005

Discovery of a "white-gray-opaque" tristable phenotypic switching system in candida albicans: roles of non-genetic diversity in host adaptation.

PubMed

Tao, Li; Du, Han; Guan, Guobo; Dai, Yu; Nobile, Clarissa J; Liang, Weihong; Cao, Chengjun; Zhang, Qiuyu; Zhong, Jin; Huang, Guanghua

2014-04-01

Non-genetic phenotypic variations play a critical role in the adaption to environmental changes in microbial organisms. Candida albicans, a major human fungal pathogen, can switch between several morphological phenotypes. This ability is critical for its commensal lifestyle and for its ability to cause infections. Here, we report the discovery of a novel morphological form in C. albicans, referred to as the "gray" phenotype, which forms a tristable phenotypic switching system with the previously reported white and opaque phenotypes. White, gray, and opaque cell types differ in a number of aspects including cellular and colony appearances, mating competency, secreted aspartyl proteinase (Sap) activities, and virulence. Of the three cell types, gray cells exhibit the highest Sap activity and the highest ability to cause cutaneous infections. The three phenotypes form a tristable phenotypic switching system, which is independent of the regulation of the mating type locus (MTL). Gray cells mate over 1,000 times more efficiently than do white cells, but less efficiently than do opaque cells. We further demonstrate that the master regulator of white-opaque switching, Wor1, is essential for opaque cell formation, but is not required for white-gray transitions. The Efg1 regulator is required for maintenance of the white phenotype, but is not required for gray-opaque transitions. Interestingly, the wor1/wor1 efg1/efg1 double mutant is locked in the gray phenotype, suggesting that Wor1 and Efg1 could function coordinately and play a central role in the regulation of gray cell formation. Global transcriptional analysis indicates that white, gray, and opaque cells exhibit distinct gene expression profiles, which partly explain their differences in causing infections, adaptation ability to diverse host niches, metabolic profiles, and stress responses. Therefore, the white-gray-opaque tristable phenotypic switching system in C. albicans may play a significant role in a wide range of biological aspects in this common commensal and pathogenic fungus.

Self-regulated learning and self-directed study in a pre-college sample

PubMed Central

Abar, Beau; Loken, Eric

2009-01-01

Self-regulated learning (SRL) is a multi-dimensional construct that has been difficult to operationalize using traditional, variable-centered methodologies. The current paper takes a person-centered approach to the study of SRL in a sample of 205 high-school students. Using latent profile analysis on self-reports of seven aspects of SRL, three groups were identified: high SRL, low SRL, and average SRL. Student self-reports of goal orientation were used as validation for the profile solution, with the high academic self- regulation group reporting the highest levels of mastery orientation while the low self-regulation group reported highest levels of avoidant orientation. Profiles were also compared on independently collected, behavioral measures of study behaviors, with the highly self-regulated group tending to study more material and for a longer time than less self-regulated individuals. PMID:20161484

Towards precision medicine-based therapies for glioblastoma: interrogating human disease genomics and mouse phenotypes.

PubMed

Chen, Yang; Gao, Zhen; Wang, Bingcheng; Xu, Rong

2016-08-22

Glioblastoma (GBM) is the most common and aggressive brain tumors. It has poor prognosis even with optimal radio- and chemo-therapies. Since GBM is highly heterogeneous, drugs that target on specific molecular profiles of individual tumors may achieve maximized efficacy. Currently, the Cancer Genome Atlas (TCGA) projects have identified hundreds of GBM-associated genes. We develop a drug repositioning approach combining disease genomics and mouse phenotype data towards predicting targeted therapies for GBM. We first identified disease specific mouse phenotypes using the most recently discovered GBM genes. Then we systematically searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with GBM. We evaluated the ranks for approved and novel GBM drugs, and compared with an existing approach, which also use the mouse phenotype data but not the disease genomics data. We achieved significantly higher ranks for the approved and novel GBM drugs than the earlier approach. For all positive examples of GBM drugs, we achieved a median rank of 9.2 45.6 of the top predictions have been demonstrated effective in inhibiting the growth of human GBM cells. We developed a computational drug repositioning approach based on both genomic and phenotypic data. Our approach prioritized existing GBM drugs and outperformed a recent approach. Overall, our approach shows potential in discovering new targeted therapies for GBM.

Genetic Polymorphisms and Phenotypic Profiles of Sulfadiazine-Resistant and Sensitive Toxoplasma gondii Isolates Obtained from Newborns with Congenital Toxoplasmosis in Minas Gerais, Brazil.

PubMed

Silva, Letícia Azevedo; Reis-Cunha, João Luís; Bartholomeu, Daniella Castanheira; Vítor, Ricardo Wagner Almeida

2017-01-01

Previous Toxoplasma gondii studies revealed that mutations in the dhps (dihydropteroate synthase) gene are associated with resistance to sulfonamides. Although Brazilian strains are genotypically different, very limited data are available regarding the susceptibility of strains obtained from human to sulfonamides. The aim of this study was to evaluate the efficacy of sulfadiazine (SDZ) against Brazilian isolates of T. gondii and verify whether isolates present polymorphisms in the dhps gene. We also investigated whether the virulence-phenotype and/or genotype were associated with the profile of susceptibility to SDZ. Five T. gondii isolates obtained from newborns with congenital toxoplasmosis were used to verify susceptibility. Mice were infected with 104 tachyzoites and orally treated with different doses of SDZ. The mortality curve was evaluated by the Log-rank test. The presence of polymorphisms in the dhps gene was verified using sequencing. A descriptive analysis for 11 Brazilian isolates was used to assess the association between susceptibility, genotype, and virulence-phenotype. Statistical analysis showed that TgCTBr03, 07, 08, and 16 isolates were susceptible to SDZ, whereas TgCTBr11 isolate presented a profile of resistance to SDZ. Nineteen polymorphisms were identified in dhps exons. Seven polymorphisms corresponded to non-synonymous mutations, with four being new mutations, described for the first time in this study. No association was found between the profile of susceptibility and the virulence-phenotype or genotype of the parasite. There is a high variability in the susceptibilities of Brazilian T. gondii strains to SDZ, with evidence of drug resistance. Despite the large number of polymorphisms identified, the profile of susceptibility to SDZ was not associated with any of the dhps variants identified in this study. Other genetic factors, not yet determined, may be associated with the resistance to SDZ; thus, further studies are needed as a basis for a more adequate toxoplasmosis treatment.

Genetic Polymorphisms and Phenotypic Profiles of Sulfadiazine-Resistant and Sensitive Toxoplasma gondii Isolates Obtained from Newborns with Congenital Toxoplasmosis in Minas Gerais, Brazil

PubMed Central

Silva, Letícia Azevedo; Reis-Cunha, João Luís; Bartholomeu, Daniella Castanheira; Vítor, Ricardo Wagner Almeida

2017-01-01

Background Previous Toxoplasma gondii studies revealed that mutations in the dhps (dihydropteroate synthase) gene are associated with resistance to sulfonamides. Although Brazilian strains are genotypically different, very limited data are available regarding the susceptibility of strains obtained from human to sulfonamides. The aim of this study was to evaluate the efficacy of sulfadiazine (SDZ) against Brazilian isolates of T. gondii and verify whether isolates present polymorphisms in the dhps gene. We also investigated whether the virulence-phenotype and/or genotype were associated with the profile of susceptibility to SDZ. Methods Five T. gondii isolates obtained from newborns with congenital toxoplasmosis were used to verify susceptibility. Mice were infected with 104 tachyzoites and orally treated with different doses of SDZ. The mortality curve was evaluated by the Log-rank test. The presence of polymorphisms in the dhps gene was verified using sequencing. A descriptive analysis for 11 Brazilian isolates was used to assess the association between susceptibility, genotype, and virulence-phenotype. Results Statistical analysis showed that TgCTBr03, 07, 08, and 16 isolates were susceptible to SDZ, whereas TgCTBr11 isolate presented a profile of resistance to SDZ. Nineteen polymorphisms were identified in dhps exons. Seven polymorphisms corresponded to non-synonymous mutations, with four being new mutations, described for the first time in this study. No association was found between the profile of susceptibility and the virulence-phenotype or genotype of the parasite. Conclusions There is a high variability in the susceptibilities of Brazilian T. gondii strains to SDZ, with evidence of drug resistance. Despite the large number of polymorphisms identified, the profile of susceptibility to SDZ was not associated with any of the dhps variants identified in this study. Other genetic factors, not yet determined, may be associated with the resistance to SDZ; thus, further studies are needed as a basis for a more adequate toxoplasmosis treatment. PMID:28118394

QuantWorm: a comprehensive software package for Caenorhabditis elegans phenotypic assays.

PubMed

Jung, Sang-Kyu; Aleman-Meza, Boanerges; Riepe, Celeste; Zhong, Weiwei

2014-01-01

Phenotypic assays are crucial in genetics; however, traditional methods that rely on human observation are unsuitable for quantitative, large-scale experiments. Furthermore, there is an increasing need for comprehensive analyses of multiple phenotypes to provide multidimensional information. Here we developed an automated, high-throughput computer imaging system for quantifying multiple Caenorhabditis elegans phenotypes. Our imaging system is composed of a microscope equipped with a digital camera and a motorized stage connected to a computer running the QuantWorm software package. Currently, the software package contains one data acquisition module and four image analysis programs: WormLifespan, WormLocomotion, WormLength, and WormEgg. The data acquisition module collects images and videos. The WormLifespan software counts the number of moving worms by using two time-lapse images; the WormLocomotion software computes the velocity of moving worms; the WormLength software measures worm body size; and the WormEgg software counts the number of eggs. To evaluate the performance of our software, we compared the results of our software with manual measurements. We then demonstrated the application of the QuantWorm software in a drug assay and a genetic assay. Overall, the QuantWorm software provided accurate measurements at a high speed. Software source code, executable programs, and sample images are available at www.quantworm.org. Our software package has several advantages over current imaging systems for C. elegans. It is an all-in-one package for quantifying multiple phenotypes. The QuantWorm software is written in Java and its source code is freely available, so it does not require use of commercial software or libraries. It can be run on multiple platforms and easily customized to cope with new methods and requirements.

Phenotypic characteristics of adolescents with concave and convex facial profiles - The National Health Examination Survey.

PubMed

Hujoel, P P; Bollen, A-M; Yuen, K C J; Hujoel, I A

2016-10-01

It has been suggested that facial traits are informative on the inherited susceptibility to tuberculosis and obesity, two current global health issues. Our aim was to compare the phenotypic characteristics of adolescents with dental markers for a concave (n=420), a convex (n=978), and a straight (n=3542) facial profile in a nationally representative sample of United States adolescents. The results show that adolescents with a concave facial profile, when compared to a straight facial profile, had an increased waist-to-height ratio (Δ, 1.1 [95% CI 0.5-1.7], p<0.003) and an increased acne prevalence (OR, 1.5 [95% CI 1.2-1.9], p<0.001). Adolescents with a convex facial profile, when compared to a straight facial profile, had an increased prevalence of tuberculosis (OR, 4.3 [95% CI 1.4-13.1], p<0.02), increased ectomorphy (Δ, 0.3 [95% CI 0.2-0.4], p<0.0001), increased left-handedness (OR, 1.4 [95% CI 1.1-1.7], p<0.007), increased color-blindness (OR, 1.7 [95% CI 1.3-2.3], p<0.004), and rhesus ee phenotype (OR, 1.3 [95% CI 1.1-1.5], p<0.008). Adolescents with a concave facial profile, when compared to a convex profile, had increased mesomorphy (Δ, 1.3 [95% CI 1.1-1.5], p<0.0001), increased endomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), lower ectomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), and lower vocabulary test scores (Δ, 2.3 [95% CI 0.8-3.8], p<0.008). It is concluded that population-based survey data confirm that distinct facial features are associated with distinct somatotypes and distinct disease susceptibilities. Copyright © 2016 Elsevier GmbH. All rights reserved.

Phenotypic factors influencing the variation in response of circulating cholesterol level to personalised dietary advice in the Food4Me study.

PubMed

Kirwan, Laura; Walsh, Marianne C; Celis-Morales, Carlos; Marsaux, Cyril F M; Livingstone, Katherine M; Navas-Carretero, Santiago; Fallaize, Rosalind; O'Donovan, Clare B; Woolhead, Clara; Forster, Hannah; Kolossa, Silvia; Daniel, Hannelore; Moschonis, George; Manios, Yannis; Surwillo, Agnieszka; Godlewska, Magdalena; Traczyk, Iwona; Drevon, Christian A; Gibney, Mike J; Lovegrove, Julie A; Martinez, J Alfredo; Saris, Wim H M; Mathers, John C; Gibney, Eileen R; Brennan, Lorraine

2016-12-01

Individual response to dietary interventions can be highly variable. The phenotypic characteristics of those who will respond positively to personalised dietary advice are largely unknown. The objective of this study was to compare the phenotypic profiles of differential responders to personalised dietary intervention, with a focus on total circulating cholesterol. Subjects from the Food4Me multi-centre study were classified as responders or non-responders to dietary advice on the basis of the change in cholesterol level from baseline to month 6, with lower and upper quartiles defined as responder and non-responder groups, respectively. There were no significant differences between demographic and anthropometric profiles of the groups. Furthermore, with the exception of alcohol, there was no significant difference in reported dietary intake, at baseline. However, there were marked differences in baseline fatty acid profiles. The responder group had significantly higher levels of stearic acid (18 : 0, P=0·034) and lower levels of palmitic acid (16 : 0, P=0·009). Total MUFA (P=0·016) and total PUFA (P=0·008) also differed between the groups. In a step-wise logistic regression model, age, baseline total cholesterol, glucose, five fatty acids and alcohol intakes were selected as factors that successfully discriminated responders from non-responders, with sensitivity of 82 % and specificity of 83 %. The successful delivery of personalised dietary advice may depend on our ability to identify phenotypes that are responsive. The results demonstrate the potential use of metabolic profiles in identifying response to an intervention and could play an important role in the development of precision nutrition.

Effects of a weight loss program on body composition and the metabolic profile in obese postmenopausal women displaying various obesity phenotypes: a MONET group study.

PubMed

Normandin, Eve; Doucet, Eric; Rabasa-Lhoret, Rémi; Brochu, Martin

2015-07-01

Obesity is a heterogeneous condition, since the metabolic profile may differ greatly from one individual to another. The objective of this study was to compare the effect of a 6-month diet-induced weight loss program on body composition and the metabolic profile in obese individuals displaying different obesity phenotypes. Secondary analyses were done on 129 obese (% body fat: 46% ± 4%) postmenopausal women (age: 57 ± 4 years). Outcome measures included body composition, body fat distribution, glucose homeostasis, fasting lipids, and blood pressure. Obesity phenotypes were determined based on lean body mass (LBM) index (LBMI = LBM/height(2)) and visceral fat (VF) accumulation, as follows: 1, lower VF and lower LBMI (n = 35); 2, lower VF and higher LBMI (n = 19); 3, higher VF and lower LBMI (n = 14); and 4, higher VF and higher LBMI (n = 61). All groups had significantly improved measures of body composition after the intervention (P < 0.0001). Greater decreases in LBM and LBMI were observed in the higher LBMI groups than in the lower LBMI groups (P < 0.0001). Similarly, decreases in VF were greater in the higher VF groups than in the lower VF groups (P < 0.05). Overall, fasting insulin levels and glucose disposal improved following the intervention, with higher LBMI groups showing a trend for greater improvements (P = 0.06 and 0.07, respectively). Overall, no difference was observed among the different obesity phenotypes regarding improvements in the metabolic profile in response to weight loss. Individuals displaying higher VF or higher LBMI at baseline experienced significantly greater decreases for these variables after the intervention.

Language Phenotypes and Intervention Planning: Bridging Research and Practice

ERIC Educational Resources Information Center

Fidler, Deborah J.; Philofsky, Amy; Hepburn, Susan L.

2007-01-01

This paper focuses on the communication and language phenotypes associated with three genetic disorders: Down syndrome, Williams syndrome, and fragile X syndrome. It is argued that there is empirical evidence that these disorders predispose children to specific profiles of strength and weakness in some areas of speech, language, and communication,…

Cognitive and Psychiatric Phenotypes of Movement Disorders in Children: A Systematic Review

ERIC Educational Resources Information Center

Ben-Pazi, Hilla; Jaworowski, Solomon; Shalev, Ruth S

2011-01-01

Aim: The cognitive and psychiatric aspects of adult movement disorders are well established, but specific behavioural profiles for paediatric movement disorders have not been delineated. Knowledge of non-motor phenotypes may guide treatment and determine which symptoms are suggestive of a specific movement disorder and which indicate medication…

Integrating multiple analytical datasets to compare metabolite profiles of mouse colonic-cecal contents and feces

USDA-ARS?s Scientific Manuscript database

The pattern of metabolites produced by the gut microbiome comprises a phenotype indicative of the means by which that microbiome affects the gut. We characterized that phenotype in mice by conducting metabolomic analyses of the colonic-cecal contents, comparing that to the metabolite patterns of fec...

Consensus-phenotype integration of transcriptomic and metabolomic data implies a role for metabolism in the chemosensitivity of tumour cells.

PubMed

Cavill, Rachel; Kamburov, Atanas; Ellis, James K; Athersuch, Toby J; Blagrove, Marcus S C; Herwig, Ralf; Ebbels, Timothy M D; Keun, Hector C

2011-03-01

Using transcriptomic and metabolomic measurements from the NCI60 cell line panel, together with a novel approach to integration of molecular profile data, we show that the biochemical pathways associated with tumour cell chemosensitivity to platinum-based drugs are highly coincident, i.e. they describe a consensus phenotype. Direct integration of metabolome and transcriptome data at the point of pathway analysis improved the detection of consensus pathways by 76%, and revealed associations between platinum sensitivity and several metabolic pathways that were not visible from transcriptome analysis alone. These pathways included the TCA cycle and pyruvate metabolism, lipoprotein uptake and nucleotide synthesis by both salvage and de novo pathways. Extending the approach across a wide panel of chemotherapeutics, we confirmed the specificity of the metabolic pathway associations to platinum sensitivity. We conclude that metabolic phenotyping could play a role in predicting response to platinum chemotherapy and that consensus-phenotype integration of molecular profiling data is a powerful and versatile tool for both biomarker discovery and for exploring the complex relationships between biological pathways and drug response.

Protein Interactome of Muscle Invasive Bladder Cancer

PubMed Central

Bhat, Akshay; Heinzel, Andreas; Mayer, Bernd; Perco, Paul; Mühlberger, Irmgard; Husi, Holger; Merseburger, Axel S.; Zoidakis, Jerome; Vlahou, Antonia; Schanstra, Joost P.; Mischak, Harald; Jankowski, Vera

2015-01-01

Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder. PMID:25569276

Using convolutional neural networks to explore the microbiome.

PubMed

Reiman, Derek; Metwally, Ahmed; Yang Dai

2017-07-01

The microbiome has been shown to have an impact on the development of various diseases in the host. Being able to make an accurate prediction of the phenotype of a genomic sample based on its microbial taxonomic abundance profile is an important problem for personalized medicine. In this paper, we examine the potential of using a deep learning framework, a convolutional neural network (CNN), for such a prediction. To facilitate the CNN learning, we explore the structure of abundance profiles by creating the phylogenetic tree and by designing a scheme to embed the tree to a matrix that retains the spatial relationship of nodes in the tree and their quantitative characteristics. The proposed CNN framework is highly accurate, achieving a 99.47% of accuracy based on the evaluation on a dataset 1967 samples of three phenotypes. Our result demonstrated the feasibility and promising aspect of CNN in the classification of sample phenotype.

The oral spelling profile of posterior cortical atrophy and the nature of the graphemic representation.

PubMed

Primativo, Silvia; Yong, Keir X X; Shakespeare, Timothy J; Crutch, Sebastian J

2017-01-08

Spelling is a complex cognitive task where central and peripheral components are involved in engaging resources from many different cognitive processes. The present paper aims to both characterize the oral spelling deficit in a population of patients affected by a neurodegenerative condition and to clarify the nature of the graphemic representation within the currently available spelling models. Indeed, the nature of graphemic representation as a linear or multi-componential structure is still debated. Different hypotheses have been raised about its nature in the orthographic lexicon, with one positing that graphemes are complex objects whereby quantity and identity are separately represented in orthographic representations and can thus be selectively impaired. Posterior cortical atrophy (PCA) is a neurodegenerative condition that mainly affects visuoperceptual and visuospatial functions. Spelling impairments are considered part of the disease. Nonetheless the spelling deficit has received little attention so far and often it has been interpreted in relation to peripheral impairments such as writing difficulties associated with visuoperceptual and visuospatial deficits. In the present study we provide a detailed characterization of the oral spelling profile in PCA. The data suggest that multiple deficits underpin oral spelling problems in PCA, with elements of surface and phonological dysgraphia but also suggesting the involvement of the graphemic buffer. A large phenotypic individual variability is reported. Moreover, the larger proportion and the specific nature of errors involving geminate (i.e., double) as compared to non-geminate (i.e., non-double) letters suggest that a further central impairment might be associated with the abstract graphemic representation of letter numerosity. The present study contributes to the clinical characterization of PCA and to the current debate in the cognitive literature on spelling models; findings, despite not definitive, support the hypothesis that graphemic representations are multidimensional mental objects that separately encode information about grapheme identity and quantity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative Molecular Phenotyping of Gill Remodeling in a Cichlid Fish Responding to Salinity Stress*

PubMed Central

Kültz, Dietmar; Li, Johnathon; Gardell, Alison; Sacchi, Romina

2013-01-01

A two-tiered label-free quantitative (LFQ) proteomics workflow was used to elucidate how salinity affects the molecular phenotype, i.e. proteome, of gills from a cichlid fish, the euryhaline tilapia (Oreochromis mossambicus). The workflow consists of initial global profiling of relative tryptic peptide abundances in treated versus control samples followed by targeted identification (by MS/MS) and quantitation (by chromatographic peak area integration) of validated peptides for each protein of interest. Fresh water acclimated tilapia were independently exposed in separate experiments to acute short-term (34 ppt) and gradual long-term (70 ppt, 90 ppt) salinity stress followed by molecular phenotyping of the gill proteome. The severity of salinity stress can be deduced with high technical reproducibility from the initial global label-free quantitative profiling step alone at both peptide and protein levels. However, an accurate regulation ratio can only be determined by targeted label-free quantitative profiling because not all peptides used for protein identification are also valid for quantitation. Of the three salinity challenges, gradual acclimation to 90 ppt has the most pronounced effect on gill molecular phenotype. Known salinity effects on tilapia gills, including an increase in the size and number of mitochondria-rich ionocytes, activities of specific ion transporters, and induction of specific molecular chaperones are reflected in the regulation of abundances of the corresponding proteins. Moreover, specific protein isoforms that are responsive to environmental salinity change are resolved and it is revealed that salinity effects on the mitochondrial proteome are nonuniform. Furthermore, protein NDRG1 has been identified as a novel key component of molecular phenotype restructuring during salinity-induced gill remodeling. In conclusion, besides confirming known effects of salinity on gills of euryhaline fish, molecular phenotyping reveals novel insight into proteome changes that underlie the remodeling of tilapia gill epithelium in response to environmental salinity change. PMID:24065692

RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans

PubMed Central

Hall, Sarah E.; Chirn, Gung-Wei; Lau, Nelson C.; Sengupta, Piali

2013-01-01

Early environmental experiences profoundly influence adult phenotypes through complex mechanisms that are poorly understood. We previously showed that adult Caenorhabditis elegans that transiently passed through the stress-induced dauer larval stage (post-dauer adults) exhibit significant changes in gene expression profiles, chromatin states, and life history traits when compared with adults that bypassed the dauer stage (control adults). These wild-type, isogenic animals of equivalent developmental stages exhibit different signatures of molecular marks that reflect their distinct developmental trajectories. To gain insight into the mechanisms that contribute to these developmental history-dependent phenotypes, we profiled small RNAs from post-dauer and control adults by deep sequencing. RNA interference (RNAi) pathways are known to regulate genome-wide gene expression both at the chromatin and post-transcriptional level. By quantifying changes in endogenous small interfering RNA (endo-siRNA) levels in post-dauer as compared with control animals, our analyses identified a subset of genes that are likely targets of developmental history-dependent reprogramming through a complex RNAi-mediated mechanism. Mutations in specific endo-siRNA pathways affect expected gene expression and chromatin state changes for a subset of genes in post-dauer animals, as well as disrupt their increased brood size phenotype. We also find that both chromatin state and endo-siRNA distribution in dauers are unique, and suggest that remodeling in dauers provides a template for the subsequent establishment of adult post-dauer profiles. Our results indicate a role for endo-siRNA pathways as a contributing mechanism to early experience-dependent phenotypic plasticity in adults, and describe how developmental history can program adult physiology and behavior via epigenetic mechanisms. PMID:23329696

The National Niemann-Pick Type C1 Disease Database: correlation of lipid profiles, mutations, and biochemical phenotypes

PubMed Central

Garver, William S.; Jelinek, David; Meaney, F. John; Flynn, James; Pettit, Kathleen M.; Shepherd, Glen; Heidenreich, Randall A.; Vockley, Cate M. Walsh; Castro, Graciela; Francis, Gordon A.

2010-01-01

Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage disorder characterized by neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration. The present study provides the lipid profiles, mutations, and corresponding associations with the biochemical phenotype obtained from NPC1 patients who participated in the National NPC1 Disease Database. Lipid profiles were obtained from 34 patients (39%) in the survey and demonstrated significantly reduced plasma LDL cholesterol (LDL-C) and increased plasma triglycerides in the majority of patients. Reduced plasma HDL cholesterol (HDL-C) was the most consistent lipoprotein abnormality found in male and female NPC1 patients across age groups and occurred independent of changes in plasma triglycerides. A subset of 19 patients for whom the biochemical severity of known NPC1 mutations could be correlated with their lipid profile showed a strong inverse correlation between plasma HDL-C and severity of the biochemical phenotype. Gene mutations were available for 52 patients (59%) in the survey, including 52 different mutations and five novel mutations (Y628C, P887L, I923V, A1151T, and 3741_3744delACTC). Together, these findings provide novel information regarding the plasma lipoprotein changes and mutations in NPC1 disease, and suggest plasma HDL-C represents a potential biomarker of NPC1 disease severity. PMID:19744920

Identification of Clinical Isolates of Actinomyces Species by Amplified 16S Ribosomal DNA Restriction Analysis

PubMed Central

Hall, Val; Talbot, P. R.; Stubbs, S. L.; Duerden, B. I.

2001-01-01

Amplified 16S ribosomal DNA (rDNA) restriction analysis (ARDRA), using enzymes HaeIII and HpaII, was applied to 176 fresh and 299 stored clinical isolates of putative Actinomyces spp. referred to the Anaerobe Reference Unit of the Public Health Laboratory Service for confirmation of identity. Results were compared with ARDRA results obtained previously for reference strains and with conventional phenotypic reactions. Identities of some strains were confirmed by analysis of partial 16S rDNA sequences. Of the 475 isolates, 331 (70%) were clearly assigned to recognized Actinomyces species, including 94 isolates assigned to six recently described species. A further 52 isolates in 12 ARDRA profiles were designated as apparently resembling recognized species, and 44 isolates, in 18 novel profiles, were confirmed as members of genera other than Actinomyces. The identities of 48 isolates in nine profiles remain uncertain, and they may represent novel species of Actinomyces. For the majority of species, phenotypic results, published reactions for the species, and ARDRA profiles concurred. However, of 113 stored isolates originally identified as A. meyeri or resembling A. meyeri by phenotypic tests, only 21 were confirmed as A. meyeri by ARDRA; 63 were reassigned as A. turicensis, 7 as other recognized species, and 22 as unidentified actinomycetes. Analyses of incidence and clinical associations of Actinomyces spp. add to the currently sparse knowledge of some recently described species. PMID:11574572

[Behavioural phenotypes in Prader-Willi syndrome].

PubMed

Rosell-Raga, L

2003-02-01

The behavioural phenotype of Prader-Willi syndrome (PWS) is defined by a neurological profile and a characteristic pattern of behavioural disorders which include cognitive deficits, learning difficulties and behavioural problems, which increase with age, both in number and gravity. We review the behavioural phenotype of the cases of PWS in the Valencian Community, together with their peculiar behaviours, and analyse how these generate family and social problems. The description of a peculiar behaviour opens up new horizons when understanding and treating PWS, both from a pharmacological and neuropsychological perspective.

Specific identification of Bacillus anthracis strains

NASA Astrophysics Data System (ADS)

Krishnamurthy, Thaiya; Deshpande, Samir; Hewel, Johannes; Liu, Hongbin; Wick, Charles H.; Yates, John R., III

2007-01-01

Accurate identification of human pathogens is the initial vital step in treating the civilian terrorism victims and military personnel afflicted in biological threat situations. We have applied a powerful multi-dimensional protein identification technology (MudPIT) along with newly generated software termed Profiler to identify the sequences of specific proteins observed for few strains of Bacillus anthracis, a human pathogen. Software termed Profiler was created to initially screen the MudPIT data of B. anthracis strains and establish the observed proteins specific for its strains. A database was also generated using Profiler containing marker proteins of B. anthracis and its strains, which in turn could be used for detecting the organism and its corresponding strains in samples. Analysis of the unknowns by our methodology, combining MudPIT and Profiler, led to the accurate identification of the anthracis strains present in samples. Thus, a new approach for the identification of B. anthracis strains in unknown samples, based on the molecular mass and sequences of marker proteins, has been ascertained.

Mitochondrial Transfer by Photothermal Nanoblade Restores Metabolite Profile in Mammalian Cells.

PubMed

Wu, Ting-Hsiang; Sagullo, Enrico; Case, Dana; Zheng, Xin; Li, Yanjing; Hong, Jason S; TeSlaa, Tara; Patananan, Alexander N; McCaffery, J Michael; Niazi, Kayvan; Braas, Daniel; Koehler, Carla M; Graeber, Thomas G; Chiou, Pei-Yu; Teitell, Michael A

2016-05-10

mtDNA sequence alterations are challenging to generate but desirable for basic studies and potential correction of mtDNA diseases. Here, we report a new method for transferring isolated mitochondria into somatic mammalian cells using a photothermal nanoblade, which bypasses endocytosis and cell fusion. The nanoblade rescued the pyrimidine auxotroph phenotype and respiration of ρ0 cells that lack mtDNA. Three stable isogenic nanoblade-rescued clones grown in uridine-free medium showed distinct bioenergetics profiles. Rescue lines 1 and 3 reestablished nucleus-encoded anapleurotic and catapleurotic enzyme gene expression patterns and had metabolite profiles similar to the parent cells from which the ρ0 recipient cells were derived. By contrast, rescue line 2 retained a ρ0 cell metabolic phenotype despite growth in uridine-free selection. The known influence of metabolite levels on cellular processes, including epigenome modifications and gene expression, suggests metabolite profiling can help assess the quality and function of mtDNA-modified cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

PubMed

Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco

2017-05-18

Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coordinated transcriptional regulation patterns associated with infertility phenotypes in men

PubMed Central

Ellis, Peter J I; Furlong, Robert A; Conner, Sarah J; Kirkman‐Brown, Jackson; Afnan, Masoud; Barratt, Christopher; Griffin, Darren K; Affara, Nabeel A

2007-01-01

Introduction Microarray gene‐expression profiling is a powerful tool for global analysis of the transcriptional consequences of disease phenotypes. Understanding the genetic correlates of particular pathological states is important for more accurate diagnosis and screening of patients, and thus for suggesting appropriate avenues of treatment. As yet, there has been little research describing gene‐expression profiling of infertile and subfertile men, and thus the underlying transcriptional events involved in loss of spermatogenesis remain unclear. Here we present the results of an initial screen of 33 patients with differing spermatogenic phenotypes. Methods Oligonucleotide array expression profiling was performed on testis biopsies for 33 patients presenting for testicular sperm extraction. Significantly regulated genes were selected using a mixed model analysis of variance. Principle components analysis and hierarchical clustering were used to interpret the resulting dataset with reference to the patient history, clinical findings and histological composition of the biopsies. Results Striking patterns of coordinated gene expression were found. The most significant contains multiple germ cell‐specific genes and corresponds to the degree of successful spermatogenesis in each patient, whereas a second pattern corresponds to inflammatory activity within the testis. Smaller‐scale patterns were also observed, relating to unique features of the individual biopsies. PMID:17496197

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

PubMed

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.

Abuse Experiences of Family Members, Child Maltreatment, and the Development of Sex Offending Among Incarcerated Adolescent Males.

PubMed

McCuish, Evan C; Cale, Jesse; Corrado, Raymond R

2017-02-01

Child sexual abuse is considered a risk factor for the development of sexual offending in adolescence. Beyond this, comparisons of the risk factor profiles between adolescent sex offenders (ASOs) and adolescent non-sex offenders (ANSOs) have uncovered minimal differences. However, differences between ASOs and ANSOs in terms of patterns in the abuse histories of their family members have rarely been studied. The aim in the current study was to retrospectively examine histories of abuse among family members of ASOs compared with ANSOs to determine whether and how these were related to youth abuse experiences and sexual offending in adolescence. The current study is based on a sample of 482 incarcerated male adolescents (ASOs = 67, ANSOs = 415). Latent class analysis was conducted to determine multidimensional familial abuse profiles, and a series of logistic regression models were used to examine the relationship between family abuse profiles, youth abuse experiences, and adolescent sexual offending. Overall, familial abuse profiles were related to subsequent youth abuse experiences and sexual offending, and these abuse profiles differentiated ASOs and ANSOs.

Disentangling Heterogeneity of Childhood Disruptive Behavior Problems Into Dimensions and Subgroups.

PubMed

Bolhuis, Koen; Lubke, Gitta H; van der Ende, Jan; Bartels, Meike; van Beijsterveldt, Catharina E M; Lichtenstein, Paul; Larsson, Henrik; Jaddoe, Vincent W V; Kushner, Steven A; Verhulst, Frank C; Boomsma, Dorret I; Tiemeier, Henning

2017-08-01

Irritable and oppositional behaviors are increasingly considered as distinct dimensions of oppositional defiant disorder. However, few studies have explored this multidimensionality across the broader spectrum of disruptive behavior problems (DBPs). This study examined the presence of dimensions and distinct subgroups of childhood DBPs, and the cross-sectional and longitudinal associations between these dimensions. Using factor mixture models (FMMs), the presence of dimensions and subgroups of DBPs was assessed in the Generation R Study at ages 6 (n = 6,209) and 10 (n = 4,724) years. Replications were performed in two population-based cohorts (Netherlands Twin Registry, n = 4,402, and Swedish Twin Study of Child and Adolescent Development, n = 1,089) and a clinical sample (n = 1,933). We used cross-lagged modeling in the Generation R Study to assess cross-sectional and longitudinal associations between dimensions. DBPs were assessed using mother-reported responses to the Child Behavior Checklist. Empirically obtained dimensions of DBPs were oppositional behavior (age 6 years), disobedient behavior, rule-breaking behavior (age 10 years), physical aggression, and irritability (both ages). FMMs suggested that one-class solutions had the best model fit for all dimensions in all three population-based cohorts. Similar results were obtained in the clinical sample. All three dimensions, including irritability, predicted subsequent physical aggression (range, 0.08-0.16). This study showed that childhood DBPs should be regarded as a multidimensional phenotype rather than comprising distinct subgroups. Incorporating multidimensionality will improve diagnostic accuracy and refine treatment. Future studies need to address the biological validity of the DBP dimensions observed in this study; herein lies an important opportunity for neuroimaging and genetic measures. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Surface modified capillary electrophoresis combined with in solution isoelectric focusing and MALDI-TOF/TOF MS: a gel-free multidimensional electrophoresis approach for proteomic profiling--exemplified on human follicular fluid.

PubMed

Hanrieder, Jörg; Zuberovic, Aida; Bergquist, Jonas

2009-04-24

Development of miniaturized analytical tools continues to be of great interest to face the challenges in proteomic analysis of complex biological samples such as human body fluids. In the light of these challenges, special emphasis is put on the speed and simplicity of newly designed technological approaches as well as the need for cost efficiency and low sample consumption. In this study, we present an alternative multidimensional bottom-up approach for proteomic profiling for fast, efficient and sensitive protein analysis in complex biological matrices. The presented setup was based on sample pre-fractionation using microscale in solution isoelectric focusing (IEF) followed by tryptic digestion and subsequent capillary electrophoresis (CE) coupled off-line to matrix assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI TOF MS/MS). For high performance CE-separation, PolyE-323 modified capillaries were applied to minimize analyte-wall interactions. The potential of the analytical setup was demonstrated on human follicular fluid (hFF) representing a typical complex human body fluid with clinical implication. The obtained results show significant identification of 73 unique proteins (identified at 95% significance level), including mostly acute phase proteins but also protein identities that are well known to be extensively involved in follicular development.

Integrating Gene Transcription-Based Biomarkers to Understand Desert Tortoise and Ecosystem Health.

PubMed

Bowen, Lizabeth; Miles, A Keith; Drake, K Kristina; Waters, Shannon C; Esque, Todd C; Nussear, Kenneth E

2015-09-01

Tortoises are susceptible to a wide variety of environmental stressors, and the influence of human disturbances on health and survival of tortoises is difficult to detect. As an addition to current diagnostic methods for desert tortoises, we have developed the first leukocyte gene transcription biomarker panel for the desert tortoise (Gopherus agassizii), enhancing the ability to identify specific environmental conditions potentially linked to declining animal health. Blood leukocyte transcript profiles have the potential to identify physiologically stressed animals in lieu of clinical signs. For desert tortoises, the gene transcript profile included a combination of immune or detoxification response genes with the potential to be modified by biological or physical injury and consequently provide information on the type and magnitude of stressors present in the animal's habitat. Blood from 64 wild adult tortoises at three sites in Clark County, NV, and San Bernardino, CA, and from 19 captive tortoises in Clark County, NV, was collected and evaluated for genes indicative of physiological status. Statistical analysis using a priori groupings indicated significant differences among groups for several genes, while multidimensional scaling and cluster analyses of transcription C T values indicated strong differentiation of a large cluster and multiple outlying individual tortoises or small clusters in multidimensional space. These analyses highlight the effectiveness of the gene panel at detecting environmental perturbations as well as providing guidance in determining the health of the desert tortoise.

Integrating gene transcription-based biomarkers to understand desert tortoise and ecosystem health

USGS Publications Warehouse

Bowen, Lizabeth; Miles, A. Keith; Drake, Karla K.; Waters, Shannon C.; Esque, Todd C.; Nussear, Kenneth E.

2015-01-01

Tortoises are susceptible to a wide variety of environmental stressors, and the influence of human disturbances on health and survival of tortoises is difficult to detect. As an addition to current diagnostic methods for desert tortoises, we have developed the first leukocyte gene transcription biomarker panel for the desert tortoise (Gopherus agassizii), enhancing the ability to identify specific environmental conditions potentially linked to declining animal health. Blood leukocyte transcript profiles have the potential to identify physiologically stressed animals in lieu of clinical signs. For desert tortoises, the gene transcript profile included a combination of immune or detoxification response genes with the potential to be modified by biological or physical injury and consequently provide information on the type and magnitude of stressors present in the animal’s habitat. Blood from 64 wild adult tortoises at three sites in Clark County, NV, and San Bernardino, CA, and from 19 captive tortoises in Clark County, NV, was collected and evaluated for genes indicative of physiological status. Statistical analysis using a priori groupings indicated significant differences among groups for several genes, while multidimensional scaling and cluster analyses of transcriptionC T values indicated strong differentiation of a large cluster and multiple outlying individual tortoises or small clusters in multidimensional space. These analyses highlight the effectiveness of the gene panel at detecting environmental perturbations as well as providing guidance in determining the health of the desert tortoise.

Associations between Repetitive Questioning, Resistance to Change, Temper Outbursts and Anxiety in Prader-Willi and Fragile-X Syndromes

ERIC Educational Resources Information Center

Woodcock, K.; Oliver, C.; Humphreys, G.

2009-01-01

Background: The behavioural phenotypes of Prader-Willi (PWS) and Fragile-X (FraX) syndromes both comprise repetitive behaviours with differences between the profiles. In this study we investigated the context and antecedents to the repetitive behaviours and the association with other behavioural phenotypic characteristics in order to generate…

Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota.

PubMed

Serino, Matteo; Luche, Elodie; Gres, Sandra; Baylac, Audrey; Bergé, Mathieu; Cenac, Claire; Waget, Aurelie; Klopp, Pascale; Iacovoni, Jason; Klopp, Christophe; Mariette, Jerome; Bouchez, Olivier; Lluch, Jerome; Ouarné, Francoise; Monsan, Pierre; Valet, Philippe; Roques, Christine; Amar, Jacques; Bouloumié, Anne; Théodorou, Vassilia; Burcelin, Remy

2012-04-01

The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.

Gene profiling-based phenotyping for identification of cellular parameters that contribute to fitness, stress-tolerance and virulence of Listeria monocytogenes variants.

PubMed

Koomen, Jeroen; den Besten, Heidy M W; Metselaar, Karin I; Tempelaars, Marcel H; Wijnands, Lucas M; Zwietering, Marcel H; Abee, Tjakko

2018-06-07

Microbial population heterogeneity allows for a differential microbial response to environmental stresses and can lead to the selection of stress resistant variants. In this study, we have used two different stress resistant variants of Listeria monocytogenes LO28 with mutations in the rpsU gene encoding ribosomal protein S21, to elucidate features that can contribute to fitness, stress-tolerance and host interaction using a comparative gene profiling and phenotyping approach. Transcriptome analysis showed that 116 genes were upregulated and 114 genes were downregulated in both rpsU variants. Upregulated genes included a major contribution of SigB-controlled genes such as intracellular acid resistance-associated glutamate decarboxylase (GAD) (gad3), genes involved in compatible solute uptake (opuC), glycerol metabolism (glpF, glpK, glpD), and virulence (inlA, inlB). Downregulated genes in the two variants involved mainly genes involved in flagella synthesis and motility. Phenotyping results of the two rpsU variants matched the gene profiling data including enhanced freezing resistance conceivably linked to compatible solute accumulation, higher glycerol utilisation rates, and better adhesion to Caco 2 cells presumably linked to higher expression of internalins. Also, bright field and electron microscopy analysis confirmed reduced flagellation of the variants. The activation of SigB-mediated stress defence offers an explanation for the multiple-stress resistant phenotype in rpsU variants. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality

PubMed Central

Bárcena, Paloma; Jara-Acevedo, María; Tabernero, María Dolores; López, Antonio; Sánchez, María Luz; García-Montero, Andrés C.; Muñoz-García, Noemí; Vidriales, María Belén; Paiva, Artur; Lecrevisse, Quentin; Lima, Margarida; Langerak, Anton W.; Böttcher, Sebastian; van Dongen, Jacques J.M.

2015-01-01

Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56low NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56low NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94hi/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality. PMID:26556869

Local Context Finder (LCF) reveals multidimensional relationships among mRNA expression profiles of Arabidopsis responding to pathogen infection

PubMed Central

Katagiri, Fumiaki; Glazebrook, Jane

2003-01-01

A major task in computational analysis of mRNA expression profiles is definition of relationships among profiles on the basis of similarities among them. This is generally achieved by pattern recognition in the distribution of data points representing each profile in a high-dimensional space. Some drawbacks of commonly used pattern recognition algorithms stem from their use of a globally linear space and/or limited degrees of freedom. A pattern recognition method called Local Context Finder (LCF) is described here. LCF uses nonlinear dimensionality reduction for pattern recognition. Then it builds a network of profiles based on the nonlinear dimensionality reduction results. LCF was used to analyze mRNA expression profiles of the plant host Arabidopsis interacting with the bacterial pathogen Pseudomonas syringae. In one case, LCF revealed two dimensions essential to explain the effects of the NahG transgene and the ndr1 mutation on resistant and susceptible responses. In another case, plant mutants deficient in responses to pathogen infection were classified on the basis of LCF analysis of their profiles. The classification by LCF was consistent with the results of biological characterization of the mutants. Thus, LCF is a powerful method for extracting information from expression profile data. PMID:12960373

HIV serostatus disclosure: development and validation of indicators considering target and modality. Results from a community-based research in 5 countries.

PubMed

Préau, Marie; Beaulieu-Prévost, Dominic; Henry, Emilie; Bernier, Adeline; Veillette-Bourbeau, Ludivine; Otis, Joanne

2015-12-01

HIV serostatus disclosure is a complex challenge for persons living with HIV (PLHIV). Despite its beneficial effects, it can also lead to stigmatization and rejection. The current lack of multi-dimensional measurement tools impede an in-depth understanding of the dynamic of disclosure. To develop and validate complex measures of serostatus disclosure. This international community based research study was performed by joint research teams (researchers/community based organizations (CBO)) in five countries (Democratic Republic of the Congo, Ecuador, Mali, Morocco and Romania). A convenience sample of 1500 people living with HIV (PLHIV) in contact with local CBO were recruited in 2011 (300 in each country). Face-to-face interviews were performed using a 125-item questionnaire covering HIV status disclosure to 23 potential disclosure targets and related issues (including personal history with HIV, people's reaction to disclosure, sexuality). A principal component analysis and a hierarchical cluster analysis were performed, in order to identify the main components of HIV disclosure, create measures and classify participants into profiles. Patterns of disclosure were summarized using two main measures: direct and indirect disclosure. Disclosure to sexual partners, whether steady or not, was different from patterns of disclosure to other targets. Among the participants, three profiles emerged - labelled Restricted disclosure, Mainly indirect disclosure and Mainly direct disclosure, respectively representing 61%, 13% and 26% of the total sample. The profiles were associated with different aspects of PLHIV's lives, including self-efficacy, functional limitations and social exclusion. Patterns varied across the five studied countries. Results suggest that multi-dimensional constructs should be used to measure disclosure in order to improve understanding of the disclosure process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-metric multidimensional performance indicator scaling reveals seasonal and team dissimilarity within the National Rugby League.

PubMed

Woods, Carl T; Robertson, Sam; Sinclair, Wade H; Collier, Neil French

2018-04-01

Analysing the dissimilarity of seasonal and team profiles within elite sport may reveal the evolutionary dynamics of game-play, while highlighting the similarity of individual team profiles. This study analysed seasonal and team dissimilarity within the National Rugby League (NRL) between the 2005 to 2016 seasons. Longitudinal. Total seasonal values for 15 performance indicators were collected for every NRL team over the analysed period (n=190 observations). Non-metric multidimensional scaling was used to reveal seasonal and team dissimilarity. Compared to the 2005 to 2011 seasons, the 2012 to 2016 seasons were in a state of flux, with a relative dissimilarity in the positioning of team profiles on the ordination surface. There was an abrupt change in performance indicator characteristics following the 2012 season, with the 2014 season reflecting a large increase in the total count of 'all run metres' (d=1.21; 90% CI=0.56-1.83), 'kick return metres' (d=2.99; 90% CI=2.12-3.84) and decrease in 'missed tackles' (d=-2.43; 90% CI=-3.19 to -1.64) and 'tackle breaks' (d=-2.41; 90% CI=-3.17 to -1.62). Interpretation of team ordination plots showed that certain teams evolved in (dis)similar ways over the analysed period. It appears that NRL match-types evolved following the 2012 season and are in a current state of flux. The modification of coaching tactics and rule changes may have contributed to these observations. Coaches could use these results when designing prospective game strategies in the NRL. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal

PubMed Central

Gao, Jianjiong; Aksoy, Bülent Arman; Dogrusoz, Ugur; Dresdner, Gideon; Gross, Benjamin; Sumer, S. Onur; Sun, Yichao; Jacobsen, Anders; Sinha, Rileen; Larsson, Erik; Cerami, Ethan; Sander, Chris; Schultz, Nikolaus

2014-01-01

The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics. PMID:23550210

"Heroes" and "villains" of world history across cultures.

PubMed

Hanke, Katja; Liu, James H; Sibley, Chris G; Paez, Dario; Gaines, Stanley O; Moloney, Gail; Leong, Chan-Hoong; Wagner, Wolfgang; Licata, Laurent; Klein, Olivier; Garber, Ilya; Böhm, Gisela; Hilton, Denis J; Valchev, Velichko; Khan, Sammyh S; Cabecinhas, Rosa

2015-01-01

Emergent properties of global political culture were examined using data from the World History Survey (WHS) involving 6,902 university students in 37 countries evaluating 40 figures from world history. Multidimensional scaling and factor analysis techniques found only limited forms of universality in evaluations across Western, Catholic/Orthodox, Muslim, and Asian country clusters. The highest consensus across cultures involved scientific innovators, with Einstein having the most positive evaluation overall. Peaceful humanitarians like Mother Theresa and Gandhi followed. There was much less cross-cultural consistency in the evaluation of negative figures, led by Hitler, Osama bin Laden, and Saddam Hussein. After more traditional empirical methods (e.g., factor analysis) failed to identify meaningful cross-cultural patterns, Latent Profile Analysis (LPA) was used to identify four global representational profiles: Secular and Religious Idealists were overwhelmingly prevalent in Christian countries, and Political Realists were common in Muslim and Asian countries. We discuss possible consequences and interpretations of these different representational profiles.

Cognitive Profile of Turner Syndrome

ERIC Educational Resources Information Center

Hong, David; Kent, Jamie Scaletta; Kesler, Shelli

2009-01-01

Turner syndrome (TS) is a relatively common neurogenetic disorder characterized by complete or partial monosomy-X in a phenotypic female. TS is associated with a cognitive profile that typically includes intact intellectual function and verbal abilities with relative weaknesses in visual-spatial, executive, and social cognitive domains. In this…

Phenotypic Characterization of Retinoic Acid Differentiated SH-SY5Y Cells by Transcriptional Profiling

PubMed Central

Korecka, Joanna A.; van Kesteren, Ronald E.; Blaas, Eva; Spitzer, Sonia O.; Kamstra, Jorke H.; Smit, August B.; Swaab, Dick F.; Verhaagen, Joost; Bossers, Koen

2013-01-01

Multiple genetic and environmental factors play a role in the development and progression of Parkinson’s disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributors to the disease process, there is a great need for readily accessible cells with prominent DAergic features that can be used for reproducible in vitro cellular screening. Here, we investigated the molecular phenotype of retinoic acid (RA) differentiated SH-SY5Y cells using genome wide transcriptional profiling combined with gene ontology, transcription factor and molecular pathway analysis. We demonstrated that RA induces a general neuronal differentiation program in SH-SY5Y cells and that these cells develop a predominantly mature DAergic-like neurotransmitter phenotype. This phenotype is characterized by increased dopamine levels together with a substantial suppression of other neurotransmitter phenotypes, such as those for noradrenaline, acetylcholine, glutamate, serotonin and histamine. In addition, we show that RA differentiated SH-SY5Y cells express the dopamine and noradrenalin neurotransmitter transporters that are responsible for uptake of MPP(+), a well known DAergic cell toxicant. MPP(+) treatment alters mitochondrial activity according to its proposed cytotoxic effect in DAergic neurons. Taken together, RA differentiated SH-SY5Y cells have a DAergic-like phenotype, and provide a good cellular screening tool to find novel genes or compounds that affect cytotoxic processes that are associated with PD. PMID:23724009

Motivational profiles in table tennis players: Relations with performance anxiety and subjective vitality.

PubMed

Chu, Tsz Lun Alan; Zhang, Tao; Hung, Tsung-Min

2018-06-27

Research has suggested the need to use a person-centred approach to examine multidimensionality of motivation. Guided by self-determination theory (Deci & Ryan, 1985), the primary aim of the present study was to examine the motivational profiles in table tennis players and their composition by gender, country, training status, and competition levels (from recreational to international). The secondary aim was to examine the differences in performance anxiety and subjective vitality across the motivational profiles. Participants were 281 table tennis players from multiple countries, mostly the U.S. and China. Hierarchical and nonhierarchical cluster analyses were conducted and showed three motivational profiles with distinct quantity and quality: "low", "controlled", and "self-determined". Chi-square tests of independence demonstrated significant differences in their cluster membership by country, formal training with a coach, and competition levels, but not gender. MANCOVA results indicated differences in performance anxiety and subjective vitality across the motivational profiles, in which the controlled profile had the greatest anxiety symptoms. These differences are attributed to the quality over quantity of motivation, which have meaningful implications for table tennis coaches and sport psychology consultants to diagnose and intervene with players in order to reduce their performance anxiety and improve their well-being.

Metabolomic mapping of cancer stem cells for reducing and exploiting tumor heterogeneity.

PubMed

Cuyàs, Elisabet; Verdura, Sara; Fernández-Arroyo, Salvador; Bosch-Barrera, Joaquim; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

2017-11-21

Personalized cancer medicine based on the analysis of tumors en masse is limited by tumor heterogeneity, which has become a major obstacle to effective cancer treatment. Cancer stem cells (CSC) are emerging as key drivers of inter- and intratumoral heterogeneity. CSC have unique metabolic dependencies that are required not only for specific bioenergetic/biosynthetic demands but also for sustaining their operational epigenetic traits, i.e. self-renewal, tumor-initiation, and plasticity. Given that the metabolome is the final downstream product of all the -omic layers and, therefore, most representative of the biological phenotype, we here propose that a novel approach to better understand the complexity of tumor heterogeneity is by mapping and cataloging small numbers of CSC metabolomic phenotypes. The narrower metabolomic diversity of CSC states could be employed to reduce multidimensional tumor heterogeneity into dynamic models of fewer actionable sub-phenotypes. The identification of the driver nodes that are used differentially by CSC states to metabolically regulate self-renewal and tumor initation and escape chemotherapy might open new preventive and therapeutic avenues. The mapping of CSC metabolomic states could become a pioneering strategy to reduce the dimensionality of tumor heterogeneity and improve our ability to examine changes in tumor cell populations for cancer detection, prognosis, prediction/monitoring of therapy response, and detection of therapy resistance and recurrent disease. The identification of driver metabolites and metabolic nodes accounting for a large amount of variance within the CSC metabolomic sub-phenotypes might offer new unforeseen opportunities for reducing and exploiting tumor heterogeneity via metabolic targeting of CSC.

Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

PubMed

Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

2015-02-01

Tumor genome sequencing leads to documenting thousands of DNA mutations and other genomic alterations. At present, these data cannot be analyzed adequately to aid in the understanding of tumorigenesis and its evolution. Moreover, we have little insight into how to use these data to predict clinical phenotypes and tumor progression to better design patient treatment. To meet these challenges, we discuss a cancer hallmark network framework for modeling genome sequencing data to predict cancer clonal evolution and associated clinical phenotypes. The framework includes: (1) cancer hallmarks that can be represented by a few molecular/signaling networks. 'Network operational signatures' which represent gene regulatory logics/strengths enable to quantify state transitions and measures of hallmark traits. Thus, sets of genomic alterations which are associated with network operational signatures could be linked to the state/measure of hallmark traits. The network operational signature transforms genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e., hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection of hallmark traits). Furthermore, the framework considers regulatory logics of the hallmark networks under tumor evolutionary dynamics and therefore also includes: (2) a self-promoting positive feedback loop that is dominated by a genomic instability network and a cell survival/proliferation network is the main driver of tumor clonal evolution. Surrounding tumor stroma and its host immune systems shape the evolutionary paths; (3) cell motility initiating metastasis is a byproduct of the above self-promoting loop activity during tumorigenesis; (4) an emerging hallmark network which triggers genome duplication dominates a feed-forward loop which in turn could act as a rate-limiting step for tumor formation; (5) mutations and other genomic alterations have specific patterns and tissue-specificity, which are driven by aging and other cancer-inducing agents. This framework represents the logics of complex cancer biology as a myriad of phenotypic complexities governed by a limited set of underlying organizing principles. It therefore adds to our understanding of tumor evolution and tumorigenesis, and moreover, potential usefulness of predicting tumors' evolutionary paths and clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for cancer patients, as well as cancer risks for healthy individuals are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial impact on timely diagnosis, personalized treatment and personalized prevention of cancer. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways

PubMed Central

Koumakis, Lefteris; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Vassou, Despoina; Marias, Kostas; Moustakis, Vassilis; Potamias, George

2016-01-01

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the unique characteristic to color regulatory relations between genes and reveal their phenotype inclination. This unique characteristic makes MinePath a valuable tool for in silico molecular biology experimentation as it serves the biomedical researchers’ exploratory needs to reveal and interpret the regulatory mechanisms that underlie and putatively govern the expression of target phenotypes. PMID:27832067

MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways.

PubMed

Koumakis, Lefteris; Kanterakis, Alexandros; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Tsiknakis, Manolis; Vassou, Despoina; Kafetzopoulos, Dimitris; Marias, Kostas; Moustakis, Vassilis; Potamias, George

2016-11-01

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the unique characteristic to color regulatory relations between genes and reveal their phenotype inclination. This unique characteristic makes MinePath a valuable tool for in silico molecular biology experimentation as it serves the biomedical researchers' exploratory needs to reveal and interpret the regulatory mechanisms that underlie and putatively govern the expression of target phenotypes.

Latent Profiles of Temperament and Their Relations of Psychopathology and Wellness

ERIC Educational Resources Information Center

Rettew, David C.; Althoff, Robert R.; Dumenci, Levent; Ayer, Lynsay; Hudziak, James J.

2008-01-01

The study applies latent profiles analysis to a group of children and adolescents to test temperament phenotypes in order to examine their association to wellness and psychopathology. One of the results concluded that lifetime disorder was lower in the steady class as compared to moderate class.

Short-term phenotypic plasticity in long-chain cuticular hydrocarbons

PubMed Central

Thomas, Melissa L.; Simmons, Leigh W.

2011-01-01

Cuticular hydrocarbons provide arthropods with the chemical equivalent of the visually extravagant plumage of birds. Their long chain length, together with the number and variety of positions in which methyl branches and double bonds occur, provide cuticular hydrocarbons with an extraordinary level of information content. Here, we demonstrate phenotypic plasticity in an individual's cuticular hydrocarbon profile. Using solid-phase microextraction, a chemical technique that enables multiple sampling of the same individual, we monitor short-term changes in cuticular hydrocarbon profiles of individual crickets, Teleogryllus oceanicus, in response to a social challenge. We experimentally manipulate the dominance status of males and find that dominant males, on losing fights with other dominant males, change their hydrocarbon profile to more closely resemble that of a subordinate. This result demonstrates that cuticular hydrocarbons can be far more responsive to changes in social dominance than previously realized. PMID:21367785

Species diversity driven by morphological and ecological disparity: a case study of comparative seed morphology and anatomy across a large monocot order.

PubMed

Benedict, John C; Smith, Selena Y; Specht, Chelsea D; Collinson, Margaret E; Leong-Škorničková, Jana; Parkinson, Dilworth Y; Marone, Federica

2016-01-01

Phenotypic variation can be attributed to genetic heritability as well as biotic and abiotic factors. Across Zingiberales, there is a high variation in the number of species per clade and in phenotypic diversity. Factors contributing to this phenotypic variation have never been studied in a phylogenetic or ecological context. Seeds of 166 species from all eight families in Zingiberales were analyzed for 51 characters using synchrotron based 3D X-ray tomographic microscopy to determine phylogenetically informative characters and to understand the distribution of morphological disparity within the order. All families are distinguishable based on seed characters. Non-metric multidimensional scaling analyses show Zingiberaceae occupy the largest seed morphospace relative to the other families, and environmental analyses demonstrate that Zingiberaceae inhabit both temperate and tropical regions, while other Zingiberales are almost exclusively tropical. Temperate species do not cluster in morphospace nor do they share a common suite of character states. This suggests that the diversity seen is not driven by adaptation to temperate niches; rather, the morphological disparity seen likely reflects an underlying genetic plasticity that allowed Zingiberaceae to repeatedly colonize temperate environments. The notable morphoanatomical variety in Zingiberaceae seeds may account for their extraordinary ecological success and high species diversity as compared to other Zingiberales. © The Authors 2016. Published by Oxford University Press on behalf of the Annals of Botany Company.

Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes

PubMed Central

Haaker, Jan; Glotzbach-Schoon, Evelyn; Schümann, Dirk; Andreatta, Marta; Mechias, Marie-Luise; Raczka, Karolina; Gartmann, Nina; Büchel, Christian; Mühlberger, Andreas; Pauli, Paul; Reif, Andreas; Kalisch, Raffael; Lonsdorf, Tina B.

2016-01-01

Abstract Being a complex phenotype with substantial heritability, anxiety and related phenotypes are characterized by a complex polygenic basis. Thereby, one candidate pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning processes. Using a multi-dimensional and -methodological replication approach, we investigated the impact of a functional promoter polymorphism (NOS1-ex1f-VNTR) on human anxiety-related phenotypes in a total of 1019 healthy controls in five different studies. Homozygous carriers of the NOS1-ex1f short-allele displayed enhanced trait anxiety, worrying and depression scores. Furthermore, short-allele carriers were characterized by increased anxious apprehension during contextual fear conditioning. While autonomous measures (fear-potentiated startle) provided only suggestive evidence for a modulatory role of NOS1-ex1f-VNTR on (contextual) fear conditioning processes, neural activation at the amygdala/anterior hippocampus junction was significantly increased in short-allele carriers during context conditioning. Notably, this could not be attributed to morphological differences. In accordance with data from a plethora of rodent studies, we here provide converging evidence from behavioral, subjective, psychophysiological and neuroimaging studies in large human cohorts that NOS-I plays an important role in anxious apprehension but provide only limited evidence for a role in (contextual) fear conditioning. PMID:26746182

SM2PH-db: an interactive system for the integrated analysis of phenotypic consequences of missense mutations in proteins involved in human genetic diseases.

PubMed

Friedrich, Anne; Garnier, Nicolas; Gagnière, Nicolas; Nguyen, Hoan; Albou, Laurent-Philippe; Biancalana, Valérie; Bettler, Emmanuel; Deléage, Gilbert; Lecompte, Odile; Muller, Jean; Moras, Dino; Mandel, Jean-Louis; Toursel, Thierry; Moulinier, Luc; Poch, Olivier

2010-02-01

Understanding how genetic alterations affect gene products at the molecular level represents a first step in the elucidation of the complex relationships between genotypic and phenotypic variations, and is thus a major challenge in the postgenomic era. Here, we present SM2PH-db (http://decrypthon.igbmc.fr/sm2ph), a new database designed to investigate structural and functional impacts of missense mutations and their phenotypic effects in the context of human genetic diseases. A wealth of up-to-date interconnected information is provided for each of the 2,249 disease-related entry proteins (August 2009), including data retrieved from biological databases and data generated from a Sequence-Structure-Evolution Inference in Systems-based approach, such as multiple alignments, three-dimensional structural models, and multidimensional (physicochemical, functional, structural, and evolutionary) characterizations of mutations. SM2PH-db provides a robust infrastructure associated with interactive analysis tools supporting in-depth study and interpretation of the molecular consequences of mutations, with the more long-term goal of elucidating the chain of events leading from a molecular defect to its pathology. The entire content of SM2PH-db is regularly and automatically updated thanks to a computational grid data federation facilities provided in the context of the Decrypthon program. (c) 2009 Wiley-Liss, Inc.

Increased glutamate/GABA+ ratio in a shared autistic and schizotypal trait phenotype termed Social Disorganisation.

PubMed

Ford, Talitha C; Nibbs, Richard; Crewther, David P

2017-01-01

Autism and schizophrenia are multi-dimensional spectrum disorders that have substantial phenotypic overlap. This overlap is readily identified in the non-clinical population, and has been conceptualised as Social Disorganisation (SD). This study investigates the balance of excitatory glutamate and inhibitory γ -aminobutyric acid (GABA) concentrations in a non-clinical sample with high and low trait SD, as glutamate and GABA abnormalities are reported across the autism and schizophrenia spectrum disorders. Participants were 18 low (10 females) and 19 high (9 females) SD scorers aged 18 to 40 years who underwent 1 H-MRS for glutamate and GABA+macromolecule (GABA+) concentrations in right and left hemisphere superior temporal (ST) voxels. Reduced GABA+ concentration ( p  = 0.03) and increased glutamate/GABA+ ratio ( p  = 0.003) in the right ST voxel for the high SD group was found, and there was increased GABA+ concentration in the left compared to right ST voxel ( p  = 0.047). Bilateral glutamate concentration was increased for the high SD group ( p  = 0.006); there was no hemisphere by group interaction ( p  = 0.772). Results suggest that a higher expression of the SD phenotype may be associated with increased glutamate/GABA+ ratio in the right ST region, which may affect speech prosody processing, and lead behavioural characteristics that are shared within the autistic and schizotypal spectra.

The down syndrome behavioral phenotype: implications for practice and research in occupational therapy.

PubMed

Daunhauer, Lisa A; Fidler, Deborah J

2011-01-01

ABSTRACT Down syndrome (DS) is the most common chromosomal cause of intellectual disability. The genetic causes of DS are associated with characteristic outcomes, such as relative strengths in visual-spatial skills and relative challenges in motor planning. This profile of outcomes, called the DS behavioral phenotype, may be a critical tool for intervention planning and research in this population. In this article, aspects of the DS behavioral phenotype potentially relevant to occupational therapy practice are reviewed. Implications and challenges for etiology-informed research and practice are discussed.

The broad autism phenotype predicts relationship outcomes in newly formed college roommates.

PubMed

Faso, Daniel J; Corretti, Conrad A; Ackerman, Robert A; Sasson, Noah J

2016-05-01

Although previous studies have reported that the broad autism phenotype is associated with reduced relationship quality within established relationships, understanding how this association emerges requires assessment prior to relationship development. In the present longitudinal study, college roommates with minimal familiarity prior to cohabitation (N = 162) completed the broad autism phenotype questionnaire and intermittently reported on their relationship quality and interpersonal behaviors toward their roommate over their first 10 weeks of living together. Actor-Partner Interdependence Models demonstrated that roommates mismatched on aloofness (one high and one low) had lower relationship satisfaction than those matched on it, with the interpersonal behavior of warmth mediating this association. Because relationship satisfaction remained high when both roommates were aloof, satisfaction does not appear predicated upon the presence of aloofness generally but rather reflects a product of dissimilarity in aloof profiles between roommates. In contrast, although participants reported less relationship satisfaction and commitment with roommates higher on pragmatic language abnormalities, mismatches on this broad autism phenotype trait, and on rigid personality, were less consequential. In sum, these findings suggest that complementary profiles of social motivation may facilitate relationship quality during the early course of relationship development. © The Author(s) 2015.

TRAC-PD2 posttest analysis of the CCTF Evaluation-Model Test C1-19 (Run 38). [PWR

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

Motley, F.

The results of a Transient Reactor Analysis Code posttest analysis of the Cylindral Core Test Facility Evaluation-Model Test agree very well with the results of the experiment. The good agreement obtained verifies the multidimensional analysis capability of the TRAC code. Because of the steep radial power profile, the importance of using fine noding in the core region was demonstrated (as compared with poorer results obtained from an earlier pretest prediction that used a coarsely noded model).

Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset | Office of Cancer Genomics

Cancer.gov

Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset.

A European multi-centre External Quality Assessment (EQA) study on phenotypic and genotypic methods used for Herpes Simplex Virus (HSV) drug resistance testing.

PubMed

Afshar, Baharak; Bibby, David F; Piorkowska, Renata; Ohemeng-Kumi, Natasha; Snoeck, Robert; Andrei, Graciela; Gillemot, Sarah; Morfin, Florence; Frobert, Emilie; Burrel, Sonia; Boutolleau, David; Crowley, Brendan; Mbisa, Jean L

2017-11-01

Herpes Simplex Virus (HSV) drug resistance is a significant public health concern among immunocompromised individuals. Phenotypic assays are considered the gold standard method for detecting HSV drug resistance. However, plaque reduction assays (PRAs) are technically demanding, often with long turnaround times of up to four weeks. In contrast, genotypic tests can be performed within a few days. The development and coordination of the first European External Quality Assessment (EQA) study to evaluate phenotypic and genotypic methods used for HSV drug resistance testing in specialised reference laboratories. Four HSV-1 or HSV-2 strains with different antiviral susceptibility profiles were isolated from clinical samples. Isolates were quantified by qPCR, and aliquoted in culture medium. One isolate was distributed at two dilutions to help assess assay sensitivity. The panel was distributed to five European centres with a six-week deadline for the return of phenotypic and genotypic results, together with clinical reports. Four out of five participating labs returned results by the deadline. Limited results were later available from the fifth lab. Phenotypic and genotypic data were largely, but not completely, concordant. An unusual resistance profile shown by one of the samples was explained by the detection of a mixed virus population after extensive further investigation by one of the centres. Discordant clinical outputs reflecting the diversity of phenotypic methodologies demonstrated the utility of this exercise. With emerging genotypic technologies looking to supplant phenotyping, there is a need for curated public databases, accessible interpretation tools and standardised control materials for quality management. By establishing a network of testing laboratories, we hope that this EQA scheme will facilitate ongoing progress in this area. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Genetic variation in aryl N-acetyltransferase results in significant differences in the pharmacokinetic and safety profiles of amifampridine (3,4-diaminopyridine) phosphate.

PubMed

Haroldsen, Peter E; Garovoy, Marvin R; Musson, Donald G; Zhou, Huiyu; Tsuruda, Laurie; Hanson, Boyd; O'Neill, Charles A

2015-02-01

The clinical use of amifampridine phosphate for neuromuscular junction disorders is increasing. The metabolism of amifampridine occurs via polymorphic aryl N-acetyltransferase (NAT), yet its pharmacokinetic (PK) and safety profiles, as influenced by this enzyme system, have not been investigated. The objective of this study was to assess the effect of NAT phenotype and genotype on the PK and safety profiles of amifampridine in healthy volunteers (N = 26). A caffeine challenge test and NAT2 genotyping were used to delineate subjects into slow and fast acetylators for PK and tolerability assessment of single, escalating doses of amifampridine (up to 30 mg) and in multiple daily doses (20 mg QID) of amifampridine. The results showed that fast acetylator phenotypes displayed significantly lower C max, AUC, and shorter t 1/2 for amifampridine than slow acetylators. Plasma concentrations of the N-acetyl metabolite were approximately twofold higher in fast acetylators. Gender differences were not observed. Single doses of amifampridine demonstrated dose linear PKs. Amifampridine achieved steady state plasma levels within 1 day of dosing four times daily. No accumulation or time-dependent changes in amifampridine PK parameters occurred. Overall, slow acetylators reported 73 drug-related treatment-emergent adverse events versus 6 in fast acetylators. Variations in polymorphic NAT corresponding with fast and slow acetylator phenotypes significantly affects the PK and safety profiles of amifampridine.

Meloidogyne partityla on Pecan Isozyme Phenotypes and Other Host.

PubMed

Starr, J L; Tomaszewski, E K; Mundo-Ocampo, M; Baldwin, J G

1996-12-01

Meloidogyne sp. from five pecan (Carya illinoensis) orchards in Texas were distinctive in host range and iszoyme profiles from common species of Meloidogyne but were morphologically congruent with Meloidogyne partityla Kleynhans, a species previously known only in South Africa. In addition to pecan, species of walnut (Juglans hindsii and J. regia) and hickory (C. ovata) also were hosts. No reproduction was observed on 15 other plant species from nine families, including several common hosts of other Meloidogyne spp. Three esterase phenotypes and two malate dehydrogenase phenotypes of M. partityla were identified by polyacrylamide gel electrophoresis. Each of these isozyme phenotypes was distinct from those of the more common species M. arenaria, M. hapla, M. incognita, and M. javanica.

Prenatal lipopolysaccharide exposure affects sexual dimorphism in different germlines of mice with a depressive phenotype.

PubMed

Reis-Silva, Thiago M; Cohn, Daniel W H; Sandini, Thaísa M; Udo, Mariana S B; Teodorov, Elizabeth; Bernardi, Maria Martha

2016-03-15

The objective of the present study was to investigate whether prenatal lipopolysaccharide (LPS) administration modifies the expression of depressive and non-depressive-like behavior in male and female mice across two generations. The sexual dimorphism of these mice was also examined in the open-field test. Male and female mice of the parental (F0) generation were selected for depressive- or non-depressive-like behavioral profiles using the tail suspension test (TST). Animals with similar profiles were matched for further mating. On gestation day (GD) 15, pregnant F0 mice received LPS (100μg/kg, i.p.) and were allowed to nurture their offspring freely. Adult male and female of the F1 generation were then selected according to behavioral profiles and observed in the open field. Male and female mice of the two behavioral profiles were then mated to obtain the F2 generation. Adults from the F2 generation were also behaviorally phenotyped, and open field behavior was assessed. Male mice that were selected for depressive- and non-depressive-like behaviors and treated or not with LPS in the parental generation exhibited similar proportions of behavioral profiles in both filial lines, but LPS exposure increased the number of depressive-like behavior. An effect of gender was observed in the F1 and F2 generations, in which male mice were more sensitive to the intergenerational effects of LPS in the TST. These data indicate that prenatal LPS exposure on GD15 in the F0 generation influenced the transmission of depressive- and non-depressive-like behavior across filial lines, with sexual dimorphism between phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

Divergent Label-free Cell Phenotypic Pharmacology of Ligands at the Overexpressed β2-Adrenergic Receptors

NASA Astrophysics Data System (ADS)

Ferrie, Ann M.; Sun, Haiyan; Zaytseva, Natalya; Fang, Ye

2014-01-01

We present subclone sensitive cell phenotypic pharmacology of ligands at the β2-adrenergic receptor (β2-AR) stably expressed in HEK-293 cells. The parental cell line was transfected with green fluorescent protein (GFP)-tagged β2-AR. Four stable subclones were established and used to profile a library of sixty-nine AR ligands. Dynamic mass redistribution (DMR) profiling resulted in a pharmacological activity map suggesting that HEK293 endogenously expresses functional Gi-coupled α2-AR and Gs-coupled β2-AR, and the label-free cell phenotypic activity of AR ligands are subclone dependent. Pathway deconvolution revealed that the DMR of epinephrine is originated mostly from the remodeling of actin microfilaments and adhesion complexes, to less extent from the microtubule networks and receptor trafficking, and certain agonists displayed different efficacy towards the cAMP-Epac pathway. We demonstrate that receptor signaling and ligand pharmacology is sensitive to the receptor expression level, and the organization of the receptor and its signaling circuitry.

Phage phenomics: Physiological approaches to characterize novel viral proteins

ScienceCinema

Sanchez, Savannah E. [San Diego State Univ., San Diego, CA (United States); Cuevas, Daniel A. [San Diego State Univ., San Diego, CA (United States); Rostron, Jason E. [San Diego State Univ., San Diego, CA (United States); Liang, Tiffany Y. [San Diego State Univ., San Diego, CA (United States); Pivaroff, Cullen G. [San Diego State Univ., San Diego, CA (United States); Haynes, Matthew R. [San Diego State Univ., San Diego, CA (United States); Nulton, Jim [San Diego State Univ., San Diego, CA (United States); Felts, Ben [San Diego State Univ., San Diego, CA (United States); Bailey, Barbara A. [San Diego State Univ., San Diego, CA (United States); Salamon, Peter [San Diego State Univ., San Diego, CA (United States); Edwards, Robert A. [San Diego State Univ., San Diego, CA (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Burgin, Alex B. [Broad Institute, Cambridge, MA (United States); Segall, Anca M. [San Diego State Univ., San Diego, CA (United States); Rohwer, Forest [San Diego State Univ., San Diego, CA (United States)

2018-06-21

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysis by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.

Untargeted Metabolic Quantitative Trait Loci Analyses Reveal a Relationship between Primary Metabolism and Potato Tuber Quality1[W][OA

PubMed Central

Carreno-Quintero, Natalia; Acharjee, Animesh; Maliepaard, Chris; Bachem, Christian W.B.; Mumm, Roland; Bouwmeester, Harro; Visser, Richard G.F.; Keurentjes, Joost J.B.

2012-01-01

Recent advances in -omics technologies such as transcriptomics, metabolomics, and proteomics along with genotypic profiling have permitted dissection of the genetics of complex traits represented by molecular phenotypes in nonmodel species. To identify the genetic factors underlying variation in primary metabolism in potato (Solanum tuberosum), we have profiled primary metabolite content in a diploid potato mapping population, derived from crosses between S. tuberosum and wild relatives, using gas chromatography-time of flight-mass spectrometry. In total, 139 polar metabolites were detected, of which we identified metabolite quantitative trait loci for approximately 72% of the detected compounds. In order to obtain an insight into the relationships between metabolic traits and classical phenotypic traits, we also analyzed statistical associations between them. The combined analysis of genetic information through quantitative trait locus coincidence and the application of statistical learning methods provide information on putative indicators associated with the alterations in metabolic networks that affect complex phenotypic traits. PMID:22223596

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

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma.

PubMed

Arora, Shilpi; Gonzales, Irma M; Hagelstrom, R Tanner; Beaudry, Christian; Choudhary, Ashish; Sima, Chao; Tibes, Raoul; Mousses, Spyro; Azorsa, David O

2010-08-18

Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma.

Infection of hematopoietic stem cells by Leishmania infantum increases erythropoiesis and alters the phenotypic and functional profiles of progeny.

PubMed

Carvalho-Gontijo, Raquel; Moreira, Diana Raquel; Resende, Mariana; Costa-Silva, Matheus Fernandes; Peruhype-Magalhães, Vanessa; Ribeiro, Cláudia Maria Franco; Ribeiro, Daniel Dias; Silvestre, Ricardo; Cordeiro-da-Silva, Anabela; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa

2018-04-01

Immunosuppression is a well-established risk factor for Visceral Leishmaniasis. Post-immunosuppression leishmaniasis is characterized by an increase of parasite burden, hematopoietic disorders and unusual clinical manifestations. Although there are many reports on bone marrow findings in VL, less is known about the relationship between parasite dynamics in this organ and the function of either hematopoietic stem cells and progenitor cells themselves. In the present study, we tackle these issues using a new approach of infecting human stem cells derived from bone marrow with L. infantum. Using this strategy, we show that human hematopoietic stem cells (hHSC) are able to phagocytize L. infantum promastigotes and release modulatory and pro-inflammatory cytokines, mainly TNF-α. Our results demonstrated that L. infantum infection in vitro enhances hematopoiesis, favoring the development of erythrocitic lineage through a mechanism yet unknown. Moreover, we found that L. infantum infection alters the phenotypic profile of the hematopoietic progeny; modifying the surface markers expression of differentiated cells. Thus, our study represents a rare opportunity to monitor the in vitro differentiation of human stem cells experimentally infected by L. infantum to better understand the consequences of the infection on phenotypic and functional profile of the cell progeny. Copyright © 2017. Published by Elsevier Inc.

Osteosarcopenic Visceral Obesity and Osteosarcopenic Subcutaneous Obesity, Two New Phenotypes of Sarcopenia: Prevalence, Metabolic Profile, and Risk Factors

PubMed Central

Spadaccini, Daniele; Nichetti, Mara; Avanzato, Ilaria; Faliva, Milena Anna

2018-01-01

Background The main criticism of the definition of “osteosarcopenic obesity” (OSO) is the lack of division between subcutaneous and visceral fat. This study describes the prevalence, metabolic profile, and risk factors of two new phenotypes of sarcopenia: osteosarcopenic visceral obesity (OSVAT) and osteosarcopenic subcutaneous obesity (OSSAT). Methods A standardized geriatric assessment was performed by anthropometric and biochemical measures. Dual-energy X-ray absorptiometry (DXA) was used to assess body composition, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), osteoporosis, and sarcopenia. Results A sample of 801 subjects were assessed (247 men; 554 women). The prevalence of osteosarcopenic obesity (OSO) was 6.79%; OSSAT and OSOVAT were, respectively, 2.22% and 4.56%. OSVAT (versus the others) showed a higher level of inflammation (CRP and ESR, p < 0.05), bilirubin (p < 0.05), and risk of fractures (FRAX index over 15%, p < 0.001). Subjects with OSSAT did not show any significant risk factors associated to obesity. Conclusions The osteosarcopenic visceral obesity phenotype (OSVAT) seems to be associated with a higher risk of fractures, inflammation, and a worse metabolic profile. These conditions in OSVAT cohort are associated with an increase of visceral adipose tissue, while patients with OSSAT seem to benefit related to the “obesity paradox”. PMID:29862078

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

PubMed Central

Boyd, Penelope J.; Shorrock, Hannah K.; Carter, Roderick N.; Powis, Rachael A.; Thomson, Sophie R.; Thomson, Derek; Graham, Laura C.; Motyl, Anna A. L.; Highley, J. Robin; Becker, Thomas; Becker, Catherina G.; Heath, Paul R.

2017-01-01

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo. PMID:28426667

MicroCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system.

PubMed

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.

Molecular and Biochemical Analysis of the Galactose Phenotype of Dairy Streptococcus thermophilus Strains Reveals Four Different Fermentation Profiles

PubMed Central

de Vin, Filip; Rådström, Peter; Herman, Lieve; De Vuyst, Luc

2005-01-01

Lactose-limited fermentations of 49 dairy Streptococcus thermophilus strains revealed four distinct fermentation profiles with respect to galactose consumption after lactose depletion. All the strains excreted galactose into the medium during growth on lactose, except for strain IMDOST40, which also displayed extremely high galactokinase (GalK) activity. Among this strain collection eight galactose-positive phenotypes sensu stricto were found and their fermentation characteristics and Leloir enzyme activities were measured. As the gal promoter seems to play an important role in the galactose phenotype, the galR-galK intergenic region was sequenced for all strains yielding eight different nucleotide sequences (NS1 to NS8). The gal promoter played an important role in the Gal-positive phenotype but did not determine it exclusively. Although GalT and GalE activities were detected for all Gal-positive strains, GalK activity could only be detected for two out of eight Gal-positive strains. This finding suggests that the other six S. thermophilus strains metabolize galactose via an alternative route. For each type of fermentation profile obtained, a representative strain was chosen and four complete Leloir gene clusters were sequenced. It turned out that Gal-positive strains contained more amino acid differences within their gal genes than Gal-negative strains. Finally, the biodiversity regarding lactose-galactose utilization among the different S. thermophilus strains used in this study was shown by RAPD-PCR. Five Gal-positive strains that contain nucleotide sequence NS2 in their galR-galK intergenic region were closely related. PMID:16000774

A Discrepancy in Comprehension and Production in Early Language Development in ASD: Is It Clinically Relevant?

ERIC Educational Resources Information Center

Davidson, Meghan M.; Ellis Weismer, Susan

2017-01-01

This study examined the extent to which a discrepant comprehension-production profile (i.e., relatively more delayed comprehension than production) is characteristic of the early language phenotype in autism spectrum disorders (ASD) and tracked the developmental progression of the profile. Our findings indicated that a discrepant…

Compound annotation with real time cellular activity profiles to improve drug discovery.

PubMed

Fang, Ye

2016-01-01

In the past decade, a range of innovative strategies have been developed to improve the productivity of pharmaceutical research and development. In particular, compound annotation, combined with informatics, has provided unprecedented opportunities for drug discovery. In this review, a literature search from 2000 to 2015 was conducted to provide an overview of the compound annotation approaches currently used in drug discovery. Based on this, a framework related to a compound annotation approach using real-time cellular activity profiles for probe, drug, and biology discovery is proposed. Compound annotation with chemical structure, drug-like properties, bioactivities, genome-wide effects, clinical phenotypes, and textural abstracts has received significant attention in early drug discovery. However, these annotations are mostly associated with endpoint results. Advances in assay techniques have made it possible to obtain real-time cellular activity profiles of drug molecules under different phenotypes, so it is possible to generate compound annotation with real-time cellular activity profiles. Combining compound annotation with informatics, such as similarity analysis, presents a good opportunity to improve the rate of discovery of novel drugs and probes, and enhance our understanding of the underlying biology.

EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

PubMed Central

Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

2014-01-01

BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant methylation subtype in meningioma. CIMP-positivity with aberrant methylation in recurrent/malignant meningioma suggests a potential therapeutic target for clinically aggressive cases.

B and T Cell Phenotypic Profiles of African HIV-Infected and HIV-Exposed Uninfected Infants: Associations with Antibody Responses to the Pentavalent Rotavirus Vaccine.

PubMed

Weinberg, Adriana; Lindsey, Jane; Bosch, Ronald; Persaud, Deborah; Sato, Paul; Ogwu, Anthony; Asmelash, Aida; Bwakura-Dangarambezi, Mutsa; Chi, Benjamin H; Canniff, Jennifer; Lockman, Shahin; Gaseitsiwe, Simani; Moyo, Sikhulile; Smith, Christiana Elizabeth; Moraka, Natasha O; Levin, Myron J

2017-01-01

We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequencies of activated and inflammatory T cells of PHIV and PHEU positively correlated with the frequency of immature B cells. Correlations were not affected by HIV status and persisted over time. PHIV and PHEU antibody responses to RV5 positively correlated with CD4+ T cell counts and negatively with the proportion of immature B cells, similarly to what has been previously described in chronic HIV infection. Unique to PHIV and PHEU, anti-RV5 antibodies positively correlated with CD4+/CD8+FOXP3+CD25+% and negatively with CD4+IL10+% Tregs. In conclusion, PHEU shared with PHIV abnormal B and T cell phenotypic profiles. PHIV and PHEU antibody responses to RV5 were modulated by typical HIV-associated immune response modifiers except for the association between CD4+/CD8+FOXP3+CD25+Treg and increased antibody production.

B and T Cell Phenotypic Profiles of African HIV-Infected and HIV-Exposed Uninfected Infants: Associations with Antibody Responses to the Pentavalent Rotavirus Vaccine

PubMed Central

Weinberg, Adriana; Lindsey, Jane; Bosch, Ronald; Persaud, Deborah; Sato, Paul; Ogwu, Anthony; Asmelash, Aida; Bwakura-Dangarambezi, Mutsa; Chi, Benjamin H.; Canniff, Jennifer; Lockman, Shahin; Gaseitsiwe, Simani; Moyo, Sikhulile; Smith, Christiana Elizabeth; Moraka, Natasha O.; Levin, Myron J.; Fane, Charles

2018-01-01

We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequencies of activated and inflammatory T cells of PHIV and PHEU positively correlated with the frequency of immature B cells. Correlations were not affected by HIV status and persisted over time. PHIV and PHEU antibody responses to RV5 positively correlated with CD4+ T cell counts and negatively with the proportion of immature B cells, similarly to what has been previously described in chronic HIV infection. Unique to PHIV and PHEU, anti-RV5 antibodies positively correlated with CD4+/CD8+FOXP3+CD25+% and negatively with CD4+IL10+% Tregs. In conclusion, PHEU shared with PHIV abnormal B and T cell phenotypic profiles. PHIV and PHEU antibody responses to RV5 were modulated by typical HIV-associated immune response modifiers except for the association between CD4+/CD8+FOXP3+CD25+Treg and increased antibody production. PMID:29403482

Suggestive Linkage of the Child Behavior Checklist Juvenile Bipolar Disorder Phenotype to 1p21, 6p21, and 8q21

ERIC Educational Resources Information Center

Doyle, Alysa E.; Biederman, Joseph; Ferreira, Manuel A. R.; Wong, Patricia; Smoller, Jordan W.; Faraone, Stephen V.

2010-01-01

Objective: Several studies have documented a profile of elevated scores on the Attention Problems, Aggressive Behavior and Anxious/Depressed scales of the Child Behavior Checklist (CBCL) in youth with bipolar disorder. The sum of these scales, referred to as the CBCL Juvenile Bipolar Disorder (JBD) phenotype, has modest diagnostic utility, and…

Comparative Transcriptomics of Seasonal Phenotypic Flexibility in Two North American Songbirds.

PubMed

Cheviron, Z A; Swanson, D L

2017-11-01

Phenotypic flexibility allows organisms to reversibly alter their phenotypes to match the changing demands of seasonal environments. Because phenotypic flexibility is mediated, at least in part, by changes in gene regulation, comparative transcriptomic studies can provide insights into the mechanistic underpinnings of seasonal phenotypic flexibility, and the extent to which regulatory responses to changing seasons are conserved across species. To begin to address these questions, we sampled individuals of two resident North American songbird species, American goldfinch (Spinus tristis) and black-capped chickadee (Poecile atricapillus) in summer and winter to measure seasonal variation in pectoralis transcriptomic profiles and to identify conserved and species-specific elements of these seasonal profiles. We found that very few genes exhibited divergent responses to changes in season between species, and instead, a core set of over 1200 genes responded to season concordantly in both species. Moreover, several key metabolic pathways, regulatory networks, and gene functional classes were commonly recruited to induce seasonal phenotypic shifts in these species. The seasonal transcriptomic responses mirror winter increases in pectoralis mass and cellular metabolic intensity documented in previous studies of both species, suggesting that these seasonal phenotypic responses are due in part to changes in gene expression. Despite growing evidence of muscle nonshivering thermogenesis (NST) in young precocial birds, we did not find strong evidence of upregulation of genes putatively involved in NST during winter in either species, suggesting that seasonal modification of muscular NST is not a prominent contributor to winter increases in thermogenic capacity for adult passerine birds. Together, these results provide the first comprehensive overview of potential common regulatory mechanisms underlying seasonally flexible phenotypes in wild, free-ranging birds. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Domesticated, Genetically Engineered, and Wild Plant Relatives Exhibit Unintended Phenotypic Differences: A Comparative Meta-Analysis Profiling Rice, Canola, Maize, Sunflower, and Pumpkin

PubMed Central

Hernández-Terán, Alejandra; Wegier, Ana; Benítez, Mariana; Lira, Rafael; Escalante, Ana E.

2017-01-01

Agronomic management of plants is a powerful evolutionary force acting on their populations. The management of cultivated plants is carried out by the traditional process of human selection or plant breeding and, more recently, by the technologies used in genetic engineering (GE). Even though crop modification through GE is aimed at specific traits, it is possible that other non-target traits can be affected by genetic modification due to the complex regulatory processes of plant metabolism and development. In this study, we conducted a meta-analysis profiling the phenotypic consequences of plant breeding and GE, and compared modified cultivars with wild relatives in five crops of global economic and cultural importance: rice, maize, canola, sunflower, and pumpkin. For these five species, we analyzed the literature with documentation of phenotypic traits that are potentially related to fitness for the same species in comparable conditions. The information was analyzed to evaluate whether the different processes of modification had influenced the phenotype in such a way as to cause statistical differences in the state of specific phenotypic traits or grouping of the organisms depending on their genetic origin [wild, domesticated with genetic engineering (domGE), and domesticated without genetic engineering (domNGE)]. In addition, we tested the hypothesis that, given that transgenic plants are a construct designed to impact, in many cases, a single trait of the plant (e.g., lepidopteran resistance), the phenotypic differences between domGE and domNGE would be either less (or inexistent) than between the wild and domesticated relatives (either domGE or domNGE). We conclude that (1) genetic modification (either by selective breeding or GE) can be traced phenotypically when comparing wild relatives with their domesticated relatives (domGE and domNGE) and (2) the existence and the magnitude of the phenotypic differences between domGE and domNGE of the same crop suggest consequences of genetic modification beyond the target trait(s). PMID:29259610

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

PubMed

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

2010-06-01

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

Understanding and predicting profile structure and parametric scaling of intrinsic rotation

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

Wang, W. X.; Grierson, B. A.; Ethier, S.

2017-08-10

This study reports on a recent advance in developing physical understanding and a first-principles-based model for predicting intrinsic rotation profiles in magnetic fusion experiments. It is shown for the first time that turbulent fluctuation-driven residual stress (a non-diffusive component of momentum flux) along with diffusive momentum flux can account for both the shape and magnitude of the observed intrinsic toroidal rotation profile. Both the turbulence intensity gradient and zonal flow E×B shear are identified as major contributors to the generation of the k ∥-asymmetry needed for the residual stress generation. The model predictions of core rotation based on global gyrokineticmore » simulations agree well with the experimental measurements of main ion toroidal rotation for a set of DIII-D ECH discharges. The validated model is further used to investigate the characteristic dependence of residual stress and intrinsic rotation profile structure on the multi-dimensional parametric space covering the turbulence type, q-profile structure, and up-down asymmetry in magnetic geometry with the goal of developing the physics understanding needed for rotation profile control and optimization. It is shown that in the flat-q profile regime, intrinsic rotations driven by ITG and TEM turbulence are in the opposite direction (i.e., intrinsic rotation reverses). The predictive model also produces reversed intrinsic rotation for plasmas with weak and normal shear q-profiles.« less

The lipid phenotype of breast cancer cells characterized by Raman microspectroscopy: towards a stratification of malignancy.

PubMed

Nieva, Claudia; Marro, Monica; Santana-Codina, Naiara; Rao, Satish; Petrov, Dmitri; Sierra, Angels

2012-01-01

Although molecular classification brings interesting insights into breast cancer taxonomy, its implementation in daily clinical care is questionable because of its expense and the information supplied in a single sample allocation is not sufficiently reliable. New approaches, based on a panel of small molecules derived from the global or targeted analysis of metabolic profiles of cells, have found a correlation between activation of de novo lipogenesis and poorer prognosis and shorter disease-free survival for many tumors. We hypothesized that the lipid content of breast cancer cells might be a useful indirect measure of a variety of functions coupled to breast cancer progression. Raman microspectroscopy was used to characterize metabolism of breast cancer cells with different degrees of malignancy. Raman spectra from MDA-MB-435, MDA-MB-468, MDA-MB-231, SKBR3, MCF7 and MCF10A cells were acquired with an InVia Raman microscope (Renishaw) with a backscattered configuration. We used Principal Component Analysis and Partial Least Squares Discriminant Analyses to assess the different profiling of the lipid composition of breast cancer cells. Characteristic bands related to lipid content were found at 3014, 2935, 2890 and 2845 cm(-1), and related to lipid and protein content at 2940 cm(-1). A classificatory model was generated which segregated metastatic cells and non-metastatic cells without basal-like phenotype with a sensitivity of 90% and a specificity of 82.1%. Moreover, expression of SREBP-1c and ABCA1 genes validated the assignation of the lipid phenotype of breast cancer cells. Indeed, changes in fatty acid unsaturation were related with the epithelial-to-mesenchymal transition phenotype. Raman microspectroscopy is a promising technique for characterizing and classifying the malignant phenotype of breast cancer cells on the basis of their lipid profiling. The algorithm for the discrimination of metastatic ability is a first step towards stratifying breast cancer cells using this rapid and reagent-free tool.

Autism Phenotypes in Tuberous Sclerosis Complex: Diagnostic and Treatment Considerations.

PubMed

Gipson, Tanjala T; Poretti, Andrea; Thomas, Emily A; Jenkins, Kosunique T; Desai, Sonal; Johnston, Michael V

2015-12-01

Tuberous sclerosis complex is a multisystem, chronic genetic condition characterized by systemic growth of benign tumors and often accompanied by epilepsy, autism spectrum disorders, and intellectual disability. Nonetheless, the neurodevelopmental phenotype of these patients is not often detailed. The authors describe 3 individuals with tuberous sclerosis complex who share common characteristics that can help to identify a distinct profile of autism spectrum disorder. These findings include typical cognitive development, expressive and pragmatic language deficits, and anxiety. The authors also describe features specific to tuberous sclerosis complex that require consideration before diagnosing an autism spectrum disorder. Identifying distinct profiles of autism spectrum disorder in tuberous sclerosis complex can help optimize treatment across the life span. © The Author(s) 2015.

Long-term phenotypic evolution of bacteria.

PubMed

Plata, Germán; Henry, Christopher S; Vitkup, Dennis

2015-01-15

For many decades comparative analyses of protein sequences and structures have been used to investigate fundamental principles of molecular evolution. In contrast, relatively little is known about the long-term evolution of species' phenotypic and genetic properties. This represents an important gap in our understanding of evolution, as exactly these proprieties play key roles in natural selection and adaptation to diverse environments. Here we perform a comparative analysis of bacterial growth and gene deletion phenotypes using hundreds of genome-scale metabolic models. Overall, bacterial phenotypic evolution can be described by a two-stage process with a rapid initial phenotypic diversification followed by a slow long-term exponential divergence. The observed average divergence trend, with approximately similar fractions of phenotypic properties changing per unit time, continues for billions of years. We experimentally confirm the predicted divergence trend using the phenotypic profiles of 40 diverse bacterial species across more than 60 growth conditions. Our analysis suggests that, at long evolutionary distances, gene essentiality is significantly more conserved than the ability to utilize different nutrients, while synthetic lethality is significantly less conserved. We also find that although a rapid phenotypic evolution is sometimes observed within the same species, a transition from high to low phenotypic similarity occurs primarily at the genus level.

Meloidogyne partityla on Pecan Isozyme Phenotypes and Other Host

PubMed Central

Starr, J. L.; Tomaszewski, E. K.; Mundo-Ocampo, M.; Baldwin, J. G.

1996-01-01

Meloidogyne sp. from five pecan (Carya illinoensis) orchards in Texas were distinctive in host range and iszoyme profiles from common species of Meloidogyne but were morphologically congruent with Meloidogyne partityla Kleynhans, a species previously known only in South Africa. In addition to pecan, species of walnut (Juglans hindsii and J. regia) and hickory (C. ovata) also were hosts. No reproduction was observed on 15 other plant species from nine families, including several common hosts of other Meloidogyne spp. Three esterase phenotypes and two malate dehydrogenase phenotypes of M. partityla were identified by polyacrylamide gel electrophoresis. Each of these isozyme phenotypes was distinct from those of the more common species M. arenaria, M. hapla, M. incognita, and M. javanica. PMID:19277175

Cognitive Dysfunction Is Worse among Pediatric Patients with Bipolar Disorder Type I than Type II

ERIC Educational Resources Information Center

Schenkel, Lindsay S.; West, Amy E.; Jacobs, Rachel; Sweeney, John A.; Pavuluri, Mani N.

2012-01-01

Background: Impaired profiles of neurocognitive function have been consistently demonstrated among pediatric patients with bipolar disorder (BD), and may aid in the identification of endophenotypes across subtypes of the disorder. This study aims to determine phenotypic cognitive profiles of patients with BD Type I and II. Methods: Subjects (N =…

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

PubMed

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.

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

PubMed Central

2010-01-01

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. PMID:20214782

Pathogen profiling for disease management and surveillance.

PubMed

Sintchenko, Vitali; Iredell, Jonathan R; Gilbert, Gwendolyn L

2007-06-01

The usefulness of rapid pathogen genotyping is widely recognized, but its effective interpretation and application requires integration into clinical and public health decision-making. How can pathogen genotyping data best be translated to inform disease management and surveillance? Pathogen profiling integrates microbial genomics data into communicable disease control by consolidating phenotypic identity-based methods with DNA microarrays, proteomics, metabolomics and sequence-based typing. Sharing data on pathogen profiles should facilitate our understanding of transmission patterns and the dynamics of epidemics.

A Source Area Approach Demonstrates Moderate Predictive Ability but Pronounced Variability of Invasive Species Traits

PubMed Central

Essl, Franz; Dullinger, Stefan

2016-01-01

The search for traits that make alien species invasive has mostly concentrated on comparing successful invaders and different comparison groups with respect to average trait values. By contrast, little attention has been paid to trait variability among invaders. Here, we combine an analysis of trait differences between invasive and non-invasive species with a comparison of multidimensional trait variability within these two species groups. We collected data on biological and distributional traits for 1402 species of the native, non-woody vascular plant flora of Austria. We then compared the subsets of species recorded and not recorded as invasive aliens anywhere in the world, respectively, first, with respect to the sampled traits using univariate and multiple regression models; and, second, with respect to their multidimensional trait diversity by calculating functional richness and dispersion metrics. Attributes related to competitiveness (strategy type, nitrogen indicator value), habitat use (agricultural and ruderal habitats, occurrence under the montane belt), and propagule pressure (frequency) were most closely associated with invasiveness. However, even the best multiple model, including interactions, only explained a moderate fraction of the differences in invasive success. In addition, multidimensional variability in trait space was even larger among invasive than among non-invasive species. This pronounced variability suggests that invasive success has a considerable idiosyncratic component and is probably highly context specific. We conclude that basing risk assessment protocols on species trait profiles will probably face hardly reducible uncertainties. PMID:27187616

A Source Area Approach Demonstrates Moderate Predictive Ability but Pronounced Variability of Invasive Species Traits.

PubMed

Klonner, Günther; Fischer, Stefan; Essl, Franz; Dullinger, Stefan

2016-01-01

The search for traits that make alien species invasive has mostly concentrated on comparing successful invaders and different comparison groups with respect to average trait values. By contrast, little attention has been paid to trait variability among invaders. Here, we combine an analysis of trait differences between invasive and non-invasive species with a comparison of multidimensional trait variability within these two species groups. We collected data on biological and distributional traits for 1402 species of the native, non-woody vascular plant flora of Austria. We then compared the subsets of species recorded and not recorded as invasive aliens anywhere in the world, respectively, first, with respect to the sampled traits using univariate and multiple regression models; and, second, with respect to their multidimensional trait diversity by calculating functional richness and dispersion metrics. Attributes related to competitiveness (strategy type, nitrogen indicator value), habitat use (agricultural and ruderal habitats, occurrence under the montane belt), and propagule pressure (frequency) were most closely associated with invasiveness. However, even the best multiple model, including interactions, only explained a moderate fraction of the differences in invasive success. In addition, multidimensional variability in trait space was even larger among invasive than among non-invasive species. This pronounced variability suggests that invasive success has a considerable idiosyncratic component and is probably highly context specific. We conclude that basing risk assessment protocols on species trait profiles will probably face hardly reducible uncertainties.

Free-Energy Landscape and Proton Transfer Pathways in Oxidative Deamination by Methylamine Dehydrogenase.

PubMed

Zelleke, Theodros; Marx, Dominik

2017-01-18

The rate-determining step in the reductive half-reaction of the bacterial enzyme methylamine dehydrogenase, which is proton abstraction from the native substrate methylamine, is investigated using accelerated QM/MM molecular dynamics simulations at room temperature. Generation of the multidimensional thermal free-energy landscape without restriction of the degrees of freedom beyond a multidimensional reaction subspace maps two rather similar pathways for the underlying proton transfer to one of two aspartate carboxyl oxygen atoms, termed OD1 and OD2, which hydrogen bond with Thr122 and Trp108, respectively. Despite significant large-amplitude motion perpendicular to the one-dimensional proton transfer coordinate, due to fluctuations of the donor-acceptor distance of about 3 Å, it is found that the one-dimensional proton transfer free-energy profiles are essentially identical to the minimum free-energy pathways on the multidimensional free-energy landscapes for both proton transfer channels. Proton transfer to one of the acceptor oxygen atoms-the OD2 site-is slightly favored in methylamine dehydrogenase by approximately 2 kcal mol -1 , both kinetically and thermodynamically. Mechanistic analyses reveal that the hydrogen bond between Thr122β and OD1 is always present in the transition state independently of the proton transfer channel. Population analysis confirms that the electronic charge gained upon oxidation of the substrate is delocalized within the ring systems of the tryptophan tryptophylquinone cofactor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of pain behavior profiles and functional disability in outpatient physical therapy clinics.

PubMed

Hankin, H A; Spencer, T; Kegerreis, S; Worrell, T; Rice, J M

2001-02-01

Descriptive, ex post facto. To determine the proportion of physical therapy outpatients with pain who exhibit various pain behavior profiles, and to determine whether there are differences in functional disability across the profiles. Physical therapists treat many patients who have chronic pain. Research suggests that early identification and multidisciplinary treatment are effective and economical for these patients. The Multidimensional Pain Inventory (MPI) and the Pain Disability Index (PDI) are potential screening tools that could be used in physical therapy clinics to determine which patients should be referred for multidisciplinary treatment. MPI and PDI data were gathered on 57 physical therapy outpatients (mean age 44.3 +/- 14.5 years, 22 men and 35 women) with pain of 3 or more months duration. ANOVA was used to analyze differences in mean PDI scores across the MPI profiles. Of all patients, 42.1% fit the Adaptive Coper profile, 29.8% fit the Interpersonally Distressed profile, and 28.1% fit the Dysfunctional profile. There were significant differences in PDI scores among profile groups. Post hoc analysis showed that the PDI scores of the Adaptive Coper and Interpersonally Distressed groups were different from the Dysfunctional group, but that there was no difference between the Adaptive Coper and Interpersonally Distressed groups. Many patients in outpatient physical therapy settings exhibit behavioral, affective, and cognitive characteristics associated with chronic pain. Thirty-three patients (57.9%) had MPI profiles (interpersonally distressed and dysfunctional) that suggest they might benefit from multidisciplinary treatment.

“Heroes” and “Villains” of World History across Cultures

PubMed Central

Hanke, Katja; Liu, James H.; Sibley, Chris G.; Paez, Dario; Gaines, Stanley O.; Moloney, Gail; Leong, Chan-Hoong; Wagner, Wolfgang; Licata, Laurent; Klein, Olivier; Garber, Ilya; Böhm, Gisela; Hilton, Denis J.; Valchev, Velichko; Khan, Sammyh S.; Cabecinhas, Rosa

2015-01-01

Emergent properties of global political culture were examined using data from the World History Survey (WHS) involving 6,902 university students in 37 countries evaluating 40 figures from world history. Multidimensional scaling and factor analysis techniques found only limited forms of universality in evaluations across Western, Catholic/Orthodox, Muslim, and Asian country clusters. The highest consensus across cultures involved scientific innovators, with Einstein having the most positive evaluation overall. Peaceful humanitarians like Mother Theresa and Gandhi followed. There was much less cross-cultural consistency in the evaluation of negative figures, led by Hitler, Osama bin Laden, and Saddam Hussein. After more traditional empirical methods (e.g., factor analysis) failed to identify meaningful cross-cultural patterns, Latent Profile Analysis (LPA) was used to identify four global representational profiles: Secular and Religious Idealists were overwhelmingly prevalent in Christian countries, and Political Realists were common in Muslim and Asian countries. We discuss possible consequences and interpretations of these different representational profiles. PMID:25651504

Using cluster analysis to examine the combinations of motivation regulations of physical education students.

PubMed

Ullrich-French, Sarah; Cox, Anne

2009-06-01

According to self-determination theory, motivation is multidimensional, with motivation regulations lying along a continuum of self-determination (Ryan & Deci, 2007). Accounting for the different types of motivation in physical activity research presents a challenge. This study used cluster analysis to identify motivation regulation profiles and examined their utility by testing profile differences in relative levels of self-determination (i.e., self-determination index), and theoretical antecedents (i.e., competence, autonomy, relatedness) and consequences (i.e., enjoyment, worry, effort, value, physical activity) of physical education motivation. Students (N= 386) in 6th- through 8th-grade physical education classes completed questionnaires of the variables listed above. Five profiles emerged, including average (n = 81), motivated (n = 82), self-determined (n = 91), low motivation (n = 73), and external (n = 59). Group difference analyses showed that students with greater levels of self-determined forms of motivation, regardless of non-self-determined motivation levels, reported the most adaptive physical education experiences.

Potential forensic biogeographic application of diatom colony consistency analysis employing pyrosequencing profiles of the 18S rDNA V7 region.

PubMed

Zhao, Yuancun; Chen, Xiaogang; Yang, Yiwen; Zhao, Xiaohong; Zhang, Shu; Gao, Zehua; Fang, Ting; Wang, Yufang; Zhang, Ji

2018-05-07

Diatom examination has always been used for the diagnosis of drowning in forensic practice. However, traditional examination of the microscopic features of diatom frustules is time-consuming and requires taxonomic expertise. In this study, we demonstrate a potential DNA-based method of inferring suspected drowning site using pyrosequencing (PSQ) of the V7 region of 18S ribosome DNA (18S rDNA) as a diatom DNA barcode. By employing a sparse representation-based AdvISER-M-PYRO algorithm, the original PSQ signals of diatom DNA mixtures were deciphered to determine the corresponding taxa of the composite diatoms. Additionally, we evaluated the possibility of correlating water samples to collection sites by analyzing the PSQ signal profiles of diatom mixtures contained in the water samples via multidimensional scaling. The results suggest that diatomaceous PSQ profile analysis could be used as a cost-effective method to deduce the geographical origin of an environmental bio-sample.

Fractal Clustering and Knowledge-driven Validation Assessment for Gene Expression Profiling.

PubMed

Wang, Lu-Yong; Balasubramanian, Ammaiappan; Chakraborty, Amit; Comaniciu, Dorin

2005-01-01

DNA microarray experiments generate a substantial amount of information about the global gene expression. Gene expression profiles can be represented as points in multi-dimensional space. It is essential to identify relevant groups of genes in biomedical research. Clustering is helpful in pattern recognition in gene expression profiles. A number of clustering techniques have been introduced. However, these traditional methods mainly utilize shape-based assumption or some distance metric to cluster the points in multi-dimension linear Euclidean space. Their results shows poor consistence with the functional annotation of genes in previous validation study. From a novel different perspective, we propose fractal clustering method to cluster genes using intrinsic (fractal) dimension from modern geometry. This method clusters points in such a way that points in the same clusters are more self-affine among themselves than to the points in other clusters. We assess this method using annotation-based validation assessment for gene clusters. It shows that this method is superior in identifying functional related gene groups than other traditional methods.

Functional or constructive attitudes: Which type drives consumers' evaluation of meat products?

PubMed

Hamlin, Robert

2016-07-01

Consumer attitudes towards meat can be divided up into two types: Functional attitudes which are stable and exist over long periods of time, and constructive attitudes which are ephemeral and usually constructed at the point of sale. This research investigated the temporal and situational stability of meat consumers' attitudes by using the same established functional, multidimensional attitude instrument to generate attitude profiles for the four meat types: chicken/beef/lamb/poultry both as an abstracted construct and as a cue on a range of meat and meat-based products. The results showed that strong attitude profile was generated by the meat types as abstracted constructs, but that this profile broke down completely when the food products carrying the same meat types were evaluated. This result indicates that consumer attitudes may not be temporally or situationally stable, which in turn suggests that consumers' evaluation and choice of meat products may be driven to a greater or lesser extent by constructive rather than functional attitudes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Planck intermediate results. XVI. Profile likelihoods for cosmological parameters

NASA Astrophysics Data System (ADS)

Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Bartlett, J. G.; Battaner, E.; Benabed, K.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bielewicz, P.; Bobin, J.; Bonaldi, A.; Bond, J. R.; Bouchet, F. R.; Burigana, C.; Cardoso, J.-F.; Catalano, A.; Chamballu, A.; Chiang, H. C.; Christensen, P. R.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Couchot, F.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Dickinson, C.; Diego, J. M.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Dupac, X.; Enßlin, T. A.; Eriksen, H. K.; Finelli, F.; Forni, O.; Frailis, M.; Franceschi, E.; Galeotta, S.; Galli, S.; Ganga, K.; Giard, M.; Giraud-Héraud, Y.; González-Nuevo, J.; Górski, K. M.; Gregorio, A.; Gruppuso, A.; Hansen, F. K.; Harrison, D. L.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hovest, W.; Huffenberger, K. M.; Jaffe, A. H.; Jaffe, T. R.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Knox, L.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lähteenmäki, A.; Lamarre, J.-M.; Lasenby, A.; Lawrence, C. R.; Leonardi, R.; Liddle, A.; Liguori, M.; Lilje, P. B.; Linden-Vørnle, M.; López-Caniego, M.; Lubin, P. M.; Macías-Pérez, J. F.; Maffei, B.; Maino, D.; Mandolesi, N.; Maris, M.; Martin, P. G.; Martínez-González, E.; Masi, S.; Massardi, M.; Matarrese, S.; Mazzotta, P.; Melchiorri, A.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Noviello, F.; Novikov, D.; Novikov, I.; Oxborrow, C. A.; Pagano, L.; Pajot, F.; Paoletti, D.; Pasian, F.; Perdereau, O.; Perotto, L.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski∗, S.; Pointecouteau, E.; Polenta, G.; Popa, L.; Pratt, G. W.; Puget, J.-L.; Rachen, J. P.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Ricciardi, S.; Riller, T.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Roudier, G.; Rouillé d'Orfeuil, B.; Rubiño-Martín, J. A.; Rusholme, B.; Sandri, M.; Savelainen, M.; Savini, G.; Spencer, L. D.; Spinelli, M.; Starck, J.-L.; Sureau, F.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Tristram, M.; Tucci, M.; Umana, G.; Valenziano, L.; Valiviita, J.; Van Tent, B.; Vielva, P.; Villa, F.; Wade, L. A.; Wandelt, B. D.; White, M.; Yvon, D.; Zacchei, A.; Zonca, A.

2014-06-01

We explore the 2013 Planck likelihood function with a high-precision multi-dimensional minimizer (Minuit). This allows a refinement of the ΛCDM best-fit solution with respect to previously-released results, and the construction of frequentist confidence intervals using profile likelihoods. The agreement with the cosmological results from the Bayesian framework is excellent, demonstrating the robustness of the Planck results to the statistical methodology. We investigate the inclusion of neutrino masses, where more significant differences may appear due to the non-Gaussian nature of the posterior mass distribution. By applying the Feldman-Cousins prescription, we again obtain results very similar to those of the Bayesian methodology. However, the profile-likelihood analysis of the cosmic microwave background (CMB) combination (Planck+WP+highL) reveals a minimum well within the unphysical negative-mass region. We show that inclusion of the Planck CMB-lensing information regularizes this issue, and provide a robust frequentist upper limit ∑ mν ≤ 0.26 eV (95% confidence) from the CMB+lensing+BAO data combination.

PROSPECT improves cis-acting regulatory element prediction by integrating expression profile data with consensus pattern searches

PubMed Central

Fujibuchi, Wataru; Anderson, John S. J.; Landsman, David

2001-01-01

Consensus pattern and matrix-based searches designed to predict cis-acting transcriptional regulatory sequences have historically been subject to large numbers of false positives. We sought to decrease false positives by incorporating expression profile data into a consensus pattern-based search method. We have systematically analyzed the expression phenotypes of over 6000 yeast genes, across 121 expression profile experiments, and correlated them with the distribution of 14 known regulatory elements over sequences upstream of the genes. Our method is based on a metric we term probabilistic element assessment (PEA), which is a ranking of potential sites based on sequence similarity in the upstream regions of genes with similar expression phenotypes. For eight of the 14 known elements that we examined, our method had a much higher selectivity than a naïve consensus pattern search. Based on our analysis, we have developed a web-based tool called PROSPECT, which allows consensus pattern-based searching of gene clusters obtained from microarray data. PMID:11574681

Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy.

PubMed

Montero, Joan; Sarosiek, Kristopher A; DeAngelo, Joseph D; Maertens, Ophélia; Ryan, Jeremy; Ercan, Dalia; Piao, Huiying; Horowitz, Neil S; Berkowitz, Ross S; Matulonis, Ursula; Jänne, Pasi A; Amrein, Philip C; Cichowski, Karen; Drapkin, Ronny; Letai, Anthony

2015-02-26

There is a lack of effective predictive biomarkers to precisely assign optimal therapy to cancer patients. While most efforts are directed at inferring drug response phenotype based on genotype, there is very focused and useful phenotypic information to be gained from directly perturbing the patient's living cancer cell with the drug(s) in question. To satisfy this unmet need, we developed the Dynamic BH3 Profiling technique to measure early changes in net pro-apoptotic signaling at the mitochondrion ("priming") induced by chemotherapeutic agents in cancer cells, not requiring prolonged ex vivo culture. We find in cell line and clinical experiments that early drug-induced death signaling measured by Dynamic BH3 Profiling predicts chemotherapy response across many cancer types and many agents, including combinations of chemotherapies. We propose that Dynamic BH3 Profiling can be used as a broadly applicable predictive biomarker to predict cytotoxic response of cancers to chemotherapeutics in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

Methylation-sensitive amplified polymorphism-based genome-wide analysis of cytosine methylation profiles in Nicotiana tabacum cultivars.

PubMed

Jiao, J; Wu, J; Lv, Z; Sun, C; Gao, L; Yan, X; Cui, L; Tang, Z; Yan, B; Jia, Y

2015-11-26

This study aimed to investigate cytosine methylation profiles in different tobacco (Nicotiana tabacum) cultivars grown in China. Methylation-sensitive amplified polymorphism was used to analyze genome-wide global methylation profiles in four tobacco cultivars (Yunyan 85, NC89, K326, and Yunyan 87). Amplicons with methylated C motifs were cloned by reamplified polymerase chain reaction, sequenced, and analyzed. The results show that geographical location had a greater effect on methylation patterns in the tobacco genome than did sampling time. Analysis of the CG dinucleotide distribution in methylation-sensitive polymorphic restriction fragments suggested that a CpG dinucleotide cluster-enriched area is a possible site of cytosine methylation in the tobacco genome. The sequence alignments of the Nia1 gene (that encodes nitrate reductase) in Yunyan 87 in different regions indicate that a C-T transition might be responsible for the tobacco phenotype. T-C nucleotide replacement might also be responsible for the tobacco phenotype and may be influenced by geographical location.

Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy.

PubMed

Azevedo de Lima, Patricia; Baldini Prudêncio, Mariana; Murakami, Daniela Kawamoto; Pereira de Brito Sampaio, Leticia; Figueiredo Neto, Antônio Martins; Teixeira Damasceno, Nágila Raquel

2017-01-01

The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy. This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system. The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD. KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant Gram-negative bacteria in solid-organ transplantation patients: a comparative study.

PubMed

Karampatakis, Theodoros; Geladari, Anastasia; Politi, Lida; Antachopoulos, Charalampos; Iosifidis, Elias; Tsiatsiou, Olga; Karyoti, Aggeliki; Papanikolaou, Vasileios; Tsakris, Athanassios; Roilides, Emmanuel

2017-07-31

Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004). The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii isolates are clonally related.

High prevalence of low HDL-c in the Philippines compared to the U.S.: population differences in associations with diet and BMI

PubMed Central

Rutherford, Julienne N.; McDade, Thom W.; Feranil, Alan; Adair, Linda; Kuzawa, Christopher

2011-01-01

Cardiovascular disease (CVD) is a leading cause of death in the Philippines, although few studies here have examined the lipid profiles underlying disease risk. The isolated low high density lipoprotein cholesterol (HDL-c) phenotype has been implicated as a CVD risk factor, the prevalence of which exhibits significant variation across populations. To assess population variation in individual lipid components and their associations with diet and anthropometric characteristics, we compare lipid profiles in a population of adult Filipino women (n=1877) to U.S. women participating in the National Health and Nutrition Examination Survey (n=477). We conducted multilinear regression models to assess the relationship between lipid components and BMI and dietary variables in the two populations. We measured the prevalence of lipid phenotypes, and logistic regression models determined the predictors of the isolated low HDL-c phenotype. HDL-c was lower in the Philippines (40.8±0.2 mg/dL) than in NHANES (60.7±0.7 mg/dL). The prevalence of the isolated low HDL-c phenotype was 28.8%, compared to 2.10% in NHANES. High prevalence among Filipinos was relatively invariant across all levels of BMI, but was strongly inversely related to BMI in NHANES and exhibited only at the BMI>25 kg/m2 threshold. Diet did not predict the low-HDL phenotype in Filipinos. Filipino women exhibit a high prevalence of the isolated low HDL-c phenotype, which is largely decoupled from anthropometric factors. The relationship of CVD to population variation in dyslipidemia and body composition needs further study, particularly in populations where the burden of cardiovascular and metabolic disease is rapidly increasing. PMID:20199988

Phenotypic & Genotypic Characteristics of Inflammatory Bowel Disease (IBD) in French-Canadians: comparison with a large North American repository

PubMed Central

Bhat, Mamatha; Nguyen, Geoffrey C.; Pare, Pierre; Lahaie, Raymond; Deslandres, Colette; Bernard, Edmond-Jean; Aumais, Guy; Jobin, Gilles; Wild, Gary; Cohen, Albert; Langelier, Diane; Brant, Steven; Dassopoulos, Themistocles; McGovern, Dermot; Torres, Esther; Duerr, Richard; Regueiro, Miguel; Silverberg, Mark S; Steinhart, Hillary; Griffiths, Anne M.; Elkadri, Abdul; Cho, Judy; Proctor, Deborah; Goyette, Philippe; Rioux, John; Bitton, Alain

2009-01-01

BACKGROUND Phenotype characteristics of inflammatory bowel disease (IBD) may differ significantly among ethnic subpopulations. The aim of this study was to characterize the IBD phenotype in French-Canadians, the most prominent founder population in North America. METHODS Using well-characterized phenotype data in the NIDDK-IBD Genetics Consortium repository on IBD patients, we compared phenotypic characteristics of 202 French-Canadians to those of 1287 other Caucasian patients. These included: diagnosis, anatomical location, disease behaviour, extraintestinal manifestations, surgical history, and family history of IBD. RESULTS French-Canadian CD patients were less likely to have stricturing disease (11 vs 21%, P=0.005; OR 0.45, 95% CI: 0.24– 0.85). Using a stringent definition of ethnicity (3 out of 4 grandparents being French-Canadian, as opposed to self-report, n= 148), French-Canadians had a tendency towards developing fistulizing CD (37% vs 28%, p= 0.07), and there was an increased prevalence of sacroiliitis among French-Canadians with IBD (4% vs 2%, p=0.045). Among French-Canadians, the numbers of current smokers in CD (40 vs 25%, p=0.006) and former smokers in UC (35% vs 20%, p=0.03) were significantly higher. The prevalence of one of the three main variant NOD2 SNPs among French-Canadian CD patients was 43.2%. The 3020insC SNP correlated with small bowel disease in French-Canadians (75% versus 0%, P=0.006). CONCLUSION French-Canadians exhibit an IBD phenotype profile distinct from other Caucasian IBD populations, with an accentuated association between smoking status and IBD. This unique profile may have implications regarding the need for a different approach to management of IBD in this population. PMID:19513023

Behavioural phenotypes predict disease susceptibility and infectiousness

PubMed Central

Araujo, Alessandra; Kirschman, Lucas

2016-01-01

Behavioural phenotypes may provide a means for identifying individuals that disproportionally contribute to disease spread and epizootic outbreaks. For example, bolder phenotypes may experience greater exposure and susceptibility to pathogenic infection because of distinct interactions with conspecifics and their environment. We tested the value of behavioural phenotypes in larval amphibians for predicting ranavirus transmission in experimental trials. We found that behavioural phenotypes characterized by latency-to-food and swimming profiles were predictive of disease susceptibility and infectiousness defined as the capacity of an infected host to transmit an infection by contacts. While viral shedding rates were positively associated with transmission, we also found an inverse relationship between contacts and infections. Together these results suggest intrinsic traits that influence behaviour and the quantity of pathogens shed during conspecific interactions may be an important contributor to ranavirus transmission. These results suggest that behavioural phenotypes provide a means to identify individuals more likely to spread disease and thus give insights into disease outbreaks that threaten wildlife and humans. PMID:27555652

Behavioural phenotypes predict disease susceptibility and infectiousness.

PubMed

Araujo, Alessandra; Kirschman, Lucas; Warne, Robin W

2016-08-01

Behavioural phenotypes may provide a means for identifying individuals that disproportionally contribute to disease spread and epizootic outbreaks. For example, bolder phenotypes may experience greater exposure and susceptibility to pathogenic infection because of distinct interactions with conspecifics and their environment. We tested the value of behavioural phenotypes in larval amphibians for predicting ranavirus transmission in experimental trials. We found that behavioural phenotypes characterized by latency-to-food and swimming profiles were predictive of disease susceptibility and infectiousness defined as the capacity of an infected host to transmit an infection by contacts. While viral shedding rates were positively associated with transmission, we also found an inverse relationship between contacts and infections. Together these results suggest intrinsic traits that influence behaviour and the quantity of pathogens shed during conspecific interactions may be an important contributor to ranavirus transmission. These results suggest that behavioural phenotypes provide a means to identify individuals more likely to spread disease and thus give insights into disease outbreaks that threaten wildlife and humans. © 2016 The Author(s).

The development of behavioral abnormalities in the motor neuron degeneration (mnd) mouse.

PubMed

Bolivar, Valerie J; Scott Ganus, J; Messer, Anne

2002-05-24

The motor neuron degeneration (mnd) mouse, which has widespread abnormal accumulating lipoprotein and neuronal degeneration, has a mutation in CLN8, the gene for human progressive epilepsy with mental retardation (EPMR). EPMR is one of the neuronal ceroid lipofuscinoses (NCLs), a group of neurological disorders characterized by autofluorescent lipopigment accumulation, blindness, seizures, motor deterioration, and dementia. The human phenotype of EPMR suggests that, in addition to the motor symptoms previously categorized, various types of progressive behavioral abnormalities would be expected in mnd mice. We have therefore examined exploratory behavior, fear conditioning, and aggression in 2-3 month and 4-5 month old male mnd mice and age-matched C57BL/6 (B6) controls. The mnd mice displayed increased activity with decreased habituation in the activity monitor, poor contextual and cued memory, and heightened aggression relative to B6 controls. These behavioral deficits were most prominent at 4-5 months of age, which is prior to the onset of gross motor symptoms at 6 months. Our results provide a link from the mutation via pathology to a quantifiable multidimensional behavioral phenotype of this naturally occurring mouse model of NCL.

21st century toolkit for optimizing population health through precision nutrition.

PubMed

O'Sullivan, Aifric; Henrick, Bethany; Dixon, Bonnie; Barile, Daniela; Zivkovic, Angela; Smilowitz, Jennifer; Lemay, Danielle; Martin, William; German, J Bruce; Schaefer, Sara Elizabeth

2017-07-05

Scientific, technological, and economic progress over the last 100 years all but eradicated problems of widespread food shortage and nutrient deficiency in developed nations. But now society is faced with a new set of nutrition problems related to energy imbalance and metabolic disease, which require new kinds of solutions. Recent developments in the area of new analytical tools enable us to systematically study large quantities of detailed and multidimensional metabolic and health data, providing the opportunity to address current nutrition problems through an approach called Precision Nutrition. This approach integrates different kinds of "big data" to expand our understanding of the complexity and diversity of human metabolism in response to diet. With these tools, we can more fully elucidate each individual's unique phenotype, or the current state of health, as determined by the interactions among biology, environment, and behavior. The tools of precision nutrition include genomics, metabolomics, microbiomics, phenotyping, high-throughput analytical chemistry techniques, longitudinal tracking with body sensors, informatics, data science, and sophisticated educational and behavioral interventions. These tools are enabling the development of more personalized and predictive dietary guidance and interventions that have the potential to transform how the public makes food choices and greatly improve population health.

Profile Analysis of Psychological Symptoms Associated With Misophonia: A Community Sample.

PubMed

McKay, Dean; Kim, Se-Kang; Mancusi, Lauren; Storch, Eric A; Spankovich, Christopher

2018-03-01

Misophonia is characterized by extreme aversive reactions to certain classes of sounds. It has recently been recognized as a condition associated with significant disability. Research has begun to evaluate psychopathological correlates of misophonia. This study sought to identify profiles of psychopathology that characterize misophonia in a large community sample. A total of N = 628 adult participants completed a battery of measures assessing anxiety and anxiety sensitivity, depression, stress responses, anger, dissociative experiences, obsessive-compulsive symptoms and beliefs, distress tolerance, bodily perceptions, as well as misophonia severity. Profile Analysis via Multidimensional Scaling (PAMS) was employed to evaluate profiles associated with elevated misophonia and those without symptoms. Three profiles were extracted. The first two accounted for 70% total variance and did not show distinctions between groups. The third profile accounted for 11% total variance, and showed that misophonia is associated with lower obsessive-compulsive symptoms for neutralizing, obsessions generally, and washing compared to those not endorsing misophonia, and higher levels of obsessive-compulsive symptoms associated with ordering and harm avoidance. This third profile extracted also showed significant differences between those with and without misophonia on the scale assessing physical concerns (that is, sensitivity to interoceptive sensations) as assessed with the ASI-3. Further research is called for involving diagnostic interviewing and experimental methods to clarify these putative mechanisms associated with misophonia. Copyright © 2017. Published by Elsevier Ltd.

Detonation initiation in a model of explosive: Comparative atomistic and hydrodynamics simulations

NASA Astrophysics Data System (ADS)

Murzov, S. A.; Sergeev, O. V.; Dyachkov, S. A.; Egorova, M. S.; Parshikov, A. N.; Zhakhovsky, V. V.

2016-11-01

Here we extend consistent simulations to reactive materials by the example of AB model explosive. The kinetic model of chemical reactions observed in a molecular dynamics (MD) simulation of self-sustained detonation wave can be used in hydrodynamic simulation of detonation initiation. Kinetic coefficients are obtained by minimization of difference between profiles of species calculated from the kinetic model and observed in MD simulations of isochoric thermal decomposition with a help of downhill simplex method combined with random walk in multidimensional space of fitting kinetic model parameters.

The multiuniverse transition in superfluid 3He

NASA Astrophysics Data System (ADS)

Bunkov, Yury

2013-10-01

The symmetry-breaking phase transitions of the universe and of superfluid 3He may lead to the formation of different states with different order parameters. In both cases the energy potential below the transition temperature has a complicated multidimensional profile with many local minima and saddle points, which correspond to different states. Consequently, not only topological defects, but also islands of different metastable states can be created. Using 3He we can analyse the properties and experimental consequences of such transitions and, in particular, the first-order phase transition between the two low symmetry states.

The multiuniverse transition in superfluid 3He.

PubMed

Bunkov, Yury

2013-10-09

The symmetry-breaking phase transitions of the universe and of superfluid (3)He may lead to the formation of different states with different order parameters. In both cases the energy potential below the transition temperature has a complicated multidimensional profile with many local minima and saddle points, which correspond to different states. Consequently, not only topological defects, but also islands of different metastable states can be created. Using (3)He we can analyse the properties and experimental consequences of such transitions and, in particular, the first-order phase transition between the two low symmetry states.

Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes.

PubMed

Kuhn, Manuel; Haaker, Jan; Glotzbach-Schoon, Evelyn; Schümann, Dirk; Andreatta, Marta; Mechias, Marie-Luise; Raczka, Karolina; Gartmann, Nina; Büchel, Christian; Mühlberger, Andreas; Pauli, Paul; Reif, Andreas; Kalisch, Raffael; Lonsdorf, Tina B

2016-05-01

Being a complex phenotype with substantial heritability, anxiety and related phenotypes are characterized by a complex polygenic basis. Thereby, one candidate pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning processes. Using a multi-dimensional and -methodological replication approach, we investigated the impact of a functional promoter polymorphism (NOS1-ex1f-VNTR) on human anxiety-related phenotypes in a total of 1019 healthy controls in five different studies. Homozygous carriers of the NOS1-ex1f short-allele displayed enhanced trait anxiety, worrying and depression scores. Furthermore, short-allele carriers were characterized by increased anxious apprehension during contextual fear conditioning. While autonomous measures (fear-potentiated startle) provided only suggestive evidence for a modulatory role of NOS1-ex1f-VNTR on (contextual) fear conditioning processes, neural activation at the amygdala/anterior hippocampus junction was significantly increased in short-allele carriers during context conditioning. Notably, this could not be attributed to morphological differences. In accordance with data from a plethora of rodent studies, we here provide converging evidence from behavioral, subjective, psychophysiological and neuroimaging studies in large human cohorts that NOS-I plays an important role in anxious apprehension but provide only limited evidence for a role in (contextual) fear conditioning. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

A Multivariate Twin Study of the DSM-IV Criteria for Antisocial Personality Disorder

PubMed Central

Kendler, Kenneth S.; Aggen, Steven H.; Patrick, Christopher J.

2012-01-01

BACKGROUND Many assessment instruments for psychopathy are multidimensional, suggesting that distinguishable factors are needed to effectively capture variation in this personality domain. However, no prior study has examined the factor structure of the DSM-IV criteria for antisocial personality disorder (ASPD). METHODS Self-report questionnaire items reflecting all A criteria for DSM-IV ASPD were available from 4,291 twins (including both members of 1,647 pairs) from the Virginia Adult Study of Psychiatric and Substance Use Disorders. Exploratory factor analysis and twin model fitting were performed using, respectively, Mplus and Mx. RESULTS Phenotypic factor analysis produced evidence for 2 correlated factors: aggressive-disregard and disinhibition. The best-fitting multivariate twin model included two genetic and one unique environmental common factor, along with criteria-specific genetic and environmental effects. The two genetic factors closely resembled the phenotypic factors and varied in their prediction of a range of relevant criterion variables. Scores on the genetic aggressive-disregard factor score were more strongly associated with risk for conduct disorder, early and heavy alcohol use, and low educational status, whereas scores on the genetic disinhibition factor score were more strongly associated with younger age, novelty seeking, and major depression. CONCLUSION From a genetic perspective, the DSM-IV criteria for ASPD do not reflect a single dimension of liability but rather are influenced by two dimensions of genetic risk reflecting aggressive-disregard and disinhibition. The phenotypic structure of the ASPD criteria results largely from genetic and not from environmental influences. PMID:21762879

Population and performance analyses of four major populations with Illumina's FGx Forensic Genomics System.

PubMed

Churchill, Jennifer D; Novroski, Nicole M M; King, Jonathan L; Seah, Lay Hong; Budowle, Bruce

2017-09-01

The MiSeq FGx Forensic Genomics System (Illumina) enables amplification and massively parallel sequencing of 59 STRs, 94 identity informative SNPs, 54 ancestry informative SNPs, and 24 phenotypic informative SNPs. Allele frequency and population statistics data were generated for the 172 SNP loci included in this panel on four major population groups (Chinese, African Americans, US Caucasians, and Southwest Hispanics). Single-locus and combined random match probability values were generated for the identity informative SNPs. The average combined STR and identity informative SNP random match probabilities (assuming independence) across all four populations were 1.75E-67 and 2.30E-71 with length-based and sequence-based STR alleles, respectively. Ancestry and phenotype predictions were obtained using the ForenSeq™ Universal Analysis System (UAS; Illumina) based on the ancestry informative and phenotype informative SNP profiles generated for each sample. Additionally, performance metrics, including profile completeness, read depth, relative locus performance, and allele coverage ratios, were evaluated and detailed for the 725 samples included in this study. While some genetic markers included in this panel performed notably better than others, performance across populations was generally consistent. The performance and population data included in this study support that accurate and reliable profiles were generated and provide valuable background information for laboratories considering internal validation studies and implementation. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics.

PubMed

Austdal, Marie; Thomsen, Liv Cecilie Vestrheim; Tangerås, Line Haugstad; Skei, Bente; Mathew, Seema; Bjørge, Line; Austgulen, Rigmor; Bathen, Tone Frost; Iversen, Ann-Charlotte

2015-12-01

Preeclampsia is a heterogeneous gestational disease characterized by maternal hypertension and proteinuria, affecting 2-7% of pregnancies. The disorder is initiated by insufficient placental development, but studies characterizing the placental disease components are lacking. Our aim was to phenotype the preeclamptic placenta using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS MRS). Placental samples collected after delivery from women with preeclampsia (n = 19) and normotensive pregnancies (n = 15) were analyzed for metabolic biomarkers including amino acids, osmolytes, and components of the energy and phospholipid metabolism. The metabolic biomarkers were correlated to clinical characteristics and inflammatory biomarkers in the maternal sera. Principal component analysis showed inherent differences in placental metabolic profiles between preeclamptic and normotensive pregnancies. Significant differences in metabolic profiles were found between placentas from severe and non-severe preeclampsia, but not between preeclamptic pregnancies with fetal growth restricted versus normal weight neonates. The placental metabolites correlated with the placental stress marker sFlt-1 and triglycerides in maternal serum, suggesting variation in placental stress signaling between different placental phenotypes. HR-MAS MRS is a sensitive method for defining the placental disease component of preeclampsia, identifying several altered metabolic pathways. Placental HR-MAS MRS analysis may improve insight into processes affected in the preeclamptic placenta, and represents a novel long-required tool for a sensitive placental phenotyping of this heterogeneous disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

ProtPhylo: identification of protein-phenotype and protein-protein functional associations via phylogenetic profiling.

PubMed

Cheng, Yiming; Perocchi, Fabiana

2015-07-01

ProtPhylo is a web-based tool to identify proteins that are functionally linked to either a phenotype or a protein of interest based on co-evolution. ProtPhylo infers functional associations by comparing protein phylogenetic profiles (co-occurrence patterns of orthology relationships) for more than 9.7 million non-redundant protein sequences from all three domains of life. Users can query any of 2048 fully sequenced organisms, including 1678 bacteria, 255 eukaryotes and 115 archaea. In addition, they can tailor ProtPhylo to a particular kind of biological question by choosing among four main orthology inference methods based either on pair-wise sequence comparisons (One-way Best Hits and Best Reciprocal Hits) or clustering of orthologous proteins across multiple species (OrthoMCL and eggNOG). Next, ProtPhylo ranks phylogenetic neighbors of query proteins or phenotypic properties using the Hamming distance as a measure of similarity between pairs of phylogenetic profiles. Candidate hits can be easily and flexibly prioritized by complementary clues on subcellular localization, known protein-protein interactions, membrane spanning regions and protein domains. The resulting protein list can be quickly exported into a csv text file for further analyses. ProtPhylo is freely available at http://www.protphylo.org. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Characterizing partial AZFc deletions of the Y chromosome with amplicon-specific sequence markers

PubMed Central

Navarro-Costa, Paulo; Pereira, Luísa; Alves, Cíntia; Gusmão, Leonor; Proença, Carmen; Marques-Vidal, Pedro; Rocha, Tiago; Correia, Sónia C; Jorge, Sónia; Neves, António; Soares, Ana P; Nunes, Joaquim; Calhaz-Jorge, Carlos; Amorim, António; Plancha, Carlos E; Gonçalves, João

2007-01-01

Background The AZFc region of the human Y chromosome is a highly recombinogenic locus containing multi-copy male fertility genes located in repeated DNA blocks (amplicons). These AZFc gene families exhibit slight sequence variations between copies which are considered to have functional relevance. Yet, partial AZFc deletions yield phenotypes ranging from normospermia to azoospermia, thwarting definite conclusions on their real impact on fertility. Results The amplicon content of partial AZFc deletion products was characterized with novel amplicon-specific sequence markers. Data indicate that partial AZFc deletions are a male infertility risk [odds ratio: 5.6 (95% CI: 1.6–30.1)] and although high diversity of partial deletion products and sequence conversion profiles were recorded, the AZFc marker profiles detected in fertile men were also observed in infertile men. Additionally, the assessment of rearrangement recurrence by Y-lineage analysis indicated that while partial AZFc deletions occurred in highly diverse samples, haplotype diversity was minimal in fertile men sharing identical marker profiles. Conclusion Although partial AZFc deletion products are highly heterogeneous in terms of amplicon content, this plasticity is not sufficient to account for the observed phenotypical variance. The lack of causative association between the deletion of specific gene copies and infertility suggests that AZFc gene content might be part of a multifactorial network, with Y-lineage evolution emerging as a possible phenotype modulator. PMID:17903263

Multi-dimensional optimization of a terawatt seeded tapered Free Electron Laser with a Multi-Objective Genetic Algorithm

DOE PAGES

Wu, Juhao; Hu, Newman; Setiawan, Hananiel; ...

2016-11-20

There is a great interest in generating high-power hard X-ray Free Electron Laser (FEL) in the terawatt (TW) level that can enable coherent diffraction imaging of complex molecules like proteins and probe fundamental high-field physics. A feasibility study of producing such X-ray pulses was carried out in this paper employing a configuration beginning with a Self-Amplified Spontaneous Emission FEL, followed by a “self-seeding” crystal monochromator generating a fully coherent seed, and finishing with a long tapered undulator where the coherent seed recombines with the electron bunch and is amplified to high power. The undulator tapering profile, the phase advance inmore » the undulator break sections, the quadrupole focusing strength, etc. are parameters to be optimized. A Genetic Algorithm (GA) is adopted for this multi-dimensional optimization. Concrete examples are given for LINAC Coherent Light Source (LCLS) and LCLS-II-type systems. Finally, analytical estimate is also developed to cross check the simulation and optimization results as a quick and complimentary tool.« less

Autism Spectrum Disorder Phenotype in Children with Ambulatory Cerebral Palsy: A Descriptive Cross-Sectional Study

ERIC Educational Resources Information Center

Smile, S.; Dupuis, A.; MacArthur, C.; Roberts, W.; Fehlings, D.

2013-01-01

The current study aims to describe the cognitive profile, autism profile, medical and behavioral presentation of children with a dual diagnosis of cerebral palsy (CP) and autism spectrum disorder (ASD). Little is known about the dual presentation of CP and ASD. Timely diagnosis is imperative as early intervention may impact a child's developmental…

Behavioural Phenotypes in the Classroom: A Qualitative Study of Parental and Teacher Knowledge of Classroom Guidelines and Teacher Views on Best Practices

ERIC Educational Resources Information Center

Reilly, Colin; Murtagh, Lelia; Senior, Joyce

2016-01-01

Research suggests that genetic syndromes associated with intellectual disability often have specific cognitive and behavioural profiles. It has been suggested that educational approaches need to reflect these profiles. Parents (n = 381) and teachers (n = 204) of children with one of four syndromes, fragile X syndrome, Prader-Willi syndrome,…

Methods, applications and concepts of metabolite profiling: primary metabolism.

PubMed

Steinhauser, Dirk; Kopka, Joachim

2007-01-01

In the 1990s the concept of a comprehensive analysis of the metabolic complement in biological systems, termed metabolomics or alternately metabonomics, was established as the last of four cornerstones for phenotypic studies in the post-genomic era. With genomic, transcriptomic, and proteomic technologies in place and metabolomic phenotyping under rapid development all necessary tools appear to be available today for a fully functional assessment of biological phenomena at all major system levels of life. This chapter attempts to describe and discuss crucial steps of establishing and maintaining a gas chromatography/electron impact ionization/ mass spectrometry (GC-EI-MS)-based metabolite profiling platform. GC-EI-MS can be perceived as the first and exemplary profiling technology aimed at simultaneous and non-biased analysis of primary metabolites from biological samples. The potential and constraints of this profiling technology are among the best understood. Most problems are solved as well as pitfalls identified. Thus GC-EI-MS serves as an ideal example for students and scientists who intend to enter the field of metabolomics. This chapter will be biased towards GC-EI-MS analyses but aims at discussing general topics, such as experimental design, metabolite identification, quantification and data mining.

Phage phenomics: Physiological approaches to characterize novel viral proteins

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

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

Phage phenomics: Physiological approaches to characterize novel viral proteins

DOE PAGES

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.; ...

2015-06-11

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

Phenotypic Variations in the Foliar Chemical Profile of Persea americana Mill. cv. Hass.

PubMed

García-Rodríguez, Yolanda Magdalena; Torres-Gurrola, Guadalupe; Meléndez-González, Claudio; Espinosa-García, Francisco J

2016-12-01

The Hass avocado tree Persea americana cv. Hass was derived from a single hybrid tree of P. americana var. drymifolia and P. americana var. guatemalensis, and it is propagated clonally by grafting. This cultivar is the most widely planted in the world but its profile of secondary metabolites has been studied rarely despite of its importance in plant protection. We illustrate the variability of the volatilome of mature leaves by describing the average chemical composition and the phenotypic variability found in 70 trees. Contrary to the uniformity expected in the Hass cultivar, high variability coefficients were found for most of the 36 detected foliar volatile compounds; furthermore we found six chemotypes grouping the foliar phenotypes of the sampled trees using hierarchical cluster analysis. About 48% of trees were grouped in one chemotype; five chemotypes grouped the remaining trees. The compounds that determined these chemotypes were: estragole, α-farnesene, β-caryophyllene, germacrene D, α-cubebene and eugenol. This striking variation in a cultivar propagated clonally is discussed in terms of somatic mutation. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

Motivational Profiles and Motivation for Lifelong Learning of Medical Specialists.

PubMed

van der Burgt, Stéphanie M E; Kusurkar, Rashmi A; Wilschut, Janneke A; Tjin A Tsoi, Sharon L N M; Croiset, Gerda; Peerdeman, Saskia M

2018-05-22

Medical specialists face the challenge of maintaining their knowledge and skills and continuing professional development, that is, lifelong learning. Motivation may play an integral role in many of the challenges facing the physician workforce today including maintenance of a high performance. The aim of this study was to determine whether medical specialists show different motivational profiles and if these profiles predict differences in motivation for lifelong learning. An online questionnaire was sent to every medical specialist working in five hospitals in the Netherlands. The questionnaire included the validated Multidimensional Work Motivation Scale and the Jefferson Scale of Physician Lifelong Learning together with background questions like age, gender, and type of hospital. Respondents were grouped into different motivational profiles by using a two-step clustering approach. Four motivational profiles were identified: (1) HAMC profile (for High Autonomous and Moderate Controlled motivation), (2) MAMC profile (for Moderate Autonomous and Moderate Controlled motivation), (3) MALC profile (for Moderate Autonomous and Low Controlled motivation), and (4) HALC profile (for High Autonomous and Low Controlled motivation). Most of the female specialists that work in an academic hospital and specialists with a surgical specialty were represented in the HALC profile. Four motivational profiles were found among medical specialists, differing in gender, experience and type of specialization. The profiles are based on the combination of autonomous motivation (AM) and controlled motivation (CM) in the specialists. The profiles that have a high score on autonomous motivation have a positive association with lifelong learning.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

High-Throughput Microbore UPLC-MS Metabolic Phenotyping of Urine for Large-Scale Epidemiology Studies.

PubMed

Gray, Nicola; Lewis, Matthew R; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K

2015-06-05

A new generation of metabolic phenotyping centers are being created to meet the increasing demands of personalized healthcare, and this has resulted in a major requirement for economical, high-throughput metabonomic analysis by liquid chromatography-mass spectrometry (LC-MS). Meeting these new demands represents an emerging bioanalytical problem that must be solved if metabolic phenotyping is to be successfully applied to large clinical and epidemiological sample sets. Ultraperformance (UP)LC-MS-based metabolic phenotyping, based on 2.1 mm i.d. LC columns, enables comprehensive metabolic phenotyping but, when employed for the analysis of thousands of samples, results in high solvent usage. The use of UPLC-MS employing 1 mm i.d. columns for metabolic phenotyping rather than the conventional 2.1 mm i.d. methodology shows that the resulting optimized microbore method provided equivalent or superior performance in terms of peak capacity, sensitivity, and robustness. On average, we also observed, when using the microbore scale separation, an increase in response of 2-3 fold over that obtained with the standard 2.1 mm scale method. When applied to the analysis of human urine, the 1 mm scale method showed no decline in performance over the course of 1000 analyses, illustrating that microbore UPLC-MS represents a viable alternative to conventional 2.1 mm i.d. formats for routine large-scale metabolic profiling studies while also resulting in a 75% reduction in solvent usage. The modest increase in sensitivity provided by this methodology also offers the potential to either reduce sample consumption or increase the number of metabolite features detected with confidence due to the increased signal-to-noise ratios obtained. Implementation of this miniaturized UPLC-MS method of metabolic phenotyping results in clear analytical, economic, and environmental benefits for large-scale metabolic profiling studies with similar or improved analytical performance compared to conventional UPLC-MS.

Determination of resistance and virulence genes in Enterococcus faecalis and E. faecium strains isolated from poultry and their genotypic characterization by ADSRRS-fingerprinting.

PubMed

Nowakiewicz, A; Ziólkowska, G; Troscianczyk, A; Zieba, P; Gnat, S

2017-04-01

The aim of this study was to determine the antimicrobial resistance of E. faecalis and E. faecium strains isolated from poultry and to carry out genotypic characterization thereof with the ADSRRS-fingerprinting method (amplification of DNA fragments surrounding rare restriction sites) and analysis of the genetic relatedness between the isolates with different resistance and virulence determinants. Samples were collected from 70 4-week-old chickens and tested for Enterococcus. Minimum inhibitory concentrations of 11 antimicrobials were determined using the broth microdilution method. Detection of antibiotic resistance and virulence genes was performed using PCR, and molecular analysis was carried out using the ADSRRS-fingerprinting method. The highest percentage of strains was resistant to tetracycline (60.5%) and erythromycin (54.4%), and a large number exhibited high-level resistance to both kanamycin (42.1%) and streptomycin (34.2%). Among 8 genes encoding AME, the tested strains showed mainly the presence of [aph(3΄)-IIIa], [ant(6)-Ia], [aac(6΄)-Ie-aph(2΄΄)-Ia], and [ant(9)-Ia] genes. Phenotypic resistance to erythromycin was encoded in 98.4% strains by the ermB gene. Genotypic resistance to tetracycline in E. faecium was associated with the presence of tetM and tetL (respectively, in 95.5 and 57.7% of the isolates); in contrast, E. faecalis strains were characterized mainly by the presence of tetO (83.3%). The virulence profile was homogenous for all E. faecium strains and included only efaAfm and ccf genes. All E. faecalis strains exhibited efaAfs, gelE, and genes encoding sex pheromones. The strains tested exhibited 34 genotypic profiles. Comparative analysis of phenotypic and genotypic resistance and virulence profiles and confrontation thereof with the genotypes of the strains tested showed that strains assigned to a particular genotype have an identical phenotypic resistance profile and a panel of resistance and virulence genes. The results of this study confirm that poultry can be a reservoir of resistant E. faecium and E. faecalis strains with multiple combinations of resistance and virulence genes, whose specific panel determines not only phenotypic characteristics but also has a strong correlation with the genotypic profiles of the strains. © 2016 Poultry Science Association Inc.

Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells.

PubMed

Tien, Joe; Truslow, James G; Nelson, Celeste M

2012-01-01

This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.

Do Children with Specific Language Impairment have a Cognitive Profile Reminiscent of Autism? A Review of the Literature.

PubMed

Taylor, Lauren J; Maybery, Murray T; Whitehouse, Andrew J O

2012-10-01

There is debate regarding the relationship between autism and specific language impairment (SLI), with some researchers proposing aetiological overlap between the conditions and others maintaining their aetiological distinction. Although considerable research has investigated the language phenotypes of these disorders, the relationship between the cognitive phenotypes has been left relatively unexplored. This paper reviews relevant literature on whether individuals with SLI exhibit cognitive characteristics reminiscent of autism. Overall, findings are inconsistent and there is a lack of substantive evidence supporting overlapping cognitive phenotypes in autism and SLI. Better powered and more rigorous experimental designs, as well as studies directly comparing the cognitive phenotype of children with SLI and those with autism will further elucidate the aetiological relationship between these two conditions.

Attention deficits and hyperactivity–impulsivity: What have we learned, what next?

PubMed Central

NIGG, JOEL T.

2015-01-01

The domains of self-regulation, self-control, executive function, inattention, and impulsivity cut across broad swathes of normal and abnormal development. Attention-deficit/hyperactivity disorder is a common syndrome that encompasses a portion of these domains. In the past 25 years research on attention-deficit/hyperactivity disorder has been characterized by dramatic advances in genetic, neural, and neuropsychological description of the syndrome as well as clarification of its multidimensional phenotypic structure. The limited clinical applicability of these research findings poses the primary challenge for the next generation. It is likely that clinical breakthroughs will require further refinement in describing heterogeneity or clinical/biological subgroups, renewed focus on the environment in the form of etiological events as well as psychosocial contexts of development, and integration of both with biological understanding. PMID:24342852

Merging Electronic Health Record Data and Genomics for Cardiovascular Research

PubMed Central

Hall, Jennifer L.; Ryan, John J.; Bray, Bruce E.; Brown, Candice; Lanfear, David; Newby, L. Kristin; Relling, Mary V.; Risch, Neil J.; Roden, Dan M.; Shaw, Stanley Y.; Tcheng, James E.; Tenenbaum, Jessica; Wang, Thomas N.; Weintraub, William S.

2017-01-01

The process of scientific discovery is rapidly evolving. The funding climate has influenced a favorable shift in scientific discovery toward the use of existing resources such as the electronic health record. The electronic health record enables long-term outlooks on human health and disease, in conjunction with multidimensional phenotypes that include laboratory data, images, vital signs, and other clinical information. Initial work has confirmed the utility of the electronic health record for understanding mechanisms and patterns of variability in disease susceptibility, disease evolution, and drug responses. The addition of biobanks and genomic data to the information contained in the electronic health record has been demonstrated. The purpose of this statement is to discuss the current challenges in and the potential for merging electronic health record data and genomics for cardiovascular research. PMID:26976545

Metabolic risk assessment of Indian women with polycystic ovarian syndrome in relation to four Rotterdam criteria based phenotypes.

PubMed

Tripathy, Priyadarshini; Sahu, Asutosh; Sahu, Mahija; Nagy, Attila

2018-05-01

Though polycystic ovarian syndrome (PCOS) is associated with multiple metabolic abnormalities, the metabolic risk profile of various PCOS phenotypes is still debated. Here we sought to compare the clinical, biochemical and metabolic parameters among the different PCOS phenotypes and controls. A total of 394 newly diagnosed PCOS women and 108 controls were enrolled consecutively. PCOS women were divided into four phenotypes based on the presence of two of the following Rotterdam criteria: oligo/anovulation (O), hyperandrogenism (H), and polycystic ovaries (P): A (O + H + P), B (O + H), C (H + P), D (O + P). Phenotype A (55.8%) was the most common phenotype in the PCOS cohort. Prevalence of metabolic syndrome was highest in phenotype A and B compared to other two phenotypes and controls. The clinical, biochemical and metabolic characteristics, of phenotypes A and B, were similar, but phenotype A had higher hirsutism score and androgen level. Phenotype C had intermediate metabolic characteristics between A and controls whereas phenotype D had the mildest metabolic abnormalities among the four phenotypes. Significant predictors for metabolic syndrome within the PCOS cohort are waist circumference >80 cm, hypertension, fasting glucose >100 mg/dL, HDL-cholesterol <50 mg/dL and triglyceride >150 mg/dL (p < 0.001). Indian PCOS women with Phenotype A and B lie at increased metabolic risk compared to other phenotypes. Phenotypic classification of PCOS women may facilitate more effective application of screening and treatment strategies for high-risk metabolic phenotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

GenomeCAT: a versatile tool for the analysis and integrative visualization of DNA copy number variants.

PubMed

Tebel, Katrin; Boldt, Vivien; Steininger, Anne; Port, Matthias; Ebert, Grit; Ullmann, Reinhard

2017-01-06

The analysis of DNA copy number variants (CNV) has increasing impact in the field of genetic diagnostics and research. However, the interpretation of CNV data derived from high resolution array CGH or NGS platforms is complicated by the considerable variability of the human genome. Therefore, tools for multidimensional data analysis and comparison of patient cohorts are needed to assist in the discrimination of clinically relevant CNVs from others. We developed GenomeCAT, a standalone Java application for the analysis and integrative visualization of CNVs. GenomeCAT is composed of three modules dedicated to the inspection of single cases, comparative analysis of multidimensional data and group comparisons aiming at the identification of recurrent aberrations in patients sharing the same phenotype, respectively. Its flexible import options ease the comparative analysis of own results derived from microarray or NGS platforms with data from literature or public depositories. Multidimensional data obtained from different experiment types can be merged into a common data matrix to enable common visualization and analysis. All results are stored in the integrated MySQL database, but can also be exported as tab delimited files for further statistical calculations in external programs. GenomeCAT offers a broad spectrum of visualization and analysis tools that assist in the evaluation of CNVs in the context of other experiment data and annotations. The use of GenomeCAT does not require any specialized computer skills. The various R packages implemented for data analysis are fully integrated into GenomeCATs graphical user interface and the installation process is supported by a wizard. The flexibility in terms of data import and export in combination with the ability to create a common data matrix makes the program also well suited as an interface between genomic data from heterogeneous sources and external software tools. Due to the modular architecture the functionality of GenomeCAT can be easily extended by further R packages or customized plug-ins to meet future requirements.

Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition

PubMed Central

Juss, Jatinder K.; House, David; Amour, Augustin; Begg, Malcolm; Herre, Jurgen; Storisteanu, Daniel M. L.; Hoenderdos, Kim; Bradley, Glyn; Lennon, Mark; Summers, Charlotte; Hessel, Edith M.; Condliffe, Alison

2016-01-01

Rationale: Acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease’s complex pathophysiology, yet these cells have been little studied. Objectives: To examine the functional and transcriptional profiles of patient blood and alveolar neutrophils compared with healthy volunteer cells, and to define their sensitivity to phosphoinositide 3-kinase inhibition. Methods: Twenty-three ventilated patients underwent bronchoalveolar lavage. Alveolar and blood neutrophil apoptosis, phagocytosis, and adhesion molecules were quantified by flow cytometry, and oxidase responses were quantified by chemiluminescence. Cytokine and transcriptional profiling were used in multiplex and GeneChip arrays. Measurements and Main Results: Patient blood and alveolar neutrophils were distinct from healthy circulating cells, with increased CD11b and reduced CD62L expression, delayed constitutive apoptosis, and primed oxidase responses. Incubating control cells with disease bronchoalveolar lavage recapitulated the aberrant functional phenotype, and this could be reversed by phosphoinositide 3-kinase inhibitors. In contrast, the prosurvival phenotype of patient cells was resistant to phosphoinositide 3-kinase inhibition. RNA transcriptomic analysis revealed modified immune, cytoskeletal, and cell death pathways in patient cells, aligning closely to sepsis and burns datasets but not to phosphoinositide 3-kinase signatures. Conclusions: Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed prosurvival profile and transcriptional signature. The enhanced respiratory burst was phosphoinositide 3-kinase–dependent but delayed apoptosis and the altered transcriptional profile were not. These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of evaluating novel therapeutic strategies in patient-derived cells. PMID:27064380

Molecular and cellular characterization of a Salmonella enterica serovar Paratyphi a outbreak strain and the human immune response to infection.

PubMed

Gal-Mor, Ohad; Suez, Jotham; Elhadad, Dana; Porwollik, Steffen; Leshem, Eyal; Valinsky, Lea; McClelland, Michael; Schwartz, Eliezer; Rahav, Galia

2012-02-01

Enteric fever is an invasive life-threatening systemic disease caused by the Salmonella enterica human-adapted serovars Typhi and Paratyphi. Increasing incidence of infections with Salmonella enterica serovar Paratyphi A and the spreading of its antibiotic-resistant derivates pose a significant health concern in some areas of the world. Herein, we describe a molecular and phenotypic characterization of an S. Paratyphi A strain accounted for a recent paratyphoid outbreak in Nepal that affected at least 37 travelers. Pulsed-field gel electrophoresis analysis of the outbreak isolates revealed one genetic clone (pulsotype), confirming a single infecting source. Genetic profiling of the outbreak strain demonstrated the contribution of specific bacteriophages as a prime source of genetic diversity among clinical isolates of S. Paratyphi A. Phenotypic characterization in comparison with the S. Paratyphi A ATCC 9150 reference sequenced strain showed differences in flagellar morphology and increased abilities of the outbreak strain with respect to its motility, invasion into nonphagocytic cells, intracellular multiplication, survival within macrophages, and higher induction of interleukin-8 (IL-8) secreted by host cells. Collectively, these differences suggest an enhanced virulence potential of this strain and demonstrate an interesting phenotypic variation among S. Paratyphi A isolates. In vivo profiling of 16 inflammatory cytokines in patients infected with the outbreak strain revealed a common profile of a remarkable gamma interferon (IFN-γ) induction together with elevated concentrations of tumor necrosis factor alpha (TNF-α), IL-6, IL-8, IL-10, and IL-15, but not IL-12, which was previously demonstrated as elevated in nontyphoidal Salmonella infections. This apparent profile implies a distinct immune response to paratyphoid infections.

Elucidation of the Metabolic Network of Helicobacter pylori J99 and Malaysian Clinical Strains by Phenotype Microarray.

PubMed

Lee, Woon Ching; Goh, Khean Lee; Loke, Mun Fai; Vadivelu, Jamuna

2017-02-01

Helicobacter pylori colonizes almost half of the human population worldwide. H. pylori strains are genetically diverse, and the specific genotypes are associated with various clinical manifestations including gastric adenocarcinoma, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). However, our current knowledge of the H. pylori metabolism is limited. To understand the metabolic differences among H. pylori strains, we investigated four Malaysian H. pylori clinical strains, which had been previously sequenced, and a standard strain, H. pylori J99, at the phenotypic level. The phenotypes of the H. pylori strains were profiled using the Biolog Phenotype Microarray system to corroborate genomic data. We initiated the analyses by predicting carbon and nitrogen metabolic pathways from the H. pylori genomic data from the KEGG database. Biolog PM aided the validation of the prediction and provided a more intensive analysis of the H. pylori phenomes. We have identified a core set of metabolic nutrient sources that was utilized by all strains tested and another set that was differentially utilized by only the local strains. Pentose sugars are the preferred carbon nutrients utilized by H. pylori. The amino acids l-aspartic acid, d-alanine, and l-asparagine serve as both carbon and nitrogen sources in the metabolism of the bacterium. The phenotypic profile based on this study provides a better understanding on the survival of H. pylori in its natural host. Our data serve as a foundation for future challenges in correlating interstrain metabolic differences in H. pylori. © 2016 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

The pathological and molecular but not clinical phenotypes are maintained after second passage of experimental atypical bovine spongiform encephalopathy in cattle.

PubMed

Konold, Timm; Phelan, Laura J; Clifford, Derek; Chaplin, Melanie J; Cawthraw, Saira; Stack, Michael J; Simmons, Marion M

2014-10-02

Atypical bovine spongiform encephalopathies (BSEs), classified as H-type and L-type BSE based on the Western immunoblot profiles, are naturally occurring diseases in cattle, which are phenotypically different to classical BSE. Transmission studies in cattle using the intracerebral route resulted in disease where the phenotypes were maintained irrespective of BSE type but clinically affected cattle with a shorter survival time displayed a nervous form whereas cattle with a longer survival time displayed a dull form. A second transmission study is reported here where four cattle were intracerebrally inoculated with brain tissue from experimentally infected cattle presenting with either the nervous or dull form of H- or L-type BSE to determine whether the phenotype is maintained. The four inoculated cattle were culled at 16.5-19.5 months post inoculation after presenting with difficulty getting up, a positive scratch response (all) and dullness (three cattle), which was not observed in two non-inoculated control cattle, each housed with either group of inoculated cattle. Only the inoculated cattle had detectable prion protein in the brain based on immunohistochemical examination, and the Western immunoblot profile was consistent with the H-type or L-type BSE of the respective donor cattle. Second passage of H-type and L-type BSE in cattle produced a TSE where the majority of cattle displayed the dull form regardless of clinical disease form of the donor cattle. The pathological and molecular phenotypes of H- and L-type BSE were maintained.

Multidimensional poverty, household environment and short-term morbidity in India.

PubMed

Dehury, Bidyadhar; Mohanty, Sanjay K

2017-01-01

Using the unit data from the second round of the Indian Human Development Survey (IHDS-II), 2011-2012, which covered 42,152 households, this paper examines the association between multidimensional poverty, household environmental deprivation and short-term morbidities (fever, cough and diarrhoea) in India. Poverty is measured in a multidimensional framework that includes the dimensions of education, health and income, while household environmental deprivation is defined as lack of access to improved sanitation, drinking water and cooking fuel. A composite index combining multidimensional poverty and household environmental deprivation has been computed, and households are classified as follows: multidimensional poor and living in a poor household environment, multidimensional non-poor and living in a poor household environment, multidimensional poor and living in a good household environment and multidimensional non-poor and living in a good household environment. Results suggest that about 23% of the population belonging to multidimensional poor households and living in a poor household environment had experienced short-term morbidities in a reference period of 30 days compared to 20% of the population belonging to multidimensional non-poor households and living in a poor household environment, 19% of the population belonging to multidimensional poor households and living in a good household environment and 15% of the population belonging to multidimensional non-poor households and living in a good household environment. Controlling for socioeconomic covariates, the odds of short-term morbidity was 1.47 [CI 1.40-1.53] among the multidimensional poor and living in a poor household environment, 1.28 [CI 1.21-1.37] among the multidimensional non-poor and living in a poor household environment and 1.21 [CI 1.64-1.28] among the multidimensional poor and living in a good household environment compared to the multidimensional non-poor and living in a good household environment. Results are robust across states and hold good for each of the three morbidities: fever, cough and diarrhoea. This establishes that along with poverty, household environmental conditions have a significant bearing on short-term morbidities in India. Public investment in sanitation, drinking water and cooking fuel can reduce the morbidity and improve the health of the population.

DeDaL: Cytoscape 3 app for producing and morphing data-driven and structure-driven network layouts.

PubMed

Czerwinska, Urszula; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

2015-08-14

Visualization and analysis of molecular profiling data together with biological networks are able to provide new mechanistic insights into biological functions. Currently, it is possible to visualize high-throughput data on top of pre-defined network layouts, but they are not always adapted to a given data analysis task. A network layout based simultaneously on the network structure and the associated multidimensional data might be advantageous for data visualization and analysis in some cases. We developed a Cytoscape app, which allows constructing biological network layouts based on the data from molecular profiles imported as values of node attributes. DeDaL is a Cytoscape 3 app, which uses linear and non-linear algorithms of dimension reduction to produce data-driven network layouts based on multidimensional data (typically gene expression). DeDaL implements several data pre-processing and layout post-processing steps such as continuous morphing between two arbitrary network layouts and aligning one network layout with respect to another one by rotating and mirroring. The combination of all these functionalities facilitates the creation of insightful network layouts representing both structural network features and correlation patterns in multivariate data. We demonstrate the added value of applying DeDaL in several practical applications, including an example of a large protein-protein interaction network. DeDaL is a convenient tool for applying data dimensionality reduction methods and for designing insightful data displays based on data-driven layouts of biological networks, built within Cytoscape environment. DeDaL is freely available for downloading at http://bioinfo-out.curie.fr/projects/dedal/.

Anxiety is not enough to drive me away: A latent profile analysis on math anxiety and math motivation.

PubMed

Wang, Zhe; Shakeshaft, Nicholas; Schofield, Kerry; Malanchini, Margherita

2018-01-01

Mathematics anxiety (MA) and mathematics motivation (MM) are important multi-dimensional non-cognitive factors in mathematics learning. While the negative relation between global MA and MM is well replicated, the relations between specific dimensions of MA and MM are largely unexplored. The present study utilized latent profile analysis to explore profiles of various aspects of MA (including learning MA and exam MA) and MM (including importance, self-perceived ability, and interest), to provide a more holistic understanding of the math-specific emotion and motivation experiences. In a sample of 927 high school students (13-21 years old), we found 8 distinct profiles characterized by various combinations of dimensions of MA and MM, revealing the complexity in the math-specific emotion-motivation relation beyond a single negative correlation. Further, these profiles differed on mathematics learning behaviors and mathematics achievement. For example, the highest achieving students reported modest exam MA and high MM, whereas the most engaged students were characterized by a combination of high exam MA and high MM. These results call for the need to move beyond linear relations among global constructs to address the complexity in the emotion-motivation-cognition interplay in mathematics learning, and highlight the importance of customized intervention for these heterogeneous groups.

Anxiety is not enough to drive me away: A latent profile analysis on math anxiety and math motivation

PubMed Central

Shakeshaft, Nicholas; Schofield, Kerry; Malanchini, Margherita

2018-01-01

Mathematics anxiety (MA) and mathematics motivation (MM) are important multi-dimensional non-cognitive factors in mathematics learning. While the negative relation between global MA and MM is well replicated, the relations between specific dimensions of MA and MM are largely unexplored. The present study utilized latent profile analysis to explore profiles of various aspects of MA (including learning MA and exam MA) and MM (including importance, self-perceived ability, and interest), to provide a more holistic understanding of the math-specific emotion and motivation experiences. In a sample of 927 high school students (13–21 years old), we found 8 distinct profiles characterized by various combinations of dimensions of MA and MM, revealing the complexity in the math-specific emotion-motivation relation beyond a single negative correlation. Further, these profiles differed on mathematics learning behaviors and mathematics achievement. For example, the highest achieving students reported modest exam MA and high MM, whereas the most engaged students were characterized by a combination of high exam MA and high MM. These results call for the need to move beyond linear relations among global constructs to address the complexity in the emotion-motivation-cognition interplay in mathematics learning, and highlight the importance of customized intervention for these heterogeneous groups. PMID:29444137

Impact of Profiling Technologies in the Understanding of Recombinant Protein Production

NASA Astrophysics Data System (ADS)

Vijayendran, Chandran; Flaschel, Erwin

Since expression profiling methods have been available in a high throughput fashion, the implication of these technologies in the field of biotechnology has increased dramatically. Microarray technology is one such unique and efficient methodology for simultaneous exploration of expression levels of numerous genes. Likewise, two-dimensional gel electrophoresis or multidimensional liquid chromatography coupled with mass spectrometry are extensively utilised for studying expression levels of numerous proteins. In the field of biotechnology these highly parallel analytical methods have paved the way to study and understand various biological phenomena depending on expression patterns. The next phenomenological level is represented by the metabolome and the (metabolic) fluxome. However, this chapter reviews gene and protein profiling and their impact on understanding recombinant protein production. We focus on the computational methods utilised for the analyses of data obtained from these profiling technologies as well as prominent results focusing on recombinant protein expression with Escherichia coli. Owing to the knowledge accumulated with respect to cellular signals triggered during recombinant protein production, this field is on the way to design strategies for developing improved processes. Both gene and protein profiling have exhibited a handful of functional categories to concentrate on in order to identify target genes and proteins, respectively, involved in the signalling network with major impact on recombinant protein production.

A Gene Expression Profile of BRCAness that Predicts for Responsiveness to Platinum and PARP Inhibitors

DTIC Science & Technology

2013-08-01

like ( NBL ) corresponding to tumors predicted to have a BRCAness phenotype (BL tumors) or not ( NBL tumors). In the previous years we performed a...TCGA EOC project that have been characterized as BL or NBL by our profile to identify 3 candidate miRNAs (let-7f-2*, miR-744*, miR-342-5p) that may be

Diagnostic Classification of Eating Disorders in Children and Adolescents: How Does DSM-IV-TR Compare to Empirically-Derived Categories?

ERIC Educational Resources Information Center

Eddy, Kamryn T.; Le Grange, Daniel; Crosby, Ross D.; Hoste, Renee Rienecke; Doyle, Angela Celio; Smyth, Angela; Herzog, David B.

2010-01-01

Objective: The purpose of this study was to empirically derive eating disorder phenotypes in a clinical sample of children and adolescents using latent profile analysis (LPA), and to compare these latent profile (LP) groups to the DSM-IV-TR eating disorder categories. Method: Eating disorder symptom data collected from 401 youth (aged 7 through 19…

An image analysis toolbox for high-throughput C. elegans assays

PubMed Central

Wählby, Carolina; Kamentsky, Lee; Liu, Zihan H.; Riklin-Raviv, Tammy; Conery, Annie L.; O’Rourke, Eyleen J.; Sokolnicki, Katherine L.; Visvikis, Orane; Ljosa, Vebjorn; Irazoqui, Javier E.; Golland, Polina; Ruvkun, Gary; Ausubel, Frederick M.; Carpenter, Anne E.

2012-01-01

We present a toolbox for high-throughput screening of image-based Caenorhabditis elegans phenotypes. The image analysis algorithms measure morphological phenotypes in individual worms and are effective for a variety of assays and imaging systems. This WormToolbox is available via the open-source CellProfiler project and enables objective scoring of whole-animal high-throughput image-based assays of C. elegans for the study of diverse biological pathways relevant to human disease. PMID:22522656

The 482Ser of PPARGC1A and 12Pro of PPARG2 Alleles Are Associated with Reduction of Metabolic Risk Factors Even Obesity in a Mexican-Mestizo Population.

PubMed

Vázquez-Del Mercado, Mónica; Guzmán-Ornelas, Milton-Omar; Corona Meraz, Fernanda-Isadora; Ríos-Ibarra, Clara-Patricia; Reyes-Serratos, Eduardo-Alejandro; Castro-Albarran, Jorge; Ruíz-Quezada, Sandra-Luz; Navarro-Hernández, Rosa-Elena

2015-01-01

The aim of this study was to investigate the relationship between functional polymorphisms Gly482Ser in PPARGC1A and Pro12Ala in PPARG2 with the presence of obesity and metabolic risk factors. We included 375 individuals characterized as Mexican-Mestizos and classified by the body mass index (BMI). Body dimensions and distribution of body fat were measured. The HOMA-IR and adiposity indexes were calculated. Adipokines and metabolic profile quantification were performed by ELISA and routine methods. Genetic polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism analysis. A difference between obese and nonobese subjects in polymorphism PPARGC1A distribution was observed. Among obese individuals, carriers of genotype 482Gly/Gly were observed to have decreased body fat, BMI, and body fat ratio versus 482Ser/Ser carriers and increased resistin and leptin levels in carriers Gly+ phenotype versus Gly- phenotype. Subjects with PPARG2 Ala- phenotype (genotype 12Pro/Pro) showed a decreased HOMA-IR index versus individuals with Ala+ phenotype (genotypes 12Pro/Ala plus 12Ala/Ala). We propose that, in obese Mexican-Mestizos, the combination of alleles 482Ser in PPARGC1A and 12Pro in PPARG2 represents a reduced metabolic risk profile, even when the adiposity indexes are increased.

An integrated one-step system to extract, analyze and annotate all relevant information from image-based cell screening of chemical libraries.

PubMed

Rabal, Obdulia; Link, Wolfgang; Serelde, Beatriz G; Bischoff, James R; Oyarzabal, Julen

2010-04-01

Here we report the development and validation of a complete solution to manage and analyze the data produced by image-based phenotypic screening campaigns of small-molecule libraries. In one step initial crude images are analyzed for multiple cytological features, statistical analysis is performed and molecules that produce the desired phenotypic profile are identified. A naïve Bayes classifier, integrating chemical and phenotypic spaces, is built and utilized during the process to assess those images initially classified as "fuzzy"-an automated iterative feedback tuning. Simultaneously, all this information is directly annotated in a relational database containing the chemical data. This novel fully automated method was validated by conducting a re-analysis of results from a high-content screening campaign involving 33 992 molecules used to identify inhibitors of the PI3K/Akt signaling pathway. Ninety-two percent of confirmed hits identified by the conventional multistep analysis method were identified using this integrated one-step system as well as 40 new hits, 14.9% of the total, originally false negatives. Ninety-six percent of true negatives were properly recognized too. A web-based access to the database, with customizable data retrieval and visualization tools, facilitates the posterior analysis of annotated cytological features which allows identification of additional phenotypic profiles; thus, further analysis of original crude images is not required.

The 482Ser of PPARGC1A and 12Pro of PPARG2 Alleles Are Associated with Reduction of Metabolic Risk Factors Even Obesity in a Mexican-Mestizo Population

PubMed Central

Vázquez-Del Mercado, Mónica; Guzmán-Ornelas, Milton-Omar; Corona Meraz, Fernanda-Isadora; Ríos-Ibarra, Clara-Patricia; Reyes-Serratos, Eduardo-Alejandro; Castro-Albarran, Jorge; Ruíz-Quezada, Sandra-Luz; Navarro-Hernández, Rosa-Elena

2015-01-01

The aim of this study was to investigate the relationship between functional polymorphisms Gly482Ser in PPARGC1A and Pro12Ala in PPARG2 with the presence of obesity and metabolic risk factors. We included 375 individuals characterized as Mexican-Mestizos and classified by the body mass index (BMI). Body dimensions and distribution of body fat were measured. The HOMA-IR and adiposity indexes were calculated. Adipokines and metabolic profile quantification were performed by ELISA and routine methods. Genetic polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism analysis. A difference between obese and nonobese subjects in polymorphism PPARGC1A distribution was observed. Among obese individuals, carriers of genotype 482Gly/Gly were observed to have decreased body fat, BMI, and body fat ratio versus 482Ser/Ser carriers and increased resistin and leptin levels in carriers Gly+ phenotype versus Gly− phenotype. Subjects with PPARG2 Ala− phenotype (genotype 12Pro/Pro) showed a decreased HOMA-IR index versus individuals with Ala+ phenotype (genotypes 12Pro/Ala plus 12Ala/Ala). We propose that, in obese Mexican-Mestizos, the combination of alleles 482Ser in PPARGC1A and 12Pro in PPARG2 represents a reduced metabolic risk profile, even when the adiposity indexes are increased. PMID:26185753

High-Resolution Metabolic Phenotyping of Genetically and Environmentally Diverse Potato Tuber Systems. Identification of Phenocopies

PubMed Central

Roessner, Ute; Willmitzer, Lothar; Fernie, Alisdair R.

2001-01-01

We conducted a comprehensive metabolic phenotyping of potato (Solanum tuberosum L. cv Desiree) tuber tissue that had been modified either by transgenesis or exposure to different environmental conditions using a recently developed gas chromatography-mass spectrometry profiling protocol. Applying this technique, we were able to identify and quantify the major constituent metabolites of the potato tuber within a single chromatographic run. The plant systems that we selected to profile were tuber discs incubated in varying concentrations of fructose, sucrose, and mannitol and transgenic plants impaired in their starch biosynthesis. The resultant profiles were then compared, first at the level of individual metabolites and then using the statistical tools hierarchical cluster analysis and principal component analysis. These tools allowed us to assign clusters to the individual plant systems and to determine relative distances between these clusters; furthermore, analyzing the loadings of these analyses enabled identification of the most important metabolites in the definition of these clusters. The metabolic profiles of the sugar-fed discs were dramatically different from the wild-type steady-state values. When these profiles were compared with one another and also with those we assessed in previous studies, however, we were able to evaluate potential phenocopies. These comparisons highlight the importance of such an approach in the functional and qualitative assessment of diverse systems to gain insights into important mediators of metabolism. PMID:11706160

Profiles of Resilience and Psychosocial Outcomes among Young Black Gay and Bisexual Men.

PubMed

Wilson, Patrick A; Meyer, Ilan H; Antebi-Gruszka, Nadav; Boone, Melissa R; Cook, Stephanie H; Cherenack, Emily M

2016-03-01

Young Black gay/bisexual men (YBGBM) are affected by contextual stressors-namely syndemic conditions and minority stress-that threaten their health and well-being. Resilience is a process through which YBGBM achieve positive psychosocial outcomes in the face of adverse conditions. Self-efficacy, hardiness and adaptive coping, and social support may be important resilience factors for YBGBM. This study explores different profiles of these resilience factors in 228 YBGBM in New York City and compares profiles on psychological distress, mental health, and other psychosocial factors. Four profiles of resilience were identified: (a) Low self-efficacy and hardiness/adaptive coping (23.5%); (b) Low peer and parental support (21.2%); (c) High peer support, low father support (34.5%); and (d) High father and mother support, self-efficacy, and hardiness/adaptive coping (20.8%). YBGBM in profile 1 scored markedly higher on distress (d = .74) and lower on mental health functioning (d = .93) compared to men in the other profiles. Results suggest that self-efficacy and hardiness/adaptive coping may play a more important role in protecting YBGBM from risks compared to social support and should be targeted in interventions. The findings show that resilience is a multidimensional construct and support the notion that there are different patterns of resilience among YBGBM. © Society for Community Research and Action 2016.

Evolutionary profiles from the QR factorization of multiple sequence alignments

PubMed Central

Sethi, Anurag; O'Donoghue, Patrick; Luthey-Schulten, Zaida

2005-01-01

We present an algorithm to generate complete evolutionary profiles that represent the topology of the molecular phylogenetic tree of the homologous group. The method, based on the multidimensional QR factorization of numerically encoded multiple sequence alignments, removes redundancy from the alignments and orders the protein sequences by increasing linear dependence, resulting in the identification of a minimal basis set of sequences that spans the evolutionary space of the homologous group of proteins. We observe a general trend that these smaller, more evolutionarily balanced profiles have comparable and, in many cases, better performance in database searches than conventional profiles containing hundreds of sequences, constructed in an iterative and computationally intensive procedure. For more diverse families or superfamilies, with sequence identity <30%, structural alignments, based purely on the geometry of the protein structures, provide better alignments than pure sequence-based methods. Merging the structure and sequence information allows the construction of accurate profiles for distantly related groups. These structure-based profiles outperformed other sequence-based methods for finding distant homologs and were used to identify a putative class II cysteinyl-tRNA synthetase (CysRS) in several archaea that eluded previous annotation studies. Phylogenetic analysis showed the putative class II CysRSs to be a monophyletic group and homology modeling revealed a constellation of active site residues similar to that in the known class I CysRS. PMID:15741270

Multidimensional chromatography in food analysis.

PubMed

Herrero, Miguel; Ibáñez, Elena; Cifuentes, Alejandro; Bernal, Jose

2009-10-23

In this work, the main developments and applications of multidimensional chromatographic techniques in food analysis are reviewed. Different aspects related to the existing couplings involving chromatographic techniques are examined. These couplings include multidimensional GC, multidimensional LC, multidimensional SFC as well as all their possible combinations. Main advantages and drawbacks of each coupling are critically discussed and their key applications in food analysis described.

Random whole metagenomic sequencing for forensic discrimination of soils.

PubMed

Khodakova, Anastasia S; Smith, Renee J; Burgoyne, Leigh; Abarno, Damien; Linacre, Adrian

2014-01-01

Here we assess the ability of random whole metagenomic sequencing approaches to discriminate between similar soils from two geographically distinct urban sites for application in forensic science. Repeat samples from two parklands in residential areas separated by approximately 3 km were collected and the DNA was extracted. Shotgun, whole genome amplification (WGA) and single arbitrarily primed DNA amplification (AP-PCR) based sequencing techniques were then used to generate soil metagenomic profiles. Full and subsampled metagenomic datasets were then annotated against M5NR/M5RNA (taxonomic classification) and SEED Subsystems (metabolic classification) databases. Further comparative analyses were performed using a number of statistical tools including: hierarchical agglomerative clustering (CLUSTER); similarity profile analysis (SIMPROF); non-metric multidimensional scaling (NMDS); and canonical analysis of principal coordinates (CAP) at all major levels of taxonomic and metabolic classification. Our data showed that shotgun and WGA-based approaches generated highly similar metagenomic profiles for the soil samples such that the soil samples could not be distinguished accurately. An AP-PCR based approach was shown to be successful at obtaining reproducible site-specific metagenomic DNA profiles, which in turn were employed for successful discrimination of visually similar soil samples collected from two different locations.

Stability of an empirical psychosocial taxonomy across type of diabetes and treatment.

PubMed

Nouwen, A; Breton, M-C; Urquhart Law, G; Descôteaux, J

2007-01-01

The aims of the study were (i) to examine whether an empirical psychosocial taxonomy, based on key diabetes-related variables, is independent of type of diabetes and treatment, and (ii) to further establish the external validation of the taxonomy. In a cross-sectional study, 82 patients with Type 1 and 86 patients with Type 2 diabetes mellitus were assigned to one of three psychosocial patient profiles based on their Multidimensional Diabetes Questionnaire (MDQ) scores. General psychological and diabetes-specific measures were obtained through self-report and HbA(1c) was measured. Equal proportions of Type 1 and Type 2 patients, and of patients using insulin and oral medication/diet only were classified within each of the three psychosocial profiles. External validation confirmed the validity and distinctiveness of the patients' profiles. The patient profiles were independent of demographic variables, body mass index, duration of diabetes, complexity of treatment, number of complications, social desirability, and major stress levels. The Psychosocial Taxonomy for Patients with Diabetes provides a new way to categorize individuals who may have more in common than just their type of diabetes and/or its treatment and can help target interventions to individual patients' needs.

Multidimensional Riemann problem with self-similar internal structure - part III - a multidimensional analogue of the HLLI Riemann solver for conservative hyperbolic systems

NASA Astrophysics Data System (ADS)

Balsara, Dinshaw S.; Nkonga, Boniface

2017-10-01

Just as the quality of a one-dimensional approximate Riemann solver is improved by the inclusion of internal sub-structure, the quality of a multidimensional Riemann solver is also similarly improved. Such multidimensional Riemann problems arise when multiple states come together at the vertex of a mesh. The interaction of the resulting one-dimensional Riemann problems gives rise to a strongly-interacting state. We wish to endow this strongly-interacting state with physically-motivated sub-structure. The fastest way of endowing such sub-structure consists of making a multidimensional extension of the HLLI Riemann solver for hyperbolic conservation laws. Presenting such a multidimensional analogue of the HLLI Riemann solver with linear sub-structure for use on structured meshes is the goal of this work. The multidimensional MuSIC Riemann solver documented here is universal in the sense that it can be applied to any hyperbolic conservation law. The multidimensional Riemann solver is made to be consistent with constraints that emerge naturally from the Galerkin projection of the self-similar states within the wave model. When the full eigenstructure in both directions is used in the present Riemann solver, it becomes a complete Riemann solver in a multidimensional sense. I.e., all the intermediate waves are represented in the multidimensional wave model. The work also presents, for the very first time, an important analysis of the dissipation characteristics of multidimensional Riemann solvers. The present Riemann solver results in the most efficient implementation of a multidimensional Riemann solver with sub-structure. Because it preserves stationary linearly degenerate waves, it might also help with well-balancing. Implementation-related details are presented in pointwise fashion for the one-dimensional HLLI Riemann solver as well as the multidimensional MuSIC Riemann solver.

Determination of antibiotic resistance and high-performance liquid chromatography profiles for Mycobacterium species.

PubMed

Toka Özer, Türkan; Yula, Erkan; Doğan, Metin; Baskın, Hüseyin

2018-04-27

Incidence of mycobacterial infections has been increasing. However, diagnosis and treatment of mycobacterial infections can be difficult. The aim of this study was to investigate high-performance liquid chromatography (HPLC) analysis of the mycolic acids for rapid identification and dendrogram cluster analysis of mycobacterium species. Clinical specimens received for mycobacterial culture and antimicrobial susceptibility test were processed by standard laboratory protocols. Positive cultures were analyzed with HPLC method. Mycolic acid analysis with HPLC was used for diagnosis of tuberculosis and other mycobacterial infections. These reports were compared with Sherlock Library mycobacterial species, and the similarity index was analyzed. This value was formed by a software in multidimensional space that was the calculation of the average distance between the nearest library profile and unknown profile. The ninety-two samples were identified as M. tuberculosis. (similarity index between 0.593 and 0.994). One of the other strains was identified as M. avium intracellulare (strain No. 82) (SI = 0.906); one of them was identified as M. interjectum (strain no. 89) (SI = 0.644). Total 94 samples were identified, and dendrogram was applied to these samples. Profile A (10.6%), profile B (59.6%), profile C (11.7%), profile D (3.2%), and other profiles as single different profiles were identified. Rates for each as 1% (89, 94, 1, 82, 26, 42, 32, 41, 100, 43, 47, 44, 40, 35). High-performance liquid chromatography is a useful, rapid, reliable, and practical method for diagnosis of mycobacterium species. © 2018 Wiley Periodicals, Inc.

A Computational Methodology for Simulating Thermal Loss Testing of the Advanced Stirling Convertor

NASA Technical Reports Server (NTRS)

Reid, Terry V.; Wilson, Scott D.; Schifer, Nicholas A.; Briggs, Maxwell H.

2012-01-01

The U.S. Department of Energy (DOE) and Lockheed Martin Space Systems Company (LMSSC) have been developing the Advanced Stirling Radioisotope Generator (ASRG) for use as a power system for space science missions. This generator would use two highefficiency Advanced Stirling Convertors (ASCs), developed by Sunpower Inc. and NASA Glenn Research Center (GRC). The ASCs convert thermal energy from a radioisotope heat source into electricity. As part of ground testing of these ASCs, different operating conditions are used to simulate expected mission conditions. These conditions require achieving a particular operating frequency, hot end and cold end temperatures, and specified electrical power output for a given net heat input. In an effort to improve net heat input predictions, numerous tasks have been performed which provided a more accurate value for net heat input into the ASCs, including the use of multidimensional numerical models. Validation test hardware has also been used to provide a direct comparison of numerical results and validate the multi-dimensional numerical models used to predict convertor net heat input and efficiency. These validation tests were designed to simulate the temperature profile of an operating Stirling convertor and resulted in a measured net heat input of 244.4 W. The methodology was applied to the multi-dimensional numerical model which resulted in a net heat input of 240.3 W. The computational methodology resulted in a value of net heat input that was 1.7 percent less than that measured during laboratory testing. The resulting computational methodology and results are discussed.

Multidimensional improvements induced by an intensive obesity inpatients rehabilitation programme.

PubMed

Giordano, Francesca; Berteotti, Michela; Budui, Simona; Calgaro, Nicole; Franceschini, Laura; Gilli, Federica; Masiero, Marina; Raschellà, Guido; Salvetti, Sabrina; Taddei, Micol; Schena, Federico; Busetto, Luca

2017-06-01

To analyse the short-term effectiveness of an intensive multidimensional inpatient programme specifically developed for patients with severe obesity. A multidisciplinary team managed a 3-week residential programme characterised by the integration of nutritional and physical rehabilitation with psychological and educational intervention. All patients consecutively admitted in 10 months were analysed at admission and discharge for changes in the following domains: anthropometry (weight, body mass index (BMI), waist and neck circumferences), cardiovascular risk factors (glycaemia, HbA1c, lipid profile, blood pressure), quality of life, eating behaviour, and physical performance (VO 2peak by incremental cycle ergometer test, 6-min walking test (6MWT), chair stands test). 136 subjects (61% females, median age 52.7 years) with obesity (mean BMI 43.2 kg/m 2 ) and multiple comorbidities were analysed. A 3.9% BMI reduction and a reduction in waist (-3.8%) and neck (-3.3%) circumferences were observed. Glycaemic control was achieved in 68% of patients with uncontrolled diabetes at admission. Blood pressure control was achieved in all patients with uncontrolled hypertension at admission. Total cholesterol (-16%), LDL-cholesterol (-19%) and triglycerides (-9%) were significantly reduced. Psychometric assessment showed improvements in quality of life perception and binge eating disorder. Finally, a significant improvement in physical performance (+4.7% improvement in VO 2peak , with longer distances in 6MWT and a higher number of standings) was observed. Our preliminary data prove that a 3-week programme determined a clinically significant multi-dimensional improvement in patients with severe obesity. Long-term follow-up data are needed to confirm the efficacy of our rehabilitation setting.

Short communication: Cytokine profiles from blood mononuclear cells of dairy cows classified with divergent immune response phenotypes.

PubMed

Martin, C E; Paibomesai, M A; Emam, S M; Gallienne, J; Hine, B C; Thompson-Crispi, K A; Mallard, B A

2016-03-01

Genetic selection for enhanced immune response has been shown to decrease disease occurrence in dairy cattle. Cows can be classified as high (H), average, or low responders based on antibody-mediated immune response (AMIR), predominated by type-2 cytokine production, and cell-mediated immune response (CMIR) through estimated breeding values for these traits. The purpose of this study was to identify in vitro tests that correlate with in vivo immune response phenotyping in dairy cattle. Blood mononuclear cells (BMC) isolated from cows classified as H-AMIR and H-CMIR through estimated breeding values for immune response traits were stimulated with concanavalin A (ConA; Sigma Aldrich, St. Louis, MO) and gene expression, cytokine production, and cell proliferation was determined at multiple time points. A repeated measures model, which included the effects of immune response group, parity, and stage of lactation, was used to compare differences between immune response phenotype groups. The H-AMIR cows produced more IL-4 protein than H-CMIR cows at 48 h; however, no difference in gene expression of type-2 transcription factor GATA3 or IL4 was noted. The BMC from H-CMIR cows had increased production of IFN-γ protein at 48, 72, and 96 h compared with H-AMIR animals. Further, H-CMIR cows had increased expression of the IFNG gene at 16, 24, and 48 h post-treatment with ConA, although expression of the type-1 transcription factor gene TBX21 did not differ between immune response groups. Although proliferation of BMC increased from 24 to 72 h after ConA stimulation, no differences were found between the immune response groups. Overall, stimulation of H-AMIR and H-CMIR bovine BMC with ConA resulted in distinct cytokine production profiles according to genetically defined groups. These distinct cytokine profiles could be used to define disease resistance phenotypes in dairy cows according to stimulation in vitro; however, other immune response phenotypes should be assessed. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of simulated microgravity on gene expression and biological phenotypes of a single generation Caenorhabditis elegans cultured on 2 different media

NASA Astrophysics Data System (ADS)

Tee, Ling Fei; Neoh, Hui-min; Then, Sue Mian; Murad, Nor Azian; Asillam, Mohd Fairos; Hashim, Mohd Helmy; Nathan, Sheila; Jamal, Rahman

2017-11-01

Studies of multigenerational Caenorhabditis elegans exposed to long-term spaceflight have revealed expression changes of genes involved in longevity, DNA repair, and locomotion. However, results from spaceflight experiments are difficult to reproduce as space missions are costly and opportunities are rather limited for researchers. In addition, multigenerational cultures of C. elegans used in previous studies contribute to mixture of gene expression profiles from both larvae and adult worms, which were recently reported to be different. Usage of different culture media during microgravity simulation experiments might also give rise to differences in the gene expression and biological phenotypes of the worms. In this study, we investigated the effects of simulated microgravity on the gene expression and biological phenotype profiles of a single generation of C. elegans worms cultured on 2 different culture media. A desktop Random Positioning Machine (RPM) was used to simulate microgravity on the worms for approximately 52 to 54 h. Gene expression profile was analysed using the Affymetrix GeneChip® C. elegans 1.0 ST Array. Only one gene (R01H2.2) was found to be downregulated in nematode growth medium (NGM)-cultured worms exposed to simulated microgravity. On the other hand, eight genes were differentially expressed for C. elegans Maintenance Medium (CeMM)-cultured worms in microgravity; six were upregulated, while two were downregulated. Five of the upregulated genes (C07E3.15, C34H3.21, C32D5.16, F35H8.9 and C34F11.17) encode non-coding RNAs. In terms of biological phenotype, we observed that microgravity-simulated worms experienced minimal changes in terms of lifespan, locomotion and reproductive capabilities in comparison with the ground controls. Taking it all together, simulated microgravity on a single generation of C. elegans did not confer major changes to their gene expression and biological phenotype. Nevertheless, exposure of the worms to microgravity lead to higher expression of non-coding RNA genes, which may play an epigenetic role in the worms during longer terms of microgravity exposure.

Depolarization Alters Phenotype, Maintains Plasticity of Predifferentiated Mesenchymal Stem Cells

PubMed Central

Sundelacruz, Sarah; Levin, Michael

2013-01-01

Although adult stem cell transplantation has been implemented as a therapy for tissue repair, it is limited by the availability of functional adult stem cells. A potential approach to generate stem and progenitor cells may be to modulate the differentiated status of somatic cells. Therefore, there is a need for a better understanding of how the differentiated phenotype of mature cells is regulated. We hypothesize that bioelectric signaling plays an important role in the maintenance of the differentiated state, as it is a functional regulator of the differentiation process in various cells and tissues. In this study, we asked whether the mature phenotype of osteoblasts and adipocytes derived from human mesenchymal stem cells (hMSCs) could be altered by modulation of their membrane potential. hMSC-derived osteoblasts and adipocytes were depolarized by treatment with ouabain, a Na+/K+ ATPase inhibitor, or by treatment with high concentrations of extracellular K+. To characterize the effect of voltage modulation on the differentiated state, the depolarized cells were evaluated for (1) the loss of differentiation markers; (2) the up-regulation of stemness markers and stem properties; and (3) differences in gene expression profiles in response to voltage modulation. hMSC-derived osteoblasts and adipocytes exhibited significant down-regulation of bone and fat tissue markers in response to depolarization, despite the presence of differentiation-inducing soluble factors, suggesting that bioelectric signaling overrides biochemical signaling in the maintenance of cell state. Suppression of the osteoblast or adipocyte phenotype was not accompanied by up-regulation of genes associated with the stem state. Thus, depolarization does not activate the stem cell genetic signature and, therefore, does not induce a full reprogramming event. However, after transdifferentiating the depolarized cells to evaluate for multi-lineage potential, depolarized osteoblasts demonstrated improved ability to achieve correct adipocyte morphology compared with nondepolarized osteoblasts. The present study thus demonstrates that depolarization reduces the differentiated phenotype of hMSC-derived cells and improves their transdifferentiation capacity, but does not restore a stem-like genetic profile. Through global transcript profiling of depolarized osteoblasts, we identified pathways that may mediate the effects of voltage signaling on cell state, which will require a detailed mechanistic inquiry in future studies. PMID:23738690

Envirotyping for deciphering environmental impacts on crop plants.

PubMed

Xu, Yunbi

2016-04-01

Global climate change imposes increasing impacts on our environments and crop production. To decipher environmental impacts on crop plants, the concept "envirotyping" is proposed, as a third "typing" technology, complementing with genotyping and phenotyping. Environmental factors can be collected through multiple environmental trials, geographic and soil information systems, measurement of soil and canopy properties, and evaluation of companion organisms. Envirotyping contributes to crop modeling and phenotype prediction through its functional components, including genotype-by-environment interaction (GEI), genes responsive to environmental signals, biotic and abiotic stresses, and integrative phenotyping. Envirotyping, driven by information and support systems, has a wide range of applications, including environmental characterization, GEI analysis, phenotype prediction, near-iso-environment construction, agronomic genomics, precision agriculture and breeding, and development of a four-dimensional profile of crop science involving genotype (G), phenotype (P), envirotype (E) and time (T) (developmental stage). In the future, envirotyping needs to zoom into specific experimental plots and individual plants, along with the development of high-throughput and precision envirotyping platforms, to integrate genotypic, phenotypic and envirotypic information for establishing a high-efficient precision breeding and sustainable crop production system based on deciphered environmental impacts.

Circadian Phenotype Composition is a Major Predictor of Diurnal Physical Performance in Teams.

PubMed

Facer-Childs, Elise; Brandstaetter, Roland

2015-01-01

Team performance is a complex phenomenon involving numerous influencing factors including physiology, psychology, and management. Biological rhythms and the impact of circadian phenotype have not been studied for their contribution to this array of factors so far despite our knowledge of the circadian regulation of key physiological processes involved in physical and mental performance. This study involved 216 individuals from 12 different teams who were categorized into circadian phenotypes using the novel RBUB chronometric test. The composition of circadian phenotypes within each team was used to model predicted daily team performance profiles based on physical performance tests. Our results show that the composition of circadian phenotypes within teams is variable and unpredictable. Predicted physical peak performance ranged from 1:52 to 8:59 p.m. with performance levels fluctuating by up to 14.88% over the course of the day. The major predictor for peak performance time in the course of a day in a team is the occurrence of late circadian phenotypes. We conclude that circadian phenotype is a performance indicator in teams that allows new insight and a better understanding of team performance variation in the course of a day as often observed in different groupings of individuals.

Circadian Phenotype Composition is a Major Predictor of Diurnal Physical Performance in Teams

PubMed Central

Facer-Childs, Elise; Brandstaetter, Roland

2015-01-01

Team performance is a complex phenomenon involving numerous influencing factors including physiology, psychology, and management. Biological rhythms and the impact of circadian phenotype have not been studied for their contribution to this array of factors so far despite our knowledge of the circadian regulation of key physiological processes involved in physical and mental performance. This study involved 216 individuals from 12 different teams who were categorized into circadian phenotypes using the novel RBUB chronometric test. The composition of circadian phenotypes within each team was used to model predicted daily team performance profiles based on physical performance tests. Our results show that the composition of circadian phenotypes within teams is variable and unpredictable. Predicted physical peak performance ranged from 1:52 to 8:59 p.m. with performance levels fluctuating by up to 14.88% over the course of the day. The major predictor for peak performance time in the course of a day in a team is the occurrence of late circadian phenotypes. We conclude that circadian phenotype is a performance indicator in teams that allows new insight and a better understanding of team performance variation in the course of a day as often observed in different groupings of individuals. PMID:26483754

Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

PubMed Central

Iriki, Atsushi; Isoda, Masaki

2015-01-01

Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

A Multidimensional Approach to Characterizing Psychosocial Health During Pregnancy.

PubMed

Maxson, Pamela J; Edwards, Sharon E; Valentiner, Ellis M; Miranda, Marie Lynn

2016-06-01

Objectives Domains of psychosocial health have been separately connected to pregnancy outcomes. This study explores the relationship between five domains of psychosocial health and their joint association with prenatal health and pregnancy outcomes. Methods Women from a prospective cohort study in Durham, North Carolina were clustered based on measures of paternal support, perceived stress, social support, depression, and self-efficacy. Clusters were constructed using the K-means algorithm. We examined associations between psychosocial health and maternal health correlates, pregnancy intention, and pregnancy outcomes using Chi square tests and multivariable models. Results Three psychosocial health profiles were identified, with the first (Resilient; n = 509) characterized by low depression and perceived stress and high interpersonal support, paternal support, and self-efficacy. The second profile (Vulnerable; n = 278) was marked by high depression and perceived stress, and low interpersonal support, paternal support, and self-efficacy. The third profile (Moderate, n = 526) fell between the other profiles on all domains. Health correlates, pregnancy intention, and pregnancy outcomes varied significantly across profiles. Women with the vulnerable profile were more likely to have risky health correlates, have an unintended pregnancy, and deliver preterm. Women with the resilient profile had better birth outcomes and fewer deleterious health correlates, preconception and prenatally. Conclusions We posit that vulnerable psychosocial health, deleterious health correlates, and the stress which often accompanies pregnancy may interact to magnify risk during pregnancy. Identifying and intervening with women experiencing vulnerable psychosocial health may improve outcomes for women and their children.

Multidimensional spectrometer

DOEpatents

Zanni, Martin Thomas; Damrauer, Niels H.

2010-07-20

A multidimensional spectrometer for the infrared, visible, and ultraviolet regions of the electromagnetic spectrum, and a method for making multidimensional spectroscopic measurements in the infrared, visible, and ultraviolet regions of the electromagnetic spectrum. The multidimensional spectrometer facilitates measurements of inter- and intra-molecular interactions.

Mouse Models as Predictors of Human Responses: Evolutionary Medicine.

PubMed

Uhl, Elizabeth W; Warner, Natalie J

Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into mouse models allow for unique opportunities to characterize the effects of diet, different gene expression profiles, and microbiomics underlying human drug responses and disease phenotypes.

Proanthocyanidin profile of cowpea (Vigna unguiculata) reveals catechin-O-glucoside as the dominant compound.

PubMed

Ojwang, Leonnard O; Yang, Liyi; Dykes, Linda; Awika, Joseph

2013-08-15

Proanthocyanidin (PA) profile and content can have important nutritional and health implications on plant foods. Six diverse cowpea phenotypes (black, red, green, white, light-brown and golden-brown) were investigated for PA composition using normal-phase HPLC and reversed-phase UPLC-TQD-MS. Catechin and (epi)afzelechin were the major flavan-3-ol units. Unusual composition was observed in all cowpea phenotypes with significant degrees of glycosylation in the monomers and dimers. The PA content of cowpea (dry basis) ranged between 2.2 and 6.3 mg/g. Monomeric flavan-3-ols were the largest group of PA (36-69%) in cowpea, with catechin-7-O-glucoside accounting for most (about 88%) of the monomers. The oligomers with degree of polymerization (DP) 2-4 ranged from 0.41 to 1.3 mg/g (15-20%), whereas DP>10 polymers accounted for only 13.5% of PA. Future studies that highlight the impact of the unusual cowpea PA profile on nutritional and bioactive properties of this important legume are warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.

High Mobility Group N Proteins Modulate the Fidelity of the Cellular Transcriptional Profile in a Tissue- and Variant-specific Manner*

PubMed Central

Kugler, Jamie E.; Horsch, Marion; Huang, Di; Furusawa, Takashi; Rochman, Mark; Garrett, Lillian; Becker, Lore; Bohla, Alexander; Hölter, Sabine M.; Prehn, Cornelia; Rathkolb, Birgit; Racz, Ildikó; Aguilar-Pimentel, Juan Antonio; Adler, Thure; Adamski, Jerzy; Beckers, Johannes; Busch, Dirk H.; Eickelberg, Oliver; Klopstock, Thomas; Ollert, Markus; Stöger, Tobias; Wolf, Eckhard; Wurst, Wolfgang; Yildirim, Ali Önder; Zimmer, Andreas; Gailus-Durner, Valérie; Fuchs, Helmut; Hrabě de Angelis, Martin; Garfinkel, Benny; Orly, Joseph; Ovcharenko, Ivan; Bustin, Michael

2013-01-01

The nuclei of most vertebrate cells contain members of the high mobility group N (HMGN) protein family, which bind specifically to nucleosome core particles and affect chromatin structure and function, including transcription. Here, we study the biological role of this protein family by systematic analysis of phenotypes and tissue transcription profiles in mice lacking functional HMGN variants. Phenotypic analysis of Hmgn1tm1/tm1, Hmgn3tm1/tm1, and Hmgn5tm1/tm1 mice and their wild type littermates with a battery of standardized tests uncovered variant-specific abnormalities. Gene expression analysis of four different tissues in each of the Hmgntm1/tm1 lines reveals very little overlap between genes affected by specific variants in different tissues. Pathway analysis reveals that loss of an HMGN variant subtly affects expression of numerous genes in specific biological processes. We conclude that within the biological framework of an entire organism, HMGNs modulate the fidelity of the cellular transcriptional profile in a tissue- and HMGN variant-specific manner. PMID:23620591

Detection of Rare Antimicrobial Resistance Profiles by Active and Passive Surveillance Approaches

PubMed Central

Mather, Alison E.; Reeve, Richard; Mellor, Dominic J.; Matthews, Louise; Reid-Smith, Richard J.; Haydon, Daniel T.; Reid, Stuart W. J.

2016-01-01

Antimicrobial resistance (AMR) surveillance systems are generally not specifically designed to detect emerging resistances and usually focus primarily on resistance to individual drugs. Evaluating the diversity of resistance, using ecological metrics, allows the assessment of sampling protocols with regard to the detection of rare phenotypes, comprising combinations of resistances. Surveillance data of phenotypic AMR of Canadian poultry Salmonella Heidelberg and swine Salmonella Typhimurium var. 5- were used to contrast active (representative isolates derived from healthy animals) and passive (diagnostic isolates) surveillance and assess their suitability for detecting emerging resistance patterns. Although in both datasets the prevalences of resistance to individual antimicrobials were not significantly different between the two surveillance systems, analysis of the diversity of entire resistance phenotypes demonstrated that passive surveillance of diagnostic isolates detected more unique phenotypes. Whilst the most appropriate surveillance method will depend on the relevant objectives, under the conditions of this study, passive surveillance of diagnostic isolates was more effective for the detection of rare and therefore potentially emerging resistance phenotypes. PMID:27391966

Common genetic variation drives molecular heterogeneity in human iPSCs.

PubMed

Kilpinen, Helena; Goncalves, Angela; Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard; Stegle, Oliver; Gaffney, Daniel J

2017-06-15

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

Food allergy phenotypes: The key to personalized therapy.

PubMed

Deschildre, A; Lejeune, S; Cap, M; Flammarion, S; Jouannic, L; Amat, F; Just, J

2017-09-01

Food allergies (FAs) are of increasing public health concern and are characterized by a large spectrum of diseases. Their diversity is well known for immunologic pathways (IgE, non-IgE-mediated FAs) and natural history. Many other factors and patient characteristics are involved including type of food, exposure route, allergic comorbidities, gender, racial and ethnic backgrounds, cofactors and health conditions. Food allergen components and sensitization profiles are also involved in FA phenotypes. A new approach to chronic disorders based on the identification of phenotypes through extensive knowledge of all the complex components is also applicable to FAs and could lead towards integrative care management. Diagnostic biomarkers for FAs are emerging which also contribute to better care modalities. The aim of this article was to highlight current knowledge regarding the phenotypic diversity of FA. This review will focus on IgE-mediated FAs and how identifying phenotypes may help to better understand the pathophysiological complexity, improve diagnosis and lead to personalized treatment strategies. © 2017 John Wiley & Sons Ltd.

Common genetic variation drives molecular heterogeneity in human iPSCs

PubMed Central

Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard

2017-01-01

Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study outlines the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells. PMID:28489815

A specific pathway can be identified between genetic characteristics and behaviour profiles in Prader-Willi syndrome via cognitive, environmental and physiological mechanisms.

PubMed

Woodcock, K A; Oliver, C; Humphreys, G W

2009-06-01

Behavioural phenotypes associated with genetic syndromes have been extensively investigated in order to generate rich descriptions of phenomenology, determine the degree of specificity of behaviours for a particular syndrome, and examine potential interactions between genetic predispositions for behaviour and environmental influences. However, relationships between different aspects of behavioural phenotypes have been less frequently researched and although recent interest in potential cognitive phenotypes or endophenotypes has increased, these are frequently studied independently of the behavioural phenotypes. Taking Prader-Willi syndrome (PWS) as an example, we discuss evidence suggesting specific relationships between apparently distinct aspects of the PWS behavioural phenotype and relate these to specific endophenotypic characteristics. The framework we describe progresses through biological, cognitive, physiological and behavioural levels to develop a pathway from genetic characteristics to behaviour with scope for interaction with the environment at any stage. We propose this multilevel approach as useful in setting out hypotheses in order to structure research that can more rapidly advance theory.

In situ calibration of the foil detector for an infrared imaging video bolometer using a carbon evaporation technique

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

Mukai, K., E-mail: mukai.kiyofumi@LHD.nifs.ac.jp; Peterson, B. J.; SOKENDAI

The InfraRed imaging Video Bolometer (IRVB) is a useful diagnostic for the multi-dimensional measurement of plasma radiation profiles. For the application of IRVB measurement to the neutron environment in fusion plasma devices such as the Large Helical Device (LHD), in situ calibration of the thermal characteristics of the foil detector is required. Laser irradiation tests of sample foils show that the reproducibility and uniformity of the carbon coating for the foil were improved using a vacuum evaporation method. Also, the principle of the in situ calibration system was justified.

Is the Good-Imitator-Poor-Talker Profile Syndrome-Specific in Down Syndrome?: Evidence from Standardised Imitation and Language Measures

ERIC Educational Resources Information Center

Vanvuchelen, M.; Feys, H.; De Weerdt, W.

2011-01-01

The emergence of the Down syndrome (DS) behavioural phenotype during early development may be of great importance for early intervention. The main goal of this study was to investigate the good-imitator-poor-talker developmental profile in DS at preschool age. Twenty children with Down syndrome (DS; mean nonverbal mental age NMA 1 y10 m) and 15…

A multivariate twin study of the DSM-IV criteria for antisocial personality disorder.

PubMed

Kendler, Kenneth S; Aggen, Steven H; Patrick, Christopher J

2012-02-01

Many assessment instruments for psychopathy are multidimensional, suggesting that distinguishable factors are needed to effectively capture variation in this personality domain. However, no prior study has examined the factor structure of the DSM-IV criteria for antisocial personality disorder (ASPD). Self-report questionnaire items reflecting all A criteria for DSM-IV ASPD were available from 4291 twins (including both members of 1647 pairs) from the Virginia Adult Study of Psychiatric and Substance Use Disorders. Exploratory factor analysis and twin model fitting were performed using, respectively, Mplus and Mx. Phenotypic factor analysis produced evidence for two correlated factors: aggressive-disregard and disinhibition. The best-fitting multivariate twin model included two genetic and one unique environmental common factor, along with criteria-specific genetic and environmental effects. The two genetic factors closely resembled the phenotypic factors and varied in their prediction of a range of relevant criterion variables. Scores on the genetic aggressive-disregard factor score were more strongly associated with risk for conduct disorder, early and heavy alcohol use, and low educational status, whereas scores on the genetic disinhibition factor score were more strongly associated with younger age, novelty seeking, and major depression. From a genetic perspective, the DSM-IV criteria for ASPD do not reflect a single dimension of liability but rather are influenced by two dimensions of genetic risk reflecting aggressive-disregard and disinhibition. The phenotypic structure of the ASPD criteria results largely from genetic and not from environmental influences. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

OBSERVATIONAL SIGNATURES OF CONVECTIVELY DRIVEN WAVES IN MASSIVE STARS

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

Aerts, C.; Rogers, T. M.

We demonstrate observational evidence for the occurrence of convectively driven internal gravity waves (IGWs) in young massive O-type stars observed with high-precision CoRoT space photometry. This evidence results from a comparison between velocity spectra based on two-dimensional hydrodynamical simulations of IGWs in a differentially rotating massive star and the observed spectra. We also show that the velocity spectra caused by IGWs may lead to detectable line-profile variability and explain the occurrence of macroturbulence in the observed line profiles of OB stars. Our findings provide predictions that can readily be tested by including a sample of bright, slowly and rapidly rotatingmore » OB-type stars in the scientific program of the K2 mission accompanied by high-precision spectroscopy and their confrontation with multi-dimensional hydrodynamic simulations of IGWs for various masses and ages.« less

Systems genetics: a paradigm to improve discovery of candidate genes and mechanisms underlying complex traits.

PubMed

Feltus, F Alex

2014-06-01

Understanding the control of any trait optimally requires the detection of causal genes, gene interaction, and mechanism of action to discover and model the biochemical pathways underlying the expressed phenotype. Functional genomics techniques, including RNA expression profiling via microarray and high-throughput DNA sequencing, allow for the precise genome localization of biological information. Powerful genetic approaches, including quantitative trait locus (QTL) and genome-wide association study mapping, link phenotype with genome positions, yet genetics is less precise in localizing the relevant mechanistic information encoded in DNA. The coupling of salient functional genomic signals with genetically mapped positions is an appealing approach to discover meaningful gene-phenotype relationships. Techniques used to define this genetic-genomic convergence comprise the field of systems genetics. This short review will address an application of systems genetics where RNA profiles are associated with genetically mapped genome positions of individual genes (eQTL mapping) or as gene sets (co-expression network modules). Both approaches can be applied for knowledge independent selection of candidate genes (and possible control mechanisms) underlying complex traits where multiple, likely unlinked, genomic regions might control specific complex traits. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Time series modeling of live-cell shape dynamics for image-based phenotypic profiling.

PubMed

Gordonov, Simon; Hwang, Mun Kyung; Wells, Alan; Gertler, Frank B; Lauffenburger, Douglas A; Bathe, Mark

2016-01-01

Live-cell imaging can be used to capture spatio-temporal aspects of cellular responses that are not accessible to fixed-cell imaging. As the use of live-cell imaging continues to increase, new computational procedures are needed to characterize and classify the temporal dynamics of individual cells. For this purpose, here we present the general experimental-computational framework SAPHIRE (Stochastic Annotation of Phenotypic Individual-cell Responses) to characterize phenotypic cellular responses from time series imaging datasets. Hidden Markov modeling is used to infer and annotate morphological state and state-switching properties from image-derived cell shape measurements. Time series modeling is performed on each cell individually, making the approach broadly useful for analyzing asynchronous cell populations. Two-color fluorescent cells simultaneously expressing actin and nuclear reporters enabled us to profile temporal changes in cell shape following pharmacological inhibition of cytoskeleton-regulatory signaling pathways. Results are compared with existing approaches conventionally applied to fixed-cell imaging datasets, and indicate that time series modeling captures heterogeneous dynamic cellular responses that can improve drug classification and offer additional important insight into mechanisms of drug action. The software is available at http://saphire-hcs.org.

Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis.

PubMed

Araújo, Márcio Sobreira Silva; de Andrade, Renata Aline; Sathler-Avelar, Renato; Magalhães, Camila Paula; Carvalho, Andréa Teixeira; Andrade, Mariléia Chaves; Campolina, Sabrina Sidney; Mello, Maria Norma; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Rocha, Luciana Morais; Martins-Filho, Olindo Assis

2011-05-15

In this study, we summarized the major phenotypic/functional aspects of circulating leukocytes following canine immunization with Leishvaccine and Leishmune®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune(®) induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4+ and CD8+ and B-lymphocytes, whereas Leishmune(®) promoted a selective response, mainly associated with CD8+ T-cell activation. Mixed cytokine profile (IFN-γ/IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN-γ/NO) was induced by Leishmune® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmania antigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL). Copyright © 2011 Elsevier B.V. All rights reserved.

Moraxella lincolnii sp. nov., isolated from the human respiratory tract, and reevaluation of the taxonomic position of Moraxella osloensis.

PubMed

Vandamme, P; Gillis, M; Vancanneyt, M; Hoste, B; Kersters, K; Falsen, E

1993-07-01

A polyphasic taxonomic study was performed to determine the relationships of 10 Moraxella-like strains isolated mainly from the human respiratory tract in Sweden. Two of the strains formed a separate subgroup on the basis of both their protein contents and their fatty acid contents. However, the overall protein and fatty acid profiles revealed that all 10 strains were highly related. Representative strains of the two subgroups exhibited high DNA binding values (98%) with each other and had an identical DNA base ratio (44 mol% G+C). DNA-rRNA hybridizations revealed that this taxon can be included in the genus Moraxella, which is only distantly related to phenotypically similar genera, such as the genera Neisseria and Kingella. The results of an extensive phenotypic analysis indicated that the general biochemical profile of the 10 strains conforms with the description of the genus Moraxella given in Bergey's Manual of Systematic Bacteriology. We therefore consider these organisms members of a new Moraxella species, for which the name Moraxella lincolnii is proposed. Furthermore, we also conclude that Moraxella osloensis belongs, genotypically as well as phenotypically, to the genus Moraxella.

The culturable soil antibiotic resistome: a community of multi-drug resistant bacteria.

PubMed

Walsh, Fiona; Duffy, Brion

2013-01-01

Understanding the soil bacterial resistome is essential to understanding the evolution and development of antibiotic resistance, and its spread between species and biomes. We have identified and characterized multi-drug resistance (MDR) mechanisms in the culturable soil antibiotic resistome and linked the resistance profiles to bacterial species. We isolated 412 antibiotic resistant bacteria from agricultural, urban and pristine soils. All isolates were multi-drug resistant, of which greater than 80% were resistant to 16-23 antibiotics, comprising almost all classes of antibiotic. The mobile resistance genes investigated, (ESBL, bla NDM-1, and plasmid mediated quinolone resistance (PMQR) resistance genes) were not responsible for the respective resistance phenotypes nor were they present in the extracted soil DNA. Efflux was demonstrated to play an important role in MDR and many resistance phenotypes. Clinically relevant Burkholderia species are intrinsically resistant to ciprofloxacin but the soil Burkholderia species were not intrinsically resistant to ciprofloxacin. Using a phenotypic enzyme assay we identified the antibiotic specific inactivation of trimethoprim in 21 bacteria from different soils. The results of this study identified the importance of the efflux mechanism in the soil resistome and variations between the intrinsic resistance profiles of clinical and soil bacteria of the same family.

Influence of in vivo growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions

PubMed Central

Camphausen, Kevin; Purow, Benjamin; Sproull, Mary; Scott, Tamalee; Ozawa, Tomoko; Deen, Dennis F.; Tofilon, Philip J.

2005-01-01

Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the in situ tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown in vitro and in vivo as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the gene expression profile generated from tissue culture was significantly different from that generated from the s.c. tumor, which was significantly different from those grown i.c. The disparity between the i.c gene expression profiles and those generated from s.c. xenografts suggests that whereas an in vivo growth environment modulates gene expression, orthotopic growth conditions induce a different set of modifications. In this study the U251 and U87 gene expression profiles generated under the three growth conditions were also compared. As expected, the profiles of the two glioma cell lines were significantly different when grown as monolayer cultures. However, the glioma cell lines had similar gene expression profiles when grown i.c. These results suggest that tumor cell gene expression, and thus phenotype, as defined in vitro is affected not only by in vivo growth but also by orthotopic growth, which may have implications regarding the identification of relevant targets for cancer therapy. PMID:15928080

Estimating Between-Person and Within-Person Subscore Reliability with Profile Analysis.

PubMed

Bulut, Okan; Davison, Mark L; Rodriguez, Michael C

2017-01-01

Subscores are of increasing interest in educational and psychological testing due to their diagnostic function for evaluating examinees' strengths and weaknesses within particular domains of knowledge. Previous studies about the utility of subscores have mostly focused on the overall reliability of individual subscores and ignored the fact that subscores should be distinct and have added value over the total score. This study introduces a profile reliability approach that partitions the overall subscore reliability into within-person and between-person subscore reliability. The estimation of between-person reliability and within-person reliability coefficients is demonstrated using subscores from number-correct scoring, unidimensional and multidimensional item response theory scoring, and augmented scoring approaches via a simulation study and a real data study. The effects of various testing conditions, such as subtest length, correlations among subscores, and the number of subtests, are examined. Results indicate that there is a substantial trade-off between within-person and between-person reliability of subscores. Profile reliability coefficients can be useful in determining the extent to which subscores provide distinct and reliable information under various testing conditions.

Comparing internal migration across the countries of Latin America: A multidimensional approach

PubMed Central

Bernard, Aude; Rowe, Francisco; Bell, Martin; Ueffing, Philipp; Charles-Edwards, Elin

2017-01-01

While considerable progress has been made in understanding the way particular aspects of internal migration, such as its intensity, age profile and spatial impact, vary between countries around the world, little attention to date has been given to establishing how these dimensions of migration interact in different national settings. We use recently developed measures of internal migration that are scale-independent to compare the overall intensity, age composition, spatial impact, and distance profile of internal migration in 19 Latin American countries. Comparisons reveal substantial cross-national variation but cluster analysis suggests the different dimensions of migration evolve systematically to form a broad sequence characterised by low intensities, young ages at migration, unbalanced flows and high friction of distance at lower levels of development, trending to high intensities, an older age profile of migration, more closely balanced flows and lower friction of distance at later stages of development. However, the transition is not linear and local contingencies, such as international migration and political control, often distort the migration-development nexus, leading to unique migration patterns in individual national contexts. PMID:28328932

On the Analytical Superiority of 1D NMR for Fingerprinting the Higher Order Structure of Protein Therapeutics Compared to Multidimensional NMR Methods.

PubMed

Poppe, Leszek; Jordan, John B; Rogers, Gary; Schnier, Paul D

2015-06-02

An important aspect in the analytical characterization of protein therapeutics is the comprehensive characterization of higher order structure (HOS). Nuclear magnetic resonance (NMR) is arguably the most sensitive method for fingerprinting HOS of a protein in solution. Traditionally, (1)H-(15)N or (1)H-(13)C correlation spectra are used as a "structural fingerprint" of HOS. Here, we demonstrate that protein fingerprint by line shape enhancement (PROFILE), a 1D (1)H NMR spectroscopy fingerprinting approach, is superior to traditional two-dimensional methods using monoclonal antibody samples and a heavily glycosylated protein therapeutic (Epoetin Alfa). PROFILE generates a high resolution structural fingerprint of a therapeutic protein in a fraction of the time required for a 2D NMR experiment. The cross-correlation analysis of PROFILE spectra allows one to distinguish contributions from HOS vs protein heterogeneity, which is difficult to accomplish by 2D NMR. We demonstrate that the major analytical limitation of two-dimensional methods is poor selectivity, which renders these approaches problematic for the purpose of fingerprinting large biological macromolecules.

A benchmark for evaluation of algorithms for identification of cellular correlates of clinical outcomes.

PubMed

Aghaeepour, Nima; Chattopadhyay, Pratip; Chikina, Maria; Dhaene, Tom; Van Gassen, Sofie; Kursa, Miron; Lambrecht, Bart N; Malek, Mehrnoush; McLachlan, G J; Qian, Yu; Qiu, Peng; Saeys, Yvan; Stanton, Rick; Tong, Dong; Vens, Celine; Walkowiak, Sławomir; Wang, Kui; Finak, Greg; Gottardo, Raphael; Mosmann, Tim; Nolan, Garry P; Scheuermann, Richard H; Brinkman, Ryan R

2016-01-01

The Flow Cytometry: Critical Assessment of Population Identification Methods (FlowCAP) challenges were established to compare the performance of computational methods for identifying cell populations in multidimensional flow cytometry data. Here we report the results of FlowCAP-IV where algorithms from seven different research groups predicted the time to progression to AIDS among a cohort of 384 HIV+ subjects, using antigen-stimulated peripheral blood mononuclear cell (PBMC) samples analyzed with a 14-color staining panel. Two approaches (FlowReMi.1 and flowDensity-flowType-RchyOptimyx) provided statistically significant predictive value in the blinded test set. Manual validation of submitted results indicated that unbiased analysis of single cell phenotypes could reveal unexpected cell types that correlated with outcomes of interest in high dimensional flow cytometry datasets. © 2015 International Society for Advancement of Cytometry.

Brain shape convergence in the adaptive radiation of New World monkeys

PubMed Central

Aristide, Leandro; dos Reis, Sergio Furtado; Machado, Alessandra C.; Lima, Inaya; Lopes, Ricardo T.; Perez, S. Ivan

2016-01-01

Primates constitute one of the most diverse mammalian clades, and a notable feature of their diversification is the evolution of brain morphology. However, the evolutionary processes and ecological factors behind these changes are largely unknown. In this work, we investigate brain shape diversification of New World monkeys during their adaptive radiation in relation to different ecological dimensions. Our results reveal that brain diversification in this clade can be explained by invoking a model of adaptive peak shifts to unique and shared optima, defined by a multidimensional ecological niche hypothesis. Particularly, we show that the evolution of convergent brain phenotypes may be related to ecological factors associated with group size (e.g., social complexity). Together, our results highlight the complexity of brain evolution and the ecological significance of brain shape changes during the evolutionary diversification of a primate clade. PMID:26858427

Abundance and characteristics of the recreational water quality indicator bacteria Escherichia coli and enterococci in gull faeces

USGS Publications Warehouse

Fogarty, L.R.; Haack, S.K.; Wolcott, M.J.; Whitman, R.L.

2003-01-01

Aims: To evaluate the numbers and selected phenotypic and genotypic characteristics of the faecal indicator bacteria Escherichia coli and enterococci in gull faeces at representative Great Lakes swimming beaches in the United States. Methods and Results: E. coli and enterococci were enumerated in gull faeces by membrane filtration. E. coli genotypes (rep-PCR genomic profiles) and E. coli (Vitek?? GNI+) and enterococci (API?? rapid ID 32 Strep and resistance to streptomycin, gentamicin, vancomycin, tetracycline and ampicillin) phenotypes were determined for isolates obtained from gull faeces both early and late in the swimming season. Identical E. coli genotypes were obtained only from single gull faecal samples but most faecal samples yielded more than one genotype (median of eight genotypes for samples with 10 isolates). E. coli isolates from the same site that clustered at ???85% similarity were from the same sampling date and shared phenotypic characteristics, and at this similarity level there was population overlap between the two geographically isolated beach sites. Enterococcus API?? profiles varied with sampling date. Gull enterococci displayed wide variation in antibiotic resistance patterns, and high-level resistance to some antibiotics. Conclusions: Gull faeces could be a major contributor of E. coli (105-109 CFU g-1) and enterococci (104-108 CFU g-1) to Great Lakes recreational waters. E. coli and enterococci in gull faeces are highly variable with respect to their genotypic and phenotypic characteristics and may exhibit temporal or geographic trends in these features. Significance and Impact of the Study: The high degree of variation in genotypic or phenotypic characteristics of E. coli or enterococci populations within gull hosts will require extensive sampling for adequate characterization, and will influence methods that use these characteristics to determine faecal contamination sources for recreational waters.

Immune response phenotype of allergic versus clinically tolerant pigs in a neonatal swine model of allergy.

PubMed

Schmied, Julie; Rupa, Prithy; Garvie, Sarah; Wilkie, Bruce

2013-07-15

The prevalence of childhood food allergy and the duration of these allergies, particularly those considered to be transient, like egg and milk allergy, are increasing. The identification of allergic individuals using minimally invasive, non-anaphylaxis-threatening methods is therefore of increasing importance. In this experiment, correlates were sought of an allergic immune response (IR) phenotype in pigs. Using pigs pre-treated with heat-killed bacteria or bacterial components before allergic sensitization with the egg white protein ovomucoid (Ovm), differences were determined in IR phenotype of pigs in the categories treated-allergic, treated-tolerant, control-allergic (CA) and control-tolerant. Phenotype was established by measuring immunoglobulin (Ig)-associated antibody activity (AbA), cytokine profiles and the proportion of blood T-regulatory cells (T-regs) and observing late-phase allergen-specific skin tests (ST). Although 100% of pigs became sensitized to Ovm, only 33% of pigs had clinical signs of allergy after oral challenge with egg white. Pigs without clinical signs were classified as clinically tolerant. Sixty-seven percent of allergic pigs had a positive, late-phase ST classified as very strong or strong, while 84% of clinically tolerant pigs did not have late-phase ST. Treated-allergic pigs and CA pigs had greater total antibody IgG (H+L), IgE and IgG1 AbA than clinically tolerant pigs. Cytokine profiles of allergic pigs and the proportion of circulating T-regs, did not differ significantly between allergic and clinically tolerant pigs. Therefore, measurement of allergen-specific IgG, IgG1 and/or IgE activity and evaluation of late-phase ID ST may be useful in identifying allergic IR phenotypes in swine models of food allergy, which may be extended toward human use. Copyright © 2013 Elsevier B.V. All rights reserved.

Association of height and pubertal timing with lipoprotein subclass profile: exploring the role of genetic and environmental effects.

PubMed

Jelenkovic, Aline; Bogl, Leonie H; Rose, Richard J; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Kaprio, Jaakko; Silventoinen, Karri

2013-01-01

Little is known about the relationship between growth and lipoprotein profile. We aimed to analyze common genetic and environmental factors in the association of height from late childhood to adulthood and pubertal timing with serum lipid and lipoprotein subclass profile. A longitudinal cohort of Finnish twin pairs (FinnTwin12) was analyzed using self-reported height at 11-12, 14, 17 years and measured stature at adult age (21-24 years). Data were available for 719 individual twins including 298 complete pairs. Serum lipids and lipoprotein subclasses were measured by proton nuclear magnetic resonance spectroscopy. Multivariate variance component models for twin data were fitted. Cholesky decomposition was used to partition the phenotypic covariation among traits into additive genetic and unique environmental correlations. In men, the strongest associations for both adult height and puberty were observed with total cholesterol, low-density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, and low-density lipoprotein particle subclasses (max. r = -0.19). In women, the magnitude of the correlations was weaker (max. r = -0.13). Few associations were detected between height during adolescence and adult lipid profile. Early onset of puberty was related to an adverse lipid profile, but delayed pubertal development in girls was associated with an unfavorable profile, as well. All associations were mediated mainly by additive genetic factors, but unique environmental effects cannot be disregarded. Early puberty and shorter adult height relate to higher concentrations of atherogenic lipids and lipoprotein particles in early adulthood. Common genetic effects behind these phenotypes substantially contribute to the observed associations. Copyright © 2013 Wiley Periodicals, Inc.

Effect of tibial bone resection on the development of fast- and slow-twitch skeletal muscles in foetal sheep.

PubMed

West, J M; Williams, N A; Luff, A R; Walker, D W

2000-04-01

To determine if longitudinal bone growth affects the differentiation of fast- and slow-twitch muscles, the tibial bone was sectioned at 90 days gestation in foetal sheep so that the lower leg was permanently without structural support. At 140 days (term is approximately 147 days) the contractile properties of whole muscles, activation profiles of single fibres and ultrastructure of fast- and slow-twitch muscles from the hindlimbs were studied. The contractile and activation profiles of the slow-twitch soleus muscles were significantly affected by tibial bone resection (TIBX). The soleus muscles from the TIBX hindlimbs showed: (1) a decrease in the time to peak of the twitch responses from 106.2 +/- 10.7 ms (control, n = 4) to 65.1 +/- 2.48 ms (TIBX, n = 5); (2) fatigue profiles more characteristic of those observed in the fast-twitch muscles: and (3) Ca2+ - and Sr2+ -activation profiles of skinned fibres similar to those from intact hindlimbs at earlier stages of gestation. In the FDL, TIBX did not significantly change whole muscle twitch contraction time, the fatigue profile or the Ca2+ - and Sr2+ -activation profiles of skinned fibres. Electron microscopy showed an increased deposition of glycogen in both soleus and FDL muscles. This study shows that the development of the slow-twitch phenotype is impeded in the absence of the physical support normally provided by the tibial bone. We suggest that longitudinal stretch is an important factor in allowing full expression of the slow-twitch phenotype.

Genetic profiling of two phenotypically distinct outbred rats derived from a colony of the Zucker fatty rats maintained at Tokyo Medical University

PubMed Central

Nakanishi, Satoshi; Kuramoto, Takashi; Kashiwazaki, Naomi; Yokoi, Norihide

2016-01-01

The Zucker fatty (ZF) rat is an outbred rat and a well-known model of obesity without diabetes, harboring a missense mutation (fatty, abbreviated as fa) in the leptin receptor gene (Lepr). Slc:Zucker (Slc:ZF) outbred rats exhibit obesity while Hos:ZFDM-Leprfa (Hos:ZFDM) outbred rats exhibit obesity and type 2 diabetes. Both outbred rats have been derived from an outbred ZF rat colony maintained at Tokyo Medical University. So far, genetic profiles of these outbred rats remain unknown. Here, we applied a simple genotyping method using Ampdirect reagents and FTA cards (Amp-FTA) in combination with simple sequence length polymorphisms (SSLP) markers to determine genetic profiles of Slc:ZF and Hos:ZFDM rats. Among 27 SSLP marker loci, 24 loci (89%) were fixed for specific allele at each locus in Slc:ZF rats and 26 loci (96%) were fixed in Hos:ZFDM rats, respectively. This indicates the low genetic heterogeneity in both colonies of outbred rats. Nine loci (33%) showed different alleles between the two outbred rats, suggesting considerably different genetic profiles between the two outbred rats in spite of the same origin. Additional analysis using 72 SSLP markers further supported these results and clarified the profiles in detail. This study revealed that genetic profiles of the Slc:ZF and Hos:ZFDM outbred rats are different for about 30% of the SSLP marker loci, which is the underlying basis for the phenotypic difference between the two outbred rats. PMID:27795491

Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles.

PubMed

Zoratti, Edward; Havstad, Suzanne; Wegienka, Ganesa; Nicholas, Charlotte; Bobbitt, Kevin R; Woodcroft, Kimberley J; Ownby, Dennis R; Johnson, Christine Cole

2014-07-01

Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population. To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults. Participants included 18- to 21-year-old members (n = 540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. Phorbol myristate acetate-stimulated whole blood interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, IL-17A, IL-17F, IL-22, and interferon-γ secretory responses were analyzed for associations comparing participants with allergic vs nonallergic asthma phenotypes with those without asthma. T-helper cell type (TH) 2-polarized responses, measured as higher mean IL-5 and IL-13 secretions and lower ratios of interferon-γ and IL-12 to 3 TH2 cytokines (IL-4, IL-5, or IL-13), were observed only in participants with allergic asthma. Nonallergic asthma was associated with TH1-polarized responses, including higher adjusted interferon-γ secretion compared with participants with allergic asthma and, surprisingly, those without asthma (odds ratio 2.5, confidence interval 1.2-5.1, P < .01). As expected, young adults with a history of an allergic asthma phenotype exhibited a TH2-polarized cytokine response after polyclonal stimulation. However, TH1 polarization was observed in patients with a history of nonallergic asthma. Allergic and nonallergic asthma are associated with etiologically distinct immune endotypes, underscoring the importance of discriminating these endotypes in research analyses and clinical management. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Numeric invariants from multidimensional persistence

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

Skryzalin, Jacek; Carlsson, Gunnar

2017-05-19

In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be usedmore » to study data.« less

Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium

PubMed Central

Begum, Jusnara; Lal, Neeraj; Zuo, Jianmin; Beggs, Andrew; Moss, Paul

2016-01-01

Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01–24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people. PMID:27606804

PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy

PubMed Central

Dai, Xudong; Souza, Angus T. De; Dai, Hongyue; Lewis, David L; Lee, Chang-kyu; Spencer, Andy G; Herweijer, Hans; Hagstrom, Jim E; Linsley, Peter S; Bassett, Douglas E; Ulrich, Roger G; He, Yudong D

2007-01-01

Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs) against the gene for peroxisome proliferator-activated receptor α (Ppara), our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARα-induced liver hypertrophy is supported by their ability to predict non-PPARα–induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005). Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced toxicity from siRNA-treated expression profiles. When combined with phenotypic evaluation, our approach should help to unleash the full potential of siRNAs in systematically unveiling the molecular mechanism of biological events. PMID:17335344

A short protocol using dexamethasone and monophosphoryl lipid A generates tolerogenic dendritic cells that display a potent migratory capacity to lymphoid chemokines

PubMed Central

2013-01-01

Background Generation of tolerogenic dendritic cells (TolDCs) for therapy is challenging due to its implications for the design of protocols suitable for clinical applications, which means not only using safe products, but also working at defining specific biomarkers for TolDCs identification, developing shorter DCs differentiation methods and obtaining TolDCs with a stable phenotype. We describe here, a short-term protocol for TolDCs generation, which are characterized in terms of phenotypic markers, cytokines secretion profile, CD4+ T cell-stimulatory ability and migratory capacity. Methods TolDCs from healthy donors were generated by modulation with dexamethasone plus monophosphoryl lipid A (MPLA-tDCs). We performed an analysis of MPLA-tDCs in terms of yield, viability, morphology, phenotypic markers, cytokines secretion profile, stability, allogeneic and antigen-specific CD4+ T-cell stimulatory ability and migration capacity. Results After a 5-day culture, MPLA-tDCs displayed reduced expression of costimulatory and maturation molecules together to an anti-inflammatory cytokines secretion profile, being able to maintain these tolerogenic features even after the engagement of CD40 by its cognate ligand. In addition, MPLA-tDCs exhibited reduced capabilities to stimulate allogeneic and antigen-specific CD4+ T cell proliferation, and induced an anti-inflammatory cytokine secretion pattern. Among potential tolerogenic markers studied, only TLR-2 was highly expressed in MPLA-tDCs when compared to mature and immature DCs. Remarkable, like mature DCs, MPLA-tDCs displayed a high CCR7 and CXCR4 expression, both chemokine receptors involved in migration to secondary lymphoid organs, and even more, in an in vitro assay they exhibited a high migration response towards CCL19 and CXCL12. Conclusion We describe a short-term protocol for TolDC generation, which confers them a stable phenotype and migratory capacity to lymphoid chemokines, essential features for TolDCs to be used as therapeutics for autoimmunity and prevention of graft rejection. PMID:23706017

Reprint of: The new approach to epilepsy classification: Cognition and behavior in adult epilepsy syndromes.

PubMed

Baxendale, Sallie; Thompson, Pamela

2016-11-01

The revised terminology and concepts for the organization of seizures and epilepsy proposed by the ILAE Commission on Classification and Terminology in 2010 allows for a number of new opportunities in the study of cognition and behavior in adults. This review examines the literature that has looked for behavioral and cognitive correlates of the newly recognized genetic epilepsies in adults. While some studies report clear cognitive phenotypes associated with specific genetic mutations in adults with epilepsy, others report remarkable clinical heterogeneity. In the second part of this review, we discuss some of the factors that may influence the findings in this literature. Cognitive function is the product of both genetic and environmental influences. Neuropsychological phenotypes under direct genetic influence may be wider and more subtle than specific deficits within discreet cognitive domains and may be reflected in broader, multidimensional measures of cognitive function than those tapped by scores on standardized tests of function. Future studies must be carefully designed to reflect these factors. It is also imperative that studies with negative findings are assigned as much value as those with positive results and published accordingly. This article is part of a Special Issue titled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Model-Based Phenotypic Signatures Governing the Dynamics of the Stem and Semi-differentiated Cell Populations in Dysplastic Colonic Crypts.

PubMed

Nikolov, Svetoslav; Santos, Guido; Wolkenhauer, Olaf; Vera, Julio

2018-02-01

Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression. The models suggest that stem cell and semi-differentiated cell population dynamics in colonic crypts can display chaotic behavior. In addition, we found that clinical profiling of colorectal cancer correlates with the in silico phenotypes proposed by the mathematical model. Further, potential therapeutic targets for chemotherapy resistant phenotypes are proposed, which in any case will require experimental validation.

Genomic Study of Cardiovascular Continuum Comorbidity.

PubMed

Makeeva, O A; Sleptsov, A A; Kulish, E V; Barbarash, O L; Mazur, A M; Prokhorchuk, E B; Chekanov, N N; Stepanov, V A; Puzyrev, V P

2015-01-01

Comorbidity or a combination of several diseases in the same individual is a common and widely investigated phenomenon. However, the genetic background for non-random disease combinations is not fully understood. Modern technologies and approaches to genomic data analysis enable the investigation of the genetic profile of patients burdened with several diseases (polypathia, disease conglomerates) and its comparison with the profiles of patients with single diseases. An association study featuring three groups of patients with various combinations of cardiovascular disorders and a control group of relatively healthy individuals was conducted. Patients were selected as follows: presence of only one disease, ischemic heart disease (IHD); a combination of two diseases, IHD and arterial hypertension (AH); and a combination of several diseases, including IHD, AH, type 2 diabetes mellitus (T2DM), and hypercholesterolemia (HC). Genotyping was performed using the "My Gene" genomic service (www.i-gene.ru). An analysis of 1,400 polymorphic genetic variants and their associations with the studied phenotypes are presented. A total of 14 polymorphic variants were associated with the phenotype "IHD only," including those in the APOB, CD226, NKX2-5, TLR2, DPP6, KLRB1, VDR, SCARB1, NEDD4L, and SREBF2 genes, and intragenic variants rs12487066, rs7807268, rs10896449, and rs944289. A total of 13 genetic markers were associated with the "IHD and AH" phenotype, including variants in the BTNL2, EGFR, CNTNAP2, SCARB1, and HNF1A genes, and intragenic polymorphisms rs801114, rs10499194, rs13207033, rs2398162, rs6501455, and rs1160312. A total of 14 genetic variants were associated with a combination of several diseases of cardiovascular continuum (CVC), including those in the TAS2R38, SEZ6L, APOA2, KLF7, CETP, ITGA4, RAD54B, LDLR, and MTAP genes, along with intragenic variants rs1333048, rs1333049, and rs6501455. One common genetic marker was identified for the "IHD only" and "IHD and AH" phenotypes: rs4765623 in the SCARB1 gene; two common genetic markers, rs663048 in SEZ6L and intragenic rs6501455, were identified for the "IHD and AH" phenotype and a combination of several diseases (syntropy); there were no common genetic markers for the "syntropy" and "IHD only" phenotypes. Classificatory analysis of the relationships between the associated genes and metabolic pathways revealed that lipid-metabolizing genes are involved in the development of all three CVC variants, whereas immunity-response genes are specific to the "IHD only" phenotype. The study demonstrated that comorbidity presents additional challenges in association studies of disease predisposition, since the genetic profile of combined forms of pathology can be markedly different from those for isolated "single" forms of a disease.

Study of cellular oncometabolism via multidimensional protein identification technology.

PubMed

Aukim-Hastie, Claire; Garbis, Spiros D

2014-01-01

Cellular proteomics is becoming a widespread clinical application, matching the definition of bench-to-bedside translation. Among various fields of investigation, this approach can be applied to the study of the metabolic alterations that accompany oncogenesis and tumor progression, which are globally referred to as oncometabolism. Here, we describe a multidimensional protein identification technology (MuDPIT)-based strategy that can be employed to study the cellular proteome of malignant cells and tissues. This method has previously been shown to be compatible with the reproducible, in-depth analysis of up to a thousand proteins in clinical samples. The possibility to employ this technique to study clinical specimens demonstrates its robustness. MuDPIT is advantageous as compared to other approaches because it is direct, highly sensitive, and reproducible, it provides high resolution with ultra-high mass accuracy, it allows for relative quantifications, and it is compatible with multiplexing (thus limiting costs).This method enables the direct assessment of the proteomic profile of neoplastic cells and tissues and could be employed in the near future as a high-throughput, rapid, quantitative, and cost-effective screening platform for clinical samples. © 2014 Elsevier Inc. All rights reserved.

Multidimensional profiling of plasma lipoproteins by size exclusion chromatography followed by reverse-phase protein arrays

PubMed Central

Dernick, Gregor; Obermüller, Stefan; Mangold, Cyrill; Magg, Christine; Matile, Hugues; Gutmann, Oliver; von der Mark, Elisabeth; Handschin, Corinne; Maugeais, Cyrille; Niesor, Eric J.

2011-01-01

The composition of lipoproteins and the association of proteins with various particles are of much interest in the context of cardiovascular disease. Here, we describe a technique for the multidimensional analysis of lipoproteins and their associated apolipoproteins. Plasma is separated by size exclusion chromatography (SEC), and fractions are analyzed by reverse-phase arrays. SEC fractions are spotted on nitrocellulose slides and incubated with different antibodies against individual apolipoproteins or antibodies against various apolipoproteins. In this way, tens of analytes can be measured simultaneously in 100 μl of plasma from a single SEC separation. This methodology is particularly suited to simultaneous analysis of multiple proteins that may change their distribution to lipoproteins or alter their conformation, depending on factors that influence circulating lipoprotein size or composition. We observed changes in the distribution of exchangeable apolipoproteins following addition of recombinant apolipoproteins or interaction with exogenous compounds. While the cholesteryl ester transfer protein (CETP)-dependent formation of pre-β-HDL was inhibited by the CETP inhibitors torcetrapib and anacetrapib, it was not reduced by the CETP modulator dalcetrapib. This finding was elucidated using this technique. PMID:21971713

A Comparative Study of Online Item Calibration Methods in Multidimensional Computerized Adaptive Testing

ERIC Educational Resources Information Center

Chen, Ping

2017-01-01

Calibration of new items online has been an important topic in item replenishment for multidimensional computerized adaptive testing (MCAT). Several online calibration methods have been proposed for MCAT, such as multidimensional "one expectation-maximization (EM) cycle" (M-OEM) and multidimensional "multiple EM cycles"…

Best Design for Multidimensional Computerized Adaptive Testing with the Bifactor Model

ERIC Educational Resources Information Center

Seo, Dong Gi; Weiss, David J.

2015-01-01

Most computerized adaptive tests (CATs) have been studied using the framework of unidimensional item response theory. However, many psychological variables are multidimensional and might benefit from using a multidimensional approach to CATs. This study investigated the accuracy, fidelity, and efficiency of a fully multidimensional CAT algorithm…

Multidimensional Measurement of Poverty among Women in Sub-Saharan Africa

ERIC Educational Resources Information Center

Batana, Yele Maweki

2013-01-01

Since the seminal work of Sen, poverty has been recognized as a multidimensional phenomenon. The recent availability of relevant databases renewed the interest in this approach. This paper estimates multidimensional poverty among women in fourteen Sub-Saharan African countries using the Alkire and Foster multidimensional poverty measures, whose…

The Efficacy of Multidimensional Constraint Keys in Database Query Performance

ERIC Educational Resources Information Center

Cardwell, Leslie K.

2012-01-01

This work is intended to introduce a database design method to resolve the two-dimensional complexities inherent in the relational data model and its resulting performance challenges through abstract multidimensional constructs. A multidimensional constraint is derived and utilized to implement an indexed Multidimensional Key (MK) to abstract a…

Microbiota-induced obesity requires farnesoid X receptor

PubMed Central

Parséus, Ava; Sommer, Nina; Sommer, Felix; Caesar, Robert; Molinaro, Antonio; Ståhlman, Marcus; Greiner, Thomas U; Perkins, Rosie; Bäckhed, Fredrik

2017-01-01

Objective The gut microbiota has been implicated as an environmental factor that modulates obesity, and recent evidence suggests that microbiota-mediated changes in bile acid profiles and signalling through the bile acid nuclear receptor farnesoid X receptor (FXR) contribute to impaired host metabolism. Here we investigated if the gut microbiota modulates obesity and associated phenotypes through FXR. Design We fed germ-free (GF) and conventionally raised (CONV-R) wild-type and Fxr−/− mice a high-fat diet (HFD) for 10 weeks. We monitored weight gain and glucose metabolism and analysed the gut microbiota and bile acid composition, beta-cell mass, accumulation of macrophages in adipose tissue, liver steatosis, and expression of target genes in adipose tissue and liver. We also transferred the microbiota of wild-type and Fxr-deficient mice to GF wild-type mice. Results The gut microbiota promoted weight gain and hepatic steatosis in an FXR-dependent manner, and the bile acid profiles and composition of faecal microbiota differed between Fxr−/− and wild-type mice. The obese phenotype in colonised wild-type mice was associated with increased beta-cell mass, increased adipose inflammation, increased steatosis and expression of genes involved in lipid uptake. By transferring the caecal microbiota from HFD-fed Fxr−/− and wild-type mice into GF mice, we showed that the obesity phenotype was transferable. Conclusions Our results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition. PMID:26740296

Integrating Milk Metabolite Profile Information for the Prediction of Traditional Milk Traits Based on SNP Information for Holstein Cows

PubMed Central

Melzer, Nina; Wittenburg, Dörte; Repsilber, Dirk

2013-01-01

In this study the benefit of metabolome level analysis for the prediction of genetic value of three traditional milk traits was investigated. Our proposed approach consists of three steps: First, milk metabolite profiles are used to predict three traditional milk traits of 1,305 Holstein cows. Two regression methods, both enabling variable selection, are applied to identify important milk metabolites in this step. Second, the prediction of these important milk metabolite from single nucleotide polymorphisms (SNPs) enables the detection of SNPs with significant genetic effects. Finally, these SNPs are used to predict milk traits. The observed precision of predicted genetic values was compared to the results observed for the classical genotype-phenotype prediction using all SNPs or a reduced SNP subset (reduced classical approach). To enable a comparison between SNP subsets, a special invariable evaluation design was implemented. SNPs close to or within known quantitative trait loci (QTL) were determined. This enabled us to determine if detected important SNP subsets were enriched in these regions. The results show that our approach can lead to genetic value prediction, but requires less than 1% of the total amount of (40,317) SNPs., significantly more important SNPs in known QTL regions were detected using our approach compared to the reduced classical approach. Concluding, our approach allows a deeper insight into the associations between the different levels of the genotype-phenotype map (genotype-metabolome, metabolome-phenotype, genotype-phenotype). PMID:23990900

Heterogeneous vancomycin-intermediate susceptibility phenotype in bloodstream methicillin-resistant Staphylococcus aureus isolates from an international cohort of patients with infective endocarditis: prevalence, genotype, and clinical significance.

PubMed

Bae, In-Gyu; Federspiel, Jerome J; Miró, José M; Woods, Christopher W; Park, Lawrence; Rybak, Michael J; Rude, Thomas H; Bradley, Suzanne; Bukovski, Suzana; de la Maria, Cristina Garcia; Kanj, Souha S; Korman, Tony M; Marco, Francesc; Murdoch, David R; Plesiat, Patrick; Rodriguez-Creixems, Marta; Reinbott, Porl; Steed, Lisa; Tattevin, Pierre; Tripodi, Marie-Françoise; Newton, Karly L; Corey, G Ralph; Fowler, Vance G

2009-11-01

The significance of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is unknown. Using a multinational collection of isolates from methicillin-resistant S. aureus (MRSA) infective endocarditis (IE), we characterized patients with IE with and without hVISA, and we genotyped the infecting strains. MRSA bloodstream isolates from 65 patients with definite IE from 8 countries underwent polymerase chain reaction (PCR) for 31 virulence genes, pulsed-field gel electrophoresis, and multilocus sequence typing. hVISA was defined using population analysis profiling. Nineteen (29.2%) of 65 MRSA IE isolates exhibited the hVISA phenotype by population analysis profiling. Isolates from Oceania and Europe were more likely to exhibit the hVISA phenotype than isolates from the United States (77.8% and 35.0% vs 13.9%; P < .001). The prevalence of hVISA was higher among isolates with a vancomycin minimum inhibitory concentration of 2 mg/L (P = .026). hVISA-infected patients were more likely to have persistent bacteremia (68.4% vs 37.0%; P = .029) and heart failure (47.4% vs 19.6%; P = .033). Mortality did not differ between hVISA- and non-hVISA-infected patients (42.1% vs 34.8%, P = .586). hVISA and non-hVISA isolates were genotypically similar. In these analyses, the hVISA phenotype occurred in more than one-quarter of MRSA IE isolates, was associated with certain IE complications, and varied in frequency by geographic region.

Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity.

PubMed

Montoliu, Ivan; Scherer, Max; Beguelin, Fiona; DaSilva, Laeticia; Mari, Daniela; Salvioli, Stefano; Martin, Francois-Pierre J; Capri, Miriam; Bucci, Laura; Ostan, Rita; Garagnani, Paolo; Monti, Daniela; Biagi, Elena; Brigidi, Patrizia; Kussmann, Martin; Rezzi, Serge; Franceschi, Claudio; Collino, Sebastiano

2014-01-01

As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis.

PubMed

Rajamani, Deepa; Bhasin, Manoj K

2016-05-03

Pancreatic cancer is an aggressive cancer with dismal prognosis, urgently necessitating better biomarkers to improve therapeutic options and early diagnosis. Traditional approaches of biomarker detection that consider only one aspect of the biological continuum like gene expression alone are limited in their scope and lack robustness in identifying the key regulators of the disease. We have adopted a multidimensional approach involving the cross-talk between the omics spaces to identify key regulators of disease progression. Multidimensional domain-specific disease signatures were obtained using rank-based meta-analysis of individual omics profiles (mRNA, miRNA, DNA methylation) related to pancreatic ductal adenocarcinoma (PDAC). These domain-specific PDAC signatures were integrated to identify genes that were affected across multiple dimensions of omics space in PDAC (genes under multiple regulatory controls, GMCs). To further pin down the regulators of PDAC pathophysiology, a systems-level network was generated from knowledge-based interaction information applied to the above identified GMCs. Key regulators were identified from the GMC network based on network statistics and their functional importance was validated using gene set enrichment analysis and survival analysis. Rank-based meta-analysis identified 5391 genes, 109 miRNAs and 2081 methylation-sites significantly differentially expressed in PDAC (false discovery rate ≤ 0.05). Bimodal integration of meta-analysis signatures revealed 1150 and 715 genes regulated by miRNAs and methylation, respectively. Further analysis identified 189 altered genes that are commonly regulated by miRNA and methylation, hence considered GMCs. Systems-level analysis of the scale-free GMCs network identified eight potential key regulator hubs, namely E2F3, HMGA2, RASA1, IRS1, NUAK1, ACTN1, SKI and DLL1, associated with important pathways driving cancer progression. Survival analysis on individual key regulators revealed that higher expression of IRS1 and DLL1 and lower expression of HMGA2, ACTN1 and SKI were associated with better survival probabilities. It is evident from the results that our hierarchical systems-level multidimensional analysis approach has been successful in isolating the converging regulatory modules and associated key regulatory molecules that are potential biomarkers for pancreatic cancer progression.

Psychological profiles in patients with Sjögren's syndrome related to fatigue: a cluster analysis.

PubMed

van Leeuwen, Ninke; Bossema, Ercolie R; Knoop, Hans; Kruize, Aike A; Bootsma, Hendrika; Bijlsma, Johannes W J; Geenen, Rinie

2015-05-01

Fatigue is a highly prevalent and debilitating symptom in the autoimmune disease SS. Although the disease process plays a role in fatigue, psychological factors may influence fatigue and the ability to deal with its consequences. Profiles of co-occurring psychological factors may suggest potential targets for the treatment of fatigue. The aim of this study was to identify psychological profiles in patients with SS and the accompanying levels of fatigue. Three hundred patients with primary SS (mean age 57 years, 93% female) completed questionnaires on fatigue (multidimensional fatigue inventory), physical activity cognitions (TAMPA-SK), illness cognitions, cognitive regulation, emotion processing and regulation [Toronto Alexithymia Scale 20, Emotion Regulation Questionnaire (ERQ), Berkeley Expressivity Questionnaire], coping strategies (Brief COPE) and social support. Principal axis factor analysis (oblimin rotation) yielded six psychological factors: social support, negative thinking, positive thinking, emotional expressivity, avoidance and alexithymia (i.e. the inability to differentiate emotions). Using cluster analyses, these factors were grouped in four psychological profiles: functional (39%), alexithymic (27%), self-reliant (23%) and dysfunctional (11%). Irrespective of the psychological profile, the level of fatigue was substantially higher in patients than in the general population. Patients with a dysfunctional or an alexithymic profile reported more fatigue than those with a self-reliant profile. Our study in SS yielded four psychological profiles that were differentially associated with fatigue. These profiles can be used to examine determinants and prognosis of fatigue as well as the possibility of customizing cognitive behavioural interventions for chronic fatigue. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Psychometric properties of the Greek TCI-R and its clinical correlates: schizotypy and the self-regulation of affective and cognitive functioning.

PubMed

Giakoumaki, Stella G; Karagiannopoulou, Leda; Rózsa, Sándor; Zouraraki, Chrysoula; Karamaouna, Penny; Cloninger, C Robert

2016-01-01

Background. The revised Temperament and Character Inventory (TCI-R) measures Cloninger's psychobiological model of personality. The average effects of individual temperament and character traits have been associated with schizotypy and with impaired regulation of affect and cognition. We extended prior research by testing predictions about the association of specific multidimensional configurations of temperament and character traits on schizotypy, affect balance, and self-perceived cognitive functioning. Method. A well-educated sample of native Greeks (N = 483), completed a new Greek translation of the TCI-R, as well as the Schizotypal Personality Questionnaire (SPQ), the Positive/Negative Affect Schedule (PANAS) and the Cognitive Failures Questionnaire (CFQ). The factor structure of the TCI-R was examined with exploratory and confirmatory tests. Associations between reported measures were examined with correlational and regression analyses. Results. The TCI-R had good psychometric properties as expected from studies in other countries. As predicted, specific configurations of temperament and character were associated with schizotypy, negative affect balance, and cognitive lapses. The "Borderline/Explosive temperament" (high Novelty Seeking, high Harm Avoidance, low Reward Dependence), "Schizotypal/Disorganized character" (low Self-directedness, low Cooperativeness, high Self-transcendence), and "Low Ego Strength/Fragile" profile (high Harm Avoidance, low Persistence, low Self-Directedness) were each strongly associated with higher stereotypy, negative affect balance (low positive affect and high negative affect), and subjective cognitive lapses compared to their contrast groups. Discussion. Multidimensional TCI profiles are strongly related to individual differences in schizotypy and self-reported regulation of affect and cognition. The Greek translation of the TCI-R is psychometrically sound and useful for clinical assessment and research.

Psychometric properties of the Greek TCI-R and its clinical correlates: schizotypy and the self-regulation of affective and cognitive functioning

PubMed Central

Karagiannopoulou, Leda; Rózsa, Sándor; Zouraraki, Chrysoula; Karamaouna, Penny; Cloninger, C. Robert

2016-01-01

Background. The revised Temperament and Character Inventory (TCI-R) measures Cloninger’s psychobiological model of personality. The average effects of individual temperament and character traits have been associated with schizotypy and with impaired regulation of affect and cognition. We extended prior research by testing predictions about the association of specific multidimensional configurations of temperament and character traits on schizotypy, affect balance, and self-perceived cognitive functioning. Method. A well-educated sample of native Greeks (N = 483), completed a new Greek translation of the TCI-R, as well as the Schizotypal Personality Questionnaire (SPQ), the Positive/Negative Affect Schedule (PANAS) and the Cognitive Failures Questionnaire (CFQ). The factor structure of the TCI-R was examined with exploratory and confirmatory tests. Associations between reported measures were examined with correlational and regression analyses. Results. The TCI-R had good psychometric properties as expected from studies in other countries. As predicted, specific configurations of temperament and character were associated with schizotypy, negative affect balance, and cognitive lapses. The “Borderline/Explosive temperament” (high Novelty Seeking, high Harm Avoidance, low Reward Dependence), “Schizotypal/Disorganized character” (low Self-directedness, low Cooperativeness, high Self-transcendence), and “Low Ego Strength/Fragile” profile (high Harm Avoidance, low Persistence, low Self-Directedness) were each strongly associated with higher stereotypy, negative affect balance (low positive affect and high negative affect), and subjective cognitive lapses compared to their contrast groups. Discussion. Multidimensional TCI profiles are strongly related to individual differences in schizotypy and self-reported regulation of affect and cognition. The Greek translation of the TCI-R is psychometrically sound and useful for clinical assessment and research. PMID:27019787

Profiling protein function with small molecule microarrays

PubMed Central

Winssinger, Nicolas; Ficarro, Scott; Schultz, Peter G.; Harris, Jennifer L.

2002-01-01

The regulation of protein function through posttranslational modification, local environment, and protein–protein interaction is critical to cellular function. The ability to analyze on a genome-wide scale protein functional activity rather than changes in protein abundance or structure would provide important new insights into complex biological processes. Herein, we report the application of a spatially addressable small molecule microarray to an activity-based profile of proteases in crude cell lysates. The potential of this small molecule-based profiling technology is demonstrated by the detection of caspase activation upon induction of apoptosis, characterization of the activated caspase, and inhibition of the caspase-executed apoptotic phenotype using the small molecule inhibitor identified in the microarray-based profile. PMID:12167675

Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells

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

Igarashi, Kaori; Sakimoto, Ippei; Kataoka, Keiko

The effects of ionizing radiation (IR) on tumor angiogenesis still remain largely unknown. In this study, we found that IR (8 Gy) induces a high-frequency (80-90%) senescence-like phenotype in vascular endothelial cells (ECs) undergoing exponential growth. This finding allowed us to characterize the IR-induced senescence-like (IRSL) phenotype by examining the gene expression profiles and in vitro angiogenic activities of these ECs. The expression levels of genes associated with cell cycle progression and DNA replication were remarkably reduced in the IRSL ECs. Additionally, the in vitro invasion and migration activities of these cells through Matrigel were significantly suppressed. We also foundmore » that confluent ECs exhibited a high-frequency IRSL phenotype when they were replated immediately after irradiation, whereas incubation in plateau-phase conditions reduced the induction of this phenotype and enhanced colony formation. The kinetics of DNA double-strand break repair, which showed a faster time course in confluent ECs than in growing ECs, may contribute to the protective mechanism associated with the IRSL phenotype. These results imply that the IRSL phenotype may be important for determining the angiogenic activity of ECs following irradiation. The present study should contribute to the understanding of the effects of IR on tumor angiogenesis.« less

Identification of genus Acinetobacter: Standardization of in-house PCR and its comparison with conventional phenotypic methods.

PubMed

Kulkarni, Sughosh S; Madalgi, Radhika; Ajantha, Ganavalli S; Kulkarni, Raghavendra D

2017-01-01

Acinetobacter is grouped under nonfermenting Gram-negative bacilli. It is increasingly isolated from pathological samples. The ability of this genus to acquire drug resistance and spread in the hospital settings is posing a grave problem in healthcare. Specific treatment protocols are advocated for Acinetobacter infections. Hence, rapid identification and drug susceptibility profiling are critical in the management of these infections. To standardize an in-house polymerase chain reaction (PCR) for identification of genus Acinetobacter and to compare PCR with two protocols for its phenotypic identification. A total of 96 clinical isolates of Acinetobacter were included in the study. An in-house PCR for genus level identification of Acinetobacter was standardized. All the isolates were phenotypically identified by two protocols. The results of PCR and phenotypic identification protocols were compared. The in-house PCR standardized was highly sensitive and specific for the genus Acinetobacter . There was 100% agreement between the phenotypic and molecular identification of the genus. The preliminary identification tests routinely used in clinical laboratories were also in complete agreement with phenotypic and molecular identification. The in-house PCR for genus level identification is specific and sensitive. However, it may not be essential for routine identification as the preliminary phenotypic identification tests used in the clinical laboratory reliably identify the genus Acinetobacter .

Computational evaluation of exome sequence data using human and model organism phenotypes improves diagnostic efficiency

PubMed Central

Bone, William P.; Washington, Nicole L.; Buske, Orion J.; Adams, David R.; Davis, Joie; Draper, David; Flynn, Elise D.; Girdea, Marta; Godfrey, Rena; Golas, Gretchen; Groden, Catherine; Jacobsen, Julius; Köhler, Sebastian; Lee, Elizabeth M. J.; Links, Amanda E.; Markello, Thomas C.; Mungall, Christopher J.; Nehrebecky, Michele; Robinson, Peter N.; Sincan, Murat; Soldatos, Ariane G.; Tifft, Cynthia J.; Toro, Camilo; Trang, Heather; Valkanas, Elise; Vasilevsky, Nicole; Wahl, Colleen; Wolfe, Lynne A.; Boerkoel, Cornelius F.; Brudno, Michael; Haendel, Melissa A.; Gahl, William A.; Smedley, Damian

2016-01-01

Purpose: Medical diagnosis and molecular or biochemical confirmation typically rely on the knowledge of the clinician. Although this is very difficult in extremely rare diseases, we hypothesized that the recording of patient phenotypes in Human Phenotype Ontology (HPO) terms and computationally ranking putative disease-associated sequence variants improves diagnosis, particularly for patients with atypical clinical profiles. Genet Med 18 6, 608–617. Methods: Using simulated exomes and the National Institutes of Health Undiagnosed Diseases Program (UDP) patient cohort and associated exome sequence, we tested our hypothesis using Exomiser. Exomiser ranks candidate variants based on patient phenotype similarity to (i) known disease–gene phenotypes, (ii) model organism phenotypes of candidate orthologs, and (iii) phenotypes of protein–protein association neighbors. Genet Med 18 6, 608–617. Results: Benchmarking showed Exomiser ranked the causal variant as the top hit in 97% of known disease–gene associations and ranked the correct seeded variant in up to 87% when detectable disease–gene associations were unavailable. Using UDP data, Exomiser ranked the causative variant(s) within the top 10 variants for 11 previously diagnosed variants and achieved a diagnosis for 4 of 23 cases undiagnosed by clinical evaluation. Genet Med 18 6, 608–617. Conclusion: Structured phenotyping of patients and computational analysis are effective adjuncts for diagnosing patients with genetic disorders. Genet Med 18 6, 608–617. PMID:26562225

Aggregating available soil water holding capacity data for crop yield models

NASA Technical Reports Server (NTRS)

Seubert, C. E.; Daughtry, C. S. T.; Holt, D. A.; Baumgardner, M. F.

1984-01-01

The total amount of water available to plants that is held against gravity in a soil is usually estimated as the amount present at -0.03 MPa average water potential minus the amount present at -1.5 MPa water potential. This value, designated available water-holding capacity (AWHC), is a very important soil characteristic that is strongly and positively correlated to the inherent productivity of soils. In various applications, including assessing soil moisture status over large areas, it is necessary to group soil types or series as to their productivity. Current methods to classify AWHC of soils consider only total capacity of soil profiles and thus may group together soils which differ greatly in AWHC as a function of depth in the profile. A general approach for evaluating quantitatively the multidimensional nature of AWHC in soils is described. Data for 902 soil profiles, representing 184 soil series, in Indiana were obtained from the Soil Characterization Laboratory at Purdue University. The AWHC for each of ten 150-mm layers in each soil was established, based on soil texture and parent material. A multivariate clustering procedure was used to classify each soil profile into one of 4, 8, or 12 classes based upon ten-dimensional AWHC values. The optimum number of classes depends on the range of AWHC in the population of oil profiles analyzed and on the sensitivity of a crop to differences in distribution of water within the soil profile.

Phenotype in combination with genotype improves outcome prediction in acute myeloid leukemia: a report from Children’s Oncology Group protocol AAML0531

PubMed Central

Voigt, Andrew P.; Brodersen, Lisa Eidenschink; Alonzo, Todd A.; Gerbing, Robert B.; Menssen, Andrew J.; Wilson, Elisabeth R.; Kahwash, Samir; Raimondi, Susana C.; Hirsch, Betsy A.; Gamis, Alan S.; Meshinchi, Soheil; Wells, Denise A.; Loken, Michael R.

2017-01-01

Diagnostic biomarkers can be used to determine relapse risk in acute myeloid leukemia, and certain genetic aberrancies have prognostic relevance. A diagnostic immunophenotypic expression profile, which quantifies the amounts of distinct gene products, not just their presence or absence, was established in order to improve outcome prediction for patients with acute myeloid leukemia. The immunophenotypic expression profile, which defines each patient’s leukemia as a location in 15-dimensional space, was generated for 769 patients enrolled in the Children’s Oncology Group AAML0531 protocol. Unsupervised hierarchical clustering grouped patients with similar immunophenotypic expression profiles into eleven patient cohorts, demonstrating high associations among phenotype, genotype, morphology, and outcome. Of 95 patients with inv(16), 79% segregated in Cluster A. Of 109 patients with t(8;21), 92% segregated in Clusters A and B. Of 152 patients with 11q23 alterations, 78% segregated in Clusters D, E, F, G, or H. For both inv(16) and 11q23 abnormalities, differential phenotypic expression identified patient groups with different survival characteristics (P<0.05). Clinical outcome analysis revealed that Cluster B (predominantly t(8;21)) was associated with favorable outcome (P<0.001) and Clusters E, G, H, and K were associated with adverse outcomes (P<0.05). Multivariable regression analysis revealed that Clusters E, G, H, and K were independently associated with worse survival (P range <0.001 to 0.008). The Children’s Oncology Group AAML0531 trial: clinicaltrials.gov Identifier: 00372593. PMID:28883080

Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis.

PubMed

Iorio, Andrea; De Lillo, Antonella; De Angelis, Flavio; Di Girolamo, Marco; Luigetti, Marco; Sabatelli, Mario; Pradotto, Luca; Mauro, Alessandro; Mazzeo, Anna; Stancanelli, Claudia; Perfetto, Federico; Frusconi, Sabrina; My, Filomena; Manfellotto, Dario; Fuciarelli, Maria; Polimanti, Renato

2017-09-01

Coding mutations in TTR gene cause a rare hereditary form of systemic amyloidosis, which has a complex genotype-phenotype correlation. We investigated the role of non-coding variants in regulating TTR gene expression and consequently amyloidosis symptoms. We evaluated the genotype-phenotype correlation considering the clinical information of 129 Italian patients with TTR amyloidosis. Then, we conducted a re-sequencing of TTR gene to investigate how non-coding variants affect TTR expression and, consequently, phenotypic presentation in carriers of amyloidogenic mutations. Polygenic scores for genetically determined TTR expression were constructed using data from our re-sequencing analysis and the GTEx (Genotype-Tissue Expression) project. We confirmed a strong phenotypic heterogeneity across coding mutations causing TTR amyloidosis. Considering the effects of non-coding variants on TTR expression, we identified three patient clusters with specific expression patterns associated with certain phenotypic presentations, including late onset, autonomic neurological involvement, and gastrointestinal symptoms. This study provides novel data regarding the role of non-coding variation and the gene expression profiles in patients affected by TTR amyloidosis, also putting forth an approach that could be used to investigate the mechanisms at the basis of the genotype-phenotype correlation of the disease.

Novel clustering of items from the Autism Diagnostic Interview-Revised to define phenotypes within autism spectrum disorders

PubMed Central

Hu, Valerie W.; Steinberg, Mara E.

2009-01-01

Heterogeneity in phenotypic presentation of ASD has been cited as one explanation for the difficulty in pinpointing specific genes involved in autism. Recent studies have attempted to reduce the “noise” in genetic and other biological data by reducing the phenotypic heterogeneity of the sample population. The current study employs multiple clustering algorithms on 123 item scores from the Autism Diagnostic Interview-Revised (ADI-R) diagnostic instrument of nearly 2000 autistic individuals to identify subgroups of autistic probands with clinically relevant behavioral phenotypes in order to isolate more homogeneous groups of subjects for gene expression analyses. Our combined cluster analyses suggest optimal division of the autistic probands into 4 phenotypic clusters based on similarity of symptom severity across the 123 selected item scores. One cluster is characterized by severe language deficits, while another exhibits milder symptoms across the domains. A third group possesses a higher frequency of savant skills while the fourth group exhibited intermediate severity across all domains. Grouping autistic individuals by multivariate cluster analysis of ADI-R scores reveals meaningful phenotypes of subgroups within the autistic spectrum which we show, in a related (accompanying) study, to be associated with distinct gene expression profiles. PMID:19455643

Accessing Multi-Dimensional Images and Data Cubes in the Virtual Observatory

NASA Astrophysics Data System (ADS)

Tody, Douglas; Plante, R. L.; Berriman, G. B.; Cresitello-Dittmar, M.; Good, J.; Graham, M.; Greene, G.; Hanisch, R. J.; Jenness, T.; Lazio, J.; Norris, P.; Pevunova, O.; Rots, A. H.

2014-01-01

Telescopes across the spectrum are routinely producing multi-dimensional images and datasets, such as Doppler velocity cubes, polarization datasets, and time-resolved “movies.” Examples of current telescopes producing such multi-dimensional images include the JVLA, ALMA, and the IFU instruments on large optical and near-infrared wavelength telescopes. In the near future, both the LSST and JWST will also produce such multi-dimensional images routinely. High-energy instruments such as Chandra produce event datasets that are also a form of multi-dimensional data, in effect being a very sparse multi-dimensional image. Ensuring that the data sets produced by these telescopes can be both discovered and accessed by the community is essential and is part of the mission of the Virtual Observatory (VO). The Virtual Astronomical Observatory (VAO, http://www.usvao.org/), in conjunction with its international partners in the International Virtual Observatory Alliance (IVOA), has developed a protocol and an initial demonstration service designed for the publication, discovery, and access of arbitrarily large multi-dimensional images. The protocol describing multi-dimensional images is the Simple Image Access Protocol, version 2, which provides the minimal set of metadata required to characterize a multi-dimensional image for its discovery and access. A companion Image Data Model formally defines the semantics and structure of multi-dimensional images independently of how they are serialized, while providing capabilities such as support for sparse data that are essential to deal effectively with large cubes. A prototype data access service has been deployed and tested, using a suite of multi-dimensional images from a variety of telescopes. The prototype has demonstrated the capability to discover and remotely access multi-dimensional data via standard VO protocols. The prototype informs the specification of a protocol that will be submitted to the IVOA for approval, with an operational data cube service to be delivered in mid-2014. An associated user-installable VO data service framework will provide the capabilities required to publish VO-compatible multi-dimensional images or data cubes.

Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy.

PubMed

Honeyborne, Isobella; McHugh, Timothy D; Kuittinen, Iitu; Cichonska, Anna; Evangelopoulos, Dimitrios; Ronacher, Katharina; van Helden, Paul D; Gillespie, Stephen H; Fernandez-Reyes, Delmiro; Walzl, Gerhard; Rousu, Juho; Butcher, Philip D; Waddell, Simon J

2016-04-07

New treatment options are needed to maintain and improve therapy for tuberculosis, which caused the death of 1.5 million people in 2013 despite potential for an 86 % treatment success rate. A greater understanding of Mycobacterium tuberculosis (M.tb) bacilli that persist through drug therapy will aid drug development programs. Predictive biomarkers for treatment efficacy are also a research priority. Genome-wide transcriptional profiling was used to map the mRNA signatures of M.tb from the sputa of 15 patients before and 3, 7 and 14 days after the start of standard regimen drug treatment. The mRNA profiles of bacilli through the first 2 weeks of therapy reflected drug activity at 3 days with transcriptional signatures at days 7 and 14 consistent with reduced M.tb metabolic activity similar to the profile of pre-chemotherapy bacilli. These results suggest that a pre-existing drug-tolerant M.tb population dominates sputum before and after early drug treatment, and that the mRNA signature at day 3 marks the killing of a drug-sensitive sub-population of bacilli. Modelling patient indices of disease severity with bacterial gene expression patterns demonstrated that both microbiological and clinical parameters were reflected in the divergent M.tb responses and provided evidence that factors such as bacterial load and disease pathology influence the host-pathogen interplay and the phenotypic state of bacilli. Transcriptional signatures were also defined that predicted measures of early treatment success (rate of decline in bacterial load over 3 days, TB test positivity at 2 months, and bacterial load at 2 months). This study defines the transcriptional signature of M.tb bacilli that have been expectorated in sputum after two weeks of drug therapy, characterizing the phenotypic state of bacilli that persist through treatment. We demonstrate that variability in clinical manifestations of disease are detectable in bacterial sputa signatures, and that the changing M.tb mRNA profiles 0-2 weeks into chemotherapy predict the efficacy of treatment 6 weeks later. These observations advocate assaying dynamic bacterial phenotypes through drug therapy as biomarkers for treatment success.

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

PubMed

Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

2011-06-13

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches aimed to study genes or pathways involved in ccRCC etiopathogenesis and to identify novel clinical markers or therapeutic targets. Moreover, SNP array technology proved to be a powerful tool to better define the cell composition and homogeneity of RCC primary cultures. © 2011 Cifola et al; licensee BioMed Central Ltd.

Multidimensional Unfolding by Nonmetric Multidimensional Scaling of Spearman Distances in the Extended Permutation Polytope

ERIC Educational Resources Information Center

Van Deun, Katrijn; Heiser, Willem J.; Delbeke, Luc

2007-01-01

A multidimensional unfolding technique that is not prone to degenerate solutions and is based on multidimensional scaling of a complete data matrix is proposed: distance information about the unfolding data and about the distances both among judges and among objects is included in the complete matrix. The latter information is derived from the…

Distribution of phenotypes among Bacillus thuringiensis strains.

PubMed

Martin, Phyllis A W; Gundersen-Rindal, Dawn E; Blackburn, Michael B

2010-06-01

An extensive collection of Bacillus thuringiensis isolates from around the world were phenotypically profiled using standard biochemical tests. Six phenotypic traits occurred in 20-86% of the isolates and were useful in distinguishing isolates: production of urease (U; 20.5% of isolates), hydrolysis of esculin (E; 32.3% of isolates), acid production from salicin (A; 37.4% of isolates), acid production from sucrose (S; 34.0% of isolates), production of phospholipase C or lecithinase (L; 79.7% of isolates), and hydrolysis of starch (T; 85.8% of isolates). With the exception of acid production from salicin and hydrolysis of esculin, which were associated, the traits assorted independently. Of the 64 possible combinations of these six phenotypic characteristics, 15 combinations accounted for ca. 80% of all isolates, with the most common phenotype being TL (23.6% of isolates). Surprisingly, while the biochemical traits generally assorted independently, certain phenotypic traits associated with the parasporal crystal were correlated with certain combinations of biochemical traits. Crystals that remained attached to spores (which tended to be non-toxic to insects) were highly correlated with the phenotypes that included both L and S. Among the 15 most abundant phenotypes characterizing B. thuringiensis strains, amorphous crystals were associated with TLE, TL, T, and Ø (the absence of positive tested biochemical traits). Amorphous crystal types displayed a distinct bias toward toxicity to dipteran insects. Although all common phenotypes included B. thuringiensis isolates producing bipyramidal crystals toxic to lepidopteran insects, those with the highest abundance of these toxic crystals displayed phenotypes TLU, TLUA, TLUAE, and TLAE.

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

Merkley, Eric D.; Sego, Landon H.; Lin, Andy

Adaptive processes in bacterial species can occur rapidly in laboratory culture, leading to genetic divergence between naturally occurring and laboratory-adapted strains. Differentiating wild and closely-related laboratory strains is clearly important for biodefense and bioforensics; however, DNA sequence data alone has thus far not provided a clear signature, perhaps due to lack of understanding of how diverse genome changes lead to adapted phenotypes. Protein abundance profiles from mass spectrometry-based proteomics analyses are a molecular measure of phenotype. Proteomics data contains sufficient information that powerful statistical methods can uncover signatures that distinguish wild strains of Yersinia pestis from laboratory-adapted strains.

Odd MECP2-mutated Rett variant-long-term follow-up profile to age 25.

PubMed

Hagberg, Bengt; Erlandsson, Anna; Kyllerman, Mårten; Larsson, Gunillla

2003-01-01

A 25-year-old MECP2-mutated female with odd developmental and dyspraxic/ataxic features, followed up through two decades, is reported. She does not fit either the classical Rett syndrome or the criteria required for any Rett variant phenotypes so far described. Nevertheless, she belongs clinically to the latter group. This case deserves attention in order, among other things, to provide important clues to better understand the puzzling battery of neuroimpairments and behavioural abnormalities met in classical Rett phenotypes and Rett variants defined thus far.

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

PubMed

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.

Cancer biomarker discovery: the entropic hallmark.

PubMed

Berretta, Regina; Moscato, Pablo

2010-08-18

It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.

Understanding and Predicting Profile Structure and Parametric Scaling of Intrinsic Rotation

NASA Astrophysics Data System (ADS)

Wang, Weixing

2016-10-01

It is shown for the first time that turbulence-driven residual Reynolds stress can account for both the shape and magnitude of the observed intrinsic toroidal rotation profile. Nonlinear, global gyrokinetic simulations using GTS of DIII-D ECH plasmas indicate a substantial ITG fluctuation-induced non-diffusive momentum flux generated around a mid-radius-peaked intrinsic toroidal rotation profile. The non-diffusive momentum flux is dominated by the residual stress with a negligible contribution from the momentum pinch. The residual stress profile shows a robust anti-gradient, dipole structure in a set of ECH discharges with varying ECH power. Such interesting features of non-diffusive momentum fluxes, in connection with edge momentum sources and sinks, are found to be critical to drive the non-monotonic core rotation profiles in the experiments. Both turbulence intensity gradient and zonal flow ExB shear are identified as major contributors to the generation of the k∥-asymmetry needed for the residual stress generation. By balancing the residual stress and the momentum diffusion, a self-organized, steady-state rotation profile is calculated. The predicted core rotation profiles agree well with the experimentally measured main-ion toroidal rotation. The validated model is further used to investigate the characteristic dependence of global rotation profile structure in the multi-dimensional parametric space covering turbulence type, q-profile structure and collisionality with the goal of developing physics understanding needed for rotation profile control and optimization. Interesting results obtained include intrinsic rotation reversal induced by ITG-TEM transition in flat-q profile regime and by change in q-profile from weak to normal shear.. Fluctuation-generated poloidal Reynolds stress is also shown to significantly modify the neoclassical poloidal rotation in a way consistent with experimental observations. Finally, the first-principles-based model is applied to studying the ρ * -scaling and predicting rotations in ITER regime. Work supported by U.S. DOE Contract DE-AC02-09-CH11466.

Keratin expression profiling of transitional epithelium in the painful bladder syndrome/interstitial cystitis.

PubMed

Laguna, Pilar; Smedts, Frank; Nordling, Jörgen; Horn, Thomas; Bouchelouche, Kirsten; Hopman, Anton; de la Rosette, Jean

2006-01-01

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a severely debilitating condition. Its cause is poorly understood; therapy is symptomatic and often unsuccessful. To study urothelial involvement, we characterized the keratin phenotype of bladder urothelium in 18 patients with PBS/IC using a panel of 11 keratin antibodies recognizing simple keratins found in columnar epithelia (keratins 7, 8, 18, and 20) and keratins associated with basal cell compartments of squamous epithelia (keratins 5, 13, 14, and 17). We also tested 2 antibodies recognizing more than 1 keratin also directed against basal cell compartments of squamous epithelia (D5/16 B4 and 34betaE12). Bladder urothelium in PBS/IC showed distinct differences in the profiles of keratins 7, 8, 14, 17, 18, and 20 compared with literature reports for normal bladder urothelium. These were characterized by a shift from the normal bladder urothelial keratin phenotype to a more squamous keratin profile, despite the lack of morphologic evidence of squamous epithelial differentiation and a loss of compartmentalization of keratin expression. The severity of these changes varied between biopsy specimens. Whether these changes are primary or secondary to another underlying condition remains to be determined.

Characterization of Methicillin Resistant Staphylococcus aureus isolated from human and animal samples in Egypt.

PubMed

Bendary, M M; Solyman, S M; Azab, M M; Mahmoud, N F; Hanora, A M

2016-02-29

Staphylococcus aureus (S. aureus) has been one of the most problematic pathogens. Methicillin Resistant S. aureus (MRSA) has emerged as a major concern for both human and animal. Antibiotic resistance genes dissemination might be possible between human and animal bacteria. The aim of this study is to show phenotypic and genotypic diversity of human and animal MRSA isolates. Antibiogram typing and biofilm production were used as a primary phenotypic typing tool for the characterization of (40) animal and (38) human MRSA isolates. Genetic typing based on sequencing of 16S rRNA gene and virulence gene profiles were done. Antimicrobial resistance profiles of the animal isolates showed little evidence of widespread of resistance, although this was seen in many human isolates. The biofilm production was detected in higher percentage among animal isolates. Based on the genetic typing and multiple antibiotic resistance (MAR) index, the majority of animal isolates clustered into lineages that were not found in human isolates. Animal and human MRSA isolates showed diversity in antibiotic resistance and virulence gene profiles may be due to host adaptation or chances for contamination between the two hosts were not present in our study.

Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

PubMed Central

Martínez, María Sofía; Palmar, Jim; Bautista, Jordan; Chávez-Castillo, Mervin; Gómez, Alexis; Bermúdez, Valmore

2015-01-01

Cardiovascular disease (CVD) is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-γ, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD. PMID:26491604

Behavioral phenotypes of genetic syndromes with intellectual disability: comparison of adaptive profiles.

PubMed

Di Nuovo, Santo; Buono, Serafino

2011-10-30

The study of distinctive and consistent behaviors in the most common genetic syndromes with intellectual disability is useful to explain abnormalities or associated psychiatric disorders. The behavioral phenotypes revealed outcomes totally or partially specific for each syndrome. The aim of our study was to compare similarities and differences in the adaptive profiles of the five most frequent genetic syndromes, i.e. Down syndrome, Williams syndrome, Angelman syndrome, Prader-Willi syndrome, and Fragile-X syndrome (fully mutated), taking into account the relation with chronological age and the overall IQ level. The research was carried out using the Vineland Adaptive Behavior Scale (beside the Wechsler Intelligence scales to obtain IQ) with a sample of 181 persons (107 males and 74 females) showing genetic syndromes and mental retardation. Syndrome-based groups were matched for chronological age and mental age (excluding the Angelman group, presenting with severe mental retardation). Similarities and differences in the adaptive profiles are described, relating them to IQs and maladaptive behaviors. The results might be useful in obtaining a global index of adjustment for the assessment of intellectual disability level as well as for educational guidance and rehabilitative plans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators

PubMed Central

Sirimahachaiyakul, Pornthep; Sood, Ravi F.; Muffley, Lara A.; Seaton, Max; Lin, Cheng-Ta; Qiao, Liang; Armaly, Jeffrey S.; Hocking, Anne M.; Gibran, Nicole S.

2015-01-01

Introduction Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses. Methods and Materials Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium. Results Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium. Discussion Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring. PMID:26418010

Metabolic profiling of Arabidopsis thaliana epidermal cells

PubMed Central

Ebert, Berit; Zöller, Daniela; Erban, Alexander; Fehrle, Ines; Hartmann, Jürgen; Niehl, Annette; Kopka, Joachim; Fisahn, Joachim

2010-01-01

Metabolic phenotyping at cellular resolution may be considered one of the challenges in current plant physiology. A method is described which enables the cell type-specific metabolic analysis of epidermal cell types in Arabidopsis thaliana pavement, basal, and trichome cells. To achieve the required high spatial resolution, single cell sampling using microcapillaries was combined with routine gas chromatography-time of flight-mass spectrometry (GC-TOF-MS) based metabolite profiling. The identification and relative quantification of 117 mostly primary metabolites has been demonstrated. The majority, namely 90 compounds, were accessible without analytical background correction. Analyses were performed using cell type-specific pools of 200 microsampled individual cells. Moreover, among these identified metabolites, 38 exhibited differential pool sizes in trichomes, basal or pavement cells. The application of an independent component analysis confirmed the cell type-specific metabolic phenotypes. Significant pool size changes between individual cells were detectable within several classes of metabolites, namely amino acids, fatty acids and alcohols, alkanes, lipids, N-compounds, organic acids and polyhydroxy acids, polyols, sugars, sugar conjugates and phenylpropanoids. It is demonstrated here that the combination of microsampling and GC-MS based metabolite profiling provides a method to investigate the cellular metabolism of fully differentiated plant cell types in vivo. PMID:20150518

Predicting new drug indications from network analysis

NASA Astrophysics Data System (ADS)

Mohd Ali, Yousoff Effendy; Kwa, Kiam Heong; Ratnavelu, Kurunathan

This work adapts centrality measures commonly used in social network analysis to identify drugs with better positions in drug-side effect network and drug-indication network for the purpose of drug repositioning. Our basic hypothesis is that drugs having similar phenotypic profiles such as side effects may also share similar therapeutic properties based on related mechanism of action and vice versa. The networks were constructed from Side Effect Resource (SIDER) 4.1 which contains 1430 unique drugs with side effects and 1437 unique drugs with indications. Within the giant components of these networks, drugs were ranked based on their centrality scores whereby 18 prominent drugs from the drug-side effect network and 15 prominent drugs from the drug-indication network were identified. Indications and side effects of prominent drugs were deduced from the profiles of their neighbors in the networks and compared to existing clinical studies while an optimum threshold of similarity among drugs was sought for. The threshold can then be utilized for predicting indications and side effects of all drugs. Similarities of drugs were measured by the extent to which they share phenotypic profiles and neighbors. To improve the likelihood of accurate predictions, only profiles such as side effects of common or very common frequencies were considered. In summary, our work is an attempt to offer an alternative approach to drug repositioning using centrality measures commonly used for analyzing social networks.

Phenotypic spectrum and hormonal profile in hypogonadotropic hypogonadism

PubMed Central

Păun, D; Gherlan, I; Popescu, I; Procopiuc, C; Dumitrescu, C; Brehar, A; Dinu, D; Neamtu, C; Poiana, C; Dumitrache, C

2014-01-01

Abstract Background: Hypogonadotropic hypogonadism (HH) is characterized by inappropriately low serum concentration of LH (luteinizing hormone) and FSH (follicle-stimulated hormone) in the setting of hypogonadism. A number of pathologic processes cause Hypogonadotropic hypogonadism but it can also occur as a part of various congenital syndromes. Objectives. To characterize the morphotypes and the hormonal profile of the HH patients enrolled in the COST Action BM1105 within “C.I. Parhon” National Institute of Endocrinology from May 2012 onward. Methods. The eligible patients were selected by using a general protocol that included: a detailed familial and personal history; a clinical evaluation focusing on genital development; a hormonal evaluation that aimed to exclude the acquired causes of HH and to characterize the basal/stimulated (triptoreline) profile of gonadotropins; a DNA extraction for genetic studies. Results: We examinated the medical records of patients admitted in our institute with the diagnosis of hypogonadotropic hypogonadism from May 2012 onward. There were 19 patients: 12 males and 7 females, age at diagnosis 28.03±11.45 years (13.4-56 years). The phenotypic expressions were variable and the hormonal evaluation showed low values of basal and stimulated gonadotropins. Conclusions: Although hypogonadotropic hypogonadism is a rare disease, the monospeciality profile of National Institute of Endocrinology enable the enrolment of a high number of patients in order to create clinical guidelines for evaluation/diagnosis and for treating GnRH deficient patients. PMID:24653756

Phenotypic spectrum and hormonal profile in hypogonadotropic hypogonadism.

PubMed

Păun, D; Gherlan, I; Popescu, I; Procopiuc, C; Dumitrescu, C; Brehar, A; Dinu, D; Neamtu, C; Poiana, C; Dumitrache, C

2014-03-15

Hypogonadotropic hypogonadism (HH) is characterized by inappropriately low serum concentration of LH (luteinizing hormone) and FSH (follicle-stimulated hormone) in the setting of hypogonadism. A number of pathologic processes cause Hypogonadotropic hypogonadism but it can also occur as a part of various congenital syndromes. Objectives. To characterize the morphotypes and the hormonal profile of the HH patients enrolled in the COST Action BM1105 within "C.I. Parhon" National Institute of Endocrinology from May 2012 onward. Methods. The eligible patients were selected by using a general protocol that included: a detailed familial and personal history; a clinical evaluation focusing on genital development; a hormonal evaluation that aimed to exclude the acquired causes of HH and to characterize the basal/stimulated (triptoreline) profile of gonadotropins; a DNA extraction for genetic studies. We examinated the medical records of patients admitted in our institute with the diagnosis of hypogonadotropic hypogonadism from May 2012 onward. There were 19 patients: 12 males and 7 females, age at diagnosis 28.03 ± 11.45 years (13.4-56 years). The phenotypic expressions were variable and the hormonal evaluation showed low values of basal and stimulated gonadotropins. Although hypogonadotropic hypogonadism is a rare disease, the monospeciality profile of National Institute of Endocrinology enable the enrolment of a high number of patients in order to create clinical guidelines for evaluation/diagnosis and for treating GnRH deficient patients.

Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.

PubMed

Seys, Sven F; Scheers, Hans; Van den Brande, Paul; Marijsse, Gudrun; Dilissen, Ellen; Van Den Bergh, Annelies; Goeminne, Pieter C; Hellings, Peter W; Ceuppens, Jan L; Dupont, Lieven J; Bullens, Dominique M A

2017-02-23

Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking. Patients (n = 205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10 th /90 th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles. Half of patients (n = 108; 52.6%) had a classical T(h)2-high ("IL-4-, IL-5- and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4- and/or IL-13-high" pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F- and IL-25- high" profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high" (n = 16), "IL-6-high" (n = 8), "IL-22-high" (n = 25). Cluster 5 (n = 132) consists of patients without "cytokine-high" pattern or patients with only high IL-4 and/or IL-13. We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.

Alcohol Use in College: The Relationship Between Religion, Spirituality, and Proscriptive Attitudes Toward Alcohol.

PubMed

Kathol, Nicole; Sgoutas-Emch, Sandra

2017-04-01

Developing interventions to address the problem of college drinking requires the identification of contributing factors to drinking behavior. It is believed that religion and spirituality (R/S) play a role, but the mechanism is unclear. Using a multi-dimensional R/S measure, an alcohol behavior inventory, and a religious affiliation proscription question, this study was designed to dive deeper into this connection. This study found that religious singing/chanting and reading sacred text were the best predictors of lower alcohol consumption. Furthermore, participants who perceive their religious tradition to be proscriptive reported less alcohol consumption and higher religious/spiritual profiles.

Old worries and new anxieties: behavioral symptoms and mild cognitive impairment in a population study.

PubMed

Andreescu, Carmen; Teverovsky, Esther; Fu, Bo; Hughes, Tiffany F; Chang, Chung-Chou H; Ganguli, Mary

2014-03-01

To disentangle the complex associations of depression and anxiety with mild cognitive impairment (MCI) at the population level. We examined subgroups of anxiety symptoms and depression symptom profiles in relation to MCI, which we defined using both cognitive and functional approaches. We used an epidemiologic, cross-sectional study with an age-stratified, random, population-based sample of 1,982 individuals aged 65 years and over. Three definitions of MCI were used: 1) a purely cognitive classification into amnestic and nonamnestic MCI, 2) a combined cognitive-functional definition by International Working Group (IWG) criteria, and 3) a purely functional definition by the Clinical Dementia Rating (CDR) of 0.5. Three depression profiles were identified by factor analysis of the modified Center for Epidemiological Studies-Depression Scale: core mood, self-esteem/interpersonal, and apathy/neurovegetative profiles. Three anxiety groups, chronic mild worry, chronic severe anxiety, and recent-onset anxiety, were based on screening questions. Recent-onset anxiety was associated with MCI by nonamnestic and IWG criteria, chronic severe anxiety was associated with MCI by all definitions, and chronic mild worry was associated with none. Of the depression profiles, the core mood profile was associated with CDR-defined MCI, the apathy/neurovegetative profile was associated with MCI by amnestic, IWG, and CDR definitions, and the self-esteem/interpersonal profile was associated with none. In this population-based sample, subgroups with different anxiety and depression profiles had different relationships with cognitive and functional definitions of MCI. Anxiety, depression, and MCI are all multidimensional entities, interacting in complex ways that may shed light on underlying neural mechanisms. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

MaizeCyc: Metabolic networks in maize

USDA-ARS?s Scientific Manuscript database

MaizeCyc is a catalog of known and predicted metabolic and transport pathways that enables plant researchers to graphically represent the metabolome of maize (Zea mays), thereby supporting integrated systems-biology analysis. Supported analyses include molecular and genetic/phenotypic profiling (e.g...

Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken

PubMed Central

Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

2018-01-01

Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers. PMID:29642504

The Culturable Soil Antibiotic Resistome: A Community of Multi-Drug Resistant Bacteria

PubMed Central

Walsh, Fiona; Duffy, Brion

2013-01-01

Understanding the soil bacterial resistome is essential to understanding the evolution and development of antibiotic resistance, and its spread between species and biomes. We have identified and characterized multi-drug resistance (MDR) mechanisms in the culturable soil antibiotic resistome and linked the resistance profiles to bacterial species. We isolated 412 antibiotic resistant bacteria from agricultural, urban and pristine soils. All isolates were multi-drug resistant, of which greater than 80% were resistant to 16–23 antibiotics, comprising almost all classes of antibiotic. The mobile resistance genes investigated, (ESBL, bla NDM-1, and plasmid mediated quinolone resistance (PMQR) resistance genes) were not responsible for the respective resistance phenotypes nor were they present in the extracted soil DNA. Efflux was demonstrated to play an important role in MDR and many resistance phenotypes. Clinically relevant Burkholderia species are intrinsically resistant to ciprofloxacin but the soil Burkholderia species were not intrinsically resistant to ciprofloxacin. Using a phenotypic enzyme assay we identified the antibiotic specific inactivation of trimethoprim in 21 bacteria from different soils. The results of this study identified the importance of the efflux mechanism in the soil resistome and variations between the intrinsic resistance profiles of clinical and soil bacteria of the same family. PMID:23776501

Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile

PubMed Central

Martín-Martín, Lourdes; López, Antonio; Vidriales, Belén; Caballero, María Dolores; Rodrigues, António Silva; Ferreira, Silvia Inês; Lima, Margarida; Almeida, Sérgio; Valverde, Berta; Martínez, Pilar; Ferrer, Ana; Candeias, Jorge; Ruíz-Cabello, Francisco; Buadesa, Josefa Marco; Sempere, Amparo; Villamor, Neus

2015-01-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56− phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment. PMID:26056082

Integrating mRNA and Protein Sequencing Enables the Detection and Quantitative Profiling of Natural Protein Sequence Variants of Populus trichocarpa.

PubMed

Abraham, Paul E; Wang, Xiaojing; Ranjan, Priya; Nookaew, Intawat; Zhang, Bing; Tuskan, Gerald A; Hettich, Robert L

2015-12-04

Next-generation sequencing has transformed the ability to link genotypes to phenotypes and facilitates the dissection of genetic contribution to complex traits. However, it is challenging to link genetic variants with the perturbed functional effects on proteins encoded by such genes. Here we show how RNA sequencing can be exploited to construct genotype-specific protein sequence databases to assess natural variation in proteins, providing information about the molecular toolbox driving cellular processes. For this study, we used two natural genotypes selected from a recent genome-wide association study of Populus trichocarpa, an obligate outcrosser with tremendous phenotypic variation across the natural population. This strategy allowed us to comprehensively catalogue proteins containing single amino acid polymorphisms (SAAPs), as well as insertions and deletions. We profiled the frequency of 128 types of naturally occurring amino acid substitutions, including both expected (neutral) and unexpected (non-neutral) SAAPs, with a subset occurring in regions of the genome having strong polymorphism patterns consistent with recent positive and/or divergent selection. By zeroing in on the molecular signatures of these important regions that might have previously been uncharacterized, we now provide a high-resolution molecular inventory that should improve accessibility and subsequent identification of natural protein variants in future genotype-to-phenotype studies.

Interaction of rearing environment and reproductive tactic on gene expression profiles in Atlantic salmon

USGS Publications Warehouse

Aubin-Horth, N.; Letcher, B.H.; Hofmann, H.A.

2005-01-01

Organisms that share the same genotype can develop into divergent phenotypes, depending on environmental conditions. In Atlantic salmon, young males of the same age can be found either as sneakers or immature males that are future anadromous fish. Just as the organism-level phenotype varies between divergent male developmental trajectories, brain gene expression is expected to vary as well. We hypothesized that rearing environment can also have an important effect on gene expression in the brain and possibly interact with the reproductive tactic adopted. We tested this hypothesis by comparing brain gene expression profiles of the two male tactics in fish from the same population that were reared in either a natural stream or under laboratory conditions. We found that expression of certain genes was affected by rearing environment only, while others varied between male reproductive tactics independent of rearing environment. Finally, more than half of all genes that showed variable expression varied between the two male tactics only in one environment. Thus, in these fish, very different molecular pathways can give rise to similar macro-phenotypes depending on rearing environment. This result gives important insights into the molecular underpinnings of developmental plasticity in relationship to the environment. ?? 2005 The American Genetic Association.

Maternal Weaning Modulates Emotional Behavior and Regulates the Gut-Brain Axis

PubMed Central

Farshim, Pamela; Walton, Gemma; Chakrabarti, Bhismadev; Givens, Ian; Saddy, Doug; Kitchen, Ian; R. Swann, Jonathan; Bailey, Alexis

2016-01-01

Evidence shows that nutritional and environmental stress stimuli during postnatal period influence brain development and interactions between gut and brain. In this study we show that in rats, prevention of weaning from maternal milk results in depressive-like behavior, which is accompanied by changes in the gut bacteria and host metabolism. Depressive-like behavior was studied using the forced-swim test on postnatal day (PND) 25 in rats either weaned on PND 21, or left with their mother until PND 25 (non-weaned). Non-weaned rats showed an increased immobility time consistent with a depressive phenotype. Fluorescence in situ hybridization showed non-weaned rats to harbor significantly lowered Clostridium histolyticum bacterial groups but exhibit marked stress-induced increases. Metabonomic analysis of urine from these animals revealed significant differences in the metabolic profiles, with biochemical phenotypes indicative of depression in the non-weaned animals. In addition, non-weaned rats showed resistance to stress-induced modulation of oxytocin receptors in amygdala nuclei, which is indicative of passive stress-coping mechanism. We conclude that delaying weaning results in alterations to the gut microbiota and global metabolic profiles which may contribute to a depressive phenotype and raise the issue that mood disorders at early developmental ages may reflect interplay between mammalian host and resident bacteria. PMID:26903212

Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken.

PubMed

Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

2018-04-08

Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism ( ACACA , FASN , SCD , ACSL5 , FADS2 , FABP1 , APOA4 and ME1 ). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers.

Life events and personality in late adolescence: genetic and environmental relations.

PubMed

Billig, J P; Hershberger, S L; Iacono, W G; McGue, M

1996-11-01

The relationship between life events and personality was investigated in the Minnesota Twin/Family Study, using 216 monozygotic and 114 dizygotic 17-year-old male twin pairs. Participants completed a life events interview designed for adolescents and the Multidimensional Personality Questionnaire. Life events were categorized into three types: life events to which all members of a family would be subject and those affecting an individual, which can be broadly construed as either nonindependent or independent. Univariate genetic model fitting indicated the presence of significant genetic effects (h2 = 49%) for nonindependent nonfamily life events but not for the other two types of life events. Bivariate genetic model fitting further confirmed that the significant phenotypic correlation between nonindependent life events and personality is in part genetically mediated. Specifically, the findings suggest that genetically influenced individual differences in constraint play a substantial role in life events whose occurrence is not independent of the individual's behavior.

Merging Electronic Health Record Data and Genomics for Cardiovascular Research: A Science Advisory From the American Heart Association.

PubMed

Hall, Jennifer L; Ryan, John J; Bray, Bruce E; Brown, Candice; Lanfear, David; Newby, L Kristin; Relling, Mary V; Risch, Neil J; Roden, Dan M; Shaw, Stanley Y; Tcheng, James E; Tenenbaum, Jessica; Wang, Thomas N; Weintraub, William S

2016-04-01

The process of scientific discovery is rapidly evolving. The funding climate has influenced a favorable shift in scientific discovery toward the use of existing resources such as the electronic health record. The electronic health record enables long-term outlooks on human health and disease, in conjunction with multidimensional phenotypes that include laboratory data, images, vital signs, and other clinical information. Initial work has confirmed the utility of the electronic health record for understanding mechanisms and patterns of variability in disease susceptibility, disease evolution, and drug responses. The addition of biobanks and genomic data to the information contained in the electronic health record has been demonstrated. The purpose of this statement is to discuss the current challenges in and the potential for merging electronic health record data and genomics for cardiovascular research. © 2016 American Heart Association, Inc.

The genetical theory of social behaviour

PubMed Central

Lehmann, Laurent; Rousset, François

2014-01-01

We survey the population genetic basis of social evolution, using a logically consistent set of arguments to cover a wide range of biological scenarios. We start by reconsidering Hamilton's (Hamilton 1964 J. Theoret. Biol. 7, 1–16 (doi:10.1016/0022-5193(64)90038-4)) results for selection on a social trait under the assumptions of additive gene action, weak selection and constant environment and demography. This yields a prediction for the direction of allele frequency change in terms of phenotypic costs and benefits and genealogical concepts of relatedness, which holds for any frequency of the trait in the population, and provides the foundation for further developments and extensions. We then allow for any type of gene interaction within and between individuals, strong selection and fluctuating environments and demography, which may depend on the evolving trait itself. We reach three conclusions pertaining to selection on social behaviours under broad conditions. (i) Selection can be understood by focusing on a one-generation change in mean allele frequency, a computation which underpins the utility of reproductive value weights; (ii) in large populations under the assumptions of additive gene action and weak selection, this change is of constant sign for any allele frequency and is predicted by a phenotypic selection gradient; (iii) under the assumptions of trait substitution sequences, such phenotypic selection gradients suffice to characterize long-term multi-dimensional stochastic evolution, with almost no knowledge about the genetic details underlying the coevolving traits. Having such simple results about the effect of selection regardless of population structure and type of social interactions can help to delineate the common features of distinct biological processes. Finally, we clarify some persistent divergences within social evolution theory, with respect to exactness, synergies, maximization, dynamic sufficiency and the role of genetic arguments. PMID:24686929

Translation: screening for novel therapeutics with disease-relevant cell types derived from human stem cell models.

PubMed

Haggarty, Stephen J; Perlis, Roy H

2014-06-15

The advent of somatic cell reprogramming technologies-which enables the generation of patient-specific, induced pluripotent stem cell and other trans-differentiated human neuronal cell models-provides new means of gaining insight into the molecular mechanisms and neural substrates of psychiatric disorders. By allowing a more precise understanding of genotype-phenotype relationship in disease-relevant human cell types, the use of reprogramming technologies in tandem with emerging genome engineering approaches provides a previously "missing link" between basic research and translational efforts. In this review, we summarize advances in applying human pluripotent stem cell and reprogramming technologies to generate specific neural subtypes with a focus on the use of these in vitro systems for the discovery of small molecule-probes and novel therapeutics. Examples are given where human cell models of psychiatric disorders have begun to reveal new mechanistic insight into pathophysiology and simultaneously have provided the foundation for developing disease-relevant, phenotypic assays suitable for both functional genomic and chemical screens. A number of areas for future research are discussed, including the need to develop robust methodology for the reproducible, large-scale production of disease-relevant neural cell types in formats compatible with high-throughput screening modalities, including high-content imaging, multidimensional, signature-based screening, and in vitro network with multielectrode arrays. Limitations, including the challenges in recapitulating neurocircuits and non-cell autonomous phenotypes are discussed. Although these technologies are still in active development, we conclude that, as our understanding of how to efficiently generate and probe the plasticity of patient-specific stem models improves, their utility is likely to advance rapidly. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The genetical theory of social behaviour.

PubMed

Lehmann, Laurent; Rousset, François

2014-05-19

We survey the population genetic basis of social evolution, using a logically consistent set of arguments to cover a wide range of biological scenarios. We start by reconsidering Hamilton's (Hamilton 1964 J. Theoret. Biol. 7, 1-16 (doi:10.1016/0022-5193(64)90038-4)) results for selection on a social trait under the assumptions of additive gene action, weak selection and constant environment and demography. This yields a prediction for the direction of allele frequency change in terms of phenotypic costs and benefits and genealogical concepts of relatedness, which holds for any frequency of the trait in the population, and provides the foundation for further developments and extensions. We then allow for any type of gene interaction within and between individuals, strong selection and fluctuating environments and demography, which may depend on the evolving trait itself. We reach three conclusions pertaining to selection on social behaviours under broad conditions. (i) Selection can be understood by focusing on a one-generation change in mean allele frequency, a computation which underpins the utility of reproductive value weights; (ii) in large populations under the assumptions of additive gene action and weak selection, this change is of constant sign for any allele frequency and is predicted by a phenotypic selection gradient; (iii) under the assumptions of trait substitution sequences, such phenotypic selection gradients suffice to characterize long-term multi-dimensional stochastic evolution, with almost no knowledge about the genetic details underlying the coevolving traits. Having such simple results about the effect of selection regardless of population structure and type of social interactions can help to delineate the common features of distinct biological processes. Finally, we clarify some persistent divergences within social evolution theory, with respect to exactness, synergies, maximization, dynamic sufficiency and the role of genetic arguments.

Multidimensional effects in nonadiabatic statistical theories of spin- forbidden kinetics. A case study of 3O + CO → CO 2

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

Jasper, Ahren

2015-04-14

The appropriateness of treating crossing seams of electronic states of different spins as nonadiabatic transition states in statistical calculations of spin-forbidden reaction rates is considered. We show that the spin-forbidden reaction coordinate, the nuclear coordinate perpendicular to the crossing seam, is coupled to the remaining nuclear degrees of freedom. We found that this coupling gives rise to multidimensional effects that are not typically included in statistical treatments of spin-forbidden kinetics. Three qualitative categories of multidimensional effects may be identified: static multidimensional effects due to the geometry-dependence of the local shape of the crossing seam and of the spin–orbit coupling, dynamicalmore » multidimensional effects due to energy exchange with the reaction coordinate during the seam crossing, and nonlocal(history-dependent) multidimensional effects due to interference of the electronic variables at second, third, and later seam crossings. Nonlocal multidimensional effects are intimately related to electronic decoherence, where electronic dephasing acts to erase the history of the system. A semiclassical model based on short-time full-dimensional trajectories that includes all three multidimensional effects as well as a model for electronic decoherence is presented. The results of this multidimensional nonadiabatic statistical theory (MNST) for the 3O + CO → CO 2 reaction are compared with the results of statistical theories employing one-dimensional (Landau–Zener and weak coupling) models for the transition probability and with those calculated previously using multistate trajectories. The MNST method is shown to accurately reproduce the multistate decay-of-mixing trajectory results, so long as consistent thresholds are used. Furthermore, the MNST approach has several advantages over multistate trajectory approaches and is more suitable in chemical kinetics calculations at low temperatures and for complex systems. The error in statistical calculations that neglect multidimensional effects is shown to be as large as a factor of 2 for this system, with static multidimensional effects identified as the largest source of error.« less

Gene Expression Profiling of Benign and Malignant Pheochromocytoma

PubMed Central

BROUWERS, FREDERIEKE M.; ELKAHLOUN, ABDEL G.; MUNSON, PETER J.; EISENHOFER, GRAEME; BARB, JENNIFER; LINEHAN, W. MARSTON; LENDERS, JACQUES W.M.; DE KRIJGER, RONALD; MANNELLI, MASSIMO; UDELSMAN, ROBERT; OCAL, IDRIS T.; SHULKIN, BARRY L.; BORNSTEIN, STEFAN R.; BREZA, JAN; KSINANTOVA, LUCIA; PACAK, KAREL

2016-01-01

There are currently no reliable diagnostic and prognostic markers or effective treatments for malignant pheochromocytoma. This study used oligonucleotide microarrays to examine gene expression profiles in pheochromocytomas from 90 patients, including 20 with malignant tumors, the latter including metastases and primary tumors from which metastases developed. Other subgroups of tumors included those defined by tissue norepinephrine compared to epinephrine contents (i.e., noradrenergic versus adrenergic phenotypes), adrenal versus extra-adrenal locations, and presence of germline mutations of genes pre-disposing to the tumor. Correcting for the confounding influence of nora-drenergic versus adrenergic catecholamine phenotype by the analysis of variance revealed a larger and more accurate number of genes that discriminated benign from malignant pheochromocytomas than when the confounding influence of catecholamine phenotype was not considered. Seventy percent of these genes were underexpressed in malignant compared to benign tumors. Similarly, 89% of genes were underexpressed in malignant primary tumors compared to benign tumors, suggesting that malignant potential is largely characterized by a less-differentiated pattern of gene expression. The present database of differentially expressed genes provides a unique resource for mapping the pathways leading to malignancy and for establishing new targets for treatment and diagnostic and prognostic markers of malignant disease. The database may also be useful for examining mechanisms of tumorigenesis and genotype–phenotype relationships. Further progress on the basis of this database can be made from follow-up confirmatory studies, application of bioinformatics approaches for data mining and pathway analyses, testing in pheochromocytoma cell culture and animal model systems, and retrospective and prospective studies of diagnostic markers. PMID:17102123

Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity.

PubMed

Di Bonito, P; Pacifico, L; Chiesa, C; Valerio, G; Miraglia Del Giudice, E; Maffeis, C; Morandi, A; Invitti, C; Licenziati, M R; Loche, S; Tornese, G; Franco, F; Manco, M; Baroni, M G

2017-04-01

To investigate in a large sample of overweight/obese (OW/OB) children and adolescents the prevalence of prediabetic phenotypes such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and to assess their association with cardiometabolic risk (CMR) factors including hepatic steatosis (HS). Population data were obtained from the CARdiometabolic risk factors in children and adolescents in ITALY study. Between 2003 and 2013, 3088 youths (972 children and 2116 adolescents) received oral glucose tolerance test (OGTT) and were included in the study. In 798 individuals, abdominal ultrasound for identification of HS was available. The prevalence of IFG (3.2 vs. 3.3%) and IGT (4.6 vs. 5.0%) was similar between children and adolescents. Children with isolated IGT had a 2-11 fold increased risk of high LDL-C, non-HDL-C, Tg/HDL-C ratio, and low insulin sensitivity, when compared to those with normal glucose tolerance (NGT). No significant association of IFG with any CMR factor was found in children. Among adolescents, IGT subjects, and to a lesser extent those with IFG, showed a worse CMR profile compared to NGT subgroup. In the overall sample, IGT phenotype showed a twofold increased risk of HS compared to NGT subgroup. Our study shows an unexpected similar prevalence of IFG and IGT between children and adolescents with overweight/obesity. The IGT phenotype was associated with a worse CMR profile in both children and adolescents. Phenotyping prediabetes conditions by OGTT should be done as part of prediction and prevention of cardiometabolic diseases in OW/OB youth since early childhood.

Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of Microbiome-Behavior Relationships.

PubMed

Lyte, Mark; Fodor, Anthony A; Chapman, Clinton D; Martin, Gary G; Perez-Chanona, Ernesto; Jobin, Christian; Dess, Nancy K

2016-06-01

The microbiota-gut-brain axis is increasingly implicated in obesity, anxiety, stress, and other health-related processes. Researchers have proposed that gut microbiota may influence dietary habits, and pathways through the microbiota-gut-brain axis make such a relationship feasible; however, few data bear on the hypothesis. As a first step in the development of a model system, the gut microbiome was examined in rat lines selectively outbred on a taste phenotype with biobehavioral profiles that have diverged with respect to energy regulation, anxiety, and stress. Occidental low and high-saccharin-consuming rats were assessed for body mass and chow, water, and saccharin intake; littermate controls had shared cages with rats in the experimental group but were not assessed. Cecum and colon microbial communities were profiled using Illumina 16S rRNA sequencing and multivariate analysis of microbial diversity and composition. The saccharin phenotype was confirmed (low-saccharin-consuming rats, 0.7Δ% [0.9Δ%]; high-saccharin-consuming rats, 28.1Δ% [3.6Δ%]). Regardless of saccharin exposure, gut microbiota differed between lines in terms of overall community similarity and taxa at lower phylogenetic levels. Specifically, 16 genera in three phyla distinguished the lines at a 10% false discovery rate. The study demonstrates for the first time that rodent lines created through selective pressure on taste and differing on functionally related correlates host different microbial communities. Whether the microbiota are causally related to the taste phenotype or its correlates remains to be determined. These findings encourage further inquiry on the relationship of the microbiome to taste, dietary habits, emotion, and health.

Defining the Relationship Between Phenotypic and Genotypic Resistance Profiles of Multidrug-Resistant Enterobacterial Clinical Isolates.

PubMed

Galal, Lamis; Abdel Aziz, Neveen A; Hassan, Walaa M

2018-05-11

Fluoroquinolones and aminoglycosides offer effective therapy for extended-spectrum beta-lactamase (ESBL)-producing enterobacterial infections, but their usefulness is threatened by increasing resistant strains. This study was conducted to demonstrate the phenotypic outcomes of the coexistence of genetic determinants mediating resistance to extended-spectrum cephalosporins and quinolones in enterobacterial isolates collected from patients with health-care-associated infections in Egypt. ESBL phenotype was determined using double-disk synergy test (DDST). The PCR technique was used to detect the presence of the genes mediating quinolone resistance (qnr and aac(6')-Ib-cr) and coexistence with ESBL genes. We also examined the association between the genetic makeup of the isolates and their resistance profiles including effect on MIC results. Phenotypically ESBLs were detected in 60-82% of the enterobacterial isolates. ESBL, qnr and aac(6')-Ib-cr genes were detected with the following percentages in Citrobacter isolates (69%, 69%, and 43%, respectively), E.coli isolates (65%, 70%, and 45%, respectively), Enterobacter isolates (56%, 67%, and 33%, respectively), and finally Klebsiella isolates (42%, 66%, and 25%, respectively). The coexistence of these multiresistant genetic elements significantly increased the MIC values of the tested antibiotics from different classes. We suggest using blaTEM, blaCTX-M-15, qnr, and aac(6')-Ib-cr genes for better and faster prediction of suitable antibiotic therapy with effective doses against ESBL-producing isolates harboring plasmid-mediated quinolone resistance (PMQR) determinants. Amikacin, meropenem, gentamicin, and imipenem seem to be better choices of treatment for such life-threatening infections, because of their remaining highest activity.

Latent Cognitive Phenotypes in De Novo Parkinson's Disease: A Person-Centered Approach.

PubMed

LaBelle, Denise R; Walsh, Ryan R; Banks, Sarah J

2017-08-01

Cognitive impairment is an important aspect of Parkinson's disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson's Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor ("Weak-Overall"), average ("Typical-Overall"), and strong ("Strong-Overall") cognition. The remaining classes demonstrated unique patterns of cognition, characterized by "Strong-Memory," "Weak-Visuospatial," and "Amnestic" profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer's disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive change in the disease. (JINS, 2017, 23, 551-563).

Delving deeper into technological innovations to understand differences in rice quality.

PubMed

Calingacion, Mariafe; Fang, Lu; Quiatchon-Baeza, Lenie; Mumm, Roland; Riedel, Arthur; Hall, Robert D; Fitzgerald, Melissa

2015-12-01

Increasing demand for better quality rice varieties, which are also more suited to growth under sub-optimal cultivation conditions, is driving innovation in rice research. Here we have used a multi-disciplinary approach, involving SNP-based genotyping together with phenotyping based on yield analysis, metabolomic analysis of grain volatiles, and sensory panel analysis to determine differences between two contrasting rice varieties, Apo and IR64. Plants were grown under standard and drought-induced conditions. Results revealed important differences between the volatile profiles of the two rice varieties and we relate these differences to those perceived by the sensory panel. Apo, which is the more drought tolerant variety, was less affected by the drought condition concerning both sensory profile and yield; IR64, which has higher quality but is drought sensitive, showed greater differences in these characteristics in response to the two growth conditions. Metabolomics analyses using GCxGC-MS, followed by multivariate statistical analyses of the data, revealed a number of discriminatory compounds between the varieties, but also effects of the difference in cultivation conditions. Results indicate the complexity of rice volatile profile, even of non-aromatic varieties, and how metabolomics can be used to help link changes in aroma profile with the sensory phenotype. Our outcomes also suggest valuable multi-disciplinary approaches which can be used to help define the aroma profile in rice, and its underlying genetic background, in order to support breeders in the generation of improved rice varieties combining high yield with high quality, and tolerance of both these traits to climate change.

Text-mined phenotype annotation and vector-based similarity to improve identification of similar phenotypes and causative genes in monogenic disease patients.

PubMed

Saklatvala, Jake R; Dand, Nick; Simpson, Michael A

2018-05-01

The genetic diagnosis of rare monogenic diseases using exome/genome sequencing requires the true causal variant(s) to be identified from tens of thousands of observed variants. Typically a virtual gene panel approach is taken whereby only variants in genes known to cause phenotypes resembling the patient under investigation are considered. With the number of known monogenic gene-disease pairs exceeding 5,000, manual curation of personalized virtual panels using exhaustive knowledge of the genetic basis of the human monogenic phenotypic spectrum is challenging. We present improved probabilistic methods for estimating phenotypic similarity based on Human Phenotype Ontology annotation. A limitation of existing methods for evaluating a disease's similarity to a reference set is that reference diseases are typically represented as a series of binary (present/absent) observations of phenotypic terms. We evaluate a quantified disease reference set, using term frequency in phenotypic text descriptions to approximate term relevance. We demonstrate an improved ability to identify related diseases through the use of a quantified reference set, and that vector space similarity measures perform better than established information content-based measures. These improvements enable the generation of bespoke virtual gene panels, facilitating more accurate and efficient interpretation of genomic variant profiles from individuals with rare Mendelian disorders. These methods are available online at https://atlas.genetics.kcl.ac.uk/~jake/cgi-bin/patient_sim.py. © 2018 Wiley Periodicals, Inc.

On the Need for Multidimensional Stirling Simulations

NASA Technical Reports Server (NTRS)

Dyson, Rodger W.; Wilson, Scott D.; Tew, Roy C.; Demko, Rikako

2005-01-01

Given the cost and complication of simulating Stirling convertors, do we really need multidimensional modeling when one-dimensional capabilities exist? This paper provides a comprehensive description of when and why multidimensional simulation is needed.

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms

PubMed Central

Esplin, M Sean; Manuck, Tracy A.; Varner, Michael W.; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

2015-01-01

Objective We sought to employ an innovative tool based on common biological pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB), in order to enhance investigators' ability to identify to highlight common mechanisms and underlying genetic factors responsible for SPTB. Study Design A secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks gestation. Each woman was assessed for the presence of underlying SPTB etiologies. A hierarchical cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis using VEGAS software. Results 1028 women with SPTB were assigned phenotypes. Hierarchical clustering of the phenotypes revealed five major clusters. Cluster 1 (N=445) was characterized by maternal stress, cluster 2 (N=294) by premature membrane rupture, cluster 3 (N=120) by familial factors, and cluster 4 (N=63) by maternal comorbidities. Cluster 5 (N=106) was multifactorial, characterized by infection (INF), decidual hemorrhage (DH) and placental dysfunction (PD). These three phenotypes were highly correlated by Chi-square analysis [PD and DH (p<2.2e-6); PD and INF (p=6.2e-10); INF and DH (p=0.0036)]. Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarchal clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors underlying SPTB. PMID:26070700

Specific CAPN10 gene haplotypes influence the clinical profile of polycystic ovary patients.

PubMed

Gonzalez, Alejandro; Abril, Eduardo; Roca, Alfredo; Aragón, Maria José; Figueroa, Maria José; Velarde, Pilar; Ruiz, Rocío; Fayez, Omar; Galán, José Jorge; Herreros, José Antonio; Real, Luis Miguel; Ruiz, Agustín

2003-11-01

Recently, several research groups have evaluated CAPN10 gene in polycystic ovarian syndrome (PCOS) patients and other phenotypes, including hirsutism or intermediate phenotypes of PCOS. Molecular genetic analysis of CAPN10 gene indicates that different alleles may play a role in PCOS susceptibility and could be associated with idiopathic hirsutism. However, these observations are not exempt from controversy, because independent studies cannot replicate these preliminary findings. We present a haplotype-phenotype correlation study of CAPN10 haplotypes in 148 women showing ecographically detected polycystic ovaries (PCO) combined with one or more of these clinical symptoms: amenorrhea or severe oligomenorrhea, hyperandrogenism, and anovulatory infertility, as well as 93 unrelated controls. We have reconstructed and analyzed 482 CAPN10 haplotypes in patients and controls. We detected the association of UCSNP-44 allele with PCO phenotype in the Spanish population (P = 0.02). In addition, we identified several CAPN10 alleles associated to phenotypic differences observed between PCO patients, such as the presence of hypercholesterolemia (haplotype 1121, P = 0.005), presence of hyperandrogenic features (P = 0.05), and familial cancer incidence (haplotype 1111, P = 0.0005). Our results confirm the association of UCSNP-44 allele with PCO phenotype in the Spanish population. Moreover, we have identified novel candidate risk alleles and genotypes, within CAPN10 gene, that could be associated with important phenotypic and prognosis differences observed in PCOS patients.

Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study.

PubMed

Loza, Matthew J; Djukanovic, Ratko; Chung, Kian Fan; Horowitz, Daniel; Ma, Keying; Branigan, Patrick; Barnathan, Elliot S; Susulic, Vedrana S; Silkoff, Philip E; Sterk, Peter J; Baribaud, Frédéric

2016-12-15

Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. NCT01274507 (ADEPT), registered October 28, 2010 and NCT01982162 (U-BIOPRED), registered October 30, 2013.