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Sample records for multidimensional phenotypic profiling

  1. Multidimensionality of behavioural phenotypes in Atlantic cod, Gadus morhua.

    PubMed

    Meager, Justin J; Fernö, Anders; Skjæraasen, Jon Egil; Järvi, Torbjörn; Rodewald, Petra; Sverdrup, Gisle; Winberg, Svante; Mayer, Ian

    2012-06-25

    Much of the inter-individual variation observed in animal behaviour is now attributed to the existence of behavioural phenotypes or animal personalities. Such phenotypes may be fundamental to fisheries and aquaculture, yet there have been few detailed studies of this phenomenon in exploited marine animals. We investigated the behavioural and neuroendocrine responses of Atlantic cod (Gadus morhua L.), to situations reflecting critical ecological challenges: predator attacks and territorial challenges. Both hatchery-reared and wild fish were tested and behavioural profiles were compared with baseline conditions. We then used an objective, multivariate approach, rather than assigning individuals along one-dimensional behavioural axes, to examine whether distinct behavioural phenotypes were present. Our results indicate that two distinct behavioural phenotypes were evident in fish from each background. In hatchery-reared fish, phenotypes displayed divergent locomotor activity, sheltering, brain monoamine concentrations and responses to competitive challenges. In wild fish, phenotypes were distinguished primarily by locomotor activity, sheltering and responsiveness to predator stimuli. Hatcheries presumably represent a more stressful social environment, and social behaviour and neuroendocrine responses were important in discerning behavioural phenotypes in hatchery fish, whereas antipredator responses were important in discerning phenotypes in wild fish that have previously encountered predators. In both fish types, behavioural and physiological traits that classified individuals into phenotypes were not the same as those that were correlated across situations. These results highlight the multidimensionality of animal personalities, and that the processes that regulate one suite of behavioural traits may be very different to the processes that regulate other behaviours. PMID:22465310

  2. Multidimensional Clinical Phenotyping of an Adult Cystic Fibrosis Patient Population

    PubMed Central

    Conrad, Douglas J.; Bailey, Barbara A.

    2015-01-01

    Background Cystic Fibrosis (CF) is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease. Methods The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM) algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier. Findings Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1) a low lung health scores phenotype, 2) a younger, well-nourished, male-dominated class, 3) various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency. Interpretation This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study. PMID:25822311

  3. Multidimensional profiling of cell surface proteins and nuclear markers

    SciTech Connect

    Han, Ju; Chang, Hang; Andarawewa, Kumari; Yaswen, Paul; Helen Barcellos-Hoff, Mary; Parvin, Bahram

    2009-01-30

    Cell membrane proteins play an important role in tissue architecture and cell-cell communication. We hypothesize that segmentation and multidimensional characterization of the distribution of cell membrane proteins, on a cell-by-cell basis, enable improved classification of treatment groups and identify important characteristics that can otherwise be hidden. We have developed a series of computational steps to (i) delineate cell membrane protein signals and associate them with a specific nucleus; (ii) compute a coupled representation of the multiplexed DNA content with membrane proteins; (iii) rank computed features associated with such a multidimensional representation; (iv) visualize selected features for comparative evaluation through heatmaps; and (v) discriminate between treatment groups in an optimal fashion. The novelty of our method is in the segmentation of the membrane signal and the multidimensional representation of phenotypic signature on a cell-by-cell basis. To test the utility of this method, the proposed computational steps were applied to images of cells that have been irradiated with different radiation qualities in the presence and absence of other small molecules. These samples are labeled for their DNA content and E-cadherin membrane proteins. We demonstrate that multidimensional representations of cell-by-cell phenotypes improve predictive and visualization capabilities among different treatment groups, and identify hidden variables.

  4. Estimating Cognitive Profiles Using Profile Analysis via Multidimensional Scaling (PAMS)

    ERIC Educational Resources Information Center

    Kim, Se-Kang; Frisby, Craig L.; Davison, Mark L.

    2004-01-01

    Two of the most popular methods of profile analysis, cluster analysis and modal profile analysis, have limitations. First, neither technique is adequate when the sample size is large. Second, neither method will necessarily provide profile information in terms of both level and pattern. A new method of profile analysis, called Profile Analysis via…

  5. 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

  6. Evaluating the Invariance of Cognitive Profile Patterns Derived from Profile Analysis via Multidimensional Scaling (PAMS): A Bootstrapping Approach

    ERIC Educational Resources Information Center

    Kim, Se-Kang

    2010-01-01

    The aim of the current study is to validate the invariance of major profile patterns derived from multidimensional scaling (MDS) by bootstrapping. Profile Analysis via Multidimensional Scaling (PAMS) was employed to obtain profiles and bootstrapping was used to construct the sampling distributions of the profile coordinates and the empirical…

  7. Multidimensional Dyspnea Profile: an instrument for clinical and laboratory research

    PubMed Central

    O'Donnell, Carl R.; Guilfoyle, Tegan E.; Parshall, Mark B.; Schwartzstein, Richard M.; Meek, Paula M.; Gracely, Richard H.; Lansing, Robert W.

    2015-01-01

    There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence regarding its measurement properties and discuss its use and interpretation. The MDP assesses dyspnoea during a specific time or a particular activity (focus period) and is designed to examine individual items that are theoretically aligned with separate mechanisms. In contrast, other multidimensional dyspnoea scales assess recalled recent dyspnoea over a period of days using aggregate scores. Previous psychophysical and psychometric studies using the MDP show that: 1) subjects exposed to different laboratory stimuli could discriminate between air hunger and work/effort sensation, and found air hunger more unpleasant; 2) the MDP immediate unpleasantness scale (A1) was convergent with common dyspnoea scales; 3) in emergency department patients, two domains were distinguished (immediate perception, emotional response); 4) test–retest reliability over hours was high; 5) the instrument responded to opioid treatment of experimental dyspnoea and to clinical improvement; 6) convergent validity with common instruments was good; and 7) items responded differently from one another as predicted for multiple dimensions. PMID:25792641

  8. Target deconvolution techniques in modern phenotypic profiling

    PubMed Central

    Lee, Jiyoun; Bogyo, Matthew

    2013-01-01

    The past decade has seen rapid growth in the use of diverse compound libraries in classical phenotypic screens to identify modulators of a given process. The subsequent process of identifying the molecular targets of active hits, also called ‘target deconvolution’, is an essential step for understanding compound mechanism of action and for using the identified hits as tools for further dissection of a given biological process. Recent advances in ‘omics’ technologies, coupled with in silico approaches and the reduced cost of whole genome sequencing, have greatly improved the workflow of target deconvolution and have contributed to a renaissance of ‘modern’ phenotypic profiling. In this review, we will outline how both new and old techniques are being used in the difficult process of target identification and validation as well as discuss some of the ongoing challenges remaining for phenotypic screening. PMID:23337810

  9. Bifactor Approach to Modeling Multidimensionality of Physical Self-Perception Profile

    ERIC Educational Resources Information Center

    Chung, ChihMing; Liao, Xiaolan; Song, Hairong; Lee, Taehun

    2016-01-01

    The multi-dimensionality of Physical Self-Perception Profile (PSPP) has been acknowledged by the use of correlated-factor model and second-order model. In this study, the authors critically endorse the bifactor model, as a substitute to address the multi-dimensionality of PSPP. To cross-validate the models, analyses are conducted first in…

  10. Multidimensional Profiling Platforms Reveal Metabolic Dysregulation caused by Organophosphorus Pesticides

    PubMed Central

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

    2014-01-01

    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 utilizing multidimensional profiling approaches to obtain a more complete understanding of toxicities associated with environmental chemicals. PMID:24205821

  11. Tissue dynamics spectroscopy for phenotypic profiling of drug effects in three-dimensional culture.

    PubMed

    Nolte, David D; An, Ran; Turek, John; Jeong, Kwan

    2012-11-01

    Coherence-gated dynamic light scattering captures cellular dynamics through ultra-low-frequency (0.005-5 Hz) speckle fluctuations and Doppler shifts that encode a broad range of cellular and subcellular motions. The dynamic physiological response of tissues to applied drugs is the basis for a new type of phenotypic profiling for drug screening on multicellular tumor spheroids. Volumetrically resolved tissue-response fluctuation spectrograms act as fingerprints that are segmented through feature masks into high-dimensional feature vectors. Drug-response clustering is achieved through multidimensional scaling with simulated annealing to construct phenotypic drug profiles that cluster drugs with similar responses. Hypoxic vs. normoxic tissue responses present two distinct phenotypes with differentiated responses to environmental perturbations and to pharmacological doses. PMID:23162721

  12. A Grand Challenge. 2. Phenotypic Profiling of a Natural Product Library on Parkinson's Patient-Derived Cells.

    PubMed

    Vial, Marie-Laure; Zencak, Dusan; Grkovic, Tanja; Gorse, Alain-Dominique; Mackay-Sim, Alan; Mellick, George D; Wood, Stephen A; Quinn, Ronald J

    2016-08-26

    Harnessing the inherent biological relevance of natural products requires a method for the recognition of biological effects that may subsequently lead to the discovery of particular targets. An unbiased multidimensional profiling method was used to examine the activities of natural products on primary cells derived from a Parkinson's disease patient. The biological signature of 482 natural products was examined using multiparametric analysis to investigate known cellular pathways and organelles implicated in Parkinson's disease such as mitochondria, lysosomes, endosomes, apoptosis, and autophagy. By targeting several cell components simultaneously the chance of finding a phenotype was increased. The phenotypes were then clustered using an uncentered correlation. The multidimensional phenotypic screening showed that all natural products, in our screening set, were biologically relevant compounds as determined by an observed phenotypic effect. Multidimensional phenotypic screening can predict the cellular function and subcellular site of activity of new compounds, while the cluster analysis provides correlation with compounds with known mechanisms of action. This study reinforces the value of natural products as biologically relevant compounds. PMID:27447544

  13. Advances in Human B Cell Phenotypic Profiling

    PubMed Central

    Kaminski, Denise A.; Wei, Chungwen; Qian, Yu; Rosenberg, Alexander F.; Sanz, Ignacio

    2012-01-01

    To advance our understanding and treatment of disease, research immunologists have been called-upon to place more centralized emphasis on impactful human studies. Such endeavors will inevitably require large-scale study execution and data management regulation (“Big Biology”), necessitating standardized and reliable metrics of immune status and function. A well-known example setting this large-scale effort in-motion is identifying correlations between eventual disease outcome and T lymphocyte phenotype in large HIV-patient cohorts using multiparameter flow cytometry. However, infection, immunodeficiency, and autoimmunity are also characterized by correlative and functional contributions of B lymphocytes, which to-date have received much less attention in the human Big Biology enterprise. Here, we review progress in human B cell phenotyping, analysis, and bioinformatics tools that constitute valuable resources for the B cell research community to effectively join in this effort. PMID:23087687

  14. Determining the significance of scale values from multidimensional scaling profile analysis using a resampling method.

    PubMed

    Ding, Cody S

    2005-02-01

    Although multidimensional scaling (MDS) profile analysis is widely used to study individual differences, there is no objective way to evaluate the statistical significance of the estimated scale values. In the present study, a resampling technique (bootstrapping) was used to construct confidence limits for scale values estimated from MDS profile analysis. These bootstrap confidence limits were used, in turn, to evaluate the significance of marker variables of the profiles. The results from analyses of both simulation data and real data suggest that the bootstrap method may be valid and may be used to evaluate hypotheses about the statistical significance of marker variables of MDS profiles. PMID:16097342

  15. Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles

    PubMed Central

    Hu, Shijia; Parker, Joel; Divaris, Kimon; Padilla, Ricardo; Murrah, Valerie; Wright, John Timothy

    2016-01-01

    Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50–80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human “dentome”) for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p < 0.05). Common pathways altered in both clusters included cell-cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer-driving genes such as TP53 and members of the MAPkinase pathways. The pre-secretory ameloblast cluster exhibited higher activation of inflammatory pathways while the odontoblast cluster showed greater disturbances in transcription regulators. Our results are suggestive of underlying inter-tumor molecular heterogeneity of ameloblastoma sub-types and have implications for the use of tailored treatment. PMID:27491308

  16. Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles.

    PubMed

    Hu, Shijia; Parker, Joel; Divaris, Kimon; Padilla, Ricardo; Murrah, Valerie; Wright, John Timothy

    2016-01-01

    Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50-80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human "dentome") for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p < 0.05). Common pathways altered in both clusters included cell-cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer-driving genes such as TP53 and members of the MAPkinase pathways. The pre-secretory ameloblast cluster exhibited higher activation of inflammatory pathways while the odontoblast cluster showed greater disturbances in transcription regulators. Our results are suggestive of underlying inter-tumor molecular heterogeneity of ameloblastoma sub-types and have implications for the use of tailored treatment. PMID:27491308

  17. Multidimensional assessment of neuroendocrine and psychopathological profiles in maltreated youth.

    PubMed

    Puetz, Vanessa B; Zweerings, Jana; Dahmen, Brigitte; Ruf, Caroline; Scharke, Wolfgang; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2016-09-01

    It has been debated whether children who have experienced early life stress (ELS), such as early caregiver separation show elevated risk for stress-related psychiatric disorders and a multi-symptom psychopathological profile that is not fully reflected in categorical assessments. In this study, we investigated dimensional measures of stress-related psychopathology in children in permanent out-of-home care, taking into account potential neuroendocrine interactions. In the current study, 25 children who had been placed in permanent out-of-home care before age 3 (years) and 26 controls (aged 10.6 ± 1.75 years) were investigated with categorical (DSM-IV) and dimensional assessments (CBCL) of psychopathology and diurnal salivary cortisol levels were assessed. Semi-structured interviews (K-DIPS) revealed no significant group differences in full-scale psychiatric diagnoses, whereas dimensional assessment (CBCL) revealed significant group differences in externalizing and total problem behaviours within the clinical range for children with ELS. Only children with ELS showed a combined symptom profile of clinical-range internalizing and externalizing problems. Lower morning cortisol values and subsequent flatter decline was found in subjects with ELS children compared to controls, showing group differences in diurnal cortisol secretion. Lower morning cortisol values were associated with more problem behaviour in the ELS group. Results show that ELS children exhibited increased psychopathological symptom severity and complexity associated with lower morning cortisol levels, which was not fully reflected in categorical assessments. This highlights the importance of incorporating dimensional assessments and neurobiological factors into psychopathological evaluations of children in out-of-home care in order to facilitate early identification of children at high risk for stress-related disorders. PMID:26875183

  18. Phenotype Microarray Profiling of Zymomonas mobilis ZM4

    SciTech Connect

    Bochner, Barry; Gomez, Vanessa; Ziman, michael; Yang, Shihui; Brown, Steven D

    2009-01-01

    In this study, we developed a Phenotype MicroArray{trademark} (PM) protocol to profile cellular phenotypes in Zymomonas mobilis, which included a standard set of nearly 2,000 assays for carbon, nitrogen, phosphorus and sulfur source utilization, nutrient stimulation, pH and osmotic stresses, and chemical sensitivities with 240 inhibitory chemicals. We observed two positive assays for C-source utilization (fructose and glucose) using the PM screen, which uses redox chemistry and cell respiration as a universal reporter to profile growth phenotypes in a high-throughput 96-well plate-based format. For nitrogen metabolism, the bacterium showed a positive test results for ammonia, aspartate, asparagine, glutamate, glutamine, and peptides. Z. mobilis appeared to use a diverse array of P-sources with two exceptions being pyrophosphate and tripolyphosphate. The assays suggested that Z. mobilis uses both inorganic and organic compounds as S-sources. No stimulation by nutrients was detected; however, there was evidence of partial inhibition by purines and pyrimidines, NAD, and deferoxamine. Z. mobilis was relatively resistant to acid pH, tolerating a pH down to about 4.0. It also tolerated phosphate, sulfate, and nitrate, but was rather sensitive to chloride and nitrite. Z. mobilis showed resistance to a large number of diverse chemicals that inhibit most bacteria. The information from PM analysis provides an overview of Z. mobilis physiology and a foundation for future comparisons of other wild-type and mutant Z. mobilis strains.

  19. Differentiating Asthma Phenotypes in Young Adults through Polyclonal Cytokine Profiles

    PubMed Central

    Zoratti, Edward; Havstad, Suzanne; Wegienka, Ganesa; Nicholas, Charlotte; Bobbitt, Kevin R.; Woodcroft, Kimberley J.; Ownby, Dennis R.; Johnson, Christine Cole

    2014-01-01

    Background Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiological and clinical studies. While allergic asthma and non-allergic asthma are frequently combined into one disease category in observational research and clinical trials, few studies have investigated the extent to which these two separate phenotypes are associated with distinct cytokine immunological profiles in a representative young adult population. Objective To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and non-allergic asthma among a population-based birth cohort evaluated as young adults. Methods Subjects included 18–21 year-old members (n=540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. PMA-stimulated whole blood IL4, IL5, IL10, IL12, IL13, IL17A, IL17F, IL22 and IFNγ secretory responses were analyzed for associations comparing participants with allergic versus non-allergic asthma phenotypes to those without asthma. Results Th2-polarized responses, measured as higher mean IL5 and IL13 secretion and lower ratios of IFNγ and IL12 to three Th2 cytokines IL4, IL5, or IL13, were observed only in allergic asthmatics. Non-allergic asthma was associated with Th1-polarized responses including higher adjusted IFNγ secretion compared to both allergic asthmatics and surprisingly, to those without asthma [OR=2.5 (1.2–5.1), p<0.01]. Conclusions As expected, young adults with a history of an allergic asthma phenotype exhibit a Th2-polarized cytokine response after polyclonal stimulation. However, Th1-polarization was observed in subjects with a history of non-allergic asthma. Allergic and non-allergic asthma are associated with etiologically distinct immune endotypes underscoring the importance of discriminating these endotypes in research analyses and clinical management. PMID:24801891

  20. Automated Analysis and Classification of Histological Tissue Features by Multi-Dimensional Microscopic Molecular Profiling

    PubMed Central

    Riordan, Daniel P.; Varma, Sushama; West, Robert B.; Brown, Patrick O.

    2015-01-01

    Characterization of the molecular attributes and spatial arrangements of cells and features within complex human tissues provides a critical basis for understanding processes involved in development and disease. Moreover, the ability to automate steps in the analysis and interpretation of histological images that currently require manual inspection by pathologists could revolutionize medical diagnostics. Toward this end, we developed a new imaging approach called multidimensional microscopic molecular profiling (MMMP) that can measure several independent molecular properties in situ at subcellular resolution for the same tissue specimen. MMMP involves repeated cycles of antibody or histochemical staining, imaging, and signal removal, which ultimately can generate information analogous to a multidimensional flow cytometry analysis on intact tissue sections. We performed a MMMP analysis on a tissue microarray containing a diverse set of 102 human tissues using a panel of 15 informative antibody and 5 histochemical stains plus DAPI. Large-scale unsupervised analysis of MMMP data, and visualization of the resulting classifications, identified molecular profiles that were associated with functional tissue features. We then directly annotated H&E images from this MMMP series such that canonical histological features of interest (e.g. blood vessels, epithelium, red blood cells) were individually labeled. By integrating image annotation data, we identified molecular signatures that were associated with specific histological annotations and we developed statistical models for automatically classifying these features. The classification accuracy for automated histology labeling was objectively evaluated using a cross-validation strategy, and significant accuracy (with a median per-pixel rate of 77% per feature from 15 annotated samples) for de novo feature prediction was obtained. These results suggest that high-dimensional profiling may advance the development of computer

  1. Quantitative phenotypic and pathway profiling guides rational drug combination strategies

    PubMed Central

    Dawson, John C.; Carragher, Neil O.

    2014-01-01

    Advances in target-based drug discovery strategies have enabled drug discovery groups in academia and industry to become very effective at generating molecules that are potent and selective against single targets. However, it has become apparent from disappointing results in recent clinical trials that a major challenge to the development of successful targeted therapies for treating complex multifactorial diseases is overcoming heterogeneity in target mechanism among patients and inherent or acquired drug resistance. Consequently, reductionist target directed drug-discovery approaches are not appropriately tailored toward identifying and optimizing multi-targeted therapeutics or rational drug combinations for complex disease. In this article, we describe the application of emerging high-content phenotypic profiling and analysis tools to support robust evaluation of drug combination performance following dose-ratio matrix screening. We further describe how the incorporation of high-throughput reverse phase protein microarrays with phenotypic screening can provide rational drug combination hypotheses but also confirm the mechanism-of-action of novel drug combinations, to facilitate future preclinical and clinical development strategies. PMID:24904421

  2. Further Evidence Supporting the Validity of Both a Multidimensional Profile and an Overall Evaluation of Teaching Effectiveness

    ERIC Educational Resources Information Center

    Burdsal, Charles A.; Harrison, Paul D.

    2008-01-01

    The purpose of this research is to provide additional empirical evidence supporting the use of both a multidimensional profile and an overall evaluation of teaching effectiveness as valid indicators of student perceptions of effective classroom instruction. A factor analytic teaching evaluation instrument was used that also included open-ended…

  3. Plasma exosome profiles from dairy cows with divergent fertility phenotypes.

    PubMed

    Mitchell, M D; Scholz-Romero, K; Reed, S; Peiris, H N; Koh, Y Q; Meier, S; Walker, C G; Burke, C R; Roche, J R; Rice, G; Salomon, C

    2016-09-01

    Cell-to-cell communication in physiological and pathological conditions may be influenced by neighboring cells, distant tissues, or local environmental factors. Exosomes are specific subsets of extracellular vesicles that internalize and deliver their content to near and distant sites. Exosomes may play a role in the maternal-embryo crosstalk vital for the recognition and maintenance of a pregnancy; however, their role in dairy cow reproduction has not been established. This study aimed to characterize the exosome profile in the plasma of 2 strains of dairy cow with divergent fertility phenotypes. Plasma was obtained and characterized on the basis of genetic ancestry as fertile (FERT; <23% North American genetics, New Zealand Holstein-Friesian strain, n=8) or subfertile (SUBFERT; >92% North American genetics, North American Holstein-Friesian strain, n=8). Exosomes were isolated by differential and buoyant density centrifugation and characterized by size distribution (nanoparticle tracking analysis, NanoSight NS500, NanoSight Ltd., Amesbury, UK), the presence of CD63 (Western blot), and their morphology (electron microscopy). The total number of exosomes was determined by quantifying the immunoreactive CD63 (ExoELISA kit, System Biosciences), and the protein content established by mass spectrometry. Enriched exosome fractions were identified as cup-shape vesicles with diameters around 100 nm and positive for the CD63 marker. The concentration of exosomes was 50% greater in FERT cows. Mass spectrometry identified 104 and 117 proteins in FERT and SUBFERT cows, of which 23 and 36 were unique, respectively. Gene ontology analysis revealed enrichment for proteins involved in immunomodulatory processes and cell-to-cell communication. Although the role of exosomes in dairy cow reproduction remains to be elucidated, their quantification and content in models with divergent fertility phenotypes could provide novel information to support both physiological and genetic

  4. Next-generation biobanking of metastases to enable multidimensional molecular profiling in personalized medicine.

    PubMed

    Diaz, Zuanel; Aguilar-Mahecha, Adriana; Paquet, Eric R; Basik, Mark; Orain, Michèle; Camlioglu, Errol; Constantin, André; Benlimame, Naciba; Bachvarov, Dimcho; Jannot, Guillaume; Simard, Martin J; Chabot, Benoit; Gologan, Adrian; Klinck, Roscoe; Gagnon-Kugler, Thérèse; Lespérance, Bernard; Samson, Benoit; Kavan, Petr; Alcindor, Thierry; Dalfen, Richard; Lan, Cathy; Chabot, Catherine; Buchanan, Marguerite; Przybytkowski, Ewa; Qureshi, Samia; Rousseau, Caroline; Spatz, Alan; Têtu, Bernard; Batist, Gerald

    2013-11-01

    Great advances in analytical technology coupled with accelerated new drug development and growing understanding of biological challenges, such as tumor heterogeneity, have required a change in the focus for biobanking. Most current banks contain samples of primary tumors, but linking molecular signatures to therapeutic questions requires serial biopsies in the setting of metastatic disease, next-generation of biobanking. Furthermore, an integration of multidimensional analysis of various molecular components, that is, RNA, DNA, methylome, microRNAome and post-translational modifications of the proteome, is necessary for a comprehensive view of a tumor's biology. While data using such biopsies are now regularly presented, the preanalytical variables in tissue procurement and processing in multicenter studies are seldom detailed and therefore are difficult to duplicate or standardize across sites and across studies. In the context of a biopsy-driven clinical trial, we generated a detailed protocol that includes morphological evaluation and isolation of high-quality nucleic acids from small needle core biopsies obtained from liver metastases. The protocol supports stable shipping of samples to a central laboratory, where biopsies are subsequently embedded in support media. Designated pathologists must evaluate all biopsies for tumor content and macrodissection can be performed if necessary to meet our criteria of >60% neoplastic cells and <20% necrosis for genomic isolation. We validated our protocol in 40 patients who participated in a biopsy-driven study of therapeutic resistance in metastatic colorectal cancer. To ensure that our protocol was compatible with multiplex discovery platforms and that no component of the processing interfered with downstream enzymatic reactions, we performed array comparative genomic hybridization, methylation profiling, microRNA profiling, splicing variant analysis and gene expression profiling using genomic material isolated from

  5. Extracting body image symptom dimensions among eating disorder patients: the Profile Analysis via Multidimensional Scaling (PAMS) approach.

    PubMed

    Olatunji, Bunmi O; Kim, Se-Kang; Wall, David

    2015-09-01

    The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a procedure for extracting dimensions, in order to identify core eating disorder symptoms in a clinical sample. A large sample of patients with eating disorders (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI-2; Garner, 1991), and PAMS was then employed to estimate individual profile weights that reflect the degree to which an individual's observed symptom profile approximates the pattern of the dimensions. The findings revealed three symptom dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent analysis using individual level data illustrate that the PAMS profiles properly operate as prototypical profiles that encapsulate all individuals' response patterns. The implications of these dimensional findings for the assessment and diagnosis of eating disorders are discussed. PMID:25996520

  6. Unique DNA methylome profiles in CpG island methylator phenotype colon cancers.

    PubMed

    Xu, Yaomin; Hu, Bo; Choi, Ae-Jin; Gopalan, Banu; Lee, Byron H; Kalady, Matthew F; Church, James M; Ting, Angela H

    2012-02-01

    A subset of colorectal cancers was postulated to have the CpG island methylator phenotype (CIMP), a higher propensity for CpG island DNA methylation. The validity of CIMP, its molecular basis, and its prognostic value remain highly controversial. Using MBD-isolated genome sequencing, we mapped and compared genome-wide DNA methylation profiles of normal, non-CIMP, and CIMP colon specimens. Multidimensional scaling analysis revealed that each specimen could be clearly classified as normal, non-CIMP, and CIMP, thus signifying that these three groups have distinctly different global methylation patterns. We discovered 3780 sites in various genomic contexts that were hypermethylated in both non-CIMP and CIMP colon cancers when compared with normal colon. An additional 2026 sites were found to be hypermethylated in CIMP tumors only; and importantly, 80% of these sites were located in CpG islands. These data demonstrate on a genome-wide level that the additional hypermethylation seen in CIMP tumors occurs almost exclusively at CpG islands and support definitively that these tumors were appropriately named. When these sites were examined more closely, we found that 25% were adjacent to sites that were also hypermethylated in non-CIMP tumors. Thus, CIMP is also characterized by more extensive methylation of sites that are already prone to be hypermethylated in colon cancer. These observations indicate that CIMP tumors have specific defects in controlling both DNA methylation seeding and spreading and serve as an important first step in delineating molecular mechanisms that control these processes. PMID:21990380

  7. Phenotype profile of a genetic mouse model for Muenke syndrome

    PubMed Central

    Koyama, Eiki; Agochukwu, Nneamaka B.; Bartlett, Scott P.; Muenke, Maximilian

    2014-01-01

    Purpose The Muenke syndrome mutation (FGFR3P250R), which was discovered 15 years ago, represents the single most common craniosynostosis mutation. Muenke syndrome is characterized by coronal suture synostosis, mid-face hypoplasia, subtle limb anomalies, and hearing loss. However, the spectrum of clinical presentation continues to expand. To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3P244R) and compare them with human phenotypes. Conclusions FgfR3P244R mutant mice show premature fusion of facial sutures, premaxillary and/or zygomatic sutures, but rarely the coronal suture. The mice also lack the typical limb phenotype. On the other hand, the mutant mice display maxillary retrusion in association with a shortening of the anterior cranial base and a premature closure of intersphenoidal and spheno-occipital synchondroses, resembling human midface hypoplasia. In addition, sensorineural hearing loss is detected in all FgfR3P244R mutant mice as in the majority of Muenke syndrome patients. It is caused by a defect in the mechanism of cell fate determination in the organ of Corti. The mice also express phenotypes that have not been previously described in humans, such as reduced cortical bone thickness, hypoplastic trabecular bone, and defective temporomandibular joint structure. Therefore, the FgfR3P244R mouse provides an excellent opportunity to study disease mechanisms of some classical phenotypes of Muenke syndrome and to test novel therapeutic strategies. The mouse model can also be further explored to discover previously unreported yet potentially significant phenotypes of Muenke syndrome. PMID:22872265

  8. Toward a multidimensional understanding of residential neighborhood: a latent profile analysis of Los Angeles neighborhoods and longitudinal adult excess weight

    PubMed Central

    Jones, Malia; Huh, Jimi

    2015-01-01

    People are embedded in a complex socio-spatial context that may affect their weight status through multiple mechanisms, including food & physical activity opportunities and chronic stress exposure. However, research to date has been unable to resolve what features of neighborhoods are causally related to weight status. We used latent profile analysis to identify three “types” of neighborhoods (based on five dimensions of neighborhood social status) in Los Angeles, CA. Our neighborhood types were both substantively interpretable and predictive of excess weight in both cross-sectional and longitudinal models. Our results are promising for a research community attempting to operationalize neighborhoods as multidimensional, complex systems. PMID:24607872

  9. Phenotypic and functional profiling of mouse intestinal antigen presenting cells.

    PubMed

    Harusato, Akihito; Flannigan, Kyle L; Geem, Duke; Denning, Timothy L

    2015-06-01

    The microbiota that populates the mammalian intestine consists of hundreds of trillions of bacteria that are separated from underlying immune cells by a single layer of epithelial cells. The intestinal immune system effectively tolerates components of the microbiota that provide benefit to the host while remaining poised to eliminate those that are harmful. Antigen presenting cells, especially macrophages and dendritic cells, play important roles in maintaining intestinal homeostasis via their ability to orchestrate appropriate responses to the microbiota. Paramount to elucidating intestinal macrophage- and dendritic cell-mediated functions is the ability to effectively isolate and identify these cells from a complex cellular environment. In this review, we summarize methodology for the isolation and phenotypic characterization of macrophages and DCs from the mouse intestine and discuss how this may be useful for gaining insight into the mechanisms by which mucosal immune tolerance is maintained. PMID:25891794

  10. Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes

    PubMed Central

    Chen, Rui; Mias, George I.; Li-Pook-Than, Jennifer; Jiang, Lihua; Lam, Hugo Y. K.; Chen, Rong; Miriami, Elana; Karczewski, Konrad J.; Hariharan, Manoj; Dewey, Frederick E.; Cheng, Yong; Clark, Michael J.; Im, Hogune; Habegger, Lukas; Balasubramanian, Suganthi; O'Huallachain, Maeve; Dudley, Joel T.; Hillenmeyer, Sara; Haraksingh, Rajini; Sharon, Donald; Euskirchen, Ghia; Lacroute, Phil; Bettinger, Keith; Boyle, Alan P.; Kasowski, Maya; Grubert, Fabian; Seki, Scott; Garcia, Marco; Whirl-Carrillo, Michelle; Gallardo, Mercedes; Blasco, Maria A.; Greenberg, Peter L.; Snyder, Phyllis; Klein, Teri E.; Altman, Russ B.; Butte, Atul; Ashley, Euan A.; Nadeau, Kari C.; Gerstein, Mark; Tang, Hua; Snyder, Michael

    2012-01-01

    SUMMARY Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here we present an integrative Personal Omics Profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14-month period. Our iPOP analysis revealed various medical risks, including Type II diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high coverage genomic and transcriptomic data, which provide the basis of our iPOP, discovered extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and disease states by connecting genomic information with additional dynamic omics activity. PMID:22424236

  11. Phenotypic Profiling of Antibiotic Response Signatures in Escherichia coli Using Raman Spectroscopy

    PubMed Central

    Athamneh, A. I. M.; Alajlouni, R. A.; Wallace, R. S.; Seleem, M. N.

    2014-01-01

    Identifying the mechanism of action of new potential antibiotics is a necessary but time-consuming and costly process. Phenotypic profiling has been utilized effectively to facilitate the discovery of the mechanism of action and molecular targets of uncharacterized drugs. In this research, Raman spectroscopy was used to profile the phenotypic response of Escherichia coli to applied antibiotics. The use of Raman spectroscopy is advantageous because it is noninvasive, label free, and prone to automation, and its results can be obtained in real time. In this research, E. coli cultures were subjected to three times the MICs of 15 different antibiotics (representing five functional antibiotic classes) with known mechanisms of action for 30 min before being analyzed by Raman spectroscopy (using a 532-nm excitation wavelength). The resulting Raman spectra contained sufficient biochemical information to distinguish between profiles induced by individual antibiotics belonging to the same class. The collected spectral data were used to build a discriminant analysis model that identified the effects of unknown antibiotic compounds on the phenotype of E. coli cultures. Chemometric analysis showed the ability of Raman spectroscopy to predict the functional class of an unknown antibiotic and to identify individual antibiotics that elicit similar phenotypic responses. Results of this research demonstrate the power of Raman spectroscopy as a cellular phenotypic profiling methodology and its potential impact on antibiotic drug development research. PMID:24295982

  12. Transcriptional profiling identifies the metabolic phenotype of gonococcal biofilms.

    PubMed

    Falsetta, Megan L; Bair, Thomas B; Ku, Shan Chi; Vanden Hoven, Rachel N; Steichen, Christopher T; McEwan, Alastair G; Jennings, Michael P; Apicella, Michael A

    2009-09-01

    Neisseria gonorrhoeae, the etiologic agent of gonorrhea, is frequently asymptomatic in women, often leading to chronic infections. One factor contributing to this may be biofilm formation. N. gonorrhoeae can form biofilms on glass and plastic surfaces. There is also evidence that biofilm formation may occur during natural cervical infection. To further study the mechanism of gonococcal biofilm formation, we compared transcriptional profiles of N. gonorrhoeae biofilms to planktonic profiles. Biofilm RNA was extracted from N. gonorrhoeae 1291 grown for 48 h in continuous-flow chambers over glass. Planktonic RNA was extracted from the biofilm runoff. In comparing biofilm with planktonic growth, 3.8% of the genome was differentially regulated. Genes that were highly upregulated in biofilms included aniA, norB, and ccp. These genes encode enzymes that are central to anaerobic respiratory metabolism and stress tolerance. Downregulated genes included members of the nuo gene cluster, which encodes the proton-translocating NADH dehydrogenase. Furthermore, it was observed that aniA, ccp, and norB insertional mutants were attenuated for biofilm formation on glass and transformed human cervical epithelial cells. These data suggest that biofilm formation by the gonococcus may represent a response that is linked to the control of nitric oxide steady-state levels during infection of cervical epithelial cells. PMID:19528210

  13. Phenotyping drug polypharmacology via eicosanoid profiling of blood[S

    PubMed Central

    Song, Jiao; Liu, Xuejun; Rao, Tadimeti S.; Chang, Leon; Meehan, Michael J.; Blevitt, Jonathan M.; Wu, Jiejun; Dorrestein, Pieter C.; Milla, Marcos E.

    2015-01-01

    It is widely accepted that small-molecule drugs, despite their selectivity at primary targets, exert pharmacological effects (and safety liabilities) through a multiplicity of pathways. As such, it has proved extremely difficult to experimentally assess polypharmacology in an agnostic fashion. Profiling of metabolites produced as part of physiological responses to pharmacological stimuli provides a unique opportunity to explore drug pharmacology. A total of 122 eicosanoid lipids in human whole blood were monitored from 10 different donors upon stimulation with several inducers of immunological responses and treatment with modulators of prostaglandin (PG) and leukotriene biosynthesis, including clinical and investigational molecules. Such analysis revealed differentiation between drugs nominally targeting different eicosanoid biosynthetic enzymes, or even those designed to target the same enzyme. Profiled agents, some of them marketed products, affect eicosanoid biosynthesis in ways that cannot be predicted from information on their intended targets. As an example, we used this platform to discriminate drugs based on their ability to silence PG biosynthesis in response to bacterial lipopolysaccharide, resulting in differential pharmacological activity in an in vivo model of endotoxemia. Some of the observed effects are subject to variability among individuals, indicating a potential application of this methodology to the patient stratification, based on their responses to benchmark drugs and experimental compounds read on the eicosanome via a simple blood test. PMID:26022804

  14. Profiling of phospholipids and related lipid structures using multidimensional ion mobility spectrometry-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Trimpin, Sarah; Tan, Bo; Bohrer, Brian C.; O'Dell, David K.; Merenbloom, Samuel I.; Pazos, Mauricio X.; Clemmer, David E.; Walker, J. Michael

    2009-10-01

    Increasingly comprehensive questions related to the biosynthesis of lipids relevant to understanding new signaling pathways have created daunting tasks for their chemical analysis. Here, ion mobility spectrometry (IMS) and mass spectrometry (MS) techniques combined with electrospray ionization have been used to examine mixtures of closely related lipid structures. The drift time distributions of sphingomyelins show baseline separations for ethylene chain length differences ([Delta] ~ 1.2 ms) and partial separations in single unsaturation differences ([Delta] ~ 0.3 ms) revealing that the most compact structures are observed with shorter chains and increasing unsaturation. Drift time distributions of different ionizations frequently fall into families with the same drift times (isodrifts) indicating that the ion attached to the lipid has little structural influence. The present data show that phospholipids, especially phosphatidylinositol, aggregate to form inverted micelles. Phospholipids (phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylinositol) are effectively separated according to their polar head groups. This method also provides information about the mixture composition of the chemically different lipids N-palmitoyl glycine, N-arachidonoyl ethanolamide, and phosphatidylcholine existing over an array of charge states and sizes (inverted micelles) depending on mixture concentration. Multidimensional IMS3-MS introduces an additional dimension to fragmentation analysis by separating the fragmented ions into groups related to size, shape and charge and allows determination of sn-1 and sn-2 substitution as is shown for phosphatidylglycerols. This contribution provides evidence for extending the targeted approach to global lipidomics analysis using the high-efficiency gas-phase separation afforded by multidimensional IMS-MS.

  15. Multiparametric Biomechanical and Biochemical Phenotypic Profiling of Single Cancer Cells Using an Elasticity Microcytometer.

    PubMed

    Hu, Shuhuan; Liu, Guangyu; Chen, Weiqiang; Li, Xiang; Lu, Wei; Lam, Raymond H W; Fu, Jianping

    2016-05-01

    Deep phenotyping of single cancer cells is of critical importance in the era of precision medicine to advance understanding of relationships between gene mutation and cell phenotype and to elucidate the biological nature of tumor heterogeneity. Existing microfluidic single-cell phenotyping tools, however, are limited to phenotypic measurements of 1-2 selected morphological and physiological features of single cells. Herein a microfluidic elasticity microcytometer is reported for multiparametric biomechanical and biochemical phenotypic profiling of free-floating, live single cancer cells for quantitative, simultaneous characterizations of cell size, cell deformability/stiffness, and surface receptors. The elasticity microcytometer is implemented for measurements and comparisons of four human cell lines with distinct metastatic potentials and derived from different human tissues. An analytical model is developed from first principles for the first time to convert cell deformation and adhesion information of single cancer cells encapsulated inside the elasticity microcytometer to cell deformability/stiffness and surface protein expression. Together, the elasticity microcytometer holds great promise for comprehensive molecular, cellular, and biomechanical phenotypic profiling of live cancer cells at the single cell level, critical for studying intratumor cellular and molecular heterogeneity using low-abundance, clinically relevant human cancer cells. PMID:26929029

  16. Computational models for prediction of yeast strain potential for winemaking from phenotypic profiles.

    PubMed

    Mendes, Inês; Franco-Duarte, Ricardo; 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

  17. Identification of Intrinsic Imaging Phenotypes for Breast Cancer Tumors: Preliminary Associations with Gene Expression Profiles1

    PubMed Central

    Ashraf, Ahmed Bilal; Daye, Dania; Gavenonis, Sara; Mies, Carolyn; Feldman, Michael; Rosen, Mark; Kontos, Despina

    2015-01-01

    Purpose To present a method for identifying intrinsic imaging phenotypes in breast cancer tumors and to investigate their association with prognostic gene expression profiles. Materials and Methods The authors retrospectively analyzed dynamic contrast material–enhanced (DCE) magnetic resonance (MR) images of the breast in 56 women (mean age, 55.6 years; age range, 37–74 years) diagnosed with estrogen receptor–positive breast cancer between 2005 and 2010. The study was approved by the institutional review board and compliant with HIPAA. The requirement to obtain informed consent was waived. Primary tumors were assayed with a validated gene expression assay that provides a score for the likelihood of recurrence. A multiparametric imaging phenotype vector was extracted for each tumor by using quantitative morphologic, kinetic, and spatial heterogeneity features. Multivariate linear regression was performed to test associations between DCE MR imaging features and recurrence likelihood. To identify intrinsic imaging phenotypes, hierarchical clustering was performed on the extracted feature vectors. Multivariate logistic regression was used to classify tumors at high versus low or medium risk of recurrence. To determine the additional value of intrinsic phenotypes, the phenotype category was tested as an additional variable. Receiver operating characteristic analysis and the area under the receiver operating characteristic curve (Az) were used to assess classification performance. Results There was a moderate correlation (r = 0.71, R2 = 0.50, P < .001) between DCE MR imaging features and the recurrence score. DCE MR imaging features were predictive of recurrence risk as determined by the surrogate assay, with an Az of 0.77 (P < .01). Four dominant imaging phenotypes were detected, with two including only low- and medium-risk tumors. When the phenotype category was used as an additional variable, the Az increased to 0.82 (P < .01). Conclusion Intrinsic imaging

  18. Bacterial profiling of soil using genus-specific markers and multidimensional scaling.

    PubMed

    Lenz, Erin J; Foran, David R

    2010-11-01

    Forensic identification of soil based on microbial DNA fingerprinting has met with mixed success, with research efforts rarely considering temporal variability or local heterogeneity in soil's microbial makeup. In the research presented, the nitrogen fixing bacteria rhizobia were specifically examined. Soils were collected monthly from five habitats for 1 year, and quarterly in each cardinal direction from the main collection site. When all habitats were compared simultaneously using Terminal Restriction Fragment Length Polymorphism analysis of the rhizobial recA gene and multidimensional scaling, only two were differentiated over a year's time, however pairwise comparisons allowed four of five soils to be effectively differentiated. Adding in 10-foot distant soils as "questioned" samples correctly grouped them in 40-70% of cases, depending on restriction enzyme used. The results indicate that the technique has potential for forensic soil identification, although extensive anthropogenic manipulation of a soil makes such identification much more tentative. PMID:20533986

  19. Native profiles of α1A-adrenoceptor phenotypes in rabbit prostate

    PubMed Central

    Su, T-H; Morishima, S; Suzuki, F; Yoshiki, H; Anisuzzaman, A S M; Tanaka, T; Cheng, J-T; Muramatsu, I

    2008-01-01

    Background and purpose: α1-Adrenoceptors in the rabbit prostate have been studied because of their controversial pharmacological profiles in functional and radioligand binding studies. The purpose of the present study is to determine the native profiles of α1-adrenoceptor phenotypes and to clarify their relationship. Experimental approach: Binding experiments with [3H]-silodosin and [3H]-prazosin were performed using intact tissue segments and crude membrane preparations of rabbit prostate and the results were compared with α1-adrenoceptor-mediated prostate contraction. Key results: [3H]-Silodosin at subnanomolar concentrations bound specifically to intact tissue segments of rabbit prostate. However, [3H]-prazosin at the same range of concentrations failed to bind to α1-adrenoceptors of intact segments. Binding sites of [3H]-silodosin in intact segments were composed of α1L phenotype with low affinities for prazosin (pKi=7.1), 5-methyurapidil and N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-α,α-dimethyl-1H-indole-3-ethamine hydrochloride (RS-17053), and α1A-like phenotype with moderate affinity for prazosin (pKi=8.8) but high affinity for 5-methyurapidil and RS-17053. In contrast, both radioligands bound to a single population of α1-adrenoceptors in the membrane preparations at the same density with a subnanomolar affinity, showing a typical profile of ‘classical' α1A-adrenoceptors (pKi for prazosin=9.8). The pharmacological profile of α1-adrenoceptor-mediated prostate contraction was in accord with the α1L phenotype observed by intact segment binding approach. Conclusions and implications: Three distinct phenotypes (α1L and α1A-like phenotypes in the intact segments and a classical α1A phenotype in the membranes) with different affinities for prazosin were detected in rabbit prostate. It appears that the three phenotypes are phenotypic subtypes of α1A-adrenoceptors, but are not genetically different subtypes. PMID:18695643

  20. Shade Avoidance Components and Pathways in Adult Plants Revealed by Phenotypic Profiling

    PubMed Central

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

    2015-01-01

    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. PMID:25874869

  1. 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,…

  2. cellXpress: a fast and user-friendly software platform for profiling cellular phenotypes

    PubMed Central

    2013-01-01

    Background High-throughput, image-based screens of cellular responses to genetic or chemical perturbations generate huge numbers of cell images. Automated analysis is required to quantify and compare the effects of these perturbations. However, few of the current freely-available bioimage analysis software tools are optimized for efficient handling of these images. Even fewer of them are designed to transform the phenotypic features measured from these images into discriminative profiles that can reveal biologically meaningful associations among the tested perturbations. Results We present a fast and user-friendly software platform called "cellXpress" to segment cells, measure quantitative features of cellular phenotypes, construct discriminative profiles, and visualize the resulting cell masks and feature values. We have also developed a suite of library functions to load the extracted features for further customizable analysis and visualization under the R computing environment. We systematically compared the processing speed, cell segmentation accuracy, and phenotypic-profile clustering performance of cellXpress to other existing bioimage analysis software packages or algorithms. We found that cellXpress outperforms these existing tools on three different bioimage datasets. We estimate that cellXpress could finish processing a genome-wide gene knockdown image dataset in less than a day on a modern personal desktop computer. Conclusions The cellXpress platform is designed to make fast and efficient high-throughput phenotypic profiling more accessible to the wider biological research community. The cellXpress installation packages for 64-bit Windows and Linux, user manual, installation guide, and datasets used in this analysis can be downloaded freely from http://www.cellXpress.org. PMID:24564609

  3. 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

  4. Immune Neuroendocrine Phenotypes in Coturnix coturnix: Do Avian Species Show LEWIS/FISCHER-Like Profiles?

    PubMed Central

    Nazar, F. Nicolas; Barrios, Bibiana E.; Kaiser, Pete; Marin, Raul H.; Correa, Silvia G.

    2015-01-01

    Immunoneuroendocrinology studies have identified conserved communicational paths in birds and mammals, e.g. the Hypothalamus-Pituitary-Adrenal axis with anti-inflammatory activity mediated by glucocorticoids. Immune neuroendocrine phenotypes (INPs) have been proposed for mammals implying the categorization of a population in subgroups underlying divergent immune-neuroendocrine interactions. These phenotypes were studied in the context of the LEWIS/FISCHER paradigm (rats expressing high or low pro-inflammatory profiles, respectively). Although avian species have some common immunological mechanisms with mammals, they have also evolved some distinct strategies and, until now, it has not been studied whether birds may also share with mammals similar INPs. Based on corticosterone levels we determined the existence of two divergent groups in Coturnix coturnix that also differed in other immune-neuroendocrine responses. Quail with lowest corticosterone showed higher lymphoproliferative and antibody responses, interferon-γ and interleukin-1β mRNA expression levels and lower frequencies of leukocyte subpopulations distribution and interleukin-13 levels, than their higher corticosterone counterparts. Results suggest the existence of INPs in birds, comparable to mammalian LEWIS/FISCHER profiles, where basal corticosterone also underlies responses of comparable variables associated to the phenotypes. Concluding, INP may not be a mammalian distinct feature, leading to discuss whether these profiles represent a parallel phenomenon evolved in birds and mammals, or a common feature inherited from a reptilian ancestor millions of years ago. PMID:25793369

  5. Multidimensional profiles of welfare and work dynamics: development, validation, and associations with child cognitive and mental health outcomes.

    PubMed

    Yoshikawa, H; Seidman, E

    2001-12-01

    This prospective longitudinal study addresses the research gap in the literature regarding multidimensional variation in welfare use and employment patterns, and relationships of such variation with parent earnings and child development outcomes. This study also aims to address the limitations of welfare dynamics studies that do not examine how multiple dimensions of welfare receipt and employment co-occur Cluster analysis was utilized, using monthly welfare and employment data from the National Longitudinal Survey of Youth, to examine variation within the welfare population in their welfare and work patterns across the first 5 years of children's lives. Six cluster profiles of welfare and work dynamics were found: Short-Term, Short-Term Work Exit, Working Cyclers, Nonworking Cyclers, Cycle to Long-Term Exit, and Long-Term. The clusters were validated using mother's 6th-year earnings as the criterion. The clusters' associations with child development outcomes in the cognitive and mental health domains (at ages 6 and 7) were then explored. Work following short-term welfare use was associated with higher child reading scores than that following long-term use (a moderate-size effect). Cycling on and off welfare in the context of high levels of employment was associated with higher child internalizing symptoms than cycling accompanied by low levels of employment (a moderate-size effect). Implications for evaluation of TANF welfare-to-work policies are discussed. PMID:11800512

  6. Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.

    PubMed

    Mizotani, Yuji; Itoh, Shun; Hotta, Kohji; Tashiro, Etsu; Oka, Kotaro; Imoto, Masaya

    2015-08-01

    In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets. PMID:26043689

  7. A GIS-based Computational Tool for Multidimensional Flow Velocity by Acoustic Doppler Current Profilers

    NASA Astrophysics Data System (ADS)

    Kim, D.; Winkler, M.; Muste, M.

    2015-06-01

    Acoustic Doppler Current Profilers (ADCPs) provide efficient and reliable flow measurements compared to other tools for characteristics of the riverine environments. In addition to originally targeted discharge measurements, ADCPs are increasingly utilized to assess river flow characteristics. The newly developed VMS (Velocity Mapping Software) aims at providing an efficient process for quality assurance, mapping velocity vectors for visualization and facilitating comparison with physical and numerical model results. VMS was designed to provide efficient and smooth work flows for processing groups of transects. The software allows the user to select group of files and subsequently to conduct statistical and graphical quality assurance on the files as a group or individually as appropriate. VMS also enables spatial averaging in horizontal and vertical plane for ADCP data in a single or multiple transects over the same or consecutive cross sections. The analysis results are displayed in numerical and graphical formats.

  8. Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum.

    PubMed

    Donti, Taraka R; Cappuccio, Gerarda; Hubert, Leroy; Neira, Juanita; Atwal, Paldeep S; Miller, Marcus J; Cardon, Aaron L; Sutton, V Reid; Porter, Brenda E; Baumer, Fiona M; Wangler, Michael F; Sun, Qin; Emrick, Lisa T; Elsea, Sarah H

    2016-09-01

    Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal recessive neurometabolic disorder that presents with a broad-spectrum of neurological and physiological symptoms. The ADSL gene produces an enzyme with binary molecular roles in de novo purine synthesis and purine nucleotide recycling. The biochemical phenotype of ADSL deficiency, accumulation of SAICAr and succinyladenosine (S-Ado) in biofluids of affected individuals, serves as the traditional target for diagnosis with targeted quantitative urine purine analysis employed as the predominate method of detection. In this study, we report the diagnosis of ADSL deficiency using an alternative method, untargeted metabolomic profiling, an analytical scheme capable of generating semi-quantitative z-score values for over 1000 unique compounds in a single analysis of a specimen. Using this method to analyze plasma, we diagnosed ADSL deficiency in four patients and confirmed these findings with targeted quantitative biochemical analysis and molecular genetic testing. ADSL deficiency is part of a large a group of neurometabolic disorders, with a wide range of severity and sharing a broad differential diagnosis. This phenotypic similarity among these many inborn errors of metabolism (IEMs) has classically stood as a hurdle in their initial diagnosis and subsequent treatment. The findings presented here demonstrate the clinical utility of metabolomic profiling in the diagnosis of ADSL deficiency and highlights the potential of this technology in the diagnostic evaluation of individuals with neurologic phenotypes. PMID:27504266

  9. Metabolic profiles to define the genome: can we hear the phenotypes?

    PubMed Central

    Griffin, Julian L

    2004-01-01

    There is an increased reliance on genetically modified organisms as a functional genomic tool to elucidate the role of genes and their protein products. Despite this, many models do not express the expected phenotype thought to be associated with the gene or protein. There is thus an increased need to further define the phenotype resultant from a genetic modification to understand how the transcriptional or proteomic network may conspire to alter the expected phenotype. This is best typified by the description of the silent phenotype in genetic manipulations of yeast. High-resolution proton nuclear magnetic resonance ((1)H NMR) spectroscopy provides an ideal mechanism for the profiling of metabolites within biofluids, tissue extracts or, with recent advances, intact tissues. These metabolic datasets can be readily mined using a range of pattern recognition techniques, including hierarchical cluster analysis, principal components analysis, partial least squares and neural networks, with the combined approach being termed metabolomics. This review describes the application of NMR-based metabolomics or metabonomics to genetic and chemical interventions in a number of different species, demonstrating the versatility of such an approach, as well as suggesting how it may be integrated with other "omic" technologies. PMID:15306403

  10. Metabolic Profiling and Phenotyping of Central Nervous System Diseases: Metabolites Bring Insights into Brain Dysfunctions.

    PubMed

    Dumas, Marc-Emmanuel; Davidovic, Laetitia

    2015-09-01

    Metabolic phenotyping corresponds to the large-scale quantitative and qualitative analysis of the metabolome i.e., the low-molecular weight <1 KDa fraction in biological samples, and provides a key opportunity to advance neurosciences. Proton nuclear magnetic resonance and mass spectrometry are the main analytical platforms used for metabolic profiling, enabling detection and quantitation of a wide range of compounds of particular neuro-pharmacological and physiological relevance, including neurotransmitters, secondary messengers, structural lipids, as well as their precursors, intermediates and degradation products. Metabolic profiling is therefore particularly indicated for the study of central nervous system by probing metabolic and neurochemical profiles of the healthy or diseased brain, in preclinical models or in human samples. In this review, we introduce the analytical and statistical requirements for metabolic profiling. Then, we focus on key studies in the field of metabolic profiling applied to the characterization of animal models and human samples of central nervous system disorders. We highlight the potential of metabolic profiling for pharmacological and physiological evaluation, diagnosis and drug therapy monitoring of patients affected by brain disorders. Finally, we discuss the current challenges in the field, including the development of systems biology and pharmacology strategies improving our understanding of metabolic signatures and mechanisms of central nervous system diseases. PMID:25616565

  11. Cancer RNA-Seq Nexus: a database of phenotype-specific transcriptome profiling in cancer cells.

    PubMed

    Li, Jian-Rong; Sun, Chuan-Hu; Li, Wenyuan; Chao, Rou-Fang; Huang, Chieh-Chen; Zhou, Xianghong Jasmine; Liu, Chun-Chi

    2016-01-01

    The genome-wide transcriptome profiling of cancerous and normal tissue samples can provide insights into the molecular mechanisms of cancer initiation and progression. RNA Sequencing (RNA-Seq) is a revolutionary tool that has been used extensively in cancer research. However, no existing RNA-Seq database provides all of the following features: (i) large-scale and comprehensive data archives and analyses, including coding-transcript profiling, long non-coding RNA (lncRNA) profiling and coexpression networks; (ii) phenotype-oriented data organization and searching and (iii) the visualization of expression profiles, differential expression and regulatory networks. We have constructed the first public database that meets these criteria, the Cancer RNA-Seq Nexus (CRN, http://syslab4.nchu.edu.tw/CRN). CRN has a user-friendly web interface designed to facilitate cancer research and personalized medicine. It is an open resource for intuitive data exploration, providing coding-transcript/lncRNA expression profiles to support researchers generating new hypotheses in cancer research and personalized medicine. PMID:26602695

  12. Multidimensional spectrometer

    SciTech Connect

    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.

  13. 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…

  14. OCT4 Remodels the Phenotype and Promotes Angiogenesis of HUVECs by Changing the Gene Expression Profile

    PubMed Central

    Mou, Yan; Yue, Zhen; Wang, Xiaotong; Li, Wenxue; Zhang, Haiying; Wang, Yang; Li, Ronggui; Sun, Xin

    2016-01-01

    It has been shown that forced expression of four mouse stem cell factors (OCT4, Sox2, Klf4, and c-Myc) changed the phenotype of rat endothelial cells to vascular progenitor cells. The present study aimed to explore whether the expression of OCT4 alone might change the phenotype of human umbilical vein endothelial cells (HUVECs) to endothelial progenitor cells and, if so, to examine the possible mechanism involved. A Matrigel-based in vitro angiogenesis assay was used to evaluate the angiogenesis of the cells; the gene expression profile was analyzed by an oligonucleotide probe-based gene array chip and validated by RT-QPCR. The cellular functions of the mRNAs altered by OCT4 were analyzed with Gene Ontology. We found that induced ectopic expression of mouse OCT4 in HUVECs significantly enhanced angiogenesis of the cells, broadly changed the gene expression profile and particularly increased the expression of CD133, CD34, and VEGFR2 (KDR) which are characteristic marker molecules for endothelial progenitor cells (EPCs). Furthermore by analyzing the cellular functions that were targeted by the mRNAs altered by OCT4 we found that stem cell maintenance and cell differentiation were among the top functional response targeted by up-regulated and down-regulated mRNAs upon forced expression of OCT4. These results support the argument that OCT4 remodels the phenotype of HUVECs from endothelial cells to EPCs by up-regulating the genes responsible for stem cell maintenance and down-regulating the genes for cell differentiation. PMID:27226779

  15. Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated with Early Childhood Diarrhea in Rural Egypt

    PubMed Central

    Shaheen, Hind I.; Khalil, Sami B.; Rao, Malla R.; Elyazeed, Remon Abu; Wierzba, Thomas F.; Peruski, Leonard F.; Putnam, Shannon; Navarro, Armando; Morsy, Badria Z.; Cravioto, Alejandro; Clemens, John D.; Svennerholm, Ann-Mari; Savarino, Stephen J.

    2004-01-01

    Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We determined the phenotypic profiles of 915 ETEC diarrheal isolates derived from Egyptian children under 3 years of age who participated in a 3-year population-based study. For each strain, we ascertained enterotoxin and colonization factor (CF) expression, the O:H serotype, and antimicrobial susceptibility. Sixty-one percent of the strains expressed heat-stable enterotoxin (ST) only, 26% expressed heat-labile enterotoxin (LT) alone, and 12% 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 CS1 plus CS3 (4%). Fifty-nine percent of the strains did not express any of the 12 CFs included in our test panel. Resistance of ETEC strains to ampicillin (63%), trimethoprim-sulfamethoxazole (52%), and tetracycline (43%) was common, while resistance to quinolone antibiotics was rarely detected. As for the distribution of observed serotypes, there was an unusually wide diversity of O antigens and H types represented among the 915 ETEC strains. The most commonly recognized composite ETEC phenotypes were ST CS14 O78:H18 (4%), ST (or LTST) CFA/I O128:H12 (3%), ST CS1+CS3 O6:H16 (2%), and ST CFA/I O153:H45 (1.5%). Temporal plots of diarrheal episodes associated with ETEC strains bearing common composite phenotypes were consistent with discrete community outbreaks either within a single or over successive warm seasons. These data suggest that a proportion of the disease that is endemic to young children in rural Egypt represents the confluence of small epidemics by clonally related ETEC strains that are transiently introduced or that persist in a community reservoir. PMID:15583286

  16. Expanding the phenotypic profile of boys with 47, XXY: the impact of familial learning disabilities.

    PubMed

    Samango-Sprouse, Carole A; Stapleton, Emily J; Mitchell, Francie L; Sadeghin, Teresa; Donahue, Thomas P; Gropman, Andrea L

    2014-06-01

    The aim of the study was to examine the impact of familial learning disabilities (FLD) on the phenotypic profile of 47, XXY males and the possibility that 47, XXY males with more severe cognitive deficits may be partially a consequence of familial dyslexia/reading disorder. We wondered if FLD could pose an additional risk for complex neurodevelopmental differences in 47, XXY. The neurodevelopmental profile of males with 47, XXY has been characterized by developmental dyspraxia, language-based learning disorders, executive dysfunction, reading, and attentional deficits. One hundred eighteen boys with 47, XXY diagnosed prenatally who did not receive early hormonal treatment were divided into two groups based on positive histories of FLD and given comprehensive neurodevelopmental evaluations between 36 and 108 months. The assessments included intelligence (nonverbal and verbal), neuromotor (fine and gross), speech, and language. The group with FLD performed significantly lower in multiple neurodevelopmental domains of the Wechsler of VIQ P = 0.015, FSIQ P = 0.0005, the Brief IQ P = 0.0525 of the Leiter, in Auditory Comprehension P = 0.0505, Expressive Communication P = 0.0055, and neuromotor domains of Manual Coordination P = 0.0032, Fine Motor Control P = 0.0378, and Motor Coordination P = 0.008. Our study demonstrates the influence of FLD on neurodevelopment and expands the phenotypic profile of 47, XXY, suggesting some neurodevelopmental variability is attributable to other factors than the additional X. FLD may increase the vulnerability of the 47, XXY children and anticipatory guidance should be provided to families. PMID:24715716

  17. Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype

    PubMed Central

    Gustafsson, Charlotte; Mjösberg, Jenny; Matussek, Andreas; Geffers, Robert; Matthiesen, Leif; Berg, Göran; Sharma, Surendra; Buer, Jan; Ernerudh, Jan

    2008-01-01

    Background Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known. Methodology/Principal Findings Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications. Conclusions/Significance The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells. PMID:18446208

  18. 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…

  19. Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes

    PubMed Central

    Dominguez, Eduardo; Galmozzi, Andrea; Chang, Jae Won; Hsu, Ku-Lung; Pawlak, Joanna; Li, Weiwei; Godio, Cristina; Thomas, Jason; Partida, David; Niessen, Sherry; O'Brien, Paul E.; Russell, Aaron P.; Watt, Matthew J.; Nomura, Daniel K.; Cravatt, Benjamin F.; Saez, Enrique

    2014-01-01

    Phenotypic screening is making a comeback in drug discovery as the maturation of chemical proteomics methods has facilitated target identification for bioactive small molecules. A limitation of these approaches is that time-consuming genetic methods or other means is often required to determine the biologically relevant target(s) from among multiple protein-compound interactions that are typically detected. Here, we have combined phenotypic screening of a directed small-molecule library with competitive activity-based protein profiling to map and functionally characterize the targets of screening hits. Using this approach, we identify carboxylesterase 3 (Ces3 or Ces1d) as a primary molecular target of bioactive compounds that promote lipid storage in adipocytes. We further show that Ces3 activity is dramatically elevated during adipocyte differentiation. Treatment of two mouse models of obesity-diabetes with a Ces3 inhibitor ameliorates multiple features of metabolic syndrome, illustrating the power of the described strategy to accelerate the identification and pharmacologic validation of new therapeutic targets. PMID:24362705

  20. Mitochondria Biogenesis and Bioenergetics Gene Profiles in Isogenic Prostate Cells with Different Malignant Phenotypes

    PubMed Central

    Burch, Tanya C.; Rhim, Johng S.

    2016-01-01

    Background. The most significant hallmarks of cancer are directly or indirectly linked to deregulated mitochondria. In this study, we sought to profile mitochondria associated genes in isogenic prostate cell lines with different tumorigenic phenotypes from the same patient. Results. Two isogenic human prostate cell lines RC77N/E (nonmalignant cells) and RC77T/E (malignant cells) were profiled for expression of mitochondrial biogenesis and energy metabolism genes by qRT-PCR using the Human Mitochondria and the Mitochondrial Energy Metabolism RT2 PCR arrays. Forty-seven genes were differentially regulated between the two cell lines. The interaction and regulatory networks of these genes were generated by Ingenuity Pathway Analysis. UCP2 was the most significantly upregulated gene in primary adenocarcinoma cells in the current study. The overexpression of UCP2 upon malignant transformation was further validated using human prostatectomy clinical specimens. Conclusions. This study demonstrates the overexpression of multiple genes that are involved in mitochondria biogenesis, bioenergetics, and modulation of apoptosis. These genes may play a role in malignant transformation and disease progression. The upregulation of some of these genes in clinical samples indicates that some of the differentially transcribed genes could be the potential targets for therapeutic interventions. PMID:27478826

  1. Mitochondria Biogenesis and Bioenergetics Gene Profiles in Isogenic Prostate Cells with Different Malignant Phenotypes.

    PubMed

    Burch, Tanya C; Rhim, Johng S; Nyalwidhe, Julius O

    2016-01-01

    Background. The most significant hallmarks of cancer are directly or indirectly linked to deregulated mitochondria. In this study, we sought to profile mitochondria associated genes in isogenic prostate cell lines with different tumorigenic phenotypes from the same patient. Results. Two isogenic human prostate cell lines RC77N/E (nonmalignant cells) and RC77T/E (malignant cells) were profiled for expression of mitochondrial biogenesis and energy metabolism genes by qRT-PCR using the Human Mitochondria and the Mitochondrial Energy Metabolism RT(2) PCR arrays. Forty-seven genes were differentially regulated between the two cell lines. The interaction and regulatory networks of these genes were generated by Ingenuity Pathway Analysis. UCP2 was the most significantly upregulated gene in primary adenocarcinoma cells in the current study. The overexpression of UCP2 upon malignant transformation was further validated using human prostatectomy clinical specimens. Conclusions. This study demonstrates the overexpression of multiple genes that are involved in mitochondria biogenesis, bioenergetics, and modulation of apoptosis. These genes may play a role in malignant transformation and disease progression. The upregulation of some of these genes in clinical samples indicates that some of the differentially transcribed genes could be the potential targets for therapeutic interventions. PMID:27478826

  2. Correlation of Lactobacillus rhamnosus Genotypes and Carbohydrate Utilization Signatures Determined by Phenotype Profiling

    PubMed Central

    Lambert, Jolanda; van Limpt, Kees; Wels, Michiel; Smokvina, Tamara; Knol, Jan; Kleerebezem, Michiel

    2015-01-01

    Lactobacillus rhamnosus is a bacterial species commonly colonizing the gastrointestinal (GI) tract of humans and also frequently used in food products. While some strains have been studied extensively, physiological variability among isolates of the species found in healthy humans or their diet is largely unexplored. The aim of this study was to characterize the diversity of carbohydrate utilization capabilities of human isolates and food-derived strains of L. rhamnosus in relation to their niche of isolation and genotype. We investigated the genotypic and phenotypic diversity of 25 out of 65 L. rhamnosus strains from various niches, mainly human feces and fermented dairy products. Genetic fingerprinting of the strains by amplified fragment length polymorphism (AFLP) identified 11 distinct subgroups at 70% similarity and suggested niche enrichment within particular genetic clades. High-resolution carbohydrate utilization profiling (OmniLog) identified 14 carbon sources that could be used by all of the strains tested for growth, while the utilization of 58 carbon sources differed significantly between strains, enabling the stratification of L. rhamnosus strains into three metabolic clusters that partially correlate with the genotypic clades but appear uncorrelated with the strain's origin of isolation. Draft genome sequences of 8 strains were generated and employed in a gene-trait matching (GTM) analysis together with the publicly available genomes of L. rhamnosus GG (ATCC 53103) and HN001 for several carbohydrates that were distinct for the different metabolic clusters: l-rhamnose, cellobiose, l-sorbose, and α-methyl-d-glucoside. From the analysis, candidate genes were identified that correlate with l-sorbose and α-methyl-d-glucoside utilization, and the proposed function of these genes could be confirmed by heterologous expression in a strain lacking the genes. This study expands our insight into the phenotypic and genotypic diversity of the species L. rhamnosus

  3. Correlation of Lactobacillus rhamnosus Genotypes and Carbohydrate Utilization Signatures Determined by Phenotype Profiling.

    PubMed

    Ceapa, Corina; Lambert, Jolanda; van Limpt, Kees; Wels, Michiel; Smokvina, Tamara; Knol, Jan; Kleerebezem, Michiel

    2015-08-15

    Lactobacillus rhamnosus is a bacterial species commonly colonizing the gastrointestinal (GI) tract of humans and also frequently used in food products. While some strains have been studied extensively, physiological variability among isolates of the species found in healthy humans or their diet is largely unexplored. The aim of this study was to characterize the diversity of carbohydrate utilization capabilities of human isolates and food-derived strains of L. rhamnosus in relation to their niche of isolation and genotype. We investigated the genotypic and phenotypic diversity of 25 out of 65 L. rhamnosus strains from various niches, mainly human feces and fermented dairy products. Genetic fingerprinting of the strains by amplified fragment length polymorphism (AFLP) identified 11 distinct subgroups at 70% similarity and suggested niche enrichment within particular genetic clades. High-resolution carbohydrate utilization profiling (OmniLog) identified 14 carbon sources that could be used by all of the strains tested for growth, while the utilization of 58 carbon sources differed significantly between strains, enabling the stratification of L. rhamnosus strains into three metabolic clusters that partially correlate with the genotypic clades but appear uncorrelated with the strain's origin of isolation. Draft genome sequences of 8 strains were generated and employed in a gene-trait matching (GTM) analysis together with the publicly available genomes of L. rhamnosus GG (ATCC 53103) and HN001 for several carbohydrates that were distinct for the different metabolic clusters: l-rhamnose, cellobiose, l-sorbose, and α-methyl-d-glucoside. From the analysis, candidate genes were identified that correlate with l-sorbose and α-methyl-d-glucoside utilization, and the proposed function of these genes could be confirmed by heterologous expression in a strain lacking the genes. This study expands our insight into the phenotypic and genotypic diversity of the species L. rhamnosus

  4. Metabolomics profiling in plasma samples from glioma patients correlates with tumor phenotypes

    PubMed Central

    Zhao, Hua; Heimberger, Amy B.; Lu, Zhimin; Wu, Xifeng; Hodges, Tiffany R.; Song, Renduo; Shen, Jie

    2016-01-01

    Background Tumor-based molecular biomarkers have redefined in the classification gliomas. However, the association of systemic metabolomics with glioma phenotype has not been explored yet. Methods In this study, we conducted two-step (discovery and validation) metabolomic profiling in plasma samples from 87 glioma patients. The metabolomics data were tested for correlation with glioma grade (high vs low), glioblastoma (GBM) versus malignant gliomas, and IDH mutation status. Results Five metabolites, namely uracil, arginine, lactate, cystamine, and ornithine, significantly differed between high- and low-grade glioma patients in both the discovery and validation cohorts. When the discovery and validation cohorts were combined, we identified 29 significant metabolites with 18 remaining significant after adjusting for multiple comparisons. Those 18 significant metabolites separated high- from low-grade glioma patients with 91.1% accuracy. In the pathway analysis, a total of 18 significantly metabolic pathways were identified. Similarly, we identified 2 and 6 metabolites that significantly differed between GBM and non-GBM, and IDH mutation positive and negative patients after multiple comparison adjusting. Those 6 significant metabolites separated IDH1 mutation positive from negative glioma patients with 94.4% accuracy. Three pathways were identified to be associated with IDH mutation status. Within arginine and proline metabolism, levels of intermediate metabolites in creatine pathway were all significantly lower in IDH mutation positive than in negative patients, suggesting an increased activity of creatine pathway in IDH mutation positive tumors. Conclusion Our findings identified metabolites and metabolic pathways that differentiated tumor phenotypes. These may be useful as host biomarker candidates to further help glioma molecular classification. PMID:26967252

  5. 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

  6. Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells

    PubMed Central

    Summers, Carolyn M.; Hammons, Andrea L.; Arora, Jasbir; Zhang, Suhong; Jochems, Jeanine; Blair, Ian A.; Whitehead, Alexander S.

    2014-01-01

    EA.hy 926 cells grown under low folate conditions adopt a “pro-atherosclerotic” morphology and biochemical phenotype. Pharmacologically relevant doses of the antifolate drug methotrexate (MTX) were applied to EA.hy 926 cells maintained in normal (Hi) and low (Lo) folate culture media. Under both folate conditions, MTX caused inhibition of cell proliferation without significantly compromising metabolic activity. MTX treated Hi cells were depleted of folate derivatives, which were present in altered proportions relative to untreated cells. Transcript profiling using microarrays indicated that MTX treatment modified the transciptome in similar ways for both Hi and Lo cells. Many inflammation-related genes, most prominently those encoding C3 and IL-8, were up-regulated, whereas many genes involved in cell division were down-regulated. The results for C3 and IL-8 were confirmed by quantitative RT-PCR and ELISA. MTX appears to modify the inflammatory potential of EA.hy 926 cells such that its therapeutic properties may, at least under some conditions, be accompanied by the induction of a subset of gene products that promote and/or maintain comorbid pathologies. PMID:24657277

  7. The hairless gene of the mouse: relationship of phenotypic effects with expression profile and genotype.

    PubMed

    Cachón-González, M B; San-José, I; Cano, A; Vega, J A; García, N; Freeman, T; Schimmang, T; Stoye, J P

    1999-10-01

    Various mutations of the hairless (hr) gene of mice result in hair loss and other integument defects. To examine the role of the hr gene in mouse development, the expression profile of hr has been determined by in situ hybridisation and correlated to the nature of genetic changes and morphological abnormalities in different mutant animals. Four variant alleles have been characterised at the molecular level. hr/hr mice produce reduced, but significant, levels of hr mRNA whereas other alleles contain mutations which would be expected to preclude the synthesis of functional product, demonstrating a correlation between allelic variation at the hr locus and phenotypic severity. hr expression was shown to be widespread and temporally regulated. It was identified in novel tissues such as cartilage, developing tooth, inner ear, retina, and colon as well as in skin and brain. Analysis of mice homozygous for the rhino allele of hairless revealed that, although no morphological defects were detectable in many tissues normally expressing hr, previously undescribed abnormalities were present in several tissues including inner ear, retina, and colon. These findings indicate that the hairless gene product plays a wider role in development than previously suspected. Dev Dyn 1999;216:113-126. PMID:10536052

  8. The Matchmaker Exchange API: automating patient matching through the exchange of structured phenotypic and genotypic profiles.

    PubMed

    Buske, Orion J; Schiettecatte, François; Hutton, Benjamin; Dumitriu, Sergiu; Misyura, Andriy; Huang, Lijia; Hartley, Taila; Girdea, Marta; Sobreira, Nara; Mungall, Chris; Brudno, Michael

    2015-10-01

    Despite the increasing prevalence of clinical sequencing, the difficulty of identifying additional affected families is a key obstacle to solving many rare diseases. There may only be a handful of similar patients worldwide, and their data may be stored in diverse clinical and research databases. Computational methods are necessary to enable finding similar patients across the growing number of patient repositories and registries. We present the Matchmaker Exchange Application Programming Interface (MME API), a protocol and data format for exchanging phenotype and genotype profiles to enable matchmaking among patient databases, facilitate the identification of additional cohorts, and increase the rate with which rare diseases can be researched and diagnosed. We designed the API to be straightforward and flexible in order to simplify its adoption on a large number of data types and workflows. We also provide a public test data set, curated from the literature, to facilitate implementation of the API and development of new matching algorithms. The initial version of the API has been successfully implemented by three members of the Matchmaker Exchange and was immediately able to reproduce previously identified matches and generate several new leads currently being validated. The API is available at https://github.com/ga4gh/mme-apis. PMID:26255989

  9. Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic and Phenotypic Profiles

    PubMed Central

    Fuh, Jong-Ling; Chern, Chang-Ming; Lee, Wei-Ju; Guo, Yuh-Cherng; Wang, Shuu-Jiun; Lee, I-Hui; Liu, Yo-Tsen; Wang, Yen-Feng; Chang, Feng-Chi; Chang, Ming-Hung; Soong, Bing-Wen; Lee, Yi-Chung

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3–6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal involvement, older age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer occurrence of migraine. Subgroup analyses revealed that the R544C mutation is associated with lower frequency of anterior temporal involvement, later age at onset and higher frequency of cognitive dysfunction. In conclusion, the present study broadens the spectrum of NOTCH3 mutations and provides additional insights for the clinical and molecular characteristics of CADASIL patients of Han-Chinese descents. PMID:26308724

  10. High-throughput phenotypic profiling of gene-environment interactions by quantitative growth curve analysis in Saccharomyces cerevisiae.

    PubMed

    Weiss, Andrew; Delproposto, James; Giroux, Craig N

    2004-04-01

    Cell-based assays are widely used in high-throughput screening to determine the effects of toxicants and drugs on their biological targets. To enable a functional genomics modeling of gene-environment interactions, quantitative assays are required both for gene expression and for the phenotypic responses to environmental challenge. To address this need, we describe an automated high-throughput methodology that provides phenotypic profiling of the cellular responses to environmental stress in Saccharomyces cerevisiae. Standardized assay conditions enable the use of a single metric value to quantify yeast microculture growth curves. This assay format allows precise control of both genetic and environmental determinants of the cellular responses to oxidative stress, a common mechanism of environmental insult. These yeast-cell-based assays are validated with hydrogen peroxide, a simple direct-acting oxidant. Phenotypic profiling of the oxidative stress response of a yap1 mutant strain demonstrates the mechanistic analysis of genetic susceptibility to oxidative stress. As a proof of concept for analysis of more complex gene-environment interactions, we describe a combinatorial assay design for phenotypic profiling of the cellular responses to tert-butyl hydroperoxide, a complex oxidant that is actively metabolized by its target cells. Thus, the yeast microculture assay format supports comprehensive applications in toxicogenomics. PMID:15033507

  11. Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile.

    PubMed

    McDonnell, Aoibhinn; Schulman, Betsy; Ali, Zahid; Dib-Hajj, Sulayman D; Brock, Fiona; Cobain, Sonia; Mainka, Tina; Vollert, Jan; Tarabar, Sanela; Waxman, Stephen G

    2016-04-01

    Inherited erythromelalgia, the first human pain syndrome linked to voltage-gated sodium channels, is widely regarded as a genetic model of human pain. Because inherited erythromelalgia was linked to gain-of-function changes of sodium channel Na(v)1.7 only a decade ago, the literature has mainly consisted of reports of genetic and/or clinical characterization of individual patients. This paper describes the pattern of pain, natural history, somatosensory profile, psychosocial status and olfactory testing of 13 subjects with primary inherited erythromelalgia with mutations of SCN9A, the gene encoding Na(v)1.7. Subjects were clinically profiled using questionnaires, quantitative sensory testing and olfaction testing during the in-clinic phase of the study. In addition, a detailed pain phenotype for each subject was obtained over a 3-month period at home using diaries, enabling subjects to self-report pain attacks, potential triggers, duration and severity of pain. All subjects reported pain and heat in the extremities (usually feet and/or hands), with pain attacks triggered by heat or exercise and relieved mainly by non-pharmacological manoeuvres such as cooling. A large proportion of pain attacks (355/1099; 32%) did not involve a specific trigger. There was considerable variability in the number, duration and severity of pain attacks between subjects, even those carrying the same mutation within a family, and within individuals over the 12-13 week observation period. Most subjects (11/13) had pain between attacks. For these subjects, mean pain severity between pain attacks was usually lower than that during an attack. Olfaction testing using the Sniffin'T test did not demonstrate hyperosmia. One subject had evidence of orthostatic hypotension. Overall, there was a statistically significant correlation between total Hospital Anxiety and Depression Scale scores (P= 0.005) and pain between attacks and for Hospital Anxiety and Depression Scale Depression scores and pain

  12. 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. PMID:27127450

  13. 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

  14. A semi-parametric approach to estimate risk functions associated with multi-dimensional exposure profiles: application to smoking and lung cancer

    PubMed Central

    2013-01-01

    Background A common characteristic of environmental epidemiology is the multi-dimensional aspect of exposure patterns, frequently reduced to a cumulative exposure for simplicity of analysis. By adopting a flexible Bayesian clustering approach, we explore the risk function linking exposure history to disease. This approach is applied here to study the relationship between different smoking characteristics and lung cancer in the framework of a population based case control study. Methods Our study includes 4658 males (1995 cases, 2663 controls) with full smoking history (intensity, duration, time since cessation, pack-years) from the ICARE multi-centre study conducted from 2001-2007. We extend Bayesian clustering techniques to explore predictive risk surfaces for covariate profiles of interest. Results We were able to partition the population into 12 clusters with different smoking profiles and lung cancer risk. Our results confirm that when compared to intensity, duration is the predominant driver of risk. On the other hand, using pack-years of cigarette smoking as a single summary leads to a considerable loss of information. Conclusions Our method estimates a disease risk associated to a specific exposure profile by robustly accounting for the different dimensions of exposure and will be helpful in general to give further insight into the effect of exposures that are accumulated through different time patterns. PMID:24152389

  15. MicroRNA expression profiling in children with different asthma phenotypes.

    PubMed

    Midyat, Levent; Gulen, Figen; Karaca, Emin; Ozkinay, Ferda; Tanac, Remziye; Demir, Esen; Cogulu, Ozgur; Aslan, Asli; Ozkinay, Cihangir; Onay, Huseyin; Atasever, Mesude

    2016-06-01

    An improved understanding of the molecular mechanisms in asthma through exploring the role of microRNAs may offer promise to reveal new approaches for primary prevention and identification of new therapeutic targets in childhood asthma. The primary goal of this study is to identify the microRNAs that play a role in the pathogenesis of asthma in pediatric age group. The secondary goal is to analyze these microRNAs according to the asthma phenotype, atopic status, and severity of the disease exacerbation. To our knowledge, this is the first research project in the literature which studies the relationship between microRNA expression and the severity of childhood asthma. One hundred children between 6 and 18 years old with a diagnosis of asthma, and 100 age-matched healthy children were enrolled in this study, and the analyses of microRNA expression profiles were performed in the Medical Genetics Laboratories of Ege University between November 2009 and June 2010. The expression of 10 microRNAs were shown to be higher in patients with more severe asthma, and the expression of these microRNAs were also found to be higher in patients who present with more severe acute asthma exacerbation symptoms (P < 0.001). Also, five microRNAs were found to be expressed more than twofold in allergic patients when compared to non-allergic participants (P <0.001). Asthma is one of the best examples of complex genetic diseases, and further studies, which will investigate the relationship between these microRNA's and their target genes, are needed to learn more about the specific roles of microRNAs in respiratory diseases. Pediatr Pulmonol. 2016;51:582-587. © 2015 Wiley Periodicals, Inc. PMID:26422695

  16. Expansion of the phenotypic profile of the young child with XXY.

    PubMed

    Samango-Sprouse, Carole

    2010-12-01

    XXY is a common chromosomal abnormality which remains under diagnosed and not well understood, although it was first described more than 50 years ago. In the last ten years, with advancement in neuroimaging technology and the greater understanding of behavioral neurogenetics, there has been a resurgence of interest in children and adults with XXY. This homogenous population provides insight into the interaction between learning dysfunction, brain development and behavioral performance that may be investigated from birth onward. The unique attributes of the child from birth to 6 years of age with XXY is discussed in this paper. This paper postulates a novel reconceptualization of the phenotypic presentation of the boys with XXY. The neurodevelopmental profile of XXY is actually quite consistent over time with the common thread of speech and language deficits, motor dysfunction and frontal lobe deficits including attention, planning and organization. The early motor and speech disturbances are not random developmental delays, but rather the early presentation of the central nervous system dysfunction associated with XXY. Muscle tonus abnormalities are present in trunk, upper extremities and oral facial musculature in more than 80% of the infants with XXY.Androgen deficiency may be an integral part of the delays observed in boys with XXY, since androgen is influential in brain organization, neurobehavioral development, temperament and mood in humans. It is plausible that the earliest biomarker for androgen deficiency in XXY may be the decreased muscle tonus. Androgen deficiency may not be the only causative factor in the neurodevelopmental disturbance in individuals with XXY, but may promote a restorative function if timing and dosage is appropriate. The study of children with XXY offers an opportunity to observe the impact of the genetic and chromosomal influence on learning and behavior in a population with great homogeneity. XXY is a multifaceted spectrum disorder

  17. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila.

    PubMed

    Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K

    2015-12-01

    Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context. PMID:26530416

  18. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila

    PubMed Central

    Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K.

    2015-01-01

    Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual’s genetic and environmental context. PMID:26530416

  19. 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…

  20. Transcriptional profiling of phenotypically different Epo-Fc expressing CHO clones by cross-species microarray analysis.

    PubMed

    Trummer, Evelyn; Ernst, Wolfgang; Hesse, Friedemann; Schriebl, Kornelia; Lattenmayer, Christine; Kunert, Renate; Vorauer-Uhl, Karola; Katinger, Hermann; Müller, Dethardt

    2008-07-01

    Chinese hamster ovary (CHO) cells exhibit large variabilities regarding growth, recombinant protein production and post-translational processing during cell line development and clone selection. To accelerate the development of stable high quality cell factories, new efficient strategies for cell screening and clone selection are required. In our work, we combined phenotypic characterisation of recombinant CHO clones during early cell line development with transcription profile analysis using cross-species microarrays. The objective was to identify genes or gene patterns that correlate with clone specific alterations in terms of productivity, sialylation capacity and stress resistance. In all high producer clones transcriptional profiling revealed a common enrichment of gene ontology categories related to protein metabolism, transcription, nucleus and nucleolus, whereas no common genes were differentially regulated in clones showing higher sialylation capacities. Furthermore, we identified predictive stress-related marker genes that were up-regulated in one clone without showing the corresponding phenotype at an early stage of development. Thus, we successfully applied gene expression profiling to allocate transcriptomal differences to specific phenotypes that changed during cell line development. These promising results will further increase our efforts to develop CHO specific microarrays that deliver information about the suitability of a clone candidate for industrial production. PMID:18481264

  1. Multi-dimensional TOF-SIMS analysis for effective profiling of disease-related ions from the tissue surface

    PubMed Central

    Park, Ji-Won; Jeong, Hyobin; Kang, Byeongsoo; Kim, Su Jin; Park, Sang Yoon; Kang, Sokbom; Kim, Hark Kyun; Choi, Joon Sig; Hwang, Daehee; Lee, Tae Geol

    2015-01-01

    Time-of-flight secondary ion mass spectrometry (TOF-SIMS) emerges as a promising tool to identify the ions (small molecules) indicative of disease states from the surface of patient tissues. In TOF-SIMS analysis, an enhanced ionization of surface molecules is critical to increase the number of detected ions. Several methods have been developed to enhance ionization capability. However, how these methods improve identification of disease-related ions has not been systematically explored. Here, we present a multi-dimensional SIMS (MD-SIMS) that combines conventional TOF-SIMS and metal-assisted SIMS (MetA-SIMS). Using this approach, we analyzed cancer and adjacent normal tissues first by TOF-SIMS and subsequently by MetA-SIMS. In total, TOF- and MetA-SIMS detected 632 and 959 ions, respectively. Among them, 426 were commonly detected by both methods, while 206 and 533 were detected uniquely by TOF- and MetA-SIMS, respectively. Of the 426 commonly detected ions, 250 increased in their intensities by MetA-SIMS, whereas 176 decreased. The integrated analysis of the ions detected by the two methods resulted in an increased number of discriminatory ions leading to an enhanced separation between cancer and normal tissues. Therefore, the results show that MD-SIMS can be a useful approach to provide a comprehensive list of discriminatory ions indicative of disease states. PMID:26046669

  2. Multi-Parametric Profiling Network Based on Gene Expression and Phenotype Data: A Novel Approach to Developmental Neurotoxicity Testing

    PubMed Central

    Nagano, Reiko; Akanuma, Hiromi; Qin, Xian-Yang; Imanishi, Satoshi; Toyoshiba, Hiroyoshi; Yoshinaga, Jun; Ohsako, Seiichiroh; Sone, Hideko

    2012-01-01

    The establishment of more efficient approaches for developmental neurotoxicity testing (DNT) has been an emerging issue for children’s environmental health. Here we describe a systematic approach for DNT using the neuronal differentiation of mouse embryonic stem cells (mESCs) as a model of fetal programming. During embryoid body (EB) formation, mESCs were exposed to 12 chemicals for 24 h and then global gene expression profiling was performed using whole genome microarray analysis. Gene expression signatures for seven kinds of gene sets related to neuronal development and neuronal diseases were selected for further analysis. At the later stages of neuronal cell differentiation from EBs, neuronal phenotypic parameters were determined using a high-content image analyzer. Bayesian network analysis was then performed based on global gene expression and neuronal phenotypic data to generate comprehensive networks with a linkage between early events and later effects. Furthermore, the probability distribution values for the strength of the linkage between parameters in each network was calculated and then used in principal component analysis. The characterization of chemicals according to their neurotoxic potential reveals that the multi-parametric analysis based on phenotype and gene expression profiling during neuronal differentiation of mESCs can provide a useful tool to monitor fetal programming and to predict developmentally neurotoxic compounds. PMID:22312247

  3. Phenotypic profile of early-onset familial Alzheimer's disease caused by presenilin-1 E280A mutation.

    PubMed

    Sepulveda-Falla, Diego; Glatzel, Markus; Lopera, Francisco

    2012-01-01

    Presenilin 1 (PS1) mutations are the most common cause of early-onset familial Alzheimer's disease (EOFAD). They show a common phenotypic profile characterized by early age of onset, severe dementia and distinct neurodegeneration. The largest population of EOFAD carries the E280A mutation in PS1 and resides in Antioquia, Colombia, currently comprising around 5,000 individuals. Carriers start showing memory impairment in the third decade of life, followed by progressive impairment of language and other cognitive processes. They reach mild cognitive impairment around 45 and dementia around 50 years of age. There is some phenotypic variability among the carriers of this single PS1 mutation. Some patients present with epilepsy, verbal impairment, and cerebellar ataxia. Neuropathologically, PS1 E280A cases show pronounced brain atrophy, severe amyloid-β pathology, distinct hyperphosphorylated tau-related pathology, and cerebellar damage. The earliest event identified by functional magnetic imaging resonance is hyperactivation within the right anterior hippocampus around 33 years of age. This well-studied population with a clear pre-clinical profile and wide phenotypic variability in age of onset and clinical presentation is ideally suited for clinical trials and to study molecular mechanisms of Alzheimer's disease. PMID:22766738

  4. Multi-parametric profiling network based on gene expression and phenotype data: a novel approach to developmental neurotoxicity testing.

    PubMed

    Nagano, Reiko; Akanuma, Hiromi; Qin, Xian-Yang; Imanishi, Satoshi; Toyoshiba, Hiroyoshi; Yoshinaga, Jun; Ohsako, Seiichiroh; Sone, Hideko

    2012-01-01

    The establishment of more efficient approaches for developmental neurotoxicity testing (DNT) has been an emerging issue for children's environmental health. Here we describe a systematic approach for DNT using the neuronal differentiation of mouse embryonic stem cells (mESCs) as a model of fetal programming. During embryoid body (EB) formation, mESCs were exposed to 12 chemicals for 24 h and then global gene expression profiling was performed using whole genome microarray analysis. Gene expression signatures for seven kinds of gene sets related to neuronal development and neuronal diseases were selected for further analysis. At the later stages of neuronal cell differentiation from EBs, neuronal phenotypic parameters were determined using a high-content image analyzer. Bayesian network analysis was then performed based on global gene expression and neuronal phenotypic data to generate comprehensive networks with a linkage between early events and later effects. Furthermore, the probability distribution values for the strength of the linkage between parameters in each network was calculated and then used in principal component analysis. The characterization of chemicals according to their neurotoxic potential reveals that the multi-parametric analysis based on phenotype and gene expression profiling during neuronal differentiation of mESCs can provide a useful tool to monitor fetal programming and to predict developmentally neurotoxic compounds. PMID:22312247

  5. 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

  6. Oligonucleotide microarray expression profiling of contrasting invasive phenotypes in colorectal cancer.

    PubMed

    Thorn, Christopher C; Williams, Deborah; Freeman, Thomas C

    2011-01-01

    This chapter refers to the application of laser-capture microdissection with oligonucleotide microarray analysis. The protocol described has been successfully used to identify differential transcript expression between contrasting colorectal cancer invasive phenotypes. Tissue processing, RNA extraction, quality control, amplification, fluorescent labelling, purification, hybridisation, and elements of data analysis are covered. PMID:21761306

  7. Gene expression profiles of soybeans with mid-oleic acid seed phenotype

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seeds of the mid-oleic acid soybean mutant M23 accumulate higher levels of oleic acid (50-60% oleate) by virtue of a deletion of GmFAD2-1A, an isoform of the microsomal omega-6 oleate desaturase gene. In other less well characterized natural soybean varieties that are phenotypically mid-oleic, litt...

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

    SciTech Connect

    Joyner, Dominique; Fortney, Julian; Chakraborty, Romy; Hazen, Terry

    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 reducing 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

  9. Genomic Profiles of Diversification and Genotype-Phenotype Association in Island Nematode Lineages.

    PubMed

    McGaughran, Angela; Rödelsperger, Christian; Grimm, Dominik G; Meyer, Jan M; Moreno, Eduardo; Morgan, Katy; Leaver, Mark; Serobyan, Vahan; Rakitsch, Barbara; Borgwardt, Karsten M; Sommer, Ralf J

    2016-09-01

    Understanding how new species form requires investigation of evolutionary forces that cause phenotypic and genotypic changes among populations. However, the mechanisms underlying speciation vary and little is known about whether genomes diversify in the same ways in parallel at the incipient scale. We address this using the nematode, Pristionchus pacificus, which resides at an interesting point on the speciation continuum (distinct evolutionary lineages without reproductive isolation), and inhabits heterogeneous environments subject to divergent environmental pressures. Using whole genome re-sequencing of 264 strains, we estimate FST to identify outlier regions of extraordinary differentiation (∼1.725 Mb of the 172.5 Mb genome). We find evidence for shared divergent genomic regions occurring at a higher frequency than expected by chance among populations of the same evolutionary lineage. We use allele frequency spectra to find that, among lineages, 53% of divergent regions are consistent with adaptive selection, whereas 24% and 23% of such regions suggest background selection and restricted gene flow, respectively. In contrast, among populations from the same lineage, similar proportions (34-48%) of divergent regions correspond to adaptive selection and restricted gene flow, whereas 13-22% suggest background selection. Because speciation often involves phenotypic and genomic divergence, we also evaluate phenotypic variation, focusing on pH tolerance, which we find is diverging in a manner corresponding to environmental differences among populations. Taking a genome-wide association approach, we functionally validate a significant genotype-phenotype association for this trait. Our results are consistent with P. pacificus undergoing heterogeneous genotypic and phenotypic diversification related to both evolutionary and environmental processes. PMID:27189551

  10. Cytokine profiles and phenotype regulation of antigen presenting cells by genotype-I porcine reproductive and respiratory syndrome virus isolates

    PubMed Central

    2011-01-01

    The present study examined the immunological response of antigen presenting cells (APC) to genotype-I isolates of porcine reproductive and respiratory syndrome virus (PRRSV) infection by analysing the cytokine profile induced and evaluating the changes taking place upon infection on immunologically relevant cell markers (MHCI, MHCII, CD80/86, CD14, CD16, CD163, CD172a, SWC9). Several types of APC were infected with 39 PRRSV isolates. The results show that different isolates were able to induce different patterns of IL-10 and TNF-α. The four possible phenotypes based on the ability to induce IL-10 and/or TNF-α were observed, although different cell types seemed to have different capabilities. In addition, isolates inducing different cytokine-release profiles on APC could induce different expression of cell markers. PMID:21314968

  11. Cytokine profiles and phenotype regulation of antigen presenting cells by genotype-I porcine reproductive and respiratory syndrome virus isolates.

    PubMed

    Gimeno, Mariona; Darwich, Laila; Diaz, Ivan; de la Torre, Eugenia; Pujols, Joan; Martín, Marga; Inumaru, Shigeki; Cano, Esmeralda; Domingo, Mariano; Montoya, Maria; Mateu, Enric

    2011-01-01

    The present study examined the immunological response of antigen presenting cells (APC) to genotype-I isolates of porcine reproductive and respiratory syndrome virus (PRRSV) infection by analysing the cytokine profile induced and evaluating the changes taking place upon infection on immunologically relevant cell markers (MHCI, MHCII, CD80/86, CD14, CD16, CD163, CD172a, SWC9). Several types of APC were infected with 39 PRRSV isolates. The results show that different isolates were able to induce different patterns of IL-10 and TNF-α. The four possible phenotypes based on the ability to induce IL-10 and/or TNF-α were observed, although different cell types seemed to have different capabilities. In addition, isolates inducing different cytokine-release profiles on APC could induce different expression of cell markers. PMID:21314968

  12. Mapping of Genotype–Phenotype Diversity among Clinical Isolates of Mycobacterium tuberculosis by Sequence-Based Transcriptional Profiling

    PubMed Central

    Rose, Graham; Cortes, Teresa; Comas, Iñaki; Coscolla, Mireia; Gagneux, Sebastien; Young, Douglas B.

    2013-01-01

    Genome sequencing has identified an extensive repertoire of single nucleotide polymorphisms among clinical isolates of Mycobacterium tuberculosis, but the extent to which these differences influence phenotypic properties of the bacteria remains to be elucidated. To determine whether these polymorphisms give rise to phenotypic diversity, we have integrated genome data sets with RNA sequencing to assess their impact on the comparative transcriptome profiles of strains belonging to M. tuberculosis Lineages 1 and 2. We observed clear correlations between genotype and transcriptional phenotype. These arose by three mechanisms. First, lineage-specific changes in amino acid sequence of transcriptional regulators were associated with alterations in their ability to control gene expression. Second, changes in nucleotide sequence were associated with alteration of promoter activity and generation of novel transcriptional start sites in intergenic regions and within coding sequences. We show that in some cases this mechanism is expected to generate functionally active truncated proteins involved in innate immune recognition. Finally, genes showing lineage-specific patterns of differential expression not linked directly to primary mutations were characterized by a striking overrepresentation of toxin–antitoxin pairs. Taken together, these findings advance our understanding of mycobacterial evolution, contribute to a systems level understanding of this important human pathogen, and more broadly demonstrate the application of state-of-the-art techniques to provide novel insight into mechanisms by which intergenic and silent mutations contribute to diversity. PMID:24115728

  13. Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles.

    PubMed

    Ou, Guangshuo; Koga, Makato; Blacque, Oliver E; Murayama, Takashi; Ohshima, Yasumi; Schafer, Jenny C; Li, Chunmei; Yoder, Bradley K; Leroux, Michel R; Scholey, Jonathan M

    2007-05-01

    Sensory cilium biogenesis within Caenorhabditis elegans neurons depends on the kinesin-2-dependent intraflagellar transport (IFT) of ciliary precursors associated with IFT particles to the axoneme tip. Here we analyzed the molecular organization of the IFT machinery by comparing the in vivo transport and phenotypic profiles of multiple proteins involved in IFT and ciliogenesis. Based on their motility in wild-type and bbs (Bardet-Biedl syndrome) mutants, IFT proteins were classified into groups with similar transport profiles that we refer to as "modules." We also analyzed the distribution and transport of fluorescent IFT particles in multiple known ciliary mutants and 49 new ciliary mutants. Most of the latter mutants were snip-SNP mapped and one, namely dyf-14(ks69), was cloned and found to encode a conserved protein essential for ciliogenesis. The products of these ciliogenesis genes could also be assigned to the aforementioned set of modules or to specific aspects of ciliogenesis, based on IFT particle dynamics and ciliary mutant phenotypes. Although binding assays would be required to confirm direct physical interactions, the results are consistent with the hypothesis that the C. elegans IFT machinery has a modular design, consisting of modules IFT-subcomplex A, IFT-subcomplex B, and a BBS protein complex, in addition to motor and cargo modules, with each module contributing to distinct functional aspects of IFT or ciliogenesis. PMID:17314406

  14. ProtPhylo: identification of protein–phenotype and protein–protein functional associations via phylogenetic profiling

    PubMed Central

    Cheng, Yiming; Perocchi, Fabiana

    2015-01-01

    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. PMID:25956654

  15. 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

  16. Developmental phenotypic-genotypic associations of tyrosinase and melanocortin 1 receptor genes with changing profiles in chicken plumage pigmentation.

    PubMed

    Liu, W B; Chen, S R; Zheng, J X; Qu, L J; Xu, G Y; Yang, N

    2010-06-01

    The tyrosinase (TYR) and melanocortin 1 receptor (MC1R) genes have been accepted as major genes involved in the plumage pigmentation of chickens. The co-segregation of plumage coloration and sequence polymorphism in TYR and MC1R genes were investigated using an intercross between black and white plumage color types of the Dongxiang blue-shelled chicken. Profiles of plumage color changing and genes expression levels of TYR and MC1R were observed from hatch to 112 d of age using quantitative real-time reverse transcription-PCR. Intercrossed offspring were classified by phenotypes of plumage colors. The phenotypes of black and amber chicks with genotypes of E_C_ exhibited a black feather pattern, whereas white, gray, and buff chicks with genotypes of E_cc and eecc belonged to the white feather pattern. Although TYR in cooperation with MC1R determined the coloration feather patterns, the different phenotypes did not correspond completely with the genotypes. During the period studied, plumage phenotype changed dramatically, and the buff and gray down were gradually replaced by whiteness feathers. Real-time reverse transcription-PCR studies showed that 1) expression levels of TYR declined dramatically with age, and expression at hatch was highest (P<0.01) during the ages studied; 2) expression level of MC1R was higher at 28 d than at younger and older ages; and 3) expression of TYR in chickens carrying E/E and E/e alleles on MC1R loci were higher than those carrying e/e alleles from hatch to 28 d. PMID:20460655

  17. Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes

    PubMed Central

    Ho, Jennifer E.; Larson, Martin G.; Ghorbani, Anahita; Cheng, Susan; Chen, Ming-Huei; Keyes, Michelle; Rhee, Eugene P.; Clish, Clary B.; Vasan, Ramachandran S.

    2016-01-01

    Background Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling. Methods and Results We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI) was associated with 69 of 217 metabolites (P<0.00023 for all), including aromatic (tyrosine, phenylalanine) and branched chain amino acids (valine, isoleucine, leucine). Additional metabolic pathways associated with BMI included the citric acid cycle (isocitrate, alpha-ketoglutarate, aconitate), the tryptophan pathway (kynurenine, kynurenic acid), and the urea cycle. There was considerable overlap in metabolite profiles between BMI, abdominal adiposity, insulin resistance [IR] and dyslipidemia, modest overlap of metabolite profiles between BMI and hyperglycemia, and little overlap with fasting glucose or elevated blood pressure. Metabolite profiles were associated with longitudinal changes in fasting glucose, but the involved metabolites (ornithine, 5-HIAA, aminoadipic acid, isoleucine, cotinine) were distinct from those associated with baseline glucose or other traits. Obesity status appeared to “modify” the association of 9 metabolites with IR. For example, bile acid metabolites were strongly associated with IR among obese but not lean individuals, whereas isoleucine had a stronger association with IR in lean individuals. Conclusions In this large-scale metabolite profiling study, body mass index was associated with a broad range of metabolic alterations. Metabolite profiling highlighted considerable overlap with

  18. Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma

    PubMed Central

    Gunawardhana, Lakshitha P; Gibson, Peter G; Simpson, Jodie L; Benton, Miles C; Lea, Rodney A; Baines, Katherine J

    2014-01-01

    Epigenetic changes including DNA methylation caused by environmental exposures may contribute to the heterogeneous inflammatory response in asthma. Here we investigate alterations in DNA methylation of purified blood monocytes that are associated with inflammatory phenotypes of asthma. Peripheral blood was collected from adults with eosinophilic asthma (EA; n = 21), paucigranulocytic asthma (PGA; n = 22), neutrophilic asthma (NA; n = 9), and healthy controls (n = 10). Blood monocytes were isolated using ficoll density gradient and immuno-magnetic cell separation. Bisulfite converted genomic DNA was hybridized to Illumina Infinium Methylation27 arrays and analyzed for differential methylation using R/Bioconductor packages; networks of gene interactions were identified using the STRING database. Compared with healthy controls, differentially methylated CpG loci were identified in EA (n = 413), PGA (n = 495), and NA (n = 89). We found that 223, 237, and 72 loci were significantly hypermethylated in EA, PGA, and NA, respectively. Nine genes were common to all three phenotypes and showed increased methylation in asthma. Three pathway networks were identified in EA, involved in purine metabolism, calcium signaling, and ECM-receptor interaction. In PGA, two networks were identified, involved in neuroactive ligand-receptor interaction and ubiquitin mediated proteolysis. In NA, one network was identified involving sFRP1 as a key node, over representing the Wnt signaling pathway. We have identified characteristic alterations in DNA methylation that are associated with inflammatory phenotypes of asthma and may contribute to the disease mechanisms. This network-based characterization may help in the development of epigenetic biomarkers and therapeutic targets for asthma. PMID:25147914

  19. 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…

  20. Prevalent phenotypic and genotypic profile of enterotoxigenic Escherichia coli among Iranian children.

    PubMed

    Nazarian, Shahram; Gargari, Seyed Latif Mousavi; Rasooli, Iraj; Alerasol, Masoome; Bagheri, Samane; Alipoor, Shakiba Darvish

    2014-01-01

    Enterotoxigenic Escherichia coli (ETEC) is the most common cause of diarrhea among children. ETEC strains express colonization factors (CFs), which mediate adherence to the small intestinal epithelium and produce entrotoxins that induce diarrhea. Here, we characterized the phenotypes and genotypes of ETEC strains from 261 diarrheal stool samples from Iranian children. The prevalence of ETEC was 8.04%. Most of the isolates were positive for heat-labile and heat-stable toxins. CFA/I, CS3, CS2, and CS5 were detected from some of the clinical isolates. 33.3% of the isolates did not express CFs. The majority of ETEC isolates were identified as O127 and O128 serotypes, and 57% of the strains were resistant to more than 1 antimicrobial agent. Heat-labile enterotoxin activity was confirmed using the Y1 adrenal cell assay, rabbit ileal loop and adenylate cyclase activation tests. Regional phenotypic and genotypic characterization could help to elucidate the ecology and pathogenicity of ETEC to efficiently reduce the burden of illness brought about by ETEC. This study may lead to development of effective prophylactic measures. PMID:24647248

  1. Microgenomics profile the endogenous angiogenic phenotype in subpopulations of aggressive melanoma.

    PubMed

    Demou, Zoe N; Hendrix, Mary J C

    2008-10-01

    Beyond the elemental role of blood vessels in tumor growth, fluid conducting networks lacking endothelium (termed vasculogenic mimicry) were identified previously in metastatic melanoma and other cancer types. The etiology remains unclear, though it appears to involve dysregulation of the tumor-specific phenotype and transdifferentiation. Instigating the molecular deciphering of this phenomenon, we established a novel technique for microdissecting the spontaneously formed vascular-like networks and the randomly arranged cells (nests) from living 3D cultures of melanoma and performed microgenomics analysis. For the first time we show that despite the shared genotype, transcription was differentially regulated among the phenotypically distinct melanoma structures in vasculogenic mimicry. Several angiogenesis-specific genes were differentially expressed in higher levels in network cells of both uveal and cutaneous melanoma with intriguing representation of the ephrin family of angiogenesis factors, which was confirmed with immunocytochemistry. Interestingly, the adjacent nest-cells over-expressed ECM-related genes. Moreover, expression of angiogenesis-specific genes in melanoma resembled that of normal microvascular cells and was enhanced in melanoma disseminating hematogenously. The findings suggest that melanoma plasticity could enable autopoiesis of vascular-mimicking elements within the tumor infrastructure with significant clinical implications, such as response to anti-angiogenic treatments. Identifying factors regulating tumor plasticity and heterogeneity at the molecular level is essential in designing effective anti-cancer therapies. PMID:18655191

  2. Phenotypic Profiling of Scedosporium aurantiacum, an Opportunistic Pathogen Colonizing Human Lungs

    PubMed Central

    Kaur, Jashanpreet; Duan, Shu Yao; Vaas, Lea A. I.; Penesyan, Anahit; Meyer, Wieland; Paulsen, Ian T.; Nevalainen, Helena

    2015-01-01

    Genotyping studies of Australian Scedosporium isolates have revealed the strong prevalence of a recently described species: Scedosporium aurantiacum. In addition to occurring in the environment, this fungus is also known to colonise the respiratory tracts of cystic fibrosis (CF) patients. A high throughput Phenotype Microarray (PM) analysis using 94 assorted substrates (sugars, amino acids, hexose-acids and carboxylic acids) was carried out for four isolates exhibiting different levels of virulence, determined using a Galleria mellonella infection model. A significant difference was observed in the substrate utilisation patterns of strains displaying differential virulence. For example, certain sugars such as sucrose (saccharose) were utilised only by low virulence strains whereas some sugar derivatives such as D-turanose promoted respiration only in the more virulent strains. Strains with a higher level of virulence also displayed flexibility and metabolic adaptability at two different temperature conditions tested (28 and 37°C). Phenotype microarray data were integrated with the whole-genome sequence data of S. aurantiacum to reconstruct a pathway map for the metabolism of selected substrates to further elucidate differences between the strains. PMID:25811884

  3. 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

  4. Multidimensional scaling

    PubMed Central

    Papesh, Megan H.; Goldinger, Stephen D.

    2012-01-01

    The concept of similarity, or a sense of "sameness" among things, is pivotal to theories in the cognitive sciences and beyond. Similarity, however, is a difficult thing to measure. Multidimensional scaling (MDS) is a tool by which researchers can obtain quantitative estimates of similarity among groups of items. More formally, MDS refers to a set of statistical techniques that are used to reduce the complexity of a data set, permitting visual appreciation of the underlying relational structures contained therein. The current paper provides an overview of MDS. We discuss key aspects of performing this technique, such as methods that can be used to collect similarity estimates, analytic techniques for treating proximity data, and various concerns regarding interpretation of the MDS output. MDS analyses of two novel data sets are also included, highlighting in step-by-step fashion how MDS is performed, and key issues that may arise during analysis. PMID:23359318

  5. Fibroblasts from phenotypically normal palmar fascia exhibit molecular profiles highly similar to fibroblasts from active disease in Dupuytren's Contracture

    PubMed Central

    2012-01-01

    Background Dupuytren's contracture (DC) is a fibroproliferative disorder characterized by the progressive development of a scar-like collagen-rich cord that affects the palmar fascia of the hand and leads to digital flexion contractures. DC is most commonly treated by surgical resection of the diseased tissue, but has a high reported recurrence rate ranging from 27% to 80%. We sought to determine if the transcriptomic profiles of fibroblasts derived from DC-affected palmar fascia, adjacent phenotypically normal palmar fascia, and non-DC palmar fascial tissues might provide mechanistic clues to understanding the puzzle of disease predisposition and recurrence in DC. Methods To achieve this, total RNA was obtained from fibroblasts derived from primary DC-affected palmar fascia, patient-matched unaffected palmar fascia, and palmar fascia from non-DC patients undergoing carpal tunnel release (6 patients in each group). These cells were grown on a type-1 collagen substrate (to better mimic their in vivo environments). Microarray analyses were subsequently performed using Illumina BeadChip arrays to compare the transcriptomic profiles of these three cell populations. Data were analyzed using Significance Analysis of Microarrays (SAM v3.02), hierarchical clustering, concordance mapping and Venn diagram. Results We found that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected fascia of DC patients exhibited a much greater overlap than fibroblasts derived from the palmar fascia of patients undergoing carpal tunnel release. Quantitative real time RT-PCR confirmed the differential expression of select genes validating the microarray data analyses. These data are consistent with the hypothesis that predisposition and recurrence in DC may stem, at least in part, from intrinsic similarities in the basal gene expression of diseased and phenotypically unaffected palmar fascia fibroblasts. These data also demonstrate that a collagen

  6. Gene Expression Profiling of H9c2 Myoblast Differentiation towards a Cardiac-Like Phenotype

    PubMed Central

    Branco, Ana F.; Pereira, Susana P.; Gonzalez, Susana; Gusev, Oleg; Rizvanov, Albert A.; Oliveira, Paulo J.

    2015-01-01

    H9c2 myoblasts are a cell model used as an alternative for cardiomyocytes. H9c2 cells have the ability to differentiate towards a cardiac phenotype when the media serum is reduced in the presence of all-trans-retinoic acid (RA), creating multinucleated cells with low proliferative capacity. In the present study, we performed for the first time a transcriptional analysis of the H9c2 cell line in two differentiation states, i.e. embryonic cells and differentiated cardiac-like cells. The results show that RA-induced H9c2 differentiation increased the expression of genes encoding for cardiac sarcomeric proteins such as troponin T, or calcium transporters and associated machinery, including SERCA2, ryanodine receptor and phospholamban as well as genes associated with mitochondrial energy production including respiratory chain complexes subunits, mitochondrial creatine kinase, carnitine palmitoyltransferase I and uncoupling proteins. Undifferentiated myoblasts showed increased gene expression of pro-survival proteins such as Bcl-2 as well as cell cycle-regulating proteins. The results indicate that the differentiation of H9c2 cells lead to an increase of transcripts and protein levels involved in calcium handling, glycolytic and mitochondrial metabolism, confirming that H9c2 cell differentiation induced by RA towards a more cardiac-like phenotype involves remodeled mitochondrial function. PI3K, PDK1 and p-CREB also appear to be involved on H9c2 differentiation. Furthermore, complex analysis of differently expressed transcripts revealed significant up-regulation of gene expression related to cardiac muscle contraction, dilated cardiomyopathy and other pathways specific for the cardiac tissue. Metabolic and gene expression remodeling impacts cell responses to different stimuli and determine how these cells are used for biochemical assays. PMID:26121149

  7. Gene Expression Profiling of H9c2 Myoblast Differentiation towards a Cardiac-Like Phenotype.

    PubMed

    Branco, Ana F; Pereira, Susana P; Gonzalez, Susana; Gusev, Oleg; Rizvanov, Albert A; Oliveira, Paulo J

    2015-01-01

    H9c2 myoblasts are a cell model used as an alternative for cardiomyocytes. H9c2 cells have the ability to differentiate towards a cardiac phenotype when the media serum is reduced in the presence of all-trans-retinoic acid (RA), creating multinucleated cells with low proliferative capacity. In the present study, we performed for the first time a transcriptional analysis of the H9c2 cell line in two differentiation states, i.e. embryonic cells and differentiated cardiac-like cells. The results show that RA-induced H9c2 differentiation increased the expression of genes encoding for cardiac sarcomeric proteins such as troponin T, or calcium transporters and associated machinery, including SERCA2, ryanodine receptor and phospholamban as well as genes associated with mitochondrial energy production including respiratory chain complexes subunits, mitochondrial creatine kinase, carnitine palmitoyltransferase I and uncoupling proteins. Undifferentiated myoblasts showed increased gene expression of pro-survival proteins such as Bcl-2 as well as cell cycle-regulating proteins. The results indicate that the differentiation of H9c2 cells lead to an increase of transcripts and protein levels involved in calcium handling, glycolytic and mitochondrial metabolism, confirming that H9c2 cell differentiation induced by RA towards a more cardiac-like phenotype involves remodeled mitochondrial function. PI3K, PDK1 and p-CREB also appear to be involved on H9c2 differentiation. Furthermore, complex analysis of differently expressed transcripts revealed significant up-regulation of gene expression related to cardiac muscle contraction, dilated cardiomyopathy and other pathways specific for the cardiac tissue. Metabolic and gene expression remodeling impacts cell responses to different stimuli and determine how these cells are used for biochemical assays. PMID:26121149

  8. Microbial Forensics: Predicting Phenotypic Characteristics and Environmental Conditions from Large-Scale Gene Expression Profiles

    PubMed Central

    Kim, Minseung; Zorraquino, Violeta; Tagkopoulos, Ilias

    2015-01-01

    A tantalizing question in cellular physiology is whether the cellular state and environmental conditions can be inferred by the expression signature of an organism. To investigate this relationship, we created an extensive normalized gene expression compendium for the bacterium Escherichia coli that was further enriched with meta-information through an iterative learning procedure. We then constructed an ensemble method to predict environmental and cellular state, including strain, growth phase, medium, oxygen level, antibiotic and carbon source presence. Results show that gene expression is an excellent predictor of environmental structure, with multi-class ensemble models achieving balanced accuracy between 70.0% (±3.5%) to 98.3% (±2.3%) for the various characteristics. Interestingly, this performance can be significantly boosted when environmental and strain characteristics are simultaneously considered, as a composite classifier that captures the inter-dependencies of three characteristics (medium, phase and strain) achieved 10.6% (±1.0%) higher performance than any individual models. Contrary to expectations, only 59% of the top informative genes were also identified as differentially expressed under the respective conditions. Functional analysis of the respective genetic signatures implicates a wide spectrum of Gene Ontology terms and KEGG pathways with condition-specific information content, including iron transport, transferases, and enterobactin synthesis. Further experimental phenotypic-to-genotypic mapping that we conducted for knock-out mutants argues for the information content of top-ranked genes. This work demonstrates the degree at which genome-scale transcriptional information can be predictive of latent, heterogeneous and seemingly disparate phenotypic and environmental characteristics, with far-reaching applications. PMID:25774498

  9. Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes

    PubMed Central

    Rodriguez-Palacios, Alex; Kodani, Tomohiro; Kaydo, Lindsey; Pietropaoli, Davide; Corridoni, Daniele; Howell, Scott; Katz, Jeffry; Xin, Wei; Pizarro, Theresa T.; Cominelli, Fabio

    2015-01-01

    Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) to rapidly profile the entire intestinal topography and assess inflammation. We examine the mucosal surface of >700 mice (encompassing >16 strains and various IBD-models), create a profiling catalogue of 3D-stereomicroscopic abnormalities and demonstrate that mice with comparable histological scores display unique sub-clusters of 3D-structure-patterns of IBD pathology, which we call 3D-stereoenterotypes, and which are otherwise indiscernible histologically. We show that two ileal IBD-stereoenterotypes (‘cobblestones' versus ‘villous mini-aggregation') cluster separately within two distinct mouse lines of spontaneous ileitis, suggesting that host genetics drive unique and divergent inflammatory 3D-structural patterns in the gut. In humans, stereomicroscopy reveals ‘liquefaction' lesions and hierarchical fistulous complexes, enriched with clostridia/segmented filamentous bacteria, running under healthy mucosa in Crohn's disease. We suggest that stereomicroscopic (3D-SMAPgut) profiling can be easily implemented and enable the comprehensive study of inflammatory 3D structures, genetics and flora in IBD. PMID:26154811

  10. Molecular and phenotypic profiling from the base to the crown in maritime pine wood-forming tissue.

    PubMed

    Paiva, Jorge A P; Garcés, Marcelo; Alves, Ana; Garnier-Géré, Pauline; Rodrigues, José Carlos; Lalanne, Céline; Porcon, Stéphane; Le Provost, Grégoire; Perez, Denilson da Silva; Brach, Jean; Frigerio, Jean-Marc; Claverol, Stéphane; Barré, Aurélien; Fevereiro, Pedro; Plomion, Christophe

    2008-01-01

    Environmental, developmental and genetic factors affect variation in wood properties at the chemical, anatomical and physical levels. Here, the phenotypic variation observed along the tree stem was explored and the hypothesis tested that this variation could be the result of the differential expression of genes/proteins during wood formation. Differentiating xylem samples of maritime pine (Pinus pinaster) were collected from the top (crown wood, CW) to the bottom (base wood, BW) of adult trees. These samples were characterized by Fourier transform infrared spectroscopy (FTIR) and analytical pyrolysis. Two main groups of samples, corresponding to CW and BW, could be distinguished from cell wall chemical composition. A genomic approach, combining large-scale production of expressed sequence tags (ESTs), gene expression profiling and quantitative proteomics analysis, allowed identification of 262 unigenes (out of 3512) and 231 proteins (out of 1372 spots) that were differentially expressed along the stem. A good relationship was found between functional categories from transcriptomic and proteomic data. A good fit between the molecular mechanisms involved in CW-BW formation and these two types of wood phenotypic differences was also observed. This work provides a list of candidate genes for wood properties that will be tested in forward genetics. PMID:18298434

  11. Phenotypic characterization of Mycoplasma synoviae induced changes in the metabolic and sensitivity profile of in vitro infected chicken chondrocytes.

    PubMed

    Dušanić, Daliborka; Benčina, Dušan; Narat, Mojca; Oven, Irena

    2014-01-01

    In infectious synovitis caused by Mycoplasma synoviae chicken chondrocytes (CCH) may come into direct contact with these bacteria that are also capable of invading CCH in vitro. In this study, phenotype microarrays were used to evaluate the influence of Mycoplasma synoviae on the global metabolic activity of CCH. Therefore, CCH were cultured in the presence of 504 individual compounds, spotted in wells of 11 phenotype microarrays for eukaryotic cells, and exposed to Mycoplasma synoviae membranes or viable Mycoplasma synoviae. Metabolic activity and sensitivity of normal cells versus infected cells were evaluated. Metabolic profiles of CCH treated with viable Mycoplasma synoviae or its membranes were significantly different from those of CCH alone. CCH treated with Mycoplasma synoviae membranes were able to use 48 carbon/nitrogen sources not used by CCH alone. Treatment also influenced ion uptake in CCH and intensified the sensitivity to 13 hormones, 5 immune mediators, and 29 cytotoxic chemicals. CCH were even more sensitive to hormones/immune mediators when exposed to viable Mycoplasma synoviae. Our results indicate that exposure to Mycoplasma synoviae or its membranes induces a wide range of metabolic and sensitivity modifications in CCH that can contribute to pathological processes in the development of infectious synovitis. PMID:25243158

  12. From genotypes to phenotypes: classification of the tumour profiles for different variants of the cadherin adhesion pathway

    NASA Astrophysics Data System (ADS)

    Ramis-Conde, Ignacio; Drasdo, Dirk

    2012-06-01

    The E-cadherin adhesive profile expressed by a tumour is a characterization of the intracellular and intercellular protein interactions that control cell-cell adhesion. Within the intracellular proteins that determine the tumour adhesive profile, Src and PI3 are two essentials to initiate the formation of the E-cadherin adhesion complex. On the other hand, Src has also the capability of disrupting the β-catenin-E-cadherin complex and down-regulating cell-cell adhesion. In this paper, using a multi-scale mathematical model, we study the role of each of these proteins in the adhesive profile and invasive properties of the tumour. To do this, we create three versions of an intracellular model that explains the interplay between the proteins E-cadherin, β-catenin, Src and PI3; and we couple them to the strength of the cell-cell adhesion forces within an individual-cell-based model. The simulation results show how the tumour profile and its aggressive potential may change depending on the intrinsic characteristics of the protein pathways, and how these pathways may influence the early stages of cancer invasion. Our major findings may be summarized as follows. (1) Intermediate levels of Src synthesis rates generate the least invasive tumour phenotype. (2) Conclusions drawn from findings obtained from the intracellular molecular dynamics (here cadherin-catenin binding complexes) to the multi-cellular invasive potential of a tumour may be misleading or erroneous. The conclusions should be validated in a multi-cellular context on timescales relevant for population growth. (3) Monoclonal populations of more cohesive cells with otherwise equal properties tend to grow slower. (4) Less cohesive cells tend to outcompete more cohesive cells. (5) Less cohesive cells have a larger probability of invasion as migration forces can more easily outbalance cohesive forces.

  13. Phenotypic side effects prediction by optimizing correlation with chemical and target profiles of drugs.

    PubMed

    Kanji, Rakesh; Sharma, Abhinav; Bagler, Ganesh

    2015-11-01

    Despite technological progresses and improved understanding of biological systems, discovery of novel drugs is an inefficient, arduous and expensive process. Research and development cost of drugs is unreasonably high, largely attributed to the high attrition rate of candidate drugs due to adverse drug reactions. Computational methods for accurate prediction of drug side effects, rooted in empirical data of drugs, have the potential to enhance the efficacy of the drug discovery process. Identification of features critical for specifying side effects would facilitate efficient computational procedures for their prediction. We devised a generalized ordinary canonical correlation model for prediction of drug side effects based on their chemical properties as well as their target profiles. While the former is based on 2D and 3D chemical features, the latter enumerates a systems-level property of drugs. We find that the model incorporating chemical features outperforms that incorporating target profiles. Furthermore we identified the 2D and 3D chemical properties that yield best results, thereby implying their relevance in specifying adverse drug reactions. PMID:26252576

  14. In Situ Characterizing Membrane Lipid Phenotype of Human Lung Cancer Cell Lines Using Mass Spectrometry Profiling

    PubMed Central

    He, Manwen; Guo, Shuai; Ren, Junling; Li, Zhili

    2016-01-01

    Abnormal lipid metabolisms are closely associated with cancers. In this study, mass spectrometry was employed to in situ investigate the associations of membrane lipid phenotypes of six human lung cancer cell lines (i.e., A549, H1650, H1975 from adenocarcinoma, H157 and H1703 from squamous cell carcinomas, and H460 from a large cell carcinoma) with cancer cell types and finally total 230 lipids were detected. Based these 230 lipids, partial least-square discriminant analysis indicated that fifteen lipids (i.e., PE 18:0_18:1, PI 18:0_20:4, SM 42:2, PE 16:0_20:4, PE 36:2, PC 36:2, SM 34:1, PA 38:3,C18:0, C22:4, PA 34:2, C20:5, C20:2, C18:2, and CerP 36:2) with variable importance in the projection (VIP) value of > 1.0 could be used to differentiate six cancer cell lines with the Predicted Residual Sum of Square (PRESS) score of 0.1974. Positive correlation between polyunsaturated fatty acids (i.e., C20:4, C22:4, C22:5, and C22:6) and polyunsaturated phospholipids (PE 16:0_20:4, PE 38:4, and PI 18:0_20:4) was observed in lung adenocarcinoma cells, especially for H1975 cells. Three adenocarcinoma cell lines (i.e., A549, H1650, and H1975) could be differentiated from other lung cancer cell lines based on the expression of C18:1, C20:1, C20:2, C20:5, and C22:6. PMID:27162539

  15. In Situ Characterizing Membrane Lipid Phenotype of Human Lung Cancer Cell Lines Using Mass Spectrometry Profiling.

    PubMed

    He, Manwen; Guo, Shuai; Ren, Junling; Li, Zhili

    2016-01-01

    Abnormal lipid metabolisms are closely associated with cancers. In this study, mass spectrometry was employed to in situ investigate the associations of membrane lipid phenotypes of six human lung cancer cell lines (i.e., A549, H1650, H1975 from adenocarcinoma, H157 and H1703 from squamous cell carcinomas, and H460 from a large cell carcinoma) with cancer cell types and finally total 230 lipids were detected. Based these 230 lipids, partial least-square discriminant analysis indicated that fifteen lipids (i.e., PE 18:0_18:1, PI 18:0_20:4, SM 42:2, PE 16:0_20:4, PE 36:2, PC 36:2, SM 34:1, PA 38:3,C18:0, C22:4, PA 34:2, C20:5, C20:2, C18:2, and CerP 36:2) with variable importance in the projection (VIP) value of > 1.0 could be used to differentiate six cancer cell lines with the Predicted Residual Sum of Square (PRESS) score of 0.1974. Positive correlation between polyunsaturated fatty acids (i.e., C20:4, C22:4, C22:5, and C22:6) and polyunsaturated phospholipids (PE 16:0_20:4, PE 38:4, and PI 18:0_20:4) was observed in lung adenocarcinoma cells, especially for H1975 cells. Three adenocarcinoma cell lines (i.e., A549, H1650, and H1975) could be differentiated from other lung cancer cell lines based on the expression of C18:1, C20:1, C20:2, C20:5, and C22:6. PMID:27162539

  16. Evaluation of a 7-Gene Genetic Profile for Athletic Endurance Phenotype in Ironman Championship Triathletes.

    PubMed

    Grealy, Rebecca; Herruer, Jasper; Smith, Carl L E; Hiller, Doug; Haseler, Luke J; Griffiths, Lyn R

    2015-01-01

    Polygenic profiling has been proposed for elite endurance performance, using an additive model determining the proportion of optimal alleles in endurance athletes. To investigate this model's utility for elite triathletes, we genotyped seven polymorphisms previously associated with an endurance polygenic profile (ACE Ins/Del, ACTN3 Arg577Ter, AMPD1 Gln12Ter, CKMM 1170bp/985+185bp, HFE His63Asp, GDF8 Lys153Arg and PPARGC1A Gly482Ser) in a cohort of 196 elite athletes who participated in the 2008 Kona Ironman championship triathlon. Mean performance time (PT) was not significantly different in individual marker analysis. Age, sex, and continent of origin had a significant influence on PT and were adjusted for. Only the AMPD1 endurance-optimal Gln allele was found to be significantly associated with an improvement in PT (model p = 5.79 x 10-17, AMPD1 genotype p = 0.01). Individual genotypes were combined into a total genotype score (TGS); TGS distribution ranged from 28.6 to 92.9, concordant with prior studies in endurance athletes (mean±SD: 60.75±12.95). TGS distribution was shifted toward higher TGS in the top 10% of athletes, though the mean TGS was not significantly different (p = 0.164) and not significantly associated with PT even when adjusted for age, sex, and origin. Receiver operating characteristic curve analysis determined that TGS alone could not significantly predict athlete finishing time with discriminating sensitivity and specificity for three outcomes (less than median PT, less than mean PT, or in the top 10%), though models with the age, sex, continent of origin, and either TGS or AMPD1 genotype could. These results suggest three things: that more sophisticated genetic models may be necessary to accurately predict athlete finishing time in endurance events; that non-genetic factors such as training are hugely influential and should be included in genetic analyses to prevent confounding; and that large collaborations may be necessary to obtain

  17. Evaluation of a 7-Gene Genetic Profile for Athletic Endurance Phenotype in Ironman Championship Triathletes

    PubMed Central

    Grealy, Rebecca; Herruer, Jasper; Smith, Carl L. E.; Hiller, Doug; Haseler, Luke J.; Griffiths, Lyn R.

    2015-01-01

    Polygenic profiling has been proposed for elite endurance performance, using an additive model determining the proportion of optimal alleles in endurance athletes. To investigate this model’s utility for elite triathletes, we genotyped seven polymorphisms previously associated with an endurance polygenic profile (ACE Ins/Del, ACTN3 Arg577Ter, AMPD1 Gln12Ter, CKMM 1170bp/985+185bp, HFE His63Asp, GDF8 Lys153Arg and PPARGC1A Gly482Ser) in a cohort of 196 elite athletes who participated in the 2008 Kona Ironman championship triathlon. Mean performance time (PT) was not significantly different in individual marker analysis. Age, sex, and continent of origin had a significant influence on PT and were adjusted for. Only the AMPD1 endurance-optimal Gln allele was found to be significantly associated with an improvement in PT (model p = 5.79 x 10−17, AMPD1 genotype p = 0.01). Individual genotypes were combined into a total genotype score (TGS); TGS distribution ranged from 28.6 to 92.9, concordant with prior studies in endurance athletes (mean±SD: 60.75±12.95). TGS distribution was shifted toward higher TGS in the top 10% of athletes, though the mean TGS was not significantly different (p = 0.164) and not significantly associated with PT even when adjusted for age, sex, and origin. Receiver operating characteristic curve analysis determined that TGS alone could not significantly predict athlete finishing time with discriminating sensitivity and specificity for three outcomes (less than median PT, less than mean PT, or in the top 10%), though models with the age, sex, continent of origin, and either TGS or AMPD1 genotype could. These results suggest three things: that more sophisticated genetic models may be necessary to accurately predict athlete finishing time in endurance events; that non-genetic factors such as training are hugely influential and should be included in genetic analyses to prevent confounding; and that large collaborations may be necessary to obtain

  18. Characterisation of Phenotypic and Genotypic Antibiotic Resistance Profile of Enterococci from Cheeses in Turkey.

    PubMed

    Kürekci, Cemil; Önen, Sevda Pehlivanlar; Yipel, Mustafa; Aslantaş, Özkan; Gündoğdu, Aycan

    2016-01-01

    The aim of this study was to determine the prevalence of enterococci in cheese samples and to characterize their antimicrobial resistance profiles as well as the associated resistance genes. A total of 139 enterococci were isolated from 99 cheese samples, the isolates were identified as E. faecalis (61.2%), E. faecium (15.1%), E. gallinarum (12.9%), E. durans (5.0%), E. casseliflavis (2.9%) and E. avium (2.9%). The most frequent antimicrobial resistance observed in enterococci isolates was to lincomycin (88.5%), followed by kanamycin (84.2%), gentamycin (low level, 51.1%), rifampin (46.8%) and tetracycline (33.8%). Among the isolates, the frequencies of high level gentamycin and streptomycin resistant enterococci strains were 2.2% and 5.8%, respectively. Apart from the mentioned antibiotics, low levels of resistance to ciprofloxacin, erythromycin and chloramphenicol were found. Moreover no resistance was observed against penicillin and ampicillin. The antimicrobial resistance genes including tetM, tetL, ermB, cat, aph(3')-IIIa, ant(6)-Ia and aac(6')-Ieaph(2")-Ia were found in enterococci from Turkish cheese samples. In the current study, we provided data for antibiotic resistance and the occurrence of resistance genes among enterococci. Regulatory and quality control programs for milk and other dairy products from farms to retail outlets has to be established and strengthened to monitor trends in antimicrobial resistance among emerging food borne pathogens in Turkey. PMID:27433106

  19. Characterisation of Phenotypic and Genotypic Antibiotic Resistance Profile of Enterococci from Cheeses in Turkey

    PubMed Central

    Yipel, Mustafa; Aslantaş, Özkan; Gündoğdu, Aycan

    2016-01-01

    The aim of this study was to determine the prevalence of enterococci in cheese samples and to characterize their antimicrobial resistance profiles as well as the associated resistance genes. A total of 139 enterococci were isolated from 99 cheese samples, the isolates were identified as E. faecalis (61.2%), E. faecium (15.1%), E. gallinarum (12.9%), E. durans (5.0%), E. casseliflavis (2.9%) and E. avium (2.9%). The most frequent antimicrobial resistance observed in enterococci isolates was to lincomycin (88.5%), followed by kanamycin (84.2%), gentamycin (low level, 51.1%), rifampin (46.8%) and tetracycline (33.8%). Among the isolates, the frequencies of high level gentamycin and streptomycin resistant enterococci strains were 2.2% and 5.8%, respectively. Apart from the mentioned antibiotics, low levels of resistance to ciprofloxacin, erythromycin and chloramphenicol were found. Moreover no resistance was observed against penicillin and ampicillin. The antimicrobial resistance genes including tetM, tetL, ermB, cat, aph(3’)-IIIa, ant(6)-Ia and aac(6’)-Ieaph(2”)-Ia were found in enterococci from Turkish cheese samples. In the current study, we provided data for antibiotic resistance and the occurrence of resistance genes among enterococci. Regulatory and quality control programs for milk and other dairy products from farms to retail outlets has to be established and strengthened to monitor trends in antimicrobial resistance among emerging food borne pathogens in Turkey. PMID:27433106

  20. Phenotype discovery by gene expression profiling: mapping of biological processes linked to BMP-2-mediated osteoblast differentiation.

    PubMed

    Balint, Eva; Lapointe, David; Drissi, Hicham; van der Meijden, Caroline; Young, Daniel W; van Wijnen, Andre J; Stein, Janet L; Stein, Gary S; Lian, Jane B

    2003-05-15

    Understanding physiological control of osteoblast differentiation necessitates characterization of the regulatory signals that initiate the events directing a cell to lineage commitment and establishing competency for bone formation. The bone morphogenetic protein, BMP-2, a member of the TGFbeta superfamily, induces osteoblast differentiation and functions through the Smad signal transduction pathway during in vivo bone formation. However, the molecular targets of BMP-mediated gene transcription during the process of osteoblast differentiation have not been comprehensively identified. In the present study, BMP-2 responsive factors involved in the early stages of commitment and differentiation to the osteoblast phenotype were analyzed by microarray gene expression profiling in samples ranging from 1 to 24 h following BMP-2 dependent differentiation of C2C12 premyoblasts into the osteogenic lineage. A total of 1,800 genes were responsive to BMP-2 and expression was modulated from 3- to 14-fold for less than 100 genes during the time course. Approximately 50% of these 100 genes are either up- or downregulated. Major events associated with phenotypic changes towards the osteogenic lineage were identified from hierarchical and functional clustering analyses. BMP-2 immediately responsive genes (1-4 h), which exhibited either transient or sustained expression, reflect activation and repression of non-osseous BMP-2 developmental systems. This initial response was followed by waves of expression of nuclear proteins and developmental regulatory factors including inhibitors of DNA binding, Runx2, C/EBP, Zn finger binding proteins, forkhead, and numerous homeobox proteins (e.g., CDP/cut, paired, distaless, Hox) which are expressed at characterized stages during osteoblast differentiation. A sequential profile of genes mediating changes in cell morphology, cell growth, and basement membrane formation is observed as a secondary transient early response (2-8 h). Commitment to the

  1. Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

    PubMed

    Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

    2015-08-01

    Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. PMID:25926055

  2. Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies.

    PubMed

    Gray, Nicola; Adesina-Georgiadis, Kyrillos; Chekmeneva, Elena; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K

    2016-06-01

    A rapid gradient microbore ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) method has been developed to provide a high-throughput analytical platform for the metabolic phenotyping of urine from large sample cohorts. The rapid microbore metabolic profiling (RAMMP) approach was based on scaling a conventional reversed-phase UPLC-MS method for urinary profiling from 2.1 mm × 100 mm columns to 1 mm × 50 mm columns, increasing the linear velocity of the solvent, and decreasing the gradient time to provide an analysis time of 2.5 min/sample. Comparison showed that conventional UPLC-MS and rapid gradient approaches provided peak capacities of 150 and 50, respectively, with the conventional method detecting approximately 19 000 features compared to the ∼6 000 found using the rapid gradient method. Similar levels of repeatability were seen for both methods. Despite the reduced peak capacity and the reduction in ions detected, the RAMMP method was able to achieve similar levels of group discrimination as conventional UPLC-MS when applied to rat urine samples obtained from investigative studies on the effects of acute 2-bromophenol and chronic acetaminophen administration. When compared to a direct infusion MS method of similar analysis time the RAMMP method provided superior selectivity. The RAMMP approach provides a robust and sensitive method that is well suited to high-throughput metabonomic analysis of complex mixtures such as urine combined with a 5-fold reduction in analysis time compared with the conventional UPLC-MS method. PMID:27116471

  3. Multiparametric Phenotypic Screening System for Profiling Bioactive Compounds Using Human Fetal Hippocampal Neural Stem/Progenitor Cells.

    PubMed

    Tabata, Yoshikuni; Murai, Norio; Sasaki, Takeo; Taniguchi, Sachie; Suzuki, Shuichi; Yamazaki, Kazuto; Ito, Masashi

    2015-10-01

    Stem cell research has been progressing rapidly, contributing to regenerative biology and regenerative medicine. In this field, small-molecule compounds affecting stem cell proliferation/differentiation have been explored to understand stem cell biology and support regenerative medicine. In this study, we established a multiparametric screening system to detect bioactive compounds affecting the cell fate of human neural stem/progenitor cells (NSCs/NPCs), using human fetal hippocampal NSCs/NPCs, HIP-009 cells. We examined effects of 410 compounds, which were collected based on mechanisms of action (MOAs) and chemotypes, on HIP-009's cell fate (self-renewal, neuronal and astrocytic differentiation) and morphology by automated multiparametric assays and profiled induced cellular phenotypes. We found that this screening classified compounds with the same MOAs into subgroups according to additional pharmacological effects (e.g., mammalian target of rapamycin complex 1 [mTORC1] inhibitors and mTORC1/mTORC2 dual inhibitors among mTOR inhibitors). Moreover, it identified compounds that have off-target effects under matrix analyses of MOAs and structure similarities (e.g., neurotropic effects of amitriptyline among tri- and tetracyclic compounds). Therefore, this automated, medium-throughput and multiparametric screening system is useful for finding compounds that affect the cell fate of human NSCs/NPCs for supporting regenerative medicine and to fingerprint compounds based on human stem cells' multipotency, leading to understanding of stem cell biology. PMID:26245650

  4. Phenotypic and transcriptional profiling in Entamoeba histolytica reveal costs to fitness and adaptive responses associated with metronidazole resistance

    PubMed Central

    Penuliar, Gil M.; Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2015-01-01

    Antimicrobial chemotherapy is critical in the fight against infectious diseases caused by Entamoeba histolytica. Among the drugs available for the treatment of amebiasis, metronidazole (MTZ) is considered the drug of choice. Recently, in vitro studies have described MTZ resistance and the potential mechanisms involved. Costs to fitness and adaptive responses associated with resistance, however, have not been investigated. In this study we generated an HM-1 derived strain resistant to 12 μM MTZ (MTZR). We examined its phenotypic and transcriptional profile to determine the consequences and mRNA level changes associated with MTZ resistance. Our results indicated increased cell size and granularity, and decreased rates in cell division, adhesion, phagocytosis, cytopathogenicity, and glucose consumption. Transcriptome analysis revealed 142 differentially expressed genes in MTZR. In contrast to other MTZ resistant parasites, MTZR did not down-regulate pyruvate:ferredoxin oxidoreductase, but showed increased expression of genes for a hypothetical protein (HP1) and several iron-sulfur flavoproteins, and downregulation of genes for leucine-rich proteins. Fisher's exact test showed 24 significantly enriched GO terms in MTZR, and a 3-way comparison of modulated genes in MTZR against those of MTZR cultured without MTZ and HM-1 cultured with MTZ, showed that 88 genes were specific to MTZR. Overall, our findings suggested that MTZ resistance is associated with specific transcriptional changes and decreased parasite virulence. PMID:25999919

  5. Isolation and Molecular Profiling of Primary Mouse Retinal Ganglion Cells: Comparison of Phenotypes from Healthy and Glaucomatous Retinas

    PubMed Central

    Chintalapudi, Sumana R.; Djenderedjian, Levon; Stiemke, Andrew B.; Steinle, Jena J.; Jablonski, Monica M.; Morales-Tirado, Vanessa M.

    2016-01-01

    Loss of functional retinal ganglion cells (RGC) is an element of retinal degeneration that is poorly understood. This is in part due to the lack of a reliable and validated protocol for the isolation of primary RGCs. Here we optimize a feasible, reproducible, standardized flow cytometry-based protocol for the isolation and enrichment of homogeneous RGC with the Thy1.2hiCD48negCD15negCD57neg surface phenotype. A three-step validation process was performed by: (1) genomic profiling of 25-genes associated with retinal cells; (2) intracellular labeling of homogeneous sorted cells for the intracellular RGC-markers SNCG, brain-specific homeobox/POU domain protein 3A (BRN3A), TUJ1, and RNA-binding protein with multiple splicing (RBPMS); and (3) by applying the methodology on RGC from a mouse model with elevated intraocular pressure (IOP) and optic nerve damage. Use of primary RGC cultures will allow for future careful assessment of important cell specific pathways in RGC to provide mechanistic insights into the declining of visual acuity in aged populations and those suffering from retinal neurodegenerative diseases. PMID:27242509

  6. Proteomic and transcriptomic profiling of Staphylococcus aureus surface LPXTG-proteins: correlation with agr genotypes and adherence phenotypes.

    PubMed

    Ythier, Mathilde; Resch, Grégory; Waridel, Patrice; Panchaud, Alexandre; Gfeller, Aurélie; Majcherczyk, Paul; Quadroni, Manfredo; Moreillon, Philippe

    2012-11-01

    Staphylococcus aureus infections involve numerous adhesins and toxins, which expression depends on complex regulatory networks. Adhesins include a family of surface proteins covalently attached to the peptidoglycan via a conserved LPXTG motif. Here we determined the protein and mRNA expression of LPXTG-proteins of S. aureus Newman in time-course experiments, and their relation to fibrinogen adherence in vitro. Experiments were performed with mutants in the global accessory-gene regulator (agr), surface protein A (Spa), and fibrinogen-binding protein A (ClfA), as well as during growth in iron-rich or iron-poor media. Surface proteins were recovered by trypsin-shaving of live bacteria. Released peptides were analyzed by liquid chromatography coupled to tandem mass-spectrometry. To unambiguously identify peptides unique to LPXTG-proteins, the analytical conditions were refined using a reference library of S. aureus LPXTG-proteins heterogeneously expressed in surrogate Lactococcus lactis. Transcriptomes were determined by microarrays. Sixteen of the 18 LPXTG-proteins present in S. aureus Newman were detected by proteomics. Nine LPXTG-proteins showed a bell-shape agr-like expression that was abrogated in agr-negative mutants including Spa, fibronectin-binding protein A (FnBPA), ClfA, iron-binding IsdA, and IsdB, immunomodulator SasH, functionally uncharacterized SasD, biofilm-related SasG and methicillin resistance-related FmtB. However, only Spa and SasH modified their proteomic and mRNA profiles in parallel in the parent and its agr- mutant, whereas all other LPXTG-proteins modified their proteomic profiles independently of their mRNA. Moreover, ClfA became highly transcribed and active in fibrinogen-adherence tests during late growth (24 h), whereas it remained poorly detected by proteomics. On the other hand, iron-regulated IsdA-B-C increased their protein expression by >10-times in iron-poor conditions. Thus, proteomic, transcriptomic, and adherence-phenotype

  7. Comparative Proteomic Profiling of Divergent Phenotypes for Water Holding Capacity across the Post Mortem Ageing Period in Porcine Muscle Exudate

    PubMed Central

    Di Luca, Alessio; Hamill, Ruth M.; Mullen, Anne Maria; Slavov, Nikolai; Elia, Giuliano

    2016-01-01

    Two dimensional Difference Gel Electrophoresis (2-D DIGE) and mass spectrometry were applied to investigate the changes in metabolic proteins that occur over a seven day (day 1, 3 and 7) post mortem ageing period in porcine centrifugal exudate from divergent meat quality phenotypes. The objectives of the research were to enhance our understanding of the phenotype (water holding capacity) and search for biomarkers of this economically significant pork quality attribute. Major changes in protein abundance across nine phenotype-by-time conditions were observed. Proteomic patterns were dominated by post mortem ageing timepoint. Using a machine learning algorithm (l1-regularized logistic regression), a model was derived with the ability to discriminate between high drip and low drip phenotypes using a subset of 25 proteins with an accuracy of 63%. Models discriminating between divergent phenotypes with accuracy of 72% and 73% were also derived comparing respectively, high drip plus intermediate phenotype (considered as one phenotype) versus low drip and comparing low drip plus intermediate phenotype (considered as one phenotype) versus high drip. In all comparisons, the general classes of discriminatory proteins identified include metabolic enzymes, stress response, transport and structural proteins. In this research we have enhanced our understanding of the protein related processes underpinning this phenotype and provided strong data to work toward development of protein biomarkers for water holding capacity. PMID:26950297

  8. Phenotypic Transition as a Survival Strategy of Glioma

    PubMed Central

    ICHIKAWA, Tomotsugu; OTANI, Yoshihiro; KUROZUMI, Kazuhiko; DATE, Isao

    2016-01-01

    Malignant glioma is characterized by rapid proliferation, invasion into surrounding central nervous system tissues, and aberrant vascularization. There is increasing evidence that shows gliomas are more complex than previously thought, as each tumor comprises considerable intratumoral heterogeneity with mixtures of genetically and phenotypically distinct subclones. Heterogeneity within and across tumors is recognized as a critical factor that limits therapeutic progress for malignant glioma. Recent genotyping and expression profiling of gliomas has allowed for the creation of classification schemes that assign tumors to subtypes based on similarity to defined expression signatures. Also, malignant gliomas frequently shift their biological features upon recurrence and progression. The ability of glioma cells to resist adverse conditions such as hypoxia and metabolic stress is necessary for sustained tumor growth and strongly influences tumor behaviors. In general, glioma cells are in one of two phenotypic categories: higher proliferative activity with angiogenesis, or higher migratory activity with attenuated proliferative ability. Further, they switch phenotypic categories depending on the situation. To date, a multidimensional approach has been employed to clarify the mechanisms of phenotypic shift of glioma. Various molecular and signaling pathways are involved in phenotypic shifts of glioma, possibly with crosstalk between them. In this review, we discuss molecular and phenotypic heterogeneity of glioma cells and mechanisms of phenotypic shifts in regard to the glioma proliferation, angiogenesis, and invasion. A better understanding of the molecular mechanisms that underlie phenotypic shifts of glioma may provide new insights into targeted therapeutic strategies. PMID:27169497

  9. Phenotypic, antimicrobial susceptibility profile and virulence factors of Klebsiella pneumoniae isolated from buffalo and cow mastitic milk

    PubMed Central

    Osman, Kamelia M; Hassan, Hany M; Orabi, Ahmed; Abdelhafez, Ahmed S T

    2014-01-01

    Studies on the prevalence and virulence genes of Klebsiella mastitis pathogens in a buffalo population are undocumented. Also, the association of rmpA kfu, uge, magA, Aerobactin, K1 and K2 virulent factors with K. pneumoniae buffalo, and cow mastitis is unreported. The virulence of K. pneumoniae was evaluated through both phenotypic and molecular assays. In vivo virulence was assessed by the Vero cell cytotoxicity, suckling mouse assay and mice lethality test. Antimicrobial susceptibility was tested by disk diffusion method. The 45 K. pneumoniae isolates from buffalo (n = 10/232) and cow (n = 35/293) milk were isolated (45/525; 8.6%) and screened via PCR for seven virulence genes encoding uridine diphosphate galactose 4 epimerase encoding gene responsible for capsule and smooth lipopolysaccharide synthesis (uge), siderophores (kfu and aerobactin), protectines or invasins (rmpA and magA), and the capsule and hypermucoviscosity (K1 and K2). The most common virulence genes were rmpA, kfu, uge, and magA (77.8% each). Aerobactin and K1 genes were found at medium rates of 66.7% each and K2 (55.6%). The Vero cell cytotoxicity and LD (50) in mice were found in 100% of isolates. A multidrug resistance pattern was observed for 40% of the antimicrobials. The distribution of virulence profiles indicate a role of rmpA, kfu, uge, magA, Aerobactin, and K1 and K2 in pathogenicity of K. pneumoniae in udder infections and invasiveness, and constitutes a threat for vulnerable animals, even more if they are in combination with antibiotic resistance. PMID:24915048

  10. Effect of dendritic cell state and antigen-presentation conditions on resulting T-cell phenotypes and Th cytokine profiles.

    PubMed

    de Lastic, Anne-Lise; Rodi, Maria; Mouzaki, Athanasia

    2016-08-01

    T cells play a pivotal role in controlling the immune response and have been the focus of extensive research. We studied the process of in vitro generation of antigen-specific T effector cells (Teffs) to assess the dynamics of antigen presentation and determine the best conditions for cell therapy. We used a peptidic construct consisting of combined HLA class I and II epitopes of the tumor antigen MAGE-3 as an antigen. Monocytes were isolated from healthy donors and were differentiated to dendritic cells (DCs) in vitro. The peptide was added to the DC culture, the pulsed cells were transferred to a co-culture with lymphocytes from the same donor, either as irradiated feeders or untreated, and were cultured in the presence or absence of IL-2. Several rounds of restimulation followed. The cells were analyzed by Flow Cytometry, and cytokine levels were measured by ELISA and Cytometric Bead Array for Th1/Th2/Th17 profiling. The results showed that the lymphocytes in culture upregulated their activation markers and produced Th1 proinflammatory cytokines in response to the peptide, optimally when it was presented by non-irradiated dendritic cells in the presence of IL-2. In contrast, DC irradiation resulted in low activation potential and a shift toward a suppressive phenotype. After prolonged antigenic stimulation, the culture displayed Th17 polarization. In conclusion, the functional integrity of DCs is necessary for the development of antigen-specific Teffs, and culture conditions can be developed to create Teffs with specific properties for eventual use in cell therapy applications. PMID:27130240

  11. Expanding the phenotypic profile of Kleefstra syndrome: A female with low-average intelligence and childhood apraxia of speech.

    PubMed

    Samango-Sprouse, Carole; Lawson, Patrick; Sprouse, Courtney; Stapleton, Emily; Sadeghin, Teresa; Gropman, Andrea

    2016-05-01

    Kleefstra syndrome (KS) is a rare neurogenetic disorder most commonly caused by deletion in the 9q34.3 chromosomal region and is associated with intellectual disabilities, severe speech delay, and motor planning deficits. To our knowledge, this is the first patient (PQ, a 6-year-old female) with a 9q34.3 deletion who has near normal intelligence, and developmental dyspraxia with childhood apraxia of speech (CAS). At 6, the Wechsler Preschool and Primary Intelligence testing (WPPSI-III) revealed a Verbal IQ of 81 and Performance IQ of 79. The Beery Buktenica Test of Visual Motor Integration, 5th Edition (VMI) indicated severe visual motor deficits: VMI = 51; Visual Perception = 48; Motor Coordination < 45. On the Receptive One Word Picture Vocabulary Test-R (ROWPVT-R), she had standard scores of 96 and 99 in contrast to an Expressive One Word Picture Vocabulary-R (EOWPVT-R) standard scores of 73 and 82, revealing a discrepancy in vocabulary domains on both evaluations. Preschool Language Scale-4 (PLS-4) on PQ's first evaluation reveals a significant difference between auditory comprehension and expressive communication with standard scores of 78 and 57, respectively, further supporting the presence of CAS. This patient's near normal intelligence expands the phenotypic profile as well as the prognosis associated with KS. The identification of CAS in this patient provides a novel explanation for the previously reported speech delay and expressive language disorder. Further research is warranted on the impact of CAS on intelligence and behavioral outcome in KS. Therapeutic and prognostic implications are discussed. PMID:26833960

  12. Levels of alpha-toxin correlate with distinct phenotypic response profiles of blood mononuclear cells and with agr background of community-associated Staphylococcus aureus isolates.

    PubMed

    Mairpady Shambat, Srikanth; Haggar, Axana; Vandenesch, Francois; Lina, Gerard; van Wamel, Willem J B; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2014-01-01

    Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of α-toxin than did the proliferative supernatants. Addition of α-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, δ-toxin or phenol soluble modulin α-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes. PMID:25166615

  13. The Value of HBME-1 and Claudin-1 Expression Profile in the Distinction of BRAF-Like and RAS-Like Phenotypes in Papillary Thyroid Carcinoma.

    PubMed

    Gucer, Hasan; Bagci, Pelin; Bedir, Recep; Sehitoglu, Ibrahim; Mete, Ozgur

    2016-09-01

    This study compared the expression profile of HBME-1 and claudin-1 in 90 papillary thyroid carcinomas (PTCs) with respect to the tumor architecture and invasive growth as reflected in 46 BRAF-like, 31 non-invasive RAS, and 13 invasive RAS-like phenotypes. Individual tumors were given an expression score (max 300) by multiplying the percent positive tumor cells by the intensity score (range 0-3). The higher expression of HBME-1 and claudin-1 distinguished BRAF-like phenotype from RAS-like phenotype. The same correlation was also retained for both markers when comparing BRAF-like phenotype with non-invasive and invasive RAS-like phenotypes. The expression scores and positivity rates for both markers did not yield any statistical difference among BRAF-like PTCs. Except the higher positivity rate of HBME-1, invasive RAS-like tumors were not statistically different than their non-invasive counterparts with respect to the positivity rate of claudin-1 and the expression scores of both markers. A central lymph node dissection or selective lymph node sampling was available in 20 specimens. The absence of claudin-1 expression has not been a feature of lymph node metastasis in this series. Despite the limited number of nodal sampling, BRAF-like phenotype and claudin-1 positivity status have been considered the best determinants of positive predictive value and negative predictive value in the prediction of lymph node metastasis among variables, respectively. Adoption of the simplified architectural classification approach to PTCs showed distinct biomarker expression profile in this series; however, immunohistochemistry for HBME-1 and claudin-1 does not seem to be useful in the distinction of invasive RAS-like PTCs from their non-invasive counterparts. Given the overlapping molecular signatures within the RAS-like phenotype, further studies with additional biomarkers are still needed to identify distinct protein expression signatures of non-invasive RAS-like phenotype as this

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  15. Metabolic profiling of plant extracts using direct-injection electrospray ionization mass spectrometry allows for high-throughput phenotypic characterization according to genetic and environmental effects.

    PubMed

    García-Flores, Martín; Juárez-Colunga, Sheila; García-Casarrubias, Adrián; Trachsel, Samuel; Winkler, Robert; Tiessen, Axel

    2015-01-28

    In comparison to the exponential increase of genotyping methods, phenotyping strategies are lagging behind in agricultural sciences. Genetic improvement depends upon the abundance of quantitative phenotypic data and the statistical partitioning of variance into environmental, genetic, and random effects. A metabolic phenotyping strategy was adapted to increase sample throughput while saving reagents, reducing cost, and simplifying data analysis. The chemical profiles of stem extracts from maize plants grown under low nitrogen (LN) or control trial (CT) were analyzed using optimized protocols for direct-injection electrospray ionization mass spectrometry (DIESI-MS). Specific ions significantly decreased or increased because of environmental (LN versus CT) or genotypic effects. Biochemical profiling with DIESI-MS had a superior cost-benefit compared to other standard analytical technologies (e.g., ultraviolet, near-infrared reflectance spectroscopy, high-performance liquid chromatography, and gas chromatography with flame ionization detection) routinely used for plant breeding. The method can be successfully applied in maize, strawberry, coffee, and other crop species. PMID:25588121

  16. Bi-content micro-collagen chip provides contractility-based biomechanical readout for phenotypic drug screening with expanded and profiled targets.

    PubMed

    Zhao, Hui; Zhou, Lyu; Zhang, Qiang; Zhou, Xiaoying; Zhang, Yonghui; Chen, Huijun; Du, Yanan

    2015-09-01

    Phenotypic screening has regained momentum in the pharmaceutical industry owing to its success over target-based screening. Most phenotypic screening relies on nonspecific biochemical readouts regarding cellular viability, which hampers the discovery of novel drug mechanisms of action (MOAs). Here we present a Contractility-based bi-Content micro-Collagen Chip (3CChip), which establishes cellular contractility as a biomechanics-related phenotype for drug screening. Bi-content analysis of cell contractility (imaged by iPhone) and viability suggests that the label-free contractility-based analysis exhibits superior sensitivity to compounds targeting contractile elements (e.g. focal adhesion, cytoskeleton), resulting in a enlarged target pool for drug assessment. Six typical readout patterns of drug response are summarized according to the relative positions of the contraction/viability curves, and drug targets are profiled into three categories (biomechanical, biochemical and housekeeping) by 3CChip, which will benefit subsequent target identification. The simple-to-use and effective 3CChip offers a robust platform for micro-tissue-based functional screening and may lead to a new era of mechanism-informed phenotypic drug discovery. PMID:26219255

  17. Multidimensional Liquid Chromatography Platform for Profiling Alterations of Clusterin N-Glycosylation in the Plasma of Patients with Renal Cell Carcinoma

    PubMed Central

    Tousi, Fateme; Bones, Jonathan; Iliopoulos, Othon; Hancock, William S.; Hincapie, Marina

    2012-01-01

    Identification of potential changes in the glycosylation of existing cancer biomarkers can result in a higher level of diagnostic sensitivity and specificity. Clusterin (Apolipoprotein J) has been implicated in renal cell carcinoma (RCC) and other types of malignancy as potential biomarker. In the present work, an automated multidimensional HPLC platform enabling high throughput affinity enrichment of clusterin from plasma samples was developed. Integrated with two dimensional gel electrophoresis, high purity clusterin in microgram quantities suitable for glycan characterization was isolated. The analytical platform was applied to study clusterin glycosylation in a small group of RCC patients before and after nephrectopy as a pilot study to evaluate the performance of the platform. A statistically significant decrease was observed in the levels of a bi-antennary digalactosyl disialylated (A2G2S(3)2) glycans while the levels of a core fucosylated bi-antennary digalactosyl disialylated glycan (FA2G2S(6)2) and a tri-antennary trigalactosyl disialylated glycan (A3G3S(6)2) were increased in the post-surgery plasma samples. PMID:22885037

  18. Multidimensional liquid chromatography platform for profiling alterations of clusterin N-glycosylation in the plasma of patients with renal cell carcinoma.

    PubMed

    Tousi, Fateme; Bones, Jonathan; Iliopoulos, Othon; Hancock, William S; Hincapie, Marina

    2012-09-21

    Identification of potential changes in the glycosylation of existing cancer biomarkers can result in a higher level of diagnostic sensitivity and specificity. Clusterin (Apolipoprotein J) has been implicated in renal cell carcinoma (RCC) and other types of malignancy as potential biomarker. In the present work, an automated multi-dimensional HPLC platform enabling high throughput affinity enrichment of clusterin from plasma samples was developed. Integrated with two dimensional gel electrophoresis, high purity clusterin in microgram quantities suitable for glycan characterization was isolated. The analytical platform was applied to study clusterin glycosylation in a small group of RCC patients before and after nephrectopy as a pilot study to evaluate the performance of the platform. A statistically significant decrease was observed in the levels of a bi-antennary digalactosyl disialylated (A2G2S(3)2) glycans while the levels of a core fucosylated bi-antennary digalactosyl disialylated glycan (FA2G2S(6)2) and a tri-antennary trigalactosyl disialylated glycan (A3G3S(6)2) were increased in the post-surgery plasma samples. PMID:22885037

  19. 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…

  20. Multidimensional Risk Analysis: MRISK

    NASA Technical Reports Server (NTRS)

    McCollum, Raymond; Brown, Douglas; O'Shea, Sarah Beth; Reith, William; Rabulan, Jennifer; Melrose, Graeme

    2015-01-01

    Multidimensional Risk (MRISK) calculates the combined multidimensional score using Mahalanobis distance. MRISK accounts for covariance between consequence dimensions, which de-conflicts the interdependencies of consequence dimensions, providing a clearer depiction of risks. Additionally, in the event the dimensions are not correlated, Mahalanobis distance reduces to Euclidean distance normalized by the variance and, therefore, represents the most flexible and optimal method to combine dimensions. MRISK is currently being used in NASA's Environmentally Responsible Aviation (ERA) project o assess risk and prioritize scarce resources.

  1. Saccular Transcriptome Profiles of the Seasonal Breeding Plainfin Midshipman Fish (Porichthys notatus), a Teleost with Divergent Sexual Phenotypes.

    PubMed

    Faber-Hammond, Joshua; Samanta, Manoj P; Whitchurch, Elizabeth A; Manning, Dustin; Sisneros, Joseph A; Coffin, Allison B

    2015-01-01

    Acoustic communication is essential for the reproductive success of the plainfin midshipman fish (Porichthys notatus). During the breeding season, type I males use acoustic cues to advertise nest location to potential mates, creating an audible signal that attracts reproductive females. Type II (sneaker) males also likely use this social acoustic signal to find breeding pairs from which to steal fertilizations. Estrogen-induced changes in the auditory system of breeding females are thought to enhance neural encoding of the advertisement call, and recent anatomical data suggest the saccule (the main auditory end organ) as one possible target for this seasonal modulation. Here we describe saccular transcriptomes from all three sexual phenotypes (females, type I and II males) collected during the breeding season as a first step in understanding the mechanisms underlying sexual phenotype-specific and seasonal differences in auditory function. We used RNA-Seq on the Ion Torrent platform to create a combined transcriptome dataset containing over 79,000 assembled transcripts representing almost 9,000 unique annotated genes. These identified genes include several with known inner ear function and multiple steroid hormone receptors. Transcripts most closely matched to published genomes of nile tilapia and large yellow croaker, inconsistent with the phylogenetic relationship between these species but consistent with the importance of acoustic communication in their life-history strategies. We then compared the RNA-Seq results from the saccules of reproductive females with a separate transcriptome from the non-reproductive female phenotype and found over 700 differentially expressed transcripts, including members of the Wnt and Notch signaling pathways that mediate cell proliferation and hair cell addition in the inner ear. These data constitute a valuable resource for furthering our understanding of the molecular basis for peripheral auditory function as well as a range of

  2. Saccular Transcriptome Profiles of the Seasonal Breeding Plainfin Midshipman Fish (Porichthys notatus), a Teleost with Divergent Sexual Phenotypes

    PubMed Central

    Faber-Hammond, Joshua; Samanta, Manoj P.; Whitchurch, Elizabeth A.; Manning, Dustin; Sisneros, Joseph A.; Coffin, Allison B.

    2015-01-01

    Acoustic communication is essential for the reproductive success of the plainfin midshipman fish (Porichthys notatus). During the breeding season, type I males use acoustic cues to advertise nest location to potential mates, creating an audible signal that attracts reproductive females. Type II (sneaker) males also likely use this social acoustic signal to find breeding pairs from which to steal fertilizations. Estrogen-induced changes in the auditory system of breeding females are thought to enhance neural encoding of the advertisement call, and recent anatomical data suggest the saccule (the main auditory end organ) as one possible target for this seasonal modulation. Here we describe saccular transcriptomes from all three sexual phenotypes (females, type I and II males) collected during the breeding season as a first step in understanding the mechanisms underlying sexual phenotype-specific and seasonal differences in auditory function. We used RNA-Seq on the Ion Torrent platform to create a combined transcriptome dataset containing over 79,000 assembled transcripts representing almost 9,000 unique annotated genes. These identified genes include several with known inner ear function and multiple steroid hormone receptors. Transcripts most closely matched to published genomes of nile tilapia and large yellow croaker, inconsistent with the phylogenetic relationship between these species but consistent with the importance of acoustic communication in their life-history strategies. We then compared the RNA-Seq results from the saccules of reproductive females with a separate transcriptome from the non-reproductive female phenotype and found over 700 differentially expressed transcripts, including members of the Wnt and Notch signaling pathways that mediate cell proliferation and hair cell addition in the inner ear. These data constitute a valuable resource for furthering our understanding of the molecular basis for peripheral auditory function as well as a range of

  3. Neuropsychological and Dimensional Behavioral Trait Profiles in Costa Rican ADHD Sib Pairs: Potential Intermediate Phenotypes for Genetic Studies

    PubMed Central

    Peskin, Viviana A.; Ordóñez, Anna; Mackin, R. Scott; Delucchi, Kevin; Monge, Silvia; McGough, James J.; Chavira, Denise A.; Berrocal, Monica; Cheung, Erika; Fournier, Eduardo; Badner, Judith A.; Herrera, Luis Diego; Mathews, Carol A.

    2015-01-01

    Introduction Attention deficit hyperactivity disorder (ADHD) is associated with substantial functional impairment in children and in adults. Many individuals with ADHD have clear neurocognitive deficits, including problems with visual attention, processing speed, and set shifting. ADHD is etiologically complex, and although genetic factors play a role in its development, much of the genetic contribution to ADHD remains unidentified. Methods We conducted clinical and neuropsychological assessments of 294 individuals (269 with ADHD) from 163 families (48 multigenerational families created using genealogical reconstruction, 78 affected sib pair families, and 37 trios) from the Central Valley of Costa Rica (CVCR). We used principal components analysis (PCA) to group neurocognitive and behavioral variables using the subscales of the Child Behavior Checklist (CBCL) and 15 neuropsychological measures, and created quantitative traits for heritability analyses. Results We identified seven cognitive and two behavioral domains. Individuals with ADHD were significantly more impaired than their unaffected siblings on most behavioral and cognitive domains. The verbal IQ domain had the highest heritability (92%), followed by auditory attention (87%), visual processing speed and problem solving (85%), and externalizing symptoms (81%). Conclusions The quantitative traits identified here have high heritabilities, similar to the reported heritability of ADHD (70–90%), and may represent appropriate alternative phenotypes for genetic studies. The use of multigenerational families from a genetically isolated population may facilitate the identification of ADHD risk genes in the face of phenotypic and genetic heterogeneity. PMID:25832558

  4. Neuropsychological and dimensional behavioral trait profiles in Costa Rican ADHD sib pairs: Potential intermediate phenotypes for genetic studies.

    PubMed

    Peskin, Viviana A; Ordóñez, Anna; Mackin, R Scott; Delucchi, Kevin; Monge, Silvia; McGough, James J; Chavira, Denise A; Berrocal, Monica; Cheung, Erika; Fournier, Eduardo; Badner, Judith A; Herrera, Luis Diego; Mathews, Carol A

    2015-06-01

    Attention deficit hyperactivity disorder (ADHD) is associated with substantial functional impairment in children and in adults. Many individuals with ADHD have clear neurocognitive deficits, including problems with visual attention, processing speed, and set shifting. ADHD is etiologically complex, and although genetic factors play a role in its development, much of the genetic contribution to ADHD remains unidentified. We conducted clinical and neuropsychological assessments of 294 individuals (269 with ADHD) from 163 families (48 multigenerational families created using genealogical reconstruction, 78 affected sib pair families, and 37 trios) from the Central Valley of Costa Rica (CVCR). We used principal components analysis (PCA) to group neurocognitive and behavioral variables using the subscales of the Child Behavior Checklist (CBCL) and 15 neuropsychological measures, and created quantitative traits for heritability analyses. We identified seven cognitive and two behavioral domains. Individuals with ADHD were significantly more impaired than their unaffected siblings on most behavioral and cognitive domains. The verbal IQ domain had the highest heritability (92%), followed by auditory attention (87%), visual processing speed and problem solving (85%), and externalizing symptoms (81%). The quantitative traits identified here have high heritabilities, similar to the reported heritability of ADHD (70-90%), and may represent appropriate alternative phenotypes for genetic studies. The use of multigenerational families from a genetically isolated population may facilitate the identification of ADHD risk genes in the face of phenotypic and genetic heterogeneity. PMID:25832558

  5. Multidimensional spectral load balancing

    SciTech Connect

    Hendrickson, B.; Leland, R.

    1993-01-01

    We describe an algorithm for the static load balancing of scientific computations that generalizes and improves upon spectral bisection. Through a novel use of multiple eigenvectors, our new spectral algorithm can divide a computation into 4 or 8 pieces at once. These multidimensional spectral partitioning algorithms generate balanced partitions that have lower communication overhead and are less expensive to compute than those produced by spectral bisection. In addition, they automatically work to minimize message contention on a hypercube or mesh architecture. These spectral partitions are further improved by a multidimensional generalization of the Kernighan-Lin graph partitioning algorithm. Results on several computational grids are given and compared with other popular methods.

  6. Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish.

    PubMed

    Haggard, Derik E; Noyes, Pamela D; Waters, Katrina M; Tanguay, Robert L

    2016-10-01

    Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120hpf (EC80) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC80 (7.37μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value≤0.05; fold change ≥2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. PMID:27538710

  7. Real-life assessment of the multidimensional nature of dyspnoea in COPD outpatients.

    PubMed

    Morélot-Panzini, Capucine; Gilet, Hélène; Aguilaniu, Bernard; Devillier, Philippe; Didier, Alain; Perez, Thierry; Pignier, Christophe; Arnould, Benoit; Similowski, Thomas

    2016-06-01

    Dyspnoea is a prominent symptom of chronic obstructive pulmonary disease (COPD). Recent multidimensional dyspnoea questionnaires like the Multidimensional Dyspnea Profile (MDP) individualise the sensory and affective dimensions of dyspnoea. We tested the MDP in COPD outpatients based on the hypothesis that the importance of the affective dimension of dyspnoea would vary according to clinical characteristics.A multicentre, prospective, observational, real-life study was conducted in 276 patients. MDP data were compared across various categories of patients (modified Medical Research Council (mMRC) dyspnoea score, COPD Assessment Test (CAT) score, Global Initiative for Chronic Obstructive Lung Disease (GOLD) airflow obstruction categories, GOLD "ABCD" categories, and Hospital Anxiety and Depression Scale (HADS)). Univariate and multivariate regressions were conducted to explore factors influencing the affective dimension of dyspnoea. Cluster analysis was conducted to create homogeneous patient profiles.The MDP identified a more marked affective dimension of dyspnoea with more severe mMRC, CAT, 12-item Short-Form Health Survey mental component, airflow obstruction and HADS. Multivariate analysis identified airflow obstruction, depressive symptoms and physical activity as determinants of the affective dimension of dyspnoea. Patients clustered into an "elderly, ex-smoker, severe disease, no rehabilitation" group exhibited the most marked affective dimension of dyspnoea.An affective/emotional dimension of dyspnoea can be identified in routine clinical practice. It can contribute to the phenotypic description of patients. Studies are needed to determine whether targeted therapeutic interventions can be designed and whether they are useful. PMID:27076585

  8. Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile

    PubMed Central

    Sánchez-Reyes, Karina; Bravo-Cuellar, Alejandro; Hernández-Flores, Georgina; Lerma-Díaz, José Manuel; Jave-Suárez, Luis Felipe; Gómez-Lomelí, Paulina; de Celis, Ruth; Aguilar-Lemarroy, Adriana; Domínguez-Rodríguez, Jorge Ramiro; Ortiz-Lazareno, Pablo Cesar

    2014-01-01

    Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages. PMID:25309919

  9. Profiling of myelin proteins by 2D-gel electrophoresis and multidimensional liquid chromatography coupled to MALDI TOF-TOF mass spectrometry.

    PubMed

    Vanrobaeys, Frank; Van Coster, Rudy; Dhondt, Goedele; Devreese, Bart; Van Beeumen, Jozef

    2005-01-01

    The myelin sheath is an electrically insulating layer that consists of lipids and proteins. It plays a key role in the functioning of the nervous system by allowing fast saltatory conduction of nerve pulses. Profiling of the proteins present in myelin is an indispensable prerequisite to better understand the molecular aspects of this dynamic, functionally active membrane. Two types of protein, the myelin basic protein and the proteolipid protein, account for nearly 85% of the protein content in myelin. Identification and characterization of the other "minor" proteins is, in this respect, a real challenge. In the present work, two proteomic strategies were applied in order to study the protein composition of myelin from the murine central nervous system. First, the protein mixture was separated by 2D-gel electrophoresis and, after spot excision and in-gel digestion, samples were analyzed by mass spectrometry. Via this approach, we identified 57 protein spots, corresponding to 38 unique proteins. Alternatively, the myelin sample was digested by trypsin and the resulting peptide mixture was further analyzed by off-line 2D-liquid chromatography. After the second-dimension separation (nanoLC), the peptides were spotted "on-line" onto a MALDI target and analyzed by MALDI TOF-TOF mass spectrometry. We identified 812 peptides by MALDI MS/MS, representing 93 proteins. Membrane proteins, low abundant proteins, and highly basic proteins were all represented in this shotgun proteomic approach. By combining the results of both approaches, we can present a comprehensive proteomic map of myelin, comprising a total of 103 protein identifications, which is of utmost importance for the molecular understanding of white matter and its disorders. PMID:16335977

  10. Gas Chromatography-Mass Spectrometry-Based Metabolite Profiling of Salmonella enterica Serovar Typhimurium Differentiates between Biofilm and Planktonic Phenotypes

    PubMed Central

    Maker, Garth L.; Trengove, Robert D.; O'Handley, Ryan M.

    2015-01-01

    The aim of this study was to utilize gas chromatography coupled with mass spectrometry (GC-MS) to compare and identify patterns of biochemical change between Salmonella cells grown in planktonic and biofilm phases and Salmonella biofilms of different ages. Our results showed a clear separation between planktonic and biofilm modes of growth. The majority of metabolites contributing to variance between planktonic and biofilm supernatants were identified as amino acids, including alanine, glutamic acid, glycine, and ornithine. Metabolites contributing to variance in intracellular profiles were identified as succinic acid, putrescine, pyroglutamic acid, and N-acetylglutamic acid. Principal-component analysis revealed no significant differences between the various ages of intracellular profiles, which would otherwise allow differentiation of biofilm cells on the basis of age. A shifting pattern across the score plot was illustrated when analyzing extracellular metabolites sampled from different days of biofilm growth, and amino acids were again identified as the metabolites contributing most to variance. An understanding of biofilm-specific metabolic responses to perturbations, especially antibiotics, can lead to the identification of novel drug targets and potential therapies for combating biofilm-associated diseases. We concluded that under the conditions of this study, GC-MS can be successfully applied as a high-throughput technique for “bottom-up” metabolomic biofilm research. PMID:25636852

  11. Probabilistic, Multidimensional Unfolding Analysis

    ERIC Educational Resources Information Center

    Zinnes, Joseph L.; Griggs, Richard A.

    1974-01-01

    Probabilistic assumptions are added to single and multidimensional versions of the Coombs unfolding model for preferential choice (Coombs, 1950) and practical ways of obtaining maximum likelihood estimates of the scale parameters and goodness-of-fit tests of the model are presented. A Monte Carlo experiment is discussed. (Author/RC)

  12. Phenotypic profiling of the human genome reveals gene products involved in plasma membrane targeting of SRC kinases

    PubMed Central

    Ritzerfeld, Julia; Remmele, Steffen; Wang, Tao; Temmerman, Koen; Brügger, Britta; Wegehingel, Sabine; Tournaviti, Stella; Strating, Jeroen R.P.M.; Wieland, Felix T.; Neumann, Beate; Ellenberg, Jan; Lawerenz, Chris; Hesser, Jürgen; Erfle, Holger; Pepperkok, Rainer; Nickel, Walter

    2011-01-01

    SRC proteins are non-receptor tyrosine kinases that play key roles in regulating signal transduction by a diverse set of cell surface receptors. They contain N-terminal SH4 domains that are modified by fatty acylation and are functioning as membrane anchors. Acylated SH4 domains are both necessary and sufficient to mediate specific targeting of SRC kinases to the inner leaflet of plasma membranes. Intracellular transport of SRC kinases to the plasma membrane depends on microdomains into which SRC kinases partition upon palmitoylation. In the present study, we established a live-cell imaging screening system to identify gene products involved in plasma membrane targeting of SRC kinases. Based on siRNA arrays and a human model cell line expressing two kinds of SH4 reporter molecules, we conducted a genome-wide analysis of SH4-dependent protein targeting using an automated microscopy platform. We identified and validated 54 gene products whose down-regulation causes intracellular retention of SH4 reporter molecules. To detect and quantify this phenotype, we developed a software-based image analysis tool. Among the identified gene products, we found factors involved in lipid metabolism, intracellular transport, and cellular signaling processes. Furthermore, we identified proteins that are either associated with SRC kinases or are related to various known functions of SRC kinases such as other kinases and phosphatases potentially involved in SRC-mediated signal transduction. Finally, we identified gene products whose function is less defined or entirely unknown. Our findings provide a major resource for future studies unraveling the molecular mechanisms that underlie proper targeting of SRC kinases to the inner leaflet of plasma membranes. PMID:21795383

  13. Influence of blood pressure profile on frailty phenotype in community-dwelling elders in Brazil - FIBRA study.

    PubMed

    Fattori, A; Santimaria, M R; Alves, R M A; Guariento, M E; Neri, A L

    2013-01-01

    Frailty is a clinical condition associated with pathological aging and biological vulnerability. In the spectrum of events related to frailty, aging of the cardiocirculatory system and abnormalities in arterial blood pressure (BP) partly explain the changes in tissue perfusion and, potentially, the decrease in physiological reserves. This study investigated the relationship between BP levels, systemic arterial hypertension (SAH) and the frailty phenotype by analyzing frailty criteria in a cross-sectional model into the FIBRA network, a populational sample of community-dwelling elders in Southeastern Brazil. Study participants with ≥65 years were selected by probabilistic sampling of residents in the urban area of the municipality of Campinas (n=900). Considering frailty as a whole and the difference between genders, there was a greater proportion of frail or pre-frail individuals among women than men. Analysis of individual frailty criteria showed that weight loss and fatigue were more common among women (18.3% vs. 12.5%, p=0.034 and 22.5% vs. 11.9%, p<0.001, respectively). Comparison of individuals with or without SAH failed to reveal any differences related to frailty criteria. Nevertheless, averages of diastolic blood pressure (DBP) and mean arterial blood pressure values were lower among elderly individuals with reduced grip strength, physical activity and the frailty classification as a whole (OR 0.986, IC 0.975-0.997) (for every 1 mmHg reduction in MBP values, the likelihood of being frail increased 1.4%). Our findings corroborate the relationship between BP values and frailty in the elderly and contribute to an understanding of the pathophysiological mechanisms of the syndrome. PMID:22939428

  14. Analysis of Detailed Phenotype Profiles Reveals CHRNA5-CHRNA3-CHRNB4 Gene Cluster Association With Several Nicotine Dependence Traits

    PubMed Central

    Broms, Ulla; Wedenoja, Juho; Largeau, Marine R.; Korhonen, Tellervo; Pitkäniemi, Janne; Keskitalo-Vuokko, Kaisu; Häppölä, Anja; Heikkilä, Katri H.; Heikkilä, Kauko; Ripatti, Samuli; Sarin, Antti-Pekka; Salminen, Outi; Paunio, Tiina; Pergadia, Michele L.; Madden, Pamela A. F.; Kaprio, Jaakko

    2012-01-01

    Introduction: The role of the nicotinic acetylcholine receptor gene cluster on chromosome 15q24-25 in the etiology of nicotine dependence (ND) is still being defined. In this study, we included all 15 tagging single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster and tested associations with 30 smoking-related phenotypes. Methods: The study sample was ascertained from the Finnish Twin Cohort study. Twin pairs born 1938–1957 and concordant for a history of cigarette smoking were recruited along with their family members (mainly siblings), as part of the Nicotine Addiction Genetics consortium. The study sample consisted of 1,428 individuals (59% males) from 735 families, with mean age 55.6 years. Results: We detected multiple novel associations for ND. DSM-IV ND symptoms associated significantly with the proxy SNP Locus 1 (rs2036527, p = .000009) and Locus 2 (rs578776, p = .0001) and tolerance factor of the Nicotine Dependence Syndrome Scale (NDSS) showed suggestive association to rs11636753 (p = .0059), rs11634351 (p = .0069), and rs1948 (p = .0071) in CHRNB4. Furthermore, we report significant association with DSM-IV ND diagnosis (rs2036527, p = .0003) for the first time in a Caucasian population. Several SNPs indicated suggestive association for traits related to ages at smoking initiation. Also, rs11636753 in CHRNB4 showed suggestive association with regular drinking (p = .0029) and the comorbidity of depression and ND (p = .0034). Conclusions: We demonstrate novel associations of DSM-IV ND symptoms and the NDSS tolerance subscale. Our results confirm and extend association findings for other ND measures. We show pleiotropic effects of this gene cluster on multiple measures of ND and also regular drinking and the comorbidity of ND and depression. PMID:22241830

  15. Sex-Related Cognitive Profile in Autism Spectrum Disorders Diagnosed Late in Life: Implications for the Female Autistic Phenotype.

    PubMed

    Lehnhardt, Fritz-Georg; Falter, Christine Michaela; Gawronski, Astrid; Pfeiffer, Kathleen; Tepest, Ralf; Franklin, Jeremy; Vogeley, Kai

    2016-01-01

    Females with high-functioning ASD are known to camouflage their autistic symptoms better than their male counterparts, making them prone to being under-ascertained and delayed in diagnostic assessment. Thus far the underlying cognitive processes that enable such successful socio-communicative adaptation are not well understood. The current results show sex-related differences in the cognitive profile of ASD individuals, which were diagnosed late in life exclusively. Higher verbal abilities were found in males (n = 69) as opposed to higher processing speed and better executive functions in females with ASD (n = 38). Since both sexes remained unidentified during childhood and adolescence, these results are suggestive for sex-distinctive cognitive strategies as an alternative to typically-developed reciprocal social behavior and social mimicry in high functioning ASD. PMID:26319250

  16. Phenotypes and gene expression profiles of Saccharopolyspora erythraea rifampicin-resistant (rif) mutants affected in erythromycin production

    PubMed Central

    Carata, Elisabetta; Peano, Clelia; Tredici, Salvatore M; Ferrari, Francesco; Talà, Adelfia; Corti, Giorgio; Bicciato, Silvio; De Bellis, Gianluca; Alifano, Pietro

    2009-01-01

    Background There is evidence from previous works that bacterial secondary metabolism may be stimulated by genetic manipulation of RNA polymerase (RNAP). In this study we have used rifampicin selection as a strategy to genetically improve the erythromycin producer Saccharopolyspora erythraea. Results Spontaneous rifampicin-resistant (rif) mutants were isolated from the parental strain NRRL2338 and two rif mutations mapping within rpoB, S444F and Q426R, were characterized. With respect to the parental strain, S444F mutants exhibited higher respiratory performance and up to four-fold higher final erythromycin yields; in contrast, Q426R mutants were slow-growing, developmental-defective and severely impaired in erythromycin production. DNA microarray analysis demonstrated that these rif mutations deeply changed the transcriptional profile of S. erythraea. The expression of genes coding for key enzymes of carbon (and energy) and nitrogen central metabolism was dramatically altered in turn affecting the flux of metabolites through erythromycin feeder pathways. In particular, the valine catabolic pathway that supplies propionyl-CoA for biosynthesis of the erythromycin precursor 6-deoxyerythronolide B was strongly up-regulated in the S444F mutants, while the expression of the biosynthetic gene cluster of erythromycin (ery) was not significantly affected. In contrast, the ery cluster was down-regulated (<2-fold) in the Q426R mutants. These strains also exhibited an impressive stimulation of the nitrogen regulon, which may contribute to lower erythromycin yields as erythromycin production was strongly inhibited by ammonium. Conclusion Rifampicin selection is a simple and reliable tool to investigate novel links between primary and secondary metabolism and morphological differentiation in S. erythraea and to improve erythromycin production. At the same time genome-wide analysis of expression profiles using DNA microarrays allowed information to be gained about the mechanisms

  17. Pemetrexed alters folate phenotype and inflammatory profile in EA.hy 926 cells grown under low-folate conditions

    PubMed Central

    Hammons, Andrea L.; Summers, Carolyn M.; Jochems, Jeanine; Arora, Jasbir S.; Zhang, Suhong; Blair, Ian A.; Whitehead, Alexander S.

    2014-01-01

    Elevated homocysteine is a risk marker for several major human pathologies. Emerging evidence suggests that perturbations of folate/homocysteine metabolism can directly modify production of inflammatory mediators. Pemetrexed acts by inhibiting thymidylate synthetase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). EA.hy 926 cells grown under low (“Lo”) and high (“Hi”) folate conditions were treated with pemetrexed. The concentrations of several intracellular folate derivatives were measured using LC-MRM/MS. Lo cells had lower total folate concentrations and a different distribution of the intracellular folate derivatives than Hi cells. Treatment with pemetrexed caused a decrease in individual folate analytes. Microarray analysis showed that several genes were significantly up or down-regulated in pemetrexed treated Lo cells. Several of the significantly up-regulated transcripts were inflammatory. Changes in transcript levels of selected targets, including C3, IL-8, and DHFR, were confirmed by quantitative RT-PCR. C3 and IL-8 transcript levels were increased in pemetrexed-treated Lo cells relative to Lo controls; DHFR transcript levels were decreased. In Lo cells, IL-8 and C3 protein concentrations were increased following pemetrexed treatment. Pemetrexed drug treatment was shown in this study to have effects that lead to an increase in pro-inflammatory mediators in Lo cells. No such changes were observed in Hi cells, suggesting that pemetrexed could not modify the inflammatory profile in the context of cellular folate sufficiency. PMID:22975265

  18. Proteomic and Glycoproteomic Profilings Reveal That Post-translational Modifications of Toxins Contribute to Venom Phenotype in Snakes.

    PubMed

    Andrade-Silva, Débora; Zelanis, André; Kitano, Eduardo S; Junqueira-de-Azevedo, Inácio L M; Reis, Marcelo S; Lopes, Aline S; Serrano, Solange M T

    2016-08-01

    Snake venoms are biological weapon systems composed of secreted proteins and peptides that are used for immobilizing or killing prey. Although post-translational modifications are widely investigated because of their importance in many biological phenomena, we currently still have little understanding of how protein glycosylation impacts the variation and stability of venom proteomes. To address these issues, here we characterized the venom proteomes of seven Bothrops snakes using a shotgun proteomics strategy. Moreover, we compared the electrophoretic profiles of native and deglycosylated venoms and, in order to assess their subproteomes of glycoproteins, we identified the proteins with affinity for three lectins with different saccharide specificities and their putative glycosylation sites. As proteinases are abundant glycosylated toxins, we examined the effect of N-deglycosylation on their catalytic activities and show that the proteinases of the seven venoms were similarly affected by removal of N-glycans. Moreover, we prospected putative glycosylation sites of transcripts of a B. jararaca venom gland data set and detected toxin family related patterns of glycosylation. Based on our global analysis, we report that Bothrops venom proteomes and glycoproteomes contain a core of components that markedly define their composition, which is conserved upon evolution in parallel to other molecular markers that determine their phylogenetic classification. PMID:27297130

  19. Diverse Bone Morphogenetic Protein Expression Profiles and Smad Pathway Activation in Different Phenotypes of Experimental Canine Mammary Tumors

    PubMed Central

    Wensman, Helena; Heldin, Nils-Erik; Pejler, Gunnar; Hellmén, Eva

    2009-01-01

    Background BMPs are currently receiving attention for their role in tumorigenesis and tumor progression. Currently, most BMP expression studies are performed on carcinomas, and not much is known about the situation in sarcomas. Methodology/Principal Findings We have investigated the BMP expression profiles and Smad activation in clones from different spontaneous canine mammary tumors. Spindle cell tumor and osteosarcoma clones expressed high levels of BMPs, in particular BMP-2, -4 and -6. Clones from a scirrhous carcinoma expressed much lower BMP levels. The various clones formed different tumor types in nude mice but only clones that expressed high levels of BMP-6 gave bone formation. Phosphorylated Smad-1/5, located in the nucleus, was detected in tumors derived from clones expressing high levels of BMPs, indicating an active BMP signaling pathway and BMP-2 stimulation of mammary tumor cell clones in vitro resulted in activation of the Smad-1/5 pathway. In contrast BMP-2 stimulation did not induce phosphorylation of the non-Smad pathway p38 MAPK. Interestingly, an increased level of the BMP-antagonist chordin-like 1 was detected after BMP stimulation of non-bone forming clones. Conclusions/Significance We conclude that the specific BMP expression repertoire differs substantially between different types of mammary tumors and that BMP-6 expression most probably has a biological role in bone formation of canine mammary tumors. PMID:19771160

  20. MicroRNA-499 Expression Distinctively Correlates to Target Genes sox6 and rod1 Profiles to Resolve the Skeletal Muscle Phenotype in Nile Tilapia

    PubMed Central

    Carvalho, Robson F.; Martins, Cesar; Pinhal, Danillo

    2015-01-01

    A class of small non-coding RNAs, the microRNAs (miRNAs), has been shown to be essential for the regulation of specific cell pathways, including skeletal muscle development, maintenance and homeostasis in vertebrates. However, the relative contribution of miRNAs for determining the red and white muscle cell phenotypes is far from being fully comprehended. To better characterize the role of miRNA in skeletal muscle cell biology, we investigated muscle-specific miRNA (myomiR) signatures in Nile tilapia fish. Quantitative (RT-qPCR) and spatial (FISH) expression analyses revealed a highly differential expression (forty-four-fold) of miR-499 in red skeletal muscle compared to white skeletal muscle, whereas the remaining known myomiRs were equally expressed in both muscle cell types. Detailed examination of the miR-499 targets through bioinformatics led us to the sox6 and rod1 genes, which had low expression in red muscle cells according to RT-qPCR, FISH, and protein immunofluorescence profiling experiments. Interestingly, we verified that the high expression of miR-499 perfectly correlates with a low expression of sox6 and rod1 target genes, as verified by a distinctive predominance of mRNA destabilization and protein translational decay to these genes, respectively. Through a genome-wide comparative analysis of SOX6 and ROD1 protein domains and through an in silico gene regulatory network, we also demonstrate that both proteins are essentially similar in vertebrate genomes, suggesting their gene regulatory network may also be widely conserved. Overall, our data shed light on the potential regulation of targets by miR-499 associated with the slow-twitch muscle fiber type phenotype. Additionally the results provide novel insights into the evolutionary dynamics of miRNA and target genes enrolled in a putative constrained molecular pathway in the skeletal muscle cells of vertebrates. PMID:25793727

  1. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring

    PubMed Central

    Short, A K; Fennell, K A; Perreau, V M; Fox, A; O'Bryan, M K; Kim, J H; Bredy, T W; Pang, T Y; Hannan, A J

    2016-01-01

    Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic–pituitary–adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light–dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene Igf2 was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including Igf2 and Bdnf. Sustained elevation of glucocorticoids is therefore involved in the transmission of

  2. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring.

    PubMed

    Short, A K; Fennell, K A; Perreau, V M; Fox, A; O'Bryan, M K; Kim, J H; Bredy, T W; Pang, T Y; Hannan, A J

    2016-01-01

    Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic-pituitary-adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light-dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene Igf2 was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including Igf2 and Bdnf. Sustained elevation of glucocorticoids is therefore involved in the transmission of paternal

  3. Behavioural and Brain Gene Expression Profiling in Pigs during Tail Biting Outbreaks - Evidence of a Tail Biting Resistant Phenotype.

    PubMed

    Brunberg, Emma; Jensen, Per; Isaksson, Anders; Keeling, Linda J

    2013-01-01

    Abnormal tail biting behaviour is a major welfare problem for pigs receiving the behaviour, as well as an indication of decreased welfare in the pigs performing it. However, not all pigs in a pen perform or receive tail biting behaviour and it has recently been shown that these 'neutral' pigs not only differ in their behaviour, but also in their gene expression compared to performers and receivers of tail biting in the same pen. To investigate whether this difference was linked to the cause or a consequence of them not being involved in the outbreak of tail biting, behaviour and brain gene expression was compared with 'control' pigs housed in pens with no tail biting. It was shown that the pigs housed in control pens performed a wider variety of pig-directed abnormal behaviour (belly nosing 0.95±1.59, tail in mouth 0.31±0.60 and 'other' abnormal 1.53±4.26; mean±S.D) compared to the neutral pigs (belly nosing 0.30±0.62, tail in mouth 0.13±0.50 and "other" abnormal 0.42±1.06). With Affymetrix gene expression arrays, 107 transcripts were identified as differently expressed (p<0.05) between these two categories of pigs. Several of these transcripts had already been shown to be differently expressed in the neutral pigs when they were compared to performers and receivers of tail biting in the same pen in an earlier study. Hence, the different expression of these genes cannot be a consequence of the neutral pigs not being involved in tail biting behaviour, but rather linked to the cause contributing to why they were not involved in tail biting interactions. These neutral pigs seem to have a genetic and behavioural profile that somehow contributes to them being resistant to performing or receiving pig-directed abnormal behaviour, such as tail biting, even when housed in an environment that elicits that behaviour in other pigs. PMID:23824700

  4. Visualization of multidimensional database

    NASA Astrophysics Data System (ADS)

    Lee, Chung

    2008-01-01

    The concept of multidimensional databases has been extensively researched and wildly used in actual database application. It plays an important role in contemporary information technology, but due to the complexity of its inner structure, the database design is a complicated process and users are having a hard time fully understanding and using the database. An effective visualization tool for higher dimensional information system helps database designers and users alike. Most visualization techniques focus on displaying dimensional data using spreadsheets and charts. This may be sufficient for the databases having three or fewer dimensions but for higher dimensions, various combinations of projection operations are needed and a full grasp of total database architecture is very difficult. This study reviews existing visualization techniques for multidimensional database and then proposes an alternate approach to visualize a database of any dimension by adopting the tool proposed by Kiviat for software engineering processes. In this diagramming method, each dimension is represented by one branch of concentric spikes. This paper documents a C++ based visualization tool with extensive use of OpenGL graphics library and GUI functions. Detailed examples of actual databases demonstrate the feasibility and effectiveness in visualizing multidimensional databases.

  5. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

    Profiles seven Black, Native American, and Chicano artists and art teachers: Hale A. Woodruff, Allan Houser, Luis Jimenez, Betrand D. Phillips, James E. Pate, I, and Fernando Navarro. This article is part of a theme issue on multicultural art. (SJL)

  6. Multidimensional reactor kinetics modeling

    SciTech Connect

    Diamond, D.J.

    1996-11-01

    There is general agreement that for many light water reactor transient calculations, it is-necessary to use a multidimensional neutron kinetics model coupled to a thermal-hydraulics model for satisfactory results. These calculations are needed for a variety of applications for licensing safety analysis, probabilistic risk assessment (PRA), operational support, and training. The latter three applications have always required best-estimate models, but in the past applications for licensing could be satisfied with relatively simple models. By using more sophisticated best-estimate models, the consequences of these calculations are better understood, and the potential for gaining relief from restrictive operating limits increases. Hence, for all of the aforementioned applications, it is important to have the ability to do best-estimate calculations with multidimensional neutron kinetics models. coupled to sophisticated thermal-hydraulic models. Specifically, this paper reviews the status of multidimensional neutron kinetics modeling which would be used in conjunction with thermal-hydraulic models to do core dynamics calculations, either coupled to a complete NSSS representation or in isolation. In addition, the paper makes recommendations as to what should be the state-of-the-art for the next ten years. The review is an update to a previous review of the status as of ten years ago. The general requirements for a core dynamics code and the modeling available for such a code, discussed in that review, are still applicable. The emphasis in the current review is on the neutron kinetics assuming that the necessary thermal-hydraulic capability exists. In addition to discussing the basic neutron kinetics, discussion is given of related modeling (other than thermal- hydraulics). The capabilities and limitations of current computer codes are presented to understand the state-of-the-art and to help clarify the future direction of model development in this area.

  7. Multidimensional Potential Burgers Turbulence

    NASA Astrophysics Data System (ADS)

    Boritchev, Alexandre

    2016-03-01

    We consider the multidimensional generalised stochastic Burgers equation in the space-periodic setting: partial {u}/partial t+(nabla f({u}) \\cdot nabla) {u}-ν Δ {u}= nabla η, quad t ≥ 0, {x} in{T}^d=({R}/ {Z})^d, under the assumption that u is a gradient. Here f is strongly convex and satisfies a growth condition, ν is small and positive, while η is a random forcing term, smooth in space and white in time. For solutions u of this equation, we study Sobolev norms of u averaged in time and in ensemble: each of these norms behaves as a given negative power of ν. These results yield sharp upper and lower bounds for natural analogues of quantities characterising the hydrodynamical turbulence, namely the averages of the increments and of the energy spectrum. These quantities behave as a power of the norm of the relevant parameter, which is respectively the separation ℓ in the physical space and the wavenumber k in the Fourier space. Our bounds do not depend on the initial condition and hold uniformly in {ν}. We generalise the results obtained for the one-dimensional case in [10], confirming the physical predictions in [4, 30]. Note that the form of the estimates does not depend on the dimension: the powers of {ν, |{{k}}|, ℓ} are the same in the one- and the multi-dimensional setting.

  8. Multidimensional Plasma Sheaths over Electrically Inhomogeneous Surfaces

    NASA Astrophysics Data System (ADS)

    Economou, Demetre

    2004-09-01

    Multidimensional plasma sheaths are encountered in a number of applications including plasma immersion ion implantation, extraction of ions (or plasma) through grids, MEMS fabrication, neutral beam sources, and plasma in contact with internal reactor parts (e.g., wafer chuck edge). The sheath may be multidimensional when: (a) plasma is in contact with surface topography, and the size of the topographical features is comparable to or larger than the plasma sheath thickness, or (b) the surface is flat but inhomogeneous, i.e., a conducting surface next to an insulating surface. In either case, the flux, energy and angular distributions of energetic species incident on the substrate are of primary importance. These quantities depend critically on the shape of the meniscus (plasma-sheath boundary) formed over the surface. A two-dimensional fluid/Monte Carlo simulation model was developed to study multidimensional sheaths. The radio frequency (RF) sheath potential evolution, and ion density and flux profiles over the surface were predicted with a self-consistent fluid simulation. The trajectories of ions and energetic neutrals (resulting by ion neutralization on surfaces or charge exchange collisions in the gas phase) were then followed with a Monte Carlo simulation. Ion flow and energy and angular distributions of ions bombarding a flat but electrically inhomogeneous surface will be reported in detail. Ion flow over trenches and holes will also be reported. Work supported by the NSF, Sandia National Laboratories and NIST.

  9. Theta vocabulary II. Multidimensional case

    NASA Astrophysics Data System (ADS)

    Kharchev, S.; Zabrodin, A.

    2016-06-01

    It is shown that the Jacobi and Riemann identities of degree four for the multidimensional theta functions as well as the Weierstrass identities emerge as algebraic consequences of the fundamental multidimensional binary identities connecting the theta functions with Riemann matrices τ and 2 τ.

  10. Multidimensional Perfectionism and the Self

    ERIC Educational Resources Information Center

    Ward, Andrew M.; Ashby, Jeffrey S.

    2008-01-01

    This study examined multidimensional perfectionism and self-development. Two hundred seventy-one undergraduates completed a measure of multidimensional perfectionism and two Kohutian measures designed to measure aspects of self-development including social connectedness, social assurance, goal instability (idealization), and grandiosity. The…

  11. Multidimensional gene search with Genehopper

    PubMed Central

    Munz, Matthias; Tönnies, Sascha; Balke, Wolf-Tilo; Simon, Eric

    2015-01-01

    The high abundance of genetic information enables researchers to gain new insights from the comparison of human genes according to their similarities. However, existing tools that allow the exploration of such gene-to-gene relationships, apply each similarity independently. To make use of multidimensional scoring, we developed a new search engine named Genehopper. It can handle two query types: (i) the typical use case starts with a term-to-gene search, i.e. an optimized full-text search for an anchor gene of interest. The web-interface can handle one or more terms including gene symbols and identifiers of Ensembl, UniProt, EntrezGene and RefSeq. (ii) When the anchor gene is defined, the user can explore its neighborhood by a gene-to-gene search as the weighted sum of nine normalized gene similarities based on sequence homology, protein domains, mRNA expression profiles, Gene Ontology Annotation, gene symbols and other features. Each weight can be adjusted by the user, allowing flexible customization of the gene search. All implemented similarities have a low pairwise correlation (max r2 = 0.4) implying a low linear dependency, i.e. any change in a single weight has an effect on the ranking. Thus, we treated them as separate dimensions in the search space. Genehopper is freely available at http://genehopper.ifis.cs.tu-bs.de. PMID:25990726

  12. Multidimensional gene search with Genehopper.

    PubMed

    Munz, Matthias; Tönnies, Sascha; Balke, Wolf-Tilo; Simon, Eric

    2015-07-01

    The high abundance of genetic information enables researchers to gain new insights from the comparison of human genes according to their similarities. However, existing tools that allow the exploration of such gene-to-gene relationships, apply each similarity independently. To make use of multidimensional scoring, we developed a new search engine named Genehopper. It can handle two query types: (i) the typical use case starts with a term-to-gene search, i.e. an optimized full-text search for an anchor gene of interest. The web-interface can handle one or more terms including gene symbols and identifiers of Ensembl, UniProt, EntrezGene and RefSeq. (ii) When the anchor gene is defined, the user can explore its neighborhood by a gene-to-gene search as the weighted sum of nine normalized gene similarities based on sequence homology, protein domains, mRNA expression profiles, Gene Ontology Annotation, gene symbols and other features. Each weight can be adjusted by the user, allowing flexible customization of the gene search. All implemented similarities have a low pairwise correlation (max r(2) = 0.4) implying a low linear dependency, i.e. any change in a single weight has an effect on the ranking. Thus, we treated them as separate dimensions in the search space. Genehopper is freely available at http://genehopper.ifis.cs.tu-bs.de. PMID:25990726

  13. 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…

  14. 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…

  15. Phenotype Microarray Profiling of Staphylococcus aureus menD and hemB Mutants with the Small-Colony-Variant Phenotype†

    PubMed Central

    von Eiff, Christof; McNamara, Peter; Becker, Karsten; Bates, Donna; Lei, Xiang-He; Ziman, Michael; Bochner, Barry R.; Peters, Georg; Proctor, Richard A.

    2006-01-01

    Standard biochemical tests have revealed that hemin and menadione auxotrophic Staphylococcus aureus small-colony variants (SCVs) exhibit multiple phenotypic changes. To provide a more complete analysis of the SCV phenotype, two genetically defined mutants with a stable SCV phenotype were comprehensively tested. These mutants, generated via mutations in menD or hemB that yielded menadione and hemin auxotrophs, were subjected to phenotype microarray (PM) analysis of over 1,500 phenotypes (including utilization of different carbon, nitrogen, phosphate, and sulfur sources; growth stimulation or inhibition by amino acids and other nutrients, osmolytes, and metabolic inhibitors; and susceptibility to antibiotics). Compared to parent strain COL, the hemB mutant was defective in utilization of a variety of carbon sources, including Krebs cycle intermediates and compounds that ultimately generate ATP via electron transport. The phenotype of the menD mutant was similar to that of the hemB mutant, but the defects in carbon metabolism were more pronounced than those seen with the hemB mutant. In both mutant strains, hexose phosphates and other carbohydrates that provide ATP in the absence of electron transport stimulated growth. Other phenotypes of SCV mutants, such as hypersensitivity to sodium selenite, sodium tellurite, and sodium nitrite, were also uncovered by the PM analysis. Key results of the PM analysis were confirmed in independent growth studies and by using Etest strips for susceptibility testing. PM technology is a new and efficient technology for assessing cellular phenotypes in S. aureus. PMID:16385058

  16. Bioimaging for quantitative phenotype analysis.

    PubMed

    Chen, Weiyang; Xia, Xian; Huang, Yi; Chen, Xingwei; Han, Jing-Dong J

    2016-06-01

    With the development of bio-imaging techniques, an increasing number of studies apply these techniques to generate a myriad of image data. Its applications range from quantification of cellular, tissue, organismal and behavioral phenotypes of model organisms, to human facial phenotypes. The bio-imaging approaches to automatically detect, quantify, and profile phenotypic changes related to specific biological questions open new doors to studying phenotype-genotype associations and to precisely evaluating molecular changes associated with quantitative phenotypes. Here, we review major applications of bioimage-based quantitative phenotype analysis. Specifically, we describe the biological questions and experimental needs addressable by these analyses, computational techniques and tools that are available in these contexts, and the new perspectives on phenotype-genotype association uncovered by such analyses. PMID:26850283

  17. Phenotypic profile of dendritic and T cells in the lymph node of Balb/C mice with breast cancer submitted to dendritic cells immunotherapy.

    PubMed

    da Cunha, Alessandra; Antoniazi Michelin, Marcia; Cândido Murta, Eddie Fernando

    2016-09-01

    Breast cancer (BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development influenced by various mutations that occur in the tumor cell and by the immune system's status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Strategies using dendritic cells (DCs) or antigen-presenting cells (APCs), therapeutic mode, in cancer have been developed for some time. The proper interaction between DCs and T cells upon antigen presentation is of greatest importance for an antitumor immune response activation. Thus, various receptors on the surface of T cells must be able to recognize ligands that are located on the surface of APCs. However, little is known about the real behavior and interaction forms of CDs and T cells after vaccination. Due to the crucial importance of DCs in an effective anti-tumor immune response activation and the search for compliant results in inducing this response by immunotherapies with DCs, the phenotypic profile of DCs and T cells in lymph nodes obtained from female Balb/C mice with breast cancer induced by 4T1 cells and DCs treated with vaccines was investigated. We evaluated through flow cytometry based on the surface and intracellular molecules marking; as well as the presence of cytokines and chemokines, IL-2, IL-4, IL-10, IL-12, IFN-γ, TNF-α and TGF-β in the supernatant of the culture of Balb/C lymph nodes by ELISA. The results show that the vaccination with DCs, in the maturation parameters used in this study, was able to stimulate the secretion of cytokines such as IFN-γ and IL-12 and inhibit the secretion of TGF-β and IL-10 in nodal lymph infiltrates, as well as co-stimulatory activating (CD86) and adhesion molecules in DCs and T cells LFA-1/ICAM-1 and inhibit the secretion of CTLA-4 present in lymph nodes. Facts that led to aTh1 profile polarization, immuno competent in relation

  18. Comparative Phenotypic and Molecular Genetic Profiling of Wild Lactococcus lactis subsp. lactis Strains of the L. lactis subsp. lactis and L. lactis subsp. cremoris Genotypes, Isolated from Starter-Free Cheeses Made of Raw Milk▿

    PubMed Central

    Fernández, Elena; Alegría, Ángel; Delgado, Susana; Martín, M. Cruz; Mayo, Baltasar

    2011-01-01

    Twenty Lactococcus lactis strains with an L. lactis subsp. lactis phenotype isolated from five traditional cheeses made of raw milk with no added starters belonging to the L. lactis subsp. lactis and L. lactis subsp. cremoris genotypes (lactis and cremoris genotypes, respectively; 10 strains each) were subjected to a series of phenotypic and genetic typing methods, with the aims of determining their phylogenetic relationships and suitability as starters. Pulsed-field gel electrophoresis (PFGE) analysis of intact genomes digested with SalI and SmaI proved that all strains were different except for three isolates of the cremoris genotype, which showed identical PFGE profiles. Multilocus sequence typing (MLST) analysis using internal sequences of seven loci (namely, atpA, rpoA, pheS, pepN, bcaT, pepX, and 16S rRNA gene) revealed considerable intergenotype nucleotide polymorphism, although deduced amino acid changes were scarce. Analysis of the MLST data for the present strains and others from other dairy and nondairy sources showed that all of them clustered into the cremoris or lactis genotype group, by using both independent and combined gene sequences. These two groups of strains also showed distinctive carbohydrate fermentation and enzyme activity profiles, with the strains in the cremoris group showing broader profiles. However, the profiles of resistance/susceptibility to 16 antibiotics were very similar, showing no atypical resistance, except for tetracycline resistance in three identical cremoris genotype isolates. The numbers and concentrations of volatile compounds produced in milk by the strains belonging to these two groups were clearly different, with the cremoris genotype strains producing higher concentrations of more branched-chain, derived compounds. Together, the present results support the idea that the lactis and cremoris genotypes of phenotypic Lactococcus lactis subsp. lactis actually represent true subspecies. Some strains of the two subspecies

  19. Multidimensional persistence in biomolecular data

    PubMed Central

    Xia, Kelin; Wei, Guo-Wei

    2015-01-01

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudo-multidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryo-electron microscopy data, and the scale dependence of nano particles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. PMID:26032339

  20. Profiling functions of ectomycorrhizal diversity and root structuring in seedlings of Norway spruce (Picea abies) with fast- and slow-growing phenotypes.

    PubMed

    Velmala, Sannakajsa M; Rajala, Tiina; Heinonsalo, Jussi; Taylor, Andy F S; Pennanen, Taina

    2014-01-01

    We studied the role of taxonomical and functional ectomycorrhizal (ECM) fungal diversity in root formation and nutrient uptake by Norway spruce (Picea abies) seedlings with fast- and slow-growing phenotypes. Seedlings were grown with an increasing ECM fungal diversity gradient from one to four species and sampled before aboveground growth differences between the two phenotypes were apparent. ECM fungal colonization patterns were determined and functional diversity was assayed via measurements of potential enzyme activities of eight exoenzymes probably involved in nutrient mobilization. Phenotypes did not vary in their receptiveness to different ECM fungal species. However, seedlings of slow-growing phenotypes had higher fine-root density and thus more condensed root systems than fast-growing seedlings, but the potential enzyme activities of ectomycorrhizas did not differ qualitatively or quantitatively. ECM species richness increased host nutrient acquisition potential by diversifying the exoenzyme palette. Needle nitrogen content correlated positively with high chitinase activity of ectomycorrhizas. Rather than fast- and slow-growing phenotypes exhibiting differing receptiveness to ECM fungi, our results suggest that distinctions in fine-root structuring and in the belowground growth strategy already apparent at early stages of seedling development may explain later growth differences between fast- and slow-growing families. PMID:24117652

  1. Multidimensionality in host manipulation mimicked by serotonin injection.

    PubMed

    Perrot-Minnot, Marie-Jeanne; Sanchez-Thirion, Kevin; Cézilly, Frank

    2014-12-01

    Manipulative parasites often alter the phenotype of their hosts along multiple dimensions. 'Multidimensionality' in host manipulation could consist in the simultaneous alteration of several physiological pathways independently of one another, or proceed from the disruption of some key physiological parameter, followed by a cascade of effects. We compared multidimensionality in 'host manipulation' between two closely related amphipods, Gammarus fossarum and Gammarus pulex, naturally and experimentally infected with Pomphorhynchus laevis (Acanthocephala), respectively. To that end, we calculated in each host-parasite association the effect size of the difference between infected and uninfected individuals for six different traits (activity, phototaxis, geotaxis, attraction to conspecifics, refuge use and metabolic rate). The effects sizes were highly correlated between host-parasite associations, providing evidence for a relatively constant 'infection syndrome'. Using the same methodology, we compared the extent of phenotypic alterations induced by an experimental injection of serotonin (5-HT) in uninfected G. pulex to that induced by experimental or natural infection with P. laevis. We observed a significant correlation between effect sizes across the six traits, indicating that injection with 5-HT can faithfully mimic the 'infection syndrome'. This is, to our knowledge, the first experimental evidence that multidimensionality in host manipulation can proceed, at least partly, from the disruption of some major physiological mechanism. PMID:25339729

  2. A Multidimensional Partial Credit Model with Associated Item and Test Statistics: An Application to Mixed-Format Tests

    ERIC Educational Resources Information Center

    Yao, Lihua; Schwarz, Richard D.

    2006-01-01

    Multidimensional item response theory (IRT) models have been proposed for better understanding the dimensional structure of data or to define diagnostic profiles of student learning. A compensatory multidimensional two-parameter partial credit model (M-2PPC) for constructed-response items is presented that is a generalization of those proposed to…

  3. Multidimensional persistence in biomolecular data.

    PubMed

    Xia, Kelin; Wei, Guo-Wei

    2015-07-30

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudomultidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high-dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness, and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryoelectron microscopy data, and the scale dependence of nanoparticles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. PMID:26032339

  4. Modeling, calculating, and analyzing multidimensional vibrational spectroscopies.

    PubMed

    Tanimura, Yoshitaka; Ishizaki, Akihito

    2009-09-15

    Spectral line shapes in a condensed phase contain information from various dynamic processes that modulate the transition energy, such as microscopic dynamics, inter- and intramolecular couplings, and solvent dynamics. Because nonlinear response functions are sensitive to the complex dynamics of chemical processes, multidimensional vibrational spectroscopies can separate these processes. In multidimensional vibrational spectroscopy, the nonlinear response functions of a molecular dipole or polarizability are measured using ultrashort pulses to monitor inter- and intramolecular vibrational motions. Because a complex profile of such signals depends on the many dynamic and structural aspects of a molecular system, researchers would like to have a theoretical understanding of these phenomena. In this Account, we explore and describe the roles of different physical phenomena that arise from the peculiarities of the system-bath coupling in multidimensional spectra. We also present simple analytical expressions for a weakly coupled multimode Brownian system, which we use to analyze the results obtained by the experiments and simulations. To calculate the nonlinear optical response, researchers commonly use a particular form of a system Hamiltonian fit to the experimental results. The optical responses of molecular vibrational motions have been studied in either an oscillator model or a vibration energy state model. In principle, both models should give the same results as long as the energy states are chosen to be the eigenstates of the oscillator model. The energy state model can provide a simple description of nonlinear optical processes because the diagrammatic Liouville space theory that developed in the electronically resonant spectroscopies can easily handle three or four energy states involved in high-frequency vibrations. However, the energy state model breaks down if we include the thermal excitation and relaxation processes in the dynamics to put the system in a

  5. Phenotypes of childhood asthma: are they real?

    PubMed

    Spycher, B D; Silverman, M; Kuehni, C E

    2010-08-01

    It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). The underlying causes are not sufficiently understood to define disease entities based on aetiology. Nevertheless, there is a need for a classification that would (i) facilitate research into aetiology and pathophysiology, (ii) allow targeted treatment and preventive measures and (iii) improve the prediction of long-term outcome. Classical attempts to define phenotypes have been one-dimensional, relying on few or single features such as triggers (exclusive viral wheeze vs. multiple trigger wheeze) or time course (early transient wheeze, persistent and late onset wheeze). These definitions are simple but essentially subjective. Recently, a multi-dimensional approach has been adopted. This approach is based on a wide range of features and relies on multivariate methods such as cluster or latent class analysis. Phenotypes identified in this manner are more complex but arguably more objective. Although phenotypes have an undisputed standing in current research on childhood asthma and wheezing, there is confusion about the meaning of the term 'phenotype' causing much circular debate. If phenotypes are meant to represent 'real' underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi-dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying

  6. Morphological Profiles of RNAi-Induced Gene Knockdown Are Highly Reproducible but Dominated by Seed Effects

    PubMed Central

    Singh, Shantanu; Wu, Xiaoyun; Ljosa, Vebjorn; Bray, Mark-Anthony; Piccioni, Federica; Root, David E.; Doench, John G.; Boehm, Jesse S.; Carpenter, Anne E.

    2015-01-01

    RNA interference and morphological profiling—the measurement of thousands of phenotypes from individual cells by microscopy and image analysis—are a potentially powerful combination. We show that morphological profiles of RNAi-induced knockdown using the Cell Painting assay are in fact highly sensitive and reproducible. However, we find that the magnitude and prevalence of off-target effects via the RNAi seed-based mechanism make morphological profiles of RNAi reagents targeting the same gene look no more similar than reagents targeting different genes. Pairs of RNAi reagents that share the same seed sequence produce image-based profiles that are much more similar to each other than profiles from pairs designed to target the same gene, a phenomenon previously observed in small-scale gene-expression profiling experiments. Various strategies have been used to enrich on-target versus off-target effects in the context of RNAi screening where a narrow set of phenotypes are measured, mostly based on comparing multiple sequences targeting the same gene; however, new approaches will be needed to make RNAi morphological profiling (that is, comparing multi-dimensional phenotypes) viable. We have shared our raw data and computational pipelines to facilitate research. PMID:26197079

  7. A log-linear multidimensional Rasch model for capture-recapture.

    PubMed

    Pelle, E; Hessen, D J; van der Heijden, P G M

    2016-02-20

    In this paper, a log-linear multidimensional Rasch model is proposed for capture-recapture analysis of registration data. In the model, heterogeneity of capture probabilities is taken into account, and registrations are viewed as dichotomously scored indicators of one or more latent variables that can account for correlations among registrations. It is shown how the probability of a generic capture profile is expressed under the log-linear multidimensional Rasch model and how the parameters of the traditional log-linear model are derived from those of the log-linear multidimensional Rasch model. Finally, an application of the model to neural tube defects data is presented. PMID:26423044

  8. 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.

  9. CellProfiler Analyst: data exploration and analysis software for complex image-based screens

    PubMed Central

    Jones, Thouis R; Kang, In Han; Wheeler, Douglas B; Lindquist, Robert A; Papallo, Adam; Sabatini, David M; Golland, Polina; Carpenter, Anne E

    2008-01-01

    Background Image-based screens can produce hundreds of measured features for each of hundreds of millions of individual cells in a single experiment. Results Here, we describe CellProfiler Analyst, open-source software for the interactive exploration and analysis of multidimensional data, particularly data from high-throughput, image-based experiments. Conclusion The system enables interactive data exploration for image-based screens and automated scoring of complex phenotypes that require combinations of multiple measured features per cell. PMID:19014601

  10. A Multidimensional Software Engineering Course

    ERIC Educational Resources Information Center

    Barzilay, O.; Hazzan, O.; Yehudai, A.

    2009-01-01

    Software engineering (SE) is a multidimensional field that involves activities in various areas and disciplines, such as computer science, project management, and system engineering. Though modern SE curricula include designated courses that address these various subjects, an advanced summary course that synthesizes them is still missing. Such a…

  11. Multidimensional Scaling of Video Surrogates.

    ERIC Educational Resources Information Center

    Goodrum, Abby A.

    2001-01-01

    Four types of video surrogates were compared under two tasks. Multidimensional scaling was used to map dimensional dispersions of users' judgments of similarity between videos and surrogates. Congruence between these maps was used to evaluate representativeness of each surrogate type. Congruence was greater for image-based than for text-based…

  12. A combined analysis of the Frost Multidimensional Perfectionism Scale (FMPS), Child and Adolescent Perfectionism Scale (CAPS), and Almost Perfect Scale-Revised (APS-R): Different perfectionist profiles in adolescent high school students.

    PubMed

    Sironic, Amanda; Reeve, Robert A

    2015-12-01

    To investigate differences and similarities in the dimensional constructs of the Frost Multidimensional Perfectionism Scale (FMPS; Frost, Marten, Lahart, & Rosenblate, 1990), Child and Adolescent Perfectionism Scale (CAPS; Flett, Hewitt, Boucher, Davidson, & Munro, 2000), and Almost Perfect Scale-Revised (APS-R; Slaney, Rice, Mobley, Trippi, & Ashby, 2001), 938 high school students completed the 3 perfectionism questionnaires, as well as the Depression Anxiety Stress Scales (DASS; Lovibond & Lovibond, 1995). Preliminary analyses revealed commonly observed factor structures for each perfectionism questionnaire. Exploratory factor analysis of item responses from the questionnaires (combined) yielded a 4-factor solution (factors were labeled High Personal Standards, Concerns, Doubts and Discrepancy, Externally Motivated Perfectionism, and Organization and Order). A latent class analysis of individuals' mean ratings on each of the 4 factors yielded a 6-class solution. Three of the 6 classes represented perfectionist subgroups (labeled adaptive perfectionist, externally motivated maladaptive perfectionist, and mixed maladaptive perfectionist), and 3 represented nonperfectionist subgroups (labeled nonperfectionist A, nonperfectionist B, and order and organization nonperfectionist). Each of the 6 subgroups was meaningfully associated with the DASS. Findings showed that 3 out of 10 students were classified as maladaptive perfectionists, and maladaptive perfectionists were more prevalent than adaptive perfectionists. In sum, it is evident that combined ratings from the FMPS, CAPS, and APS-R offer a meaningful characterization of perfectionism. PMID:25984636

  13. The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-α production.

    PubMed

    Dimitrijević, Mirjana; Stanojević, Stanislava; Kuštrimović, Nataša; Mitić, Katarina; Vujić, Vesna; Aleksić, Iva; Radojević, Katarina; Leposavić, Gordana

    2013-11-01

    The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity. PMID

  14. Molecular Profiling of Conjunctival Epithelial Side-Population Stem Cells: Atypical Cell Surface Markers and Sources of a Slow-Cycling Phenotype

    PubMed Central

    Akinci, M. A. Murat; Turner, Helen; Taveras, Maria; Barash, Alex; Wang, Zheng; Reinach, Peter; Wolosin, J. Mario

    2009-01-01

    PURPOSE Side-population (SP) cells isolated from limbal and conjunctival epithelia derive from cells that are slow cycling in vivo, a known feature of tissue stem cells. The purpose of this study was to define the molecular signature of the conjunctival SP cells and identify markers and signaling pathways associated with the phenotype of these cells. METHODS Overnight cultures of freshly isolated human conjunctival epithelial cells stained with Hoechst 33342 were sorted by flow cytometry into SP and non-SP cohorts. Isolated RNA was processed for microarray analysis using a commercial oligonucleotide spotted array. Results were validated at the gene and protein levels by quantitative PCR and immunologic methods. Data mining methods were used to identify cellular processes relevant for stem cell function. RESULTS Comparative analyses of transcripts expression based on present and absent software calls across four replicate experiments identified 16,993 conjunctival epithelial transcripts including 10,266 unique known genes of ~24,000 represented in the array. Of those genes, 1254 and 363 were overexpressed (>2-fold) or underexpressed (<0.5-fold), respectively, in the SP. The overexpressed set included genes coding for proteins that have been associated with (1) embryonic development and/or stem cell self renewal (MSX, MEIS, ID, Hes1, and SIX homeodomain genes); (2) cell survival (e.g., CYP1A1 to degrade aromatic genotoxic compounds); (3) cycling rate (e.g., DUSPs and Pax6 to foster slow cycling); and (4) genes whose expression is not typical in epithelia (e.g., CD62E). CONCLUSIONS The molecular signature of conjunctival SP cells is consistent with a stem cell phenotype. Their gene expression patterns underpin slow cycling and plasticity, features associated with tissue stem cells. The results provide valuable insights for the preservation and/or expansion of epithelial stem cells. PMID:19324848

  15. A method for analysis of phenotypic change for phenotypes described by high-dimensional data.

    PubMed

    Collyer, M L; Sekora, D J; Adams, D C

    2015-10-01

    The analysis of phenotypic change is important for several evolutionary biology disciplines, including phenotypic plasticity, evolutionary developmental biology, morphological evolution, physiological evolution, evolutionary ecology and behavioral evolution. It is common for researchers in these disciplines to work with multivariate phenotypic data. When phenotypic variables exceed the number of research subjects--data called 'high-dimensional data'--researchers are confronted with analytical challenges. Parametric tests that require high observation to variable ratios present a paradox for researchers, as eliminating variables potentially reduces effect sizes for comparative analyses, yet test statistics require more observations than variables. This problem is exacerbated with data that describe 'multidimensional' phenotypes, whereby a description of phenotype requires high-dimensional data. For example, landmark-based geometric morphometric data use the Cartesian coordinates of (potentially) many anatomical landmarks to describe organismal shape. Collectively such shape variables describe organism shape, although the analysis of each variable, independently, offers little benefit for addressing biological questions. Here we present a nonparametric method of evaluating effect size that is not constrained by the number of phenotypic variables, and motivate its use with example analyses of phenotypic change using geometric morphometric data. Our examples contrast different characterizations of body shape for a desert fish species, associated with measuring and comparing sexual dimorphism between two populations. We demonstrate that using more phenotypic variables can increase effect sizes, and allow for stronger inferences. PMID:25204302

  16. Multidimensional signatures in antimicrobial peptides

    PubMed Central

    Yount, Nannette Y.; Yeaman, Michael R.

    2004-01-01

    Conventional analyses distinguish between antimicrobial peptides by differences in amino acid sequence. Yet structural paradigms common to broader classes of these molecules have not been established. The current analyses examined the potential conservation of structural themes in antimicrobial peptides from evolutionarily diverse organisms. Using proteomics, an antimicrobial peptide signature was discovered to integrate stereospecific sequence patterns and a hallmark three-dimensional motif. This striking multidimensional signature is conserved among disulfide-containing antimicrobial peptides spanning biological kingdoms, and it transcends motifs previously limited to defined peptide subclasses. Experimental data validating this model enabled the identification of previously unrecognized antimicrobial activity in peptides of known identity. The multidimensional signature model provides a unifying structural theme in broad classes of antimicrobial peptides, will facilitate discovery of antimicrobial peptides as yet unknown, and offers insights into the evolution of molecular determinants in these and related host defense effector molecules. PMID:15118082

  17. Deterministic multidimensional nonuniform gap sampling

    NASA Astrophysics Data System (ADS)

    Worley, Bradley; Powers, Robert

    2015-12-01

    Born from empirical observations in nonuniformly sampled multidimensional NMR data relating to gaps between sampled points, the Poisson-gap sampling method has enjoyed widespread use in biomolecular NMR. While the majority of nonuniform sampling schemes are fully randomly drawn from probability densities that vary over a Nyquist grid, the Poisson-gap scheme employs constrained random deviates to minimize the gaps between sampled grid points. We describe a deterministic gap sampling method, based on the average behavior of Poisson-gap sampling, which performs comparably to its random counterpart with the additional benefit of completely deterministic behavior. We also introduce a general algorithm for multidimensional nonuniform sampling based on a gap equation, and apply it to yield a deterministic sampling scheme that combines burst-mode sampling features with those of Poisson-gap schemes. Finally, we derive a relationship between stochastic gap equations and the expectation value of their sampling probability densities.

  18. Administration of Lactobacillus evokes coordinated changes in the intestinal expression profile of genes regulating energy homeostasis and immune phenotype in mice.

    PubMed

    Nerstedt, Annika; Nilsson, Elisabeth C; Ohlson, Kajsa; Håkansson, Janet; Thomas Svensson, L; Löwenadler, Björn; Svensson, Ulla K; Mahlapuu, Margit

    2007-06-01

    Lactic acid bacteria are probiotics widely used in functional food products, with a variety of beneficial effects reported. Recently, intense research has been carried out to provide insight into the mechanism of the action of probiotic bacteria. We have used gene array technology to map the pattern of changes in the global gene expression profile of the host caused by Lactobacillus administration. Affymetrix microarrays were applied to comparatively characterize differences in gene transcription in the distal ileum of normal microflora (NMF) and germ-free (GF) mice evoked by oral administration of two Lactobacillus strains used in fermented dairy products today - Lactobacillus paracasei ssp. paracasei F19 (L. F19) or Lactobacillus acidophilus NCFB 1748. We show that feeding either of the two strains caused very similar effects on the transcriptional profile of the host. Both L. F19 and L. acidophilus NCFB 1748 evoked a complex response in the gut, reflected by differential regulation of a number of genes involved in essential physiological functions such as immune response, regulation of energy homeostasis and host defence. Notably, the changes in intestinal gene expression caused by Lactobacillus were different in the mice raised under GF v. NMF conditions, underlying the complex and dynamic nature of the host-commensal relationship. Differential expression of an array of genes described in this report evokes novel hypothesis of possible interactions between the probiotic bacteria and the host organism and warrants further studies to evaluate the functional significance of these transcriptional changes on the metabolic profile of the host. PMID:17433125

  19. Gene-expression profiling of Waldenström macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma

    PubMed Central

    Chng, Wee J.; Schop, Roelandt F.; Price-Troska, Tammy; Ghobrial, Irene; Kay, Neil; Jelinek, Diane F.; Gertz, Morie A.; Dispenzieri, Angela; Lacy, Martha; Kyle, Robert A.; Greipp, Philip R.; Tschumper, Renee C.; Fonseca, Rafael; Bergsagel, Peter Leif

    2006-01-01

    Waldenström macroglobulinemia (WM) is a B-cell malignancy characterized by the ability of the B-cell clone to differentiate into plasma cells. Although the clinical syndrome and the pathologic characteristics are well defined, little is known about its biology and controversy still exists regarding its cell of origin. In this gene-expression study, we compared the transcription profiles of WM with those of other malignant B cells including (chronic lymphocytic leukemia [CLL] and multiple myeloma [MM]) as well as normal cells (peripheral-blood B cells and bone marrow plasma cells). We found that WM has a homogenous gene expression regardless of 6q deletion status and clusters with CLL and normal B cells on unsupervised clustering with very similar expression profiles. Only a small gene set has expression profiles unique to WM compared to CLL and MM. The most significantly up-regulated gene is IL6 and the most significantly associated pathway for this set of genes is MAPK signaling. Thus, IL6 and its downstream signaling may be of biologic importance in WM. Further elucidation of the role of IL-6 in WM is warranted as this may offer a potential therapeutic avenue. PMID:16804116

  20. Multidimensional bioseparation with modular microfluidics

    DOEpatents

    Chirica, Gabriela S.; Renzi, Ronald F.

    2013-08-27

    A multidimensional chemical separation and analysis system is described including a prototyping platform and modular microfluidic components capable of rapid and convenient assembly, alteration and disassembly of numerous candidate separation systems. Partial or total computer control of the separation system is possible. Single or multiple alternative processing trains can be tested, optimized and/or run in parallel. Examples related to the separation and analysis of human bodily fluids are given.

  1. Cuba: Multidimensional numerical integration library

    NASA Astrophysics Data System (ADS)

    Hahn, Thomas

    2016-08-01

    The Cuba library offers four independent routines for multidimensional numerical integration: Vegas, Suave, Divonne, and Cuhre. The four algorithms work by very different methods, and can integrate vector integrands and have very similar Fortran, C/C++, and Mathematica interfaces. Their invocation is very similar, making it easy to cross-check by substituting one method by another. For further safeguarding, the output is supplemented by a chi-square probability which quantifies the reliability of the error estimate.

  2. Multidimensional scaling of pictorial informativeness.

    PubMed

    Antes, J R; Stone, L A

    1975-06-01

    The dimensions used in the judgment of the informativeness of picture sections were investigated by means of a recently proposed methodology, multidimensional similarity analysis. 10 judges (college students) rated the informational similarity of 32 areas within a single picture. The five extracted dimensions accounted for 86% of the judgmental variance and were all readily interpretable. These dimensions were discussed with respect to an earlier study in which eye movements of subjects viewing this picture were recorded. PMID:1178379

  3. Multidimensionality in host manipulation mimicked by serotonin injection

    PubMed Central

    Perrot-Minnot, Marie-Jeanne; Sanchez-Thirion, Kevin; Cézilly, Frank

    2014-01-01

    Manipulative parasites often alter the phenotype of their hosts along multiple dimensions. ‘Multidimensionality’ in host manipulation could consist in the simultaneous alteration of several physiological pathways independently of one another, or proceed from the disruption of some key physiological parameter, followed by a cascade of effects. We compared multidimensionality in ‘host manipulation’ between two closely related amphipods, Gammarus fossarum and Gammarus pulex, naturally and experimentally infected with Pomphorhynchus laevis (Acanthocephala), respectively. To that end, we calculated in each host–parasite association the effect size of the difference between infected and uninfected individuals for six different traits (activity, phototaxis, geotaxis, attraction to conspecifics, refuge use and metabolic rate). The effects sizes were highly correlated between host–parasite associations, providing evidence for a relatively constant ‘infection syndrome’. Using the same methodology, we compared the extent of phenotypic alterations induced by an experimental injection of serotonin (5-HT) in uninfected G. pulex to that induced by experimental or natural infection with P. laevis. We observed a significant correlation between effect sizes across the six traits, indicating that injection with 5-HT can faithfully mimic the ‘infection syndrome’. This is, to our knowledge, the first experimental evidence that multidimensionality in host manipulation can proceed, at least partly, from the disruption of some major physiological mechanism. PMID:25339729

  4. Outstanding Phenotypic Differences in the Profile of Amyloid-β between Tg2576 and APPswe/PS1dE9 Transgenic Mouse Models of Alzheimer's Disease.

    PubMed

    Allué, José Antonio; Sarasa, Leticia; Izco, María; Pérez-Grijalba, Virginia; Fandos, Noelia; Pascual-Lucas, María; Ogueta, Samuel; Pesini, Pedro; Sarasa, Manuel

    2016-05-30

    APPswe/PS1dE9 and Tg2576 are very common transgenic mouse models of Alzheimer's disease (AD), used in many laboratories as tools to research the mechanistic process leading to the disease. In order to augment our knowledge about the amyloid-β (Aβ) isoforms present in both transgenic mouse models, we have developed two chromatographic methods, one acidic and the other basic, for the characterization of the Aβ species produced in the brains of the two transgenic mouse models. After immunoprecipitation and micro-liquid chromatography-electrospray ionization mass spectrometry/mass spectrometry, 10 species of Aβ, surprisingly all of human origin, were detected in the brain of Tg2576 mouse, whereas 39 species, of both murine and human origin, were detected in the brain of the APP/PS1 mouse. To the best of our knowledge, this is the first study showing the identification of such a high number of Aβ species in the brain of the APP/PS1 transgenic mouse, whereas, in contrast, a much lower number of Aβ species were identified in the Tg2576 mouse. Therefore, this study brings to light a relevant phenotypic difference between these two popular mice models of AD. PMID:27258422

  5. Ultra high resolution SFC-MS as a high throughput platform for metabolic phenotyping: application to metabolic profiling of rat and dog bile.

    PubMed

    Jones, Michael D; Rainville, Paul D; Isaac, Giorgis; Wilson, Ian D; Smith, Norman W; Plumb, Robert S

    2014-09-01

    Ultra high resolution SFC-MS (on sub-2μm particles) coupled to mass spectrometry has been evaluated for the metabolic profiling of rat and dog bile. The selectivity of the SFC separation differed from that seen in previous reversed-phase UPLC-MS studies on bile, with the order of elution for analytes such as e.g., the bile acids showing many differences. The chromatography system showed excellent stability, reproducibility and robustness with relative standard deviation of less than 1% for retention time obtained over the course of the analysis. SFC showed excellent chromatographic performance with chromatographic peak widths in the order of 3s at the base of the peak. The use of supercritical fluid carbon dioxide as a mobile phase solvent also reduced the overall consumption of organic solvent by a factor of 3 and also reduced the overall analysis time by a factor of 30% compared to reversed-phase gradient LC. SFC-MS appear complementary to RPLC for the metabolic profiling of complex samples such as bile. PMID:24815366

  6. Distribution of phenotypes among Bacillus thuringiensis strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice.

    PubMed

    Peris-Sampedro, Fiona; Cabré, Maria; Basaure, Pia; Reverte, Ingrid; Domingo, José L; Teresa Colomina, Maria

    2015-10-01

    Increasing evidence links the widespread exposure to organophosphate (OP) pesticides to the global epidemics of type 2 diabetes and obesity. Our recent data highlighted gene×environment interactions: mice expressing the human apolipoprotein E3 (apoE3) isoform were more prone to develop obesity than those expressing apoE2 or apoE4 upon dietary challenge with chlorpyrifos (CPF), the most used OP worldwide. Thus, we aimed to further explore the contribution of the APOE3 genotype on the emergence of obesity and related metabolic dysfunctions upon subchronic exposure to CPF. Seven-month-old targeted replacement apoE3 and C57BL/6N male mice were orally exposed to CPF at 0 or 2mg/kg body weight/day for 8 consecutive weeks. We examined body weight status, food and water intake, lipid and glucose homeostasis, metabolic biomarkers concentrations, insulin levels and insulin resistance, and leptin and ghrelin profiles. CPF exposure generally increased food ingestion, glucose and total cholesterol concentrations, and tended to elevate acyl ghrelin levels. Nonetheless, excess weight gain and increased leptin levels were inherent to apoE3 mice. Moreover, the propensity towards a diabetic profile was markedly higher in these animals than in C57BL/6N, as they showed a higher homeostatic model assessment for insulin resistance index and higher insulin levels. Although both genotypes were metabolically affected by CPF, the results of the present investigation revealed that apoE3 mice were the most vulnerable to developing obesity and related disturbances following CPF administration through the diet. Since the APOE3 genotype is the most prevalent worldwide, current findings have particular implications for human health. PMID:26162960

  8. Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127low Treg Cells in Patients With Chronic Rheumatoid Arthritis

    PubMed Central

    Walter, Gina J.; Fleskens, Veerle; Frederiksen, Klaus S.; Rajasekhar, Megha; Menon, Bina; Gerwien, Jens G.; Evans, Hayley G.

    2015-01-01

    Objective Conflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA. Methods Using a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127low Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte‐derived cytokine/chemokine production, and gene expression profiles. Results No differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin‐17 [IL‐17], interferon‐γ [IFNγ], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFNγ or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines/chemokines (IL‐1β, IL‐1 receptor antagonist, IL‐7, CCL3, or CCL4) by autologous lipopolysaccharide‐activated monocytes. However, this was not observed in all patients, and other cytokines/chemokines (TNF, IL‐6, IL‐8, IL‐12, IL‐15, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls. Conclusion Our findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in

  9. Measures for a multidimensional multiverse

    NASA Astrophysics Data System (ADS)

    Chung, Hyeyoun

    2015-04-01

    We explore the phenomenological implications of generalizing the causal patch and fat geodesic measures to a multidimensional multiverse, where the vacua can have differing numbers of large dimensions. We consider a simple model in which the vacua are nucleated from a D -dimensional parent spacetime through dynamical compactification of the extra dimensions, and compute the geometric contribution to the probability distribution of observations within the multiverse for each measure. We then study how the shape of this probability distribution depends on the time scales for the existence of observers, for vacuum domination, and for curvature domination (tobs,tΛ , and tc, respectively.) In this work we restrict ourselves to bubbles with positive cosmological constant, Λ . We find that in the case of the causal patch cutoff, when the bubble universes have p +1 large spatial dimensions with p ≥2 , the shape of the probability distribution is such that we obtain the coincidence of time scales tobs˜tΛ˜tc . Moreover, the size of the cosmological constant is related to the size of the landscape. However, the exact shape of the probability distribution is different in the case p =2 , compared to p ≥3 . In the case of the fat geodesic measure, the result is even more robust: the shape of the probability distribution is the same for all p ≥2 , and we once again obtain the coincidence tobs˜tΛ˜tc . These results require only very mild conditions on the prior probability of the distribution of vacua in the landscape. Our work shows that the observed double coincidence of time scales is a robust prediction even when the multiverse is generalized to be multidimensional; that this coincidence is not a consequence of our particular Universe being (3 +1 )-dimensional; and that this observable cannot be used to preferentially select one measure over another in a multidimensional multiverse.

  10. Preconditioning for multidimensional TOMBO imaging.

    PubMed

    Horisaki, Ryoichi; Tanida, Jun

    2011-06-01

    In this Letter, we propose a preconditioning method to improve the convergence speed of iterative reconstruction algorithms in a compact, multidimensional, compound-eye imaging system called the thin observation module by bound optics. The condition number of the system matrix is improved by using a preconditioner matrix. To calculate the preconditioner matrix, the system model is expressed in the frequency domain. The proposed method is simulated by using a compressive sensing algorithm called the two-step iterative shrinkage/thresholding algorithm. The results showed improved reconstruction fidelity with a certain number of iterations for high signal-to-noise ratio measurements. PMID:21633452

  11. Structural profiling of lipopolysaccharide glycoforms expressed by non-typeable Haemophilus influenzae: phenotypic similarities between NTHi strain 162 and the genome strain Rd.

    PubMed

    Schweda, Elke K H; Landerholm, Malin K; Li, Jianjun; Richard Moxon, E; Richards, James C

    2003-11-14

    Non-typeable Haemophilus influenzae (NTHi) is a significant cause of otitis media in children. We have employed single and multiple step electrospray ionization mass spectrometry (ESIMS) and NMR spectroscopy to profile and elucidate lipopolysaccharide (LPS) structural types expressed by NTHi strain 162, a strain obtained from an epidemiological study in Finland. ESIMS on O-deacylated LPS (LPS-OH) and core oligosaccharide (OS) samples of LPS provided information on the composition and relative abundance of glycoforms differing in the number of hexoses linked to the conserved inner-core element, L-alpha-D-Hepp-(1-->2)-[PEtn-->6]-L-alpha-D-Hepp-(1-->3)-L-alpha-D-Hepp-(1-->5)-[PPEtn-->4]-alpha-Kdop-(2-->6)-Lipid A of H. influenzae LPS. The strain examined was found to elaborate Hex2 to Hex5 LPS glycoform populations having structures identical to those observed for H. influenzae strain Rd [Risberg, A.; Masoud, H.; Martin, A.; Richards, J.C.; Moxon, E.R.; Schweda, E.K.H. Eur. J. Biochem. 1999, 261, 171-180], the strain for which the complete genome has been sequenced. In addition, sialyllactose-containing glycoforms previously identified in strain Rd as well as several NTHi strains, were identified as minor components. Multiple step tandem ESIMS (MS(n)) on dephosphorylated and permethylated OS provided information on the arrangement of glycoses within the major population of glycoforms and on the existence of additional isomeric glycoforms. Minor Hex1 and Hex6 glycoforms were detected and characterized where the Hex6 glycoform was comprised of a dihexosamine-containing pentasaccharide chain attached at the proximal heptose residue of the inner-core unit. LPS structural motifs present in the NTHi strain 162 are expressed by a genetically diverse set of disease causing isolates, providing the basis for a vaccine strategy against NTHi otitis media. PMID:14670731

  12. A multidimensional version of the ziggurat algorithm

    NASA Astrophysics Data System (ADS)

    Shmerling, Efraim

    2016-06-01

    It is shown that the widely applied ziggurat algorithm for generating random values from monotone decreasing distributions and symmetric unimodal distributions can be extended to unimodal multidimensional distributions. A multidimensional version of the ziggurat that was implemented in very fast random number generators is presented.

  13. On Compensation in Multidimensional Response Modeling

    ERIC Educational Resources Information Center

    van der Linden, Wim J.

    2012-01-01

    The issue of compensation in multidimensional response modeling is addressed. We show that multidimensional response models are compensatory in their ability parameters if and only if they are monotone. In addition, a minimal set of assumptions is presented under which the MLEs of the ability parameters are also compensatory. In a recent series of…

  14. Multidimensional Scaling of Classroom Interaction Data.

    ERIC Educational Resources Information Center

    Rumery, Robert E.; Hartnett, Barbara M.

    The use of Kruskal's nonmetric multidimensional scaling model for analysis of classroom interaction data is discussed. Four distance models are proposed which lead to multidimensional representation of single sequences, sets of sequences, and behavior categories using symmetric and conditional proximity options of the model. Results of application…

  15. 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…

  16. Finding the target after screening the phenotype.

    PubMed

    Hart, Charles P

    2005-04-01

    Although most screening for new drug leads is being directed at known or emerging molecular targets, there has been a renaissance in screening based on changes in cell or organismal phenotypes. Phenotype-based screening is accompanied by the challenge of identifying the molecular target or targets bound by the drug leads and responsible for their pharmacological activity. A variety of technologies and approaches are being explored for target identification after phenotypic screening. Direct approaches employing affinity chromatography, expression cloning and protein microarrays analyze the compound bound to its target. Indirect approaches are based on comparison of the genome-wide activity profile of the compound with databases of the activity profiles of other compounds with known targets or activity profiles following specific genetic changes. This review will use case studies of target identification efforts and highlight the advantages and disadvantages of the various approaches to target identification after phenotypic screening. PMID:15809197

  17. 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

  18. Development of a Multidimensional Thinking Styles Scale Based on Theory of Mental Self-Government for Sixth Grade Students

    ERIC Educational Resources Information Center

    Chaiyapornpattana, Niorn; Wongwanich, Suwimon

    2013-01-01

    This study designed 1) to develop a multidimensional thinking styles scale based on theory of mental self-government for sixth grade student 2) to investigate quality of the developed scale 3) to study profile of styles of sixth grade student and a relation of profile of styles of student in each dimension and background of gender and grade with…

  19. New integrative computational approaches unveil the Saccharomyces cerevisiae pheno-metabolomic fermentative profile and allow strain selection for winemaking.

    PubMed

    Franco-Duarte, Ricardo; Umek, Lan; Mendes, Inês; Castro, Cristiana C; Fonseca, Nuno; Martins, Rosa; Silva-Ferreira, António C; Sampaio, Paula; Pais, Célia; Schuller, Dorit

    2016-11-15

    During must fermentation by Saccharomyces cerevisiae strains thousands of volatile aroma compounds are formed. The objective of the present work was to adapt computational approaches to analyze pheno-metabolomic diversity of a S. cerevisiae strain collection with different origins. Phenotypic and genetic characterization together with individual must fermentations were performed, and metabolites relevant to aromatic profiles were determined. Experimental results were projected onto a common coordinates system, revealing 17 statistical-relevant multi-dimensional modules, combining sets of most-correlated features of noteworthy biological importance. The present method allowed, as a breakthrough, to combine genetic, phenotypic and metabolomic data, which has not been possible so far due to difficulties in comparing different types of data. Therefore, the proposed computational approach revealed as successful to shed light into the holistic characterization of S. cerevisiae pheno-metabolome in must fermentative conditions. This will allow the identification of combined relevant features with application in selection of good winemaking strains. PMID:27283661

  20. The Multidimensional Assessment of Interoceptive Awareness (MAIA)

    PubMed Central

    Mehling, Wolf E.; Price, Cynthia; Daubenmier, Jennifer J.; Acree, Mike; Bartmess, Elizabeth; Stewart, Anita

    2012-01-01

    This paper describes the development of a multidimensional self-report measure of interoceptive body awareness. The systematic mixed-methods process involved reviewing the current literature, specifying a multidimensional conceptual framework, evaluating prior instruments, developing items, and analyzing focus group responses to scale items by instructors and patients of body awareness-enhancing therapies. Following refinement by cognitive testing, items were field-tested in students and instructors of mind-body approaches. Final item selection was achieved by submitting the field test data to an iterative process using multiple validation methods, including exploratory cluster and confirmatory factor analyses, comparison between known groups, and correlations with established measures of related constructs. The resulting 32-item multidimensional instrument assesses eight concepts. The psychometric properties of these final scales suggest that the Multidimensional Assessment of Interoceptive Awareness (MAIA) may serve as a starting point for research and further collaborative refinement. PMID:23133619

  1. The Multidimensional Audioconferencing Classification System (MACS).

    ERIC Educational Resources Information Center

    Cookson, Peter S.; Chang, Yu-bi

    1995-01-01

    Describes the development of the Multidimensional Audioconferencing Classification System (MACS), an instrument for the tabulation, analysis, and interpretation of audioconferencing instructional interactions. MACS draws on three theoretical and empirical streams: (1) systematic small group interaction analysis; (2) systematic classroom…

  2. Tourette Syndrome: A Multidimensional Approach to Treatment.

    ERIC Educational Resources Information Center

    Anderson, Donna J.

    1987-01-01

    Describes Tourette syndrome, a chronic, neurological disorder characterized by involuntary muscular movements, uncontrollable sounds, and inappropriate words. Notes that Tourette syndrome is frequently misunderstood and mistreated, presents symptoms, and suggests a multidimensional approach to treatment. (Author/NB)

  3. Mormons and Social Distance: A Multidimensional Analysis

    ERIC Educational Resources Information Center

    Bunker, Gary L.; And Others

    1977-01-01

    Issues such as Mormon variation from general cultural ethnic attitudes and generalization from ecclesiastical norms to secular tolerance/intolerance are examined in light of multi-dimensional research. (Author/AM)

  4. VH-1: Multidimensional ideal compressible hydrodynamics code

    NASA Astrophysics Data System (ADS)

    Hawley, John; Blondin, John; Lindahl, Greg; Lufkin, Eric

    2012-04-01

    VH-1 is a multidimensional ideal compressible hydrodynamics code written in FORTRAN for use on any computing platform, from desktop workstations to supercomputers. It uses a Lagrangian remap version of the Piecewise Parabolic Method developed by Paul Woodward and Phil Colella in their 1984 paper. VH-1 comes in a variety of versions, from a simple one-dimensional serial variant to a multi-dimensional version scalable to thousands of processors.

  5. Multidimensional Data Modeling for Business Process Analysis

    NASA Astrophysics Data System (ADS)

    Mansmann, Svetlana; Neumuth, Thomas; Scholl, Marc H.

    The emerging area of business process intelligence attempts to enhance the analytical capabilities of business process management systems by employing data warehousing and mining technologies. This paper presents an approach to re-engineering the business process modeling in conformity with the multidimensional data model. Since the business process and the multidimensional model are driven by rather different objectives and assumptions, there is no straightforward solution to converging these models.

  6. Operationalizing Frailty Using the Frailty Phenotype and Deficit Accumulation Approaches

    PubMed Central

    Theoua, Olga; Walstonb, Jeremy; Rockwooda, Kenneth

    2016-01-01

    In both demographic and clinical studies, frailty is understood as a multidimensional state of increased vulnerability compared with the status of others of the same age. Of the many theoretical definitions of frailty, two are commonly employed: the physical frailty/phenotypic approach and the deficit accumulation approach. The purpose of this chapter is to discuss how frailty is conceptualized and operationalized based on these two approaches. PMID:26301980

  7. Multidimensional Poverty and Child Survival in India

    PubMed Central

    Mohanty, Sanjay K.

    2011-01-01

    Background Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations) and included in the development agenda, its measurement and application are still limited. Objectives and Methodology Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses. Results The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed. Conclusion Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population. PMID:22046384

  8. Multi-dimensional laser radars

    NASA Astrophysics Data System (ADS)

    Molebny, Vasyl; Steinvall, Ove

    2014-06-01

    We introduce the term "multi-dimensional laser radar", where the dimensions mean not only the coordinates of the object in space, but its velocity and orientation, parameters of the media: scattering, refraction, temperature, humidity, wind velocity, etc. The parameters can change in time and can be combined. For example, rendezvous and docking missions, autonomous planetary landing, along with laser ranging, laser altimetry, laser Doppler velocimetry, are thought to have aboard also the 3D ladar imaging. Operating in combinations, they provide more accurate and safer navigation, docking or landing, hazard avoidance capabilities. Combination with Doppler-based measurements provides more accurate navigation for both space and cruise missile applications. Critical is the information identifying the snipers based on combination of polarization and fluctuation parameters with data from other sources. Combination of thermal imaging and vibrometry can unveil the functionality of detected targets. Hyperspectral probing with laser reveals even more parameters. Different algorithms and architectures of ladar-based target acquisition, reconstruction of 3D images from point cloud, information fusion and displaying is discussed with special attention to the technologies of flash illumination and single-photon focal-plane-array detection.

  9. Multidimensional model of cluster radioactivity

    NASA Astrophysics Data System (ADS)

    Denisov, V. Yu.

    2013-10-01

    The cluster decays 228Th→208Pb+20O, 232U→208Pb+24Ne, 236Pu→208Pb+28Mg, and 242Cm→208Pb+34Si are considered in the framework of the multidimensional cluster-preformation model. The macroscopic potential-energy surface related to the interaction between the cluster and the residue nucleus is evaluated in the framework of the nonlocal ℏ4 extended Thomas-Fermi approach with Skyrme and Coulomb forces. The shell correction to the macroscopic potential energy is also taken into account. The dynamical surface deformations of both the cluster and the residue nucleus are taken into consideration at the barrier penetration path. The heights of saddle points related to deformed nuclear shapes are lower than the barrier height between the spherical cluster and residue nuclei; therefore the dynamical deformations of nuclei increase the barrier penetrability and reduce the half-life of cluster decay. The shell-correction contribution into the potential energy between cluster and residue nucleus is important for both the potential landscape and the half-life evaluation. The experimental values of cluster-decay half-lives are well reproduced in the model.

  10. Multidimensional stochastic approximation Monte Carlo.

    PubMed

    Zablotskiy, Sergey V; Ivanov, Victor A; Paul, Wolfgang

    2016-06-01

    Stochastic Approximation Monte Carlo (SAMC) has been established as a mathematically founded powerful flat-histogram Monte Carlo method, used to determine the density of states, g(E), of a model system. We show here how it can be generalized for the determination of multidimensional probability distributions (or equivalently densities of states) of macroscopic or mesoscopic variables defined on the space of microstates of a statistical mechanical system. This establishes this method as a systematic way for coarse graining a model system, or, in other words, for performing a renormalization group step on a model. We discuss the formulation of the Kadanoff block spin transformation and the coarse-graining procedure for polymer models in this language. We also apply it to a standard case in the literature of two-dimensional densities of states, where two competing energetic effects are present g(E_{1},E_{2}). We show when and why care has to be exercised when obtaining the microcanonical density of states g(E_{1}+E_{2}) from g(E_{1},E_{2}). PMID:27415383

  11. Multidimensional stochastic approximation Monte Carlo

    NASA Astrophysics Data System (ADS)

    Zablotskiy, Sergey V.; Ivanov, Victor A.; Paul, Wolfgang

    2016-06-01

    Stochastic Approximation Monte Carlo (SAMC) has been established as a mathematically founded powerful flat-histogram Monte Carlo method, used to determine the density of states, g (E ) , of a model system. We show here how it can be generalized for the determination of multidimensional probability distributions (or equivalently densities of states) of macroscopic or mesoscopic variables defined on the space of microstates of a statistical mechanical system. This establishes this method as a systematic way for coarse graining a model system, or, in other words, for performing a renormalization group step on a model. We discuss the formulation of the Kadanoff block spin transformation and the coarse-graining procedure for polymer models in this language. We also apply it to a standard case in the literature of two-dimensional densities of states, where two competing energetic effects are present g (E1,E2) . We show when and why care has to be exercised when obtaining the microcanonical density of states g (E1+E2) from g (E1,E2) .

  12. A field-grown transgenic tomato line expressing higher levels of polyamines reveals legume cover crop mulch-specific perturbations in fruit phenotype at the levels of metabolite profiles, gene expression, and agronomic characteristics.

    PubMed

    Neelam, Anil; Cassol, Tatiana; Mehta, Roshni A; Abdul-Baki, Aref A; Sobolev, Anatoli P; Goyal, Ravinder K; Abbott, Judith; Segre, Anna L; Handa, Avtar K; Mattoo, Autar K

    2008-01-01

    Genetic modification of crop plants to introduce desirable traits such as nutritional enhancement, disease and pest resistance, and enhanced crop productivity is increasingly seen as a promising technology for sustainable agriculture and boosting food production in the world. Independently, cultural practices that utilize alternative agriculture strategies including organic cultivation subscribe to sustainable agriculture by limiting chemical usage and reduced tillage. How the two together affect fruit metabolism or plant growth in the field or whether they are compatible has not yet been tested. Fruit-specific yeast S-adenosylmethionine decarboxylase (ySAMdc) line 579HO, and a control line 556AZ were grown in leguminous hairy vetch (Vicia villosa Roth) (HV) mulch and conventional black polyethylene (BP) mulch, and their fruit analysed. Significant genotypexmulch-dependent interactions on fruit phenotype were exemplified by differential profiles of 20 fruit metabolites such as amino acids, sugars, and organic acids. Expression patterns of the ySAMdc transgene, and tomato SAMdc, E8, PEPC, and ICDHc genes were compared between the two lines as a function of growth on either BP or HV mulch. HV mulch significantly stimulated the accumulation of asparagine, glutamate, glutamine, choline, and citrate concomitant with a decrease in glucose in the 556AZ fruits during ripening as compared to BP. It enables a metabolic system in tomato somewhat akin to the one in higher polyamine-accumulating transgenic fruit that have higher phytonutrient content. Finally, synergism was found between HV mulch and transgenic tomato in up-regulating N:C indicator genes PEPC and ICDHc in the fruit. PMID:18469323

  13. A field-grown transgenic tomato line expressing higher levels of polyamines reveals legume cover crop mulch-specific perturbations in fruit phenotype at the levels of metabolite profiles, gene expression, and agronomic characteristics

    PubMed Central

    Neelam, Anil; Cassol, Tatiana; Mehta, Roshni A.; Abdul-Baki, Aref A.; Sobolev, Anatoli P.; Goyal, Ravinder K.; Abbott, Judith; Segre, Anna L.; Handa, Avtar K.; Mattoo, Autar K.

    2008-01-01

    Genetic modification of crop plants to introduce desirable traits such as nutritional enhancement, disease and pest resistance, and enhanced crop productivity is increasingly seen as a promising technology for sustainable agriculture and boosting food production in the world. Independently, cultural practices that utilize alternative agriculture strategies including organic cultivation subscribe to sustainable agriculture by limiting chemical usage and reduced tillage. How the two together affect fruit metabolism or plant growth in the field or whether they are compatible has not yet been tested. Fruit-specific yeast S-adenosylmethionine decarboxylase (ySAMdc) line 579HO, and a control line 556AZ were grown in leguminous hairy vetch (Vicia villosa Roth) (HV) mulch and conventional black polyethylene (BP) mulch, and their fruit analysed. Significant genotype×mulch-dependent interactions on fruit phenotype were exemplified by differential profiles of 20 fruit metabolites such as amino acids, sugars, and organic acids. Expression patterns of the ySAMdc transgene, and tomato SAMdc, E8, PEPC, and ICDHc genes were compared between the two lines as a function of growth on either BP or HV mulch. HV mulch significantly stimulated the accumulation of asparagine, glutamate, glutamine, choline, and citrate concomitant with a decrease in glucose in the 556AZ fruits during ripening as compared to BP. It enables a metabolic system in tomato somewhat akin to the one in higher polyamine-accumulating transgenic fruit that have higher phytonutrient content. Finally, synergism was found between HV mulch and transgenic tomato in up-regulating N:C indicator genes PEPC and ICDHc in the fruit. PMID:18469323

  14. Improved multidimensional semiclassical tunneling theory.

    PubMed

    Wagner, Albert F

    2013-12-12

    We show that the analytic multidimensional semiclassical tunneling formula of Miller et al. [Miller, W. H.; Hernandez, R.; Handy, N. C.; Jayatilaka, D.; Willets, A. Chem. Phys. Lett. 1990, 172, 62] is qualitatively incorrect for deep tunneling at energies well below the top of the barrier. The origin of this deficiency is that the formula uses an effective barrier weakly related to the true energetics but correctly adjusted to reproduce the harmonic description and anharmonic corrections of the reaction path at the saddle point as determined by second order vibrational perturbation theory. We present an analytic improved semiclassical formula that correctly includes energetic information and allows a qualitatively correct representation of deep tunneling. This is done by constructing a three segment composite Eckart potential that is continuous everywhere in both value and derivative. This composite potential has an analytic barrier penetration integral from which the semiclassical action can be derived and then used to define the semiclassical tunneling probability. The middle segment of the composite potential by itself is superior to the original formula of Miller et al. because it incorporates the asymmetry of the reaction barrier produced by the known reaction exoergicity. Comparison of the semiclassical and exact quantum tunneling probability for the pure Eckart potential suggests a simple threshold multiplicative factor to the improved formula to account for quantum effects very near threshold not represented by semiclassical theory. The deep tunneling limitations of the original formula are echoed in semiclassical high-energy descriptions of bound vibrational states perpendicular to the reaction path at the saddle point. However, typically ab initio energetic information is not available to correct it. The Supporting Information contains a Fortran code, test input, and test output that implements the improved semiclassical tunneling formula. PMID:24224758

  15. Image demodulation using multidimensional energy separation

    NASA Astrophysics Data System (ADS)

    Maragos, Petros; Bovik, Alan C.

    1995-09-01

    Locally narrow-band images can be modeled as two-dimensional (2D) spatial AM-FM signals with several applications in image texture analysis and computer vision. We formulate an image-demodulation problem and present a solution based on the multidimensional energy operator Phi (f)= \\double-vertical-bar \\inverted-Delta-triangle f \\double-vertical-bar 2-f \\inverted-Delta-triangle 2 f . This nonlinear operator is a multidimensional extension of the one-dimensional (1D) energy-tracking operator Psi (f)=( f\\prime)2 -ff\\prime\\prime , which has been found useful for demodulating 1D AM-FM and speech signals. We discuss some interesting properties of the multidimensional operator and develop a multidimensional energy-separation algorithm to estimate the amplitude envelope and instantaneous frequencies of 2D spatially varying AM-FM signals. Experiments are also presented on applying this 2D energy-demodulation algorithm to estimate the instantaneous amplitude contrast and spatial frequencies of image textures bandpass filtered by means of Gabor filters. The attractive features of the multidimensional energy operator and the 2D energy-separation algorithm are their simplicity, efficiency, and ability to track instantaneously varying

  16. A proposed multidimensional analysis function

    NASA Astrophysics Data System (ADS)

    Knight, Byron F.; Hamilton, Mark K.

    2003-08-01

    Previous work has suggested a potential value in the combination of physical property data types (e.g. magnetic and terrain slope) when searching for oil and mineral deposits. This work studies a notional multi-dimensional function to determine the likelihood of finding such deposits. Additionally, this hypothesis assumes some basic requirements must be meet in order to validate this function. The standard for determining the value of commercially gathered electro optical imagery is the same as with any optical system -- the ability to determine object in the field of view. Further, this function is defined as the ability to determine the presence of two parallel lines, vice only one. The National Imagery and Mapping Agency (NIMA) uses a function called Digital Terrain Elevation Data (DTED) to determine the elevation within a field of view. The DTED values for each pixel within a digital, commercial image can be considered similar to a gradient, whereby higher values are merely higher elevations. For the commercial electro optical system IKONOS (owned by Space Imaging, Inc.), the "resolution" is commonly referred to as 1 meter, which is the least discernable, parallel-line, separation distance. This hypothesis uses gravity and magnetic data to augment the DTED "gradient". As with the terrain values on the earth, gravity and magnetic values are continuously changing. Further, they can change for various reasons. Both are greatly affected by the changes in the subsurface materials, or the density of the soil and metallic content (e.g. iron). It is precisely these variations, through the combination of such differing forms of data, which can help determine the presence of oil and mineral deposits. The core of this work is a notional function development. Previous peer review has rightly pointed out that data fusion principles state that data must be commensurable before it can be fused. This work does not attempt to redefine data fusion concepts, but merely establish

  17. Fast adaptive estimation of multidimensional psychometric functions.

    PubMed

    DiMattina, Christopher

    2015-01-01

    Recently in vision science there has been great interest in understanding the perceptual representations of complex multidimensional stimuli. Therefore, it is becoming very important to develop methods for performing psychophysical experiments with multidimensional stimuli and efficiently estimating psychometric models that have multiple free parameters. In this methodological study, I analyze three efficient implementations of the popular Ψ method for adaptive data collection, two of which are novel approaches to psychophysical experiments. Although the standard implementation of the Ψ procedure is intractable in higher dimensions, I demonstrate that my implementations generalize well to complex psychometric models defined in multidimensional stimulus spaces and can be implemented very efficiently on standard laboratory computers. I show that my implementations may be of particular use for experiments studying how subjects combine multiple cues to estimate sensory quantities. I discuss strategies for speeding up experiments and suggest directions for future research in this rapidly growing area at the intersection of cognitive science, neuroscience, and machine learning. PMID:26200886

  18. Diagnose Test-Taker's Profile in Terms of Core Profile Patterns: Principal Component (PC) vs. Profile Analysis via MDS (PAMS) Approaches.

    ERIC Educational Resources Information Center

    Kim, Se-Kang; Davison, Mark L.

    A study was conducted to examine how principal components analysis (PCA) and Profile Analysis via Multidimensional Scaling (PAMS) can be used to diagnose individuals observed score profiles in terms of core profile patterns identified by each method. The standardization sample from the Wechsler Intelligence Scale for Children, Third Edition…

  19. Preface: Special Topic on Multidimensional Spectroscopy

    SciTech Connect

    Mukamel, Shaul; Bakker, Huib J.

    2015-06-07

    Multidimensional signals are generated by subjecting molecules to sequences of short optical pulses and recording correlation plots related to the various controlled delay periods. These techniques which span all the way from the THz to the x-ray regimes provide qualitatively new structural and dynamical molecular information not available from conventional one-dimensional techniques. This issue surveys the recent experimental and theoretical progresses in this rapidly developing 20 year old field which illustrates the novel insights provided by multidimensional techniques into electronic and nuclear motions. It should serve as a valuable source for experts in the field and help introduce newcomers to this exciting and challenging branch of nonlinear spectroscopy.

  20. Preface: Special Topic on Multidimensional Spectroscopy

    NASA Astrophysics Data System (ADS)

    Mukamel, Shaul; Bakker, Huib J.

    2015-06-01

    Multidimensional signals are generated by subjecting molecules to sequences of short optical pulses and recording correlation plots related to the various controlled delay periods. These techniques which span all the way from the THz to the x-ray regimes provide qualitatively new structural and dynamical molecular information not available from conventional one-dimensional techniques. This issue surveys the recent experimental and theoretical progresses in this rapidly developing 20 year old field which illustrates the novel insights provided by multidimensional techniques into electronic and nuclear motions. It should serve as a valuable source for experts in the field and help introduce newcomers to this exciting and challenging branch of nonlinear spectroscopy.

  1. Multidimensional stationary probability distribution for interacting active particles.

    PubMed

    Maggi, Claudio; Marconi, Umberto Marini Bettolo; Gnan, Nicoletta; Di Leonardo, Roberto

    2015-01-01

    We derive the stationary probability distribution for a non-equilibrium system composed by an arbitrary number of degrees of freedom that are subject to Gaussian colored noise and a conservative potential. This is based on a multidimensional version of the Unified Colored Noise Approximation. By comparing theory with numerical simulations we demonstrate that the theoretical probability density quantitatively describes the accumulation of active particles around repulsive obstacles. In particular, for two particles with repulsive interactions, the probability of close contact decreases when one of the two particle is pinned. Moreover, in the case of isotropic confining potentials, the radial density profile shows a non trivial scaling with radius. Finally we show that the theory well approximates the "pressure" generated by the active particles allowing to derive an equation of state for a system of non-interacting colored noise-driven particles. PMID:26021260

  2. 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

  3. Serum Biochemical Phenotypes in the Domestic Dog.

    PubMed

    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

  4. Sex Differences in the Multidimensional Self-Concepts of African American Adolescents: The Mediating Role of Gender Identity

    ERIC Educational Resources Information Center

    Thomson, Nicole Renick; Zand, Debra H.

    2007-01-01

    The present study investigates whether the gender identities of African American adolescents mediate sex differences found in their multidimensional self-concepts. The sample included 174 African American adolescents who completed the 21-item Children's Personal Attributes Questionnaire and the Self-Perception Profile for Adolescents. Results…

  5. Examination of the Structure and Grade-Related Differentiation of Multidimensional Self-Concept Instruments for Children Using ESEM

    ERIC Educational Resources Information Center

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

    2016-01-01

    This study is a substantive-methodological synergy in which exploratory structural equation modeling is applied to investigate the factor structure of multidimensional self-concept instruments. On the basis of a sample of German students (N = 1958) who completed the Self-Description Questionnaire I and the Self-Perception Profile for Children, the…

  6. 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…

  7. Longitudinal Network Analysis Using Multidimensional Scaling.

    ERIC Educational Resources Information Center

    Barnett, George A.; Palmer, Mark T.

    The Galileo System, a variant of metric multidimensional scaling, is used in this paper to analyze over-time changes in social networks. The paper first discusses the theoretical necessity for the use of this procedure and the methodological problems associated with its use. It then examines the air traffic network among 31 major cities in the…

  8. Taylor approximations of multidimensional linear differential systems

    NASA Astrophysics Data System (ADS)

    Lomadze, Vakhtang

    2016-06-01

    The Taylor approximations of a multidimensional linear differential system are of importance as they contain a complete information about it. It is shown that in order to construct them it is sufficient to truncate the exponential trajectories only. A computation of the Taylor approximations is provided using purely algebraic means, without requiring explicit knowledge of the trajectories.

  9. Multidimensional Human Dynamics in Mobile Phone Communications

    PubMed Central

    Quadri, Christian; Zignani, Matteo; Capra, Lorenzo; Gaito, Sabrina; Rossi, Gian Paolo

    2014-01-01

    In today's technology-assisted society, social interactions may be expressed through a variety of techno-communication channels, including online social networks, email and mobile phones (calls, text messages). Consequently, a clear grasp of human behavior through the diverse communication media is considered a key factor in understanding the formation of the today's information society. So far, all previous research on user communication behavior has focused on a sole communication activity. In this paper we move forward another step on this research path by performing a multidimensional study of human sociality as an expression of the use of mobile phones. The paper focuses on user temporal communication behavior in the interplay between the two complementary communication media, text messages and phone calls, that represent the bi-dimensional scenario of analysis. Our study provides a theoretical framework for analyzing multidimensional bursts as the most general burst category, that includes one-dimensional bursts as the simplest case, and offers empirical evidence of their nature by following the combined phone call/text message communication patterns of approximately one million people over three-month period. This quantitative approach enables the design of a generative model rooted in the three most significant features of the multidimensional burst - the number of dimensions, prevalence and interleaving degree - able to reproduce the main media usage attitude. The other findings of the paper include a novel multidimensional burst detection algorithm and an insight analysis of the human media selection process. PMID:25068479

  10. Multidimensional Treatment of Fear of Death.

    ERIC Educational Resources Information Center

    Hoelter, Jon W.

    1979-01-01

    Presents a multidimensional conception of fear of death and provides subscales for measuring suggested dimensions (fear of the dying process, of the dead, of being destroyed, for significant others, of the unknown, of conscious death, for body after death, and of premature death). Evidence for construct validity is provided. (Author/BEF)