analyses identified specific: Topics by Science.gov

Sample records for analyses identified specific

Personalized genomic analyses for cancer mutation discovery and interpretation

PubMed Central

Jones, Siân; Anagnostou, Valsamo; Lytle, Karli; Parpart-Li, Sonya; Nesselbush, Monica; Riley, David R.; Shukla, Manish; Chesnick, Bryan; Kadan, Maura; Papp, Eniko; Galens, Kevin G.; Murphy, Derek; Zhang, Theresa; Kann, Lisa; Sausen, Mark; Angiuoli, Samuel V.; Diaz, Luis A.; Velculescu, Victor E.

2015-01-01

Massively parallel sequencing approaches are beginning to be used clinically to characterize individual patient tumors and to select therapies based on the identified mutations. A major question in these analyses is the extent to which these methods identify clinically actionable alterations and whether the examination of the tumor tissue alone is sufficient or whether matched normal DNA should also be analyzed to accurately identify tumor-specific (somatic) alterations. To address these issues, we comprehensively evaluated 815 tumor-normal paired samples from patients of 15 tumor types. We identified genomic alterations using next-generation sequencing of whole exomes or 111 targeted genes that were validated with sensitivities >95% and >99%, respectively, and specificities >99.99%. These analyses revealed an average of 140 and 4.3 somatic mutations per exome and targeted analysis, respectively. More than 75% of cases had somatic alterations in genes associated with known therapies or current clinical trials. Analyses of matched normal DNA identified germline alterations in cancer-predisposing genes in 3% of patients with apparently sporadic cancers. In contrast, a tumor-only sequencing approach could not definitively identify germline changes in cancer-predisposing genes and led to additional false-positive findings comprising 31% and 65% of alterations identified in targeted and exome analyses, respectively, including in potentially actionable genes. These data suggest that matched tumor-normal sequencing analyses are essential for precise identification and interpretation of somatic and germline alterations and have important implications for the diagnostic and therapeutic management of cancer patients. PMID:25877891
Perceived Relational Support in Adolescence: Dimensions, Configurations, and Adolescent Adjustment.

ERIC Educational Resources Information Center

Scholte, Ron H. J.; van Lieshout, Cornelis F. M.; van Aken, Marcel A. G.

2001-01-01

Examined characteristics of perceived relational support from four key providers for 12- to 18-year-olds. Variable-centered factor analyses yielded five support dimensions, three specific to providers and two specific to provisions. Person-centered factor analyses identified five types of adolescents with different configurations of perceived…
Microarray Detection Call Methodology as a Means to Identify and Compare Transcripts Expressed within Syncytial Cells from Soybean (Glycine max) Roots Undergoing Resistant and Susceptible Reactions to the Soybean Cyst Nematode (Heterodera glycines)

PubMed Central

Klink, Vincent P.; Overall, Christopher C.; Alkharouf, Nadim W.; MacDonald, Margaret H.; Matthews, Benjamin F.

2010-01-01

Background. A comparative microarray investigation was done using detection call methodology (DCM) and differential expression analyses. The goal was to identify genes found in specific cell populations that were eliminated by differential expression analysis due to the nature of differential expression methods. Laser capture microdissection (LCM) was used to isolate nearly homogeneous populations of plant root cells. Results. The analyses identified the presence of 13,291 transcripts between the 4 different sample types. The transcripts filtered down into a total of 6,267 that were detected as being present in one or more sample types. A comparative analysis of DCM and differential expression methods showed a group of genes that were not differentially expressed, but were expressed at detectable amounts within specific cell types. Conclusion. The DCM has identified patterns of gene expression not shown by differential expression analyses. DCM has identified genes that are possibly cell-type specific and/or involved in important aspects of plant nematode interactions during the resistance response, revealing the uniqueness of a particular cell population at a particular point during its differentiation process. PMID:20508855
Identifying gene networks underlying the neurobiology of ethanol and alcoholism.

PubMed

Wolen, Aaron R; Miles, Michael F

2012-01-01

For complex disorders such as alcoholism, identifying the genes linked to these diseases and their specific roles is difficult. Traditional genetic approaches, such as genetic association studies (including genome-wide association studies) and analyses of quantitative trait loci (QTLs) in both humans and laboratory animals already have helped identify some candidate genes. However, because of technical obstacles, such as the small impact of any individual gene, these approaches only have limited effectiveness in identifying specific genes that contribute to complex diseases. The emerging field of systems biology, which allows for analyses of entire gene networks, may help researchers better elucidate the genetic basis of alcoholism, both in humans and in animal models. Such networks can be identified using approaches such as high-throughput molecular profiling (e.g., through microarray-based gene expression analyses) or strategies referred to as genetical genomics, such as the mapping of expression QTLs (eQTLs). Characterization of gene networks can shed light on the biological pathways underlying complex traits and provide the functional context for identifying those genes that contribute to disease development.
Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue transcriptomics and venom proteomics.

PubMed

Haney, Robert A; Ayoub, Nadia A; Clarke, Thomas H; Hayashi, Cheryl Y; Garb, Jessica E

2014-06-11

Animal venoms attract enormous interest given their potential for pharmacological discovery and understanding the evolution of natural chemistries. Next-generation transcriptomics and proteomics provide unparalleled, but underexploited, capabilities for venom characterization. We combined multi-tissue RNA-Seq with mass spectrometry and bioinformatic analyses to determine venom gland specific transcripts and venom proteins from the Western black widow spider (Latrodectus hesperus) and investigated their evolution. We estimated expression of 97,217 L. hesperus transcripts in venom glands relative to silk and cephalothorax tissues. We identified 695 venom gland specific transcripts (VSTs), many of which BLAST and GO term analyses indicate may function as toxins or their delivery agents. ~38% of VSTs had BLAST hits, including latrotoxins, inhibitor cystine knot toxins, CRISPs, hyaluronidases, chitinase, and proteases, and 59% of VSTs had predicted protein domains. Latrotoxins are venom toxins that cause massive neurotransmitter release from vertebrate or invertebrate neurons. We discovered ≥ 20 divergent latrotoxin paralogs expressed in L. hesperus venom glands, significantly increasing this biomedically important family. Mass spectrometry of L. hesperus venom identified 49 proteins from VSTs, 24 of which BLAST to toxins. Phylogenetic analyses showed venom gland specific gene family expansions and shifts in tissue expression. Quantitative expression analyses comparing multiple tissues are necessary to identify venom gland specific transcripts. We present a black widow venom specific exome that uncovers a trove of diverse toxins and associated proteins, suggesting a dynamic evolutionary history. This justifies a reevaluation of the functional activities of black widow venom in light of its emerging complexity.
Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades

PubMed Central

2009-01-01

Background Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. Results To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer) and functional elements in tardigrade mRNAs are analysed. We find that 39.3% of the total sequences clustered in 58 clusters of more than 20 proteins. Among these are ten tardigrade specific as well as a number of stress-specific protein clusters. Tardigrade-specific functional adaptations include strong protein, DNA- and redox protection, maintenance and protein recycling. Specific regulatory elements regulate tardigrade mRNA stability such as lox P DICE elements whereas 14 other RNA elements of higher eukaryotes are not found. Further features of tardigrade specific adaption are rapidly identified by sequence and/or pattern search on the web-tool tardigrade analyzer http://waterbear.bioapps.biozentrum.uni-wuerzburg.de. The work-bench offers nucleotide pattern analysis for promotor and regulatory element detection (tardigrade specific; nrdb) as well as rapid COG search for function assignments including species-specific repositories of all analysed data. Conclusion Different protein clusters and regulatory elements implicated in tardigrade stress adaptations are analysed including unpublished tardigrade sequences. PMID:19821996
Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades.

PubMed

Förster, Frank; Liang, Chunguang; Shkumatov, Alexander; Beisser, Daniela; Engelmann, Julia C; Schnölzer, Martina; Frohme, Marcus; Müller, Tobias; Schill, Ralph O; Dandekar, Thomas

2009-10-12

Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer) and functional elements in tardigrade mRNAs are analysed. We find that 39.3% of the total sequences clustered in 58 clusters of more than 20 proteins. Among these are ten tardigrade specific as well as a number of stress-specific protein clusters. Tardigrade-specific functional adaptations include strong protein, DNA- and redox protection, maintenance and protein recycling. Specific regulatory elements regulate tardigrade mRNA stability such as lox P DICE elements whereas 14 other RNA elements of higher eukaryotes are not found. Further features of tardigrade specific adaption are rapidly identified by sequence and/or pattern search on the web-tool tardigrade analyzer http://waterbear.bioapps.biozentrum.uni-wuerzburg.de. The work-bench offers nucleotide pattern analysis for promotor and regulatory element detection (tardigrade specific; nrdb) as well as rapid COG search for function assignments including species-specific repositories of all analysed data. Different protein clusters and regulatory elements implicated in tardigrade stress adaptations are analysed including unpublished tardigrade sequences.
Rapid Identification of Cell-Specific, Internalizing RNA Aptamers with Bioinformatics Analyses of a Cell-Based Aptamer Selection

PubMed Central

Thiel, William H.; Bair, Thomas; Peek, Andrew S.; Liu, Xiuying; Dassie, Justin; Stockdale, Katie R.; Behlke, Mark A.; Miller, Francis J.; Giangrande, Paloma H.

2012-01-01

Background The broad applicability of RNA aptamers as cell-specific delivery tools for therapeutic reagents depends on the ability to identify aptamer sequences that selectively access the cytoplasm of distinct cell types. Towards this end, we have developed a novel approach that combines a cell-based selection method (cell-internalization SELEX) with high-throughput sequencing (HTS) and bioinformatics analyses to rapidly identify cell-specific, internalization-competent RNA aptamers. Methodology/Principal Findings We demonstrate the utility of this approach by enriching for RNA aptamers capable of selective internalization into vascular smooth muscle cells (VSMCs). Several rounds of positive (VSMCs) and negative (endothelial cells; ECs) selection were performed to enrich for aptamer sequences that preferentially internalize into VSMCs. To identify candidate RNA aptamer sequences, HTS data from each round of selection were analyzed using bioinformatics methods: (1) metrics of selection enrichment; and (2) pairwise comparisons of sequence and structural similarity, termed edit and tree distance, respectively. Correlation analyses of experimentally validated aptamers or rounds revealed that the best cell-specific, internalizing aptamers are enriched as a result of the negative selection step performed against ECs. Conclusions and Significance We describe a novel approach that combines cell-internalization SELEX with HTS and bioinformatics analysis to identify cell-specific, cell-internalizing RNA aptamers. Our data highlight the importance of performing a pre-clear step against a non-target cell in order to select for cell-specific aptamers. We expect the extended use of this approach to enable the identification of aptamers to a multitude of different cell types, thereby facilitating the broad development of targeted cell therapies. PMID:22962591
Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE PAGES

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric; ...

2015-03-30

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less
Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

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

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less
Applying isozyme analyses in tree-breeding programs

Treesearch

W. T. Adams

1981-01-01

Four examples illustrate the potential for practical use of isozyme analyses in applied breeding programs. These include identifying parent trees and clones, seed sources, and parentage of controlled crosses, and evaluating the effectiveness of different procedures involving open-pollination to produce seed of specific crosses. The improved ability to assess the true...
DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruan, D; Shao, W; Low, D

Purpose: To evaluate and test the hypothesis that plan quality may be systematically affected by treatment delivery techniques and target-tocritical structure geometric relationship in radiotherapy for brain tumor. Methods: Thirty-four consecutive brain tumor patients treated between 2011–2014 were analyzed. Among this cohort, 10 were planned with 3DCRT, 11 with RadipArc, and 13 with helical IMRT on TomoTherapy. The selected dosimetric endpoints (i.e., PTV V100, maximum brainstem/chiasm/ optic nerve doses) were considered as a vector in a highdimensional space. A Pareto analysis was performed to identify the subset of Pareto-efficient plans.The geometric relationships, specifically the overlapping volume and centroid-of-mass distance betweenmore » each critical structure to the PTV were extracted as potential geometric features. The classification-tree analyses were repeated using these geometric features with and without the treatment modality as an additional categorical predictor. In both scenarios, the dominant features to prognosticate the Pareto membership were identified and the tree structures to provide optimal inference were recorded. The classification performance was further analyzed to determine the role of treatment modality in affecting plan quality. Results: Seven Pareto-efficient plans were identified based on dosimetric endpoints (3 from 3DCRT, 3 from RapicArc, 1 from Tomo), which implies that the evaluated treatment modality may have a minor influence on plan quality. Classification trees with/without the treatment modality as a predictor both achieved accuracy of 88.2%: with 100% sensitivity and 87.1% specificity for the former, and 66.7% sensitivity and 96.0% specificity for the latter. The coincidence of accuracy from both analyses further indicates no-to-weak dependence of plan quality on treatment modality. Both analyses have identified the brainstem to PTV distance as the primary predictive feature for Pareto-efficiency. Conclusion: Pareto evaluation and classification-tree analyses have indicated that plan quality depends strongly on geometry for brain tumor, specifically PTV-tobrain-stem-distance but minimally on treatment modality.« less
Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414
Worldwide wind/diesel hybrid power system study: Potential applications and technical issues

NASA Astrophysics Data System (ADS)

King, W. R.; Johnson, B. L., III

1991-04-01

The world market potential for wind/diesel hybrid technology is a function of the need for electric power, the availability of sufficient wind resource to support wind/diesel power, and the existence of buyers with the financial means to invest in the technology. This study includes data related to each of these three factors. This study does not address market penetration, which would require analysis of application specific wind/diesel economics. Buyer purchase criteria, which are vital to assessing market penetration, are discussed only generally. Countries were screened for a country-specific market analysis based on indicators of need and wind resource. Both developed countries and less developed countries (LDCs) were screened for wind/diesel market potential. Based on the results of the screening, ten countries showing high market potential were selected for more extensive market analyses. These analyses provide country-specific market data to guide wind/diesel technology developers in making design decisions that will lead to a competitive product. Section 4 presents the country-specific data developed for these analyses, including more extensive wind resource characterization, application-specific market opportunities, business conditions, and energy market characterizations. An attempt was made to identify the potential buyers with ability to pay for wind/diesel technology required to meet the application-specific market opportunities identified for each country. Additionally, the country-specific data are extended to corollary opportunities in countries not covered by the study. Section 2 gives recommendations for wind/diesel research based on the findings of the study.
DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobromir Panayotov; Andrew Grief; Brad J. Merrill

'Fusion for Energy' (F4E) develops designs and implements the European Test Blanket Systems (TBS) in ITER - Helium-Cooled Lithium-Lead (HCLL) and Helium-Cooled Pebble-Bed (HCPB). Safety demonstration is an essential element for the integration of TBS in ITER and accident analyses are one of its critical segments. A systematic approach to the accident analyses had been acquired under the F4E contract on TBS safety analyses. F4E technical requirements and AMEC and INL efforts resulted in the development of a comprehensive methodology for fusion breeding blanket accident analyses. It addresses the specificity of the breeding blankets design, materials and phenomena and atmore » the same time is consistent with the one already applied to ITER accident analyses. Methodology consists of several phases. At first the reference scenarios are selected on the base of FMEA studies. In the second place elaboration of the accident analyses specifications we use phenomena identification and ranking tables to identify the requirements to be met by the code(s) and TBS models. Thus the limitations of the codes are identified and possible solutions to be built into the models are proposed. These include among others the loose coupling of different codes or code versions in order to simulate multi-fluid flows and phenomena. The code selection and issue of the accident analyses specifications conclude this second step. Furthermore the breeding blanket and ancillary systems models are built on. In this work challenges met and solutions used in the development of both MELCOR and RELAP5 codes models of HCLL and HCPB TBSs will be shared. To continue the developed models are qualified by comparison with finite elements analyses, by code to code comparison and sensitivity studies. Finally, the qualified models are used for the execution of the accident analyses of specific scenario. When possible the methodology phases will be illustrated in the paper by limited number of tables and figures. Description of each phase and its results in detail as well the methodology applications to EU HCLL and HCPB TBSs will be published in separate papers. The developed methodology is applicable to accident analyses of other TBSs to be tested in ITER and as well to DEMO breeding blankets.« less
Analysis of Technical Specifications of the Egyptian and French Electronic Storybooks (e-Storybook)

ERIC Educational Resources Information Center

Atta, Mohammed Mahmoud; Abd El Wahab, Shaimaa Mahmoud

2015-01-01

This research aims at analysing technical specifications in a sample of Egyptian and French electronic storybooks (e-storybooks), to identify similarities and differences in technical specifications of children's e-storybooks and create a verified analysis list to be used for evaluation of e-storybooks. For this purpose, 32 e-storybooks in CD…
Developmental trajectories of paediatric headache - sex-specific analyses and predictors.

PubMed

Isensee, Corinna; Fernandez Castelao, Carolin; Kröner-Herwig, Birgit

2016-01-01

Headache is the most common pain disorder in children and adolescents and is associated with diverse dysfunctions and psychological symptoms. Several studies evidenced sex-specific differences in headache frequency. Until now no study exists that examined sex-specific patterns of change in paediatric headache across time and included pain-related somatic and (socio-)psychological predictors. Latent Class Growth Analysis (LCGA) was used in order to identify different trajectory classes of headache across four annual time points in a population-based sample (n = 3 227; mean age 11.34 years; 51.2 % girls). In multinomial logistic regression analyses the influence of several predictors on the class membership was examined. For girls, a four-class model was identified as the best fitting model. While the majority of girls reported no (30.5 %) or moderate headache frequencies (32.5 %) across time, one class with a high level of headache days (20.8 %) and a class with an increasing headache frequency across time (16.2 %) were identified. For boys a two class model with a 'no headache class' (48.6 %) and 'moderate headache class' (51.4 %) showed the best model fit. Regarding logistic regression analyses, migraine and parental headache proved to be stable predictors across sexes. Depression/anxiety was a significant predictor for all pain classes in girls. Life events, dysfunctional stress coping and school burden were also able to differentiate at least between some classes in both sexes. The identified trajectories reflect sex-specific differences in paediatric headache, as seen in the number and type of classes extracted. The documented risk factors can deliver ideas for preventive actions and considerations for treatment programmes.
Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research.

PubMed

Girman, Cynthia J; Faries, Douglas; Ryan, Patrick; Rotelli, Matt; Belger, Mark; Binkowitz, Bruce; O'Neill, Robert

2014-05-01

The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results.
Identifying and tracing potential energy surfaces of electronic excitations with specific character via their transition origins: application to oxirane.

PubMed

Li, Jian-Hao; Zuehlsdorff, T J; Payne, M C; Hine, N D M

2015-05-14

We show that the transition origins of electronic excitations identified by quantified natural transition orbital (QNTO) analysis can be employed to connect potential energy surfaces (PESs) according to their character across a wide range of molecular geometries. This is achieved by locating the switching of transition origins of adiabatic potential surfaces as the geometry changes. The transition vectors for analysing transition origins are provided by linear response time-dependent density functional theory (TDDFT) calculations under the Tamm-Dancoff approximation. We study the photochemical CO ring opening of oxirane as an example and show that the results corroborate the traditional Gomer-Noyes mechanism derived experimentally. The knowledge of specific states for the reaction also agrees well with that given by previous theoretical work using TDDFT surface-hopping dynamics that was validated by high-quality quantum Monte Carlo calculations. We also show that QNTO can be useful for considerably larger and more complex systems: by projecting the excitations to those of a reference oxirane molecule, the approach is able to identify and analyse specific excitations of a trans-2,3-diphenyloxirane molecule.
Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis

PubMed Central

Capurro, Alberto; Bodea, Liviu-Gabriel; Schaefer, Patrick; Luthi-Carter, Ruth; Perreau, Victoria M.

2015-01-01

The characterization of molecular changes in diseased tissues gives insight into pathophysiological mechanisms and is important for therapeutic development. Genome-wide gene expression analysis has proven valuable for identifying biological processes in neurodegenerative diseases using post mortem human brain tissue and numerous datasets are publically available. However, many studies utilize heterogeneous tissue samples consisting of multiple cell types, all of which contribute to global gene expression values, confounding biological interpretation of the data. In particular, changes in numbers of neuronal and glial cells occurring in neurodegeneration confound transcriptomic analyses, particularly in human brain tissues where sample availability and controls are limited. To identify cell specific gene expression changes in neurodegenerative disease, we have applied our recently published computational deconvolution method, population specific expression analysis (PSEA). PSEA estimates cell-type-specific expression values using reference expression measures, which in the case of brain tissue comprises mRNAs with cell-type-specific expression in neurons, astrocytes, oligodendrocytes and microglia. As an exercise in PSEA implementation and hypothesis development regarding neurodegenerative diseases, we applied PSEA to Parkinson's and Huntington's disease (PD, HD) datasets. Genes identified as differentially expressed in substantia nigra pars compacta neurons by PSEA were validated using external laser capture microdissection data. Network analysis and Annotation Clustering (DAVID) identified molecular processes implicated by differential gene expression in specific cell types. The results of these analyses provided new insights into the implementation of PSEA in brain tissues and additional refinement of molecular signatures in human HD and PD. PMID:25620908

MEASURING METAL SULFIDE COMPLEXES IN OXIC RIVER WATERS WITH SQUARE WAVE VOLTAMMETRY. (R825395)

EPA Science Inventory

A sulfide identification protocol was developed to quantify specific metal
sulfides that could exist in river water. Using a series of acid additions,
nitrogen purges, and voltammetric analyses, metal sulfides were identified and
semiquantified in three specific gr...
Using Additional Analyses to Clarify the Functions of Problem Behavior: An Analysis of Two Cases

ERIC Educational Resources Information Center

Payne, Steven W.; Dozier, Claudia L.; Neidert, Pamela L.; Jowett, Erica S.; Newquist, Matthew H.

2014-01-01

Functional analyses (FA) have proven useful for identifying contingencies that influence problem behavior. Research has shown that some problem behavior may only occur in specific contexts or be influenced by multiple or idiosyncratic variables. When these contexts or sources of influence are not assessed in an FA, further assessment may be…
Metabolite fingerprinting of Camptotheca acuminata and the HPLC-ESI-MS/MS analysis of camptothecin and related alkaloids.

PubMed

Montoro, Paola; Maldini, Mariateresa; Piacente, Sonia; Macchia, Mario; Pizza, Cosimo

2010-01-20

The major phytochemical constituents, namely, alkaloids, flavonoids and ellagic acid derivatives, of leaves of Camptotheca acuminata were identified using high performance liquid chromatography (HPLC) coupled with electrospray mass spectrometry (ESI-MS) in extracts of plants cultivated in Italy and collected at different growth stages. Alkaloids related to camptothecin were identified and quantified by HPLC coupled with ESI-tandem mass spectrometry (MS/MS) employing, respectively, an ion trap and a triple quadrupole mass analyser. The fragmentation patterns of alkaloids related to camptothecin were analysed and a specific Multiple Reaction Monitoring HPLC-MS/MS method was developed for the quantitative determination of these constituents. The described method provides high sensitivity and specificity for the characterisation and quantitative determination of the alkaloids in C. acuminata.
Patient-Reported Satisfaction Following Post-bariatric Surgery: A Systematic Review.

PubMed

Barone, M; Cogliandro, A; Salzillo, R; Tambone, V; Persichetti, P

2018-06-12

The aims of our study were to identify studies that evaluated patient satisfaction following post-bariatric surgery, analyse existing questionnaires, and summarise their development, psychometric properties, and content. A multistep search was undertaken on the web-based PubMed database from the National Library of Medicine to identify studies on patient satisfaction and quality of life following post-bariatric surgery. The authors summarised all the questionnaires used in every study and categorised them as generic, surgery specific, or ad hoc, and whether they contained either validated or unvalidated measures. Our search generated a total of 1754 articles. We performed a systematic review of the 12 remaining studies, because these had sufficient data and met the inclusion criteria. All the studies identified from the literature review were assessed to determine the type of surgery used, and whether or not the questionnaire used to analyse patient satisfaction had been validated. The questionnaires were analysed by reviewers to assess adherence to the rules of the US Food and Drug Administration and the Scientific Advisory Committee of the Medical Outcomes Trust. We identified 20 individual questionnaires that included 10 generic instruments that assessed quality of life, six instruments specific for post-bariatric surgery, three instruments specific for breast surgery. In post-bariatric patients, the BODY-Q was shown to be a more objective and confident measure for evaluating the quality of life of patients following post-bariatric surgery. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Genes contributing to the development of alcoholism: an overview.

PubMed

Edenberg, Howard J

2012-01-01

Genetic factors (i.e., variations in specific genes) account for a substantial portion of the risk for alcoholism. However, identifying those genes and the specific variations involved is challenging. Researchers have used both case-control and family studies to identify genes related to alcoholism risk. In addition, different strategies such as candidate gene analyses and genome-wide association studies have been used. The strongest effects have been found for specific variants of genes that encode two enzymes involved in alcohol metabolism-alcohol dehydrogenase and aldehyde dehydrogenase. Accumulating evidence indicates that variations in numerous other genes have smaller but measurable effects.
Evaluating barriers to adopting telemedicine worldwide: A systematic review.

PubMed

Scott Kruse, Clemens; Karem, Priyanka; Shifflett, Kelli; Vegi, Lokesh; Ravi, Karuna; Brooks, Matthew

2018-01-01

Introduction and objective Studies on telemedicine have shown success in reducing the geographical and time obstacles incurred in the receipt of care in traditional modalities with the same or greater effectiveness; however, there are several barriers that need to be addressed in order for telemedicine technology to spread. The aim of this review is to evaluate barriers to adopting telemedicine worldwide through the analysis of published work. Methods The authors conducted a systematic literature review by extracting the data from the Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PubMed (MEDLINE) research databases. The reviewers in this study analysed 30 articles (nine from CINAHL and 21 from Medline) and identified barriers found in the literature. This review followed the checklist from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009. The reviewers organized the results into one table and five figures that depict the data in different ways, organized by: barrier, country-specific barriers, organization-specific barriers, patient-specific barriers, and medical-staff and programmer-specific barriers. Results The reviewers identified 33 barriers with a frequency of 100 occurrences through the 30 articles. The study identified the issues with technically challenged staff (11%), followed by resistance to change (8%), cost (8%), reimbursement (5%), age of patient (5%), and level of education of patient (5%). All other barriers occurred at or less than 4% of the time. Discussion and conclusions Telemedicine is not yet ubiquitous, and barriers vary widely. The top barriers are technology-specific and could be overcome through training, change-management techniques, and alternating delivery by telemedicine and personal patient-to-provider interaction. The results of this study identify several barriers that could be eliminated by focused policy. Future work should evaluate policy to identify which one to lever to maximize the results.
Using the Domain Specific Innovativeness Scale To Identify Innovative Internet Consumers.

ERIC Educational Resources Information Center

Goldsmith, Ronald E.

2001-01-01

The Domain Specific Innovativeness Scale was included in a survey of student consumers to measure how innovative participants were with regard to buying online. Data analyses confirmed hypotheses that an innovative predisposition toward online buying would be associated positively with more hours of Internet use, greater Internet purchasing,…
Integrating evolutionary and functional approaches to infer adaptation at specific loci.

PubMed

Storz, Jay F; Wheat, Christopher W

2010-09-01

Inferences about adaptation at specific loci are often exclusively based on the static analysis of DNA sequence variation. Ideally,population-genetic evidence for positive selection serves as a stepping-off point for experimental studies to elucidate the functional significance of the putatively adaptive variation. We argue that inferences about adaptation at specific loci are best achieved by integrating the indirect, retrospective insights provided by population-genetic analyses with the more direct, mechanistic insights provided by functional experiments. Integrative studies of adaptive genetic variation may sometimes be motivated by experimental insights into molecular function, which then provide the impetus to perform population genetic tests to evaluate whether the functional variation is of adaptive significance. In other cases, studies may be initiated by genome scans of DNA variation to identify candidate loci for recent adaptation. Results of such analyses can then motivate experimental efforts to test whether the identified candidate loci do in fact contribute to functional variation in some fitness-related phenotype. Functional studies can provide corroborative evidence for positive selection at particular loci, and can potentially reveal specific molecular mechanisms of adaptation.
Neptune: a bioinformatics tool for rapid discovery of genomic variation in bacterial populations

PubMed Central

Marinier, Eric; Zaheer, Rahat; Berry, Chrystal; Weedmark, Kelly A.; Domaratzki, Michael; Mabon, Philip; Knox, Natalie C.; Reimer, Aleisha R.; Graham, Morag R.; Chui, Linda; Patterson-Fortin, Laura; Zhang, Jian; Pagotto, Franco; Farber, Jeff; Mahony, Jim; Seyer, Karine; Bekal, Sadjia; Tremblay, Cécile; Isaac-Renton, Judy; Prystajecky, Natalie; Chen, Jessica; Slade, Peter

2017-01-01

Abstract The ready availability of vast amounts of genomic sequence data has created the need to rethink comparative genomics algorithms using ‘big data’ approaches. Neptune is an efficient system for rapidly locating differentially abundant genomic content in bacterial populations using an exact k-mer matching strategy, while accommodating k-mer mismatches. Neptune’s loci discovery process identifies sequences that are sufficiently common to a group of target sequences and sufficiently absent from non-targets using probabilistic models. Neptune uses parallel computing to efficiently identify and extract these loci from draft genome assemblies without requiring multiple sequence alignments or other computationally expensive comparative sequence analyses. Tests on simulated and real datasets showed that Neptune rapidly identifies regions that are both sensitive and specific. We demonstrate that this system can identify trait-specific loci from different bacterial lineages. Neptune is broadly applicable for comparative bacterial analyses, yet will particularly benefit pathogenomic applications, owing to efficient and sensitive discovery of differentially abundant genomic loci. The software is available for download at: http://github.com/phac-nml/neptune. PMID:29048594
A Transcriptome Derived Female-Specific Marker from the Invasive Western Mosquitofish (Gambusia affinis)

PubMed Central

Lamatsch, Dunja K.; Adolfsson, Sofia; Senior, Alistair M.; Christiansen, Guntram; Pichler, Maria; Ozaki, Yuichi; Smeds, Linnea; Schartl, Manfred; Nakagawa, Shinichi

2015-01-01

Sex-specific markers are a prerequisite for understanding reproductive biology, genetic factors involved in sex differences, mechanisms of sex determination, and ultimately the evolution of sex chromosomes. The Western mosquitofish, Gambusia affinis, may be considered a model species for sex-chromosome evolution, as it displays female heterogamety (ZW/ZZ), and is also ecologically interesting as a worldwide invasive species. Here, de novo RNA-sequencing on the gonads of sexually mature G. affinis was used to identify contigs that were highly transcribed in females but not in males (i.e., transcripts with ovary-specific expression). Subsequently, 129 primer pairs spanning 79 contigs were tested by PCR to identify sex-specific transcripts. Of those primer pairs, one female-specific DNA marker was identified, Sanger sequenced and subsequently validated in 115 fish. Sequence analyses revealed a high similarity between the identified sex-specific marker and the 3´ UTR of the aminomethyl transferase (amt) gene of the closely related platyfish (Xiphophorus maculatus). This is the first time that RNA-seq has been used to successfully characterize a sex-specific marker in a fish species in the absence of a genome map. Additionally, the identified sex-specific marker represents one of only a handful of such markers in fishes. PMID:25707007
Issues Related to the Construction of a Purpose-Built Domain-Specific Word Corpus

ERIC Educational Resources Information Center

Thomas, Lisa; Pfister, H. Peter; Peterson, Peter

2004-01-01

There is growing interest in the use of semantic collections in order to identify and analyse domain knowledge. This paper describes some technical issues to consider when contemplating research which incorporates small-to-medium domain-specific word sets. The purpose of the corpus construction described was to provide an external word collection…
Genetics of alcoholism.

PubMed

Edenberg, Howard J; Foroud, Tatiana

2014-01-01

Multiple lines of evidence strongly indicate that genetic factors contribute to the risk for alcohol use disorders (AUD). There is substantial heterogeneity in AUD, which complicates studies seeking to identify specific genetic factors. To identify these genetic effects, several different alcohol-related phenotypes have been analyzed, including diagnosis and quantitative measures related to AUDs. Study designs have used candidate gene analyses, genetic linkage studies, genomewide association studies (GWAS), and analyses of rare variants. Two genes that encode enzymes of alcohol metabolism have the strongest effect on AUD: aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B each has strongly protective variants that reduce risk, with odds ratios approximately 0.2-0.4. A number of other genes important in AUD have been identified and replicated, including GABRA2 and alcohol dehydrogenases 1B and 4. GWAS have identified additional candidates. Rare variants are likely also to play a role; studies of these are just beginning. A multifaceted approach to gene identification, targeting both rare and common variations and assembling much larger datasets for meta-analyses, is critical for identifying the key genes and pathways important in AUD. © 2014 Elsevier B.V. All rights reserved.
Scheduling language and algorithm development study. Appendix: Study approach and activity summary

NASA Technical Reports Server (NTRS)

1974-01-01

The approach and organization of the study to develop a high level computer programming language and a program library are presented. The algorithm and problem modeling analyses are summarized. The approach used to identify and specify the capabilities required in the basic language is described. Results of the analyses used to define specifications for the scheduling module library are presented.
Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes.

PubMed

Tanniou, Julien; van der Tweel, Ingeborg; Teerenstra, Steven; Roes, Kit C B

2016-02-18

It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III) clinical trials, where conclusions for the overall study population might not hold. Subgroup analyses can have different and distinct purposes, requiring specific design and analysis solutions. It is relevant to evaluate methodological developments in subgroup analyses against these purposes to guide health care professionals and regulators as well as to identify gaps in current methodology. We defined four purposes for subgroup analyses: (1) Investigate the consistency of treatment effects across subgroups of clinical importance, (2) Explore the treatment effect across different subgroups within an overall non-significant trial, (3) Evaluate safety profiles limited to one or a few subgroup(s), (4) Establish efficacy in the targeted subgroup when included in a confirmatory testing strategy of a single trial. We reviewed the methodology in line with this "purpose-based" framework. The review covered papers published between January 2005 and April 2015 and aimed to classify them in none, one or more of the aforementioned purposes. In total 1857 potentially eligible papers were identified. Forty-eight papers were selected and 20 additional relevant papers were identified from their references, leading to 68 papers in total. Nineteen were dedicated to purpose 1, 16 to purpose 4, one to purpose 2 and none to purpose 3. Seven papers were dedicated to more than one purpose, the 25 remaining could not be classified unambiguously. Purposes of the methods were often not specifically indicated, methods for subgroup analysis for safety purposes were almost absent and a multitude of diverse methods were developed for purpose (1). It is important that researchers developing methodology for subgroup analysis explicitly clarify the objectives of their methods in terms that can be understood from a patient's, health care provider's and/or regulator's perspective. A clear operational definition for consistency of treatment effects across subgroups is lacking, but is needed to improve the usability of subgroup analyses in this setting. Finally, methods to particularly explore benefit-risk systematically across subgroups need more research.
The behavioral genetics of nonhuman primates: Status and prospects.

PubMed

Rogers, Jeffrey

2018-01-01

The complexity and diversity of primate behavior have long attracted the attention of ethologists, psychologists, behavioral ecologists, and neuroscientists. Recent studies have advanced our understanding of the nature of genetic influences on differences in behavior among individuals within species. A number of analyses have focused on the genetic analysis of behavioral reactions to specific experimental tests, providing estimates of the degree of genetic control over reactivity, and beginning to identify the genes involved. Substantial progress is also being made in identifying genetic factors that influence the structure and function of the primate brain. Most of the published studies on these topics have examined either cercopithecines or chimpanzees, though a few studies have addressed these questions in other primate species. One potentially important line of research is beginning to identify the epigenetic processes that influence primate behavior, thus revealing specific cellular and molecular mechanisms by which environmental experiences can influence gene expression or gene function relevant to behavior. This review summarizes many of these studies of non-human primate behavioral genetics. The primary focus is on analyses that address the nature of the genes and genetic processes that affect differences in behavior among individuals within non-human primate species. Analyses of between species differences and potential avenues for future research are also discussed. © 2018 American Association of Physical Anthropologists.
The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

PubMed

Winkler, Thomas W; Justice, Anne E; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B; Ferreira, Teresa; Heard-Costa, Nancy L; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M; Jansen, Rick; Westra, Harm-Jan; White, Charles C; Absher, Devin; Ahluwalia, Tarunveer S; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L; de Craen, Anton J M; Bis, Joshua C; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W K; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E; Jackson, Anne U; Jacobs, Kevin B; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E; Lahti, Jari; Mateo Leach, Irene; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A F; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L; Montasser, May E; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W; Renström, Frida; Rizzi, Federica; Rose, Lynda M; Ryan, Kathy A; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L; Wang, Sophie R; Wang, Zhaoming; Wild, Sarah H; Willenborg, Christina; Wilson, James F; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A; Bakker, Stephan J L; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L; Boyd, Heather A; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S; Claudi-Boehm, Simone; Cole, John; Collins, Francis S; de Geus, Eco J C; de Groot, Lisette C P G M; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G; Friedrich, Nele; Gejman, Pablo V; Gigante, Bruna; Glorioso, Nicola; Go, Alan S; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C; Hansen, Torben; Harris, Tamara B; Hartman, Catharina A; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T; Heath, Andrew C; Henders, Anjali K; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L; Hutri-Kähönen, Nina; Hysi, Pirro G; Illig, Thomas; De Jager, Philip L; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W; Morris, Andrew P; Narisu, Narisu; Nelis, Mari; Ong, Ken K; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M; Rice, Treva K; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R; Sarzynski, Mark A; Scholtens, Salome; Scott, Robert A; Scott, William R; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P Eline; Smit, Jan H; Sparsø, Thomas H; Stirrups, Kathleen; Stolk, Ronald P; Stringham, Heather M; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tan, Sian-Tsung; Thorand, Barbara; Tönjes, Anke; Tremblay, Angelo; Tsafantakis, Emmanouil; van der Most, Peter J; Völker, Uwe; Vohl, Marie-Claude; Vonk, Judith M; Waldenberger, Melanie; Walker, Ryan W; Wennauer, Roman; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Wright, Alan F; Zillikens, M Carola; van Dijk, Suzanne C; van Schoor, Natasja M; Asselbergs, Folkert W; de Bakker, Paul I W; Beckmann, Jacques S; Beilby, John; Bennett, David A; Bergman, Richard N; Bergmann, Sven; Böger, Carsten A; Boehm, Bernhard O; Boerwinkle, Eric; Boomsma, Dorret I; Bornstein, Stefan R; Bottinger, Erwin P; Bouchard, Claude; Chambers, John C; Chanock, Stephen J; Chasman, Daniel I; Cucca, Francesco; Cusi, Daniele; Dedoussis, George; Erdmann, Jeanette; Eriksson, Johan G; Evans, Denis A; de Faire, Ulf; Farrall, Martin; Ferrucci, Luigi; Ford, Ian; Franke, Lude; Franks, Paul W; Froguel, Philippe; Gansevoort, Ron T; Gieger, Christian; Grönberg, Henrik; Gudnason, Vilmundur; Gyllensten, Ulf; Hall, Per; Hamsten, Anders; van der Harst, Pim; Hayward, Caroline; Heliövaara, Markku; Hengstenberg, Christian; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hu, Frank; Huikuri, Heikki V; Hveem, Kristian; James, Alan L; Jordan, Joanne M; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Kathiresan, Sekar; Kiemeney, Lambertus A L M; Kivimaki, Mika; Knekt, Paul B; Koistinen, Heikki A; Kooner, Jaspal S; Koskinen, Seppo; Kuusisto, Johanna; Maerz, Winfried; Martin, Nicholas G; Laakso, Markku; Lakka, Timo A; Lehtimäki, Terho; Lettre, Guillaume; Levinson, Douglas F; Lind, Lars; Lokki, Marja-Liisa; Mäntyselkä, Pekka; Melbye, Mads; Metspalu, Andres; Mitchell, Braxton D; Moll, Frans L; Murray, Jeffrey C; Musk, Arthur W; Nieminen, Markku S; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J; Oostra, Ben A; Palmer, Lyle J; Pankow, James S; Pasterkamp, Gerard; Pedersen, Nancy L; Pedersen, Oluf; Penninx, Brenda W; Perola, Markus; Peters, Annette; Polašek, Ozren; Pramstaller, Peter P; Psaty, Bruce M; Qi, Lu; Quertermous, Thomas; Raitakari, Olli T; Rankinen, Tuomo; Rauramaa, Rainer; Ridker, Paul M; Rioux, John D; Rivadeneira, Fernando; Rotter, Jerome I; Rudan, Igor; den Ruijter, Hester M; Saltevo, Juha; Sattar, Naveed; Schunkert, Heribert; Schwarz, Peter E H; Shuldiner, Alan R; Sinisalo, Juha; Snieder, Harold; Sørensen, Thorkild I A; Spector, Tim D; Staessen, Jan A; Stefania, Bandinelli; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tardif, Jean-Claude; Tremoli, Elena; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; Verbeek, André L M; Vermeulen, Sita H; Viikari, Jorma S; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Waeber, Gérard; Walker, Mark; Wallaschofski, Henri; Wareham, Nicholas J; Watkins, Hugh; Zeggini, Eleftheria; Chakravarti, Aravinda; Clegg, Deborah J; Cupples, L Adrienne; Gordon-Larsen, Penny; Jaquish, Cashell E; Rao, D C; Abecasis, Goncalo R; Assimes, Themistocles L; Barroso, Inês; Berndt, Sonja I; Boehnke, Michael; Deloukas, Panos; Fox, Caroline S; Groop, Leif C; Hunter, David J; Ingelsson, Erik; Kaplan, Robert C; McCarthy, Mark I; Mohlke, Karen L; O'Connell, Jeffrey R; Schlessinger, David; Strachan, David P; Stefansson, Kari; van Duijn, Cornelia M; Hirschhorn, Joel N; Lindgren, Cecilia M; Heid, Iris M; North, Kari E; Borecki, Ingrid B; Kutalik, Zoltán; Loos, Ruth J F

2015-10-01

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

PubMed Central

Feitosa, Mary F.; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O.; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H.; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B.; Ferreira, Teresa; Heard-Costa, Nancy L.; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D.; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M.; Jansen, Rick; Westra, Harm-Jan; White, Charles C.; Absher, Devin; Ahluwalia, Tarunveer S.; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L.; de Craen, Anton J. M.; Bis, Joshua C.; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W. K.; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E.; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B.; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jackson, Anne U.; Jacobs, Kevin B.; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E.; Lahti, Jari; Leach, Irene Mateo; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A. F.; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L.; Montasser, May E.; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M.; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W.; Renström, Frida; Rizzi, Federica; Rose, Lynda M.; Ryan, Kathy A.; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J.; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P.; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L.; Wang, Sophie R.; Wang, Zhaoming; Wild, Sarah H.; Willenborg, Christina; Wilson, James F.; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M.; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A.; Bakker, Stephan J. L.; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L.; Boyd, Heather A.; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S.; Claudi-Boehm, Simone; Cole, John; Collins, Francis S.; de Geus, Eco J. C.; de Groot, Lisette C. P. G. M.; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G.; Friedrich, Nele; Gejman, Pablo V.; Gigante, Bruna; Glorioso, Nicola; Go, Alan S.; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C.; Hansen, Torben; Harris, Tamara B.; Hartman, Catharina A.; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T.; Heath, Andrew C.; Henders, Anjali K.; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L.; Hutri-Kähönen, Nina; Hysi, Pirro G.; Illig, Thomas; De Jager, Philip L.; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J. Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J.; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T.; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J.; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K.; McArdle, Wendy L.; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W.; Morris, Andrew P.; Narisu, Narisu; Nelis, Mari; Ong, Ken K.; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G.; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M.; Rice, Treva K.; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R.; Sarzynski, Mark A.; Scholtens, Salome; Scott, Robert A.; Scott, William R.; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P. Eline; Smit, Jan H.; Sparsø, Thomas H.; Stirrups, Kathleen; Stolk, Ronald P.; Stringham, Heather M.; Swertz, Morris A; Swift, Amy J.; Syvänen, Ann-Christine; Tan, Sian-Tsung; Thorand, Barbara; Tönjes, Anke; Tremblay, Angelo; Tsafantakis, Emmanouil; van der Most, Peter J.; Völker, Uwe; Vohl, Marie-Claude; Vonk, Judith M.; Waldenberger, Melanie; Walker, Ryan W.; Wennauer, Roman; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Wright, Alan F.; Zillikens, M. Carola; van Dijk, Suzanne C.; van Schoor, Natasja M.; Asselbergs, Folkert W.; de Bakker, Paul I. W.; Beckmann, Jacques S.; Beilby, John; Bennett, David A.; Bergman, Richard N.; Bergmann, Sven; Böger, Carsten A.; Boehm, Bernhard O.; Boerwinkle, Eric; Boomsma, Dorret I.; Bornstein, Stefan R.; Bottinger, Erwin P.; Bouchard, Claude; Chambers, John C.; Chanock, Stephen J.; Chasman, Daniel I.; Cucca, Francesco; Cusi, Daniele; Dedoussis, George; Erdmann, Jeanette; Eriksson, Johan G.; Evans, Denis A.; de Faire, Ulf; Farrall, Martin; Ferrucci, Luigi; Ford, Ian; Franke, Lude; Franks, Paul W.; Froguel, Philippe; Gansevoort, Ron T.; Gieger, Christian; Grönberg, Henrik; Gudnason, Vilmundur; Gyllensten, Ulf; Hall, Per; Hamsten, Anders; van der Harst, Pim; Hayward, Caroline; Heliövaara, Markku; Hengstenberg, Christian; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hu, Frank; Huikuri, Heikki V.; Hveem, Kristian; James, Alan L.; Jordan, Joanne M.; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Kathiresan, Sekar; Kiemeney, Lambertus A. L. M.; Kivimaki, Mika; Knekt, Paul B.; Koistinen, Heikki A.; Kooner, Jaspal S.; Koskinen, Seppo; Kuusisto, Johanna; Maerz, Winfried; Martin, Nicholas G; Laakso, Markku; Lakka, Timo A.; Lehtimäki, Terho; Lettre, Guillaume; Levinson, Douglas F.; Lind, Lars; Lokki, Marja-Liisa; Mäntyselkä, Pekka; Melbye, Mads; Metspalu, Andres; Mitchell, Braxton D.; Moll, Frans L.; Murray, Jeffrey C.; Musk, Arthur W.; Nieminen, Markku S.; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Oostra, Ben A.; Palmer, Lyle J; Pankow, James S.; Pasterkamp, Gerard; Pedersen, Nancy L.; Pedersen, Oluf; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Polašek, Ozren; Pramstaller, Peter P.; Psaty, Bruce M.; Qi, Lu; Quertermous, Thomas; Raitakari, Olli T.; Rankinen, Tuomo; Rauramaa, Rainer; Ridker, Paul M.; Rioux, John D.; Rivadeneira, Fernando; Rotter, Jerome I.; Rudan, Igor; den Ruijter, Hester M.; Saltevo, Juha; Sattar, Naveed; Schunkert, Heribert; Schwarz, Peter E. H.; Shuldiner, Alan R.; Sinisalo, Juha; Snieder, Harold; Sørensen, Thorkild I. A.; Spector, Tim D.; Staessen, Jan A.; Stefania, Bandinelli; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tardif, Jean-Claude; Tremoli, Elena; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; Verbeek, André L. M.; Vermeulen, Sita H.; Viikari, Jorma S.; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Waeber, Gérard; Walker, Mark; Wallaschofski, Henri; Wareham, Nicholas J.; Watkins, Hugh; Zeggini, Eleftheria; Chakravarti, Aravinda; Clegg, Deborah J.; Cupples, L. Adrienne; Gordon-Larsen, Penny; Jaquish, Cashell E.; Rao, D. C.; Abecasis, Goncalo R.; Assimes, Themistocles L.; Barroso, Inês; Berndt, Sonja I.; Boehnke, Michael; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Hunter, David J.; Ingelsson, Erik; Kaplan, Robert C.; McCarthy, Mark I.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Schlessinger, David; Strachan, David P.; Stefansson, Kari; van Duijn, Cornelia M.; Hirschhorn, Joel N.; Lindgren, Cecilia M.; Heid, Iris M.; North, Kari E.; Borecki, Ingrid B.; Kutalik, Zoltán; Loos, Ruth J. F.

2015-01-01

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape. PMID:26426971
Is there a place for extended assessments in addressing child sexual abuse allegations? How sensitivity and specificity impact professional perspectives.

PubMed

Williams, Javonda; Nelson-Gardell, Debra; Coulborn Faller, Kathleen; Tishelman, Amy; Cordisco-Steele, Linda

2014-01-01

Using data from a survey of perceptions of 932 child welfare professionals about the utility of extended assessments, the researchers constructed a scale to measure respondents' views about sensitivity (ensuring sexually abused children are correctly identified) and specificity (ensuring nonabused children are correctly identified) in child sexual abuse evaluations. On average, respondents scored high (valuing sensitivity) on the sensitivity versus specificity scale. Next, the researchers undertook bivariate analyses to identify independent variables significantly associated with the sensitivity versus specificity scale. Then those variables were entered into a multiple regression. Four independent variables were significantly related to higher sensitivity scores: encountering cases requiring extended assessments, valuing extended assessments among scarce resources, less concern about proving cases in court, and viewing the goal of extended assessments as understanding needs of child and family (adjusted R2 = .34).
Dose-response relationship between cigarette smoking and site-specific cancer risk: protocol for a systematic review with an original design combining umbrella and traditional reviews.

PubMed

Lugo, Alessandra; Bosetti, Cristina; Peveri, Giulia; Rota, Matteo; Bagnardi, Vincenzo; Gallus, Silvano

2017-11-01

Only a limited number of meta-analyses providing risk curve functions of dose-response relationships between various smoking-related variables and cancer-specific risk are available. To identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose-response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose-response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose-response relationship framework. Ethics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden attributable to cigarette smoking. This protocol was registered in the International Prospective Register of Systematic Reviews (CRD42017063991). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
An Interspecies Comparative Analysis of the Predicted Secretomes of the Necrotrophic Plant Pathogens Sclerotinia sclerotiorum and Botrytis cinerea

PubMed Central

2015-01-01

Phytopathogenic fungi form intimate associations with host plant species and cause disease. To be successful, fungal pathogens communicate with a susceptible host through the secretion of proteinaceous effectors, hydrolytic enzymes and metabolites. Sclerotinia sclerotiorum and Botrytis cinerea are economically important necrotrophic fungal pathogens that cause disease on numerous crop species. Here, a powerful bioinformatics pipeline was used to predict the refined S. sclerotiorum and B. cinerea secretomes, identifying 432 and 499 proteins respectively. Analyses focusing on S. sclerotiorum revealed that 16% of the secretome encoding genes resided in small, sequence heterogeneous, gene clusters that were distributed over 13 of the 16 predicted chromosomes. Functional analyses highlighted the importance of plant cell hydrolysis, oxidation-reduction processes and the redox state to the S. sclerotiorum and B. cinerea secretomes and potentially host infection. Only 8% of the predicted proteins were distinct between the two secretomes. In contrast to S. sclerotiorum, the B. cinerea secretome lacked CFEM- or LysM-containing proteins. The 115 fungal and oomycete genome comparison identified 30 proteins specific to S. sclerotiorum and B. cinerea, plus 11 proteins specific to S. sclerotiorum and 32 proteins specific to B. cinerea. Expressed sequence tag (EST) and proteomic analyses showed that 246 S. sclerotiorum secretome encoding genes had EST support, including 101 which were only expressed in vitro and 49 which were only expressed in planta, whilst 42 predicted proteins were experimentally proven to be secreted. These detailed in silico analyses of two important necrotrophic pathogens will permit informed choices to be made when candidate effector proteins are selected for function analyses in planta. PMID:26107498

Psychological Well-Being and the Human Conserved Transcriptional Response to Adversity

PubMed Central

Fredrickson, Barbara L.; Grewen, Karen M.; Algoe, Sara B.; Firestine, Ann M.; Arevalo, Jesusa M. G.; Ma, Jeffrey; Cole, Steve W.

2015-01-01

Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum – Short Form. Analyses of a 2- representation of eudaimonia converged in finding correlated psychological and social subdomains of eudaimonic well-being to be the primary carriers of CTRA associations. Hedonic well-being showed no consistent CTRA association independent of eudaimonic well-being, and summary measures integrating hedonic and eudaimonic well-being showed less stable CTRA associations than did focal measures of eudaimonia (psychological and social well-being). Similar results emerged from analyses of pooled discovery and confirmation samples (n = 198). Similar results also emerged from analyses of a second new generalization study of 107 healthy adults that included the more detailed Ryff Scales of Psychological Well-being and found this more robust measure of eudaimonic well-being to also associate with reduced CTRA gene expression. Five of the 6 major sub-domains of psychological well-being predicted reduced CTRA gene expression when analyzed separately, and 3 remained distinctively prognostic in mutually adjusted analyses. All associations were independent of demographic characteristics, health-related confounders, and RNA indicators of leukocyte subset distribution. These results identify specific sub-dimensions of eudaimonic well-being as promising targets for future interventions to mitigate CTRA gene expression, and provide no support for any independent favorable contribution from hedonic well-being. PMID:25811656
Phylogenetic Analysis and Classification of the Fungal bHLH Domain

PubMed Central

Sailsbery, Joshua K.; Atchley, William R.; Dean, Ralph A.

2012-01-01

The basic Helix-Loop-Helix (bHLH) domain is an essential highly conserved DNA-binding domain found in many transcription factors in all eukaryotic organisms. The bHLH domain has been well studied in the Animal and Plant Kingdoms but has yet to be characterized within Fungi. Herein, we obtained and evaluated the phylogenetic relationship of 490 fungal-specific bHLH containing proteins from 55 whole genome projects composed of 49 Ascomycota and 6 Basidiomycota organisms. We identified 12 major groupings within Fungi (F1–F12); identifying conserved motifs and functions specific to each group. Several classification models were built to distinguish the 12 groups and elucidate the most discerning sites in the domain. Performance testing on these models, for correct group classification, resulted in a maximum sensitivity and specificity of 98.5% and 99.8%, respectively. We identified 12 highly discerning sites and incorporated those into a set of rules (simplified model) to classify sequences into the correct group. Conservation of amino acid sites and phylogenetic analyses established that like plant bHLH proteins, fungal bHLH–containing proteins are most closely related to animal Group B. The models used in these analyses were incorporated into a software package, the source code for which is available at www.fungalgenomics.ncsu.edu. PMID:22114358
An Introduction to Job Analysis

ERIC Educational Resources Information Center

Boydell, T. H.

1970-01-01

Job training involves preparing a job description and specification, and, if necessary, further analyses of skills, knowledge, and attitudes in order to identify areas of difficulty which will affect the choice of what must be learned and appropriate training techniques. (DM)
Crash data analyses for vehicle-to-infrastructure communications for safety applications.

DOT National Transportation Integrated Search

2012-11-01

This report presents the potential safety benefits of wireless communication between the roadway infrastructure and vehicles, : (i.e., vehicle-to-infrastructure (V2I) safety). Specifically, it identifies the magnitude, characteristics, and cost of cr...
Novel Autism Subtype-Dependent Genetic Variants Are Revealed by Quantitative Trait and Subphenotype Association Analyses of Published GWAS Data

PubMed Central

Hu, Valerie W.; Addington, Anjene; Hyman, Alexander

2011-01-01

The heterogeneity of symptoms associated with autism spectrum disorders (ASDs) has presented a significant challenge to genetic analyses. Even when associations with genetic variants have been identified, it has been difficult to associate them with a specific trait or characteristic of autism. Here, we report that quantitative trait analyses of ASD symptoms combined with case-control association analyses using distinct ASD subphenotypes identified on the basis of symptomatic profiles result in the identification of highly significant associations with 18 novel single nucleotide polymorphisms (SNPs). The symptom categories included deficits in language usage, non-verbal communication, social development, and play skills, as well as insistence on sameness or ritualistic behaviors. Ten of the trait-associated SNPs, or quantitative trait loci (QTL), were associated with more than one subtype, providing partial replication of the identified QTL. Notably, none of the novel SNPs is located within an exonic region, suggesting that these hereditary components of ASDs are more likely related to gene regulatory processes (or gene expression) than to structural or functional changes in gene products. Seven of the QTL reside within intergenic chromosomal regions associated with rare copy number variants that have been previously reported in autistic samples. Pathway analyses of the genes associated with the QTL identified in this study implicate neurological functions and disorders associated with autism pathophysiology. This study underscores the advantage of incorporating both quantitative traits as well as subphenotypes into large-scale genome-wide analyses of complex disorders. PMID:21556359
Screening and Characterization of a Novel RNA Aptamer That Specifically Binds to Human Prostatic Acid Phosphatase and Human Prostate Cancer Cells

PubMed Central

Kong, Hoon Young; Byun, Jonghoe

2015-01-01

Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2′-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2′-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer. PMID:25591398
Expression of uncharacterized male germ cell-specific genes and discovery of novel sperm-tail proteins in mice.

PubMed

Kwon, Jun Tae; Ham, Sera; Jeon, Suyeon; Kim, Youil; Oh, Seungmin; Cho, Chunghee

2017-01-01

The identification and characterization of germ cell-specific genes are essential if we hope to comprehensively understand the mechanisms of spermatogenesis and fertilization. Here, we searched the mouse UniGene databases and identified 13 novel genes as being putatively testis-specific or -predominant. Our in silico and in vitro analyses revealed that the expressions of these genes are testis- and germ cell-specific, and that they are regulated in a stage-specific manner during spermatogenesis. We generated antibodies against the proteins encoded by seven of the genes to facilitate their characterization in male germ cells. Immunoblotting and immunofluorescence analyses revealed that one of these proteins was expressed only in testicular germ cells, three were expressed in both testicular germ cells and testicular sperm, and the remaining three were expressed in sperm of the testicular stages and in mature sperm from the epididymis. Further analysis of the latter three proteins showed that they were all associated with cytoskeletal structures in the sperm flagellum. Among them, MORN5, which is predicted to contain three MORN motifs, is conserved between mouse and human sperm. In conclusion, we herein identify 13 authentic genes with male germ cell-specific expression, and provide comprehensive information about these genes and their encoded products. Our finding will facilitate future investigations into the functional roles of these novel genes in spermatogenesis and sperm functions.
Phylogenetic and Evolutionary Patterns in Microbial Carotenoid Biosynthesis Are Revealed by Comparative Genomics

PubMed Central

Klassen, Jonathan L.

2010-01-01

Background Carotenoids are multifunctional, taxonomically widespread and biotechnologically important pigments. Their biosynthesis serves as a model system for understanding the evolution of secondary metabolism. Microbial carotenoid diversity and evolution has hitherto been analyzed primarily from structural and biosynthetic perspectives, with the few phylogenetic analyses of microbial carotenoid biosynthetic proteins using either used limited datasets or lacking methodological rigor. Given the recent accumulation of microbial genome sequences, a reappraisal of microbial carotenoid biosynthetic diversity and evolution from the perspective of comparative genomics is warranted to validate and complement models of microbial carotenoid diversity and evolution based upon structural and biosynthetic data. Methodology/Principal Findings Comparative genomics were used to identify and analyze in silico microbial carotenoid biosynthetic pathways. Four major phylogenetic lineages of carotenoid biosynthesis are suggested composed of: (i) Proteobacteria; (ii) Firmicutes; (iii) Chlorobi, Cyanobacteria and photosynthetic eukaryotes; and (iv) Archaea, Bacteroidetes and two separate sub-lineages of Actinobacteria. Using this phylogenetic framework, specific evolutionary mechanisms are proposed for carotenoid desaturase CrtI-family enzymes and carotenoid cyclases. Several phylogenetic lineage-specific evolutionary mechanisms are also suggested, including: (i) horizontal gene transfer; (ii) gene acquisition followed by differential gene loss; (iii) co-evolution with other biochemical structures such as proteorhodopsins; and (iv) positive selection. Conclusions/Significance Comparative genomics analyses of microbial carotenoid biosynthetic proteins indicate a much greater taxonomic diversity then that identified based on structural and biosynthetic data, and divides microbial carotenoid biosynthesis into several, well-supported phylogenetic lineages not evident previously. This phylogenetic framework is applicable to understanding the evolution of specific carotenoid biosynthetic proteins or the unique characteristics of carotenoid biosynthetic evolution in a specific phylogenetic lineage. Together, these analyses suggest a “bramble” model for microbial carotenoid biosynthesis whereby later biosynthetic steps exhibit greater evolutionary plasticity and reticulation compared to those closer to the biosynthetic “root”. Structural diversification may be constrained (“trimmed”) where selection is strong, but less so where selection is weaker. These analyses also highlight likely productive avenues for future research and bioprospecting by identifying both gaps in current knowledge and taxa which may particularly facilitate carotenoid diversification. PMID:20582313
Global isoform-specific transcript alterations and deregulated networks in clear cell renal cell carcinoma

PubMed Central

Hamilton, Michael J.; Girke, Thomas; Martinez, Ernest

2018-01-01

Extensive genome-wide analyses of deregulated gene expression have now been performed for many types of cancer. However, most studies have focused on deregulation at the gene-level, which may overlook the alterations of specific transcripts for a given gene. Clear cell renal cell carcinoma (ccRCC) is one of the best-characterized and most pervasive renal cancers, and ccRCCs are well-documented to have aberrant RNA processing. In the present study, we examine the extent of aberrant isoform-specific RNA expression by reporting a comprehensive transcript-level analysis, using the new kallisto-sleuth-RATs pipeline, investigating coding and non-coding differential transcript expression in ccRCC. We analyzed 50 ccRCC tumors and their matched normal samples from The Cancer Genome Altas datasets. We identified 7,339 differentially expressed transcripts and 94 genes exhibiting differential transcript isoform usage in ccRCC. Additionally, transcript-level coexpression network analyses identified vasculature development and the tricarboxylic acid cycle as the most significantly deregulated networks correlating with ccRCC progression. These analyses uncovered several uncharacterized transcripts, including lncRNAs FGD5-AS1 and AL035661.1, as potential regulators of the tricarboxylic acid cycle associated with ccRCC progression. As ccRCC still presents treatment challenges, our results provide a new resource of potential therapeutics targets and highlight the importance of exploring alternative methodologies in transcriptome-wide studies.
Discovery of novel cold-induced CISP genes encoding small RNA-binding proteins related to cold adaptation in barley.

PubMed

Ying, Mengchao; Kidou, Shin-Ichiro

2017-07-01

To adapt to cold conditions, barley plants rely on specific mechanisms, which have not been fully understood. In this study, we characterized a novel barley cold-induced gene identified using a PCR-based high coverage gene expression profiling method. The identified gene encodes a small protein that we named CISP1 (Cold-induced Small Protein 1). Homology searches of sequence databases revealed that CISP1 homologs (CISP2 and CISP3) exist in barley genome. Further database analyses showed that the CISP1 homologs were widely distributed in cold-tolerant plants such as wheat and rye. Quantitative reverse transcription PCR analyses indicated that the expression of barley CISP genes was markedly increased in roots exposed to cold conditions. In situ hybridization analyses showed that the CISP1 transcripts were localized in the root tip and lateral root primordium. We also demonstrated that the CISP1 protein bound to RNA. Taken together, these findings indicate that CISP1 and its homologs encoding small RNA-binding proteins may serve as RNA chaperones playing a vital role in the cold adaptation of barley root. This is the first report describing the likely close relationship between root-specific genes and the cold adaptation process, as well as the potential function of the identified genes. Copyright © 2017 Elsevier B.V. All rights reserved.
Neural Mechanisms of the Transformation from Objective Value to Subjective Utility: Converting from Count to Worth.

PubMed

Kurnianingsih, Yoanna A; Mullette-Gillman, O'Dhaniel A

2016-01-01

When deciding, we aim to choose the "best" possible outcome. This is not just selection of the option that is the most numerous or physically largest, as options are translated from objective value (count) to subjective value (worth or utility). We localized the neural instantiation of the value-to-utility transformation to the dorsal anterior midcingulate cortex (daMCC), with independent replication. The daMCC encodes the context-specific information necessary to convert from count to worth. This encoding is not simply a representation of utility or preference, but the interaction of the two. Specifically, the relationship of brain activation to value is dependent on individual preference, with both positive and negative slopes across the population depending on whether each individual's preference results in enhancement or diminishment of the valuation. For a given value, across participants, enhanced daMCC activation corresponds to diminished subjective valuation, deactivation to enhanced subjective valuation, and non-modulated activation with non-modulated subjective valuation. Further, functional connectivity analyses identified brain regions (positive connectivity with the inferior frontal gyrus and negative connectivity with the nucleus accumbens) through which contextual information may be integrated into the daMCC and allow for outputs to modulate valuation signals. All analyses were replicated through an independent within-study replication, with initial testing in the gains domain and replication in the intermixed and mirrored losses trials. We also present and discuss an ancillary finding: we were unable to identify parametric value signals for losses through whole-brain analyses, and ROI analyses of the vmPFC presented non-modulation across loss value levels. These results identify the neural locus of the value-to-utility transformation, and provide a specific computational function for the daMCC in the production of subjective valuation through the integration of value, context, and preferences.
Neural Mechanisms of the Transformation from Objective Value to Subjective Utility: Converting from Count to Worth

PubMed Central

Kurnianingsih, Yoanna A.; Mullette-Gillman, O'Dhaniel A.

2016-01-01

When deciding, we aim to choose the “best” possible outcome. This is not just selection of the option that is the most numerous or physically largest, as options are translated from objective value (count) to subjective value (worth or utility). We localized the neural instantiation of the value-to-utility transformation to the dorsal anterior midcingulate cortex (daMCC), with independent replication. The daMCC encodes the context-specific information necessary to convert from count to worth. This encoding is not simply a representation of utility or preference, but the interaction of the two. Specifically, the relationship of brain activation to value is dependent on individual preference, with both positive and negative slopes across the population depending on whether each individual's preference results in enhancement or diminishment of the valuation. For a given value, across participants, enhanced daMCC activation corresponds to diminished subjective valuation, deactivation to enhanced subjective valuation, and non-modulated activation with non-modulated subjective valuation. Further, functional connectivity analyses identified brain regions (positive connectivity with the inferior frontal gyrus and negative connectivity with the nucleus accumbens) through which contextual information may be integrated into the daMCC and allow for outputs to modulate valuation signals. All analyses were replicated through an independent within-study replication, with initial testing in the gains domain and replication in the intermixed and mirrored losses trials. We also present and discuss an ancillary finding: we were unable to identify parametric value signals for losses through whole-brain analyses, and ROI analyses of the vmPFC presented non-modulation across loss value levels. These results identify the neural locus of the value-to-utility transformation, and provide a specific computational function for the daMCC in the production of subjective valuation through the integration of value, context, and preferences. PMID:27881949
Systematic literature review of patient-reported outcome measures used in assessment and measurement of sleep disorders in chronic obstructive pulmonary disease.

PubMed

Garrow, Adam P; Yorke, Janelle; Khan, Naimat; Vestbo, Jørgen; Singh, Dave; Tyson, Sarah

2015-01-01

Sleep problems are common in patients with chronic obstructive pulmonary disease (COPD), but the validity of patient-reported outcome measures (PROMs) that measure sleep dysfunction has not been evaluated. We have reviewed the literature to identify disease-specific and non-disease-specific sleep PROMs that have been validated for use in COPD patients. The review also examined the psychometric properties of identified sleep outcome measures and extracted point and variability estimates of sleep instruments used in COPD studies. The online EMBASE, MEDLINE, PsycINFO, and SCOPUS databases for all years to May 2014 were used to source articles for the review. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Criteria from the Medical Outcomes Trust Scientific Advisory Committee guidelines were used to evaluate the psychometric properties of all sleep PROMs identified. One COPD-specific and six non-COPD-specific sleep outcome measures were identified and 44 papers met the review selection criteria. We only identified one instrument, the COPD and Asthma Sleep Impact Scale, which was developed specifically for use in COPD populations. Ninety percent of the identified studies used one of two non-disease-specific sleep scales, ie, the Pittsburgh Sleep Quality Index and/or the Epworth Sleep Scale, although neither has been tested for reliability or validity in people with COPD. The results highlight a need for existing non-disease-specific instruments to be validated in COPD populations and also a need for new disease-specific measures to assess the impact of sleep problems in COPD.
3M™ Molecular detection system versus MALDI-TOF mass spectrometry and molecular techniques for the identification of Escherichia coli 0157:H7, Salmonella spp. &Listeria spp.

PubMed

Loff, Marché; Mare, Louise; de Kwaadsteniet, Michele; Khan, Wesaal

2014-06-01

The aim of this study was to compare standard selective plating, conventional PCR (16S rRNA and species specific primers), MALDI-TOF MS and the 3M™ Molecular Detection System for the routine detection of the pathogens Listeria, Salmonella and Escherichia coli 0157:H7 in wastewater and river water samples. MALDI-TOF MS was able to positively identify 20/21 (95%) of the E. coli isolates obtained at genus and species level, while 16S rRNA sequencing only correctly identified 6/21 (28%) as E. coli strains. None of the presumptive positive Listeria spp. and Salmonella spp. isolates obtained by culturing on selective media were positively identified by MALDI-TOF and 16S rRNA analysis. The species-specific E. coli 0157:H7 PCR described in this present study, was not able to detect any E. coli 0157:H7 strains in the wastewater and river water samples analysed. However, E. coli strains, Listeria spp., L. monocytogenes and Salmonella spp. were detected using species specific PCR. Escherichia coli 0157:H7, Listeria spp. and Salmonella spp. were also sporadically detected throughout the sampling period in the wastewater and river water samples analysed by the 3M™ Molecular Detection System. MALDI-TOF MS, which is a simple, accurate and cost-effective detection method, efficiently identified the culturable organisms, while in the current study both species specific PCR (Listeria spp. and Salmonella spp.) and 3M™ Molecular Detection System could be utilised for the direct routine analysis of pathogens in water sources. Copyright © 2014 Elsevier B.V. All rights reserved.
Effective technologies for noninvasive remote monitoring in heart failure.

PubMed

Conway, Aaron; Inglis, Sally C; Clark, Robyn A

2014-06-01

Trials of new technologies to remotely monitor for signs and symptoms of worsening heart failure are continually emerging. The extent to which technological differences impact the effectiveness of noninvasive remote monitoring for heart failure management is unknown. This study examined the effect of specific technology used for noninvasive remote monitoring of people with heart failure on all-cause mortality and heart failure-related hospitalizations. A subanalysis of a large systematic review and meta-analysis was conducted. Studies were stratified according to the specific type of technology used, and separate meta-analyses were performed. Four different types of noninvasive remote monitoring technologies were identified, including structured telephone calls, videophone, interactive voice response devices, and telemonitoring. Only structured telephone calls and telemonitoring were effective in reducing the risk of all-cause mortality (relative risk [RR]=0.87; 95% confidence interval [CI], 0.75-1.01; p=0.06; and RR=0.62; 95% CI, 0.50-0.77; p<0.0001, respectively) and heart failure-related hospitalizations (RR=0.77; 95% CI, 0.68-0.87; p<0.001; and RR=0.75; 95% CI, 0.63-0.91; p=0.003, respectively). More research data are required for videophone and interactive voice response technologies. This subanalysis identified that only two of the four specific technologies used for noninvasive remote monitoring in heart failure improved outcomes. When results of studies that involved these disparate technologies were combined in previous meta-analyses, significant improvements in outcomes were identified. As such, this study has highlighted implications for future meta-analyses of randomized controlled trials focused on evaluating the effectiveness of remote monitoring in heart failure.
Development of a bespoke human factors taxonomy for gliding accident analysis and its revelations about highly inexperienced UK glider pilots.

PubMed

Jarvis, Steve; Harris, Don

2010-02-01

Low-hours solo glider pilots have a high risk of accidents compared to more experienced pilots. Numerous taxonomies for causal accident analysis have been produced for powered aviation but none of these is suitable for gliding, so a new taxonomy was required. A human factors taxonomy specifically for glider operations was developed and used to analyse all UK gliding accidents from 2002 to 2006 for their overall causes as well as factors specific to low hours pilots. Fifty-nine categories of pilot-related accident causation emerged, which were formed into progressively larger categories until four overall human factors groups were arrived at: 'judgement'; 'handling'; 'strategy'; 'attention'. 'Handling' accounted for a significantly higher proportion of injuries than other categories. Inexperienced pilots had considerably more accidents in all categories except 'strategy'. Approach control (path judgement, airbrake and speed handling) as well as landing flare misjudgement were chiefly responsible for the high accident rate in early solo glider pilots. Statement of Relevance: This paper uses extant accident data to produce a taxonomy of underlying human factors causes to analyse gliding accidents and identify the specific causes associated with low hours pilots. From this specific, well-targeted remedial measures can be identified.
Scaling of Ion Thrusters to Low Power

NASA Technical Reports Server (NTRS)

Patterson, Michael J.; Grisnik, Stanley P.; Soulas, George C.

1998-01-01

Analyses were conducted to examine ion thruster scaling relationships in detail to determine performance limits, and lifetime expectations for thruster input power levels below 0.5 kW. This was motivated by mission analyses indicating the potential advantages of high performance, high specific impulse systems for small spacecraft. The design and development status of a 0.1-0.3 kW prototype small thruster and its components are discussed. Performance goals include thruster efficiencies on the order of 40% to 54% over a specific impulse range of 2000 to 3000 seconds, with a lifetime in excess of 8000 hours at full power. Thruster technologies required to achieve the performance and lifetime targets are identified.
Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis.

PubMed

Zhu, Hong; Xia, Wei; Mo, Xing-Bo; Lin, Xiang; Qiu, Ying-Hua; Yi, Neng-Jun; Zhang, Yong-Hong; Deng, Fei-Yan; Lei, Shu-Feng

2016-01-01

Rheumatoid arthritis (RA) is a complex autoimmune disease. Using a gene-based association research strategy, the present study aims to detect unknown susceptibility to RA and to address the ethnic differences in genetic susceptibility to RA between European and Asian populations. Gene-based association analyses were performed with KGG 2.5 by using publicly available large RA datasets (14,361 RA cases and 43,923 controls of European subjects, 4,873 RA cases and 17,642 controls of Asian Subjects). For the newly identified RA-associated genes, gene set enrichment analyses and protein-protein interactions analyses were carried out with DAVID and STRING version 10.0, respectively. Differential expression verification was conducted using 4 GEO datasets. The expression levels of three selected 'highly verified' genes were measured by ELISA among our in-house RA cases and controls. A total of 221 RA-associated genes were newly identified by gene-based association study, including 71'overlapped', 76 'European-specific' and 74 'Asian-specific' genes. Among them, 105 genes had significant differential expressions between RA patients and health controls at least in one dataset, especially for 20 genes including 11 'overlapped' (ABCF1, FLOT1, HLA-F, IER3, TUBB, ZKSCAN4, BTN3A3, HSP90AB1, CUTA, BRD2, HLA-DMA), 5 'European-specific' (PHTF1, RPS18, BAK1, TNFRSF14, SUOX) and 4 'Asian-specific' (RNASET2, HFE, BTN2A2, MAPK13) genes whose differential expressions were significant at least in three datasets. The protein expressions of two selected genes FLOT1 (P value = 1.70E-02) and HLA-DMA (P value = 4.70E-02) in plasma were significantly different in our in-house samples. Our study identified 221 novel RA-associated genes and especially highlighted the importance of 20 candidate genes on RA. The results addressed ethnic genetic background differences for RA susceptibility between European and Asian populations and detected a long list of overlapped or ethnic specific RA genes. The study not only greatly increases our understanding of genetic susceptibility to RA, but also provides important insights into the ethno-genetic homogeneity and heterogeneity of RA in both ethnicities.
The whole-genome landscape of medulloblastoma subtypes.

PubMed

Northcott, Paul A; Buchhalter, Ivo; Morrissy, A Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M; Erkek, Serap; Jones, David T W; Worst, Barbara C; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D; Wolf, Stephan; Robinson, Giles W; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M G; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M; Mora, Jaume; McLendon, Roger E; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A; Mungall, Andrew J; Mungall, Karen L; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J M; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A; Pfister, Stefan M; Taylor, Michael D; Lichter, Peter

2017-07-19

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
A Categorical Content Analysis of Highly Cited Literature Related to Trends and Issues in Special Education.

PubMed

Arden, Sarah V; Pentimonti, Jill M; Cooray, Rochana; Jackson, Stephanie

2017-07-01

This investigation employs categorical content analysis processes as a mechanism to examine trends and issues in a sampling of highly cited (100+) literature in special education journals. The authors had two goals: (a) broadly identifying trends across publication type, content area, and methodology and (b) specifically identifying articles with disaggregated outcomes for students with learning disabilities (LD). Content analyses were conducted across highly cited (100+) articles published during a 20-year period (1992-2013) in a sample ( n = 3) of journals focused primarily on LD, and in one broad, cross-categorical journal recognized for its impact in the field. Results indicated trends in the article type (i.e., commentary and position papers), content (i.e., reading and behavior), and methodology (i.e., small proportions of experimental and quasi-experimental designs). Results also revealed stability in the proportion of intervention research studies when compared to previous analyses and a decline in the proportion of those that disaggregated data specifically for students with LD.

Systematic Characterization and Analysis of the Taxonomic Drivers of Functional Shifts in the Human Microbiome.

PubMed

Manor, Ohad; Borenstein, Elhanan

2017-02-08

Comparative analyses of the human microbiome have identified both taxonomic and functional shifts that are associated with numerous diseases. To date, however, microbiome taxonomy and function have mostly been studied independently and the taxonomic drivers of functional imbalances have not been systematically identified. Here, we present FishTaco, an analytical and computational framework that integrates taxonomic and functional comparative analyses to accurately quantify taxon-level contributions to disease-associated functional shifts. Applying FishTaco to several large-scale metagenomic cohorts, we show that shifts in the microbiome's functional capacity can be traced back to specific taxa. Furthermore, the set of taxa driving functional shifts and their contribution levels vary markedly between functions. We additionally find that similar functional imbalances in different diseases are driven by both disease-specific and shared taxa. Such integrated analysis of microbiome ecological and functional dynamics can inform future microbiome-based therapy, pinpointing putative intervention targets for manipulating the microbiome's functional capacity. Copyright © 2017 Elsevier Inc. All rights reserved.
Identification of Aspergillus sections Flavi, Nigri, and Fumigati and their differentiation using specific primers.

PubMed

Ashtiani, Nafiseh Mohebbi; Kachuei, Reza; Yalfani, Roozbeh; Harchegani, Asghar Beigi; Nosratabadi, Mohsen

2017-06-01

Aspergillus species are important in medicine, agriculture and various industries. The sections Fumigati, Flavi, and Nigri are the most important members of the Aspergillus genus. This study intended to identify and separate these three Aspergillus sections and to differentiate among them using specific primers. A bioinformatics study was initially performed to analyse the sequences of five genes, namely, beta-tubulin, calmodulin, the pre-rRNA processing protein Tsr1, the DNA-replication licensing factor Mcm7, and RNA polymerase II second largest subunit (RPB2) in the three Aspergillus sections using MEGA6 software and the NCBI database. Primers were designed to select genes for each of the Aspergillus sections being analysed. A total of 134 environmental and clinical Aspergillus species were isolated, purified and initially identified by colony morphology.. Subsequently, DNA was extracted using the phenol-chloroform method, specific primers were synthesized, PCR was performed for DNA from all isolates, and the results were compared to morphological characteristics. Of the 134 isolates tested, 56 were Nigri, 32 were Fumigati, 32 were Flavi, and the rest (14 isolates) belonged to other sections. The beta-tubulin and calmodulin genes were found to be the most suitable for differentiating among these three groups; the beta-tubulin gene was used for molecular identification of Aspergillus section Fumigati, and the calmodulin gene for identifying sections Flavi and Nigri.
Use of principal components analysis and protein microarray to explore the association of HIV-1-specific IgG responses with disease progression.

PubMed

Gerns Storey, Helen L; Richardson, Barbra A; Singa, Benson; Naulikha, Jackie; Prindle, Vivian C; Diaz-Ochoa, Vladimir E; Felgner, Phil L; Camerini, David; Horton, Helen; John-Stewart, Grace; Walson, Judd L

2014-01-01

The role of HIV-1-specific antibody responses in HIV disease progression is complex and would benefit from analysis techniques that examine clusterings of responses. Protein microarray platforms facilitate the simultaneous evaluation of numerous protein-specific antibody responses, though excessive data are cumbersome in analyses. Principal components analysis (PCA) reduces data dimensionality by generating fewer composite variables that maximally account for variance in a dataset. To identify clusters of antibody responses involved in disease control, we investigated the association of HIV-1-specific antibody responses by protein microarray, and assessed their association with disease progression using PCA in a nested cohort design. Associations observed among collections of antibody responses paralleled protein-specific responses. At baseline, greater antibody responses to the transmembrane glycoprotein (TM) and reverse transcriptase (RT) were associated with higher viral loads, while responses to the surface glycoprotein (SU), capsid (CA), matrix (MA), and integrase (IN) proteins were associated with lower viral loads. Over 12 months greater antibody responses were associated with smaller decreases in CD4 count (CA, MA, IN), and reduced likelihood of disease progression (CA, IN). PCA and protein microarray analyses highlighted a collection of HIV-specific antibody responses that together were associated with reduced disease progression, and may not have been identified by examining individual antibody responses. This technique may be useful to explore multifaceted host-disease interactions, such as HIV coinfections.
Species-specific PCR for the identification of Cooperia curticei (Nematoda: Trichostrongylidae) in sheep.

PubMed

Amarante, M R V; Bassetto, C C; Neves, J H; Amarante, A F T

2014-12-01

Agricultural ruminants usually harbour mixed infections of gastrointestinal nematodes. A specific diagnosis is important because distinct species can differ significantly in their fecundity and pathogenicity. Haemonchus spp. and Cooperia spp. are the most important gastrointestinal nematodes infecting ruminants in subtropical/tropical environments. In Brazil, C. punctata is more adapted to cattle than sheep. Additionally, C. spatulata appears to be more adapted to cattle, whereas C. curticei is more adapted to sheep. However, infection of sheep with C. punctata is common when cattle and sheep share the same pasture. Although morphological analyses have been widely used to identify nematodes, molecular methods can overcome technical limitations and help improve species-specific diagnoses. Genetic markers in the first and second internal transcribed spacers (ITS-1 and ITS-2, respectively) of nuclear ribosomal DNA (rDNA) have been used successfully to detect helminths. In the present study, the ITS-1 region was analysed and used to design a species-specific oligonucleotide primer pair to identify C. curticei. The polymerase chain reaction (PCR) product was sequenced and showed 97% similarity to C. oncophora partial ITS-1 clones and 99% similarity to the C. curticei sequence JF680982. The specificity of this primer pair was corroborated by the analysis of 17 species of helminths, including C. curticei, C. punctata and C. spatulata. Species-specific diagnosis, which has implications for rapid and reliable identification, can support studies on the biology, ecology and epidemiology of trichostrongylid nematodes in a particular geographical location.
Semiautomated TaqMan PCR screening of GMO labelled samples for (unauthorised) GMOs.

PubMed

Scholtens, Ingrid M J; Molenaar, Bonnie; van Hoof, Richard A; Zaaijer, Stephanie; Prins, Theo W; Kok, Esther J

2017-06-01

In most countries, systems are in place to analyse food products for the potential presence of genetically modified organisms (GMOs), to enforce labelling requirements and to screen for the potential presence of unauthorised GMOs. With the growing number of GMOs on the world market, a larger diversity of methods is required for informative analyses. In this paper, the specificity of an extended screening set consisting of 32 screening methods to identify different crop species (endogenous genes) and GMO elements was verified against 59 different GMO reference materials. In addition, a cost- and time-efficient strategy for DNA isolation, screening and identification is presented. A module for semiautomated analysis of the screening results and planning of subsequent event-specific tests for identification has been developed. The Excel-based module contains information on the experimentally verified specificity of the element methods and of the EU authorisation status of the GMO events. If a detected GMO element cannot be explained by any of the events as identified in the same sample, this may indicate the presence of an unknown unauthorised GMO that may not yet have been assessed for its safety for humans, animals or the environment.
Symptom-specific course trajectories and their determinants in primary care patients with Major Depressive Disorder: Evidence for two etiologically distinct prototypes.

PubMed

Wardenaar, K J; Monden, R; Conradi, H J; de Jonge, P

2015-07-01

The course-heterogeneity of Major Depressive Disorder (MDD) hampers development of better prognostic models. Although latent class growth analyses (LCGA) have been used to explain course-heterogeneity, such analyses have failed to also account for symptom-heterogeneity of depressive symptoms. Therefore, the aim was to identify more specific data-driven subgroups based on patterns of course-trajectories on different depressive symptom domains. In primary care MDD patients (n=205), the presence of the MDD criterion symptoms was determined for each week during a year. Weekly 'mood/cognition' (MC) and 'somatic' (SOM) scores were computed and parallel processes-LCGA (PP-LCGA) was used to identify subgroups based on the course on these domains. The classes׳ associations with baseline predictors and 2-/3-year outcomes were investigated. PP-LCGA identified four classes: quick recovery, persisting SOM, persisting MC, and persisting SOM+MC (chronic). Persisting SOM was specifically predicted by higher baseline somatic symptomatology and somatization, and was associated with more somatic depressive symptomatology at long-term follow-up. Persisting MC was specifically predicted by higher depressive severity, thinking insufficiencies, neuroticism, loneliness and lower self-esteem, and was associated with lower mental health related quality of life and more mood/cognitive depressive symptomatology at follow-up. The sample was small and contained only primary care MDD patients. The weekly depression assessments were collected retrospectively at 3-month intervals. The results indicate that there are two specific prototypes of depression, characterized by either persisting MC or persisting SOM, which have different sets of associated prognostic factors and long-term outcomes, and could have different etiological mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.
Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence

PubMed Central

Blevins, Tana; Aliev, Fazil; Adkins, Amy; Hack, Laura; Bigdeli, Tim; D. van der Vaart, Andrew; Web, Bradley Todd; Bacanu, Silviu-Alin; Kalsi, Gursharan; Kendler, Kenneth S.; Miles, Michael F.; Dick, Danielle; Riley, Brien P.; Dumur, Catherine; Vladimirov, Vladimir I.

2015-01-01

Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.05). Cell-type-specific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p≤ 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (χ2 test p≤ 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. PMID:26381263
Integrated omics analyses of retrograde signaling mutant delineate interrelated stress-response strata.

PubMed

Bjornson, Marta; Balcke, Gerd Ulrich; Xiao, Yanmei; de Souza, Amancio; Wang, Jin-Zheng; Zhabinskaya, Dina; Tagkopoulos, Ilias; Tissier, Alain; Dehesh, Katayoon

2017-07-01

To maintain homeostasis in the face of intrinsic and extrinsic insults, cells have evolved elaborate quality control networks to resolve damage at multiple levels. Interorganellar communication is a key requirement for this maintenance, however the underlying mechanisms of this communication have remained an enigma. Here we integrate the outcome of transcriptomic, proteomic, and metabolomics analyses of genotypes including ceh1, a mutant with constitutively elevated levels of both the stress-specific plastidial retrograde signaling metabolite methyl-erythritol cyclodiphosphate (MEcPP) and the defense hormone salicylic acid (SA), as well as the high MEcPP but SA deficient genotype ceh1/eds16, along with corresponding controls. Integration of multi-omic analyses enabled us to delineate the function of MEcPP from SA, and expose the compartmentalized role of this retrograde signaling metabolite in induction of distinct but interdependent signaling cascades instrumental in adaptive responses. Specifically, here we identify strata of MEcPP-sensitive stress-response cascades, among which we focus on selected pathways including organelle-specific regulation of jasmonate biosynthesis; simultaneous induction of synthesis and breakdown of SA; and MEcPP-mediated alteration of cellular redox status in particular glutathione redox balance. Collectively, these integrated multi-omic analyses provided a vehicle to gain an in-depth knowledge of genome-metabolism interactions, and to further probe the extent of these interactions and delineate their functional contributions. Through this approach we were able to pinpoint stress-mediated transcriptional and metabolic signatures and identify the downstream processes modulated by the independent or overlapping functions of MEcPP and SA in adaptive responses. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.
The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.

PubMed

Bizama, Carolina; Benavente, Felipe; Salvatierra, Edgardo; Gutiérrez-Moraga, Ana; Espinoza, Jaime A; Fernández, Elmer A; Roa, Iván; Mazzolini, Guillermo; Sagredo, Eduardo A; Gidekel, Manuel; Podhajcer, Osvaldo L

2014-02-15

Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer. © 2013 UICC.
Mining nutrigenetics patterns related to obesity: use of parallel multifactor dimensionality reduction.

PubMed

Karayianni, Katerina N; Grimaldi, Keith A; Nikita, Konstantina S; Valavanis, Ioannis K

2015-01-01

This paper aims to enlighten the complex etiology beneath obesity by analysing data from a large nutrigenetics study, in which nutritional and genetic factors associated with obesity were recorded for around two thousand individuals. In our previous work, these data have been analysed using artificial neural network methods, which identified optimised subsets of factors to predict one's obesity status. These methods did not reveal though how the selected factors interact with each other in the obtained predictive models. For that reason, parallel Multifactor Dimensionality Reduction (pMDR) was used here to further analyse the pre-selected subsets of nutrigenetic factors. Within pMDR, predictive models using up to eight factors were constructed, further reducing the input dimensionality, while rules describing the interactive effects of the selected factors were derived. In this way, it was possible to identify specific genetic variations and their interactive effects with particular nutritional factors, which are now under further study.
Cognitive context detection in UAS operators using eye-gaze patterns on computer screens

NASA Astrophysics Data System (ADS)

Mannaru, Pujitha; Balasingam, Balakumar; Pattipati, Krishna; Sibley, Ciara; Coyne, Joseph

2016-05-01

In this paper, we demonstrate the use of eye-gaze metrics of unmanned aerial systems (UAS) operators as effective indices of their cognitive workload. Our analyses are based on an experiment where twenty participants performed pre-scripted UAS missions of three different difficulty levels by interacting with two custom designed graphical user interfaces (GUIs) that are displayed side by side. First, we compute several eye-gaze metrics, traditional eye movement metrics as well as newly proposed ones, and analyze their effectiveness as cognitive classifiers. Most of the eye-gaze metrics are computed by dividing the computer screen into "cells". Then, we perform several analyses in order to select metrics for effective cognitive context classification related to our specific application; the objective of these analyses are to (i) identify appropriate ways to divide the screen into cells; (ii) select appropriate metrics for training and classification of cognitive features; and (iii) identify a suitable classification method.
Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained

PubMed Central

Wu, Ying; Waite, Lindsay L.; Jackson, Anne U.; Sheu, Wayne H-H.; Buyske, Steven; Absher, Devin; Arnett, Donna K.; Boerwinkle, Eric; Bonnycastle, Lori L.; Carty, Cara L.; Cheng, Iona; Cochran, Barbara; Croteau-Chonka, Damien C.; Dumitrescu, Logan; Eaton, Charles B.; Franceschini, Nora; Guo, Xiuqing; Henderson, Brian E.; Hindorff, Lucia A.; Kim, Eric; Kinnunen, Leena; Komulainen, Pirjo; Lee, Wen-Jane; Le Marchand, Loic; Lin, Yi; Lindström, Jaana; Lingaas-Holmen, Oddgeir; Mitchell, Sabrina L.; Narisu, Narisu; Robinson, Jennifer G.; Schumacher, Fred; Stančáková, Alena; Sundvall, Jouko; Sung, Yun-Ju; Swift, Amy J.; Wang, Wen-Chang; Wilkens, Lynne; Wilsgaard, Tom; Young, Alicia M.; Adair, Linda S.; Ballantyne, Christie M.; Bůžková, Petra; Chakravarti, Aravinda; Collins, Francis S.; Duggan, David; Feranil, Alan B.; Ho, Low-Tone; Hung, Yi-Jen; Hunt, Steven C.; Hveem, Kristian; Juang, Jyh-Ming J.; Kesäniemi, Antero Y.; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lee, I-Te; Leppert, Mark F.; Matise, Tara C.; Moilanen, Leena; Njølstad, Inger; Peters, Ulrike; Quertermous, Thomas; Rauramaa, Rainer; Rotter, Jerome I.; Saramies, Jouko; Tuomilehto, Jaakko; Uusitupa, Matti; Wang, Tzung-Dau; Mohlke, Karen L.

2013-01-01

Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1×10−4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies. PMID:23555291
Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

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

Xia, Jing; Rocke, David M.; Perry, George

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less
Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

DOE PAGES

Xia, Jing; Rocke, David M.; Perry, George; ...

2014-01-01

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less
Genetic Testing for Autism Spectrum Disorders

ERIC Educational Resources Information Center

Bauer, Sarah C.; Msall, Michael E.

2011-01-01

Children with autism spectrum disorders (ASD) have unique developmental and behavioral phenotypes, and they have specific challenges with communication, social skills, and repetitive behaviors. At this time, no single etiology for ASD has been identified. However, evidence from family studies and linkage analyses suggests that genetic factors play…
7 CFR 91.19 - General requirements of suitable samples.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the analyses requested. (b) Each sample must be identified with the following information: (1) Product... other information which is required by the specific program under which analysis or test is performed. ... LABORATORY TESTING PROGRAMS SERVICES AND GENERAL INFORMATION Samples § 91.19 General requirements of suitable...
7 CFR 91.19 - General requirements of suitable samples.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the analyses requested. (b) Each sample must be identified with the following information: (1) Product... other information which is required by the specific program under which analysis or test is performed. ... LABORATORY TESTING PROGRAMS SERVICES AND GENERAL INFORMATION Samples § 91.19 General requirements of suitable...
7 CFR 91.19 - General requirements of suitable samples.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the analyses requested. (b) Each sample must be identified with the following information: (1) Product... other information which is required by the specific program under which analysis or test is performed. ... LABORATORY TESTING PROGRAMS SERVICES AND GENERAL INFORMATION Samples § 91.19 General requirements of suitable...
7 CFR 91.19 - General requirements of suitable samples.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the analyses requested. (b) Each sample must be identified with the following information: (1) Product... other information which is required by the specific program under which analysis or test is performed. ... LABORATORY TESTING PROGRAMS SERVICES AND GENERAL INFORMATION Samples § 91.19 General requirements of suitable...
7 CFR 91.19 - General requirements of suitable samples.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the analyses requested. (b) Each sample must be identified with the following information: (1) Product... other information which is required by the specific program under which analysis or test is performed. ... LABORATORY TESTING PROGRAMS SERVICES AND GENERAL INFORMATION Samples § 91.19 General requirements of suitable...

Features of Computer-Based Decision Aids: Systematic Review, Thematic Synthesis, and Meta-Analyses.

PubMed

Syrowatka, Ania; Krömker, Dörthe; Meguerditchian, Ari N; Tamblyn, Robyn

2016-01-26

Patient information and education, such as decision aids, are gradually moving toward online, computer-based environments. Considerable research has been conducted to guide content and presentation of decision aids. However, given the relatively new shift to computer-based support, little attention has been given to how multimedia and interactivity can improve upon paper-based decision aids. The first objective of this review was to summarize published literature into a proposed classification of features that have been integrated into computer-based decision aids. Building on this classification, the second objective was to assess whether integration of specific features was associated with higher-quality decision making. Relevant studies were located by searching MEDLINE, Embase, CINAHL, and CENTRAL databases. The review identified studies that evaluated computer-based decision aids for adults faced with preference-sensitive medical decisions and reported quality of decision-making outcomes. A thematic synthesis was conducted to develop the classification of features. Subsequently, meta-analyses were conducted based on standardized mean differences (SMD) from randomized controlled trials (RCTs) that reported knowledge or decisional conflict. Further subgroup analyses compared pooled SMDs for decision aids that incorporated a specific feature to other computer-based decision aids that did not incorporate the feature, to assess whether specific features improved quality of decision making. Of 3541 unique publications, 58 studies met the target criteria and were included in the thematic synthesis. The synthesis identified six features: content control, tailoring, patient narratives, explicit values clarification, feedback, and social support. A subset of 26 RCTs from the thematic synthesis was used to conduct the meta-analyses. As expected, computer-based decision aids performed better than usual care or alternative aids; however, some features performed better than others. Integration of content control improved quality of decision making (SMD 0.59 vs 0.23 for knowledge; SMD 0.39 vs 0.29 for decisional conflict). In contrast, tailoring reduced quality of decision making (SMD 0.40 vs 0.71 for knowledge; SMD 0.25 vs 0.52 for decisional conflict). Similarly, patient narratives also reduced quality of decision making (SMD 0.43 vs 0.65 for knowledge; SMD 0.17 vs 0.46 for decisional conflict). Results were varied for different types of explicit values clarification, feedback, and social support. Integration of media rich or interactive features into computer-based decision aids can improve quality of preference-sensitive decision making. However, this is an emerging field with limited evidence to guide use. The systematic review and thematic synthesis identified features that have been integrated into available computer-based decision aids, in an effort to facilitate reporting of these features and to promote integration of such features into decision aids. The meta-analyses and associated subgroup analyses provide preliminary evidence to support integration of specific features into future decision aids. Further research can focus on clarifying independent contributions of specific features through experimental designs and refining the designs of features to improve effectiveness.
Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.

PubMed

Musolf, Anthony M; Simpson, Claire L; Moiz, Bilal A; Long, Kyle A; Portas, Laura; Murgia, Federico; Ciner, Elise B; Stambolian, Dwight; Bailey-Wilson, Joan E

2017-07-01

Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.
Mapping the pericentric heterochromatin by comparative genomic hybridization analysis and chromosome deletions in Drosophila melanogaster

PubMed Central

He, Bing; Caudy, Amy; Parsons, Lance; Rosebrock, Adam; Pane, Attilio; Raj, Sandeep; Wieschaus, Eric

2012-01-01

Heterochromatin represents a significant portion of eukaryotic genomes and has essential structural and regulatory functions. Its molecular organization is largely unknown due to difficulties in sequencing through and assembling repetitive sequences enriched in the heterochromatin. Here we developed a novel strategy using chromosomal rearrangements and embryonic phenotypes to position unmapped Drosophila melanogaster heterochromatic sequence to specific chromosomal regions. By excluding sequences that can be mapped to the assembled euchromatic arms, we identified sequences that are specific to heterochromatin and used them to design heterochromatin specific probes (“H-probes”) for microarray. By comparative genomic hybridization (CGH) analyses of embryos deficient for each chromosome or chromosome arm, we were able to map most of our H-probes to specific chromosome arms. We also positioned sequences mapped to the second and X chromosomes to finer intervals by analyzing smaller deletions with breakpoints in heterochromatin. Using this approach, we were able to map >40% (13.9 Mb) of the previously unmapped heterochromatin sequences assembled by the whole-genome sequencing effort on arm U and arm Uextra to specific locations. We also identified and mapped 110 kb of novel heterochromatic sequences. Subsequent analyses revealed that sequences located within different heterochromatic regions have distinct properties, such as sequence composition, degree of repetitiveness, and level of underreplication in polytenized tissues. Surprisingly, although heterochromatin is generally considered to be transcriptionally silent, we detected region-specific temporal patterns of transcription in heterochromatin during oogenesis and early embryonic development. Our study provides a useful approach to elucidate the molecular organization and function of heterochromatin and reveals region-specific variation of heterochromatin. PMID:22745230
A site specific model and analysis of the neutral somatic mutation rate in whole-genome cancer data.

PubMed

Bertl, Johanna; Guo, Qianyun; Juul, Malene; Besenbacher, Søren; Nielsen, Morten Muhlig; Hornshøj, Henrik; Pedersen, Jakob Skou; Hobolth, Asger

2018-04-19

Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation rate differs between cancer types, between patients and along the genome depending on the genetic and epigenetic context. Therefore, methods that predict the number of different types of mutations in regions or specific genomic elements must consider local genomic explanatory variables. A major drawback of most methods is the need to average the explanatory variables across the entire region or genomic element. This procedure is particularly problematic if the explanatory variable varies dramatically in the element under consideration. To take into account the fine scale of the explanatory variables, we model the probabilities of different types of mutations for each position in the genome by multinomial logistic regression. We analyse 505 cancer genomes from 14 different cancer types and compare the performance in predicting mutation rate for both regional based models and site-specific models. We show that for 1000 randomly selected genomic positions, the site-specific model predicts the mutation rate much better than regional based models. We use a forward selection procedure to identify the most important explanatory variables. The procedure identifies site-specific conservation (phyloP), replication timing, and expression level as the best predictors for the mutation rate. Finally, our model confirms and quantifies certain well-known mutational signatures. We find that our site-specific multinomial regression model outperforms the regional based models. The possibility of including genomic variables on different scales and patient specific variables makes it a versatile framework for studying different mutational mechanisms. Our model can serve as the neutral null model for the mutational process; regions that deviate from the null model are candidates for elements that drive cancer development.
IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN THE KIDNEYS OF GROWTH HORMONE TRANSGENIC MICE

PubMed Central

Coschigano, K.T.; Wetzel, A.N.; Obichere, N.; Sharma, A.; Lee, S.; Rasch, R.; Guigneaux, M.M.; Flyvbjerg, A.; Wood, T.G.; Kopchick, J.J.

2010-01-01

Objective Bovine growth hormone (bGH) transgenic mice develop severe kidney damage. This damage may be due, at least in part, to changes in gene expression. Identification of genes with altered expression in the bGH kidney may identify mechanisms leading to damage in this system that may also be relevant to other models of kidney damage. Design cDNA subtraction libraries, northern blot analyses, microarray analyses and real-time reverse transcription polymerase chain reaction (RT/PCR) assays were used to identify and verify specific genes exhibiting differential RNA expression between kidneys of bGH mice and their non-transgenic (NT) littermates. Results Immunoglobulins were the vast majority of genes identified by the cDNA subtractions and the microarray analyses as being up-regulated in bGH. Several glycoprotein genes and inflammation-related genes also showed increased RNA expression in the bGH kidney. In contrast, only a few genes were identified as being significantly down-regulated in the bGH kidney. The most notable decrease in RNA expression was for the gene encoding kidney androgen-regulated protein. Conclusions A number of genes were identified as being differentially expressed in the bGH kidney. Inclusion of two groups, immunoglobulins and inflammation-related genes, suggests a role of the immune system in bGH kidney damage. PMID:20655258
Rare copy number variants in patients with congenital conotruncal heart defects.

PubMed

Xie, Hongbo M; Werner, Petra; Stambolian, Dwight; Bailey-Wilson, Joan E; Hakonarson, Hakon; White, Peter S; Taylor, Deanne M; Goldmuntz, Elizabeth

2017-03-01

Previous studies using different cardiac phenotypes, technologies and designs suggest a burden of large, rare or de novo copy number variants (CNVs) in subjects with congenital heart defects. We sought to identify disease-related CNVs, candidate genes, and functional pathways in a large number of cases with conotruncal and related defects that carried no known genetic syndrome. Cases and control samples were divided into two cohorts and genotyped to assess each subject's CNV content. Analyses were performed to ascertain differences in overall CNV prevalence and to identify enrichment of specific genes and functional pathways in conotruncal cases relative to healthy controls. Only findings present in both cohorts are presented. From 973 total conotruncal cases, a burden of rare CNVs was detected in both cohorts. Candidate genes from rare CNVs found in both cohorts were identified based on their association with cardiac development or disease, and/or their reported disruption in published studies. Functional and pathway analyses revealed significant enrichment of terms involved in either heart or early embryonic development. Our study tested one of the largest cohorts specifically with cardiac conotruncal and related defects. These results confirm and extend previous findings that CNVs contribute to disease risk for congenital heart defects in general and conotruncal defects in particular. As disease heterogeneity renders identification of single recurrent genes or loci difficult, functional pathway and gene regulation network analyses appear to be more informative. Birth Defects Research 109:271-295, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
RNA-Seq analysis of isolate- and growth phase-specific differences in the global transcriptomes of enteropathogenic Escherichia coli prototype isolates

PubMed Central

Hazen, Tracy H.; Daugherty, Sean C.; Shetty, Amol; Mahurkar, Anup A.; White, Owen; Kaper, James B.; Rasko, David A.

2015-01-01

Enteropathogenic Escherichia coli (EPEC) are a leading cause of diarrheal illness among infants in developing countries. E. coli isolates classified as typical EPEC are identified by the presence of the locus of enterocyte effacement (LEE) and the bundle-forming pilus (BFP), and absence of the Shiga-toxin genes, while the atypical EPEC also encode LEE but do not encode BFP or Shiga-toxin. Comparative genomic analyses have demonstrated that EPEC isolates belong to diverse evolutionary lineages and possess lineage- and isolate-specific genomic content. To investigate whether this genomic diversity results in significant differences in global gene expression, we used an RNA sequencing (RNA-Seq) approach to characterize the global transcriptomes of the prototype typical EPEC isolates E2348/69, B171, C581-05, and the prototype atypical EPEC isolate E110019. The global transcriptomes were characterized during laboratory growth in two different media and three different growth phases, as well as during adherence of the EPEC isolates to human cells using in vitro tissue culture assays. Comparison of the global transcriptomes during these conditions was used to identify isolate- and growth phase-specific differences in EPEC gene expression. These analyses resulted in the identification of genes that encode proteins involved in survival and metabolism that were coordinately expressed with virulence factors. These findings demonstrate there are isolate- and growth phase-specific differences in the global transcriptomes of EPEC prototype isolates, and highlight the utility of comparative transcriptomics for identifying additional factors that are directly or indirectly involved in EPEC pathogenesis. PMID:26124752
Structural and mutational analyses of dipeptidyl peptidase 11 from Porphyromonas gingivalis reveal the molecular basis for strict substrate specificity

PubMed Central

Sakamoto, Yasumitsu; Suzuki, Yoshiyuki; Iizuka, Ippei; Tateoka, Chika; Roppongi, Saori; Fujimoto, Mayu; Inaka, Koji; Tanaka, Hiroaki; Yamada, Mitsugu; Ohta, Kazunori; Gouda, Hiroaki; Nonaka, Takamasa; Ogasawara, Wataru; Tanaka, Nobutada

2015-01-01

The dipeptidyl peptidase 11 from Porphyromonas gingivalis (PgDPP11) belongs to the S46 family of serine peptidases and preferentially cleaves substrates with Asp/Glu at the P1 position. The molecular mechanism underlying the substrate specificity of PgDPP11, however, is unknown. Here, we report the crystal structure of PgDPP11. The enzyme contains a catalytic domain with a typical double β-barrel fold and a recently identified regulatory α-helical domain. Crystal structure analyses, docking studies, and biochemical studies revealed that the side chain of Arg673 in the S1 subsite is essential for recognition of the Asp/Glu side chain at the P1 position of the bound substrate. Because S46 peptidases are not found in mammals and the Arg673 is conserved among DPP11s, we anticipate that DPP11s could be utilised as targets for antibiotics. In addition, the present structure analyses could be useful templates for the design of specific inhibitors of DPP11s from pathogenic organisms. PMID:26057589
Role of man in flight experiment payloads, phase 1. [Spacelab mission planning

NASA Technical Reports Server (NTRS)

Malone, T. B.; Kirkpatrick, M.

1974-01-01

The identification of required data for studies of Spacelab experiment functional allocation, the development of an approach to collecting these data from the payload community, and the specification of analytical methods necessary to quantitatively determine the role of man in specific Spacelab experiments are presented. A generalized Spacelab experiment operation sequence was developed, and the parameters necessary to describe each signle function in the sequence were identified. A set of functional descriptor worksheets were also drawn up. The methodological approach to defining the role of man was defined as a series of trade studies using a digial simulation technique. The tradeoff variables identified include scientific crew size, skill mix, and location. An existing digital simulation program suitable for the required analyses was identified and obtained.
Differentially co-expressed interacting protein pairs discriminate samples under distinct stages of HIV type 1 infection.

PubMed

Yoon, Dukyong; Kim, Hyosil; Suh-Kim, Haeyoung; Park, Rae Woong; Lee, KiYoung

2011-01-01

Microarray analyses based on differentially expressed genes (DEGs) have been widely used to distinguish samples across different cellular conditions. However, studies based on DEGs have not been able to clearly determine significant differences between samples of pathophysiologically similar HIV-1 stages, e.g., between acute and chronic progressive (or AIDS) or between uninfected and clinically latent stages. We here suggest a novel approach to allow such discrimination based on stage-specific genetic features of HIV-1 infection. Our approach is based on co-expression changes of genes known to interact. The method can identify a genetic signature for a single sample as contrasted with existing protein-protein-based analyses with correlational designs. Our approach distinguishes each sample using differentially co-expressed interacting protein pairs (DEPs) based on co-expression scores of individual interacting pairs within a sample. The co-expression score has positive value if two genes in a sample are simultaneously up-regulated or down-regulated. And the score has higher absolute value if expression-changing ratios are similar between the two genes. We compared characteristics of DEPs with that of DEGs by evaluating their usefulness in separation of HIV-1 stage. And we identified DEP-based network-modules and their gene-ontology enrichment to find out the HIV-1 stage-specific gene signature. Based on the DEP approach, we observed clear separation among samples from distinct HIV-1 stages using clustering and principal component analyses. Moreover, the discrimination power of DEPs on the samples (70-100% accuracy) was much higher than that of DEGs (35-45%) using several well-known classifiers. DEP-based network analysis also revealed the HIV-1 stage-specific network modules; the main biological processes were related to "translation," "RNA splicing," "mRNA, RNA, and nucleic acid transport," and "DNA metabolism." Through the HIV-1 stage-related modules, changing stage-specific patterns of protein interactions could be observed. DEP-based method discriminated the HIV-1 infection stages clearly, and revealed a HIV-1 stage-specific gene signature. The proposed DEP-based method might complement existing DEG-based approaches in various microarray expression analyses.
Job hunting in the UK using the Internet: finding your next information professional role in the health care sector and the skills employers require.

PubMed

Davies, Karen

2008-06-01

The aim of this article is to analyse 'professional' health information vacancies advertised on three specific websites for 6 months from 1 April 2006 (to 30 September 2006). The objectives for this research were to identify the frequency of health information vacancies advertised on three specified websites and on an e-mail discussion group. Each fortnight all health-related vacancies advertised directly by the hiring organizations were identified. The job descriptions and person specifications for relevant vacancies were either downloaded or requested from the hiring organization. The main criteria for determining the relevance of a vacancy was that a degree or higher qualification in an information-related subject was 'essential' or 'desirable with previous experience'. The core skills and experiences required from the job descriptions and person specifications for professional health information posts were identified. The results highlight the importance of the Internet in locating suitable vacancies. However, not one website listed all the potential job opportunities. The importance of information technology (IT) skills (including literature searching) and teaching skills were identified from the person specifications and job descriptions. The Internet is a useful tool for identifying health-related employment opportunities. However, to obtain a full list of vacancies, several websites must be searched.
Jerky driving--An indicator of accident proneness?

PubMed

Bagdadi, Omar; Várhelyi, András

2011-07-01

This study uses continuously logged driving data from 166 private cars to derive the level of jerks caused by the drivers during everyday driving. The number of critical jerks found in the data is analysed and compared with the self-reported accident involvement of the drivers. The results show that the expected number of accidents for a driver increases with the number of critical jerks caused by the driver. Jerk analyses make it possible to identify safety critical driving behaviour or "accident prone" drivers. They also facilitate the development of safety measures such as active safety systems or advanced driver assistance systems, ADAS, which could be adapted for specific groups of drivers or specific risky driving behaviour. Copyright © 2011 Elsevier Ltd. All rights reserved.
A Discovery Genome-Wide Association Study of Entrepreneurship

ERIC Educational Resources Information Center

Quaye, Lydia; Nicolaou, Nicos; Shane, Scott; Mangino, Massimo

2012-01-01

To identify specific genetic variants influencing the phenotype of entrepreneurship, we conducted a genome-wide association study (GWAS) with 3,933 Caucasian females from the TwinsUK Adult Twin Registry. Following stringent genotype quality control, GWAF (genome-wide association analyses for family data) software was used to assess the association…
A decision-support framework for using value capture to fund public transit : lessons from project-specific analyses [research brief].

DOT National Transportation Integrated Search

2012-05-01

Fiscal belt-tightening at all levels of government has lent urgency to identifying alternate sources of funding for public transportation. Value capture (VC) is one such source. Based on the benefits received principle, VC captures public infra...
Sediments as tracers for transport and deposition processes in peri-alpine lakes: A case study

NASA Astrophysics Data System (ADS)

Righetti, Maurizio; Toffolon, Marco; Lucarelli, Corrado; Serafini, Michele

2011-12-01

SummaryThe benthic sediment fingerprint is analysed in the small peri-alpine lake Levico (Trentino, Italy) to identify the causes of recurrent phenomena of turbidity peaks, particularly evident in a littoral region of the water body. In order to study the sediment transport processes, we exploit the fact that the sediment supply from the major tributary has a specific chemical composition, which differs from that of the nearby lake basin. Three elements (Fe, Al, K) have been used as tracers to identify the source and the deposition patterns of tributary sediments, and another typical element, Si, has been critically analysed because of its dual (allochthonous and autochthonous) origin. Several samples of the benthic material have been analysed using SEM-EDS, and the results of the sedimentological characterisation have been compared with the patterns of sediment accumulation at the bed of the lake obtained using a three-dimensional numerical model, in response to the tributary supply under different external forcing and stratification conditions. The coupled use of field measurements and numerical results suggests that the turbidity phenomena are strongly related to the deposition of the sediments supplied by the tributary stream, and shows that it is possible to reconstruct the process of local transport when the tributary inflow is chemically specific.
Sex-biased gene expression and sequence conservation in Atlantic and Pacific salmon lice (Lepeophtheirus salmonis).

PubMed

Poley, Jordan D; Sutherland, Ben J G; Jones, Simon R M; Koop, Ben F; Fast, Mark D

2016-07-04

Salmon lice, Lepeophtheirus salmonis (Copepoda: Caligidae), are highly important ectoparasites of farmed and wild salmonids, and cause multi-million dollar losses to the salmon aquaculture industry annually. Salmon lice display extensive sexual dimorphism in ontogeny, morphology, physiology, behavior, and more. Therefore, the identification of transcripts with differential expression between males and females (sex-biased transcripts) may help elucidate the relationship between sexual selection and sexually dimorphic characteristics. Sex-biased transcripts were identified from transcriptome analyses of three L. salmonis populations, including both Atlantic and Pacific subspecies. A total of 35-43 % of all quality-filtered transcripts were sex-biased in L. salmonis, with male-biased transcripts exhibiting higher fold change than female-biased transcripts. For Gene Ontology and functional analyses, a consensus-based approach was used to identify concordantly differentially expressed sex-biased transcripts across the three populations. A total of 127 male-specific transcripts (i.e. those without detectable expression in any female) were identified, and were enriched with reproductive functions (e.g. seminal fluid and male accessory gland proteins). Other sex-biased transcripts involved in morphogenesis, feeding, energy generation, and sensory and immune system development and function were also identified. Interestingly, as observed in model systems, male-biased L. salmonis transcripts were more frequently without annotation compared to female-biased or unbiased transcripts, suggesting higher rates of sequence divergence in male-biased transcripts. Transcriptome differences between male and female L. salmonis described here provide key insights into the molecular mechanisms controlling sexual dimorphism in L. salmonis. This analysis offers targets for parasite control and provides a foundation for further analyses exploring critical topics such as the interaction between sex and drug resistance, sex-specific factors in host-parasite relationships, and reproductive roles within L. salmonis.
Sensitivity and Specificity of Polysomnographic Criteria for Defining Insomnia

PubMed Central

Edinger, Jack D.; Ulmer, Christi S.; Means, Melanie K.

2013-01-01

Study Objectives: In recent years, polysomnography-based eligibility criteria have been increasingly used to identify candidates for insomnia research, and this has been particularly true of studies evaluating pharmacologic therapy for primary insomnia. However, the sensitivity and specificity of PSG for identifying individuals with insomnia is unknown, and there is no consensus on the criteria sets which should be used for participant selection. In the current study, an archival data set was used to test the sensitivity and specificity of PSG measures for identifying individuals with primary insomnia in both home and lab settings. We then evaluated the sensitivity and specificity of the eligibility criteria employed in a number of recent insomnia trials for identifying primary insomnia sufferers in our sample. Design: Archival data analysis. Settings: Study participants' homes and a clinical sleep laboratory. Participants: Adults: 76 with primary insomnia and 78 non-complaining normal sleepers. Measurements and Results: ROC and cross-tabs analyses were used to evaluate the sensitivity and specificity of PSG-derived total sleep time, latency to persistent sleep, wake after sleep onset, and sleep efficiency for discriminating adults with primary insomnia from normal sleepers. None of the individual criteria accurately discriminated PI from normal sleepers, and none of the criteria sets used in recent trials demonstrated acceptable sensitivity and specificity for identifying primary insomnia. Conclusions: The use of quantitative PSG-based selection criteria in insomnia research may exclude many who meet current diagnostic criteria for an insomnia disorder. Citation: Edinger JD; Ulmer CS; Means MK. Sensitivity and specificity of polysomnographic criteria for defining insomnia. J Clin Sleep Med 2013;9(5):481-491. PMID:23674940
Landscape of Conditional eQTL in Dorsolateral Prefrontal Cortex and Co-localization with Schizophrenia GWAS.

PubMed

Dobbyn, Amanda; Huckins, Laura M; Boocock, James; Sloofman, Laura G; Glicksberg, Benjamin S; Giambartolomei, Claudia; Hoffman, Gabriel E; Perumal, Thanneer M; Girdhar, Kiran; Jiang, Yan; Raj, Towfique; Ruderfer, Douglas M; Kramer, Robin S; Pinto, Dalila; Akbarian, Schahram; Roussos, Panos; Domenici, Enrico; Devlin, Bernie; Sklar, Pamela; Stahl, Eli A; Sieberts, Solveig K

2018-06-07

Causal genes and variants within genome-wide association study (GWAS) loci can be identified by integrating GWAS statistics with expression quantitative trait loci (eQTL) and determining which variants underlie both GWAS and eQTL signals. Most analyses, however, consider only the marginal eQTL signal, rather than dissect this signal into multiple conditionally independent signals for each gene. Here we show that analyzing conditional eQTL signatures, which could be important under specific cellular or temporal contexts, leads to improved fine mapping of GWAS associations. Using genotypes and gene expression levels from post-mortem human brain samples (n = 467) reported by the CommonMind Consortium (CMC), we find that conditional eQTL are widespread; 63% of genes with primary eQTL also have conditional eQTL. In addition, genomic features associated with conditional eQTL are consistent with context-specific (e.g., tissue-, cell type-, or developmental time point-specific) regulation of gene expression. Integrating the 2014 Psychiatric Genomics Consortium schizophrenia (SCZ) GWAS and CMC primary and conditional eQTL data reveals 40 loci with strong evidence for co-localization (posterior probability > 0.8), including six loci with co-localization of conditional eQTL. Our co-localization analyses support previously reported genes, identify novel genes associated with schizophrenia risk, and provide specific hypotheses for their functional follow-up. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
New Insights into the Classification and Integration Specificity of Streptococcus Integrative Conjugative Elements through Extensive Genome Exploration

PubMed Central

Ambroset, Chloé; Coluzzi, Charles; Guédon, Gérard; Devignes, Marie-Dominique; Loux, Valentin; Lacroix, Thomas; Payot, Sophie; Leblond-Bourget, Nathalie

2016-01-01

Recent genome analyses suggest that integrative and conjugative elements (ICEs) are widespread in bacterial genomes and therefore play an essential role in horizontal transfer. However, only a few of these elements are precisely characterized and correctly delineated within sequenced bacterial genomes. Even though previous analysis showed the presence of ICEs in some species of Streptococci, the global prevalence and diversity of ICEs was not analyzed in this genus. In this study, we searched for ICEs in the completely sequenced genomes of 124 strains belonging to 27 streptococcal species. These exhaustive analyses revealed 105 putative ICEs and 26 slightly decayed elements whose limits were assessed and whose insertion site was identified. These ICEs were grouped in seven distinct unrelated or distantly related families, according to their conjugation modules. Integration of these streptococcal ICEs is catalyzed either by a site-specific tyrosine integrase, a low-specificity tyrosine integrase, a site-specific single serine integrase, a triplet of site-specific serine integrases or a DDE transposase. Analysis of their integration site led to the detection of 18 target-genes for streptococcal ICE insertion including eight that had not been identified previously (ftsK, guaA, lysS, mutT, rpmG, rpsI, traG, and ebfC). It also suggests that all specificities have evolved to minimize the impact of the insertion on the host. This overall analysis of streptococcal ICEs emphasizes their prevalence and diversity and demonstrates that exchanges or acquisitions of conjugation and recombination modules are frequent. PMID:26779141
New Insights into the Classification and Integration Specificity of Streptococcus Integrative Conjugative Elements through Extensive Genome Exploration.

PubMed

Ambroset, Chloé; Coluzzi, Charles; Guédon, Gérard; Devignes, Marie-Dominique; Loux, Valentin; Lacroix, Thomas; Payot, Sophie; Leblond-Bourget, Nathalie

2015-01-01

Recent genome analyses suggest that integrative and conjugative elements (ICEs) are widespread in bacterial genomes and therefore play an essential role in horizontal transfer. However, only a few of these elements are precisely characterized and correctly delineated within sequenced bacterial genomes. Even though previous analysis showed the presence of ICEs in some species of Streptococci, the global prevalence and diversity of ICEs was not analyzed in this genus. In this study, we searched for ICEs in the completely sequenced genomes of 124 strains belonging to 27 streptococcal species. These exhaustive analyses revealed 105 putative ICEs and 26 slightly decayed elements whose limits were assessed and whose insertion site was identified. These ICEs were grouped in seven distinct unrelated or distantly related families, according to their conjugation modules. Integration of these streptococcal ICEs is catalyzed either by a site-specific tyrosine integrase, a low-specificity tyrosine integrase, a site-specific single serine integrase, a triplet of site-specific serine integrases or a DDE transposase. Analysis of their integration site led to the detection of 18 target-genes for streptococcal ICE insertion including eight that had not been identified previously (ftsK, guaA, lysS, mutT, rpmG, rpsI, traG, and ebfC). It also suggests that all specificities have evolved to minimize the impact of the insertion on the host. This overall analysis of streptococcal ICEs emphasizes their prevalence and diversity and demonstrates that exchanges or acquisitions of conjugation and recombination modules are frequent.

Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.

PubMed

Chen, Xiaowei Sylvia; Reader, Rose H; Hoischen, Alexander; Veltman, Joris A; Simpson, Nuala H; Francks, Clyde; Newbury, Dianne F; Fisher, Simon E

2017-04-25

A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential "multiple-hit" cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation.
Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment

PubMed Central

Chen, Xiaowei Sylvia; Reader, Rose H.; Hoischen, Alexander; Veltman, Joris A.; Simpson, Nuala H.; Francks, Clyde; Newbury, Dianne F.; Fisher, Simon E.

2017-01-01

A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential “multiple-hit” cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation. PMID:28440294
Large-scale transcriptome sequencing and gene analyses in the crab-eating macaque (Macaca fascicularis) for biomedical research

PubMed Central

2012-01-01

Background As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable non-human primate model for biomedical research, but the lack of genetic information on this primate has represented a significant obstacle for its broader use. Results Here, we sequenced the transcriptome of 16 tissues originated from two individuals of crab-eating macaque (male and female), and identified genes to resolve the main obstacles for understanding the biological response of the crab-eating macaque. From 4 million reads with 1.4 billion base sequences, 31,786 isotigs containing genes similar to those of humans, 12,672 novel isotigs, and 348,160 singletons were identified using the GS FLX sequencing method. Approximately 86% of human genes were represented among the genes sequenced in this study. Additionally, 175 tissue-specific transcripts were identified, 81 of which were experimentally validated. In total, 4,314 alternative splicing (AS) events were identified and analyzed. Intriguingly, 10.4% of AS events were associated with transposable element (TE) insertions. Finally, investigation of TE exonization events and evolutionary analysis were conducted, revealing interesting phenomena of human-specific amplified trends in TE exonization events. Conclusions This report represents the first large-scale transcriptome sequencing and genetic analyses of M. fascicularis and could contribute to its utility for biomedical research and basic biology. PMID:22554259
Mitochondrial electron transport chain identified as a novel molecular target of SPIO nanoparticles mediated cancer-specific cytotoxicity.

PubMed

He, Chengyong; Jiang, Shengwei; Jin, Haijing; Chen, Shuzhen; Lin, Gan; Yao, Huan; Wang, Xiaoyong; Mi, Peng; Ji, Zhiliang; Lin, Yuchun; Lin, Zhongning; Liu, Gang

2016-03-01

Superparamagnetic iron oxide nanoparticles (SPIONs) are highly cytotoxic and target cancer cells with high specificity; however, the mechanism by which SPIONs induce cancer cell-specific cytotoxicity remains unclear. Herein, the molecular mechanism of SPION-induced cancer cell-specific cytotoxicity to cancer cells is clarified through DNA microarray and bioinformatics analyses. SPIONs can interference with the mitochondrial electron transport chain (METC) in cancer cells, which further affects the production of ATP, mitochondrial membrane potential, and microdistribution of calcium, and induces cell apoptosis. Additionally, SPIONs induce the formation of reactive oxygen species in mitochondria; these reactive oxygen species trigger cancer-specific cytotoxicity due to the lower antioxidative capacity of cancer cells. Moreover, the DNA microarray and gene ontology analyses revealed that SPIONs elevate the expression of metallothioneins in both normal and cancer cells but decrease the expression of METC genes in cancer cells. Overall, these results suggest that SPIONs induce cancer cell death by targeting the METC, which is helpful for designing anti-cancer nanotheranostics and evaluating the safety of future nanomedicines. Copyright © 2016 Elsevier Ltd. All rights reserved.
Characteristics of highly rated leadership in nursing homes using item response theory.

PubMed

Backman, Annica; Sjögren, Karin; Lindkvist, Marie; Lövheim, Hugo; Edvardsson, David

2017-12-01

To identify characteristics of highly rated leadership in nursing homes. An ageing population entails fundamental social, economic and organizational challenges for future aged care. Knowledge is limited of both specific leadership behaviours and organizational and managerial characteristics which have an impact on the leadership of contemporary nursing home care. Cross-sectional. From 290 municipalities, 60 were randomly selected and 35 agreed to participate, providing a sample of 3605 direct-care staff employed in 169 Swedish nursing homes. The staff assessed their managers' (n = 191) leadership behaviours using the Leadership Behaviour Questionnaire. Data were collected from November 2013 - September 2014, and the study was completed in November 2016. A two-parameter item response theory approach and regression analyses were used to identify specific characteristics of highly rated leadership. Five specific behaviours of highly rated nursing home leadership were identified; that the manager: experiments with new ideas; controls work closely; relies on subordinates; coaches and gives direct feedback; and handles conflicts constructively. The regression analyses revealed that managers with social work backgrounds and privately run homes were significantly associated with higher leadership ratings. This study highlights the five most important leadership behaviours that characterize those nursing home managers rated highest in terms of leadership. Managers in privately run nursing homes and managers with social work backgrounds were associated with higher leadership ratings. Further work is needed to explore these behaviours and factors predictive of higher leadership ratings. © 2017 John Wiley & Sons Ltd.
Single-cell transcriptomes identify human islet cell signatures and reveal cell-type–specific expression changes in type 2 diabetes

PubMed Central

Bolisetty, Mohan; Kursawe, Romy; Sun, Lili; Sivakamasundari, V.; Kycia, Ina

2017-01-01

Blood glucose levels are tightly controlled by the coordinated action of at least four cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 (T2D) diabetes. Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet (dys)function, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single-cell transcriptomes for 638 cells from nondiabetic (ND) and T2D human islet samples. Analyses of ND single-cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single-cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell-type–specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis. PMID:27864352
Transcriptomic profiling of Melon necrotic spot virus-infected melon plants revealed virus strain and plant cultivar-specific alterations.

PubMed

Gómez-Aix, Cristina; Pascual, Laura; Cañizares, Joaquín; Sánchez-Pina, María Amelia; Aranda, Miguel A

2016-06-07

Viruses are among the most destructive and difficult to control plant pathogens. Melon (Cucumis melo L.) has become the model species for the agriculturally important Cucurbitaceae family. Approaches that take advantage of recently developed genomic tools in melon have been extremely useful for understanding viral pathogenesis and can contribute to the identification of target genes for breeding new resistant cultivars. In this work, we have used a recently described melon microarray for transcriptome profiling of two melon cultivars infected with two strains of Melon necrotic spot virus (MNSV) that only differ on their 3'-untranslated regions. Melon plant tissues from the cultivars Tendral or Planters Jumbo were locally infected with either MNSV-Mα5 or MNSV-Mα5/3'264 and analysed in a time-course experiment. Principal component and hierarchical clustering analyses identified treatment (healthy vs. infected) and sampling date (3 vs. 5 dpi) as the primary and secondary variables, respectively. Out of 7566 and 7074 genes deregulated by MNSV-Mα5 and MNSV-Mα5/3'264, 1851 and 1356, respectively, were strain-specific. Likewise, MNSV-Mα5/3'264 specifically deregulated 2925 and 1618 genes in Tendral and Planters Jumbo, respectively. The GO categories that were significantly affected were clearly different for the different virus/host combinations. Grouping genes according to their patterns of expression allowed for the identification of two groups that were specifically deregulated by MNSV-Mα5/3'264 with respect to MNSV-Mα5 in Tendral, and one group that was antagonistically regulated in Planters Jumbo vs. Tendral after MNSV-Mα5/3'264 infection. Genes in these three groups belonged to diverse functional classes, and no obvious regulatory commonalities were identified. When data on MNSV-Mα5/Tendral infections were compared to equivalent data on cucumber mosaic virus or watermelon mosaic virus infections, cytokinin-O-glucosyltransferase2 was identified as the only gene that was deregulated by all three viruses, with infection dynamics correlating with the amplitude of transcriptome remodeling. Strain-specific changes, as well as cultivar-specific changes, were identified by profiling the transcriptomes of plants from two melon cultivars infected with two MNSV strains. No obvious regulatory features shared among deregulated genes have been identified, pointing toward regulation through differential functional pathways.
Using genome wide association studies to identify common QTL regions in three different genetic backgrounds based on Iberian pig breed.

PubMed

Martínez-Montes, Ángel M; Fernández, Almudena; Muñoz, María; Noguera, Jose Luis; Folch, Josep M; Fernández, Ana I

2018-01-01

One of the major limitation for the application of QTL results in pig breeding and QTN identification has been the limited number of QTL effects validated in different animal material. The aim of the current work was to validate QTL regions through joint and specific genome wide association and haplotype analyses for growth, fatness and premier cut weights in three different genetic backgrounds, backcrosses based on Iberian pigs, which has a major role in the analysis due to its high productive relevance. The results revealed nine common QTL regions, three segregating in all three backcrosses on SSC1, 0-3 Mb, for body weight, on SSC2, 3-9 Mb, for loin bone-in weight, and on SSC7, 3 Mb, for shoulder weight, and six segregating in two of the three backcrosses, on SSC2, SSC4, SSC6 and SSC10 for backfat thickness, shoulder and ham weights. Besides, 18 QTL regions were specifically identified in one of the three backcrosses, five identified only in BC_LD, seven in BC_DU and six in BC_PI. Beyond identifying and validating QTL, candidate genes and gene variants within the most interesting regions have been explored using functional annotation, gene expression data and SNP identification from RNA-Seq data. The results allowed us to propose a promising list of candidate mutations, those identified in PDE10A, DHCR7, MFN2 and CCNY genes located within the common QTL regions and those identified near ssc-mir-103-1 considered PANK3 regulators to be further analysed.
Genomic features separating ten strains of Neorhizobium galegae with different symbiotic phenotypes.

PubMed

Österman, Janina; Mousavi, Seyed Abdollah; Koskinen, Patrik; Paulin, Lars; Lindström, Kristina

2015-05-02

The symbiotic phenotype of Neorhizobium galegae, with strains specifically fixing nitrogen with either Galega orientalis or G. officinalis, has made it a target in research on determinants of host specificity in nitrogen fixation. The genomic differences between representative strains of the two symbiovars are, however, relatively small. This introduced a need for a dataset representing a larger bacterial population in order to make better conclusions on characteristics typical for a subset of the species. In this study, we produced draft genomes of eight strains of N. galegae having different symbiotic phenotypes, both with regard to host specificity and nitrogen fixation efficiency. These genomes were analysed together with the previously published complete genomes of N. galegae strains HAMBI 540T and HAMBI 1141. The results showed that the presence of an additional rpoN sigma factor gene in the symbiosis gene region is a characteristic specific to symbiovar orientalis, required for nitrogen fixation. Also the nifQ gene was shown to be crucial for functional symbiosis in both symbiovars. Genome-wide analyses identified additional genes characteristic of strains of the same symbiovar and of strains having similar plant growth promoting properties on Galega orientalis. Many of these genes are involved in transcriptional regulation or in metabolic functions. The results of this study confirm that the only symbiosis-related gene that is present in one symbiovar of N. galegae but not in the other is an rpoN gene. The specific function of this gene remains to be determined, however. New genes that were identified as specific for strains of one symbiovar may be involved in determining host specificity, while others are defined as potential determinant genes for differences in efficiency of nitrogen fixation.
Enhancing Breast Cancer Recurrence Algorithms Through Selective Use of Medical Record Data.

PubMed

Kroenke, Candyce H; Chubak, Jessica; Johnson, Lisa; Castillo, Adrienne; Weltzien, Erin; Caan, Bette J

2016-03-01

The utility of data-based algorithms in research has been questioned because of errors in identification of cancer recurrences. We adapted previously published breast cancer recurrence algorithms, selectively using medical record (MR) data to improve classification. We evaluated second breast cancer event (SBCE) and recurrence-specific algorithms previously published by Chubak and colleagues in 1535 women from the Life After Cancer Epidemiology (LACE) and 225 women from the Women's Health Initiative cohorts and compared classification statistics to published values. We also sought to improve classification with minimal MR examination. We selected pairs of algorithms-one with high sensitivity/high positive predictive value (PPV) and another with high specificity/high PPV-using MR information to resolve discrepancies between algorithms, properly classifying events based on review; we called this "triangulation." Finally, in LACE, we compared associations between breast cancer survival risk factors and recurrence using MR data, single Chubak algorithms, and triangulation. The SBCE algorithms performed well in identifying SBCE and recurrences. Recurrence-specific algorithms performed more poorly than published except for the high-specificity/high-PPV algorithm, which performed well. The triangulation method (sensitivity = 81.3%, specificity = 99.7%, PPV = 98.1%, NPV = 96.5%) improved recurrence classification over two single algorithms (sensitivity = 57.1%, specificity = 95.5%, PPV = 71.3%, NPV = 91.9%; and sensitivity = 74.6%, specificity = 97.3%, PPV = 84.7%, NPV = 95.1%), with 10.6% MR review. Triangulation performed well in survival risk factor analyses vs analyses using MR-identified recurrences. Use of multiple recurrence algorithms in administrative data, in combination with selective examination of MR data, may improve recurrence data quality and reduce research costs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Enhancing Breast Cancer Recurrence Algorithms Through Selective Use of Medical Record Data

PubMed Central

Chubak, Jessica; Johnson, Lisa; Castillo, Adrienne; Weltzien, Erin; Caan, Bette J.

2016-01-01

Abstract Background: The utility of data-based algorithms in research has been questioned because of errors in identification of cancer recurrences. We adapted previously published breast cancer recurrence algorithms, selectively using medical record (MR) data to improve classification. Methods: We evaluated second breast cancer event (SBCE) and recurrence-specific algorithms previously published by Chubak and colleagues in 1535 women from the Life After Cancer Epidemiology (LACE) and 225 women from the Women’s Health Initiative cohorts and compared classification statistics to published values. We also sought to improve classification with minimal MR examination. We selected pairs of algorithms—one with high sensitivity/high positive predictive value (PPV) and another with high specificity/high PPV—using MR information to resolve discrepancies between algorithms, properly classifying events based on review; we called this “triangulation.” Finally, in LACE, we compared associations between breast cancer survival risk factors and recurrence using MR data, single Chubak algorithms, and triangulation. Results: The SBCE algorithms performed well in identifying SBCE and recurrences. Recurrence-specific algorithms performed more poorly than published except for the high-specificity/high-PPV algorithm, which performed well. The triangulation method (sensitivity = 81.3%, specificity = 99.7%, PPV = 98.1%, NPV = 96.5%) improved recurrence classification over two single algorithms (sensitivity = 57.1%, specificity = 95.5%, PPV = 71.3%, NPV = 91.9%; and sensitivity = 74.6%, specificity = 97.3%, PPV = 84.7%, NPV = 95.1%), with 10.6% MR review. Triangulation performed well in survival risk factor analyses vs analyses using MR-identified recurrences. Conclusions: Use of multiple recurrence algorithms in administrative data, in combination with selective examination of MR data, may improve recurrence data quality and reduce research costs. PMID:26582243
Microarray and growth analyses identify differences and similarities of early corn response to weeds, shade, and nitrogen stress

USDA-ARS?s Scientific Manuscript database

Weed interference with crop growth is often attributed to water, nutrient, or light competition; however, specific physiological responses to these stresses are not well described. This study’s objective was to compare growth, yield, and gene expression responses of corn to nitrogen (N), low light (...
76 FR 54507 - Proposed Generic Communication; Draft NRC Generic Letter 2011-XX: Seismic Risk Evaluations for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... design estimates. Analyses performed under the Generic Issue program (GIP) indicated the need to evaluate... Examination of External Events (IPEEE) for Severe Accident Vulnerabilities,'' (ADAMS Accession No. ML031150485) to request that each licensee identify and report to the NRC all plant- specific vulnerabilities to...
A case for the use of Q-methodology in disability research: lessons learned from a training workshop.

PubMed

McKenzie, Judith; Braswell, Bob; Jelsma, Jennifer; Naidoo, Nirmala

2011-01-01

Q-methodology was developed to analyse subjective responses to a range of items dealing with specific topics. This article describes the use of Q-methodology and presents the results of a Q-study on perspectives on disability carried out in a training workshop as evidence for its usefulness in disability research. A Q-sort was administered in the context of a training workshop on Q-method. The Q-sort consisted of statements related to the topic of disability. The responses were analysed using specifically developed software to identify factors that represent patterns of responses. Twenty-two of the 23 respondents loaded on four factors. These factors appeared to represent different paradigms relating to the social, medical and disability rights models of disability. The fourth factor appeared to be that of a family perspective. These are all models evident in the disability research literature and provide evidence for the validity of Q-method in disability research. Based on this opportunistic study, it would appear that Q-methodology is a useful tool for identifying different view points related to disability.
Exploring the general motor ability construct.

PubMed

Ibrahim, Halijah; Heard, N Paul; Blanksby, Brian

2011-10-01

Malaysian students ages 12 to 15 years (N = 330; 165 girls, 165 boys) took the Australian Institute of Sport Talent Identification Test (AIST) and the Balance and Movement Coordination Test (BMC), developed specifically to identify sport talent in Malaysian adolescents. To investigate evidence for general aptitude ("g") in motor ability, a higher-order factor analysis was applied to the motor skills subtests from the AIST and BMC. First-order principal components analysis indicated that scores for the adolescent boys and girls could be described by similar sets of specific motor abilities. In particular, sets of skills identified as Movement Coordination and Postural Control were found, with Balancing Ability also emerging. For the girls, a factor labeled Static Balance was indicated. However, for the boys a more general balance ability labeled Kinesthetic Integration was found, along with an ability labeled Explosive Power. These first-order analyses accounted for 45% to 60% of the variance in the scores on the motor skills tests for the boys and girls, respectively. Separate second-order factor analyses for the boys and girls extracted a single higher-order factor, which was consistent with the existence of a motoric "g".
Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis.

PubMed

Brooks, Suzanne E; Bonney, Stephanie A; Lee, Cindy; Publicover, Amy; Khan, Ghazala; Smits, Evelien L; Sigurdardottir, Dagmar; Arno, Matthew; Li, Demin; Mills, Ken I; Pulford, Karen; Banham, Alison H; van Tendeloo, Viggo; Mufti, Ghulam J; Rammensee, Hans-Georg; Elliott, Tim J; Orchard, Kim H; Guinn, Barbara-ann

2015-01-01

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms' Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8-1.4 x 10(6)). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1(126-134) (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1(950-958) epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.
Mass spectrometric identification of proteins that interact through specific domains of the poly(A) binding protein

PubMed Central

Zhang, Chongxu; Nielsen, Maria E. O.; Chiang, Yueh-Chin; Kierkegaard, Morten; Wang, Xin; Lee, Darren J.; Andersen, Jens S.; Yao, Gang

2013-01-01

Poly(A) binding protein (PAB1) is involved in a number of RNA metabolic functions in eukaryotic cells and correspondingly is suggested to associate with a number of proteins. We have used mass spectrometric analysis to identify 55 non-ribosomal proteins that specifically interact with PAB1 from Saccharomyces cerevisiae. Because many of these factors may associate only indirectly with PAB1 by being components of the PAB1-mRNP structure, we additionally conducted mass spectrometric analyses on seven metabolically defined PAB1 deletion derivatives to delimit the interactions between these proteins and PAB1. These latter analyses identified 13 proteins whose associations with PAB1 were reduced by deleting one or another of PAB1’s defined domains. Included in this list of 13 proteins were the translation initiation factors eIF4G1 and eIF4G2, translation termination factor eRF3, and PBP2, all of whose previously known direct interactions with specific PAB1 domains were either confirmed, delimited, or extended. The remaining nine proteins that interacted through a specific PAB1 domain were CBF5, SLF1, UPF1, CBC1, SSD1, NOP77, yGR250c, NAB6, and GBP2. In further study, UPF1, involved in nonsense-mediated decay, was confirmed to interact with PAB1 through the RRM1 domain. We additionally established that while the RRM1 domain of PAB1 was required for UPF1-induced acceleration of deadenylation during nonsense-mediated decay, it was not required for the more critical step of acceleration of mRNA decapping. These results begin to identify the proteins most likely to interact with PAB1 and the domains of PAB1 through which these contacts are made. PMID:22836166
Mass spectrometric identification of proteins that interact through specific domains of the poly(A) binding protein.

PubMed

Richardson, Roy; Denis, Clyde L; Zhang, Chongxu; Nielsen, Maria E O; Chiang, Yueh-Chin; Kierkegaard, Morten; Wang, Xin; Lee, Darren J; Andersen, Jens S; Yao, Gang

2012-09-01

Poly(A) binding protein (PAB1) is involved in a number of RNA metabolic functions in eukaryotic cells and correspondingly is suggested to associate with a number of proteins. We have used mass spectrometric analysis to identify 55 non-ribosomal proteins that specifically interact with PAB1 from Saccharomyces cerevisiae. Because many of these factors may associate only indirectly with PAB1 by being components of the PAB1-mRNP structure, we additionally conducted mass spectrometric analyses on seven metabolically defined PAB1 deletion derivatives to delimit the interactions between these proteins and PAB1. These latter analyses identified 13 proteins whose associations with PAB1 were reduced by deleting one or another of PAB1's defined domains. Included in this list of 13 proteins were the translation initiation factors eIF4G1 and eIF4G2, translation termination factor eRF3, and PBP2, all of whose previously known direct interactions with specific PAB1 domains were either confirmed, delimited, or extended. The remaining nine proteins that interacted through a specific PAB1 domain were CBF5, SLF1, UPF1, CBC1, SSD1, NOP77, yGR250c, NAB6, and GBP2. In further study, UPF1, involved in nonsense-mediated decay, was confirmed to interact with PAB1 through the RRM1 domain. We additionally established that while the RRM1 domain of PAB1 was required for UPF1-induced acceleration of deadenylation during nonsense-mediated decay, it was not required for the more critical step of acceleration of mRNA decapping. These results begin to identify the proteins most likely to interact with PAB1 and the domains of PAB1 through which these contacts are made.
Periodicity in marine extinction events

NASA Technical Reports Server (NTRS)

Sepkoski, J. John, Jr.; Raup, David M.

1986-01-01

The periodicity of extinction events is examined in detail. In particular, the temporal distribution of specific, identifiable extinction events is analyzed. The nature and limitations of the data base on the global fossil record is discussed in order to establish limits of resolution in statistical analyses. Peaks in extinction intensity which appear to differ significantly from background levels are considered, and new analyses of the temporal distribution of these peaks are presented. Finally, some possible causes of periodicity and of interdependence among extinction events over the last quarter billion years of earth history are examined.
European Population Genetic Substructure: Further Definition of Ancestry Informative Markers for Distinguishing Among Diverse European Ethnic Groups

PubMed Central

Tian, Chao; Kosoy, Roman; Nassir, Rami; Lee, Annette; Villoslada, Pablo; Klareskog, Lars; Hammarström, Lennart; Garchon, Henri-Jean; Pulver, Ann E.; Ransom, Michael; Gregersen, Peter K.; Seldin, Michael F.

2009-01-01

The definition of European population genetic substructure and its application to understanding complex phenotypes is becoming increasingly important. In the current study using over 4000 subjects genotyped for 300 thousand SNPs we provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs) for application in genetic studies. In general, the graphical description of these principal components analyses (PCA) of diverse European subjects showed a strong correspondence to the geographical relationships of specific countries or regions of origin. Clearer separation of different ethnic and regional populations was observed when northern and southern European groups were considered separately and the PCA results were influenced by the inclusion or exclusion of different self-identified population groups including Ashkenazi Jewish, Sardinian and Orcadian ethnic groups. SNP AIM sets were identified that could distinguish the regional and ethnic population groups. Moreover, the studies demonstrated that most allele frequency differences between different European groups could be effectively controlled in analyses using these AIM sets. The European substructure AIMs should be widely applicable to ongoing studies to confirm and delineate specific disease susceptibility candidate regions without the necessity to perform additional genome-wide SNP studies in additional subject sets. PMID:19707526

European population genetic substructure: further definition of ancestry informative markers for distinguishing among diverse European ethnic groups.

PubMed

Tian, Chao; Kosoy, Roman; Nassir, Rami; Lee, Annette; Villoslada, Pablo; Klareskog, Lars; Hammarström, Lennart; Garchon, Henri-Jean; Pulver, Ann E; Ransom, Michael; Gregersen, Peter K; Seldin, Michael F

2009-01-01

The definition of European population genetic substructure and its application to understanding complex phenotypes is becoming increasingly important. In the current study using over 4,000 subjects genotyped for 300,000 single-nucleotide polymorphisms (SNPs), we provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs) for application in genetic studies. In general, the graphical description of these principal components analyses (PCA) of diverse European subjects showed a strong correspondence to the geographical relationships of specific countries or regions of origin. Clearer separation of different ethnic and regional populations was observed when northern and southern European groups were considered separately and the PCA results were influenced by the inclusion or exclusion of different self-identified population groups including Ashkenazi Jewish, Sardinian, and Orcadian ethnic groups. SNP AIM sets were identified that could distinguish the regional and ethnic population groups. Moreover, the studies demonstrated that most allele frequency differences between different European groups could be controlled effectively in analyses using these AIM sets. The European substructure AIMs should be widely applicable to ongoing studies to confirm and delineate specific disease susceptibility candidate regions without the necessity of performing additional genome-wide SNP studies in additional subject sets.
Ancient Complexity, Opisthokont Plasticity, and Discovery of the 11th Subfamily of Arf GAP Proteins

PubMed Central

Schlacht, Alexander; Mowbrey, Kevin; Elias, Marek; Kahn, Richard A.; Dacks, Joel B.

2013-01-01

The organelle paralogy hypothesis is one model for the acquisition of non-endosymbiotic organelles, generated from molecular evolutionary analyses of proteins encoding specificity in the membrane traffic system. GTPase Activating Proteins (GAPs) for the ADP-ribosylation factor (Arfs) GTPases are additional regulators of the kinetics and fidelity of membrane traffic. Here we describe molecular evolutionary analyses of Arf GAP protein family. Of the ten subfamilies previously defined in humans, we find that five were likely present in the Last Eukaryotic Common Ancestor (LECA). Of the three more recently derived subfamilies, one was likely present in the ancestor of opisthokonts (animals and fungi) and apusomonads (flagellates classified as the sister lineage to opisthokonts), while two arose in the holozoan lineage. We also propose to have identified a novel ancient subfamily (ArfGAPC2), present in diverse eukaryotes but which is lost frequently, including in the opisthokonts. Surprisingly few ancient domains accompanying the ArfGAP domain were identified, in marked contrast to the extensively decorated human Arf GAPs. Phylogenetic analyses of the subfamilies reveal patterns of single and multiple gene duplications specific to the Holozoa, to some degree mirroring evolution of Arf GAP targets, the Arfs. Conservation, and lack thereof, of various residues in the ArfGAP structure provide contextualization of previously identified functional amino acids and their application to Arf GAP biology in general. Overall, our results yield insights into current Arf GAP biology, reveal complexity in the ancient eukaryotic ancestor, and integrate the Arf GAP family into a proposed mechanism for the evolution of non-endosymbiotic organelles. PMID:23433073
Electronic cigarettes: incorporating human factors engineering into risk assessments

PubMed Central

Yang, Ling; Rudy, Susan F; Cheng, James M; Durmowicz, Elizabeth L

2014-01-01

Objective A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes. Methods Five databases were searched through January 2014 and publications relevant to HF were incorporated. Voluntary adverse event (AE) reports submitted to the US Food and Drug Administration (FDA) and the package labelling of 12 e-cigarette products were analysed. Results No studies specifically addressing the impact of HF on e-cigarette use risks were identified. Most e-cigarette users are smokers, but data on the user population are inconsistent. No articles focused specifically on e-cigarette use environments, storage conditions, product operational requirements, product complexities, user errors or misuse. Twelve published studies analysed e-cigarette labelling and concluded that labelling was inadequate or misleading. FDA labelling analysis revealed similar concerns described in the literature. AE reports related to design concerns are increasing and fatalities related to accidental exposure and misuse have occurred; however, no publications evaluating the relationship between AEs and HF were identified. Conclusions The HF impacting e-cigarette use and related hazards are inadequately characterised. Thorough analyses of user–product–environment interfaces, product complexities and AEs associated with typical and atypical use are needed to better incorporate HF engineering principles to inform and potentially reduce or mitigate the emerging hazards associated with e-cigarette products. PMID:24732164
New approach for the identification of implausible values and outliers in longitudinal childhood anthropometric data.

PubMed

Shi, Joy; Korsiak, Jill; Roth, Daniel E

2018-03-01

We aimed to demonstrate the use of jackknife residuals to take advantage of the longitudinal nature of available growth data in assessing potential biologically implausible values and outliers. Artificial errors were induced in 5% of length, weight, and head circumference measurements, measured on 1211 participants from the Maternal Vitamin D for Infant Growth (MDIG) trial from birth to 24 months of age. Each child's sex- and age-standardized z-score or raw measurements were regressed as a function of age in child-specific models. Each error responsible for a biologically implausible decrease between a consecutive pair of measurements was identified based on the higher of the two absolute values of jackknife residuals in each pair. In further analyses, outliers were identified as those values beyond fixed cutoffs of the jackknife residuals (e.g., greater than +5 or less than -5 in primary analyses). Kappa, sensitivity, and specificity were calculated over 1000 simulations to assess the ability of the jackknife residual method to detect induced errors and to compare these methods with the use of conditional growth percentiles and conventional cross-sectional methods. Among the induced errors that resulted in a biologically implausible decrease in measurement between two consecutive values, the jackknife residual method identified the correct value in 84.3%-91.5% of these instances when applied to the sex- and age-standardized z-scores, with kappa values ranging from 0.685 to 0.795. Sensitivity and specificity of the jackknife method were higher than those of the conditional growth percentile method, but specificity was lower than for conventional cross-sectional methods. Using jackknife residuals provides a simple method to identify biologically implausible values and outliers in longitudinal child growth data sets in which each child contributes at least 4 serial measurements. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.
Features of Computer-Based Decision Aids: Systematic Review, Thematic Synthesis, and Meta-Analyses

PubMed Central

Krömker, Dörthe; Meguerditchian, Ari N; Tamblyn, Robyn

2016-01-01

Background Patient information and education, such as decision aids, are gradually moving toward online, computer-based environments. Considerable research has been conducted to guide content and presentation of decision aids. However, given the relatively new shift to computer-based support, little attention has been given to how multimedia and interactivity can improve upon paper-based decision aids. Objective The first objective of this review was to summarize published literature into a proposed classification of features that have been integrated into computer-based decision aids. Building on this classification, the second objective was to assess whether integration of specific features was associated with higher-quality decision making. Methods Relevant studies were located by searching MEDLINE, Embase, CINAHL, and CENTRAL databases. The review identified studies that evaluated computer-based decision aids for adults faced with preference-sensitive medical decisions and reported quality of decision-making outcomes. A thematic synthesis was conducted to develop the classification of features. Subsequently, meta-analyses were conducted based on standardized mean differences (SMD) from randomized controlled trials (RCTs) that reported knowledge or decisional conflict. Further subgroup analyses compared pooled SMDs for decision aids that incorporated a specific feature to other computer-based decision aids that did not incorporate the feature, to assess whether specific features improved quality of decision making. Results Of 3541 unique publications, 58 studies met the target criteria and were included in the thematic synthesis. The synthesis identified six features: content control, tailoring, patient narratives, explicit values clarification, feedback, and social support. A subset of 26 RCTs from the thematic synthesis was used to conduct the meta-analyses. As expected, computer-based decision aids performed better than usual care or alternative aids; however, some features performed better than others. Integration of content control improved quality of decision making (SMD 0.59 vs 0.23 for knowledge; SMD 0.39 vs 0.29 for decisional conflict). In contrast, tailoring reduced quality of decision making (SMD 0.40 vs 0.71 for knowledge; SMD 0.25 vs 0.52 for decisional conflict). Similarly, patient narratives also reduced quality of decision making (SMD 0.43 vs 0.65 for knowledge; SMD 0.17 vs 0.46 for decisional conflict). Results were varied for different types of explicit values clarification, feedback, and social support. Conclusions Integration of media rich or interactive features into computer-based decision aids can improve quality of preference-sensitive decision making. However, this is an emerging field with limited evidence to guide use. The systematic review and thematic synthesis identified features that have been integrated into available computer-based decision aids, in an effort to facilitate reporting of these features and to promote integration of such features into decision aids. The meta-analyses and associated subgroup analyses provide preliminary evidence to support integration of specific features into future decision aids. Further research can focus on clarifying independent contributions of specific features through experimental designs and refining the designs of features to improve effectiveness. PMID:26813512
Analysis of Odorants in Marking Fluid of Siberian Tiger (Panthera tigris altaica) Using Simultaneous Sensory and Chemical Analysis with Headspace Solid-Phase Microextraction and Multidimensional Gas Chromatography-Mass Spectrometry-Olfactometry.

PubMed

Soso, Simone B; Koziel, Jacek A

2016-06-25

Scent-marking is the most effective method of communication in the presence or absence of a signaler. These complex mixtures result in a multifaceted interaction triggered by the sense of smell. The objective was to identify volatile organic compound (VOC) composition and odors emitted by total marking fluid (MF) associated with Siberian tigers (Panthera tigris altaica). Siberian tiger, an endangered species, was chosen because its MF had never been analyzed. Solid phase microextraction (SPME) for headspace volatile collection combined with multidimensional gas chromatography-mass spectrometry-olfactometry for simultaneous chemical and sensory analyses were used. Thirty-two VOCs emitted from MF were identified. 2-acetyl-1-pyrroline, the sole previously identified compound responsible for the "characteristic" odor of P. tigris MF, was identified along with two additional compounds confirmed with standards (urea, furfural) and four tentatively identified compounds (3-methylbutanamine, (R)-3-methylcyclopentanone, propanedioic acid, and 3-hydroxybutanal) as being responsible for the characteristic aroma of Siberian tiger MF. Simultaneous chemical and sensory analyses improved characterization of scent-markings and identified compounds not previously reported in MF of other tiger species. This research will assist animal ecologists, behaviorists, and zookeepers in understanding how scents from specific MF compounds impact tiger and wildlife communication and improve management practices related to animal behavior. Simultaneous chemical and sensory analyses is applicable to unlocking scent-marking information for other species.
Analysis of microdissected neurons by 18O mass spectrometry reveals altered protein expression in Alzheimer's disease

PubMed Central

Hashimoto, Masakazu; Bogdanovic, Nenad; Nakagawa, Hiroyuki; Volkmann, Inga; Aoki, Mikio; Winblad, Bengt; Sakai, Jun; Tjernberg, Lars O

2012-01-01

Abstract It is evident that the symptoms of Alzheimer's disease (AD) are derived from severe neuronal damage, and especially pyramidal neurons in the hippocampus are affected pathologically. Here, we analysed the proteome of hippocampal neurons, isolated from post-mortem brains by laser capture microdissection. By using 18O labelling and mass spectrometry, the relative expression levels of 150 proteins in AD and controls were estimated. Many of the identified proteins are involved in transcription and nucleotide binding, glycolysis, heat-shock response, microtubule stabilization, axonal transport or inflammation. The proteins showing the most altered expression in AD were selected for immunohistochemical analysis. These analyses confirmed the altered expression levels, and showed in many AD cases a pathological pattern. For comparison, we also analysed hippocampal sections by Western blot. The expression levels found by this method showed poor correlation with the neuron-specific analysis. Hence, we conclude that cell-specific proteome analysis reveals differences in the proteome that cannot be detected by bulk analysis. PMID:21883897
Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond

PubMed Central

Washio, Jumpei; Takahashi, Nobuhiro

2016-01-01

Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the ‘Warburg effect’. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases. PMID:27271597
Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond.

PubMed

Washio, Jumpei; Takahashi, Nobuhiro

2016-06-02

Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the 'Warburg effect'. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.
How to conduct a qualitative meta-analysis: Tailoring methods to enhance methodological integrity.

PubMed

Levitt, Heidi M

2018-05-01

Although qualitative research has long been of interest in the field of psychology, meta-analyses of qualitative literatures (sometimes called meta-syntheses) are still quite rare. Like quantitative meta-analyses, these methods function to aggregate findings and identify patterns across primary studies, but their aims, procedures, and methodological considerations may vary. This paper explains the function of qualitative meta-analyses and their methodological development. Recommendations have broad relevance but are framed with an eye toward their use in psychotherapy research. Rather than arguing for the adoption of any single meta-method, this paper advocates for considering how procedures can best be selected and adapted to enhance a meta-study's methodological integrity. Through the paper, recommendations are provided to help researchers identify procedures that can best serve their studies' specific goals. Meta-analysts are encouraged to consider the methodological integrity of their studies in relation to central research processes, including identifying a set of primary research studies, transforming primary findings into initial units of data for a meta-analysis, developing categories or themes, and communicating findings. The paper provides guidance for researchers who desire to tailor meta-analytic methods to meet their particular goals while enhancing the rigor of their research.
Genome-Wide Analysis of the GRF Family Reveals Their Involvement in Abiotic Stress Response in Cassava.

PubMed

Shang, Sang; Wu, Chunlai; Huang, Chao; Tie, Weiwei; Yan, Yan; Ding, Zehong; Xia, Zhiqiang; Wang, Wenquan; Peng, Ming; Tian, Libo; Hu, Wei

2018-02-20

GENERAL REGULATORY FACTOR (GRF) proteins play vital roles in the regulation of plant growth, development, and response to abiotic stress. However, little information is known for this gene family in cassava ( Manihot esculenta ). In this study, 15 MeGRFs were identified from the cassava genome and were clustered into the ε and the non-ε groups according to phylogenetic, conserved motif, and gene structure analyses. Transcriptomic analyses showed eleven Me GRFs with constitutively high expression in stems, leaves, and storage roots of two cassava genotypes. Expression analyses revealed that the majority of GRFs showed transcriptional changes under cold, osmotic, salt, abscisic acid (ABA), and H₂O₂ treatments. Six Me GRFs were found to be commonly upregulated by abiotic stress, ABA, and H₂O₂ treatments, which may be the converging points of multiple signaling pathways. Interaction network analysis identified 18 possible interactors of MeGRFs. Taken together, this study elucidates the transcriptional control of Me GRFs in tissue development and the responses of abiotic stress and related signaling in cassava. Some constitutively expressed, tissue-specific, and abiotic stress-responsive candidate MeGRF genes were identified for the further genetic improvement of crops.
Advanced space power requirements and techniques. Task 1: Mission projections and requirements. Volume 1: Technical report

NASA Technical Reports Server (NTRS)

Wolfe, M. G.

1978-01-01

The objectives of this study were to: (1) develop projections of the NASA, DoD, and civil space power requirements for the 1980-1995 time period; (2) identify specific areas of application and space power subsystem type needs for each prospective user; (3) document the supporting and historical base, including relevant cost related measures of performance; and (4) quantify the benefits of specific technology projection advancements. The initial scope of the study included: (1) construction of likely models for NASA, DoD, and civil space systems; (2) generation of a number of future scenarios; (3) extraction of time phased technology requirements based on the scenarios; and (4) cost/benefit analyses of some of the technologies identified.
Enhanced Lipidome Coverage in Shotgun Analyses by using Gas-Phase Fractionation

NASA Astrophysics Data System (ADS)

Nazari, Milad; Muddiman, David C.

2016-11-01

A high resolving power shotgun lipidomics strategy using gas-phase fractionation and data-dependent acquisition (DDA) was applied toward comprehensive characterization of lipids in a hen ovarian tissue in an untargeted fashion. Using this approach, a total of 822 unique lipids across a diverse range of lipid categories and classes were identified based on their MS/MS fragmentation patterns. Classes of glycerophospholipids and glycerolipids, such as glycerophosphocholines (PC), glycerophosphoethanolamines (PE), and triglycerides (TG), are often the most abundant peaks observed in shotgun lipidomics analyses. These ions suppress the signal from low abundance ions and hinder the chances of characterizing low abundant lipids when DDA is used. These issues were circumvented by utilizing gas-phase fractionation, where DDA was performed on narrow m/z ranges instead of a broad m/z range. Employing gas-phase fractionation resulted in an increase in sensitivity by more than an order of magnitude in both positive- and negative-ion modes. Furthermore, the enhanced sensitivity increased the number of lipids identified by a factor of ≈4, and facilitated identification of low abundant lipids from classes such as cardiolipins that are often difficult to observe in untargeted shotgun analyses and require sample-specific preparation steps prior to analysis. This method serves as a resource for comprehensive profiling of lipids from many different categories and classes in an untargeted manner, as well as for targeted and quantitative analyses of individual lipids. Furthermore, this comprehensive analysis of the lipidome can serve as a species- and tissue-specific database for confident identification of other MS-based datasets, such as mass spectrometry imaging.
Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

PubMed Central

Margulies, Elliott H.; Cooper, Gregory M.; Asimenos, George; Thomas, Daryl J.; Dewey, Colin N.; Siepel, Adam; Birney, Ewan; Keefe, Damian; Schwartz, Ariel S.; Hou, Minmei; Taylor, James; Nikolaev, Sergey; Montoya-Burgos, Juan I.; Löytynoja, Ari; Whelan, Simon; Pardi, Fabio; Massingham, Tim; Brown, James B.; Bickel, Peter; Holmes, Ian; Mullikin, James C.; Ureta-Vidal, Abel; Paten, Benedict; Stone, Eric A.; Rosenbloom, Kate R.; Kent, W. James; Bouffard, Gerard G.; Guan, Xiaobin; Hansen, Nancy F.; Idol, Jacquelyn R.; Maduro, Valerie V.B.; Maskeri, Baishali; McDowell, Jennifer C.; Park, Morgan; Thomas, Pamela J.; Young, Alice C.; Blakesley, Robert W.; Muzny, Donna M.; Sodergren, Erica; Wheeler, David A.; Worley, Kim C.; Jiang, Huaiyang; Weinstock, George M.; Gibbs, Richard A.; Graves, Tina; Fulton, Robert; Mardis, Elaine R.; Wilson, Richard K.; Clamp, Michele; Cuff, James; Gnerre, Sante; Jaffe, David B.; Chang, Jean L.; Lindblad-Toh, Kerstin; Lander, Eric S.; Hinrichs, Angie; Trumbower, Heather; Clawson, Hiram; Zweig, Ann; Kuhn, Robert M.; Barber, Galt; Harte, Rachel; Karolchik, Donna; Field, Matthew A.; Moore, Richard A.; Matthewson, Carrie A.; Schein, Jacqueline E.; Marra, Marco A.; Antonarakis, Stylianos E.; Batzoglou, Serafim; Goldman, Nick; Hardison, Ross; Haussler, David; Miller, Webb; Pachter, Lior; Green, Eric D.; Sidow, Arend

2007-01-01

A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization. PMID:17567995
Drivers of land use/land cover changes in Munessa-Shashemene landscape of the south-central highlands of Ethiopia.

PubMed

Kindu, Mengistie; Schneider, Thomas; Teketay, Demel; Knoke, Thomas

2015-07-01

Understanding drivers of changes in land use/land cover (LULC) is essential for modeling future dynamics or development of management strategies to ameliorate or prevent further decline of natural resources. In this study, an attempt has been made to identify the main drivers behind the LULC changes that had occurred in the past four decades in Munessa-Shashemene landscape of the south-central highlands of Ethiopia. The datasets required for the study were generated through both primary and secondary sources. Combination of techniques, including descriptive statistics, GIS-based processing, and regression analyses were employed for data analyses. Changes triggered by the interplay of more than 12 drivers were identified related to social, economic, environmental, policy/institutional, and technological factors. Specifically, population growth, expansion of cultivated lands and settlements, livestock ranching, cutting of woody species for fuelwood, and charcoal making were the top six important drivers of LULC change as viewed by the local people and confirmed by quantitative analyses. Differences in respondents' perceptions related to environmental (i.e., location specific) and socioeconomic determinants (e.g., age and literacy) about drivers were statically significant (P = 0.001). LULC changes were also determined by distances to major drivers (e.g., the further a pixel is from the road, the less likelihood of changes) as shown by the landscape level analyses. Further studies are suggested targeting these drivers to explore the consequences and future options and formulate intervention strategies for sustainable development in the studied landscape and elsewhere with similar geographic settings.
Phagocytosis and Respiratory Burst Activity in Lumpsucker (Cyclopterus lumpus L.) Leucocytes Analysed by Flow Cytometry

PubMed Central

Haugland, Gyri T.; Jakobsen, Ragnhild Aakre; Vestvik, Nils; Ulven, Kristian; Stokka, Lene; Wergeland, Heidrun I.

2012-01-01

In the present study, we have isolated leucocytes from peripheral blood, head kidney and spleen from lumpsucker (Cyclopterus lumpus L.), and performed functional studies like phagocytosis and respiratory burst, as well as morphological and cytochemical analyses. Different leucocytes were identified, such as lymphocytes, monocytes/macrophages and polymorphonuclear cells with bean shaped or bilobed nuclei. In addition, cells with similar morphology as described for dendritic cells in trout were abundant among the isolated leucocytes. Flow cytometry was successfully used for measuring phagocytosis and respiratory burst activity. The phagocytic capacity and ability were very high, and cells with different morphology in all three leucocyte preparations phagocytised beads rapidly. Due to lack of available cell markers, the identity of the phagocytic cells could not be determined. The potent non-specific phagocytosis was in accordance with a high number of cells positive for myeloperoxidase, an enzyme involved in oxygen-dependent killing mechanism present in phagocytic cells. Further, high respiratory burst activity was present in the leucocytes samples, verifying a potent oxygen- dependent degradation. At present, the specific antibody immune response could not be measured, as immunoglobulin or B-cells have not yet been isolated. Therefore, analyses of the specific immune response in this fish species await further clarification. The present study presents the first analyses of lumpsucker immunity and also the first within the order Scopaeniformes. PMID:23112870
Population-specific life histories contribute to metapopulation viability

USGS Publications Warehouse

Halsey, Samniqueka J.; Bell, Timothy J.; McEachern, A. Kathryn; Pavlovic, Noel B.

2016-01-01

Restoration efforts can be improved by understanding how variations in life-history traits occur within populations of the same species living in different environments. This can be done by first understanding the demographic responses of natural occurring populations. Population viability analysis continues to be useful to species management and conservation with sensitivity analysis aiding in the understanding of population dynamics. In this study, using life-table response experiments and elasticity analyses, we investigated how population-specific life-history demographic responses contributed to the metapopulation viability of the Federally threatened Pitcher's thistle (Cirsium pitcheri). Specifically, we tested the following hypotheses: (1) Subpopulations occupying different environments within a metapopulation have independent demographic responses and (2) advancing succession results in a shift from a demographic response focused on growth and fecundity to one dominated by stasis. Our results showed that reintroductions had a positive contribution to the metapopulation growth rate as compared to native populations which had a negative contribution. We found no difference in succession on the contribution to metapopulation viability. In addition, we identified distinct population-specific contributions to metapopulation viability and were able to associate specific life-history demographic responses. For example, the positive impact of Miller High Dunes population on the metapopulation growth rate resulted from high growth contributions, whereas increased time of plant in stasis for the State Park Big Blowout population resulted in negative contributions. A greater understanding of how separate populations respond in their corresponding environment may ultimately lead to more effective management strategies aimed at reducing extinction risk. We propose the continued use of sensitivity analyses to evaluate population-specific demographic influences on metapopulation viability. In understanding the underlying causes of the projected extinction probabilities of each population and identifying broad-scale contributions of different populations to the metapopulation, the process of pinpointing target populations is simplified. More detailed analyses can then be applied to the target populations to increase population viability and consequently metapopulation viability. Based on our research, we suggest that the best approach to improve the overall metapopulation viability is to manage the contributions to population growth for each population separately.
A proposed case-control framework to probabilistically classify individual deaths as expected or excess during extreme hot weather events.

PubMed

Henderson, Sarah B; Gauld, Jillian S; Rauch, Stephen A; McLean, Kathleen E; Krstic, Nikolas; Hondula, David M; Kosatsky, Tom

2016-11-15

Most excess deaths that occur during extreme hot weather events do not have natural heat recorded as an underlying or contributing cause. This study aims to identify the specific individuals who died because of hot weather using only secondary data. A novel approach was developed in which the expected number of deaths was repeatedly sampled from all deaths that occurred during a hot weather event, and compared with deaths during a control period. The deaths were compared with respect to five factors known to be associated with hot weather mortality. Individuals were ranked by their presence in significant models over 100 trials of 10,000 repetitions. Those with the highest rankings were identified as probable excess deaths. Sensitivity analyses were performed on a range of model combinations. These methods were applied to a 2009 hot weather event in greater Vancouver, Canada. The excess deaths identified were sensitive to differences in model combinations, particularly between univariate and multivariate approaches. One multivariate and one univariate combination were chosen as the best models for further analyses. The individuals identified by multiple combinations suggest that marginalized populations in greater Vancouver are at higher risk of death during hot weather. This study proposes novel methods for classifying specific deaths as expected or excess during a hot weather event. Further work is needed to evaluate performance of the methods in simulation studies and against clinically identified cases. If confirmed, these methods could be applied to a wide range of populations and events of interest.
Gene modules associated with breast cancer distant metastasis-free survival in the PAM50 molecular subtypes.

PubMed

Liu, Rong; Zhang, Wei; Liu, Zhao-Qian; Zhou, Hong-Hao

2016-04-19

To identify PAM50 subtype-specific associations between distant metastasis-free survival (DMFS) in breast cancer (BC) patients and gene modules describing potentially targetable oncogenic pathways, a comprehensive analysis evaluating the prognostic efficacy of published gene signatures in 2027 BC patients from 13 studies was conducted. We calculated 21 gene modules and computed hazard ratios (HRs) for DMFS for one-unit increases in module score, with and without adjustment for clinical characteristics. By comparing gene expression to survival outcomes, we derived four subtype-specific prognostic signatures for BC. Univariate and multivariate analyses showed that in the luminal A subgroup, E2F3, PTEN and GGI gene module scores were associated with clinical outcome. In the luminal B tumors, RAS was associated with DMFS and in the basal-like tumors, ER was associated with DMFS. Our defined gene modules predicted high-risk patients in multivariate analyses for the basal-like (HR: 2.19, p=2.5×10-4), luminal A (HR: 3.03, p=7.2×10-5), luminal B (HR: 3.00, p=2.4×10-10) and HER2+ (HR: 5.49, p=9.7×10-10) subgroups. We found that different modules are associated with DMFS in different BC subtypes. The results of this study could help to identify new therapeutic strategies for specific molecular subgroups of BC, and could enhance efforts to improve patient-specific therapy options.
Microbial ecology in the age of genomics and metagenomics: concepts, tools, and recent advances.

PubMed

Xu, Jianping

2006-06-01

Microbial ecology examines the diversity and activity of micro-organisms in Earth's biosphere. In the last 20 years, the application of genomics tools have revolutionized microbial ecological studies and drastically expanded our view on the previously underappreciated microbial world. This review first introduces the basic concepts in microbial ecology and the main genomics methods that have been used to examine natural microbial populations and communities. In the ensuing three specific sections, the applications of the genomics in microbial ecological research are highlighted. The first describes the widespread application of multilocus sequence typing and representational difference analysis in studying genetic variation within microbial species. Such investigations have identified that migration, horizontal gene transfer and recombination are common in natural microbial populations and that microbial strains can be highly variable in genome size and gene content. The second section highlights and summarizes the use of four specific genomics methods (phylogenetic analysis of ribosomal RNA, DNA-DNA re-association kinetics, metagenomics, and micro-arrays) in analysing the diversity and potential activity of microbial populations and communities from a variety of terrestrial and aquatic environments. Such analyses have identified many unexpected phylogenetic lineages in viruses, bacteria, archaea, and microbial eukaryotes. Functional analyses of environmental DNA also revealed highly prevalent, but previously unknown, metabolic processes in natural microbial communities. In the third section, the ecological implications of sequenced microbial genomes are briefly discussed. Comparative analyses of prokaryotic genomic sequences suggest the importance of ecology in determining microbial genome size and gene content. The significant variability in genome size and gene content among strains and species of prokaryotes indicate the highly fluid nature of prokaryotic genomes, a result consistent with those from multilocus sequence typing and representational difference analyses. The integration of various levels of ecological analyses coupled to the application and further development of high throughput technologies are accelerating the pace of discovery in microbial ecology.

The Emergence and Evolution of School Psychology Literature: A Scientometric Analysis from 1907 through 2014

ERIC Educational Resources Information Center

Liu, Shuyan; Oakland, Thomas

2016-01-01

The objective of this current study is to identify the growth and development of scholarly literature that specifically references the term "school psychology" in the Science Citation Index from 1907 through 2014. Documents from Web of Science were accessed and analyzed through the use of scientometric analyses, including HistCite and…
Development of a Laboratory Project to Determine Human ABO Genotypes--Limitations Lead to Further Student Explorations

ERIC Educational Resources Information Center

Salerno, Theresa A.

2009-01-01

A multiplex allele-specific PCR analysis was developed to identify six "common" genotypes: AA, AO, BB, BO, OO, and AB. This project included a pre-laboratory exercise that provided active learning experiences and developed critical thinking skills. This laboratory resulted in many successful analyses, which were verified by student knowledge of…
Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity

USDA-ARS?s Scientific Manuscript database

Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NB-LRR or NLR) proteins, which trigger a hypersensitive response (HR), a rapid, localized cell death upon recognition of specific pathogens. The maize NLR-encoding Rp1-D21 gene is the result of an intergenic recomb...
Describing, Analysing and Judging Language Codes in Cinematic Discourse

ERIC Educational Resources Information Center

Richardson, Kay; Queen, Robin

2012-01-01

In this short commentary piece, the authors stand back from many of the specific details in the seven papers which constitute the special issue, and offer some observations which attempt to identify and assess points of similarity and difference amongst them, under a number of different general headings. To the extent that the "sociolinguistics of…
Digital and Online Learning in Vocational Education and Training in Serbia: A Case Study

ERIC Educational Resources Information Center

Brolpito, Alessandro; Lightfoot, Michael; Radišic, Jelena; Šcepanovic, Danijela

2016-01-01

This case study aims to identify relevant policies and practices for digital and online learning (DOL) in vocational education and training (VET) in Serbia, with a focus on initial VET (IVET). The study was commissioned by the European Training Foundation (ETF) with the following specific objectives: (1) gather information and analyse DOL…
Development of Health Promoting Leadership--Experiences of a Training Programme

ERIC Educational Resources Information Center

Eriksson, Andrea; Axelsson, Runo; Axelsson, Susanna Bihari

2010-01-01

Purpose: The purpose of this paper is to describe and analyse the experiences of an intervention programme for development of health promoting leadership in Gothenburg in Sweden. The more specific purpose is to identify critical aspects of such a programme as part of the development of a health promoting workplace. Design/methodology/approach: A…
Sex- and Tissue-specific Functions of Drosophila Doublesex Transcription Factor Target Genes

PubMed Central

Clough, Emily; Jimenez, Erin; Kim, Yoo-Ah; Whitworth, Cale; Neville, Megan C.; Hempel, Leonie; Pavlou, Hania J.; Chen, Zhen-Xia; Sturgill, David; Dale, Ryan; Smith, Harold E.; Przytycka, Teresa M.; Goodwin, Stephen F.; Van Doren, Mark; Oliver, Brian

2014-01-01

Primary sex determination “switches” evolve rapidly, but Doublesex (DSX) related transcription factors (DMRTs) act downstream of these switches to control sexual development in most animal species. Drosophila dsx encodes female- and male-specific isoforms (DSXF and DSXM), but little is known about how dsx controls sexual development, whether DSXF and DSXM bind different targets, or how DSX proteins direct different outcomes in diverse tissues. We undertook genome-wide analyses to identify DSX targets using in vivo occupancy, binding site prediction, and evolutionary conservation. We find that DSXF and DSXM bind thousands of the same targets in multiple tissues in both sexes, yet these targets have sex- and tissue-specific functions. Interestingly, DSX targets show considerable overlap with targets identified for mouse DMRT1. DSX targets include transcription factors and signaling pathway components providing for direct and indirect regulation of sex-biased expression. PMID:25535918
Diagnostic accuracy of different caries risk assessment methods. A systematic review.

PubMed

Senneby, Anna; Mejàre, Ingegerd; Sahlin, Nils-Eric; Svensäter, Gunnel; Rohlin, Madeleine

2015-12-01

To evaluate the accuracy of different methods used to identify individuals with increased risk of developing dental coronal caries. Studies on following methods were included: previous caries experience, tests using microbiota, buffering capacity, salivary flow rate, oral hygiene, dietary habits and sociodemographic variables. QUADAS-2 was used to assess risk of bias. Sensitivity, specificity, predictive values, and likelihood ratios (LR) were calculated. Quality of evidence based on ≥3 studies of a method was rated according to GRADE. PubMed, Cochrane Library, Web of Science and reference lists of included publications were searched up to January 2015. From 5776 identified articles, 18 were included. Assessment of study quality identified methodological limitations concerning study design, test technology and reporting. No study presented low risk of bias in all domains. Three or more studies were found only for previous caries experience and salivary mutans streptococci and quality of evidence for these methods was low. Evidence regarding other methods was lacking. For previous caries experience, sensitivity ranged between 0.21 and 0.94 and specificity between 0.20 and 1. Tests using salivary mutans streptococci resulted in low sensitivity and high specificity. For children with primary teeth at baseline, pooled LR for a positive test was 3 for previous caries experience and 4 for salivary mutans streptococci, given a threshold ≥10(5) CFU/ml. Evidence on the validity of analysed methods used for caries risk assessment is limited. As methodological quality was low, there is a need to improve study design. Low validity for the analysed methods may lead to patients with increased risk not being identified, whereas some are falsely identified as being at risk. As caries risk assessment guides individualized decisions on interventions and intervals for patient recall, improved performance based on best evidence is greatly needed. Copyright © 2015 Elsevier Ltd. All rights reserved.
Copy Number Variation in Patients with Disorders of Sex Development Due to 46,XY Gonadal Dysgenesis

PubMed Central

White, Stefan; Ohnesorg, Thomas; Notini, Amanda; Roeszler, Kelly; Hewitt, Jacqueline; Daggag, Hinda; Smith, Craig; Turbitt, Erin; Gustin, Sonja; van den Bergen, Jocelyn; Miles, Denise; Western, Patrick; Arboleda, Valerie; Schumacher, Valerie; Gordon, Lavinia; Bell, Katrina; Bengtsson, Henrik; Speed, Terry; Hutson, John; Warne, Garry; Harley, Vincent; Koopman, Peter; Vilain, Eric; Sinclair, Andrew

2011-01-01

Disorders of sex development (DSD), ranging in severity from mild genital abnormalities to complete sex reversal, represent a major concern for patients and their families. DSD are often due to disruption of the genetic programs that regulate gonad development. Although some genes have been identified in these developmental pathways, the causative mutations have not been identified in more than 50% 46,XY DSD cases. We used the Affymetrix Genome-Wide Human SNP Array 6.0 to analyse copy number variation in 23 individuals with unexplained 46,XY DSD due to gonadal dysgenesis (GD). Here we describe three discrete changes in copy number that are the likely cause of the GD. Firstly, we identified a large duplication on the X chromosome that included DAX1 (NR0B1). Secondly, we identified a rearrangement that appears to affect a novel gonad-specific regulatory region in a known testis gene, SOX9. Surprisingly this patient lacked any signs of campomelic dysplasia, suggesting that the deletion affected expression of SOX9 only in the gonad. Functional analysis of potential SRY binding sites within this deleted region identified five putative enhancers, suggesting that sequences additional to the known SRY-binding TES enhancer influence human testis-specific SOX9 expression. Thirdly, we identified a small deletion immediately downstream of GATA4, supporting a role for GATA4 in gonad development in humans. These CNV analyses give new insights into the pathways involved in human gonad development and dysfunction, and suggest that rearrangements of non-coding sequences disturbing gene regulation may account for significant proportion of DSD cases. PMID:21408189
Using genome wide association studies to identify common QTL regions in three different genetic backgrounds based on Iberian pig breed

PubMed Central

Martínez-Montes, Ángel M.; Fernández, Almudena; Muñoz, María; Noguera, Jose Luis; Folch, Josep M.

2018-01-01

One of the major limitation for the application of QTL results in pig breeding and QTN identification has been the limited number of QTL effects validated in different animal material. The aim of the current work was to validate QTL regions through joint and specific genome wide association and haplotype analyses for growth, fatness and premier cut weights in three different genetic backgrounds, backcrosses based on Iberian pigs, which has a major role in the analysis due to its high productive relevance. The results revealed nine common QTL regions, three segregating in all three backcrosses on SSC1, 0–3 Mb, for body weight, on SSC2, 3–9 Mb, for loin bone-in weight, and on SSC7, 3 Mb, for shoulder weight, and six segregating in two of the three backcrosses, on SSC2, SSC4, SSC6 and SSC10 for backfat thickness, shoulder and ham weights. Besides, 18 QTL regions were specifically identified in one of the three backcrosses, five identified only in BC_LD, seven in BC_DU and six in BC_PI. Beyond identifying and validating QTL, candidate genes and gene variants within the most interesting regions have been explored using functional annotation, gene expression data and SNP identification from RNA-Seq data. The results allowed us to propose a promising list of candidate mutations, those identified in PDE10A, DHCR7, MFN2 and CCNY genes located within the common QTL regions and those identified near ssc-mir-103-1 considered PANK3 regulators to be further analysed. PMID:29522525
Quantitative profiling of immune repertoires for minor lymphocyte counts using unique molecular identifiers.

PubMed

Egorov, Evgeny S; Merzlyak, Ekaterina M; Shelenkov, Andrew A; Britanova, Olga V; Sharonov, George V; Staroverov, Dmitriy B; Bolotin, Dmitriy A; Davydov, Alexey N; Barsova, Ekaterina; Lebedev, Yuriy B; Shugay, Mikhail; Chudakov, Dmitriy M

2015-06-15

Emerging high-throughput sequencing methods for the analyses of complex structure of TCR and BCR repertoires give a powerful impulse to adaptive immunity studies. However, there are still essential technical obstacles for performing a truly quantitative analysis. Specifically, it remains challenging to obtain comprehensive information on the clonal composition of small lymphocyte populations, such as Ag-specific, functional, or tissue-resident cell subsets isolated by sorting, microdissection, or fine needle aspirates. In this study, we report a robust approach based on unique molecular identifiers that allows profiling Ag receptors for several hundred to thousand lymphocytes while preserving qualitative and quantitative information on clonal composition of the sample. We also describe several general features regarding the data analysis with unique molecular identifiers that are critical for accurate counting of starting molecules in high-throughput sequencing applications. Copyright © 2015 by The American Association of Immunologists, Inc.
Assessment Approach for Identifying Compatibility of Restoration Projects with Geomorphic and Flooding Processes in Gravel Bed Rivers

NASA Astrophysics Data System (ADS)

DeVries, Paul; Aldrich, Robert

2015-08-01

A critical requirement for a successful river restoration project in a dynamic gravel bed river is that it be compatible with natural hydraulic and sediment transport processes operating at the reach scale. The potential for failure is greater at locations where the influence of natural processes is inconsistent with intended project function and performance. We present an approach using practical GIS, hydrologic, hydraulic, and sediment transport analyses to identify locations where specific restoration project types have the greatest likelihood of working as intended because their function and design are matched with flooding and morphologic processes. The key premise is to identify whether a specific river analysis segment (length ~1-10 bankfull widths) within a longer reach is geomorphically active or inactive in the context of vertical and lateral stabilities, and hydrologically active for floodplain connectivity. Analyses involve empirical channel geometry relations, aerial photographic time series, LiDAR data, HEC-RAS hydraulic modeling, and a time-integrated sediment transport budget to evaluate trapping efficiency within each segment. The analysis segments are defined by HEC-RAS model cross sections. The results have been used effectively to identify feasible projects in a variety of alluvial gravel bed river reaches with lengths between 11 and 80 km and 2-year flood magnitudes between ~350 and 1330 m3/s. Projects constructed based on the results have all performed as planned. In addition, the results provide key criteria for formulating erosion and flood management plans.
Assessment Approach for Identifying Compatibility of Restoration Projects with Geomorphic and Flooding Processes in Gravel Bed Rivers.

PubMed

DeVries, Paul; Aldrich, Robert

2015-08-01

A critical requirement for a successful river restoration project in a dynamic gravel bed river is that it be compatible with natural hydraulic and sediment transport processes operating at the reach scale. The potential for failure is greater at locations where the influence of natural processes is inconsistent with intended project function and performance. We present an approach using practical GIS, hydrologic, hydraulic, and sediment transport analyses to identify locations where specific restoration project types have the greatest likelihood of working as intended because their function and design are matched with flooding and morphologic processes. The key premise is to identify whether a specific river analysis segment (length ~1-10 bankfull widths) within a longer reach is geomorphically active or inactive in the context of vertical and lateral stabilities, and hydrologically active for floodplain connectivity. Analyses involve empirical channel geometry relations, aerial photographic time series, LiDAR data, HEC-RAS hydraulic modeling, and a time-integrated sediment transport budget to evaluate trapping efficiency within each segment. The analysis segments are defined by HEC-RAS model cross sections. The results have been used effectively to identify feasible projects in a variety of alluvial gravel bed river reaches with lengths between 11 and 80 km and 2-year flood magnitudes between ~350 and 1330 m(3)/s. Projects constructed based on the results have all performed as planned. In addition, the results provide key criteria for formulating erosion and flood management plans.
Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions.

PubMed

Ebner, Matthias; Birschmann, Ingvild; Peter, Andreas; Härtig, Florian; Spencer, Charlotte; Kuhn, Joachim; Blumenstock, Gunnar; Zuern, Christine S; Ziemann, Ulf; Poli, Sven

2017-09-01

In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation. Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values. Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established. Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070. © 2017 American Heart Association, Inc.
Analysis of copy number variations in Holstein cows identify potential mechanisms contributing to differences in residual feed intake.

PubMed

Hou, Yali; Bickhart, Derek M; Chung, Hoyoung; Hutchison, Jana L; Norman, H Duane; Connor, Erin E; Liu, George E

2012-11-01

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. In this study, we performed an initial analysis of copy number variations (CNVs) using BovineHD SNP genotyping data from 147 Holstein cows identified as having high or low feed efficiency as estimated by residual feed intake (RFI). We detected 443 candidate CNV regions (CNVRs) that represent 18.4 Mb (0.6 %) of the genome. To investigate the functional impacts of CNVs, we created two groups of 30 individual animals with extremely low or high estimated breeding values (EBVs) for RFI, and referred to these groups as low intake (LI; more efficient) or high intake (HI; less efficient), respectively. We identified 240 (~9.0 Mb) and 274 (~10.2 Mb) CNVRs from LI and HI groups, respectively. Approximately 30-40 % of the CNVRs were specific to the LI group or HI group of animals. The 240 LI CNVRs overlapped with 137 Ensembl genes. Network analyses indicated that the LI-specific genes were predominantly enriched for those functioning in the inflammatory response and immunity. By contrast, the 274 HI CNVRs contained 177 Ensembl genes. Network analyses indicated that the HI-specific genes were particularly involved in the cell cycle, and organ and bone development. These results relate CNVs to two key variables, namely immune response and organ and bone development. The data indicate that greater feed efficiency relates more closely to immune response, whereas cattle with reduced feed efficiency may have a greater capacity for organ and bone development.
The role of general and specific stressors in the health and well-being of call centre operators.

PubMed

Mellor, David; Moore, Kathleen A; Siong, Zhong Ming Benjamin

2015-01-01

The call centre industry has developed a reputation for generating a highly stressful work environment with high absenteeism and turnover rates. Research has identified role ambiguity, role conflict, role overload, and work-family conflict as common stressors in other settings. Call centre research has additionally identified performance monitoring, job design and job opportunities as call centre specific stressors. This study investigated the impact of the identified stressors on burnout, somatic symptomology, and turnover intent among 126 call centre representatives (CCRs) from 11 call centres in metropolitan Melbourne, Australia. Hierarchical multiple regression analyses found that the common organizational stressors significantly explained between 10% and 53% of the variance in somatic symptomology, burnout (all 3 dimensions) and turnover intent. An additional amount of variance, between 6% and 22% in each of these dependent measures was significantly accounted for by the grouped call centre specific stressors. Overall, common organizational stressors and call centre specific stressors both significantly and independently contributed to burnout, somatic symptomology and turnover intent. These findings are discussed in relation to previous research, and suggestions for improved practice within call centres to safeguard the well-being of workers and for future research are provided.
Variation of a test's sensitivity and specificity with disease prevalence.

PubMed

Leeflang, Mariska M G; Rutjes, Anne W S; Reitsma, Johannes B; Hooft, Lotty; Bossuyt, Patrick M M

2013-08-06

Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.
Variation of a test’s sensitivity and specificity with disease prevalence

PubMed Central

Leeflang, Mariska M.G.; Rutjes, Anne W.S.; Reitsma, Johannes B.; Hooft, Lotty; Bossuyt, Patrick M.M.

2013-01-01

Background: Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. Methods: We used data from 23 meta-analyses, each of which included 10–39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Results: Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. Interpretation: The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation. PMID:23798453
DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating characteristic analysis of U.S. veterans.

PubMed

Main, Keith L; Soman, Salil; Pestilli, Franco; Furst, Ansgar; Noda, Art; Hernandez, Beatriz; Kong, Jennifer; Cheng, Jauhtai; Fairchild, Jennifer K; Taylor, Joy; Yesavage, Jerome; Wesson Ashford, J; Kraemer, Helena; Adamson, Maheen M

2017-01-01

Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n = 109; Age: M = 47.2, SD = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.
Allelic variation contributes to bacterial host specificity

DOE PAGES

Yue, Min; Han, Xiangan; Masi, Leon De; ...

2015-10-30

Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population andmore » functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.« less

Engagement of the left extrastriate body area during body-part metaphor comprehension.

PubMed

Lacey, Simon; Stilla, Randall; Deshpande, Gopikrishna; Zhao, Sinan; Stephens, Careese; McCormick, Kelly; Kemmerer, David; Sathian, K

2017-03-01

Grounded cognition explanations of metaphor comprehension predict activation of sensorimotor cortices relevant to the metaphor's source domain. We tested this prediction for body-part metaphors using functional magnetic resonance imaging while participants heard sentences containing metaphorical or literal references to body parts, and comparable control sentences. Localizer scans identified body-part-specific motor, somatosensory and visual cortical regions. Both subject- and item-wise analyses showed that, relative to control sentences, metaphorical but not literal sentences evoked limb metaphor-specific activity in the left extrastriate body area (EBA), paralleling the EBA's known visual limb-selectivity. The EBA focus exhibited resting-state functional connectivity with ipsilateral semantic processing regions. In some of these regions, the strength of resting-state connectivity correlated with individual preference for verbal processing. Effective connectivity analyses showed that, during metaphor comprehension, activity in some semantic regions drove that in the EBA. These results provide converging evidence for grounding of metaphor processing in domain-specific sensorimotor cortical activity. Published by Elsevier Inc.
Heaven and Earth - `Madonne col Bambino' and `Rustiques figulines'

NASA Astrophysics Data System (ADS)

Bouquillon, A.

Analyses of the productions of della Robbia and Palissy, two masters of Renaissance ceramics in France and in Italy, have enlightened their contributions to the improvement of the glazed terracotta technique. Della Robbia used very homogeneous materials: marly clay for the bodies, and tin-opacified coloured glazes. The technique is here very robust and very mastered. Palissy used different types of clay with different colours and physical properties, associated with specific productions. So far, we have identified seven pastes. Concerning the glazes, he played with transparency and opacity, with lead glazes and with tin-opacified lead glazes. He added traditional colouring oxides as well as specific pigments (lead-tin yellow, haematite, etc.). The mixed-earth technique is specific to his palette. So, the materials used by both artists are completely different and illustrate their different philosophical approaches. To perform the different analyses, new methodologies have been developed: ICP/AES-MS, petrography and X-ray diffractometry for the bodies, PIXE and micro-PIXE, SEM coupled with EDS and Raman spectrometry for the glazes.
Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver

PubMed Central

2011-01-01

Background The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor (TF) that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE) analyses further elucidate the hepatic AhR regulatory network. Results Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate) at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS). AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR), extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'). Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t) > 0.999). Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver. Conclusions Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation. PMID:21762485
An analytical approach to the forensic identification of different classes of new psychoactive substances (NPSs) in seized materials.

PubMed

Strano Rossi, Sabina; Odoardi, Sara; Gregori, Adolfo; Peluso, Giuseppe; Ripani, Luigi; Ortar, Giorgio; Serpelloni, Giovanni; Romolo, Francesco Saverio

2014-09-15

New psychoactive substances (NPSs) are rapidly spreading worldwide, and forensic laboratories are often requested to identify new substances for which no reference standards or analytical data are available. This article describes an analytical approach that was adopted in Italy by a few collaborative centres of the Italian Early Warning System for Drugs, which has contributed many alerts for the identification of different classes of NPSs in the last 24 months. Seized crystals and powders were initially analysed via single quadrupole gas chromatography/mass spectrometry (GC/MS), followed by liquid chromatography/high-resolution mass spectrometry (LC/HRMS) in the positive electrospray ionisation (ESI) mode at 100,000 full width at half maximum resolution (FWHM) without fragmentation to elucidate the elemental compositions of unknown molecules. Different fragmentation voltages during LC/HRMS were applied to study the accurate masses of the obtained characteristic fragments. Nuclear magnetic resonance (NMR) analyses were performed to identify specific isomers when necessary. Some interesting examples of unknown NPSs from seizures later identified in our laboratories are reported, with special focus on those cases where analytical standards were not available during analyses. These cases include cathinones, such as 3-methylmethcathinone (3-MMC), methylone, bk-MBDB (butylone), 4-methylethcathinone (4-MEC), flephedrone, methylenedioxypyrovalerone (MDPV) and pentedrone, methoxetamine, apinaca or AKB48, benzydamine, meta-chlorophenylpiperazine (m-CPP), 5-MeO-N,N-dialkyl tryptamines, such as 5-MeO-DALT and 5-MeOMIPT, benzofurans, such as 6-APB and 4-APB, and diphenidine (identified for the first time in Europe). The identification of NPSs in confiscated materials was successfully achieved via GC/MS coupled with LC/HRMS and, in a few cases, NMR analyses. The availability of GC/MS libraries is of great assistance in the identification of new drugs. Alternatively, the study of characteristic molecule fragments combined with the determination of their accurate masses can be a useful approach to identify unknown samples not previously analysed. Copyright © 2014 John Wiley & Sons, Ltd.
Validity of self-reported stroke in elderly African Americans, Caribbean Hispanics, and Whites.

PubMed

Reitz, Christiane; Schupf, Nicole; Luchsinger, José A; Brickman, Adam M; Manly, Jennifer J; Andrews, Howard; Tang, Ming X; DeCarli, Charles; Brown, Truman R; Mayeux, Richard

2009-07-01

The validity of a self-reported stroke remains inconclusive. To validate the diagnosis of self-reported stroke using stroke identified by magnetic resonance imaging (MRI) as the standard. Community-based cohort study of nondemented, ethnically diverse elderly persons in northern Manhattan. High-resolution quantitative MRIs were acquired for 717 participants without dementia. Sensitivity and specificity of stroke by self-report were examined using cross-sectional analyses and the chi(2) test. Putative relationships between factors potentially influencing the reporting of stroke, including memory performance, cognitive function, and vascular risk factors, were assessed using logistic regression models. Subsequently, all analyses were repeated, stratified by age, sex, ethnic group, and level of education. In analyses of the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4%, and specificity was 78.9%. In analyses stratified by median age (80.1 years), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: sensitivity and specificity, 36.7% and 81.3% vs 27.6% and 26.2%; P = .02). Impaired memory, cognitive skills, or language ability and the presence of hypertension or myocardial infarction were associated with higher rates of false-negative results. Using brain MRI as the standard, specificity and sensitivity of stroke self-report are low. Accuracy of self-report is influenced by age, presence of vascular disease, and cognitive function. In stroke research, sensitive neuroimaging techniques rather than stroke self-report should be used to determine stroke history.
Interim Reliability Evaluation Program: analysis of the Browns Ferry, Unit 1, nuclear plant. Main report

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

Mays, S.E.; Poloski, J.P.; Sullivan, W.H.

1982-07-01

A probabilistic risk assessment (PRA) was made of the Browns Ferry, Unit 1, nuclear plant as part of the Nuclear Regulatory Commission's Interim Reliability Evaluation Program (IREP). Specific goals of the study were to identify the dominant contributors to core melt, develop a foundation for more extensive use of PRA methods, expand the cadre of experienced PRA practitioners, and apply procedures for extension of IREP analyses to other domestic light water reactors. Event tree and fault tree analyses were used to estimate the frequency of accident sequences initiated by transients and loss of coolant accidents. External events such as floods,more » fires, earthquakes, and sabotage were beyond the scope of this study and were, therefore, excluded. From these sequences, the dominant contributors to probable core melt frequency were chosen. Uncertainty and sensitivity analyses were performed on these sequences to better understand the limitations associated with the estimated sequence frequencies. Dominant sequences were grouped according to common containment failure modes and corresponding release categories on the basis of comparison with analyses of similar designs rather than on the basis of detailed plant-specific calculations.« less
Analyses in support of risk-informed natural gas vehicle maintenance facility codes and standards :

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

Ekoto, Isaac W.; Blaylock, Myra L.; LaFleur, Angela Christine

2014-03-01

Safety standards development for maintenance facilities of liquid and compressed gas fueled large-scale vehicles is required to ensure proper facility design and operation envelopes. Standard development organizations are utilizing risk-informed concepts to develop natural gas vehicle (NGV) codes and standards so that maintenance facilities meet acceptable risk levels. The present report summarizes Phase I work for existing NGV repair facility code requirements and highlights inconsistencies that need quantitative analysis into their effectiveness. A Hazardous and Operability study was performed to identify key scenarios of interest. Finally, scenario analyses were performed using detailed simulations and modeling to estimate the overpressure hazardsmore » from HAZOP defined scenarios. The results from Phase I will be used to identify significant risk contributors at NGV maintenance facilities, and are expected to form the basis for follow-on quantitative risk analysis work to address specific code requirements and identify effective accident prevention and mitigation strategies.« less
Ecological Patterns Among Bacteria and Microbial Eukaryotes Derived from Network Analyses in a Low-Salinity Lake.

PubMed

Jones, Adriane Clark; Hambright, K David; Caron, David A

2018-05-01

Microbial communities are comprised of complex assemblages of highly interactive taxa. We employed network analyses to identify and describe microbial interactions and co-occurrence patterns between microbial eukaryotes and bacteria at two locations within a low salinity (0.5-3.5 ppt) lake over an annual cycle. We previously documented that the microbial diversity and community composition within Lake Texoma, southwest USA, were significantly affected by both seasonal forces and a site-specific bloom of the harmful alga, Prymnesium parvum. We used network analyses to answer ecological questions involving both the bacterial and microbial eukaryotic datasets and to infer ecological relationships within the microbial communities. Patterns of connectivity at both locations reflected the seasonality of the lake including a large rain disturbance in May, while a comparison of the communities between locations revealed a localized response to the algal bloom. A network built from shared nodes (microbial operational taxonomic units and environmental variables) and correlations identified conserved associations at both locations within the lake. Using network analyses, we were able to detect disturbance events, characterize the ecological extent of a harmful algal bloom, and infer ecological relationships not apparent from diversity statistics alone.
Behavioural aspects of terrorism.

PubMed

Leistedt, Samuel J

2013-05-10

Behavioural and social sciences are useful in collecting and analysing intelligence data, understanding terrorism, and developing strategies to combat terrorism. This article aims to examine the psychopathological concepts of terrorism and discusses the developing roles for behavioural scientists. A systematic review was conducted of studies investigating behavioural aspects of terrorism. These studies were identified by a systematic search of databases, textbooks, and a supplementary manual search of references. Several fundamental concepts were identified that continue to influence the motives and the majority of the behaviours of those who support or engage in this kind of specific violence. Regardless of the psychological aspects and new roles for psychiatrists, the behavioural sciences will continue to be called upon to assist in developing better methods to gather and analyse intelligence, to understand terrorism, and perhaps to stem the radicalisation process. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
TEMPLE: analysing population genetic variation at transcription factor binding sites.

PubMed

Litovchenko, Maria; Laurent, Stefan

2016-11-01

Genetic variation occurring at the level of regulatory sequences can affect phenotypes and fitness in natural populations. This variation can be analysed in a population genetic framework to study how genetic drift and selection affect the evolution of these functional elements. However, doing this requires a good understanding of the location and nature of regulatory regions and has long been a major hurdle. The current proliferation of genomewide profiling experiments of transcription factor occupancies greatly improves our ability to identify genomic regions involved in specific DNA-protein interactions. Although software exists for predicting transcription factor binding sites (TFBS), and the effects of genetic variants on TFBS specificity, there are no tools currently available for inferring this information jointly with the genetic variation at TFBS in natural populations. We developed the software Transcription Elements Mapping at the Population LEvel (TEMPLE), which predicts TFBS, evaluates the effects of genetic variants on TFBS specificity and summarizes the genetic variation occurring at TFBS in intraspecific sequence alignments. We demonstrate that TEMPLE's TFBS prediction algorithms gives identical results to PATSER, a software distribution commonly used in the field. We also illustrate the unique features of TEMPLE by analysing TFBS diversity for the TF Senseless (SENS) in one ancestral and one cosmopolitan population of the fruit fly Drosophila melanogaster. TEMPLE can be used to localize TFBS that are characterized by strong genetic differentiation across natural populations. This will be particularly useful for studies aiming to identify adaptive mutations. TEMPLE is a java-based cross-platform software that easily maps the genetic diversity at predicted TFBSs using a graphical interface, or from the Unix command line. © 2016 John Wiley & Sons Ltd.
Rebalance electronics

NASA Technical Reports Server (NTRS)

Blalock, T. V.; Kennedy, E. J.

1972-01-01

Two basic types of strapdown gyroscope rebalance-electronics were analyzed and compared. These two types were a discrete-pulse ternary system and a width-modulated binary system. In the analyses, major emphasis was placed on the logic sections, the H-switches, the precision voltage reference loops, the noise performance, common-mode rejection, and loop compensation. Results of the analyses were used in identifying specific advantages and disadvantages of system details and in making accuracy and resolution comparisons. Sound engineering principles were applied in the development of both systems; however, it was concluded that each system has some disadvantages that are amenable to improvement.
Lack of specific alleles for the bovine chemokine (C-X-C) receptor type 4 (CXCR4) gene in West African cattle questions its role as a candidate for trypanotolerance.

PubMed

Álvarez, Isabel; Pérez-Pardal, Lucía; Traoré, Amadou; Fernández, Iván; Goyache, Félix

2016-08-01

A panel of 81 Asian, African and European cattle (Bos taurus and B. indicus) was analysed for the whole sequence of the CXCR4 gene (3844bp), a strong candidate for cattle trypanotolerance. Thirty-one polymorphic sites identified gave 31 different haplotypes. Neutrality tests rejected the hypothesis of either positive or purifying selection. Bayesian phylogenetic tree showed differentiation of haplotypes into two clades gathering genetic variability predating domestication. Related with clades definition, linkage disequilibrium analyses suggested the existence of one only linkage block on the CXCR4 gene. Two tag SNPs identified on exon 2 captured 50% of variability. Whatever the analysis carried out, no clear separation between cattle groups was identified. Most haplotypes identified in West African taurine cattle were also found in European cattle and in Asian and West African zebu. West African taurine samples did not carry unique variants on the CXCR4 gene sequence. The current analysis failed in identifying a causal mutation on the CXCR4 gene underlying a previously reported QTL for cattle trypanotolerance on BTA2. Copyright © 2016 Elsevier B.V. All rights reserved.
Amor and Social Stigma: ASD Beliefs Among Immigrant Mexican Parents.

PubMed

Cohen, Shana R; Miguel, Jessica

2018-06-01

This study examined cultural beliefs about ASD and its causes among Mexican-heritage families. In focus group interviews, we asked 25 immigrant parents of children with ASD to identify words they associated with ASD and its causes. Participants free-listed, ranked, and justified their responses. Mixed methods analyses utilized saliency scores to calculate responses. Deductive interview analyses justified participants' responses. Salient responses for ASD perceptions included specific characteristics about the child (e.g., loving) and perceptions about lack of resources. Salient responses for ASD causes were vaccines, genetics, and a combination of genetics and environment. Inductive analyses revealed distinct beliefs about social stigma, child characteristics, factors supporting development, and parents' emotional stress. Interpretations linked these beliefs to promising adaptations in diagnosis and treatment.
Characteristics of genomic signatures derived using univariate methods and mechanistically anchored functional descriptors for predicting drug- and xenobiotic-induced nephrotoxicity.

PubMed

Shi, Weiwei; Bugrim, Andrej; Nikolsky, Yuri; Nikolskya, Tatiana; Brennan, Richard J

2008-01-01

ABSTRACT The ideal toxicity biomarker is composed of the properties of prediction (is detected prior to traditional pathological signs of injury), accuracy (high sensitivity and specificity), and mechanistic relationships to the endpoint measured (biological relevance). Gene expression-based toxicity biomarkers ("signatures") have shown good predictive power and accuracy, but are difficult to interpret biologically. We have compared different statistical methods of feature selection with knowledge-based approaches, using GeneGo's database of canonical pathway maps, to generate gene sets for the classification of renal tubule toxicity. The gene set selection algorithms include four univariate analyses: t-statistics, fold-change, B-statistics, and RankProd, and their combination and overlap for the identification of differentially expressed probes. Enrichment analysis following the results of the four univariate analyses, Hotelling T-square test, and, finally out-of-bag selection, a variant of cross-validation, were used to identify canonical pathway maps-sets of genes coordinately involved in key biological processes-with classification power. Differentially expressed genes identified by the different statistical univariate analyses all generated reasonably performing classifiers of tubule toxicity. Maps identified by enrichment analysis or Hotelling T-square had lower classification power, but highlighted perturbed lipid homeostasis as a common discriminator of nephrotoxic treatments. The out-of-bag method yielded the best functionally integrated classifier. The map "ephrins signaling" performed comparably to a classifier derived using sparse linear programming, a machine learning algorithm, and represents a signaling network specifically involved in renal tubule development and integrity. Such functional descriptors of toxicity promise to better integrate predictive toxicogenomics with mechanistic analysis, facilitating the interpretation and risk assessment of predictive genomic investigations.
Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations.

PubMed

Hu, Yao; Li, Huaixing; Lu, Ling; Manichaikul, Ani; Zhu, Jingwen; Chen, Yii-Der I; Sun, Liang; Liang, Shuang; Siscovick, David S; Steffen, Lyn M; Tsai, Michael Y; Rich, Stephen S; Lemaitre, Rozenn N; Lin, Xu

2016-03-15

Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10(-14) and 4.30 × 10(-12), respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Unique and shared techniques in cognitive-behavioural and short-term psychodynamic psychotherapy: a content analysis of randomised trials on depression

PubMed Central

Barth, Jürgen; Michlig, Nadja; Munder, Thomas

2014-01-01

Randomised controlled trials (RCTs) of psychotherapeutic interventions assume that specific techniques are used in treatments, which are responsible for changes in the client's symptoms. This assumption also holds true for meta-analyses, where evidence for specific interventions and techniques is compiled. However, it has also been argued that different treatments share important techniques and that an upcoming consensus about useful treatment strategies is leading to a greater integration of treatments. This makes assumptions about the effectiveness of specific interventions ingredients questionable if the shared (common) techniques are more often used in interventions than are the unique techniques. This study investigated the unique or shared techniques in RCTs of cognitive-behavioural therapy (CBT) and short-term psychodynamic psychotherapy (STPP). Psychotherapeutic techniques were coded from 42 masked treatment descriptions of RCTs in the field of depression (1979–2010). CBT techniques were often used in studies identified as either CBT or STPP. However, STPP techniques were only used in STPP-identified studies. Empirical clustering of treatment descriptions did not confirm the original distinction of CBT versus STPP, but instead showed substantial heterogeneity within both approaches. Extraction of psychotherapeutic techniques from the treatment descriptions is feasible and could be used as a content-based approach to classify treatments in systematic reviews and meta-analyses. PMID:25750827
A mixed methods approach to adapting health-related quality of life measures for use in routine oncology clinical practice.

PubMed

Harley, Clare; Takeuchi, Elena; Taylor, Sally; Keding, Ada; Absolom, Kate; Brown, Julia; Velikova, Galina

2012-04-01

The current study reviewed and adapted existing health-related quality of life (HRQoL) instruments for use in routine clinical practice delivering outpatient chemotherapy for colorectal, breast and gynaecological cancers. 564 (288 gynaecological, 208 breast and 68 colorectal) outpatient consultations of 141 patients were audio-recorded and analysed to identify discussed issues. Issues were ranked from most to least commonly discussed within each disease group. Existing HRQoL instruments were evaluated against these lists and best fitting items entered into cancer-specific item banks. Item banks were evaluated during semi-structured interviews by twenty-one oncologists (13 consultants and 8 specialist registrars), four clinical nurse specialists and thirty patients, from breast, gynaecological and colorectal cancer practices. Pilot questionnaires were completed by 448 (145 breast, 148 gynaecological and 155 colorectal) patients attending outpatient clinics. Item selection and scale reliability was explored using descriptive data and psychometric methods alongside qualitative patient and clinician ratings. Each questionnaire includes five physical and three psychosocial function scales each with good internal consistency reliability (α > 0.70) plus disease-specific individual-symptom items identified as useful in clinical practice. Three cancer-specific health-related quality of life measures were developed for use in routine clinical practice. Initial analyses suggest good clinical utility and acceptable psychometric properties for the new instruments.
Identification of candidate chemosensory genes in the antennal transcriptome of Tenebrio molitor (Coleoptera: Tenebrionidae).

PubMed

Liu, Su; Rao, Xiang-Jun; Li, Mao-Ye; Feng, Ming-Feng; He, Meng-Zhu; Li, Shi-Guang

2015-03-01

We present the first antennal transcriptome sequencing information for the yellow mealworm beetle, Tenebrio molitor (Coleoptera: Tenebrionidae). Analysis of the transcriptome dataset obtained 52,216,616 clean reads, from which 35,363 unigenes were assembled. Of these, 18,820 unigenes showed significant similarity (E-value <10(-5)) to known proteins in the NCBI non-redundant protein database. Gene ontology (GO) and Cluster of Orthologous Groups (COG) analyses were used for functional classification of these unigenes. We identified 19 putative odorant-binding protein (OBP) genes, 12 chemosensory protein (CSP) genes, 20 olfactory receptor (OR) genes, 6 ionotropic receptor (IR) genes and 2 sensory neuron membrane protein (SNMP) genes. BLASTX best hit results indicated that these chemosensory genes were most identical to their respective orthologs from Tribolium castaneum. Phylogenetic analyses also revealed that the T. molitor OBPs and CSPs are closely related to those of T. castaneum. Real-time quantitative PCR assays showed that eight TmolOBP genes were antennae-specific. Of these, TmolOBP5, TmolOBP7 and TmolOBP16 were found to be predominantly expressed in male antennae, while TmolOBP17 was expressed mainly in the legs of males. Several other genes were identified that were neither tissue-specific nor sex-specific. These results establish a firm foundation for future studies of the chemosensory genes in T. molitor. Copyright © 2015 Elsevier Inc. All rights reserved.
SYMBIOmatics: synergies in Medical Informatics and Bioinformatics--exploring current scientific literature for emerging topics.

PubMed

Rebholz-Schuhman, Dietrich; Cameron, Graham; Clark, Dominic; van Mulligen, Erik; Coatrieux, Jean-Louis; Del Hoyo Barbolla, Eva; Martin-Sanchez, Fernando; Milanesi, Luciano; Porro, Ivan; Beltrame, Francesco; Tollis, Ioannis; Van der Lei, Johan

2007-03-08

The SYMBIOmatics Specific Support Action (SSA) is "an information gathering and dissemination activity" that seeks "to identify synergies between the bioinformatics and the medical informatics" domain to improve collaborative progress between both domains (ref. to http://www.symbiomatics.org). As part of the project experts in both research fields will be identified and approached through a survey. To provide input to the survey, the scientific literature was analysed to extract topics relevant to both medical informatics and bioinformatics. This paper presents results of a systematic analysis of the scientific literature from medical informatics research and bioinformatics research. In the analysis pairs of words (bigrams) from the leading bioinformatics and medical informatics journals have been used as indication of existing and emerging technologies and topics over the period 2000-2005 ("recent") and 1990-1990 ("past"). We identified emerging topics that were equally important to bioinformatics and medical informatics in recent years such as microarray experiments, ontologies, open source, text mining and support vector machines. Emerging topics that evolved only in bioinformatics were system biology, protein interaction networks and statistical methods for microarray analyses, whereas emerging topics in medical informatics were grid technology and tissue microarrays. We conclude that although both fields have their own specific domains of interest, they share common technological developments that tend to be initiated by new developments in biotechnology and computer science.
SYMBIOmatics: Synergies in Medical Informatics and Bioinformatics – exploring current scientific literature for emerging topics

PubMed Central

Rebholz-Schuhman, Dietrich; Cameron, Graham; Clark, Dominic; van Mulligen, Erik; Coatrieux, Jean-Louis; Del Hoyo Barbolla, Eva; Martin-Sanchez, Fernando; Milanesi, Luciano; Porro, Ivan; Beltrame, Francesco; Tollis, Ioannis; Van der Lei, Johan

2007-01-01

Background The SYMBIOmatics Specific Support Action (SSA) is "an information gathering and dissemination activity" that seeks "to identify synergies between the bioinformatics and the medical informatics" domain to improve collaborative progress between both domains (ref. to ). As part of the project experts in both research fields will be identified and approached through a survey. To provide input to the survey, the scientific literature was analysed to extract topics relevant to both medical informatics and bioinformatics. Results This paper presents results of a systematic analysis of the scientific literature from medical informatics research and bioinformatics research. In the analysis pairs of words (bigrams) from the leading bioinformatics and medical informatics journals have been used as indication of existing and emerging technologies and topics over the period 2000–2005 ("recent") and 1990–1990 ("past"). We identified emerging topics that were equally important to bioinformatics and medical informatics in recent years such as microarray experiments, ontologies, open source, text mining and support vector machines. Emerging topics that evolved only in bioinformatics were system biology, protein interaction networks and statistical methods for microarray analyses, whereas emerging topics in medical informatics were grid technology and tissue microarrays. Conclusion We conclude that although both fields have their own specific domains of interest, they share common technological developments that tend to be initiated by new developments in biotechnology and computer science. PMID:17430562

Elevated serum α-linolenic acid levels are associated with decreased chance of pregnancy after in vitro fertilization.

PubMed

Jungheim, Emily S; Macones, George A; Odem, Randall R; Patterson, Bruce W; Moley, Kelle H

2011-10-01

To analyze relationships between serum free fatty acid (FFA) concentrations and pregnancy. Prospective cohort. University hospital. Ninety-one women undergoing IVF. Serum was analyzed for total and specific serum FFAs, including myristic, palmitic, stearic, oleic, linoleic, and α-linolenic acids. Univariate analyses were used to identify specific FFAs and other factors associated with pregnancy after IVF. Logistic regression was performed modeling relationships between identified factors and chance of pregnancy. In unadjusted analyses, women with elevated serum α-linolenic acid (ALA) levels (highest quartile) demonstrated a decreased chance of pregnancy compared with women with the lowest levels (odds ratio 0.24, 95% confidence interval 0.052-0.792). No associations between other FFAs and pregnancy were identified. In a multivariable regression model, associations between elevated serum ALA levels and decreased chance of pregnancy remained after adjusting for patient age, body mass index, and history of endometriosis or previous live birth (adjusted odds ratio 0.139, 95% confidence interval 0.028-0.686). Elevated serum ALA levels are associated with decreased chance of pregnancy in women undergoing IVF. Further work is needed to determine whether ALA is involved in early reproductive processes and whether the relationship between ALA and pregnancy is associated with excess ALA intake, impaired ALA metabolism, or both. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
How the Best Get Better: An Analysis of the Self-Monitoring Strategies Used by Expert Golf Instructors

ERIC Educational Resources Information Center

Schempp, Paul G.; Webster, Collin; McCullick, Bryan A.; Busch, Christopher; Mason, Ilse Sannen

2007-01-01

The purpose of this study was to analyse the self-monitoring strategies that 31 expert golf instructors used to improve their teaching. Specifically, criteria characteristic of both instructional strengths and weaknesses were identified, as were the strategies these teachers used to continue to develop their strengths and improve their areas of…
The Persistence of Gender Inequality in Zimbabwe: Factors That Impede the Advancement of Women into Leadership Positions in Primary Schools

ERIC Educational Resources Information Center

Chabaya, Owence; Rembe, Symphorosa; Wadesango, Newman

2009-01-01

We investigated and analysed the factors that women teachers consider as barriers to their advancement to headship positions in Zimbabwean primary schools. Specifically, we sought to identify the factors perceived by women school heads to be causes of persistent under-representation of women in school headship positions. Data were collected…
English Textbooks for Russian Students: Problems and Specific Features

ERIC Educational Resources Information Center

Solnyshkina, Marina I.; Vishnyakova, Ol'ga D.; Gafiyatova, Elzara V.; Gabitov, Azat I.

2017-01-01

The research identifies the complexity level of eight texts from Spotlight 11 used in Russian TEFL to prepare students for National Unified Exam in English and assess their reading skills. The results of the analyses conducted with the help of T.E.R.A., an automated text processor, prove that all texts fell within the range of 6-9 Flesch-Kincaid…
Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation: long-term results from the Bio-CAPTURE registry.

PubMed

van den Reek, J M P A; Tummers, M; Zweegers, J; Seyger, M M B; van Lümig, P P M; Driessen, R J B; van de Kerkhof, P C M; Kievit, W; de Jong, E M G J

2015-03-01

Drug survival is an indicator for treatment success; insight in predictors associated with drug survival is important. To analyse the long-term drug survival for adalimumab in patients with psoriasis treated in daily practice and (II) to identify predictors of prolonged drug survival for adalimumab split for different reasons of discontinuation. Data were extracted from a prospective psoriasis cohort and analysed using Kaplan-Meier survival curves split for reasons of discontinuation. Baseline predictors associated with longer drug survival were identified using multivariate Cox-regression analysis. One hundred and sixteen patients were included with a total of 208 patient-years. Overall drug survival was 76% after 1 year and 52% after 4.5 years. In patients who stopped due to ineffectiveness, longer drug survival was associated with the absence of specific comorbidities (P = 0.03). In patients who stopped due to side-effects, longer drug survival was associated with male gender (P = 0.02). Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation. Strong, specific predictors can lead to patient-tailored treatment. © 2014 European Academy of Dermatology and Venereology.
Sensitivity and specificity of a brief personality screening instrument in predicting future substance use, emotional, and behavioral problems: 18-month predictive validity of the Substance Use Risk Profile Scale.

PubMed

Castellanos-Ryan, Natalie; O'Leary-Barrett, Maeve; Sully, Laura; Conrod, Patricia

2013-01-01

This study assessed the validity, sensitivity, and specificity of the Substance Use Risk Profile Scale (SURPS), a measure of personality risk factors for substance use and other behavioral problems in adolescence. The concurrent and predictive validity of the SURPS was tested in a sample of 1,162 adolescents (mean age: 13.7 years) using linear and logistic regressions, while its sensitivity and specificity were examined using the receiver operating characteristics curve analyses. Concurrent and predictive validity tests showed that all 4 brief scales-hopelessness (H), anxiety sensitivity (AS), impulsivity (IMP), and sensation seeking (SS)-were related, in theoretically expected ways, to measures of substance use and other behavioral and emotional problems. Results also showed that when using the 4 SURPS subscales to identify adolescents "at risk," one can identify a high number of those who developed problems (high sensitivity scores ranging from 72 to 91%). And, as predicted, because each scale is related to specific substance and mental health problems, good specificity was obtained when using the individual personality subscales (e.g., most adolescents identified at high risk by the IMP scale developed conduct or drug use problems within the next 18 months [a high specificity score of 70 to 80%]). The SURPS is a valuable tool for identifying adolescents at high risk for substance misuse and other emotional and behavioral problems. Implications of findings for the use of this measure in future research and prevention interventions are discussed. Copyright © 2012 by the Research Society on Alcoholism.
Health economic analyses in medical nutrition: a systematic literature review.

PubMed

Walzer, Stefan; Droeschel, Daniel; Nuijten, Mark; Chevrou-Séverac, Hélène

2014-01-01

Medical nutrition is a specific nutrition category either covering specific dietary needs and/or nutrient deficiency in patients or feeding patients unable to eat normally. Medical nutrition is regulated by a specific bill in Europe and in the US, with specific legislation and guidelines, and is provided to patients with special nutritional needs and indications for nutrition support. Therefore, medical nutrition products are delivered by medical prescription and supervised by health care professionals. Although these products have existed for more than 2 decades, health economic evidence of medical nutrition interventions is scarce. This research assesses the current published health economic evidence for medical nutrition by performing a systematic literature review related to health economic analysis of medical nutrition. A systematic literature search was done using standard literature databases, including PubMed, the Health Technology Assessment Database, and the National Health Service Economic Evaluation Database. Additionally, a free web-based search was conducted using the same search terms utilized in the systematic database search. The clinical background and basis of the analysis, health economic design, and results were extracted from the papers finally selected. The Drummond checklist was used to validate the quality of health economic modeling studies and the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist was used for published systematic reviews. Fifty-three papers were identified and obtained via PubMed, or directly via journal webpages for further assessment. Thirty-two papers were finally included in a thorough data extraction procedure, including those identified by a "gray literature search" utilizing the Google search engine and cross-reference searches. Results regarding content of the studies showed that malnutrition was the underlying clinical condition in most cases (32%). In addition, gastrointestinal disorders (eg, surgery, cancer) were often analyzed. In terms of settings, 56% of papers covered inpatients, whereas 14 papers (44%) captured outpatients, including patients in community centers. Interestingly, in comparison with the papers identified overall, very few health economic models were found. Most of the articles were modeling analyses and economic trials in different design settings. Overall, only eight health economic models were published and were validated applying the Drummond checklist. In summary, most of the models included were carried out to quite a high standard, although some areas were identified for further improvement. Of the two systematic health economic reviews identified, one achieved the highest quality score when applying the AMSTAR checklist. The reasons for finding only a few modeling studies but quite a large number of clinical trials with health economic endpoints, might be different. Until recently, health economics has not been required for reimbursement or coverage decisions concerning medical nutrition interventions. Further, there might be specifics of medical nutrition which might not allow easy modeling and consequently explain the limited uptake so far. The health economic data on medical nutrition generated and published is quite ample. However, it has been primarily based on database analysis and clinical studies. Only a few modeling analyses have been carried out, indicating a need for further research to understand the specifics of medical nutrition and their applicability for health economic modeling.
Extensive review of shale gas environmental impacts from scientific literature (2010-2015).

PubMed

Costa, Daniele; Jesus, João; Branco, David; Danko, Anthony; Fiúza, António

2017-06-01

Extensive reviews and meta-analyses are essential to summarize emerging developments in a specific field and offering information on the current trends in the scientific literature. Shale gas exploration and exploitation has been extensively debated in literature, but a comprehensive review of recent studies on the environmental impacts has yet to be carried out. Therefore, the goal of this article is to systematically examine scientific articles published between 2010 and 2015 and identify recent advances and existing data gaps. The examined articles were classified into six main categories (water resources, atmospheric emissions, land use, induced seismicity, occupational and public health and safety, and other impacts). These categories are analyzed separately to identify specific challenges, possibly existing consensus and data gaps yet remained in the literature.
Circadian Enhancers Coordinate Multiple Phases of Rhythmic Gene Transcription In Vivo

PubMed Central

Fang, Bin; Everett, Logan J.; Jager, Jennifer; Briggs, Erika; Armour, Sean M.; Feng, Dan; Roy, Ankur; Gerhart-Hines, Zachary; Sun, Zheng; Lazar, Mitchell A.

2014-01-01

SUMMARY Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of eRNAs that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed novel mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed new light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ. PMID:25416951
Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo.

PubMed

Fang, Bin; Everett, Logan J; Jager, Jennifer; Briggs, Erika; Armour, Sean M; Feng, Dan; Roy, Ankur; Gerhart-Hines, Zachary; Sun, Zheng; Lazar, Mitchell A

2014-11-20

Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of enhancer RNAs (eRNAs) that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ.
Multivariate Protein Signatures of Pre-Clinical Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Plasma Proteome Dataset

PubMed Central

Johnstone, Daniel; Milward, Elizabeth A.; Berretta, Regina; Moscato, Pablo

2012-01-01

Background Recent Alzheimer's disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. Methods and Findings We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10−13). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. Conclusions Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of plasma biomarkers for pre-clinical AD. While studies of independent test sets are required to validate the signatures, these analyses provide a starting point for developing a cost-effective and minimally invasive test capable of diagnosing AD in its pre-clinical stages. PMID:22485168
Formalizing the definition of meta-analysis in Molecular Ecology.

PubMed

ArchMiller, Althea A; Bauer, Eric F; Koch, Rebecca E; Wijayawardena, Bhagya K; Anil, Ammu; Kottwitz, Jack J; Munsterman, Amelia S; Wilson, Alan E

2015-08-01

Meta-analysis, the statistical synthesis of pertinent literature to develop evidence-based conclusions, is relatively new to the field of molecular ecology, with the first meta-analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta-analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta-analyses previously published in this journal. We also provide a brief overview of the many components required for meta-analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's FST and its related analogues as effect sizes in meta-analysis. We performed a literature review to identify articles published as 'meta-analyses' in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta-analyses published in Molecular Ecology have the potential to set the standard for meta-analyses in other journals. We found that while many of these reviewed articles were strong meta-analyses, others failed to follow standard meta-analytical techniques. One of these unsatisfactory meta-analyses was in fact a secondary analysis. Other studies attempted meta-analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta-analysis. By drawing attention to the inconsistency of studies labelled as meta-analyses, we emphasize the importance of understanding the components of traditional meta-analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology. © 2015 John Wiley & Sons Ltd.
Sensitivity and specificity of waist circumference as a single screening tool for identification of overweight and obesity among Malaysian adults.

PubMed

Kee, C C; Jamaiyah, H; Geeta, A; Ali, Z Ahmad; Safiza, M N Noor; Suzana, S; Khor, G L; Rahmah, R; Jamalludin, A R; Sumarni, M G; Lim, K H; Faudzi, Y Ahmad; Amal, N M

2011-12-01

Generalised obesity and central obesity are risk factors for Type II diabetes mellitus and cardiovascular diseases. Waist circumference (WC) has been suggested as a single screening tool for identification of overweight or obese subjects in lieu of the body mass index (BMI) for weight management in public health program. Currently, the recommended waist circumference cut-off points of > or = 94cm for men and > or =80cm for women (waist action level 1) and > or = 102cm for men and > or = 88cm for women (waist action level 2) used for identification of overweight and obesity are based on studies in Caucasian populations. The objective of this study was to assess the sensitivity and specificity of the recommended waist action levels, and to determine optimal WC cut-off points for identification of overweight or obesity with central fat distribution based on BMI for Malaysian adults. Data from 32,773 subjects (14,982 men and 17,791 women) aged 18 and above who participated in the Third National Health Morbidity Survey in 2006 were analysed. Sensitivity and specificity of WC at waist action level 1 were 48.3% and 97.5% for men; and 84.2% and 80.6% for women when compared to the cut-off points based on BMI > or = 25kg/m2. At waist action level 2, sensitivity and specificity were 52.4% and 98.0% for men, and 79.2% and 85.4% for women when compared with the cut-off points based on BMI (> or = 30 kg/m2). Receiver operating characteristic analyses showed that the appropriatescreening cut-off points for WC to identify subjects with overweight (> or = 25kg/m2) was 86.0cm (sensitivity=83.6%, specificity=82.5%) for men, and 79.1cm (sensitivity=85.0%, specificity=79.5%) for women. Waist circumference cut-off points to identify obese subjects (BMI > or = 30 kg/m2) was 93.2cm (sensitivity=86.5%, specificity=85.7%) for men and 85.2cm (sensitivity=77.9%, specificity=78.0%) for women. Our findings demonstrated that the current recommended waist circumference cut-off points have low sensitivity for identification of overweight and obesity in men. We suggest that these newly identified cut-off points be considered.
Altered expression of testis-specific genes, piRNAs, and transposons in the silkworm ovary masculinized by a W chromosome mutation

PubMed Central

2012-01-01

Background In the silkworm, Bombyx mori, femaleness is strongly controlled by the female-specific W chromosome. Originally, it was presumed that the W chromosome encodes female-determining gene(s), accordingly called Fem. However, to date, neither Fem nor any protein-coding gene has been identified from the W chromosome. Instead, the W chromosome is occupied with numerous transposon-related sequences. Interestingly, the silkworm W chromosome is a source of female-enriched PIWI-interacting RNAs (piRNAs). piRNAs are small RNAs of 23-30 nucleotides in length, which are required for controlling transposon activity in animal gonads. A recent study has identified a novel mutant silkworm line called KG, whose mutation in the W chromosome causes severe female masculinization. However, the molecular nature of KG line has not been well characterized yet. Results Here we molecularly characterize the KG line. Genomic PCR analyses using currently available W chromosome-specific PCR markers indicated that no large deletion existed in the KG W chromosome. Genetic analyses demonstrated that sib-crosses within the KG line suppressed masculinization. Masculinization reactivated when crossing KG females with wild type males. Importantly, the KG ovaries exhibited a significantly abnormal transcriptome. First, the KG ovaries misexpressed testis-specific genes. Second, a set of female-enriched piRNAs was downregulated in the KG ovaries. Third, several transposons were overexpressed in the KG ovaries. Conclusions Collectively, the mutation in the KG W chromosome causes broadly altered expression of testis-specific genes, piRNAs, and transposons. To our knowledge, this is the first study that describes a W chromosome mutant with such an intriguing phenotype. PMID:22452797
Multi-country health surveys: are the analyses misleading?

PubMed

Masood, Mohd; Reidpath, Daniel D

2014-05-01

The aim of this paper was to review the types of approaches currently utilized in the analysis of multi-country survey data, specifically focusing on design and modeling issues with a focus on analyses of significant multi-country surveys published in 2010. A systematic search strategy was used to identify the 10 multi-country surveys and the articles published from them in 2010. The surveys were selected to reflect diverse topics and foci; and provide an insight into analytic approaches across research themes. The search identified 159 articles appropriate for full text review and data extraction. The analyses adopted in the multi-country surveys can be broadly classified as: univariate/bivariate analyses, and multivariate/multivariable analyses. Multivariate/multivariable analyses may be further divided into design- and model-based analyses. Of the 159 articles reviewed, 129 articles used model-based analysis, 30 articles used design-based analyses. Similar patterns could be seen in all the individual surveys. While there is general agreement among survey statisticians that complex surveys are most appropriately analyzed using design-based analyses, most researchers continued to use the more common model-based approaches. Recent developments in design-based multi-level analysis may be one approach to include all the survey design characteristics. This is a relatively new area, however, and there remains statistical, as well as applied analytic research required. An important limitation of this study relates to the selection of the surveys used and the choice of year for the analysis, i.e., year 2010 only. There is, however, no strong reason to believe that analytic strategies have changed radically in the past few years, and 2010 provides a credible snapshot of current practice.
A Shortened Version of the Suicide Cognitions Scale for Identifying Chronic Pain Patients at Risk for Suicide.

PubMed

Bryan, Craig J; Kanzler, Kathryn E; Grieser, Emily; Martinez, Annette; Allison, Sybil; McGeary, Donald

2017-03-01

Research in psychiatric outpatient and inpatient populations supports the utility of the Suicide Cognitions Scale (SCS) as an indicator of current and future risk for suicidal thoughts and behaviors. Designed to assess suicide-specific thoughts and beliefs, the SCS has yet to be evaluated among chronic pain patients, a group with elevated risk for suicide. The purpose of the present study was to develop and test a shortened version of the SCS (the SCS-S). A total of 228 chronic pain patients completed a battery of self-report surveys before or after a scheduled appointment. Three outpatient medical clinics (pain medicine, orofacial pain, and clinical health psychology). Confirmatory factor analysis, multivariate regression, and graded item response theory model analyses. Results of the CFAs suggested that a 3-factor solution was optimal. A shortened 9-item scale was identified based on the results of graded item response theory model analyses. Correlation and multivariate analyses supported the construct and incremental validity of the SCS-S. Results support the reliability and validity of the SCS-S among chronic pain patients, and suggest the scale may be a useful method for identifying high-risk patients in medical settings. © 2016 World Institute of Pain.
Differences of Perceived Image Generated through the Web Site: Empirical Evidence Obtained in Spanish Destinations

PubMed Central

Blazquez-Resino, Juan J.; Muro-Rodriguez, Ana I.; Perez-Jimenez, Israel R.

2016-01-01

In this paper, a study of the perceived destination image created by promotional Web Pages is expounded in an attempt to identify their differences as generators of destination image in the consumers' mind. Specifically, it seeks to analyse whether the web sites of different Spanish regions improve the image that consumers have of the destination, identifying their main dimensions and analysing its effect on satisfaction and intentions of the future behavior of potential visitors. To achieve these objectives and verify the hypotheses, a laboratory experiment was performed, where it was determined what changes are produced in the tourist's previous image after browsing the tourist webs of three different regions. Moreover, it analyses the differences in the effect of the perceived image on satisfaction and potential visitors' future behavioral intentions. The results obtained enable us to identify differences in the composition of the perceived image according to the destination, while confirming the significant effect of different perceived image dimensions regarding satisfaction. The results allow managers to gain a better understanding of the effectiveness of their sites from a consumer perspective as well as suggestions to follow in order to achieve greater efficiency in their communication actions in order to improve the motivation of visitors to go to the destination. PMID:27933027
Differences of Perceived Image Generated through the Web Site: Empirical Evidence Obtained in Spanish Destinations.

PubMed

Blazquez-Resino, Juan J; Muro-Rodriguez, Ana I; Perez-Jimenez, Israel R

2016-01-01

In this paper, a study of the perceived destination image created by promotional Web Pages is expounded in an attempt to identify their differences as generators of destination image in the consumers' mind. Specifically, it seeks to analyse whether the web sites of different Spanish regions improve the image that consumers have of the destination, identifying their main dimensions and analysing its effect on satisfaction and intentions of the future behavior of potential visitors. To achieve these objectives and verify the hypotheses, a laboratory experiment was performed, where it was determined what changes are produced in the tourist's previous image after browsing the tourist webs of three different regions. Moreover, it analyses the differences in the effect of the perceived image on satisfaction and potential visitors' future behavioral intentions. The results obtained enable us to identify differences in the composition of the perceived image according to the destination, while confirming the significant effect of different perceived image dimensions regarding satisfaction. The results allow managers to gain a better understanding of the effectiveness of their sites from a consumer perspective as well as suggestions to follow in order to achieve greater efficiency in their communication actions in order to improve the motivation of visitors to go to the destination.
Identifying gender specific risk/need areas for male and female juvenile offenders: Factor analyses with the Structured Assessment of Violence Risk in Youth (SAVRY).

PubMed

Hilterman, Ed L B; Bongers, Ilja; Nicholls, Tonia L; van Nieuwenhuizen, Chijs

2016-02-01

By constructing risk assessment tools in which the individual items are organized in the same way for male and female juvenile offenders it is assumed that these items and subscales have similar relevance across males and females. The identification of criminogenic needs that vary in relevance for 1 of the genders, could contribute to more meaningful risk assessments, especially for female juvenile offenders. In this study, exploratory factor analyses (EFA) on a construction sample of male (n = 3,130) and female (n = 466) juvenile offenders were used to aggregate the 30 items of the Structured Assessment of Violence Risk in Youth (SAVRY) into empirically based risk/need factors and explore differences between genders. The factor models were cross-validated through confirmatory factor analyses (CFA) on a validation sample of male (n = 2,076) and female (n = 357) juvenile offenders. In both the construction sample and the validation sample, 5 factors were identified: (a) Antisocial behavior; (b) Family functioning; (c) Personality traits; (d) Social support; and (e) Treatability. The male and female models were significantly different and the internal consistency of the factors was good, both in the construction sample and the validation sample. Clustering risk/need items for male and female juvenile offenders into meaningful factors may guide clinicians in the identification of gender-specific treatment interventions. PsycINFO Database Record (c) 2016 APA, all rights reserved.
Intertumoral Heterogeneity within Medulloblastoma Subgroups.

PubMed

Cavalli, Florence M G; Remke, Marc; Rampasek, Ladislav; Peacock, John; Shih, David J H; Luu, Betty; Garzia, Livia; Torchia, Jonathon; Nor, Carolina; Morrissy, A Sorana; Agnihotri, Sameer; Thompson, Yuan Yao; Kuzan-Fischer, Claudia M; Farooq, Hamza; Isaev, Keren; Daniels, Craig; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Lee, Ji Yeoun; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Vasiljevic, Alexandre; Faure-Conter, Cecile; Jouvet, Anne; Giannini, Caterina; Nageswara Rao, Amulya A; Li, Kay Ka Wai; Ng, Ho-Keung; Eberhart, Charles G; Pollack, Ian F; Hamilton, Ronald L; Gillespie, G Yancey; Olson, James M; Leary, Sarah; Weiss, William A; Lach, Boleslaw; Chambless, Lola B; Thompson, Reid C; Cooper, Michael K; Vibhakar, Rajeev; Hauser, Peter; van Veelen, Marie-Lise C; Kros, Johan M; French, Pim J; Ra, Young Shin; Kumabe, Toshihiro; López-Aguilar, Enrique; Zitterbart, Karel; Sterba, Jaroslav; Finocchiaro, Gaetano; Massimino, Maura; Van Meir, Erwin G; Osuka, Satoru; Shofuda, Tomoko; Klekner, Almos; Zollo, Massimo; Leonard, Jeffrey R; Rubin, Joshua B; Jabado, Nada; Albrecht, Steffen; Mora, Jaume; Van Meter, Timothy E; Jung, Shin; Moore, Andrew S; Hallahan, Andrew R; Chan, Jennifer A; Tirapelli, Daniela P C; Carlotti, Carlos G; Fouladi, Maryam; Pimentel, José; Faria, Claudia C; Saad, Ali G; Massimi, Luca; Liau, Linda M; Wheeler, Helen; Nakamura, Hideo; Elbabaa, Samer K; Perezpeña-Diazconti, Mario; Chico Ponce de León, Fernando; Robinson, Shenandoah; Zapotocky, Michal; Lassaletta, Alvaro; Huang, Annie; Hawkins, Cynthia E; Tabori, Uri; Bouffet, Eric; Bartels, Ute; Dirks, Peter B; Rutka, James T; Bader, Gary D; Reimand, Jüri; Goldenberg, Anna; Ramaswamy, Vijay; Taylor, Michael D

2017-06-12

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive predictors of a common multitasking ability: Contributions from working memory, attention control, and fluid intelligence.

PubMed

Redick, Thomas S; Shipstead, Zach; Meier, Matthew E; Montroy, Janelle J; Hicks, Kenny L; Unsworth, Nash; Kane, Michael J; Hambrick, D Zachary; Engle, Randall W

2016-11-01

Previous research has identified several cognitive abilities that are important for multitasking, but few studies have attempted to measure a general multitasking ability using a diverse set of multitasks. In the final dataset, 534 young adult subjects completed measures of working memory (WM), attention control, fluid intelligence, and multitasking. Correlations, hierarchical regression analyses, confirmatory factor analyses, structural equation models, and relative weight analyses revealed several key findings. First, although the complex tasks used to assess multitasking differed greatly in their task characteristics and demands, a coherent construct specific to multitasking ability was identified. Second, the cognitive ability predictors accounted for substantial variance in the general multitasking construct, with WM and fluid intelligence accounting for the most multitasking variance compared to attention control. Third, the magnitude of the relationships among the cognitive abilities and multitasking varied as a function of the complexity and structure of the various multitasks assessed. Finally, structural equation models based on a multifaceted model of WM indicated that attention control and capacity fully mediated the WM and multitasking relationship. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Proteomic identification and purification of seed proteins from native Amazonian species displaying antifungal activity.

PubMed

Ramos, Márcio V; Brito, Daniel; Freitas, Cléverson D T; Gonçalves, José Francisco C; Porfirio, Camila T M N; Lobo, Marina D P; Monteiro-Moreira, Ana Cristina O; Souza, Luiz A C; Fernandes, Andreia V

2018-04-19

Seeds of native species from the rain forest (Amazon) are source of chitinases and their protein extracts exhibited strong and broad antifungal activity. Numerous plant species native to the Amazon have not yet been chemically studied. Studies of seeds are scarcer, since adversities in accessing study areas and seasonality pose constant hurdles to systematic research. In this study, proteins were extracted from seeds belonging to endemic Amazon species and were investigated for the first time. Proteolytic activity, peptidase inhibitors, and chitinases were identified, but chitinolytic activity predominated. Four proteins were purified through chromatography and identified as lectin and chitinases by MS/MS analyses. The proteins were examined for inhibition of a phytopathogen (Fusarium oxysporum). Analyses by fluorescence microscopy suggested binding of propidium iodide to DNA of fungal spores, revealing that spore integrity was lost when accessed by the proteins. Further structural and functional analyses of defensive proteins belonging to species facing highly complex ecosystems such as Amazonia should be conducted, since these could provide new insights into specificity and synergism involving defense proteins of plants submitted to a very complex ecosystem.
Performance Metrics for Liquid Chromatography-Tandem Mass Spectrometry Systems in Proteomics Analyses*

PubMed Central

Rudnick, Paul A.; Clauser, Karl R.; Kilpatrick, Lisa E.; Tchekhovskoi, Dmitrii V.; Neta, Pedatsur; Blonder, Nikša; Billheimer, Dean D.; Blackman, Ronald K.; Bunk, David M.; Cardasis, Helene L.; Ham, Amy-Joan L.; Jaffe, Jacob D.; Kinsinger, Christopher R.; Mesri, Mehdi; Neubert, Thomas A.; Schilling, Birgit; Tabb, David L.; Tegeler, Tony J.; Vega-Montoto, Lorenzo; Variyath, Asokan Mulayath; Wang, Mu; Wang, Pei; Whiteaker, Jeffrey R.; Zimmerman, Lisa J.; Carr, Steven A.; Fisher, Susan J.; Gibson, Bradford W.; Paulovich, Amanda G.; Regnier, Fred E.; Rodriguez, Henry; Spiegelman, Cliff; Tempst, Paul; Liebler, Daniel C.; Stein, Stephen E.

2010-01-01

A major unmet need in LC-MS/MS-based proteomics analyses is a set of tools for quantitative assessment of system performance and evaluation of technical variability. Here we describe 46 system performance metrics for monitoring chromatographic performance, electrospray source stability, MS1 and MS2 signals, dynamic sampling of ions for MS/MS, and peptide identification. Applied to data sets from replicate LC-MS/MS analyses, these metrics displayed consistent, reasonable responses to controlled perturbations. The metrics typically displayed variations less than 10% and thus can reveal even subtle differences in performance of system components. Analyses of data from interlaboratory studies conducted under a common standard operating procedure identified outlier data and provided clues to specific causes. Moreover, interlaboratory variation reflected by the metrics indicates which system components vary the most between laboratories. Application of these metrics enables rational, quantitative quality assessment for proteomics and other LC-MS/MS analytical applications. PMID:19837981
Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs

PubMed Central

Below, Jennifer E.; Parra, Esteban J.; Gamazon, Eric R.; Torres, Jason; Krithika, S.; Candille, Sophie; Lu, Yingchang; Manichakul, Ani; Peralta-Romero, Jesus; Duan, Qing; Li, Yun; Morris, Andrew P.; Gottesman, Omri; Bottinger, Erwin; Wang, Xin-Qun; Taylor, Kent D.; Ida Chen, Y.-D.; Rotter, Jerome I.; Rich, Stephen S.; Loos, Ruth J. F.; Tang, Hua; Cox, Nancy J.; Cruz, Miguel; Hanis, Craig L.; Valladares-Salgado, Adan

2016-01-01

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci. PMID:26780889
Genetic differentiation of the mitochondrial cytochrome oxidase C subunit I gene in genus Paramecium (Protista, Ciliophora).

PubMed

Zhao, Yan; Gentekaki, Eleni; Yi, Zhenzhen; Lin, Xiaofeng

2013-01-01

The mitochondrial cytochrome c oxidase subunit I (COI) gene is being used increasingly for evaluating inter- and intra-specific genetic diversity of ciliated protists. However, very few studies focus on assessing genetic divergence of the COI gene within individuals and how its presence might affect species identification and population structure analyses. We evaluated the genetic variation of the COI gene in five Paramecium species for a total of 147 clones derived from 21 individuals and 7 populations. We identified a total of 90 haplotypes with several individuals carrying more than one haplotype. Parsimony network and phylogenetic tree analyses revealed that intra-individual diversity had no effect in species identification and only a minor effect on population structure. Our results suggest that the COI gene is a suitable marker for resolving inter- and intra-specific relationships of Paramecium spp.
Genetic Differentiation of the Mitochondrial Cytochrome Oxidase c Subunit I Gene in Genus Paramecium (Protista, Ciliophora)

PubMed Central

Zhao, Yan; Gentekaki, Eleni; Yi, Zhenzhen; Lin, Xiaofeng

2013-01-01

Background The mitochondrial cytochrome c oxidase subunit I (COI) gene is being used increasingly for evaluating inter- and intra-specific genetic diversity of ciliated protists. However, very few studies focus on assessing genetic divergence of the COI gene within individuals and how its presence might affect species identification and population structure analyses. Methodology/Principal findings We evaluated the genetic variation of the COI gene in five Paramecium species for a total of 147 clones derived from 21 individuals and 7 populations. We identified a total of 90 haplotypes with several individuals carrying more than one haplotype. Parsimony network and phylogenetic tree analyses revealed that intra-individual diversity had no effect in species identification and only a minor effect on population structure. Conclusions Our results suggest that the COI gene is a suitable marker for resolving inter- and intra-specific relationships of Paramecium spp. PMID:24204730
Costs and Cost-Effectiveness of Plasmodium vivax Control.

PubMed

White, Michael T; Yeung, Shunmay; Patouillard, Edith; Cibulskis, Richard

2016-12-28

The continued success of efforts to reduce the global malaria burden will require sustained funding for interventions specifically targeting Plasmodium vivax The optimal use of limited financial resources necessitates cost and cost-effectiveness analyses of strategies for diagnosing and treating P. vivax and vector control tools. Herein, we review the existing published evidence on the costs and cost-effectiveness of interventions for controlling P. vivax, identifying nine studies focused on diagnosis and treatment and seven studies focused on vector control. Although many of the results from the much more extensive P. falciparum literature can be applied to P. vivax, it is not always possible to extrapolate results from P. falciparum-specific cost-effectiveness analyses. Notably, there is a need for additional studies to evaluate the potential cost-effectiveness of radical cure with primaquine for the prevention of P. vivax relapses with glucose-6-phosphate dehydrogenase testing. © The American Society of Tropical Medicine and Hygiene.
Costs and Cost-Effectiveness of Plasmodium vivax Control

PubMed Central

White, Michael T.; Yeung, Shunmay; Patouillard, Edith; Cibulskis, Richard

2016-01-01

The continued success of efforts to reduce the global malaria burden will require sustained funding for interventions specifically targeting Plasmodium vivax. The optimal use of limited financial resources necessitates cost and cost-effectiveness analyses of strategies for diagnosing and treating P. vivax and vector control tools. Herein, we review the existing published evidence on the costs and cost-effectiveness of interventions for controlling P. vivax, identifying nine studies focused on diagnosis and treatment and seven studies focused on vector control. Although many of the results from the much more extensive P. falciparum literature can be applied to P. vivax, it is not always possible to extrapolate results from P. falciparum–specific cost-effectiveness analyses. Notably, there is a need for additional studies to evaluate the potential cost-effectiveness of radical cure with primaquine for the prevention of P. vivax relapses with glucose-6-phosphate dehydrogenase testing. PMID:28025283
Maternal occupation and the risk of neural tube defects in offspring.

PubMed

Kim, Jihye; Langlois, Peter H; Mitchell, Laura E; Agopian, A J

2017-07-19

We evaluated the association between maternal occupation and the risk of neural tube defects (NTDs) in offspring. Data for 491 nonsyndromic cases were obtained from the Texas Birth Defects Registry for deliveries between 1999 and 2009. We randomly selected 2,291 controls among all live births in Texas during this time. Maternal occupations were classified using automated software and manual assignment. Multivariable logistic regression analyses were used to examine the relationship between maternal occupation and risk for any NTD, adjusting for maternal race/ethnicity, any diabetes, and maternal body mass index. These analyses were repeated for spina bifida specifically. Some maternal occupations, particularly those related to business/finance, health care practice, and cleaning/maintenance, were significantly associated with increased risk of spina bifida and/or any NTD. Further research is needed to identify the specific occupational exposures related to NTD risk.
Laser-induced breakdown spectroscopy (LIBS): an overview of recent progress and future potential for biomedical applications.

PubMed

Rehse, S J; Salimnia, H; Miziolek, A W

2012-02-01

The recent progress made in developing laser-induced breakdown spectroscopy (LIBS) has transformed LIBS from an elemental analysis technique to one that can be applied for the reagentless analysis of molecularly complex biological materials or clinical specimens. Rapid advances in the LIBS technology have spawned a growing number of recently published articles in peer-reviewed journals which have consistently demonstrated the capability of LIBS to rapidly detect, biochemically characterize and analyse, and/or accurately identify various biological, biomedical or clinical samples. These analyses are inherently real-time, require no sample preparation, and offer high sensitivity and specificity. This overview of the biomedical applications of LIBS is meant to summarize the research that has been performed to date, as well as to suggest to health care providers several possible specific future applications which, if successfully implemented, would be significantly beneficial to humankind.
Characterization of human breast cancer tissues by infrared imaging.

PubMed

Verdonck, M; Denayer, A; Delvaux, B; Garaud, S; De Wind, R; Desmedt, C; Sotiriou, C; Willard-Gallo, K; Goormaghtigh, E

2016-01-21

Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins.
Evaluating multiplexed next-generation sequencing as a method in palynology for mixed pollen samples.

PubMed

Keller, A; Danner, N; Grimmer, G; Ankenbrand, M; von der Ohe, K; von der Ohe, W; Rost, S; Härtel, S; Steffan-Dewenter, I

2015-03-01

The identification of pollen plays an important role in ecology, palaeo-climatology, honey quality control and other areas. Currently, expert knowledge and reference collections are essential to identify pollen origin through light microscopy. Pollen identification through molecular sequencing and DNA barcoding has been proposed as an alternative approach, but the assessment of mixed pollen samples originating from multiple plant species is still a tedious and error-prone task. Next-generation sequencing has been proposed to avoid this hindrance. In this study we assessed mixed pollen probes through next-generation sequencing of amplicons from the highly variable, species-specific internal transcribed spacer 2 region of nuclear ribosomal DNA. Further, we developed a bioinformatic workflow to analyse these high-throughput data with a newly created reference database. To evaluate the feasibility, we compared results from classical identification based on light microscopy from the same samples with our sequencing results. We assessed in total 16 mixed pollen samples, 14 originated from honeybee colonies and two from solitary bee nests. The sequencing technique resulted in higher taxon richness (deeper assignments and more identified taxa) compared to light microscopy. Abundance estimations from sequencing data were significantly correlated with counted abundances through light microscopy. Simulation analyses of taxon specificity and sensitivity indicate that 96% of taxa present in the database are correctly identifiable at the genus level and 70% at the species level. Next-generation sequencing thus presents a useful and efficient workflow to identify pollen at the genus and species level without requiring specialised palynological expert knowledge. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.
Challenges with cost-utility analyses of behavioural interventions among older adults at risk for dementia.

PubMed

Davis, Jennifer C; Bryan, Stirling; Marra, Carlo A; Hsiung, Ging-Yuek R; Liu-Ambrose, Teresa

2015-10-01

Cognitive decline is one of the most prominent healthcare issues of the 21st century. Within the context of combating cognitive decline through behavioural interventions, physical activity is a promising approach. There is a dearth of health economic data in the area of behavioural interventions for dementia prevention. Yet, economic evaluations are essential for providing information to policy makers for resource allocation. It is essential we first address population and intervention-specific methodological challenges prior to building a larger evidence base. We use a cost-utility analysis conducted alongside the exercise for cognition and everyday living (EXCEL) study to illustrate methodological challenges specific to assessing the cost-effectiveness of behavioural interventions aimed at older adults at risk of cognitive decline. A cost-utility analysis conducted concurrently with a 6-month, three-arm randomised controlled trial (ie, the EXCEL study) was used as an example to identify and discuss methodological challenges. Both the aerobic training and resistance training interventions were less costly than twice weekly balance and tone classes. In critically evaluating the economic evaluation of the EXCEL study we identified four category-specific challenges: (1) analysing costs; (2) assessing quality-adjusted life-years; (3) Incomplete data; and (4) 'Intervention' activities of the control group. Resistance training and aerobic training resulted in healthcare cost saving and were equally effective to balance and tone classes after only 6 months of intervention. To ensure this population is treated fairly in terms of claims on resources, we first need to identify areas for methodological improvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Integrating fragmented evidence by network meta-analysis: relative effectiveness of psychological interventions for adults with post-traumatic stress disorder.

PubMed

Gerger, H; Munder, T; Gemperli, A; Nüesch, E; Trelle, S; Jüni, P; Barth, J

2014-11-01

To summarize the available evidence on the effectiveness of psychological interventions for patients with post-traumatic stress disorder (PTSD). We searched bibliographic databases and reference lists of relevant systematic reviews and meta-analyses for randomized controlled trials that compared specific psychological interventions for adults with PTSD symptoms either head-to-head or against control interventions using non-specific intervention components, or against wait-list control. Two investigators independently extracted the data and assessed trial characteristics. The analyses included 4190 patients in 66 trials. An initial network meta-analysis showed large effect sizes (ESs) for all specific psychological interventions (ESs between -1.10 and -1.37) and moderate effects of psychological interventions that were used to control for non-specific intervention effects (ESs -0.58 and -0.62). ES differences between various types of specific psychological interventions were absent to small (ES differences between 0.00 and 0.27). Considerable between-trial heterogeneity occurred (τ²= 0.30). Stratified analyses revealed that trials that adhered to DSM-III/IV criteria for PTSD were associated with larger ESs. However, considerable heterogeneity remained. Heterogeneity was reduced in trials with adequate concealment of allocation and in large-sized trials. We found evidence for small-study bias. Our findings show that patients with a formal diagnosis of PTSD and those with subclinical PTSD symptoms benefit from different psychological interventions. We did not identify any intervention that was consistently superior to other specific psychological interventions. However, the robustness of evidence varies considerably between different psychological interventions for PTSD, with most robust evidence for cognitive behavioral and exposure therapies.
Gene regulation network behind drought escape, avoidance and tolerance strategies in black poplar (Populus nigra L.).

PubMed

Yıldırım, Kubilay; Kaya, Zeki

2017-06-01

Drought is the major environmental problem limiting the productivity and survival of plant species. Here, previously identified three black poplar genotypes having contrasting response to drought were subjected to gradual soil water depletion in a pot trial to identify their physiological, morphological and antioxidation related adaptations. We also performed a microarray based transcriptome analyses on the leaves of genotypes by using Affymetrix poplar Genome Array containing 56,000 transcripts. Phenotypic analyses of each genotype confirmed their differential adaptations to drought that could be classified as drought escape, avoidance and tolerance. Comparative transcriptomic analysis indicated highly divergent gene expression patterns among the genotypes in response to drought and post drought re-watering (PDR). We identified 10641, 3824 and 9411 transcripts exclusively regulated in drought escape, avoidance and tolerant genotypes, respectively. The key genes involved in metabolic pathways, such as carbohydrate metabolism, photosynthesis, lipid metabolism, generation of precursor metabolites/energy, protein folding, redox homeostasis, secondary metabolic process and cell wall component biogenesis, were affected by drought stresses in the leaves of these genotypes. Transcript isoforms showed increased expression specificity in the genes coding for bark storage proteins and small heat shock proteins in drought tolerant genotype. On the other hand, drought-avoiding genotype specifically induced the transcripts annotated to the genes functional in secondary metabolite production that linked to enhanced leaf water content and growth performance under drought stress. Transcriptome profiling of drought escape genotype indicated specific regulation of the genes functional in programmed cell death and leaf senescence. Specific upregulation of GTP cyclohydrolase II and transcription factors (WRKY and ERFs) in only this genotype were associated to ROS dependent signalling pathways and gene regulation network responsible in induction of many degrading enzymes acting on cell wall carbohydrates, fatty acids and proteins under drought stress. Our findings provide new insights into the transcriptome dynamics and components of regulatory network associated with drought adaptation strategies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors.

PubMed

Polimanti, Renato; Zhao, Hongyu; Farrer, Lindsay A; Kranzler, Henry R; Gelernter, Joel

2017-12-01

We previously mapped loci for the genome-wide association studies (GWAS) and genome-wide gene-by-alcohol dependence interaction (GW-GxAD) analyses of risky sexual behaviors (RSB). This study extends those findings by analyzing the ancestry- and sex-specific AD-stratified effects on RSB. We examined the concordance of findings for the AD-stratified GWAS and the GW-GxAD analysis of RSB, with concordance defined as genome-wide significance in one analysis and at least nominal significance in the second analysis. A total of 2,173 African-American (AA) and 1,751 European-American (EA) subjects were investigated. Information regarding RSB (lifetime experiences of unprotected sex and multiple sexual partners) and DSM-IV diagnosis of lifetime AD were derived from the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). In our ancestry- and sex-specific analyses, we identified four independent genome-wide significant (GWS) loci (p < 5*10 -8 ) and one suggestive locus (p < 6*10 -8 ). In men, we observed a GWS signal in FAM162A (rs2002594, p = 4.96*10 -8 ). In women, there was a suggestive locus in PLGRKT (rs3824435, p = 5.52*10 -8 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p = 1.25*10 -9 ). In AA men, we observed an intergenic GWS signal (rs12898370, p = 4.49*10 -8 ) near LINGO1. In EA men, there was a GWS signal in CCSER1 (rs62313897; p = 7.93*10 -10 ). The loci identified in this GWAS implicate molecular mechanisms related to psychiatric illness and personality features, suggesting that the interplay between AD and RSB is mediated by alleles associated with behavioral traits. © 2017 Wiley Periodicals, Inc.
Biomarkers of Coordinate Metabolic Reprogramming in Colorectal Tumors in Mice and Humans

PubMed Central

Manna, Soumen K.; Tanaka, Naoki; Krausz, Kristopher W.; Haznadar, Majda; Xue, Xiang; Matsubara, Tsutomu; Bowman, Elise D.; Fearon, Eric R.; Harris, Curtis C.; Shah, Yatrik M.; Gonzalez, Frank J.

2014-01-01

BACKGROUND & AIMS There are no robust noninvasive methods for colorectal cancer screening and diagnosis. Metabolomic and gene expression analyses of urine and tissue samples from mice and humans were used to identify markers of colorectal carcinogenesis. METHODS Mass spectrometry-based metabolomic analyses of urine and tissues from wild-type C57BL/6J and ApcMin/+ mice, as well as from mice with azoxymethane-induced tumors, was employed in tandem with gene expression analysis. Metabolomics profiles were also determined on colon tumor and adjacent non-tumor tissues from 39 patients. The effects of β-catenin activity on metabolic profiles were assessed in mice with colon-specific disruption of Apc. RESULTS Thirteen markers were found in urine associated with development of colorectal tumors in ApcMin/+ mice. Metabolites related to polyamine metabolism, nucleic acid metabolism, and methylation, identified tumor-bearing mice with 100% accuracy, and also accurately identified mice with polyps. Changes in gene expression in tumor samples from mice reflected the observed changes in metabolic products detected in urine; similar changes were observed in mice with azoxymethane-induced tumors and mice with colon-specific activation of β-catenin. The metabolic alterations indicated by markers in urine therefore appear to occur during early stages of tumorigenesis, when cancer cells are proliferating. In tissues from patients, tumors had stage-dependent increases in 12 metabolites associated with the same metabolic pathways identified in mice (including amino acid metabolism and polyamine metabolism). Ten metabolites that were increased in tumor tissues, compared with non-tumor tissues (proline, threonine, glutamic acid, arginine, N1-acetylspermidine, xanthine, uracil, betaine, symmetric dimethylarginine, and asymmetric-dimethylarginine), were also increased in urine from tumor-bearing mice. CONCLUSIONS Gene expression and metabolomic profiles of urine and tissue samples from mice with colorectal tumors and of colorectal tumor samples from patients revealed metabolites associated with specific metabolic changes that are indicative of early-stage tumor development. These urine and tissue markers might be used in early detection of colorectal cancer. PMID:24440673
Does the knowledge-to-action (KTA) framework facilitate physical demands analysis development for firefighter injury management and return-to-work planning?

PubMed

Sinden, Kathryn; MacDermid, Joy C

2014-03-01

Employers are tasked with developing injury management and return-to-work (RTW) programs in response to occupational health and safety policies. Physical demands analyses (PDAs) are the cornerstone of injury management and RTW development. Synthesizing and contextualizing policy knowledge for use in occupational program development, including PDAs, is challenging due to multiple stakeholder involvement. Few studies have used a knowledge translation theoretical framework to facilitate policy-based interventions in occupational contexts. The primary aim of this case study was to identify how constructs of the knowledge-to-action (KTA) framework were reflected in employer stakeholder-researcher collaborations during development of a firefighter PDA. Four stakeholder meetings were conducted with employee participants who had experience using PDAs in their occupational role. Directed content analysis informed analyses of meeting minutes, stakeholder views and personal reflections recorded throughout the case. Existing knowledge sources including local data, stakeholder experiences, policies and priorities were synthesized and tailored to develop a PDA in response to the barriers and facilitators identified by the firefighters. The flexibility of the KTA framework and synthesis of multiple knowledge sources were identified strengths. The KTA Action cycle was useful in directing the overall process but insufficient for directing the specific aspects of PDA development. Integration of specific PDA guidelines into the process provided explicit direction on best practices in tailoring the PDA and knowledge synthesis. Although the themes of the KTA framework were confirmed in our analysis, order modification of the KTA components was required. Despite a complex context with divergent perspectives successful implementation of a draft PDA was achieved. The KTA framework facilitated knowledge synthesis and PDA development but specific standards and modifications to the KTA framework were needed to enhance process structure. Flexibility for modification and integration of PDA practice guidelines were identified as assets of the KTA framework during its application.
Using fault tree analysis to identify causes of non-compliance: enhancing violation outcome data for the purposes of education and prevention.

PubMed

Emery, R J; Charlton, M A; Orders, A B; Hernandez, M

2001-02-01

An enhanced coding system for the characterization of notices of violation (NOV's) issued to radiation permit holders in the State of Texas was developed based on a series of fault tree analyses serving to identify a set of common causes. The coding system enhancement was retroactively applied to a representative sample (n = 185) of NOV's issued to specific licensees of radioactive materials in Texas during calendar year 1999. The results obtained were then compared to the currently available summary NOV information for the same year. In addition to identifying the most common NOV's, the enhanced coding system revealed that approximately 70% of the sampled NOV's were issued for non-compliance with a specific regulation as opposed to a permit condition. Furthermore, an underlying cause of 94% of the NOV's was the failure on the part of the licensee to execute a specific task. The findings suggest that opportunities exist to improve permit holder compliance through various means, including the creation of summaries which detail specific tasks to be completed, and revising training programs with more focus on the identification and scheduling of permit-related requirements. Broad application of these results is cautioned due to the bias associated with the restricted scope of the project.
Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome

PubMed Central

Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O’Connor, Timothy D.; Abecasis, Gonçalo R.; Wojcik, Genevieve L; Gignoux, Christopher R.; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E.; Bustamante, Carlos; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Qin, Zhaohui S.; Preethi Boorgula, Meher; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Ruczinski, Ingo; Scott, Alan F.; Taub, Margaret A.; Vergara, Candelaria; Levin, Albert M.; Padhukasahasram, Badri; Williams, L. Keoki; Dunston, Georgia M.; Faruque, Mezbah U.; Gietzen, Kimberly; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-Youn A.; Kumar, Rajesh; Schleimer, Robert; De La Vega, Francisco M.; Shringarpure, Suyash S.; Musharoff, Shaila; Burchard, Esteban G.; Eng, Celeste; Hernandez, Ryan D.; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Maul, Pissamai; Maul, Trevor; Watson, Harold; Ilma Araujo, Maria; Riccio Oliveira, Ricardo; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Francisco Herrera-Paz, Edwin; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Marina Vasquez, Olga; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria

2017-01-01

A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an ‘African Diaspora Power Chip’ (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry. PMID:28429804

Mission Analysis for High Specific Impulse Deep Space Exploration

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Polsgrove, Tara; Brady, Hugh J. (Technical Monitor)

2002-01-01

This paper describes trajectory calculations for high specific impulse engines. Specific impulses on the order of 10,000 to 100,000 sec are predicted in a variety of fusion powered propulsion systems. This paper and its companion paper seek to build on analyses in the literature to yield an analytical routine for determining time of flight and payload fraction to a predetermined destination. The companion paper will compare the results of this analysis to the trajectories determined by several trajectory codes. The major parameters that affect time of flight and payload fraction will be identified and their sensitivities quantified. A review of existing fusion propulsion concepts and their capabilities will also be tabulated.
Forensic Signature Detection of Yersinia Pestis Culturing Practices Across Institutions Using a Bayesian Network

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

Webb-Robertson, Bobbie-Jo M.; Corley, Courtney D.; McCue, Lee Ann

The field of bioforensics is focused on the analysis of evidence from a biocrime. Existing laboratory analyses can identify the specific strain of an organism in the evidence, as well signatures of the specific culture batch of organisms, such as low-frequency contaminants or indicators of growth and processing methods. To link these disparate types of physical data to potential suspects, investigators may need to identify institutions or individuals whose access to strains and culturing practices match those identified from the evidence. In this work we present a Bayesian statistical network to fuse different types of analytical measurements that predict themore » production environment of a Yersinia pestis sample under investigation with automated test processing of scientific publications to identify institutions with a history of growing Y. pestis under similar conditions. Furthermore, the textual and experimental signatures were evaluated recursively to determine the overall sensitivity of the network across all levels of false positives. We illustrate that institutions associated with several specific culturing practices can be accurately selected based on the experimental signature from only a few analytical measurements. These findings demonstrate that similar Bayesian networks can be generated generically for many organisms of interest and their deployment is not prohibitive due to either computational or experimental factors.« less
Old resinous turpentine stumps as an indicator of the range of longleaf pine in Southeastern Virginia

Treesearch

Thomas L. Eberhardt; Philip M. Sheridan; Jolie M. Mahfouz; Chi-Leung So

2006-01-01

Wood anatomy cannot be used to differentiate between the southern yellow pine species. Wood samples collected from old resinous turpentine stumps in coastal Virginia were subjected to chemical and spectroscopic analyses in an effort to determine if they could be identified as longleaf pine. The age and resinous nature of the samples were manifested in high specific...
Subsystem Hazard Analysis Methodology for the Ares I Upper Stage Source Controlled Items

NASA Technical Reports Server (NTRS)

Mitchell, Michael S.; Winner, David R.

2010-01-01

This article describes processes involved in developing subsystem hazard analyses for Source Controlled Items (SCI), specific components, sub-assemblies, and/or piece parts, of the NASA ARES I Upper Stage (US) project. SCIs will be designed, developed and /or procured by Boeing as an end item or an off-the-shelf item. Objectives include explaining the methodology, tools, stakeholders and products involved in development of these hazard analyses. Progress made and further challenges in identifying potential subsystem hazards are also provided in an effort to assist the System Safety community in understanding one part of the ARES I Upper Stage project.
Functional Abstraction as a Method to Discover Knowledge in Gene Ontologies

PubMed Central

Ultsch, Alfred; Lötsch, Jörn

2014-01-01

Computational analyses of functions of gene sets obtained in microarray analyses or by topical database searches are increasingly important in biology. To understand their functions, the sets are usually mapped to Gene Ontology knowledge bases by means of over-representation analysis (ORA). Its result represents the specific knowledge of the functionality of the gene set. However, the specific ontology typically consists of many terms and relationships, hindering the understanding of the ‘main story’. We developed a methodology to identify a comprehensibly small number of GO terms as “headlines” of the specific ontology allowing to understand all central aspects of the roles of the involved genes. The Functional Abstraction method finds a set of headlines that is specific enough to cover all details of a specific ontology and is abstract enough for human comprehension. This method exceeds the classical approaches at ORA abstraction and by focusing on information rather than decorrelation of GO terms, it directly targets human comprehension. Functional abstraction provides, with a maximum of certainty, information value, coverage and conciseness, a representation of the biological functions in a gene set plays a role. This is the necessary means to interpret complex Gene Ontology results thus strengthening the role of functional genomics in biomarker and drug discovery. PMID:24587272
On the Use of Biomineral Oxygen Isotope Data to Identify Human Migrants in the Archaeological Record: Intra-Sample Variation, Statistical Methods and Geographical Considerations

PubMed Central

Lightfoot, Emma; O’Connell, Tamsin C.

2016-01-01

Oxygen isotope analysis of archaeological skeletal remains is an increasingly popular tool to study past human migrations. It is based on the assumption that human body chemistry preserves the δ18O of precipitation in such a way as to be a useful technique for identifying migrants and, potentially, their homelands. In this study, the first such global survey, we draw on published human tooth enamel and bone bioapatite data to explore the validity of using oxygen isotope analyses to identify migrants in the archaeological record. We use human δ18O results to show that there are large variations in human oxygen isotope values within a population sample. This may relate to physiological factors influencing the preservation of the primary isotope signal, or due to human activities (such as brewing, boiling, stewing, differential access to water sources and so on) causing variation in ingested water and food isotope values. We compare the number of outliers identified using various statistical methods. We determine that the most appropriate method for identifying migrants is dependent on the data but is likely to be the IQR or median absolute deviation from the median under most archaeological circumstances. Finally, through a spatial assessment of the dataset, we show that the degree of overlap in human isotope values from different locations across Europe is such that identifying individuals’ homelands on the basis of oxygen isotope analysis alone is not possible for the regions analysed to date. Oxygen isotope analysis is a valid method for identifying first-generation migrants from an archaeological site when used appropriately, however it is difficult to identify migrants using statistical methods for a sample size of less than c. 25 individuals. In the absence of local previous analyses, each sample should be treated as an individual dataset and statistical techniques can be used to identify migrants, but in most cases pinpointing a specific homeland should not be attempted. PMID:27124001
An initial evaluation of the Social Communication Questionnaire for the assessment of autism spectrum disorders in children with Down syndrome.

PubMed

Magyar, Caroline I; Pandolfi, Vincent; Dill, Charles A

2012-02-01

This study investigated the psychometric properties of the Social Communication Questionnaire (SCQ) in a sample of children with Down syndrome (DS), many of whom had a co-occurring autism spectrum disorder (ASD). The SCQ is a widely used ASD screening measure; however, its measurement properties have not been comprehensively evaluated specifically in children with DS, a group that seems to be at higher risk for an ASD. Exploratory and confirmatory factor analyses, scale reliability, convergent and discriminant correlations, significance tests between groups of children with DS and DS + ASD, and diagnostic accuracy analyses were conducted. Factor analyses identified 2 reliable factors that we labeled Social-Communication and Stereotyped Behavior and Unusual Interests. Pearson correlations with Autism Diagnostic Interview-Revised subscales indicated support for the SCQ's convergent validity and some support for the discriminant validity of the factor-based scales. Significance tests and receiver operating characteristic analyses indicated that children with DS + ASD obtained significantly higher SCQ factor-based and total scores than children with DS alone, and that the SCQ Total Score evidenced good sensitivity and adequate specificity. Results indicated initial psychometric support for the SCQ as an ASD screening measure in children with DS. The SCQ should be considered as part of a multimethod evaluation when screening children with DS.
SUPPLEMENTAL ANALYSES FOR SOLVENT HOLD TANK SAMPLES MCU-11-314, MCU-11-315, MCU-11-316, MCU-11-317, MCU-11-318 AND MCU-11-319

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

Peters, T.; Washington, A; . Fondeur, F.

2011-09-29

Savannah River National Laboratory (SRNL) periodically analyses solvent samples from Modular Caustic-Side Solvent Extraction Unit (MCU) in support of continuing operations. A quarterly analysis of the solvent is required to maintain solvent composition within specifications. Analytical results of the analyses of Solvent Hold Tank (SHT) samples MCU-11-314, MCU-11-315, MCU-11-316, MCU-11-317, MCU-11-318 and MCU-11-319 have been previously reported. MCU has experienced a modest decline in cesium removal efficiency while processing the current feed, 'Macrobatch 3'. While the target decontamination factor (DF) is 200, the fiscal year 2011 DF average is 161. The results of the prior solvent analysis report did notmore » identify a specific factor that would correlate with the poor cesium decontamination beyond a low concentration of the suppressor, trioctylamine. New analyses of the quarterly sample are reported in this document, as well as a cross-check of {sup 137}Cs measurements for SRNL and F/H lab. Furthermore, in an attempt to discover the reason for the decline in DF at MCU, SRNL was tasked with analyzing numerous Caustic Wash Tank (CWT) and chemical feed samples.« less
NEW WILDLIFE HOSTS OF Leptospira interrogans IN CAMPECHE, MEXICO

PubMed Central

ESPINOSA-MARTÍNEZ, Deborah V.; SÁNCHEZ-MONTES, Daniel Sokani; LEÓN-PANIAGUA, Livia; RÍOS-MUÑOZ, César A.; BERZUNZA-CRUZ, Miriam; BECKER, Ingeborg

2015-01-01

Leptospira interrogans has been identified to cause leptospirosis, a widespread zoonotic disease that has been identified in domestic and wild animals. This work analyzed kidneys from two species of wild rodents from the state of Campeche, Mexico. Analyses were made by PCR using specific primers for detection of Leptospira interrogans DNA. The rodent species that tested positive were Heteromys gaumeri and Ototylomys phyllotis, both of which are new hosts for the bacteria in Southeastern Mexico. These records provide new insights into the disease’s transmission that should be studied carefully in order to identify other potential host species, including humans, which are at risk of becoming infected if they are in contact with infected wildlife. PMID:25923901
Development of Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid Detection of Cannabis sativa.

PubMed

Kitamura, Masashi; Aragane, Masako; Nakamura, Kou; Watanabe, Kazuhito; Sasaki, Yohei

2016-07-01

In many parts of the world, the possession and cultivation of Cannabis sativa L. are restricted by law. As chemical or morphological analyses cannot identify the plant in some cases, a simple yet accurate DNA-based method for identifying C. sativa is desired. We have developed a loop-mediated isothermal amplification (LAMP) assay for the rapid identification of C. sativa. By optimizing the conditions for the LAMP reaction that targets a highly conserved region of tetrahydrocannabinolic acid (THCA) synthase gene, C. sativa was identified within 50 min at 60-66°C. The detection limit was the same as or higher than that of conventional PCR. The LAMP assay detected all 21 specimens of C. sativa, showing high specificity. Using a simple protocol, the identification of C. sativa could be accomplished within 90 min from sample treatment to detection without use of special equipment. A rapid, sensitive, highly specific, and convenient method for detecting and identifying C. sativa has been developed and is applicable to forensic investigations and industrial quality control.
Differentiating Human Multipotent Mesenchymal Stromal Cells Regulate microRNAs: Prediction of microRNA Regulation by PDGF During Osteogenesis

PubMed Central

Goff, Loyal A.; Boucher, Shayne; Ricupero, Christopher L.; Fenstermacher, Sara; Swerdel, Mavis; Chase, Lucas; Adams, Christopher; Chesnut, Jonathan; Lakshmipathy, Uma; Hart, Ronald P.

2009-01-01

Objective Human multipotent mesenchymal stromal cells (MSC) have the potential to differentiate into multiple cell types, although little is known about factors that control their fate. Differentiation-specific microRNAs may play a key role in stem cell self renewal and differentiation. We propose that specific intracellular signalling pathways modulate gene expression during differentiation by regulating microRNA expression. Methods Illumina mRNA and NCode microRNA expression analyses were performed on MSC and their differentiated progeny. A combination of bioinformatic prediction and pathway inhibition was used to identify microRNAs associated with PDGF signalling. Results The pattern of microRNA expression in MSC is distinct from that in pluripotent stem cells such as human embryonic stem cells. Specific populations of microRNAs are regulated in MSC during differentiation targeted towards specific cell types. Complementary mRNA expression analysis increases the pool of markers characteristic of MSC or differentiated progeny. To identify microRNA expression patterns affected by signalling pathways, we examined the PDGF pathway found to be regulated during osteogenesis by microarray studies. A set of microRNAs bioinformatically predicted to respond to PDGF signalling was experimentally confirmed by direct PDGF inhibition. Conclusion Our results demonstrate that a subset of microRNAs regulated during osteogenic differentiation of MSCs is responsive to perturbation of the PDGF pathway. This approach not only identifies characteristic classes of differentiation-specific mRNAs and microRNAs, but begins to link regulated molecules with specific cellular pathways. PMID:18657893
A genome-wide association study of corneal astigmatism: The CREAM Consortium.

PubMed

Shah, Rupal L; Li, Qing; Zhao, Wanting; Tedja, Milly S; Tideman, J Willem L; Khawaja, Anthony P; Fan, Qiao; Yazar, Seyhan; Williams, Katie M; Verhoeven, Virginie J M; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W V; Hysi, Pirro G; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R; Jonas, Jost B; Mitchell, Paul; Hammond, Christopher J; Höhn, René; Baird, Paul N; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C W; Guggenheim, Jeremy A; Bailey-Wilson, Joan E

2018-01-01

To identify genes and genetic markers associated with corneal astigmatism. A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha ( PDGFRA ) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10 -9 . No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 ( CLDN7 ), acid phosphatase 2, lysosomal ( ACP2 ), and TNF alpha-induced protein 8 like 3 ( TNFAIP8L3 ). In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7 , ACP2 , and TNFAIP8L3 , that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.
Chemical identification and ethological function of soldier-specific secretion in Japanese subterranean termite Reticulitermes speratus (Rhinotermitidae).

PubMed

Nguyen, Tuan T; Kanaori, Kenji; Hojo, Masaru K; Kawada, Tatsuro; Yamaoka, Ryohei; Akino, Toshiharu

2011-01-01

We identified the soldier-specific compounds in the Japanese subterranean termite, Reticulitermes speratus, to clarify their ethological roles. Silica gel column chromatography separated one major soldier-specific compound in the hexane fraction accounting for 70-80% of the total amount of the fraction, while cuticular hydrocarbons constituted the rest. We identified the compound as β-selinene by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Comparative GC analyses of the major exocrine glands detected the compound in the soldier's frontal gland. Both soldiers and workers made aggregation to the hexane fraction, as well as to the crushed heads and head extract of the soldiers. They did not aggregate to cuticular hydrocarbons, making it likely that β-selinene was the aggregation pheromone in this species. The opportunistic predator of this termite, Lasius japonicus, was also attracted to the compounds. The ant workers, therefore, would use the termite aggregation pheromone as a kairomone for hunting them.
Cancer vulnerabilities unveiled by genomic loss

PubMed Central

Nijhawan, Deepak; Zack, Travis I.; Ren, Yin; Strickland, Matthew R.; Lamothe, Rebecca; Schumacher, Steven E.; Tsherniak, Aviad; Besche, Henrike C.; Rosenbluh, Joseph; Shehata, Shyemaa; Cowley, Glenn S.; Weir, Barbara A.; Goldberg, Alfred L.; Mesirov, Jill P.; Root, David E.; Bhatia, Sangeeta N.; Beroukhim, Rameen; Hahn, William C.

2012-01-01

Summary Due to genome instability, most cancers exhibit loss of regions containing tumor suppressor genes and collateral loss of other genes. To identify cancer-specific vulnerabilities that are the result of copy-number losses, we performed integrated analyses of genome-wide copy-number and RNAi profiles and identified 56 genes for which gene suppression specifically inhibited the proliferation of cells harboring partial copy-number loss of that gene. These CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) genes are enriched for spliceosome, proteasome and ribosome components. One CYCLOPS gene, PSMC2, encodes an essential member of the 19S proteasome. Normal cells express excess PSMC2, which resides in a complex with PSMC1, PSMD2, and PSMD5 and acts as a reservoir protecting cells from PSMC2 suppression. Cells harboring partial PSMC2 copy-number loss lack this complex and die after PSMC2 suppression. These observations define a distinct class of cancer-specific liabilities resulting from genome instability. PMID:22901813
Geochemical and microbiological fingerprinting of airborne dust that fell in Canberra, Australia, in October 2002

NASA Astrophysics Data System (ADS)

de Deckker, Patrick; Abed, Raeid M. M.; de Beer, Dirk; Hinrichs, Kai-Uwe; O'Loingsigh, Tadhg; Schefuß, Enno; Stuut, Jan-Berend W.; Tapper, Nigel J.; van der Kaars, Sander

2008-12-01

During the night of 22-23 October 2002, a large amount of airborne dust fell with rain over Canberra, located some 200 km from Australia's east coast, and at an average altitude of 650 m. It is estimated that during that night about 6 g m-2 of aeolian dust fell. We have conducted a vast number of analyses to "fingerprint" some of the dust and used the following techniques: grain size analysis; scanning electron microscope imagery; major, trace, and rare earth elemental, plus Sr and Nd isotopic analyses; organic compound analyses with respective compound-specific isotope analyses; pollen extraction to identify the vegetation sources; and molecular cloning of 16S rRNA genes in order to identify dust bacterial composition. DNA analyses show that most obtained 16S rRNA sequences belong mainly to three groups: Proteobacteria (25%), Bacteriodetes (23%), and gram-positive bacteria (23%). In addition, we investigated the meteorological conditions that led to the dust mobilization and transport using model and satellite data. Grain sizes of the mineral dust show a bimodal distribution typical of proximal dust, rather than what is found over oceans, and the bimodal aspect of size distribution confirms wet deposition by rain droplets. The inorganic geochemistry points to a source along/near the Darling River in NW New South Wales, a region that is characteristically semiarid, and both the organic chemistry and palynoflora of the dust confirm the location of this source area. Meteorological reconstructions of the event again clearly identify the area near Bourke-Cobar as being the source of the dust. This study paves the way for determining the export of Australian airborne dust both in the oceans and other continents.
Automatic Network Fingerprinting through Single-Node Motifs

PubMed Central

Echtermeyer, Christoph; da Fontoura Costa, Luciano; Rodrigues, Francisco A.; Kaiser, Marcus

2011-01-01

Complex networks have been characterised by their specific connectivity patterns (network motifs), but their building blocks can also be identified and described by node-motifs—a combination of local network features. One technique to identify single node-motifs has been presented by Costa et al. (L. D. F. Costa, F. A. Rodrigues, C. C. Hilgetag, and M. Kaiser, Europhys. Lett., 87, 1, 2009). Here, we first suggest improvements to the method including how its parameters can be determined automatically. Such automatic routines make high-throughput studies of many networks feasible. Second, the new routines are validated in different network-series. Third, we provide an example of how the method can be used to analyse network time-series. In conclusion, we provide a robust method for systematically discovering and classifying characteristic nodes of a network. In contrast to classical motif analysis, our approach can identify individual components (here: nodes) that are specific to a network. Such special nodes, as hubs before, might be found to play critical roles in real-world networks. PMID:21297963
Identification of microRNAs and their targets in Finger millet by high throughput sequencing.

PubMed

Usha, S; Jyothi, M N; Sharadamma, N; Dixit, Rekha; Devaraj, V R; Nagesh Babu, R

2015-12-15

MicroRNAs are short non-coding RNAs which play an important role in regulating gene expression by mRNA cleavage or by translational repression. The majority of identified miRNAs were evolutionarily conserved; however, others expressed in a species-specific manner. Finger millet is an important cereal crop; nonetheless, no practical information is available on microRNAs to date. In this study, we have identified 95 conserved microRNAs belonging to 39 families and 3 novel microRNAs by high throughput sequencing. For the identified conserved and novel miRNAs a total of 507 targets were predicted. 11 miRNAs were validated and tissue specificity was determined by stem loop RT-qPCR, Northern blot. GO analyses revealed targets of miRNA were involved in wide range of regulatory functions. This study implies large number of known and novel miRNAs found in Finger millet which may play important role in growth and development. Copyright © 2015 Elsevier B.V. All rights reserved.
PSEA: Kinase-specific prediction and analysis of human phosphorylation substrates

NASA Astrophysics Data System (ADS)

Suo, Sheng-Bao; Qiu, Jian-Ding; Shi, Shao-Ping; Chen, Xiang; Liang, Ru-Ping

2014-03-01

Protein phosphorylation catalysed by kinases plays crucial regulatory roles in intracellular signal transduction. With the increasing number of kinase-specific phosphorylation sites and disease-related phosphorylation substrates that have been identified, the desire to explore the regulatory relationship between protein kinases and disease-related phosphorylation substrates is motivated. In this work, we analysed the kinases' characteristic of all disease-related phosphorylation substrates by using our developed Phosphorylation Set Enrichment Analysis (PSEA) method. We evaluated the efficiency of our method with independent test and concluded that our approach is reliable for identifying kinases responsible for phosphorylated substrates. In addition, we found that Mitogen-activated protein kinase (MAPK) and Glycogen synthase kinase (GSK) families are more associated with abnormal phosphorylation. It can be anticipated that our method might be helpful to identify the mechanism of phosphorylation and the relationship between kinase and phosphorylation related diseases. A user-friendly web interface is now freely available at http://bioinfo.ncu.edu.cn/PKPred_Home.aspx.
Bi-parentally inherited species-specific markers identify hybridization between rainbow trout and cutthroat trout subspecies

USGS Publications Warehouse

Ostberg, C.O.; Rodriguez, R.J.

2004-01-01

Eight polymerase chain reaction primer sets amplifying bi-parentally inherited species-specific markers were developed that differentiate between rainbow trout (Oncorhynchus mykiss) and various cutthroat trout (O. clarki) subspecies. The primers were tested within known F1 and first generation hybrid backcrosses and were shown to amplify codominantly within hybrids. Heterozygous individuals also amplified a slower migrating band that was a heteroduplex, caused by the annealing of polymerase chain reaction products from both species. These primer sets have numerous advantages for native cutthroat trout conservation including statistical genetic analyses of known crosses and simple hybrid identification.
Technical analysis of US Army Weapons Systems and related advanced technologies of military interest. Final report

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

NONE

1991-06-14

This report summarizes the activities and accomplishments of an US Army technology security project designed to identify and develop effective policy guidelines for militarily critical technologies in specific Army systems and in broad generic technology areas of military interest, Individual systems analyses are documented in separate Weapons Systems Technical Assessments (WSTAs) and the general generic technology areas are evaluated in the Advanced Technology Assessment Reports (ATARs), However, specific details of these assessments are not addressed here, only recommendations regarding aspects of the defined approach, methodology, and format are provided and discussed.

Reproductive and developmental toxicity of the components of gasoline.

PubMed Central

Skalko, R G

1993-01-01

The reproductive, developmental, and postnatal toxicity of 14 select chemicals and mixtures that are components of gasoline has been reviewed. The majority of experimental analyses have been performed as either variations of the accepted segment 2 protocol or as traditional teratology studies. Specific deficiencies in the present database have been identified and are most obvious in the evaluation of reproductive and postnatal effects. It is recommended that future studies address the continuing need for assessment in multiple species and over a range of dosages with specific emphasis on the impact of route of administration on the results obtained. PMID:8020438
Fig volatile compounds--a first comparative study.

PubMed

Grison-Pigé, Laure; Hossaert-McKey, Martine; Greeff, Jaco M; Bessière, Jean-Marie

2002-09-01

We analysed the compounds of volatile blends released by receptive figs of twenty Ficus species to attract their specific pollinating wasps. In all, 99 different compounds were identified. The compounds are mainly terpenoids, aliphatic compounds and products from the shikimic acid pathway. In each species blend, there are few major compounds, which are generally common among floral fragrances. Most species blends also include rare compounds, but generally their proportion in the blend is low. A possible basis for species-specificity of Ficus-wasp interactions is discussed in relation to the patterns of volatiles found in this interspecies comparison. Copyright 2002 Elsevier Science Ltd.
Analyses of a Mutant Foxp3 Allele Reveal BATF as a Critical Transcription Factor in the Differentiation and Accumulation of Tissue Regulatory T Cells.

PubMed

Hayatsu, Norihito; Miyao, Takahisa; Tachibana, Masashi; Murakami, Ryuichi; Kimura, Akihiko; Kato, Takako; Kawakami, Eiryo; Endo, Takaho A; Setoguchi, Ruka; Watarai, Hiroshi; Nishikawa, Takeshi; Yasuda, Takuwa; Yoshida, Hisahiro; Hori, Shohei

2017-08-15

Foxp3 controls the development and function of regulatory T (Treg) cells, but it remains elusive how Foxp3 functions in vivo. Here, we established mouse models harboring three unique missense Foxp3 mutations that were identified in patients with the autoimmune disease IPEX. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues. Mechanistically, repressed BATF expression contributed to these A384T effects. At the molecular level, the A384T mutation altered Foxp3 interactions with its specific target genes including Batf by broadening its DNA-binding specificity. Our findings identify BATF as a critical regulator of tissue Treg cells and suggest that sequence-specific perturbations of Foxp3-DNA interactions can influence specific facets of Treg cell physiology and the immunopathologies they regulate. Copyright © 2017 Elsevier Inc. All rights reserved.
FusionAnalyser: a new graphical, event-driven tool for fusion rearrangements discovery

PubMed Central

Piazza, Rocco; Pirola, Alessandra; Spinelli, Roberta; Valletta, Simona; Redaelli, Sara; Magistroni, Vera; Gambacorti-Passerini, Carlo

2012-01-01

Gene fusions are common driver events in leukaemias and solid tumours; here we present FusionAnalyser, a tool dedicated to the identification of driver fusion rearrangements in human cancer through the analysis of paired-end high-throughput transcriptome sequencing data. We initially tested FusionAnalyser by using a set of in silico randomly generated sequencing data from 20 known human translocations occurring in cancer and subsequently using transcriptome data from three chronic and three acute myeloid leukaemia samples. in all the cases our tool was invariably able to detect the presence of the correct driver fusion event(s) with high specificity. In one of the acute myeloid leukaemia samples, FusionAnalyser identified a novel, cryptic, in-frame ETS2–ERG fusion. A fully event-driven graphical interface and a flexible filtering system allow complex analyses to be run in the absence of any a priori programming or scripting knowledge. Therefore, we propose FusionAnalyser as an efficient and robust graphical tool for the identification of functional rearrangements in the context of high-throughput transcriptome sequencing data. PMID:22570408
FusionAnalyser: a new graphical, event-driven tool for fusion rearrangements discovery.

PubMed

Piazza, Rocco; Pirola, Alessandra; Spinelli, Roberta; Valletta, Simona; Redaelli, Sara; Magistroni, Vera; Gambacorti-Passerini, Carlo

2012-09-01

Gene fusions are common driver events in leukaemias and solid tumours; here we present FusionAnalyser, a tool dedicated to the identification of driver fusion rearrangements in human cancer through the analysis of paired-end high-throughput transcriptome sequencing data. We initially tested FusionAnalyser by using a set of in silico randomly generated sequencing data from 20 known human translocations occurring in cancer and subsequently using transcriptome data from three chronic and three acute myeloid leukaemia samples. in all the cases our tool was invariably able to detect the presence of the correct driver fusion event(s) with high specificity. In one of the acute myeloid leukaemia samples, FusionAnalyser identified a novel, cryptic, in-frame ETS2-ERG fusion. A fully event-driven graphical interface and a flexible filtering system allow complex analyses to be run in the absence of any a priori programming or scripting knowledge. Therefore, we propose FusionAnalyser as an efficient and robust graphical tool for the identification of functional rearrangements in the context of high-throughput transcriptome sequencing data.
0610009K11Rik, a testis-specific and germ cell nuclear receptor-interacting protein

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

Zhang Heng; Denhard, Leslie A.; Zhou Huaxin

Using an in silico approach, a putative nuclear receptor-interacting protein 0610009K11Rik was identified in mouse testis. We named this gene testis-specific nuclear receptor-interacting protein-1 (Tnrip-1). Tnrip-1 was predominantly expressed in the testis of adult mouse tissues. Expression of Tnrip-1 in the testis was regulated during postnatal development, with robust expression in 14-day-old or older testes. In situ hybridization analyses showed that Tnrip-1 is highly expressed in pachytene spermatocytes and spermatids. Consistent with its mRNA expression, Tnrip-1 protein was detected in adult mouse testes. Immunohistochemical studies showed that Tnrip-1 is a nuclear protein and mainly expressed in pachytene spermatocytes and roundmore » spermatids. Moreover, co-immunoprecipitation analyses showed that endogenous Tnrip-1 protein can interact with germ cell nuclear receptor (GCNF) in adult mouse testes. Our results suggest that Tnrip-1 is a testis-specific and GCNF-interacting protein which may be involved in the modulation of GCNF-mediated gene transcription in spermatogenic cells within the testis.« less
Public reaction to the death of Steve Jobs: implications for cancer communication.

PubMed

Myrick, Jessica Gall; Noar, Seth M; Willoughby, Jessica Fitts; Brown, Jennifer

2014-01-01

The present study aimed to examine the public reaction to the death of Steve Jobs, focusing on general and cancer-specific information seeking and interpersonal communication. Shortly after Jobs's death, employees from a large university in the Southeastern United States (N = 1,398) completed a web-based survey. Every employee had heard about Steve Jobs's death, and 97% correctly identified pancreatic cancer as the cause of his death. General (50%) and pancreatic cancer-specific (7%) information seeking, as well as general (74%) and pancreatic cancer-specific (17%) interpersonal communication, took place in response to Steve Jobs's death. In multivariate logistic regression analyses controlling for demographics and several cancer-oriented variables, both identification with Steve Jobs and cancer worry in response to Steve Jobs's death significantly (p < .05) predicted pancreatic cancer information seeking as well as interpersonal communication about pancreatic cancer. Additional analyses revealed that cancer worry partially mediated the effects of identification on these outcome variables. Implications of these results for future research as well as cancer prevention and communication efforts are discussed.
Phylogenomic and Molecular Demarcation of the Core Members of the Polyphyletic Pasteurellaceae Genera Actinobacillus, Haemophilus, and Pasteurella

PubMed Central

Naushad, Sohail; Adeolu, Mobolaji; Goel, Nisha; Khadka, Bijendra; Al-Dahwi, Aqeel; Gupta, Radhey S.

2015-01-01

The genera Actinobacillus, Haemophilus, and Pasteurella exhibit extensive polyphyletic branching in phylogenetic trees and do not represent coherent clusters of species. In this study, we have utilized molecular signatures identified through comparative genomic analyses in conjunction with genome based and multilocus sequence based phylogenetic analyses to clarify the phylogenetic and taxonomic boundary of these genera. We have identified large clusters of Actinobacillus, Haemophilus, and Pasteurella species which represent the “sensu stricto” members of these genera. We have identified 3, 7, and 6 conserved signature indels (CSIs), which are specifically shared by sensu stricto members of Actinobacillus, Haemophilus, and Pasteurella, respectively. We have also identified two different sets of CSIs that are unique characteristics of the pathogen containing genera Aggregatibacter and Mannheimia, respectively. It is now possible to demarcate the genera Actinobacillus sensu stricto, Haemophilus sensu stricto, and Pasteurella sensu stricto on the basis of discrete molecular signatures. The other members of the genera Actinobacillus, Haemophilus, and Pasteurella that do not fall within the “sensu stricto” clades and do not contain these molecular signatures should be reclassified as other genera. The CSIs identified here also provide useful diagnostic targets for the identification of current and novel members of the indicated genera. PMID:25821780
Modular organization of the white spruce (Picea glauca) transcriptome reveals functional organization and evolutionary signatures.

PubMed

Raherison, Elie S M; Giguère, Isabelle; Caron, Sébastien; Lamara, Mebarek; MacKay, John J

2015-07-01

Transcript profiling has shown the molecular bases of several biological processes in plants but few studies have developed an understanding of overall transcriptome variation. We investigated transcriptome structure in white spruce (Picea glauca), aiming to delineate its modular organization and associated functional and evolutionary attributes. Microarray analyses were used to: identify and functionally characterize groups of co-expressed genes; investigate expressional and functional diversity of vascular tissue preferential genes which were conserved among Picea species, and identify expression networks underlying wood formation. We classified 22 857 genes as variable (79%; 22 coexpression groups) or invariant (21%) by profiling across several vegetative tissues. Modular organization and complex transcriptome restructuring among vascular tissue preferential genes was revealed by their assignment to coexpression groups with partially overlapping profiles and partially distinct functions. Integrated analyses of tissue-based and temporally variable profiles identified secondary xylem gene networks, showed their remodelling over a growing season and identified PgNAC-7 (no apical meristerm (NAM), Arabidopsis transcription activation factor (ATAF) and cup-shaped cotyledon (CUC) transcription factor 007 in Picea glauca) as a major hub gene specific to earlywood formation. Reference profiling identified comprehensive, statistically robust coexpressed groups, revealing that modular organization underpins the evolutionary conservation of the transcriptome structure. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology.

PubMed

Liu, Tao; Sims, David; Baum, Buzz

2009-01-01

In recent years RNAi screening has proven a powerful tool for dissecting gene functions in animal cells in culture. However, to date, most RNAi screens have been performed in a single cell line, and results then extrapolated across cell types and systems. Here, to dissect generic and cell type-specific mechanisms underlying cell morphology, we have performed identical kinome RNAi screens in six different Drosophila cell lines, derived from two distinct tissues of origin. This analysis identified a core set of kinases required for normal cell morphology in all lines tested, together with a number of kinases with cell type-specific functions. Most significantly, the screen identified a role for minibrain (mnb/DYRK1A), a kinase associated with Down's syndrome, in the regulation of actin-based protrusions in CNS-derived cell lines. This cell type-specific requirement was not due to the peculiarities in the morphology of CNS-derived cells and could not be attributed to differences in mnb expression. Instead, it likely reflects differences in gene expression that constitute the cell type-specific functional context in which mnb/DYRK1A acts. Using parallel RNAi screens and gene expression analyses across cell types we have identified generic and cell type-specific regulators of cell morphology, which include mnb/DYRK1A in the regulation of protrusion morphology in CNS-derived cell lines. This analysis reveals the importance of using different cell types to gain a thorough understanding of gene function across the genome and, in the case of kinases, the difficulties of using the differential gene expression to predict function.
Gender identification of Grasshopper Sparrows comparing behavioral, morphological, and molecular techniques

USGS Publications Warehouse

Ammer, F.K.; Wood, P.B.; McPherson, R.J.

2008-01-01

Correct gender identification in monomorphic species is often difficult especially if males and females do not display obvious behavioral and breeding differences. We compared gender specific morphology and behavior with recently developed DNA techniques for gender identification in the monomorphic Grasshopper Sparrow (Ammodramus savannarum). Gender was ascertained with DNA in 213 individuals using the 2550F/2718R primer set and 3% agarose gel electrophoresis. Field observations using behavior and breeding characteristics to identify gender matched DNA analyses with 100% accuracy for adult males and females. Gender was identified with DNA for all captured juveniles that did not display gender specific traits or behaviors in the field. The molecular techniques used offered a high level of accuracy and may be useful in studies of dispersal mechanisms and winter assemblage composition in monomorphic species.
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for fast and accurate identification of clinically relevant Aspergillus species.

PubMed

Alanio, A; Beretti, J-L; Dauphin, B; Mellado, E; Quesne, G; Lacroix, C; Amara, A; Berche, P; Nassif, X; Bougnoux, M-E

2011-05-01

New Aspergillus species have recently been described with the use of multilocus sequencing in refractory cases of invasive aspergillosis. The classical phenotypic identification methods routinely used in clinical laboratories failed to identify them adequately. Some of these Aspergillus species have specific patterns of susceptibility to antifungal agents, and misidentification may lead to inappropriate therapy. We developed a matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based strategy to adequately identify Aspergillus species to the species level. A database including the reference spectra of 28 clinically relevant species from seven Aspergillus sections (five common and 23 unusual species) was engineered. The profiles of young and mature colonies were analysed for each reference strain, and species-specific spectral fingerprints were identified. The performance of the database was then tested on 124 clinical and 16 environmental isolates previously characterized by partial sequencing of the β-tubulin and calmodulin genes. One hundred and thirty-eight isolates of 140 (98.6%) were correctly identified. Two atypical isolates could not be identified, but no isolate was misidentified (specificity: 100%). The database, including species-specific spectral fingerprints of young and mature colonies of the reference strains, allowed identification regardless of the maturity of the clinical isolate. These results indicate that MALDI-TOF MS is a powerful tool for rapid and accurate identification of both common and unusual species of Aspergillus. It can give better results than morphological identification in clinical laboratories. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.
Characterization of the Fine Specificity of Bovine CD8 T-Cell Responses to Defined Antigens from the Protozoan Parasite Theileria parva▿

PubMed Central

Graham, Simon P.; Pellé, Roger; Yamage, Mat; Mwangi, Duncan M.; Honda, Yoshikazu; Mwakubambanya, Ramadhan S.; de Villiers, Etienne P.; Abuya, Evelyne; Awino, Elias; Gachanja, James; Mbwika, Ferdinand; Muthiani, Anthony M.; Muriuki, Cecelia; Nyanjui, John K.; Onono, Fredrick O.; Osaso, Julius; Riitho, Victor; Saya, Rosemary M.; Ellis, Shirley A.; McKeever, Declan J.; MacHugh, Niall D.; Gilbert, Sarah C.; Audonnet, Jean-Christophe; Morrison, W. Ivan; van der Bruggen, Pierre; Taracha, Evans L. N.

2008-01-01

Immunity against the bovine intracellular protozoan parasite Theileria parva has been shown to be mediated by CD8 T cells. Six antigens targeted by CD8 T cells from T. parva-immune cattle of different major histocompatibility complex (MHC) genotypes have been identified, raising the prospect of developing a subunit vaccine. To facilitate further dissection of the specificity of protective CD8 T-cell responses and to assist in the assessment of responses to vaccination, we set out to identify the epitopes recognized in these T. parva antigens and their MHC restriction elements. Nine epitopes in six T. parva antigens, together with their respective MHC restriction elements, were successfully identified. Five of the cytotoxic-T-lymphocyte epitopes were found to be restricted by products of previously described alleles, and four were restricted by four novel restriction elements. Analyses of CD8 T-cell responses to five of the epitopes in groups of cattle carrying the defined restriction elements and immunized with live parasites demonstrated that, with one exception, the epitopes were consistently recognized by animals of the respective genotypes. The analysis of responses was extended to animals immunized with multiple antigens delivered in separate vaccine constructs. Specific CD8 T-cell responses were detected in 19 of 24 immunized cattle. All responder cattle mounted responses specific for antigens for which they carried an identified restriction element. By contrast, only 8 of 19 responder cattle displayed a response to antigens for which they did not carry an identified restriction element. These data demonstrate that the identified antigens are inherently dominant in animals with the corresponding MHC genotypes. PMID:18070892
The impact of structural uncertainty on cost-effectiveness models for adjuvant endocrine breast cancer treatments: the need for disease-specific model standardization and improved guidance.

PubMed

Frederix, Gerardus W J; van Hasselt, Johan G C; Schellens, Jan H M; Hövels, Anke M; Raaijmakers, Jan A M; Huitema, Alwin D R; Severens, Johan L

2014-01-01

Structural uncertainty relates to differences in model structure and parameterization. For many published health economic analyses in oncology, substantial differences in model structure exist, leading to differences in analysis outcomes and potentially impacting decision-making processes. The objectives of this analysis were (1) to identify differences in model structure and parameterization for cost-effectiveness analyses (CEAs) comparing tamoxifen and anastrazole for adjuvant breast cancer (ABC) treatment; and (2) to quantify the impact of these differences on analysis outcome metrics. The analysis consisted of four steps: (1) review of the literature for identification of eligible CEAs; (2) definition and implementation of a base model structure, which included the core structural components for all identified CEAs; (3) definition and implementation of changes or additions in the base model structure or parameterization; and (4) quantification of the impact of changes in model structure or parameterizations on the analysis outcome metrics life-years gained (LYG), incremental costs (IC) and the incremental cost-effectiveness ratio (ICER). Eleven CEA analyses comparing anastrazole and tamoxifen as ABC treatment were identified. The base model consisted of the following health states: (1) on treatment; (2) off treatment; (3) local recurrence; (4) metastatic disease; (5) death due to breast cancer; and (6) death due to other causes. The base model estimates of anastrazole versus tamoxifen for the LYG, IC and ICER were 0.263 years, €3,647 and €13,868/LYG, respectively. In the published models that were evaluated, differences in model structure included the addition of different recurrence health states, and associated transition rates were identified. Differences in parameterization were related to the incidences of recurrence, local recurrence to metastatic disease, and metastatic disease to death. The separate impact of these model components on the LYG ranged from 0.207 to 0.356 years, while incremental costs ranged from €3,490 to €3,714 and ICERs ranged from €9,804/LYG to €17,966/LYG. When we re-analyzed the published CEAs in our framework by including their respective model properties, the LYG ranged from 0.207 to 0.383 years, IC ranged from €3,556 to €3,731 and ICERs ranged from €9,683/LYG to €17,570/LYG. Differences in model structure and parameterization lead to substantial differences in analysis outcome metrics. This analysis supports the need for more guidance regarding structural uncertainty and the use of standardized disease-specific models for health economic analyses of adjuvant endocrine breast cancer therapies. The developed approach in the current analysis could potentially serve as a template for further evaluations of structural uncertainty and development of disease-specific models.
Co-expression networks reveal the tissue-specific regulation of transcription and splicing

PubMed Central

Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D.H.; Jo, Brian; Gao, Chuan; McDowell, Ian C.; Engelhardt, Barbara E.

2017-01-01

Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. PMID:29021288
Enhancing international medical graduates' communication: the contribution of applied linguistics.

PubMed

Dahm, Maria R; Yates, Lynda; Ogden, Kathryn; Rooney, Kim; Sheldon, Brooke

2015-08-01

International medical graduates (IMGs) make up one-third of the Australian medical workforce. Those from non-English-language backgrounds can face cultural and communication barriers, yet linguistic support is variable and medical educators are often required to provide feedback on both medical and communication issues. However, some communication difficulties may be very specific to the experiences of IMGs as second language users. This interdisciplinary study combines perspectives from applied linguistics experts and clinical educators to address IMGs' difficulties from multiple dimensions and to enhance feedback quality. Five video-recorded patient encounters with five IMGs were collected at Launceston General Hospital. Three clinical educators gave quantitative and qualitative feedback using the Rating Instrument for Clinical Consulting Skills, and two applied linguistics experts analysed the data for language, pragmatic and communication difficulties. The comparison of the educators' language-related feedback with linguistic analyses of the same interactions facilitated the exploration of differences in the difficulties identified by the two expert groups. Although the clinical educators were able to use their tacit intuitive understanding of communication issues to identify IMG difficulties, they less frequently addressed the underlying issues or suggested specific remedies in their feedback. This pilot study illustrates the effectiveness of interdisciplinary collaboration in highlighting the specific discourse features contributing to IMG communication difficulties and thus assists educators in deconstructing their intuitive knowledge. The authors suggest that linguistic insights can therefore improve communications training by assisting educators to provide more targeted feedback. © 2015 John Wiley & Sons Ltd.
Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation.

PubMed

Liang, Yuh-Jin; Kuo, Huan-Hsien; Lin, Chi-Hung; Chen, Yen-Ying; Yang, Bei-Chia; Cheng, Yuan-Yuan; Yu, Alice L; Khoo, Kay-Hooi; Yu, John

2010-12-28

A systematic survey of expression profiles of glycosphingolipids (GSLs) in two hESC lines and their differentiated embryoid body (EB) outgrowth with three germ layers was carried out using immunofluorescence, flow cytometry, and MALDI-MS and MS/MS analyses. In addition to the well-known hESC-specific markers stage-specific embryonic antigen 3 (SSEA-3) and SSEA-4, we identified several globosides and lacto-series GSLs, previously unrevealed in hESCs, including Gb(4)Cer, Lc(4)Cer, fucosyl Lc(4)Cer, Globo H, and disialyl Gb(5)Cer. During hESC differentiation into EBs, MS analysis revealed a clear-cut switch in the core structures of GSLs from globo- and lacto- to ganglio-series, which was not as evident by immunostaining with antibodies against SSEA-3 and SSEA-4, owing to their cross-reactivities with various glycosphingolipids. Such a switch was attributable to altered expression of key glycosyltransferases (GTs) in the biosynthetic pathways by the up-regulation of ganglio-series-related GTs with simultaneous down-regulation of globo- and lacto-series-related GTs. Thus, these results provide insights into the unique stage-specific transition and mechanism for alterations of GSL core structures during hESC differentiation. In addition, unique glycan structures uncovered by MS analyses may serve as surface markers for further delineation of hESCs and help identify of their functional roles not only in hESCs but also in cancers.
Assessment of Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk

PubMed Central

Czarnota, Jenna; Gennings, Chris; Wheeler, David C

2015-01-01

In evaluation of cancer risk related to environmental chemical exposures, the effect of many chemicals on disease is ultimately of interest. However, because of potentially strong correlations among chemicals that occur together, traditional regression methods suffer from collinearity effects, including regression coefficient sign reversal and variance inflation. In addition, penalized regression methods designed to remediate collinearity may have limitations in selecting the truly bad actors among many correlated components. The recently proposed method of weighted quantile sum (WQS) regression attempts to overcome these problems by estimating a body burden index, which identifies important chemicals in a mixture of correlated environmental chemicals. Our focus was on assessing through simulation studies the accuracy of WQS regression in detecting subsets of chemicals associated with health outcomes (binary and continuous) in site-specific analyses and in non-site-specific analyses. We also evaluated the performance of the penalized regression methods of lasso, adaptive lasso, and elastic net in correctly classifying chemicals as bad actors or unrelated to the outcome. We based the simulation study on data from the National Cancer Institute Surveillance Epidemiology and End Results Program (NCI-SEER) case–control study of non-Hodgkin lymphoma (NHL) to achieve realistic exposure situations. Our results showed that WQS regression had good sensitivity and specificity across a variety of conditions considered in this study. The shrinkage methods had a tendency to incorrectly identify a large number of components, especially in the case of strong association with the outcome. PMID:26005323
Assessment of weighted quantile sum regression for modeling chemical mixtures and cancer risk.

PubMed

Czarnota, Jenna; Gennings, Chris; Wheeler, David C

2015-01-01

In evaluation of cancer risk related to environmental chemical exposures, the effect of many chemicals on disease is ultimately of interest. However, because of potentially strong correlations among chemicals that occur together, traditional regression methods suffer from collinearity effects, including regression coefficient sign reversal and variance inflation. In addition, penalized regression methods designed to remediate collinearity may have limitations in selecting the truly bad actors among many correlated components. The recently proposed method of weighted quantile sum (WQS) regression attempts to overcome these problems by estimating a body burden index, which identifies important chemicals in a mixture of correlated environmental chemicals. Our focus was on assessing through simulation studies the accuracy of WQS regression in detecting subsets of chemicals associated with health outcomes (binary and continuous) in site-specific analyses and in non-site-specific analyses. We also evaluated the performance of the penalized regression methods of lasso, adaptive lasso, and elastic net in correctly classifying chemicals as bad actors or unrelated to the outcome. We based the simulation study on data from the National Cancer Institute Surveillance Epidemiology and End Results Program (NCI-SEER) case-control study of non-Hodgkin lymphoma (NHL) to achieve realistic exposure situations. Our results showed that WQS regression had good sensitivity and specificity across a variety of conditions considered in this study. The shrinkage methods had a tendency to incorrectly identify a large number of components, especially in the case of strong association with the outcome.
Methodology capture: discriminating between the "best" and the rest of community practice

PubMed Central

Eales, James M; Pinney, John W; Stevens, Robert D; Robertson, David L

2008-01-01

Background The methodologies we use both enable and help define our research. However, as experimental complexity has increased the choice of appropriate methodologies has become an increasingly difficult task. This makes it difficult to keep track of available bioinformatics software, let alone the most suitable protocols in a specific research area. To remedy this we present an approach for capturing methodology from literature in order to identify and, thus, define best practice within a field. Results Our approach is to implement data extraction techniques on the full-text of scientific articles to obtain the set of experimental protocols used by an entire scientific discipline, molecular phylogenetics. Our methodology for identifying methodologies could in principle be applied to any scientific discipline, whether or not computer-based. We find a number of issues related to the nature of best practice, as opposed to community practice. We find that there is much heterogeneity in the use of molecular phylogenetic methods and software, some of which is related to poor specification of protocols. We also find that phylogenetic practice exhibits field-specific tendencies that have increased through time, despite the generic nature of the available software. We used the practice of highly published and widely collaborative researchers ("expert" researchers) to analyse the influence of authority on community practice. We find expert authors exhibit patterns of practice common to their field and therefore act as useful field-specific practice indicators. Conclusion We have identified a structured community of phylogenetic researchers performing analyses that are customary in their own local community and significantly different from those in other areas. Best practice information can help to bridge such subtle differences by increasing communication of protocols to a wider audience. We propose that the practice of expert authors from the field of evolutionary biology is the closest to contemporary best practice in phylogenetic experimental design. Capturing best practice is, however, a complex task and should also acknowledge the differences between fields such as the specific context of the analysis. PMID:18761740

Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density

PubMed Central

Edwards, D. L.; Saleh, A. A.; Greenspan, S. L.

2015-01-01

Summary We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90 % at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. Introduction The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. Methods Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. Results One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89 % (95%CI 82–96 %) and 41 % (95%CI 23–59 %), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88 % (95%CI 79–97 %) and 55 % (95%CI 42–68 %), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90 % but always with a trade-off of relatively low specificity. Conclusions Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90 % for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. PMID:25644147
An Integrated Systems Biology Approach Identifies TRIM25 as a Key Determinant of Breast Cancer Metastasis.

PubMed

Walsh, Logan A; Alvarez, Mariano J; Sabio, Erich Y; Reyngold, Marsha; Makarov, Vladimir; Mukherjee, Suranjit; Lee, Ken-Wing; Desrichard, Alexis; Turcan, Şevin; Dalin, Martin G; Rajasekhar, Vinagolu K; Chen, Shuibing; Vahdat, Linda T; Califano, Andrea; Chan, Timothy A

2017-08-15

At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients. Our analyses confirmed established pro-metastatic transcription factors, and they uncovered TRIM25 as a key regulator of metastasis-related transcriptional programs. Further, in vivo analyses established TRIM25 as a potent regulator of metastatic disease and poor survival outcome. Our findings suggest that identifying and targeting keystone proteins, like TRIM25, can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing an innovative cancer intervention strategy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
The Effect of Executive Function on Science Achievement Among Normally Developing 10-Year Olds

NASA Astrophysics Data System (ADS)

Lederman, Sheri G.

Executive function (EF) is an umbrella term used to identify a set of discrete but interrelated cognitive abilities that enable individuals to engage in goal-directed, future-oriented action in response to a novel context. Developmental studies indicate that EF is predictive of reading and math achievement in middle childhood. The purpose of this study was to identify the association between EF and science achievement among normally developing 10 year olds. A sample of fifth grade students from a Northeastern suburban community participated in tests of EF, science, and intelligence. Consistent with adult models of EF, principal components analysis identified a three-factor model of EF organization in middle childhood, including cognitive flexibility, working memory, and inhibition. Multiple regression analyses revealed that executive function processes of cognitive flexibility, working memory, and inhibition were all predictive of science performance. Post hoc analyses revealed that high-performing science students differed significantly from low-performing students in both cognitive flexibility and working memory. These findings suggest that complex academic demands specific to science achievement rely on the emergence and maturation of EF components.
Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes.

PubMed

Ai, Rizi; Laragione, Teresina; Hammaker, Deepa; Boyle, David L; Wildberg, Andre; Maeshima, Keisuke; Palescandolo, Emanuele; Krishna, Vinod; Pocalyko, David; Whitaker, John W; Bai, Yuchen; Nagpal, Sunil; Bachman, Kurtis E; Ainsworth, Richard I; Wang, Mengchi; Ding, Bo; Gulko, Percio S; Wang, Wei; Firestein, Gary S

2018-05-15

Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
Development of a DNA microarray for species identification of quarantine aphids.

PubMed

Lee, Won Sun; Choi, Hwalran; Kang, Jinseok; Kim, Ji-Hoon; Lee, Si Hyeock; Lee, Seunghwan; Hwang, Seung Yong

2013-12-01

Aphid pests are being brought into Korea as a result of increased crop trading. Aphids exist on growth areas of plants, and thus plant growth is seriously affected by aphid pests. However, aphids are very small and have several sexual morphs and life stages, so it is difficult to identify species on the basis of morphological features. This problem was approached using DNA microarray technology. DNA targets of the cytochrome c oxidase subunit I gene were generated with a fluorescent dye-labelled primer and were hybridised onto a DNA microarray consisting of specific probes. After analysing the signal intensity of the specific probes, the unique patterns from the DNA microarray, consisting of 47 species-specific probes, were obtained to identify 23 aphid species. To confirm the accuracy of the developed DNA microarray, ten individual blind samples were used in blind trials, and the identifications were completely consistent with the sequencing data of all individual blind samples. A microarray has been developed to distinguish aphid species. DNA microarray technology provides a rapid, easy, cost-effective and accurate method for identifying aphid species for pest control management. © 2013 Society of Chemical Industry.
Managing flood risks in the Mekong Delta: How to address emerging challenges under climate change and socioeconomic developments.

PubMed

Hoang, Long Phi; Biesbroek, Robbert; Tri, Van Pham Dang; Kummu, Matti; van Vliet, Michelle T H; Leemans, Rik; Kabat, Pavel; Ludwig, Fulco

2018-02-24

Climate change and accelerating socioeconomic developments increasingly challenge flood-risk management in the Vietnamese Mekong River Delta-a typical large, economically dynamic and highly vulnerable delta. This study identifies and addresses the emerging challenges for flood-risk management. Furthermore, we identify and analyse response solutions, focusing on meaningful configurations of the individual solutions and how they can be tailored to specific challenges using expert surveys, content analysis techniques and statistical inferences. Our findings show that the challenges for flood-risk management are diverse, but critical challenges predominantly arise from the current governance and institutional settings. The top-three challenges include weak collaboration, conflicting management objectives and low responsiveness to new issues. We identified 114 reported solutions and developed six flood management strategies that are tailored to specific challenges. We conclude that the current technology-centric flood management approach is insufficient given the rapid socioecological changes. This approach therefore should be adapted towards a more balanced management configuration where technical and infrastructural measures are combined with institutional and governance resolutions. Insights from this study contribute to the emerging repertoire of contemporary flood management solutions, especially through their configurations and tailoring to specific challenges.
A double stain for total and oxidized proteins from two-dimensional fingerprints.

PubMed

Talent, J M; Kong, Y; Gracy, R W

1998-10-01

Oxidative modification of proteins plays a major role in the etiology of aging and age-related diseases. For example, in Alzheimer's disease, although evidence points to oxidation of proteins as a causative factor in loss of cognitive abilities, it is not known which specific proteins of the brain are most susceptible to these modifications. Thus, it is of interest to identify the specific proteins which are susceptible to oxidation in vivo. Two-dimensional protein fingerprint methods offer the analytical potential for resolution of thousands of individual proteins from tissues, and the oxidized proteins can be visualized with immunological probes. Sensitive methods permit recovery and sufficient amino acid sequencing to identify these proteins. However, for such analyses it is essential to simultaneously analyze both protein content and level of oxidation. We have evaluated several approaches, identified the sources of artifacts and interferences, and developed a double-staining procedure that allows visualization and quantitation of total protein patterns as well as the specific oxidized proteins from two-dimensional protein fingerprints. The method has been applied to cells grown in culture and to tissue extracts from young and old animals. Copyright 1998 Academic Press.
Genome-wide Association Study Identifies Peanut Allergy-Specific Loci and Evidence of Epigenetic Mediation in U.S. Children

PubMed Central

Hong, Xiumei; Hao, Ke; Ladd-Acosta, Christine; Hansen, Kasper D; Tsai, Hui-Ju; Liu, Xin; Xu, Xin; Thornton, Timothy A.; Caruso, Deanna; Keet, Corinne A; Sun, Yifei; Wang, Guoying; Luo, Wei; Kumar, Rajesh; Fuleihan, Ramsay; Singh, Anne Marie; Kim, Jennifer S; Story, Rachel E; Gupta, Ruchi S; Gao, Peisong; Chen, Zhu; Walker, Sheila O.; Bartell, Tami R; Beaty, Terri H; Fallin, M Daniele; Schleimer, Robert; Holt, Patrick G; Nadeau, Kari Christine; Wood, Robert A; Pongracic, Jacqueline A; Weeks, Daniel E; Wang, Xiaobin

2015-01-01

Food allergy (FA) affects 2–10% of U.S. children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk, and egg) in 2,759 U.S. participants (1,315 children; 1,444 parents) from the Chicago Food Allergy Study; and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (p=5.5×10−8) and rs9275596 (p=6.8×10−10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (p<5×10−8); and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region likely poses significant genetic risk for PA. PMID:25710614
Lymph node ratio predicts disease-specific survival in melanoma patients.

PubMed

Xing, Yan; Badgwell, Brian D; Ross, Merrick I; Gershenwald, Jeffrey E; Lee, Jeffrey E; Mansfield, Paul F; Lucci, Anthony; Cormier, Janice N

2009-06-01

The objectives of this analysis were to compare various measures associated with lymph node (LN) dissection and to identify threshold values associated with disease-specific survival (DSS) outcomes in patients with melanoma. Patients with lymph node-positive melanoma who underwent therapeutic LN dissection of the neck, axilla, and inguinal region were identified from the SEER database (1988-2005). We performed Cox multivariate analyses to determine the impact of the total number of LNs removed, number of negative LNs removed, and LN ratio on DSS. Multivariate cut-point analyses were conducted for each anatomic region to identify the threshold values associated with the largest improvement in DSS. The LN ratio was significantly associated with DSS for all LN regions. The LN ratio thresholds resulting in the greatest difference in 5-year DSS were .07, .13, and .18 for neck, axillary, and inguinal regions, respectively, corresponding to 15, 8, and 6 LNs removed per positive lymph node. After adjustment for other clinicopathologic factors, the hazard ratios (HRs) were .53 (95% confidence interval [CI], .40 to .71) in the neck, .52 (95% CI, .42 to .65) in the axillary, and .47 (95% CI, .36 to .61) in the inguinal regions for patients who met the LN ratio threshold. Among the prognostic factors examined, LN ratio was the best indicator of the extent of LN dissection, regardless of anatomic nodal region. These data provide evidence-based guidelines for defining adequate LN dissections in melanoma patients. (c) 2009 American Cancer Society.
Structural and antigenic identification of the ORF12 protein (alpha TIF) of equine herpesvirus 1.

PubMed

Lewis, J B; Thompson, Y G; Feng, X; Holden, V R; O'Callaghan, D; Caughman, G B

1997-04-14

The equine herpesvirus 1 (EHV-1) homolog of the herpes simplex virus type 1 (HSV-1) tegument phosphoprotein, alpha TIF (Vmw65; VP16), was identified previously as the product of open reading frame 12 (ORF12) and shown to transactivate immediate early (IE) gene promoters. However, a specific virion protein corresponding to the ORF12 product has not been identified definitively. In the present study the ORF12 protein, designated ETIF, was identified as a 60-kDa virion component on the basis of protein fingerprint analyses in which the limited proteolysis profiles of the major 60-kDa in vitro transcription/ translation product of an ORF12 expression vector (pT7-12) were compared to those of purified virion proteins of similar size. ETIF was localized to the viral tegument in Western blot assays of EHV-1 virions and subvirion fractions using polyclonal antiserum and monoclonal antibodies generated against a glutathione-S-transferase-ETIF fusion protein. Northern and Western blot analyses of EHV-1-infected cell lysates prepared under various metabolic blocks indicated that ORF12 is expressed as a late gene, and cross reaction of polyclonal anti-GST-ETIF with a 63.5-kDa HSV-1 protein species suggested that ETIF and HSV-1 alpha TIF are antigenically related. Last, DNA band shift assays used to assess ETIF-specific complex formation indicated that ETIF participates in an infected cell protein complex with the EHV-1 IE promoter TAATGARAT motif.
Cancer and central nervous system disorders: protocol for an umbrella review of systematic reviews and updated meta-analyses of observational studies.

PubMed

Catalá-López, Ferrán; Hutton, Brian; Driver, Jane A; Page, Matthew J; Ridao, Manuel; Valderas, José M; Alonso-Arroyo, Adolfo; Forés-Martos, Jaume; Martínez, Salvador; Gènova-Maleras, Ricard; Macías-Saint-Gerons, Diego; Crespo-Facorro, Benedicto; Vieta, Eduard; Valencia, Alfonso; Tabarés-Seisdedos, Rafael

2017-04-04

The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer's disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down's syndrome, epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes. PROSPERO CRD42016052762.
Cosa Nostra and the Camorra: Assessment of personality, alexithymic traits, and attachment styles.

PubMed

Craparo, Giuseppe; David, Vincenzo; Costanzo, Giulia; Gori, Alessio

The Mafia (Cosa Nostra) and the Camorra are criminal organizations deeply rooted in an immoral familyism in which group interests are protected to the detriment of the individual. The aim of this study was to investigate the presence of personality disorders, alexithymic traits and specific attachment styles in a sample of members belonging to these two different organized crime groups. We carried out two studies adopting two different perspectives. In the first study, we recruited 20 participants (10 members of Cosa Nostra and 10 members of the Camorra) who were serving time in the Augusta (Sicily) prison for crimes they had committed as members of the two Mafia-type organizations. The age of the Cosa Nostra members ranged from 28 to 62 years (M = 47.40, SD = 10.25); the age of the Camorra members ranged from 45 to 68 (M = 55.30, SD = 7.06). We tested personality profiles, attachment styles, alexithymia, and psychopathy and compared the results between the two groups. In this study while we did not find significant differences between the two groups, we were able to identify some discrepancies in a few of the variables analysed. In the second study, we used the Structured Interview of Personality Organization (STIPO) to analyse the personality organization of 10 of 20 participants (5 members of Cosa Nostra and 5 members of Camorra). Analysing the results at the STIPO we found a significant presence of borderline personality organization in both groups. As regards attachment style, we found that Camorra-members' scores high (75°) on the Discomfort with Closeness (related to Avoidant Attachment Style) and Relationship as Secondary factors of the Attachment Style Questionnaire. The Data collected in our study were not sufficient to identify a specific personality disorder or a specific serious psychological condition in the two groups of participants. Nonetheless, thanks to use of the STIPO we were able to determine that in the sample analysed there was not one subject with a psychotic personality organization; we did however find the presence of borderline personality organization and neurotic personality organization in some of the subjects. Copyright © 2018 Elsevier Ltd. All rights reserved.
The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

PubMed

Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

2017-06-01

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.
The experiences and support needs of people with intellectual disabilities who identify as LGBT: A review of the literature.

PubMed

McCann, Edward; Lee, Regina; Brown, Michael

2016-10-01

People who identify as lesbian, gay, bisexual and transgender (LGBT) can face many challenges in society including accessing education, care and support appropriate to individual needs. However, there is a growing and evolving evidence base about the specific needs of people with intellectual disabilities (ID) in this regard. The aim of this review was to explore the experiences of people with ID who identified as LGBT through an examination of studies that addressed their views and highlighted specific issues, concerns and service responses. A comprehensive search of relevant databases from February 1995 to February 2015 was conducted. Studies were identified that met specific criteria that included: empirical peer reviewed studies, the use of recognised research methods and focused on people with ID whom identified as LGBT. The search yielded 161 papers in total. The search was narrowed and 37 papers were screened using rigorous inclusion and exclusion criteria. Finally, 14 papers were considered suitable for the review. The data were analysed and key themes identified that included accessing health services, gender and sexual identity, attitudes of people with ID regarding their LGBT status, and education, supports and therapeutic interventions. There is a need for service providers and carers to be more responsive to the concerns of people with ID who identify as LGBT to improve their health and well-being by reducing stigma and discrimination and by increasing awareness of their care and support needs. The implications are discussed in terms of policy, education, research and practice developments. Copyright © 2016 Elsevier Ltd. All rights reserved.
Cluster Randomised Trials in Cochrane Reviews: Evaluation of Methodological and Reporting Practice.

PubMed

Richardson, Marty; Garner, Paul; Donegan, Sarah

2016-01-01

Systematic reviews can include cluster-randomised controlled trials (C-RCTs), which require different analysis compared with standard individual-randomised controlled trials. However, it is not known whether review authors follow the methodological and reporting guidance when including these trials. The aim of this study was to assess the methodological and reporting practice of Cochrane reviews that included C-RCTs against criteria developed from existing guidance. Criteria were developed, based on methodological literature and personal experience supervising review production and quality. Criteria were grouped into four themes: identifying, reporting, assessing risk of bias, and analysing C-RCTs. The Cochrane Database of Systematic Reviews was searched (2nd December 2013), and the 50 most recent reviews that included C-RCTs were retrieved. Each review was then assessed using the criteria. The 50 reviews we identified were published by 26 Cochrane Review Groups between June 2013 and November 2013. For identifying C-RCTs, only 56% identified that C-RCTs were eligible for inclusion in the review in the eligibility criteria. For reporting C-RCTs, only eight (24%) of the 33 reviews reported the method of cluster adjustment for their included C-RCTs. For assessing risk of bias, only one review assessed all five C-RCT-specific risk-of-bias criteria. For analysing C-RCTs, of the 27 reviews that presented unadjusted data, only nine (33%) provided a warning that confidence intervals may be artificially narrow. Of the 34 reviews that reported data from unadjusted C-RCTs, only 13 (38%) excluded the unadjusted results from the meta-analyses. The methodological and reporting practices in Cochrane reviews incorporating C-RCTs could be greatly improved, particularly with regard to analyses. Criteria developed as part of the current study could be used by review authors or editors to identify errors and improve the quality of published systematic reviews incorporating C-RCTs.
Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of Stevia for Diterpenoid Production1

PubMed Central

Kim, Mi Jung; Jin, Jingjing; Zheng, Junshi

2015-01-01

Stevia (Stevia rebaudiana) produces not only a group of diterpenoid glycosides known as steviol glycosides (SGs), but also other labdane-type diterpenoids that may be spatially separated from SGs. However, their biosynthetic routes and spatial distribution in leaf tissues have not yet been elucidated. Here, we integrate metabolome and transcriptome analyses of Stevia to explore the biosynthetic capacity of leaf tissues for diterpenoid metabolism. Tissue-specific chemical analyses confirmed that SGs were accumulated in leaf cells but not in trichomes. On the other hand, Stevia leaf trichomes stored other labdane-type diterpenoids such as oxomanoyl oxide and agatholic acid. RNA sequencing analyses from two different tissues of Stevia provided a comprehensive overview of dynamic metabolic activities in trichomes and leaf without trichomes. These metabolite-guided transcriptomics and phylogenetic and gene expression analyses clearly identified specific gene members encoding enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate pathway and the biosynthesis of steviol or other labdane-type diterpenoids. Additionally, our RNA sequencing analysis uncovered copalyl diphosphate synthase (SrCPS) and kaurene synthase1 (SrKS1) homologs, SrCPS2 and KS-like (SrKSL), which were specifically expressed in trichomes. In vitro and in planta assays showed that unlike SrCPS and SrKS1, SrCPS2 synthesized labda-13-en-8-ol diphosphate and successively catalyzed the formation of manoyl oxide and epi-manoyl oxide in combination with SrKSL. Our findings suggest that Stevia may have evolved to use distinct metabolic pathways to avoid metabolic interferences in leaf tissues for efficient production of diverse secondary metabolites. PMID:26438788
Thermoreception and Nociception of the Skin: A Classic Paper of Bessou and Perl and Analyses of Thermal Sensitivity during a Student Laboratory Exercise

ERIC Educational Resources Information Center

Kuhtz-Buschbeck, Johann P.; Andresen, Wiebke; Gobel, Stephan; Gilster, Rene; Stick, Carsten

2010-01-01

About four decades ago, Perl and collaborators were the first ones who unambiguously identified specifically nociceptive neurons in the periphery. In their classic work, they recorded action potentials from single C-fibers of a cutaneous nerve in cats while applying carefully graded stimuli to the skin (Bessou P, Perl ER. Response of cutaneous…
Community Composition of Bacterial Biofilms Formed on Simple Soil Based Bioelectrochemical Cell Anodes and Cathodes

DTIC Science & Technology

2012-04-01

included species of Actinobacteria ; however, only the anode biofilms produced species of Firmicutes and Proteobacteria. Analysis of TRFLP profiles...Molecular analyses, specifically of the 16S rRNA eubacterial gene, have also identified the presence of Firmicutes and Actinobacteria ERDC/CRREL TR...re- sulted in the identification of Firmicutes (typically Gram-positive) and Actinobacteria (often Gram-variable) on the anodes of fuel cells
A Laminin G-EGF-Laminin G module in Neurexin IV is essential for the apico-lateral localization of Contactin and organization of septate junctions.

PubMed

Banerjee, Swati; Paik, Raehum; Mino, Rosa E; Blauth, Kevin; Fisher, Elizabeth S; Madden, Victoria J; Fanning, Alan S; Bhat, Manzoor A

2011-01-01

Septate junctions (SJs) display a unique ultrastructural morphology with ladder-like electron densities that are conserved through evolution. Genetic and molecular analyses have identified a highly conserved core complex of SJ proteins consisting of three cell adhesion molecules Neurexin IV, Contactin, and Neuroglian, which interact with the cytoskeletal FERM domain protein Coracle. How these individual proteins interact to form the septal arrays that create the paracellular barrier is poorly understood. Here, we show that point mutations that map to specific domains of neurexin IV lead to formation of fewer septae and disorganization of SJs. Consistent with these observations, our in vivo domain deletion analyses identified the first Laminin G-EGF-Laminin G module in the extracellular region of Neurexin IV as necessary for the localization of and association with Contactin. Neurexin IV protein that is devoid of its cytoplasmic region is able to create septae, but fails to form a full complement of SJs. These data provide the first in vivo evidence that specific domains in Neurexin IV are required for protein-protein interactions and organization of SJs. Given the molecular conservation of SJ proteins across species, our studies may provide insights into how vertebrate axo-glial SJs are organized in myelinated axons.
Predation risk modifies behaviour by shaping the response of identified brain neurons.

PubMed

Magani, Fiorella; Luppi, Tomas; Nuñez, Jesus; Tomsic, Daniel

2016-04-15

Interpopulation comparisons in species that show behavioural variations associated with particular ecological disparities offer good opportunities for assessing how environmental factors may foster specific functional adaptations in the brain. Yet, studies on the neural substrate that can account for interpopulation behavioural adaptations are scarce. Predation is one of the strongest driving forces for behavioural evolvability and, consequently, for shaping structural and functional brain adaptations. We analysed the escape response of crabs ITALIC! Neohelice granulatafrom two isolated populations exposed to different risks of avian predation. Individuals from the high-risk area proved to be more reactive to visual danger stimuli (VDS) than those from an area where predators are rare. Control experiments indicate that the response difference was specific for impending visual threats. Subsequently, we analysed the response to VDS of a group of giant brain neurons that are thought to play a main role in the visually guided escape response of the crab. Neurons from animals of the population with the stronger escape response were more responsive to VDS than neurons from animals of the less reactive population. Our results suggest a robust linkage between the pressure imposed by the predation risk, the response of identified neurons and the behavioural outcome. © 2016. Published by The Company of Biologists Ltd.

Comprehensive identification and analysis of human accelerated regulatory DNA

PubMed Central

Gittelman, Rachel M.; Hun, Enna; Ay, Ferhat; Madeoy, Jennifer; Pennacchio, Len; Noble, William S.; Hawkins, R. David; Akey, Joshua M.

2015-01-01

It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared with protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered in 130 cell types. We identified 524 DHSs that are conserved in nonhuman primates but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHSs are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHSs are often active in brain or neuronal cell types; play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes; and identify striking examples of adaptive regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives. PMID:26104583
Cell Wall Remodeling in Abscission Zone Cells during Ethylene-Promoted Fruit Abscission in Citrus

PubMed Central

Merelo, Paz; Agustí, Javier; Arbona, Vicent; Costa, Mário L.; Estornell, Leandro H.; Gómez-Cadenas, Aurelio; Coimbra, Silvia; Gómez, María D.; Pérez-Amador, Miguel A.; Domingo, Concha; Talón, Manuel; Tadeo, Francisco R.

2017-01-01

Abscission is a cell separation process by which plants can shed organs such as fruits, leaves, or flowers. The process takes place in specific locations termed abscission zones. In fruit crops like citrus, fruit abscission represents a high percentage of annual yield losses. Thus, understanding the molecular regulation of abscission is of capital relevance to control production. To identify genes preferentially expressed within the citrus fruit abscission zone (AZ-C), we performed a comparative transcriptomics assay at the cell type resolution level between the AZ-C and adjacent fruit rind cells (non-abscising tissue) during ethylene-promoted abscission. Our strategy combined laser microdissection with microarray analysis. Cell wall modification-related gene families displayed prominent representation in the AZ-C. Phylogenetic analyses of such gene families revealed a link between phylogenetic proximity and expression pattern during abscission suggesting highly conserved roles for specific members of these families in abscission. Our transcriptomic data was validated with (and strongly supported by) a parallel approach consisting on anatomical, histochemical and biochemical analyses on the AZ-C during fruit abscission. Our work identifies genes potentially involved in organ abscission and provides relevant data for future biotechnology approaches aimed at controlling such crucial process for citrus yield. PMID:28228766
A Laminin G-EGF-Laminin G Module in Neurexin IV Is Essential for the Apico-Lateral Localization of Contactin and Organization of Septate Junctions

PubMed Central

Banerjee, Swati; Paik, Raehum; Mino, Rosa E.; Blauth, Kevin; Fisher, Elizabeth S.; Madden, Victoria J.; Fanning, Alan S.; Bhat, Manzoor A.

2011-01-01

Septate junctions (SJs) display a unique ultrastructural morphology with ladder-like electron densities that are conserved through evolution. Genetic and molecular analyses have identified a highly conserved core complex of SJ proteins consisting of three cell adhesion molecules Neurexin IV, Contactin, and Neuroglian, which interact with the cytoskeletal FERM domain protein Coracle. How these individual proteins interact to form the septal arrays that create the paracellular barrier is poorly understood. Here, we show that point mutations that map to specific domains of neurexin IV lead to formation of fewer septae and disorganization of SJs. Consistent with these observations, our in vivo domain deletion analyses identified the first Laminin G-EGF-Laminin G module in the extracellular region of Neurexin IV as necessary for the localization of and association with Contactin. Neurexin IV protein that is devoid of its cytoplasmic region is able to create septae, but fails to form a full complement of SJs. These data provide the first in vivo evidence that specific domains in Neurexin IV are required for protein-protein interactions and organization of SJs. Given the molecular conservation of SJ proteins across species, our studies may provide insights into how vertebrate axo-glial SJs are organized in myelinated axons. PMID:22022470
Genome-wide expression analyses of the stationary phase model of ageing in yeast.

PubMed

Wanichthanarak, Kwanjeera; Wongtosrad, Nutvadee; Petranovic, Dina

2015-07-01

Ageing processes involved in replicative lifespan (RLS) and chronological lifespan (CLS) have been found to be conserved among many organisms, including in unicellular Eukarya such as yeast Saccharomyces cerevisiae. Here we performed an integrated approach of genome wide expression profiles of yeast at different time points, during growth and starvation. The aim of the study was to identify transcriptional changes in those conditions by using several different computational analyses in order to propose transcription factors, biological networks and metabolic pathways that seem to be relevant during the process of chronological ageing in yeast. Specifically, we performed differential gene expression analysis, gene-set enrichment analysis and network-based analysis, and we identified pathways affected in the stationary phase and specific transcription factors driving transcriptional adaptations. The results indicate signal propagation from G protein-coupled receptors through signaling pathway components and other stress and nutrient-induced transcription factors resulting in adaptation of yeast cells to the lack of nutrients by activating metabolism associated with aerobic metabolism of carbon sources such as ethanol, glycerol and fatty acids. In addition, we found STE12, XBP1 and TOS8 as highly connected nodes in the subnetworks of ageing yeast. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
[Inappropriate analyses of automated external defibrillators used during out-of-hospital cardiac arrests].

PubMed

Ballesteros Peña, Sendoa

2013-04-01

To estimate the frequency of therapeutic errors and to evaluate the diagnostic accuracy in the recognition of shockable rhythms by automated external defibrillators. A retrospective descriptive study. Nine basic life support units from Biscay (Spain). Included 201 patients with cardiac arrest, since 2006 to 2011. The study was made of the suitability of treatment (shock or not) after each analysis and medical errors identified. The sensitivity, specificity and predictive values with 95% confidence intervals were then calculated. A total of 811 electrocardiographic rhythm analyses were obtained, of which 120 (14.1%), from 30 patients, corresponded to shockable rhythms. Sensitivity and specificity for appropriate automated external defibrillators management of a shockable rhythm were 85% (95% CI, 77.5% to 90.3%) and 100% (95% CI, 99.4% to 100%), respectively. Positive and negative predictive values were 100% (95% CI, 96.4% to 100%) and 97.5% (95% CI, 96% to 98.4%), respectively. There were 18 (2.2%; 95% CI, 1.3% to 3.5%) errors associated with defibrillator management, all relating to cases of shockable rhythms that were not shocked. One error was operator dependent, 6 were defibrillator dependent (caused by interaction of pacemakers), and 11 were unclassified. Automated external defibrillators have a very high specificity and moderately high sensitivity. There are few operator dependent errors. Implanted pacemakers interfere with defibrillator analyses. Copyright © 2012 Elsevier España, S.L. All rights reserved.
Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity

PubMed Central

Wang, Hui; Drake, Thomas A; Lusis, Aldons J

2006-01-01

The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, “genetical genomic” analyses have not yet addressed the degree to which their conclusions are affected by sex. We constructed and densely genotyped a large F2 intercross derived from the inbred mouse strains C57BL/6J and C3H/HeJ on an apolipoprotein E null (ApoE−/−) background. This BXH.ApoE−/− population recapitulates several “metabolic syndrome” phenotypes. The cross consists of 334 animals of both sexes, allowing us to specifically test for the dependence of linkage on sex. We detected several thousand liver gene expression quantitative trait loci, a significant proportion of which are sex-biased. We used these analyses to dissect the genetics of gonadal fat mass, a complex trait with sex-specific regulation. We present evidence for a remarkably high degree of sex-dependence on both the cis and trans regulation of gene expression. We demonstrate how these analyses can be applied to the study of the genetics underlying gonadal fat mass, a complex trait showing significantly female-biased heritability. These data have implications on the potential effects of sex on the genetic regulation of other complex traits. PMID:16462940
Economic evaluations and usefulness of standardized nursing terminologies.

PubMed

Stone, Patricia W; Lee, Nam-Ju; Giannini, Melinna; Bakken, Suzanne

2004-01-01

To review different types of economic analyses commonly found in healthcare literature, discuss methodologic considerations in framing economic analyses, identify useful resources for economic evaluations, and describe the current and potential roles of standardized nursing terminologies in providing cost and outcome data for economic analysis. The Advanced Billing Concepts Code Resource-based Relative Value Scale and Nursing Outcomes Classification. Using case studies, the applicability of standardized nursing terminologies in cost-effectiveness analysis is demonstrated. While there is potential to inform specific questions, comparisons across analyses are limited because of the many outcome measures. Including a standardized quality-of-life measure in nursing terminologies would allow for the calculation of accepted outcome measures and dollars per quality adjusted life years gained. The nurse's ability to assess and contribute to all aspects of rigorous economic evidence is an essential competency for responsible practice.
Deliberate and emergent strategies for implementing person-centred care: a qualitative interview study with researchers, professionals and patients.

PubMed

Naldemirci, Öncel; Wolf, Axel; Elam, Mark; Lydahl, Doris; Moore, Lucy; Britten, Nicky

2017-08-04

The introduction of innovative models of healthcare does not necessarily mean that they become embedded in everyday clinical practice. This study has two aims: first, to analyse deliberate and emergent strategies adopted by healthcare professionals to overcome barriers to normalization of a specific framework of person-centred care (PCC); and secondly, to explore how the recipients of PCC understand these strategies. This paper is based on a qualitative study of the implementation of PCC in a Swedish context. It draws on semi-structured interviews with 18 researchers and 17 practitioners who adopted a model of PCC on four different wards and 20 patients who were cared for in one of these wards. Data from these interviews were first coded inductively and emerging themes are analysed in relation to normalization process theory (NPT). In addition to deliberate strategies, we identify emergent strategies to normalize PCC by (i) creating and sustaining coherence in small but continuously communicating groups (ii) interpreting PCC flexibly when it meets specific local situations and (iii) enforcing teamwork between professional groups. These strategies resulted in patients perceiving PCC as bringing about (i) a sense of ease (ii) appreciation of inter-professional congruity (ii) non-hierarchical communication. NPT is useful to identify and analyse deliberate and emergent strategies relating to mechanisms of normalization. Emergent strategies should be interpreted not as trivial solutions to problems in implementation, but as a possible repertoire of tools, practices and skills developed in situ. As professionals and patients may have different understandings of implementation, it is also crucial to include patients' perceptions to evaluate outcomes.
Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository

PubMed Central

Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

2016-01-01

The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports. PMID:28269893
Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository.

PubMed

Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

2016-01-01

The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports.
Waveform identification and retracking analyses of Jason-2 altimeter satellite data for improving sea surface height estimation in Southern Java Island Waters and Java Sea, Indonesia

NASA Astrophysics Data System (ADS)

Nababan, Bisman; Hakim, Muhammad R.; Panjaitan, James P.

2018-05-01

Indonesian waters containing many small islands and shallow waters leads to a less accurate of sea surface height (SSH) estimation from satellite altimetry. Little efforts are also given for the validation of SSH estimation from the satellite in Indonesian waters. The purpose of this research was to identify and retrack waveforms of Jason-2 altimeter satellite data in southern Java island waters and Java Sea using several retrackers and performed improvement percentage analyses for new SSH estimation. The study used data of the Sensor Geophysical Data Record type D (SGDR-D) of Jason-2 satellite altimeter of the year 2010 in the southern Java island waters and 2012-2014 in Java Sea. Waveform retracking analyses were conducted using several retrackers (Offset Center of Gravity, Ice, Threshold, and Improved Threshold) and examined using a world reference undulation geoid of EGM08 and Oceanic retracker. Result showed that shape and pattern of waveforms were varied in all passes, seasons, and locations specifically along the coastal regions. In general, non-Brownish and complex waveforms were identified along coastal region specifically within the distance of 0-10 km from the shoreline. In contrary, generally Brownish waveforms were found in offshore. However, Brownish waveform can also be found within coastal region and non-Brownish waveforms within offshore region. The results were also showed that the four retrackers produced a better SSH estimation in coastal region. However, there was no dominant retracker to improve the accuracy of the SSH estimate.
Development and psychometric evaluation of a cardiovascular risk and disease management knowledge assessment tool.

PubMed

Rosneck, James S; Hughes, Joel; Gunstad, John; Josephson, Richard; Noe, Donald A; Waechter, Donna

2014-01-01

This article describes the systematic construction and psychometric analysis of a knowledge assessment instrument for phase II cardiac rehabilitation (CR) patients measuring risk modification disease management knowledge and behavioral outcomes derived from national standards relevant to secondary prevention and management of cardiovascular disease. First, using adult curriculum based on disease-specific learning outcomes and competencies, a systematic test item development process was completed by clinical staff. Second, a panel of educational and clinical experts used an iterative process to identify test content domain and arrive at consensus in selecting items meeting criteria. Third, the resulting 31-question instrument, the Cardiac Knowledge Assessment Tool (CKAT), was piloted in CR patients to ensure use of application. Validity and reliability analyses were performed on 3638 adults before test administrations with additional focused analyses on 1999 individuals completing both pretreatment and posttreatment administrations within 6 months. Evidence of CKAT content validity was substantiated, with 85% agreement among content experts. Evidence of construct validity was demonstrated via factor analysis identifying key underlying factors. Estimates of internal consistency, for example, Cronbach's α = .852 and Spearman-Brown split-half reliability = 0.817 on pretesting, support test reliability. Item analysis, using point biserial correlation, measured relationships between performance on single items and total score (P < .01). Analyses using item difficulty and item discrimination indices further verified item stability and validity of the CKAT. A knowledge instrument specifically designed for an adult CR population was systematically developed and tested in a large representative patient population, satisfying psychometric parameters, including validity and reliability.
Differential MicroRNA Analyses of Burkholderia pseudomallei- and Francisella tularensis-Exposed hPBMCs Reveal Potential Biomarkers.

PubMed

Cer, Regina Z; Herrera-Galeano, J Enrique; Frey, Kenneth G; Schully, Kevin L; Luu, Truong V; Pesce, John; Mokashi, Vishwesh P; Keane-Myers, Andrea M; Bishop-Lilly, Kimberly A

2017-01-01

Increasing evidence that microRNAs (miRNAs) play important roles in the immune response against infectious agents suggests that miRNA might be exploitable as signatures of exposure to specific infectious agents. In order to identify potential early miRNA biomarkers of bacterial infections, human peripheral blood mononuclear cells (hPBMCs) were exposed to two select agents, Burkholderia pseudomallei K96243 and Francisella tularensis SHU S4, as well as to the nonpathogenic control Escherichia coli DH5 α . RNA samples were harvested at three early time points, 30, 60, and 120 minutes postexposure, then sequenced. RNAseq analyses identified 87 miRNAs to be differentially expressed (DE) in a linear fashion. Of these, 31 miRNAs were tested using the miScript miRNA qPCR assay. Through RNAseq identification and qPCR validation, we identified differentially expressed miRNA species that may be involved in the early response to bacterial infections. Based upon its upregulation at early time points postexposure in two different individuals, hsa-mir-30c-5p is a miRNA species that could be studied further as a potential biomarker for exposure to these gram-negative intracellular pathogens. Gene ontology functional analyses demonstrated that programmed cell death is the first ranking biological process associated with miRNAs that are upregulated in F. tularensis -exposed hPBMCs.
Differential MicroRNA Analyses of Burkholderia pseudomallei- and Francisella tularensis-Exposed hPBMCs Reveal Potential Biomarkers

PubMed Central

Herrera-Galeano, J. Enrique; Frey, Kenneth G.; Schully, Kevin L.; Luu, Truong V.; Pesce, John; Mokashi, Vishwesh P.; Keane-Myers, Andrea M.; Bishop-Lilly, Kimberly A.

2017-01-01

Increasing evidence that microRNAs (miRNAs) play important roles in the immune response against infectious agents suggests that miRNA might be exploitable as signatures of exposure to specific infectious agents. In order to identify potential early miRNA biomarkers of bacterial infections, human peripheral blood mononuclear cells (hPBMCs) were exposed to two select agents, Burkholderia pseudomallei K96243 and Francisella tularensis SHU S4, as well as to the nonpathogenic control Escherichia coli DH5α. RNA samples were harvested at three early time points, 30, 60, and 120 minutes postexposure, then sequenced. RNAseq analyses identified 87 miRNAs to be differentially expressed (DE) in a linear fashion. Of these, 31 miRNAs were tested using the miScript miRNA qPCR assay. Through RNAseq identification and qPCR validation, we identified differentially expressed miRNA species that may be involved in the early response to bacterial infections. Based upon its upregulation at early time points postexposure in two different individuals, hsa-mir-30c-5p is a miRNA species that could be studied further as a potential biomarker for exposure to these gram-negative intracellular pathogens. Gene ontology functional analyses demonstrated that programmed cell death is the first ranking biological process associated with miRNAs that are upregulated in F. tularensis-exposed hPBMCs. PMID:28791299
Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

PubMed

Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

2017-07-01

Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p < 5×10 -8 ) from the NHGRI-EBI Catalog across seven disease/trait categories: cancer, cardiovascular disease, diabetes, autoimmune disease, psychiatric disease, neurological disease, and anthropometric traits. SNPs were annotated using HaploReg for the eight functional elements across any tissue: DNase sites, expression quantitative trait loci (eQTL), sequence conservation, enhancers, promoters, missense variants, sequence motifs, and protein binding sites. In addition, tissue-specific annotations were considered for brain vs. blood. Disease/trait SNPs were compared to a control set of 4809 SNPs matched to the GWAS SNPs (N = 1639) on allele frequency, gene density, distance to nearest gene, and linkage disequilibrium at ~3:1 ratio. Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference = 1.28 × 10 -6 vs. enhancers P TissueDifference = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.
An inorganic carbon transport system responsible for acclimation specific to air levels of CO2 in Chlamydomonas reinhardtii.

PubMed

Wang, Yingjun; Spalding, Martin H

2006-06-27

Many photosynthetic microorganisms acclimate to CO(2) limited environments by induction and operation of CO(2)-concentrating mechanisms (CCMs). Despite their central role in CCM function, inorganic carbon (Ci) transport systems never have been identified in eukaryotic photosynthetic organisms. In the green alga Chlamydomonas reinhardtii, a mutant, pmp1, was described in 1983 with deficiencies in Ci transport, and a Pmp1 protein-associated Ci uptake system has been proposed to be responsible for Ci uptake in low CO(2) (air level)-acclimated cells. However, even though pmp1 represents the only clear genetic link to Ci transport in microalgae and is one of only a very few mutants directly affecting the CCM itself, the identity of Pmp1 has remained unknown. Physiological analyses indicate that C. reinhardtii possesses multiple Ci transport systems responsible for acclimation to different levels of limiting CO(2) and that the Pmp1-associated transport system is required specifically for low (air level) CO(2) acclimation. In the current study, we identified and characterized a pmp1 allelic mutant, air dier 1 (ad1) that, like pmp1, cannot grow in low CO(2) (350 ppm) but can grow either in high CO(2) (5% CO(2)) or in very low CO(2) (<200 ppm). Molecular analyses revealed that the Ad1/Pmp1 protein is encoded by LciB, a gene previously identified as a CO(2)-responsive gene. LciB and three related genes in C. reinhardtii compose a unique gene family that encode four closely related, apparently soluble plastid proteins with no clearly identifiable conserved motifs.
Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

PubMed

Huang, Yen-Tsung; Yang, Hwai-I

2017-05-01

Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.
[Identification of genes that are specifically/preferentially expressed in developing cotton fibers by mRNA fluorescence differential display (FDD)].

PubMed

Sun, Jie; Li, Yuan-Li; Wang, Ruo-Hai; Xia, Gui-Xian

2004-01-01

Fluorescence differential display (FDD) technique was used to identify genes that are specifically or preferentially expressed in different developmental stages of cotton fiber cells. One hundred and nine differentially displayed cDNA fragments were isolated using 9, 21 and 27 DPA (days postanthesis) fibers as experimental materials. By a combination of two rounds of reverse Northern hybridization and Northern blot analyses, a number of such cDNA fragments were proved to represent fiber-specific/preferential genes. Sequencing determination and database searching indicated that most of these genes are novel. This work is an important step towards cloning the full-length cDNAs and characterizing the cellular functions of aforementioned genes in fiber development.
Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

PubMed Central

2012-01-01

Background Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention. Methods Using a collection of reviews identified previously, 166 references including a meta-analysis were selected for review. At least one of the primary outcomes in each review was an adverse or unintended event. The nature of the intervention, source of funding, number of individual meta-analyses performed, number of primary studies included in the review, and use of meta-analytic methods were all recorded. Specific areas of interest relating to the methods used included the choice of outcome metric, methods of dealing with sparse events, heterogeneity, publication bias and use of individual patient data. Results The 166 included reviews were published between 1994 and 2006. Interventions included drugs and surgery among other interventions. Many of the references being reviewed included multiple meta-analyses with 44.6% (74/166) including more than ten. Randomised trials only were included in 42.2% of meta-analyses (70/166), observational studies only in 33.7% (56/166) and a mix of observational studies and trials in 15.7% (26/166). Sparse data, in the form of zero events in one or both arms where the outcome was a count of events, was found in 64 reviews of two-arm studies, of which 41 (64.1%) had zero events in both arms. Conclusions Meta-analyses of adverse events data are common and useful in terms of increasing the power to detect an association with an intervention, especially when the events are infrequent. However, with regard to existing meta-analyses, a wide variety of different methods have been employed, often with no evident rationale for using a particular approach. More specifically, the approach to dealing with zero events varies, and guidelines on this issue would be desirable. PMID:22553987
Analyses of the NAC transcription factor gene family in Gossypium raimondii Ulbr.: chromosomal location, structure, phylogeny, and expression patterns.

PubMed

Shang, Haihong; Li, Wei; Zou, Changsong; Yuan, Youlu

2013-07-01

NAC domain proteins are plant-specific transcription factors known to play diverse roles in various plant developmental processes. In the present study, we performed the first comprehensive study of the NAC gene family in Gossypium raimondii Ulbr., incorporating phylogenetic, chromosomal location, gene structure, conserved motif, and expression profiling analyses. We identified 145 NAC transcription factor (NAC-TF) genes that were phylogenetically clustered into 18 distinct subfamilies. Of these, 127 NAC-TF genes were distributed across the 13 chromosomes, 80 (55%) were preferentially retained duplicates located in both duplicated regions and six were located in triplicated chromosomal regions. The majority of NAC-TF genes showed temporal-, spatial-, and tissue-specific expression patterns based on transcriptomic and qRT-PCR analyses. However, the expression patterns of several duplicate genes were partially redundant, suggesting the occurrence of sub-functionalization during their evolution. Based on their genomic organization, we concluded that genomic duplications contributed significantly to the expansion of the NAC-TF gene family in G. raimondii. Comprehensive analysis of their expression profiles could provide novel insights into the functional divergence among members of the NAC gene family in G. raimondii. © 2013 Institute of Botany, Chinese Academy of Sciences.

Coexisting Disadvantages in later Life: Demographic and Socio-Economic Inequalities.

PubMed

Heap, Josephine; Fors, Stefan; Lennartsson, Carin

2017-01-01

In this study, we aimed to identify which of certain demographic and socio-economic groups in the oldest part of the population that have an increased probability of experiencing simultaneous disadvantages in different life domains - here termed coexisting disadvantages. To do so, we compared analyses of coexisting disadvantages, measured as two or more simultaneous disadvantages, with analyses of single disadvantages and specific combinations of disadvantages. Indicators of physical health problems, ADL limitations, psychological health problems, limited financial resources, and limited social resources were included. We used nationally representative data from 2011 on people aged 76 and older in Sweden ( n = 765). Results showed that coexisting disadvantages were associated with specific demographic and socio-economic groups, particularly certain marital status groups. Moreover, the differences between the demographic and socio-economic groups were only found for those who reported coexisting disadvantages, and not for those who reported only one disadvantage, which suggests that demographic and social factors become more important as disadvantages compound. Further, we analysed pairwise combinations of disadvantages. We found that different combinations of disadvantages tended to be associated with different groups, information useful from a social planning perspective since different combinations of disadvantages may imply different needs for help and support.
Space Transportation System Liftoff Debris Mitigation Process Overview

NASA Technical Reports Server (NTRS)

Mitchell, Michael; Riley, Christopher

2011-01-01

Liftoff debris is a top risk to the Space Shuttle Vehicle. To manage the Liftoff debris risk, the Space Shuttle Program created a team with in the Propulsion Systems Engineering & Integration Office. The Shutt le Liftoff Debris Team harnesses the Systems Engineering process to i dentify, assess, mitigate, and communicate the Liftoff debris risk. T he Liftoff Debris Team leverages off the technical knowledge and expe rtise of engineering groups across multiple NASA centers to integrate total system solutions. These solutions connect the hardware and ana lyses to identify and characterize debris sources and zones contribut ing to the Liftoff debris risk. The solutions incorporate analyses sp anning: the definition and modeling of natural and induced environmen ts; material characterizations; statistical trending analyses, imager y based trajectory analyses; debris transport analyses, and risk asse ssments. The verification and validation of these analyses are bound by conservative assumptions and anchored by testing and flight data. The Liftoff debris risk mitigation is managed through vigilant collab orative work between the Liftoff Debris Team and Launch Pad Operation s personnel and through the management of requirements, interfaces, r isk documentation, configurations, and technical data. Furthermore, o n day of launch, decision analysis is used to apply the wealth of ana lyses to case specific identified risks. This presentation describes how the Liftoff Debris Team applies Systems Engineering in their proce sses to mitigate risk and improve the safety of the Space Shuttle Veh icle.
Age-Specific Gene Expression Signatures for Breast Tumors and Cross-Species Conserved Potential Cancer Progression Markers in Young Women

PubMed Central

Colak, Dilek; Nofal, Asmaa; AlBakheet, AlBandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; AL-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Kaya, Namik; Park, Ben H.; Bin Amer, Suad M.

2013-01-01

Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies. PMID:23704896
Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.

PubMed

Colak, Dilek; Nofal, Asmaa; Albakheet, Albandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; Al-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Inan, Mehmet S; Kaya, Namik; Park, Ben H; Bin Amer, Suad M

2013-01-01

Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.
40 CFR 63.7521 - What fuel analyses, fuel specification, and procedures must I use?

Code of Federal Regulations, 2011 CFR

2011-07-01

... fuel specification analyses for hydrogen sulfide and mercury according to the procedures in paragraphs... 40 Protection of Environment 13 2011-07-01 2011-07-01 false What fuel analyses, fuel specification..., Commercial, and Institutional Boilers and Process Heaters Testing, Fuel Analyses, and Initial Compliance...
Development of a real-time PCR for detection of Staphylococcus pseudintermedius using a novel automated comparison of whole-genome sequences.

PubMed

Verstappen, Koen M; Huijbregts, Loes; Spaninks, Mirlin; Wagenaar, Jaap A; Fluit, Ad C; Duim, Birgitta

2017-01-01

Staphylococcus pseudintermedius is an opportunistic pathogen in dogs and cats and occasionally causes infections in humans. S. pseudintermedius is often resistant to multiple classes of antimicrobials. It requires a reliable detection so that it is not misidentified as S. aureus. Phenotypic and currently-used molecular-based diagnostic assays lack specificity or are labour-intensive using multiplex PCR or nucleic acid sequencing. The aim of this study was to identify a specific target for real-time PCR by comparing whole genome sequences of S. pseudintermedius and non-pseudintermedius.Genome sequences were downloaded from public repositories and supplemented by isolates that were sequenced in this study. A Perl-script was written that analysed 300-nt fragments from a reference genome sequence of S. pseudintermedius and checked if this sequence was present in other S. pseudintermedius genomes (n = 74) and non-pseudintermedius genomes (n = 138). Six sequences specific for S. pseudintermedius were identified (sequence length between 300-500 nt). One sequence, which was located in the spsJ gene, was used to develop primers and a probe. The real-time PCR showed 100% specificity when testing for S. pseudintermedius isolates (n = 54), and eight other staphylococcal species (n = 43). In conclusion, a novel approach by comparing whole genome sequences identified a sequence that is specific for S. pseudintermedius and provided a real-time PCR target for rapid and reliable detection of S. pseudintermedius.
Combining Search Engines for Comparative Proteomics

PubMed Central

Tabb, David

2012-01-01

Many proteomics laboratories have found spectral counting to be an ideal way to recognize biomarkers that differentiate cohorts of samples. This approach assumes that proteins that differ in quantity between samples will generate different numbers of identifiable tandem mass spectra. Increasingly, researchers are employing multiple search engines to maximize the identifications generated from data collections. This talk evaluates four strategies to combine information from multiple search engines in comparative proteomics. The “Count Sum” model pools the spectra across search engines. The “Vote Counting” model combines the judgments from each search engine by protein. Two other models employ parametric and non-parametric analyses of protein-specific p-values from different search engines. We evaluated the four strategies in two different data sets. The ABRF iPRG 2009 study generated five LC-MS/MS analyses of “red” E. coli and five analyses of “yellow” E. coli. NCI CPTAC Study 6 generated five concentrations of Sigma UPS1 spiked into a yeast background. All data were identified with X!Tandem, Sequest, MyriMatch, and TagRecon. For both sample types, “Vote Counting” appeared to manage the diverse identification sets most effectively, yielding heightened discrimination as more search engines were added.
Ambiguities in model-independent partial-wave analysis

NASA Astrophysics Data System (ADS)

Krinner, F.; Greenwald, D.; Ryabchikov, D.; Grube, B.; Paul, S.

2018-06-01

Partial-wave analysis is an important tool for analyzing large data sets in hadronic decays of light and heavy mesons. It commonly relies on the isobar model, which assumes multihadron final states originate from successive two-body decays of well-known undisturbed intermediate states. Recently, analyses of heavy-meson decays and diffractively produced states have attempted to overcome the strong model dependences of the isobar model. These analyses have overlooked that model-independent, or freed-isobar, partial-wave analysis can introduce mathematical ambiguities in results. We show how these ambiguities arise and present general techniques for identifying their presence and for correcting for them. We demonstrate these techniques with specific examples in both heavy-meson decay and pion-proton scattering.
Identification of Colletotrichum spp. isolated from strawberry in Zhejiang Province and Shanghai City, China*

PubMed Central

Xie, Liu; Zhang, Jing-ze; Wan, Yao; Hu, Dong-wei

2010-01-01

Strawberry anthracnose, caused by Colletotrichum spp., is a major disease of cultivated strawberry. This study identifies 31 isolates of Colletotrichum spp. which cause strawberry anthracnose in Zhejiang Province and Shanghai City, China. Eleven isolates were identified as C. acutatum, 10 as C. gloeosporioides and 10 as C. fragariae based on morphological characteristics, phylogenetic and sequence analyses. Species-specific polymerase chain reaction (PCR) and enzyme digestion further confirmed the identification of the Colletotrichum spp., demonstrating that these three species are currently the causal agents of strawberry anthracnose in the studied regions. Based on analysis of rDNA internal transcribed spacers (ITS) sequences, sequences of all C. acutatum were identical, and little genetic variability was observed between C. fragariae and C. gloeosporioides. However, the conservative nature of the MvnI specific site from isolates of C. gloeosporioides was confirmed, and this site could be used to differentiate C. gloeosporioides from C. fragariae. PMID:20043353
Microbial communities in carbonate rocks-from soil via groundwater to rocks.

PubMed

Meier, Aileen; Singh, Manu K; Kastner, Anne; Merten, Dirk; Büchel, Georg; Kothe, Erika

2017-09-01

Microbial communities in soil, groundwater, and rock of two sites in limestone were investigated to determine community parameters differentiating habitats in two lithostratigraphic untis. Lower Muschelkalk and Middle Muschelkalk associated soils, groundwater, and rock samples showed different, but overlapping microbial communities linked to carbon fluxes. The microbial diversities in soil were highest, groundwater revealed overlapping taxa but lower diversity, and rock samples were predominantly characterized by endospore forming bacteria and few archaea. Physiological profiles could establish a differentiation between habitats (soil, groundwater, rock). From community analyses and physiological profiles, different element cycles in limestone could be identified for the three habitats. While in soil, nitrogen cycling was identified as specific determinant, in rock methanogenesis linked carbonate rock to atmospheric methane cycles. These patterns specifically allowed for delineation of lithostratigraphic connections to physiological parameters. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Parent Prevention Communication Profiles and Adolescent Substance Use: A Latent Profile Analysis and Growth Curve Model

PubMed Central

Choi, Hye Jeong; Miller-Day, Michelle; Shin, YoungJu; Hecht, Michael L.; Pettigrew, Jonathan; Krieger, Janice L.; Lee, JeongKyu; Graham, John W.

2017-01-01

This current study identifies distinct parent prevention communication profiles and examines whether youth with different parental communication profiles have varying substance use trajectories over time. Eleven schools in two rural school districts in the Midwestern United States were selected, and 784 students were surveyed at three time points from the beginning of 7th grade to the end of 8th grade. A series of latent profile analyses were performed to identify discrete profiles/subgroups of substance-specific prevention communication (SSPC). The results revealed a 4-profile model of SSPC: Active-Open, Passive-Open, Active-Silent, and Passive-Silent. A growth curve model revealed different rates of lifetime substance use depending on the youth’s SSPC profile. These findings have implications for parenting interventions and tailoring messages for parents to fit specific SSPC profiles. PMID:29056872
Sex differences in prenatal epigenetic programming of stress pathways.

PubMed

Bale, Tracy L

2011-07-01

Maternal stress experience is associated with neurodevelopmental disorders including schizophrenia and autism. Recent studies have examined mechanisms by which changes in the maternal milieu may be transmitted to the developing embryo and potentially translated into programming of the epigenome. Animal models of prenatal stress have identified important sex- and temporal-specific effects on offspring stress responsivity. As dysregulation of stress pathways is a common feature in most neuropsychiatric diseases, molecular and epigenetic analyses at the maternal-embryo interface, especially in the placenta, may provide unique insight into identifying much-needed predictive biomarkers. In addition, as most neurodevelopmental disorders present with a sex bias, examination of sex differences in the inheritance of phenotypic outcomes may pinpoint gene targets and specific windows of vulnerability in neurodevelopment, which have been disrupted. This review discusses the association and possible contributing mechanisms of prenatal stress in programming offspring stress pathway dysregulation and the importance of sex.
Species-Specific Identification of Human Adenoviruses in Sewage.

PubMed

Wieczorek, Magdalena; Krzysztoszek, Arleta; Witek, Agnieszka

2015-01-01

Human adenovirus (HAdV) diversity in sewage was assessed by species-specific molecular methods. Samples of raw sewage were collected in 14 sewage disposal systems from January to December 2011, in Poland. HAdVs were detected in 92.1% of the analysed sewage samples and was significantly higher at cities of over 100 000 inhabitants. HAdV DNA was detected in sewage during all seasons. The most abundant species identified were HAdV-F (average 89.6%) and -A (average 19.6%), which are associated with intestine infections. Adenoviruses from B species were not detected. The result of the present study demonstrate that human adenoviruses are consistently present in sewage in Poland, demonstrating the importance of an adequate treatment before the disposal in the environment. Multiple HAdV species identified in raw sewage provide new information about HAdV circulation in the Polish population.
Proteomic Analysis of Tendon Extracellular Matrix Reveals Disease Stage-specific Fragmentation and Differential Cleavage of COMP (Cartilage Oligomeric Matrix Protein)*

PubMed Central

Dakin, Stephanie Georgina; Smith, Roger Kenneth Whealands; Heinegård, Dick; Önnerfjord, Patrik; Khabut, Areej; Dudhia, Jayesh

2014-01-01

During inflammatory processes the extracellular matrix (ECM) is extensively remodeled, and many of the constituent components are released as proteolytically cleaved fragments. These degradative processes are better documented for inflammatory joint diseases than tendinopathy even though the pathogenesis has many similarities. The aims of this study were to investigate the proteomic composition of injured tendons during early and late disease stages to identify disease-specific cleavage patterns of the ECM protein cartilage oligomeric matrix protein (COMP). In addition to characterizing fragments released in naturally occurring disease, we hypothesized that stimulation of tendon explants with proinflammatory mediators in vitro would induce fragments of COMP analogous to natural disease. Therefore, normal tendon explants were stimulated with IL-1β and prostaglandin E2, and their effects on the release of COMP and its cleavage patterns were characterized. Analyses of injured tendons identified an altered proteomic composition of the ECM at all stages post injury, showing protein fragments that were specific to disease stage. IL-1β enhanced the proteolytic cleavage and release of COMP from tendon explants, whereas PGE2 had no catabolic effect. Of the cleavage fragments identified in early stage tendon disease, two fragments were generated by an IL-1-mediated mechanism. These fragments provide a platform for the development of neo-epitope assays specific to injury stage for tendon disease. PMID:24398684
Gene expression atlas of pigeonpea and its application to gain insights into genes associated with pollen fertility implicated in seed formation

PubMed Central

Pazhamala, Lekha T.; Purohit, Shilp; Saxena, Rachit K.; Garg, Vanika; Krishnamurthy, L.; Verdier, Jerome

2017-01-01

Abstract Pigeonpea (Cajanus cajan) is an important grain legume of the semi-arid tropics, mainly used for its protein rich seeds. To link the genome sequence information with agronomic traits resulting from specific developmental processes, a Cajanus cajan gene expression atlas (CcGEA) was developed using the Asha genotype. Thirty tissues/organs representing developmental stages from germination to senescence were used to generate 590.84 million paired-end RNA-Seq data. The CcGEA revealed a compendium of 28 793 genes with differential, specific, spatio-temporal and constitutive expression during various stages of development in different tissues. As an example to demonstrate the application of the CcGEA, a network of 28 flower-related genes analysed for cis-regulatory elements and splicing variants has been identified. In addition, expression analysis of these candidate genes in male sterile and male fertile genotypes suggested their critical role in normal pollen development leading to seed formation. Gene network analysis also identified two regulatory genes, a pollen-specific SF3 and a sucrose–proton symporter, that could have implications for improvement of agronomic traits such as seed production and yield. In conclusion, the CcGEA provides a valuable resource for pigeonpea to identify candidate genes involved in specific developmental processes and to understand the well-orchestrated growth and developmental process in this resilient crop. PMID:28338822
STD coinfections in The Netherlands: Specific sexual networks at highest risk.

PubMed

van Veen, Maaike G; Koedijk, Femke D H; van der Sande, Marianne A B

2010-07-01

Specific subpopulations infected with multiple bacterial sexually transmitted diseases (STDs) may facilitate ongoing STD transmission. To identify these subpopulations we determined the extent of concurrent incident STD infections and their risk factors among the high-risk population seen at Dutch STD clinics. STD surveillance data submitted routinely by STD clinics to the National Institute for Public Health on demographics, sexual behavior, STD testing, and diagnoses for the period 2004-2007 were analyzed. Bacterial STD coinfections were diagnosed concurrently in 2120 (7%) of the 31,754 incident bacterial STD diagnoses (chlamydia, gonorrhea, infectious syphilis). In univariate logistic regression analyses, coinfections were significantly more often diagnosed in men who have sex with men (MSM, OR = 5.4) than in heterosexuals. Multivariate analyses showed a significant interaction between age and sexual preference. Subsequent stratified analyses by sexual preference showed a linear rise in coinfections with age in MSM. In heterosexuals, by contrast, bacterial coinfections peaked in those aged 19 or less; they had 27% of coinfections, while having only 14% of monodiagnoses and 10% of consultations. Heterosexual STD clinic attendees of Surinamese or Antillean origin were significantly at higher risk for coinfection (OR = 6.5) than all other ethnicities. Attendees belonging to specific sexual networks, such as MSM, ethnic groups, and young heterosexuals were at increased risk for STD coinfections. The different trend with age in MSM versus heterosexuals suggests that these 2 high-risk networks have different determinants of higher risk, such as age-related sexual risk-taking, biologic susceptibility, and insufficient knowledge or compliance with prevention measures. Prevention should therefore be targeted differently towards specific sexual networks.
Pyrolysis-gas chromatography/mass spectrometry analyses of biological particulates collected during recent space shuttle missions

NASA Technical Reports Server (NTRS)

Matney, M. L.; Limero, T. F.; James, J. T.

1994-01-01

Biological particulates collected on air filters during shuttle missions (STS-40 and STS-42) were identified using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). A method was developed for identifying the atmospheric particles and their sources through the analysis of standard materials and the selection of "marker" compounds specific to the particle type. Pyrolysis spectra of biological standards were compared with those of airborne particles collected during two space shuttle missions; marker compounds present in the shuttle particle spectra were matched with those of the standards to identify the source of particles. Particles of 0,5--1-mm diameter and weighing as little as 40 micrograms could be identified using this technique. The Py-GC/MS method identified rat food and soilless plant-growth media as two sources of particles collected from the shuttle atmosphere during flight.
High road utilizers surveys compared to police data for road traffic crash hotspot localization in Rwanda and Sri Lanka.

PubMed

Staton, Catherine A; De Silva, Vijitha; Krebs, Elizabeth; Andrade, Luciano; Rulisa, Stephen; Mallawaarachchi, Badra Chandanie; Jin, Kezhi; RicardoVissoci, Joao; Østbye, Truls

2016-01-20

Road traffic crashes (RTCs) are a leading cause of death. In low and middle income countries (LMIC) data to conduct hotspot analyses and safety audits are usually incomplete, poor quality, and not computerized. Police data are often limited, but there are no alternative gold standards. This project evaluates high road utilizer surveys as an alternative to police data to identify RTC hotspots. Retrospective police RTC data was compared to prospective data from high road utilizer surveys regarding dangerous road locations. Spatial analysis using geographic information systems was used to map dangerous locations and identify RTC hotspots. We assessed agreement (Cohen's Kappa), sensitivity/specificity, and cost differences. In Rwanda police data identified 1866 RTC locations from 2589 records while surveys identified 1264 locations from 602 surveys. In Sri Lanka, police data identified 721 RTC locations from 752 records while survey data found 3000 locations from 300 surveys. There was high agreement (97 %, 83 %) and kappa (0.60, 0.60) for Rwanda and Sri Lanka respectively. Sensitivity and specificity are 92 % and 95 % for Rwanda and 74 % and 93 % for Sri Lanka. The cost per crash location identified was $2.88 for police and $2.75 for survey data in Rwanda and $2.75 for police and $1.21 for survey data in Sri Lanka. Surveys to locate RTC hotspots have high sensitivity and specificity compared to police data. Therefore, surveys can be a viable, inexpensive, and rapid alternative to the use of police data in LMIC.
Cognitive and family therapies for adolescent depression: treatment specificity, mediation, and moderation.

PubMed

Kolko, D J; Brent, D A; Baugher, M; Bridge, J; Birmaher, B

2000-08-01

The specificity of cognitive and family therapies, and potential treatment mediators and moderators, was examined in a randomized clinical trial for adolescent depression. After acute treatment, cognitive-behavioral therapy (CBT) exerted specific effects on cognitive distortions relative to either systemic-behavioral family therapy (SBFT) or nondirective supportive therapy (NST). At 2-year follow-up, SBFT was found to impact family conflict and parent-child relationship problems more than CBT; NST and CBT tended to show a greater reduction in anxiety symptoms than SBFT. Nonspecific therapist variables qualified few outcome analyses. No measures of cognitive distortion or family dysfunction mediated or moderated treatment outcome. As in adult studies, relatively few areas of treatment specificity or mediation were identified. The implications of these findings for clinical treatment and research in adolescent depression are discussed.
Quantitative Analysis of Swallowing Function Between Dysphagia Patients and Healthy Subjects Using High-Resolution Manometry

PubMed Central

2017-01-01

Objective To compare swallowing function between healthy subjects and patients with pharyngeal dysphagia using high resolution manometry (HRM) and to evaluate the usefulness of HRM for detecting pharyngeal dysphagia. Methods Seventy-five patients with dysphagia and 28 healthy subjects were included in this study. Diagnosis of dysphagia was confirmed by a videofluoroscopy. HRM was performed to measure pressure and timing information at the velopharynx (VP), tongue base (TB), and upper esophageal sphincter (UES). HRM parameters were compared between dysphagia and healthy groups. Optimal threshold values of significant HRM parameters for dysphagia were determined. Results VP maximal pressure, TB maximal pressure, UES relaxation duration, and UES resting pressure were lower in the dysphagia group than those in healthy group. UES minimal pressure was higher in dysphagia group than in the healthy group. Receiver operating characteristic (ROC) analyses were conducted to validate optimal threshold values for significant HRM parameters to identify patients with pharyngeal dysphagia. With maximal VP pressure at a threshold value of 144.0 mmHg, dysphagia was identified with 96.4% sensitivity and 74.7% specificity. With maximal TB pressure at a threshold value of 158.0 mmHg, dysphagia was identified with 96.4% sensitivity and 77.3% specificity. At a threshold value of 2.0 mmHg for UES minimal pressure, dysphagia was diagnosed at 74.7% sensitivity and 60.7% specificity. Lastly, UES relaxation duration of <0.58 seconds had 85.7% sensitivity and 65.3% specificity, and UES resting pressure of <75.0 mmHg had 89.3% sensitivity and 90.7% specificity for identifying dysphagia. Conclusion We present evidence that HRM could be a useful evaluation tool for detecting pharyngeal dysphagia. PMID:29201816

Quantitative Analysis of Swallowing Function Between Dysphagia Patients and Healthy Subjects Using High-Resolution Manometry.

PubMed

Park, Chul-Hyun; Kim, Don-Kyu; Lee, Yong-Taek; Yi, Youbin; Lee, Jung-Sang; Kim, Kunwoo; Park, Jung Ho; Yoon, Kyung Jae

2017-10-01

To compare swallowing function between healthy subjects and patients with pharyngeal dysphagia using high resolution manometry (HRM) and to evaluate the usefulness of HRM for detecting pharyngeal dysphagia. Seventy-five patients with dysphagia and 28 healthy subjects were included in this study. Diagnosis of dysphagia was confirmed by a videofluoroscopy. HRM was performed to measure pressure and timing information at the velopharynx (VP), tongue base (TB), and upper esophageal sphincter (UES). HRM parameters were compared between dysphagia and healthy groups. Optimal threshold values of significant HRM parameters for dysphagia were determined. VP maximal pressure, TB maximal pressure, UES relaxation duration, and UES resting pressure were lower in the dysphagia group than those in healthy group. UES minimal pressure was higher in dysphagia group than in the healthy group. Receiver operating characteristic (ROC) analyses were conducted to validate optimal threshold values for significant HRM parameters to identify patients with pharyngeal dysphagia. With maximal VP pressure at a threshold value of 144.0 mmHg, dysphagia was identified with 96.4% sensitivity and 74.7% specificity. With maximal TB pressure at a threshold value of 158.0 mmHg, dysphagia was identified with 96.4% sensitivity and 77.3% specificity. At a threshold value of 2.0 mmHg for UES minimal pressure, dysphagia was diagnosed at 74.7% sensitivity and 60.7% specificity. Lastly, UES relaxation duration of <0.58 seconds had 85.7% sensitivity and 65.3% specificity, and UES resting pressure of <75.0 mmHg had 89.3% sensitivity and 90.7% specificity for identifying dysphagia. We present evidence that HRM could be a useful evaluation tool for detecting pharyngeal dysphagia.
Determining the specific microbial populations and their spatial distribution within the stromatolite ecosystem of Shark Bay.

PubMed

Goh, Falicia; Allen, Michelle A; Leuko, Stefan; Kawaguchi, Tomohiro; Decho, Alan W; Burns, Brendan P; Neilan, Brett A

2009-04-01

The stromatolites at Shark Bay, Western Australia, are analogues of some of the oldest evidence of life on Earth. The aim of this study was to identify and spatially characterize the specific microbial communities associated with Shark Bay intertidal columnar stromatolites. Conventional culturing methods and construction of 16S rDNA clone libraries from community genomic DNA with both universal and specific PCR primers were employed. The estimated coverage, richness and diversity of stromatolite microbial populations were compared with earlier studies on these ecosystems. The estimated coverage for all clone libraries indicated that population coverage was comprehensive. Phylogenetic analyses of stromatolite and surrounding seawater sequences were performed in ARB with the Greengenes database of full-length non-chimaeric 16S rRNA genes. The communities identified exhibited extensive diversity. The most abundant sequences from the stromatolites were alpha- and gamma-proteobacteria (58%), whereas the cyanobacterial community was characterized by sequences related to the genera Euhalothece, Gloeocapsa, Gloeothece, Chroococcidiopsis, Dermocarpella, Acaryochloris, Geitlerinema and Schizothrix. All clones from the archaeal-specific clone libraries were related to the halophilic archaea; however, no archaeal sequence was identified from the surrounding seawater. Fluorescence in situ hybridization also revealed stromatolite surfaces to be dominated by unicellular cyanobacteria, in contrast to the sub-surface archaea and sulphate-reducing bacteria. This study is the first to compare the microbial composition of morphologically similar stromatolites over time and examine the spatial distribution of specific microorganismic groups in these intertidal structures and the surrounding seawater at Shark Bay. The results provide a platform for identifying the key microbial physiology groups and their potential roles in modern stromatolite morphogenesis and ecology.
Integrated analyses for genetic markers of polycystic ovary syndrome with 9 case-control studies of gene expression profiles.

PubMed

Lu, Chenqi; Liu, Xiaoqin; Wang, Lin; Jiang, Ning; Yu, Jun; Zhao, Xiaobo; Hu, Hairong; Zheng, Saihua; Li, Xuelian; Wang, Guiying

2017-01-10

Due to genetic heterogeneity and variable diagnostic criteria, genetic studies of polycystic ovary syndrome are particularly challenging. Furthermore, lack of sufficiently large cohorts limits the identification of susceptibility genes contributing to polycystic ovary syndrome. Here, we carried out a systematic search of studies deposited in the Gene Expression Omnibus database through August 31, 2016. The present analyses included studies with: 1) patients with polycystic ovary syndrome and normal controls, 2) gene expression profiling of messenger RNA, and 3) sufficient data for our analysis. Ultimately, a total of 9 studies with 13 datasets met the inclusion criteria and were performed for the subsequent integrated analyses. Through comprehensive analyses, there were 13 genetic factors overlapped in all datasets and identified as significant specific genes for polycystic ovary syndrome. After quality control assessment, there were six datasets remained. Further gene ontology enrichment and pathway analyses suggested that differentially expressed genes mainly enriched in oocyte pathways. These findings provide potential molecular markers for diagnosis and prognosis of polycystic ovary syndrome, and need in-depth studies on the exact function and mechanism in polycystic ovary syndrome.
Examining the response of larch needle carbohydrates to climate using compound-specific δ13C and concentration analyses

NASA Astrophysics Data System (ADS)

Rinne, Katja T.; Saurer, Matthias; Kirdyanov, Alexander V.; Bryukhanova, Marina V.; Prokushkin, Anatoly S.; Churakova Sidorova, Olga V.; Siegwolf, Rolf T. W.

2016-04-01

Little is known about the dynamics of concentrations and carbon isotope ratios of individual carbohydrates in leaves in response to climatic and physiological factors. Improved knowledge of the isotopic ratio in sugars will enhance our understanding of the tree ring isotope ratio and will help to decipher environmental conditions in retrospect more reliably. Carbohydrate samples from larch (Larix gmelinii) needles of two sites in the continuous permafrost zone of Siberia with differing growth conditions were analysed with the Compound-Specific Isotope Analysis (CSIA). We compared concentrations and carbon isotope values (δ13C) of sucrose, fructose, glucose and pinitol combined with phenological data. The results for the variability of the needle carbohydrates show high dynamics with distinct seasonal characteristics between and within the studied years with a clear link to the climatic conditions, particularly vapour pressure deficit. Compound-specific differences in δ13C values as a response to climate were detected. The δ13C of pinitol, which contributes up to 50% of total soluble carbohydrates, was almost invariant during the whole growing season. Our study provides the first in-depth characterization of compound-specific needle carbohydrate isotope variability, identifies involved mechanisms and shows the potential of such results for linking tree physiological responses to different climatic conditions.
The development and validation of a single SNaPshot multiplex for tiger species and subspecies identification--implications for forensic purposes.

PubMed

Kitpipit, Thitika; Tobe, Shanan S; Kitchener, Andrew C; Gill, Peter; Linacre, Adrian

2012-03-01

The tiger (Panthera tigris) is currently listed on Appendix I of the Convention on the International Trade in Endangered Species of Wild Fauna and Flora; this affords it the highest level of international protection. To aid in the investigation of alleged illegal trade in tiger body parts and derivatives, molecular approaches have been developed to identify biological material as being of tiger in origin. Some countries also require knowledge of the exact tiger subspecies present in order to prosecute anyone alleged to be trading in tiger products. In this study we aimed to develop and validate a reliable single assay to identify tiger species and subspecies simultaneously; this test is based on identification of single nucleotide polymorphisms (SNPs) within the tiger mitochondrial genome. The mitochondrial DNA sequence from four of the five extant putative tiger subspecies that currently exist in the wild were obtained and combined with DNA sequence data from 492 tiger and 349 other mammalian species available on GenBank. From the sequence data a total of 11 SNP loci were identified as suitable for further analyses. Five SNPs were species-specific for tiger and six amplify one of the tiger subspecies-specific SNPs, three of which were specific to P. t. sumatrae and the other three were specific to P. t. tigris. The multiplex assay was able to reliably identify 15 voucher tiger samples. The sensitivity of the test was 15,000 mitochondrial DNA copies (approximately 0.26 pg), indicating that it will work on trace amounts of tissue, bone or hair samples. This simple test will add to the DNA-based methods currently being used to identify the presence of tiger within mixed samples. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Data-driven subtypes of major depressive disorder: a systematic review

PubMed Central

2012-01-01

Background According to current classification systems, patients with major depressive disorder (MDD) may have very different combinations of symptoms. This symptomatic diversity hinders the progress of research into the causal mechanisms and treatment allocation. Theoretically founded subtypes of depression such as atypical, psychotic, and melancholic depression have limited clinical applicability. Data-driven analyses of symptom dimensions or subtypes of depression are scarce. In this systematic review, we examine the evidence for the existence of data-driven symptomatic subtypes of depression. Methods We undertook a systematic literature search of MEDLINE, PsycINFO and Embase in May 2012. We included studies analyzing the depression criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) of adults with MDD in latent variable analyses. Results In total, 1176 articles were retrieved, of which 20 satisfied the inclusion criteria. These reports described a total of 34 latent variable analyses: 6 confirmatory factor analyses, 6 exploratory factor analyses, 12 principal component analyses, and 10 latent class analyses. The latent class techniques distinguished 2 to 5 classes, which mainly reflected subgroups with different overall severity: 62 of 71 significant differences on symptom level were congruent with a latent class solution reflecting severity. The latent class techniques did not consistently identify specific symptom clusters. Latent factor techniques mostly found a factor explaining the variance in the symptoms depressed mood and interest loss (11 of 13 analyses), often complemented by psychomotor retardation or fatigue (8 of 11 analyses). However, differences in found factors and classes were substantial. Conclusions The studies performed to date do not provide conclusive evidence for the existence of depressive symptom dimensions or symptomatic subtypes. The wide diversity of identified factors and classes might result either from the absence of patterns to be found, or from the theoretical and modeling choices preceding analysis. PMID:23210727
Using the TIGR gene index databases for biological discovery.

PubMed

Lee, Yuandan; Quackenbush, John

2003-11-01

The TIGR Gene Index web pages provide access to analyses of ESTs and gene sequences for nearly 60 species, as well as a number of resources derived from these. Each species-specific database is presented using a common format with a homepage. A variety of methods exist that allow users to search each species-specific database. Methods implemented currently include nucleotide or protein sequence queries using WU-BLAST, text-based searches using various sequence identifiers, searches by gene, tissue and library name, and searches using functional classes through Gene Ontology assignments. This protocol provides guidance for using the Gene Index Databases to extract information.
Evaluating the effectiveness of behavior change techniques in health-related behavior: a scoping review of methods used.

PubMed

Michie, Susan; West, Robert; Sheals, Kate; Godinho, Cristina A

2018-03-01

Behavior change interventions typically contain multiple potentially active components: behavior change techniques (BCTs). Identifying which specific BCTs or BCT combinations have the potential to be effective for a given behavior in a given context presents a major challenge. The aim of this study was to review the methods that have been used to identify effective BCTs for given behaviors in given contexts and evaluate their strengths and limitations. A scoping review was conducted of studies that had sought to identify effective BCTs. Articles referring to "behavio(u)r change technique(s)" in the abstract/text were located, and ones that involved identification of effective BCTs were selected. The methods reported were coded. The methods were analyzed in general terms using "PASS" criteria: Practicability (facility to apply the method appropriately), Applicability (facility to generalize from findings to contexts and populations of interest), Sensitivity (facility to identify effective BCTs), and Specificity (facility to rule out ineffective BCTs). A sample of 10% of the studies reviewed was then evaluated using these criteria to assess how far the strengths and limitations identified in principle were borne out in practice. One hundred and thirty-five studies were identified. The methods used in those studies were experimental manipulation of BCTs, observational studies comparing outcomes in the presence or absence of BCTs, meta-analyses of BCT comparisons, meta-regressions evaluating effect sizes with and without specific BCTs, reviews of BCTs found in effective interventions, and meta-classification and regression trees. The limitations of each method meant that only weak conclusions could be drawn regarding the effectiveness of specific BCTs or BCT combinations. Methods for identifying effective BCTs linked to target behavior and context all have important inherent limitations. A strategy needs to be developed that can systematically combine the strengths of the different methods and that can link these constructs in an ontology of behavior change interventions.
Clustering of self-organizing map identifies five distinct medulloblastoma subgroups.

PubMed

Cao, Changjun; Wang, Wei; Jiang, Pucha

2016-01-01

Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples.
Identification of novel and known oocyte-specific genes using complementary DNA subtraction and microarray analysis in three different species.

PubMed

Vallée, Maud; Gravel, Catherine; Palin, Marie-France; Reghenas, Hélène; Stothard, Paul; Wishart, David S; Sirard, Marc-André

2005-07-01

The main objective of the present study was to identify novel oocyte-specific genes in three different species: bovine, mouse, and Xenopus laevis. To achieve this goal, two powerful technologies were combined: a polymerase chain reaction (PCR)-based cDNA subtraction, and cDNA microarrays. Three subtractive libraries consisting of 3456 clones were established and enriched for oocyte-specific transcripts. Sequencing analysis of the positive insert-containing clones resulted in the following classification: 53% of the clones corresponded to known cDNAs, 26% were classified as uncharacterized cDNAs, and a final 9% were classified as novel sequences. All these clones were used for cDNA microarray preparation. Results from these microarray analyses revealed that in addition to already known oocyte-specific genes, such as GDF9, BMP15, and ZP, known genes with unknown function in the oocyte were identified, such as a MLF1-interacting protein (MLF1IP), B-cell translocation gene 4 (BTG4), and phosphotyrosine-binding protein (xPTB). Furthermore, 15 novel oocyte-specific genes were validated by reverse transcription-PCR to confirm their preferential expression in the oocyte compared to somatic tissues. The results obtained in the present study confirmed that microarray analysis is a robust technique to identify true positives from the suppressive subtractive hybridization experiment. Furthermore, obtaining oocyte-specific genes from three species simultaneously allowed us to look at important genes that are conserved across species. Further characterization of these novel oocyte-specific genes will lead to a better understanding of the molecular mechanisms related to the unique functions found in the oocyte.
Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting

PubMed Central

Biesemann, Christoph; Grønborg, Mads; Luquet, Elisa; Wichert, Sven P; Bernard, Véronique; Bungers, Simon R; Cooper, Ben; Varoqueaux, Frédérique; Li, Liyi; Byrne, Jennifer A; Urlaub, Henning; Jahn, Olaf; Brose, Nils; Herzog, Etienne

2014-01-01

For decades, neuroscientists have used enriched preparations of synaptic particles called synaptosomes to study synapse function. However, the interpretation of corresponding data is problematic as synaptosome preparations contain multiple types of synapses and non-synaptic neuronal and glial contaminants. We established a novel Fluorescence Activated Synaptosome Sorting (FASS) method that substantially improves conventional synaptosome enrichment protocols and enables high-resolution biochemical analyses of specific synapse subpopulations. Employing knock-in mice with fluorescent glutamatergic synapses, we show that FASS isolates intact ultrapure synaptosomes composed of a resealed presynaptic terminal and a postsynaptic density as assessed by light and electron microscopy. FASS synaptosomes contain bona fide glutamatergic synapse proteins but are almost devoid of other synapse types and extrasynaptic or glial contaminants. We identified 163 enriched proteins in FASS samples, of which FXYD6 and Tpd52 were validated as new synaptic proteins. FASS purification thus enables high-resolution biochemical analyses of specific synapse subpopulations in health and disease. PMID:24413018
Designing normative open virtual enterprises

NASA Astrophysics Data System (ADS)

Garcia, Emilia; Giret, Adriana; Botti, Vicente

2016-03-01

There is an increasing interest on developing virtual enterprises in order to deal with the globalisation of the economy, the rapid growth of information technologies and the increase of competitiveness. In this paper we deal with the development of normative open virtual enterprises (NOVEs). They are systems with a global objective that are composed of a set of heterogeneous entities and enterprises that exchange services following a specific normative context. In order to analyse and design systems of this kind the multi-agent paradigm seems suitable because it offers a specific solution for supporting the social and contractual relationships between enterprises and for formalising their business processes. This paper presents how the Regulated Open Multi-agent systems (ROMAS) methodology, an agent-oriented software methodology, can be used to analyse and design NOVEs. ROMAS offers a complete development process that allows identifying and formalising of the structure of NOVEs, their normative context and the interactions among their members. The use of ROMAS is exemplified by means of a case study that represents an automotive supply chain.
Specificity of posttraumatic stress disorder symptoms: an investigation of comorbidity between posttraumatic stress disorder symptoms and depression in treatment-seeking veterans.

PubMed

Gros, Daniel F; Simms, Leonard J; Acierno, Ron

2010-12-01

In response to high levels of comorbidity and symptom overlap between posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and other disorders, much attention has been devoted to the role of specific and nonspecific symptoms among the disorders. The present study investigated the overlapping symptoms of PTSD and MDD in treatment-seeking veterans. Exploratory factor analyses were used to identify latent factors of both self-reported and clinician-rated symptoms of PTSD and MDD. Results of exploratory factor analyses supported a 2-factor model representing symptoms of depression and PTSD; however, a subset of PTSD symptoms, characterized by emotional numbing and dysphoria, loaded onto the depression factor, rather than the PTSD factor. These nonspecific PTSD symptoms were predictive of comorbid MDD and increased depression symptomatology in patients with PTSD. Together, these findings demonstrate the importance of accounting for nonspecific symptoms in diagnosis and treatment of PTSD, highlighting a need for revisions to our current diagnostics.
Sex-specific nonlinear associations between serum lipids and different domains of cognitive function in middle to older age individuals.

PubMed

Lu, Yanhui; An, Yu; Yu, Huanling; Che, Fengyuan; Zhang, Xiaona; Rong, Hongguo; Xi, Yuandi; Xiao, Rong

2017-08-01

To examine how serum lipids relates to specific cognitive ability domains between the men and women in Chinese middle to older age individuals. A complete lipid panel was obtained from 1444 individuals, ages 50-65, who also underwent a selection of cognitive tests. Participants were 584 men and 860 women from Linyi city, Shandong province. Multiple linear regression analyses examined serum lipids level as quadratic predictors of sex-specific measure of performance in different cognitive domains, which were adjusted for sociodemographic and lifestyle characteristics. In men, a significant quadratic effect of total cholesterol (TC) was identified for Digit Symbol (B = -0.081, P = 0.044) and also quadratic effect of low density lipoprotein-cholesterol (LDL-C) was identified for Trail Making Test B (B = -0.082, P = 0.045). Differently in women, there were significant quadratic associations between high density lipoprotein-cholesterol (HDL-C) and multiple neuropsychological tests. The nonlinear lipid-cognition associations differed between men and women and were specific to certain cognitive domains and might be of potential relevance for prevention and therapy of cognitive decline.
Quantitative chemoproteomics for site-specific analysis of protein alkylation by 4-hydroxy-2-nonenal in cells.

PubMed

Yang, Jing; Tallman, Keri A; Porter, Ned A; Liebler, Daniel C

2015-03-03

Protein alkylation by 4-hydroxy-2-nonenal (HNE), an endogenous lipid derived electrophile, contributes to stress signaling and cellular toxicity. Although previous work has identified protein targets for HNE alkylation, the sequence specificity of alkylation and dynamics in a cellular context remain largely unexplored. We developed a new quantitative chemoproteomic platform, which uses isotopically tagged, photocleavable azido-biotin reagents to selectively capture and quantify the cellular targets labeled by the alkynyl analogue of HNE (aHNE). Our analyses site-specifically identified and quantified 398 aHNE protein alkylation events (386 cysteine sites and 12 histidine sites) in intact cells. This data set expands by at least an order of magnitude the number of such modification sites previously reported. Although adducts formed by Michael addition are thought to be largely irreversible, we found that most aHNE modifications are lost rapidly in situ. Moreover, aHNE adduct turnover occurs only in intact cells and loss rates are site-selective. This quantitative chemoproteomics platform provides a versatile general approach to map bioorthogonal-chemically engineered post-translational modifications and their cellular dynamics in a site-specific and unbiased manner.
CAREGIVERS’ DIFFERING NEEDS ACROSS KEY EXPERIENCES OF THE ADVANCED CANCER DISEASE TRAJECTORY

PubMed Central

Bernard-DuBenske, Lori L.; Wen, Kuang-Yi; Gustafson, David H.; Guarnaccia, Charles A.; Cleary, James F.; Dinauer, Susan K.; McTavish, Fiona M.

2013-01-01

Familial caregivers are providing increasing amounts of care to advanced cancer patients. Increased understanding of caregivers’ needs is vital in providing necessary support to lessen caregiver burden and morbidity. Current literature has identified caregiver and patient needs at broad stages of the cancer trajectory; however, such broad stages may be too general to inform a practice of targeting specific interventions when they have the greatest utility. This study examines a variety of particular needs across a number of more discrete illness-related transition experiences specifically in the advanced cancer disease trajectory. One hundred fifty-nine female informal caregivers of people with advanced cancer completed a needs assessment survey. Analyses of these cross-sectional retrospective-report data reveal that cancer caregiver needs vary across specific key experiences occurring within the broader stages of illness identified by current literature. Furthermore, caregivers have unique needs during bereavement. While the sample characteristics are demographically limited, this study provides preliminary evidence that the broad stages are not specific enough increments for effectively examining caregiver needs, and supports the need for more precise distribution of cancer-related information at more discrete times in the illness course. PMID:18662420
An intelligent system and a relational data base for codifying helmet-mounted display symbology design requirements

NASA Astrophysics Data System (ADS)

Rogers, Steven P.; Hamilton, David B.

1994-06-01

To employ the most readily comprehensible presentation methods and symbology with helmet-mounted displays (HMDs), it is critical to identify the information elements needed to perform each pilot function and to analytically determine the attributes of these elements. The extensive analyses of mission requirements currently performed for pilot-vehicle interface design can be aided and improved by the new capabilities of intelligent systems and relational databases. An intelligent system, named ACIDTEST, has been developed specifically for organizing and applying rules to identify the best display modalities, locations, and formats. The primary objectives of the ACIDTEST system are to provide rapid accessibility to pertinent display research data, to integrate guidelines from many disciplines and identify conflicts among these guidelines, to force a consistent display approach among the design team members, and to serve as an 'audit trail' of design decisions and justifications. A powerful relational database called TAWL ORDIR has been developed to document information requirements and attributes for use by ACIDTEST as well as to greatly augment the applicability of mission analysis data. TAWL ORDIR can be used to rapidly reorganize mission analysis data components for study, perform commonality analyses for groups of tasks, determine the information content requirement for tailored display modes, and identify symbology integration opportunities.
A Meta-Analytic Test of Redundancy and Relative Importance of the Dark Triad and Five-Factor Model of Personality.

PubMed

O'Boyle, Ernest H; Forsyth, Donelson R; Banks, George C; Story, Paul A; White, Charles D

2015-12-01

We examined the relationships between Machiavellianism, narcissism, and psychopathy-the three traits of the Dark Triad (DT)-and the Five-Factor Model (FFM) of personality. The review identified 310 independent samples drawn from 215 sources and yielded information pertaining to global trait relationships and facet-level relationships. We used meta-analysis to examine (a) the bivariate relations between the DT and the five global traits and 30 facets of the FFM, (b) the relative importance of each of the FFM global traits in predicting DT, and (c) the relationship between the DT and FFM facets identified in translational models of narcissism and psychopathy. These analyses identified consistent and theoretically meaningful associations between the DT traits and the facets of the FFM. The five traits of the FFM, in a relative importance analysis, accounted for much of the variance in Machiavellianism, narcissism, and psychopathy, respectively, and facet-level analyses identified specific facets of each FFM trait that were consistently associated with narcissism (e.g., angry/hostility, modesty) and psychopathy (e.g., straightforwardness, deliberation). The FFM explained nearly all of the variance in psychopathy (R(2) c = .88) and a substantial portion of the variance in narcissism (R(2) c = .42). © 2014 Wiley Periodicals, Inc.
Resilience and Happiness After Spinal Cord Injury: A Qualitative Study.

PubMed

Duggan, Colette; Wilson, Catherine; DiPonio, Lisa; Trumpower, Brad; Meade, Michelle A

2016-01-01

Objective: The purpose of this study was to identify factors associated with resilience among individuals with spinal cord injury (SCI). Methods: Qualitative analyses were conducted of the written comments that were completed as part of a cross-sectional survey of individuals with SCI living in the community. More than 1,800 mail surveys were distributed to individuals identified as having a traumatic SCI through the records and/or membership lists of 4 organizations. Four hundred and seventy-five individuals completed and returned the survey, with approximately half (48.6%; n = 231) of respondents answering the open-ended question "Is there anything else you would like to tell us about your resilience or ability to 'bounce back' when you face a challenge?" Results: Analyses of these responses identified both specific resources and cognitive perspectives that are associated with perceived happiness. Responses fell within 8 general categories: resilience, general outlook on life, social support and social relationships, religion or faith in a higher power, mood, physical health and functioning (including pain), social comparisons, and resources. Nuanced themes within these categories were identified and were generally concordant with self-reported level of happiness. Conclusion: A majority of respondents with SCI identified themselves as happy and explained their adjustment and resilience as related to personality, good social support, and a spiritual connection. In contrast, pain and physical challenges appeared to be associated with limited ability to bounce back.
De novo assembly and analysis of the Artemisia argyi transcriptome and identification of genes involved in terpenoid biosynthesis.

PubMed

Liu, Miaomiao; Zhu, Jinhang; Wu, Shengbing; Wang, Chenkai; Guo, Xingyi; Wu, Jiawen; Zhou, Meiqi

2018-04-11

Artemisia argyi Lev. et Vant. (A. argyi) is widely utilized for moxibustion in Chinese medicine, and the mechanism underlying terpenoid biosynthesis in its leaves is suggested to play an important role in its medicinal use. However, the A. argyi transcriptome has not been sequenced. Herein, we performed RNA sequencing for A. argyi leaf, root and stem tissues to identify as many as possible of the transcribed genes. In total, 99,807 unigenes were assembled by analysing the expression profiles generated from the three tissue types, and 67,446 of those unigenes were annotated in public databases. We further performed differential gene expression analysis to compare leaf tissue with the other two tissue types and identified numerous genes that were specifically expressed or up-regulated in leaf tissue. Specifically, we identified multiple genes encoding significant enzymes or transcription factors related to terpenoid synthesis. This study serves as a valuable resource for transcriptome information, as many transcribed genes related to terpenoid biosynthesis were identified in the A. argyi transcriptome, providing a functional genomic basis for additional studies on molecular mechanisms underlying the medicinal use of A. argyi.

Problematic topic transitions in dysarthric conversation.

PubMed

Bloch, Steven; Saldert, Charlotta; Ferm, Ulrika

2015-01-01

This study examined the nature of topic transition problems associated with acquired progressive dysarthric speech in the everyday conversation of people with motor neurone disease. Using conversation analytic methods, a video collection of five naturally occurring problematic topic transitions was identified, transcribed and analysed. These were extracted from a main collection of over 200 other-initiated repair sequences and a sub-set of 15 problematic topic transition sequences. The sequences were analysed with reference to how the participants both identified and resolved the problems. Analysis revealed that topic transition by people with dysarthria can prove problematic. Conversation partners may find transitions problematic not only because of speech intelligibility but also because of a sequential disjuncture between the dysarthric speech turn and whatever topic has come prior. In addition the treatment of problematic topic transition as a complaint reveals the potential vulnerability of people with dysarthria to judgements of competence. These findings have implications for how dysarthria is conceptualized and how specific actions in conversation, such as topic transition, might be suitable targets for clinical intervention.
Candidate chemosensory ionotropic receptors in a Lepidoptera.

PubMed

Olivier, V; Monsempes, C; François, M-C; Poivet, E; Jacquin-Joly, E

2011-04-01

A new family of candidate chemosensory ionotropic receptors (IRs) related to ionotropic glutamate receptors (iGluRs) was recently discovered in Drosophila melanogaster. Through Blast analyses of an expressed sequenced tag library prepared from male antennae of the noctuid moth Spodoptera littoralis, we identified 12 unigenes encoding proteins related to D. melanogaster and Bombyx mori IRs. Their full length sequences were obtained and the analyses of their expression patterns suggest that they were exclusively expressed or clearly enriched in chemosensory organs. The deduced protein sequences were more similar to B. mori and D. melanogaster IRs than to iGluRs and showed considerable variations in the predicted ligand-binding domains; none have the three glutamate-interacting residues found in iGluRs, suggesting different binding specificities. Our data suggest that we identified members of the insect IR chemosensory receptor family in S. littoralis and we report here the first demonstration of IR expression in Lepidoptera. © 2010 The Authors. Insect Molecular Biology © 2010 The Royal Entomological Society.
Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction.

PubMed

Foth, Bernardo J; Tsai, Isheng J; Reid, Adam J; Bancroft, Allison J; Nichol, Sarah; Tracey, Alan; Holroyd, Nancy; Cotton, James A; Stanley, Eleanor J; Zarowiecki, Magdalena; Liu, Jimmy Z; Huckvale, Thomas; Cooper, Philip J; Grencis, Richard K; Berriman, Matthew

2014-07-01

Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to occupy an unusual niche, tunneling through epithelial cells of the large intestine. We report here the whole-genome sequences of the human-infective Trichuris trichiura and the mouse laboratory model Trichuris muris. On the basis of whole-transcriptome analyses, we identify many genes that are expressed in a sex- or life stage-specific manner and characterize the transcriptional landscape of a morphological region with unique biological adaptations, namely, bacillary band and stichosome, found only in whipworms and related parasites. Using RNA sequencing data from whipworm-infected mice, we describe the regulated T helper 1 (TH1)-like immune response of the chronically infected cecum in unprecedented detail. In silico screening identified numerous new potential drug targets against trichuriasis. Together, these genomes and associated functional data elucidate key aspects of the molecular host-parasite interactions that define chronic whipworm infection.
Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction

PubMed Central

Nichol, Sarah; Tracey, Alan; Holroyd, Nancy; Cotton, James A.; Stanley, Eleanor J.; Zarowiecki, Magdalena; Liu, Jimmy Z.; Huckvale, Thomas; Cooper, Philip J.; Grencis, Richard K.; Berriman, Matthew

2014-01-01

Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to occupy an unusual niche, tunneling through epithelial cells of the large intestine. Here we present the genome sequences of the human-infective Trichuris trichiura and the murine laboratory model T. muris. Based on whole transcriptome analyses we identify many genes that are expressed in a gender- or life stage-specific manner and characterise the transcriptional landscape of a morphological region with unique biological adaptations, namely bacillary band and stichosome, found only in whipworms and related parasites. Using RNAseq data from whipworm-infected mice we describe the regulated Th1-like immune response of the chronically infected cecum in unprecedented detail. In silico screening identifies numerous potential new drug targets against trichuriasis. Together, these genomes and associated functional data elucidate key aspects of the molecular host-parasite interactions that define chronic whipworm infection. PMID:24929830
[Use of the critical incident technique in the development of a measurement tool for satisfaction in psychiatry].

PubMed

Pourin, C; Daucourt, V; Barberger-Gateau, P

2001-06-01

Health care centers will have to set up a regular survey of their patients' satisfaction, in addition to the discharge questionnaire. Few instruments for measuring satisfaction are at present available. A working group associating 10 psychiatric hospitals in Aquitaine conducted a study on the specificity of this measure in psychiatry. To record the patient's perception on the stay in order to identify areas of satisfaction and dissatisfaction as perceived and reported by himself, using a qualitative approach. The critical incident technique was used in 3 volunteer hospitals, in patients hospitalised in psychiatric wards selected by their doctor. Interview using a semi-structured questionnaire were conducted by an investigator external to the departments. Data were analysed in a qualitative way. 32 interviews could be analysed, and 215 events were extracted. These events were classified in 12 themes. The events identified from these interviews have allowed identification of new areas of patient satisfaction, which could be used to build additional items centered on patients' preoccupations.
An image processing and analysis tool for identifying and analysing complex plant root systems in 3D soil using non-destructive analysis: Root1.

PubMed

Flavel, Richard J; Guppy, Chris N; Rabbi, Sheikh M R; Young, Iain M

2017-01-01

The objective of this study was to develop a flexible and free image processing and analysis solution, based on the Public Domain ImageJ platform, for the segmentation and analysis of complex biological plant root systems in soil from x-ray tomography 3D images. Contrasting root architectures from wheat, barley and chickpea root systems were grown in soil and scanned using a high resolution micro-tomography system. A macro (Root1) was developed that reliably identified with good to high accuracy complex root systems (10% overestimation for chickpea, 1% underestimation for wheat, 8% underestimation for barley) and provided analysis of root length and angle. In-built flexibility allowed the user interaction to (a) amend any aspect of the macro to account for specific user preferences, and (b) take account of computational limitations of the platform. The platform is free, flexible and accurate in analysing root system metrics.
Role of Individual, Family, and Peers in Sexual Initiation Among Late Adolescents Attending Institutions of Higher Learning in Malaysia.

PubMed

Abdul Samad, Shazimah; Hairi, Noran Naqiah; Ismail, Maslinor

2016-05-01

This cross-sectional study aimed to determine the prevalence and the factors associated with sexual initiation among the late adolescents in 6 institutions of higher learning in Malaysia. A total of 1572 students completed self-administered questionnaires between April and September 2013. Hierarchical multivariate logistic regression analyses stratified by gender were employed to identify the correlates of sexual initiation. The analyses were further adjusted by sampling weights. The overall prevalence of sexual initiation was 9.8% (95% confidence interval [CI] = 8.3-11.6), 18.1% (95% CI = 15.1-21.5) among males, and 4.1% (95% CI = 2.9-5.9) among females. The risk factors identified in this study supported the influence of the individual, family, and peer factors in the social-ecological model on adolescents' behaviors. The findings suggest the need for risk-reduction strategies aimed at the individual, family, and peer levels as well as the importance of gender-specific focus in assuring better outcomes. © 2016 APJPH.
Global analysis of the Burkholderia thailandensis quorum sensing-controlled regulon.

PubMed

Majerczyk, Charlotte; Brittnacher, Mitchell; Jacobs, Michael; Armour, Christopher D; Radey, Mathew; Schneider, Emily; Phattarasokul, Somsak; Bunt, Richard; Greenberg, E Peter

2014-04-01

Burkholderia thailandensis contains three acyl-homoserine lactone quorum sensing circuits and has two additional LuxR homologs. To identify B. thailandensis quorum sensing-controlled genes, we carried out transcriptome sequencing (RNA-seq) analyses of quorum sensing mutants and their parent. The analyses were grounded in the fact that we identified genes coding for factors shown previously to be regulated by quorum sensing among a larger set of quorum-controlled genes. We also found that genes coding for contact-dependent inhibition were induced by quorum sensing and confirmed that specific quorum sensing mutants had a contact-dependent inhibition defect. Additional quorum-controlled genes included those for the production of numerous secondary metabolites, an uncharacterized exopolysaccharide, and a predicted chitin-binding protein. This study provides insights into the roles of the three quorum sensing circuits in the saprophytic lifestyle of B. thailandensis, and it provides a foundation on which to build an understanding of the roles of quorum sensing in the biology of B. thailandensis and the closely related pathogenic Burkholderia pseudomallei and Burkholderia mallei.
Identification and functional analyses of sex determination genes in the sexually dimorphic stag beetle Cyclommatus metallifer.

PubMed

Gotoh, Hiroki; Zinna, Robert A; Warren, Ian; DeNieu, Michael; Niimi, Teruyuki; Dworkin, Ian; Emlen, Douglas J; Miura, Toru; Lavine, Laura C

2016-03-22

Genes in the sex determination pathway are important regulators of sexually dimorphic animal traits, including the elaborate and exaggerated male ornaments and weapons of sexual selection. In this study, we identified and functionally analyzed members of the sex determination gene family in the golden metallic stag beetle Cyclommatus metallifer, which exhibits extreme differences in mandible size between males and females. We constructed a C. metallifer transcriptomic database from larval and prepupal developmental stages and tissues of both males and females. Using Roche 454 pyrosequencing, we generated a de novo assembled database from a total of 1,223,516 raw reads, which resulted in 14,565 isotigs (putative transcript isoforms) contained in 10,794 isogroups (putative identified genes). We queried this database for C. metallifer conserved sex determination genes and identified 14 candidate sex determination pathway genes. We then characterized the roles of several of these genes in development of extreme sexual dimorphic traits in this species. We performed molecular expression analyses with RT-PCR and functional analyses using RNAi on three C. metallifer candidate genes--Sex-lethal (CmSxl), transformer-2 (Cmtra2), and intersex (Cmix). No differences in expression pattern were found between the sexes for any of these three genes. In the RNAi gene-knockdown experiments, we found that only the Cmix had any effect on sexually dimorphic morphology, and these mimicked the effects of Cmdsx knockdown in females. Knockdown of CmSxl had no measurable effects on stag beetle phenotype, while knockdown of Cmtra2 resulted in complete lethality at the prepupal period. These results indicate that the roles of CmSxl and Cmtra2 in the sex determination cascade are likely to have diverged in stag beetles when compared to Drosophila. Our results also suggest that Cmix has a conserved role in this pathway. In addition to those three genes, we also performed a more complete functional analysis of the C. metallifer dsx gene (Cmdsx) to identify the isoforms that regulate dimorphism more fully using exon-specific RNAi. We identified a total of 16 alternative splice variants of the Cmdsx gene that code for up to 14 separate exons. Despite the variation in RNA splice products of the Cmdsx gene, only four protein isoforms are predicted. The results of our exon-specific RNAi indicated that the essential CmDsx isoform for postembryonic male differentiation is CmDsxB, whereas postembryonic female specific differentiation is mainly regulated by CmDsxD. Taken together, our results highlight the importance of studying the function of highly conserved sex determination pathways in numerous insect species, especially those with dramatic and exaggerated sexual dimorphism, because conservation in protein structure does not always translate into conservation in downstream function.
Are nutrition messages lost in transmission? Assessing the quality and consistency of diabetes guideline recommendations on the delivery of nutrition therapy.

PubMed

Hale, Kelli; Capra, Sandra; Bauer, Judy

2016-12-01

To provide an overview of (1) the consistency of Type 2 Diabetes Clinical Practice Guidelines recommendations on the delivery of nutrition therapy and (2) Clinical Practice Guideline quality. Large international clinical practice guideline repositories, diabetes organisation websites, and electronic databases (Pubmed, Scopus), were searched to identify Clinical Practice Guidelines for adults with type 2 diabetes published 2005 to August 2014. Recommendations on the delivery of nutrition therapy were extracted and inductive content analysis was used to analyse consistency. Two researchers independently assessed guideline quality using the AGREE II tool. Nine topics were identified from the recommendations. Overall the consistency of the recommendations was related to guideline type. Compared with nutrition-specific guidelines, the broad ones had a broader focus and included more patient-focused recommendations. The ten Clinical Practice Guidelines assessed included six broad guidelines and four nutrition specific guidelines. Based on AGREE II analysis, the broad guidelines were higher quality than nutrition-specific ones. Broad Clinical Practice Guidelines were higher quality and included more patient-focused recommendations than nutrition-specific ones. Our findings suggest a need for nutrition-specific guidelines to be modified to include greater patient-focus, or for practitioners delivering nutrition therapy to adopt broad Clinical Practice Guidelines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations

PubMed Central

Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.

2015-01-01

Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087
Emotion dysregulation in hypochondriasis and depression.

PubMed

Bailer, Josef; Witthöft, Michael; Erkic, Maja; Mier, Daniela

2017-11-01

The aim of this study was to explore whether certain aspects of emotion dysregulation (i.e., facets of alexithymia and rumination) are more closely linked to hypochondriasis than to depression and vice versa. Nineteen patients with hypochondriasis (HYP), 33 patients with depression, and 52 healthy control participants completed the Toronto Alexithymia Scale, the Response Styles Questionnaire, and additional symptom and illness behaviour scales. A clinical interview was used to establish DSM-IV diagnoses and to exclude all cases with more than one axis I diagnosis. Depression patients reported more difficulties describing feelings and more symptom- and self-focused rumination than both HYP patients and healthy individuals, whereas HYP patients differed only from healthy individuals in regard to more difficulties in identifying feelings and more symptom-focused rumination. Multiple regression analyses, including all assessed facets of emotion dysregulation, showed that the degree of somatoform features (somatic symptoms, health anxiety, and illness behaviour) was specifically predicted by higher difficulties in identifying feelings scores, whereas depressive symptom levels were specifically predicted by higher rumination scores. Specific associations were found between difficulties in identifying feelings and key features of HYP, whereas depression was linked to a more generalized pattern of emotion regulation deficits. Emotion dysregulation can be found in hypochondriasis and depression Difficulties in identifying own feelings are specifically linked to somatic symptoms, health anxiety, and illness behaviour, whereas a more generalized pattern of emotion dysregulation is found in relation to depression Further research is needed to investigate whether the effectiveness of current treatments for depression, hypochondriasis, health anxiety, and related disorders could be improved by additional emotion regulation interventions. Copyright © 2017 John Wiley & Sons, Ltd.
Country-specific dietary patterns and associations with socioeconomic status in European children: the IDEFICS study.

PubMed

Fernández-Alvira, J M; Bammann, K; Pala, V; Krogh, V; Barba, G; Eiben, G; Hebestreit, A; Veidebaum, T; Reisch, L; Tornaritis, M; Kovacs, E; Huybrechts, I; Moreno, L A

2014-07-01

Children from lower socioeconomic status (SES) may be at higher risk of unhealthy eating. We described country-specific dietary patterns among children aged 2-9 years from eight European countries participating in the IDEFICS study and assessed the association of dietary patterns with an additive SES indicator. Children aged 2-9 years from eight European countries were recruited in 2007-2008. Principal component analysis was applied to identify dietary country-specific patterns. Linear regression analyses were applied to assess their association with SES. Two to four dietary patterns were identified in the participating regions. The existence of a 'processed' pattern was found in the eight regions. Also, a 'healthy' pattern was identified in seven of the eight regions. In addition, region-specific patterns were identified, reflecting the existing gastronomic and cultural differences in Europe. The 'processed' pattern was significantly inversely associated with the SES additive indicator in all countries except Sweden, whereas the 'healthy' pattern was positively associated with SES in the Belgian, Estonian, German and Hungarian regions, but was not significant in the Italian, Spanish and Swedish regions. A 'processed' pattern and a 'healthy' pattern were found in most of the participating countries in the IDEFICS study, with comparable food item profiles. The results showed a strong inverse association of SES with the 'processed' pattern, suggesting that children of parents with lower SES may be at higher risk of unhealthy eating. Therefore, special focus should be given to parents and their children from lower SES levels when developing healthy eating promotion strategies.
Organization specific predictors of job satisfaction: findings from a Canadian multi-site quality of work life cross-sectional survey.

PubMed

Krueger, Paul; Brazil, Kevin; Lohfeld, Lynne; Edward, H Gayle; Lewis, David; Tjam, Erin

2002-03-25

Organizational features can affect how staff view their quality of work life. Determining staff perceptions about quality of work life is an important consideration for employers interested in improving employee job satisfaction. The purpose of this study was to identify organization specific predictors of job satisfaction within a health care system that consisted of six independent health care organizations. 5,486 full, part and causal time (non-physician) staff on active payroll within six organizations (2 community hospitals, 1 community hospital/long-term care facility, 1 long-term care facility, 1 tertiary care/community health centre, and 1 visiting nursing agency) located in five communities in Central West Ontario, Canada were asked to complete a 65-item quality of work life survey. The self-administered questionnaires collected staff perceptions of: co-worker and supervisor support; teamwork and communication; job demands and decision authority; organization characteristics; patient/resident care; compensation and benefits; staff training and development; and impressions of the organization. Socio-demographic data were also collected. Depending on the organization, between 15 and 30 (of the 40 potential predictor) variables were found to be statistically associated with job satisfaction (univariate analyses). Logistic regression analyses identified the best predictors of job satisfaction and these are presented for each of the six organizations and for all organizations combined. The findings indicate that job satisfaction is a multidimensional construct and although there appear to be some commonalities across organizations, some predictors of job satisfaction appear to be organization and context specific.
The association between substance use and common mental disorders in young adults: results from the South African Stress and Health (SASH) Survey

PubMed Central

Saban, Amina; Flisher, Alan J; Grimsrud, Anna; Morojele, Neo; London, Leslie; Williams, David R; Stein, Dan J

2014-01-01

Introduction Although substance use is commonly associated with mental disorders, limited data on this association are available from low and middle income countries such as South Africa. The aims of the study were i) to determine patterns of substance use in young adults, ii) to identify trends of common psychiatric disorders in relation to use of specific substances, and iii) to determine whether specific psychiatric disorders were associated with use of specific substances in the South African population. Methods Data were drawn from the South African Stress and Health (SASH) study, a nationally-representative, cross-sectional survey of South African households that forms part of a World Health Organisation (WHO) World Mental Health (WMH) initiative to standardise information on the global burden of mental illness and its correlates. Data from a subset (n = 1766; aged 18 to 30 years) of the SASH sample of 4351 individuals were analysed. The Composite International Diagnostic Interview Version 3 (CIDI 3.0) was used to elicit basic demographic details and information regarding mental illness and substance use. Multiple regression analyses, adjusted for age and gender, were used to identify associations between mental disorders and substance use. Results Significant associations were found between substance use and mood and anxiety disorders, with a particularly strong relationship between cannabis use and mental disorder. Conclusion The results are consistent with those from previous studies, and reinforce the argument that comorbid substance use and mental disorders constitute a major public health burden. PMID:24624244
On the outdoor annoyance from scooter and motorbike noise in the urban environment.

PubMed

Paviotti, Marco; Vogiatzis, Konstantinos

2012-07-15

The health impacts of environmental noise are a growing concern amongst both the general public and policy-makers in Europe. Environmental noise - especially from road transportation - is widely accepted as an important environmental impact factor that can be taken as a start for the process of evaluating the impact of annoyance on the exposed urban population. Extensive urbanisation and the increase of road transport define the main driving forces for the environmental noise exposure of the population. In urban conditions, it is rather common, regarding road transportation noise, to hear from people that, especially, PTW (Powered Two Wheelers) are annoying, and many times are actually the most annoying environmental noise sources introducing a degradation of the urban environment. In this research, in Athens city centre, both scooters and motorbikes operation patterns are analysed, in the basis of their environmental impact through ad-hoc tests to establish if specific features of their emitted noise are annoying and affect the quality of life. It resulted that PTW are a relevant cause of specific environmental annoyance on pedestrians when low background noise levels and sparse traffic flow allow identifying the PTW. Based on the results of a measurement campaign, both L(max) and roughness indices are identified as characteristic noise signatures of the PTW. Results are compared to laboratory studies on annoyance found in literature and to a specific set of interviews with a large number of pedestrians in selected sites. Annoyance caused by scooters and motorbikes is analysed in the findings and conclusions. Copyright © 2012 Elsevier B.V. All rights reserved.
Elements That Define Recovery: The Experiential Perspective

PubMed Central

Kaskutas, Lee Ann; Borkman, Thomasina J; Laudet, Alexandre; Ritter, Lois A; Witbrodt, Jane; Subbaraman, Meenakshi Sabina; Stunz, Aina; Bond, Jason

2014-01-01

Objective: Although recovery increasingly guides substance use disorder services and policy, definitions of recovery continue to lack specificity, thereby hindering measure development and research. The goal of this study was to move the substance use disorders field beyond broad definitions by empirically identifying the domains and specific elements of recovery as experienced by persons in recovery from diverse pathways. Method: An Internet-based survey was completed by 9,341 individuals (54% female) who self-identified as being in recovery, recovered, in medication-assisted recovery, or as having had a problem with alcohol or drugs (but no longer do). Respondents were recruited via extensive outreach with treatment and recovery organizations, electronic media, and self-help groups. The survey included 47 recovery elements developed through qualitative work followed by an iterative reduction process. Exploratory and confirmatory factor analyses were conducted using split-half samples, followed by sensitivity analyses for key sample groupings. Results: Four recovery domains with 35 recovery elements emerged: abstinence in recovery, essentials of recovery, enriched recovery, and spirituality of recovery. The four-factor structure was robust regardless of length of recovery, 12-step or treatment exposure, and current substance use status. Four uncommon elements did not load on any factor but are presented to indicate the diversity of definitions. Conclusions: Our empirical findings offer specific items that can be used in evaluating recovery-oriented systems of care. Researchers studying recovery should include measures that extend beyond substance use and encompass elements such as those examined here—e.g., self-care, concern for others, personal growth, and developing ways of being that sustain change in substance use. PMID:25343658
Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

PubMed

Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

2017-11-01

Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.
The double-stranded break-forming activity of plant SPO11s and a novel rice SPO11 revealed by a Drosophila bioassay

PubMed Central

2012-01-01

Background SPO11 is a key protein for promoting meiotic recombination, by generating chromatin locus- and timing-specific DNA double-strand breaks (DSBs). The DSB activity of SPO11 was shown by genetic analyses, but whether SPO11 exerts DSB-forming activity by itself is still an unanswered question. DSB formation by SPO11 has not been detected by biochemical means, probably because of a lack of proper protein-folding, posttranslational modifications, and/or specific SPO11-interacting proteins required for this activity. In addition, plants have multiple SPO11-homologues. Results To determine whether SPO11 can cleave DNA by itself, and to identify which plant SPO11 homologue cleaves DNA, we developed a Drosophila bioassay system that detects the DSB signals generated by a plant SPO11 homologue expressed ectopically. We cytologically and genetically demonstrated the DSB activities of Arabidopsis AtSPO11-1 and AtSPO11-2, which are required for meiosis, in the absence of other plant proteins. Using this bioassay, we further found that a novel SPO11-homologue, OsSPO11D, which has no counterpart in Arabidopsis, displays prominent DSB-forming activity. Quantitative analyses of the rice SPO11 transcripts revealed the specific increase in OsSPO11D mRNA in the anthers containing meiotic pollen mother cells. Conclusions The Drosophila bioassay system successfully demonstrated that some plant SPO11 orthologues have intrinsic DSB activities. Furthermore, we identified a novel SPO11 homologue, OsSPO11D, with robust DSB activity and a possible meiotic function. PMID:22248237
Clinical predictors of interpersonal functioning in patients with bipolar disorder.

PubMed

Rosa, Adriane R; Bonnin, Caterina Mar; Mazzarini, Luis; Amann, Benedikt; Kapczinski, Flavio P; Vieta, Eduard

2009-04-01

Functional impairment has been repeatedly reported in patients with bipolar disorder even during clinical remission. Less is known about specific domains, such as interpersonal relationships. The aim of this study was to identify clinical predictors of poor interpersonal relationships. Using a specific subscale of the Functioning Assessment Short Test (FAST), we assessed the interpersonal relationships of a sample of 71 euthymic bipolar (Hamilton Depression Rating Scale [HAM-D] < 8; Young Mania Rating Scale [YMRS] < 5) patients. The sample was divided into two categories: low vs. high level functioning in interpersonal relationships according to the median of the sample. Multivariate analyses were applied to identify significant predictors of interpersonal functioning. Age (p=0.026), the number of previous depressive and mixed episodes and HAM-D scores differed significantly between the two groups (p<0.05). For manic episodes, only a tendency was detected (p=0.064). After running multivariate analyses, age (p=0.026), depressive symptoms (p=0.055) and the number of previous manic episodes (p=0.033) could be considered predictors of poor interpersonal functioning. The model predicted 83.3% of the variance (R=0.59; gl=1; p<0.001). Our results indicate a link between greater impairment in interpersonal relationships and being older and having more residual symptoms and a higher number of previous manic episodes. Patients with these features should be carefully monitored and specific psychosocial interventions should be implemented to improve their outcome. Copyright © 2009 Sociedad Española de Psiquiatría and Sociedad Española de Psiquiatría Biológica. Published by Elsevier Espana. All rights reserved.

Organization specific predictors of job satisfaction: findings from a Canadian multi-site quality of work life cross-sectional survey

PubMed Central

Krueger, Paul; Brazil, Kevin; Lohfeld, Lynne; Edward, H Gayle; Lewis, David; Tjam, Erin

2002-01-01

Background Organizational features can affect how staff view their quality of work life. Determining staff perceptions about quality of work life is an important consideration for employers interested in improving employee job satisfaction. The purpose of this study was to identify organization specific predictors of job satisfaction within a health care system that consisted of six independent health care organizations. Methods 5,486 full, part and causal time (non-physician) staff on active payroll within six organizations (2 community hospitals, 1 community hospital/long-term care facility, 1 long-term care facility, 1 tertiary care/community health centre, and 1 visiting nursing agency) located in five communities in Central West Ontario, Canada were asked to complete a 65-item quality of work life survey. The self-administered questionnaires collected staff perceptions of: co-worker and supervisor support; teamwork and communication; job demands and decision authority; organization characteristics; patient/resident care; compensation and benefits; staff training and development; and impressions of the organization. Socio-demographic data were also collected. Results Depending on the organization, between 15 and 30 (of the 40 potential predictor) variables were found to be statistically associated with job satisfaction (univariate analyses). Logistic regression analyses identified the best predictors of job satisfaction and these are presented for each of the six organizations and for all organizations combined. Conclusions The findings indicate that job satisfaction is a multidimensional construct and although there appear to be some commonalities across organizations, some predictors of job satisfaction appear to be organization and context specific. PMID:11914162
Analysis of the Transcriptomes Downstream of Eyeless and the Hedgehog, Decapentaplegic and Notch Signaling Pathways in Drosophila melanogaster

PubMed Central

Nfonsam, Landry E.; Cano, Carlos; Mudge, Joann; Schilkey, Faye D.; Curtiss, Jennifer

2012-01-01

Tissue-specific transcription factors are thought to cooperate with signaling pathways to promote patterned tissue specification, in part by co-regulating transcription. The Drosophila melanogaster Pax6 homolog Eyeless forms a complex, incompletely understood regulatory network with the Hedgehog, Decapentaplegic and Notch signaling pathways to control eye-specific gene expression. We report a combinatorial approach, including mRNAseq and microarray analyses, to identify targets co-regulated by Eyeless and Hedgehog, Decapentaplegic or Notch. Multiple analyses suggest that the transcriptomes resulting from co-misexpression of Eyeless+signaling factors provide a more complete picture of eye development compared to previous efforts involving Eyeless alone: (1) Principal components analysis and two-way hierarchical clustering revealed that the Eyeless+signaling factor transcriptomes are closer to the eye control transcriptome than when Eyeless is misexpressed alone; (2) more genes are upregulated at least three-fold in response to Eyeless+signaling factors compared to Eyeless alone; (3) based on gene ontology analysis, the genes upregulated in response to Eyeless+signaling factors had a greater diversity of functions compared to Eyeless alone. Through a secondary screen that utilized RNA interference, we show that the predicted gene CG4721 has a role in eye development. CG4721 encodes a neprilysin family metalloprotease that is highly up-regulated in response to Eyeless+Notch, confirming the validity of our approach. Given the similarity between D. melanogaster and vertebrate eye development, the large number of novel genes identified as potential targets of Ey+signaling factors will provide novel insights to our understanding of eye development in D. melanogaster and humans. PMID:22952997
Spatial analyses of benthic habitats to define coral reef ecosystem regions and potential biogeographic boundaries along a latitudinal gradient.

PubMed

Walker, Brian K

2012-01-01

Marine organism diversity typically attenuates latitudinally from tropical to colder climate regimes. Since the distribution of many marine species relates to certain habitats and depth regimes, mapping data provide valuable information in the absence of detailed ecological data that can be used to identify and spatially quantify smaller scale (10 s km) coral reef ecosystem regions and potential physical biogeographic barriers. This study focused on the southeast Florida coast due to a recognized, but understudied, tropical to subtropical biogeographic gradient. GIS spatial analyses were conducted on recent, accurate, shallow-water (0-30 m) benthic habitat maps to identify and quantify specific regions along the coast that were statistically distinct in the number and amount of major benthic habitat types. Habitat type and width were measured for 209 evenly-spaced cross-shelf transects. Evaluation of groupings from a cluster analysis at 75% similarity yielded five distinct regions. The number of benthic habitats and their area, width, distance from shore, distance from each other, and LIDAR depths were calculated in GIS and examined to determine regional statistical differences. The number of benthic habitats decreased with increasing latitude from 9 in the south to 4 in the north and many of the habitat metrics statistically differed between regions. Three potential biogeographic barriers were found at the Boca, Hillsboro, and Biscayne boundaries, where specific shallow-water habitats were absent further north; Middle Reef, Inner Reef, and oceanic seagrass beds respectively. The Bahamas Fault Zone boundary was also noted where changes in coastal morphologies occurred that could relate to subtle ecological changes. The analyses defined regions on a smaller scale more appropriate to regional management decisions, hence strengthening marine conservation planning with an objective, scientific foundation for decision making. They provide a framework for similar regional analyses elsewhere.
Spatial Analyses of Benthic Habitats to Define Coral Reef Ecosystem Regions and Potential Biogeographic Boundaries along a Latitudinal Gradient

PubMed Central

Walker, Brian K.

2012-01-01

Marine organism diversity typically attenuates latitudinally from tropical to colder climate regimes. Since the distribution of many marine species relates to certain habitats and depth regimes, mapping data provide valuable information in the absence of detailed ecological data that can be used to identify and spatially quantify smaller scale (10 s km) coral reef ecosystem regions and potential physical biogeographic barriers. This study focused on the southeast Florida coast due to a recognized, but understudied, tropical to subtropical biogeographic gradient. GIS spatial analyses were conducted on recent, accurate, shallow-water (0–30 m) benthic habitat maps to identify and quantify specific regions along the coast that were statistically distinct in the number and amount of major benthic habitat types. Habitat type and width were measured for 209 evenly-spaced cross-shelf transects. Evaluation of groupings from a cluster analysis at 75% similarity yielded five distinct regions. The number of benthic habitats and their area, width, distance from shore, distance from each other, and LIDAR depths were calculated in GIS and examined to determine regional statistical differences. The number of benthic habitats decreased with increasing latitude from 9 in the south to 4 in the north and many of the habitat metrics statistically differed between regions. Three potential biogeographic barriers were found at the Boca, Hillsboro, and Biscayne boundaries, where specific shallow-water habitats were absent further north; Middle Reef, Inner Reef, and oceanic seagrass beds respectively. The Bahamas Fault Zone boundary was also noted where changes in coastal morphologies occurred that could relate to subtle ecological changes. The analyses defined regions on a smaller scale more appropriate to regional management decisions, hence strengthening marine conservation planning with an objective, scientific foundation for decision making. They provide a framework for similar regional analyses elsewhere. PMID:22276204
Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

PubMed Central

Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

2017-01-01

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403
PTESFinder: a computational method to identify post-transcriptional exon shuffling (PTES) events.

PubMed

Izuogu, Osagie G; Alhasan, Abd A; Alafghani, Hani M; Santibanez-Koref, Mauro; Elliott, David J; Elliot, David J; Jackson, Michael S

2016-01-13

Transcripts, which have been subject to Post-transcriptional exon shuffling (PTES), have an exon order inconsistent with the underlying genomic sequence. These have been identified in a wide variety of tissues and cell types from many eukaryotes, and are now known to be mostly circular, cytoplasmic, and non-coding. Although there is no uniformly ascribed function, several have been shown to be involved in gene regulation. Accurate identification of these transcripts can, however, be difficult due to artefacts from a wide variety of sources. Here, we present a computational method, PTESFinder, to identify these transcripts from high throughput RNAseq data. Uniquely, it systematically excludes potential artefacts emanating from pseudogenes, segmental duplications, and template switching, and outputs both PTES and canonical exon junction counts to facilitate comparative analyses. In comparison with four existing methods, PTESFinder achieves highest specificity and comparable sensitivity at a variety of read depths. PTESFinder also identifies between 13 % and 41.6 % more structures, compared to publicly available methods recently used to identify human circular RNAs. With high sensitivity and specificity, user-adjustable filters that target known sources of false positives, and tailored output to facilitate comparison of transcript levels, PTESFinder will facilitate the discovery and analysis of these poorly understood transcripts.
How Methodologic Differences Affect Results of Economic Analyses: A Systematic Review of Interferon Gamma Release Assays for the Diagnosis of LTBI

PubMed Central

Oxlade, Olivia; Pinto, Marcia; Trajman, Anete; Menzies, Dick

2013-01-01

Introduction Cost effectiveness analyses (CEA) can provide useful information on how to invest limited funds, however they are less useful if different analysis of the same intervention provide unclear or contradictory results. The objective of our study was to conduct a systematic review of methodologic aspects of CEA that evaluate Interferon Gamma Release Assays (IGRA) for the detection of Latent Tuberculosis Infection (LTBI), in order to understand how differences affect study results. Methods A systematic review of studies was conducted with particular focus on study quality and the variability in inputs used in models used to assess cost-effectiveness. A common decision analysis model of the IGRA versus Tuberculin Skin Test (TST) screening strategy was developed and used to quantify the impact on predicted results of observed differences of model inputs taken from the studies identified. Results Thirteen studies were ultimately included in the review. Several specific methodologic issues were identified across studies, including how study inputs were selected, inconsistencies in the costing approach, the utility of the QALY (Quality Adjusted Life Year) as the effectiveness outcome, and how authors choose to present and interpret study results. When the IGRA versus TST test strategies were compared using our common decision analysis model predicted effectiveness largely overlapped. Implications Many methodologic issues that contribute to inconsistent results and reduced study quality were identified in studies that assessed the cost-effectiveness of the IGRA test. More specific and relevant guidelines are needed in order to help authors standardize modelling approaches, inputs, assumptions and how results are presented and interpreted. PMID:23505412
Risk Factors for Bloodstream Infection After Living-donor Liver Transplantation in Children.

PubMed

Shoji, Kensuke; Funaki, Takanori; Kasahara, Mureo; Sakamoto, Seisuke; Fukuda, Akinari; Vaida, Florin; Ito, Kenta; Miyairi, Isao; Saitoh, Akihiko

2015-10-01

Postoperative bloodstream infection (BSI) is the most important determinant of recipient morbidity and mortality after liver transplantation (LT). Children who underwent LT are at the highest risk of developing BSI because of the significant surgical intervention, use of multiple devices, and administration of immunosuppressive agents. However, information regarding the risk factors for BSI in children after LT is limited. We retrospectively reviewed 210 children who underwent living-donor LT at the largest pediatric LT center in Japan. Patients' characteristics, blood culture results and clinical outcomes were extracted from electronic medical records. Univariate and multivariate analyses were performed to identify the risk factors for BSI. Among the 210 LT recipients, 53 (25%) recipients experienced 86 episodes of BSI during the observational period. The source of the BSI was identified only in 38%: catheter-related BSI (27%) peritonitis (7%), urinary tract infection (2%), pneumonia (1%) and infectious endocarditis (1%). A multivariate analysis demonstrated that body weight (P = 0.03), volume of blood loss during LT (P < 0.001) and cytomegalovirus (CMV) antigenemia positivity (P = 0.04) were independently associated with the development of BSI. The risk factors for BSI differed when we analyzed the subjects according to age (≤24 months and >24 months), blood loss and pediatric end-stage liver disease/model for end-stage liver disease versus positive CMV antigenemia. The volume of blood loss, postoperative CMV antigenemia positivity and body weight were associated with the development of BSI after LT in pediatric living-donor recipients. To identify the age-specific predictors of BSI in children who underwent LT, age-specific analyses are crucial.
WHY DO YOU NEED TO USE A CARIES RISK ASSESSMENT PROTOCOL TO PROVIDE AN EFFECTIVE CARIES PREVENTIVE REGIME?

PubMed

Afuakwah, Charles; Welbury, Richard

2015-11-01

Clinical guidelines recommend an individual is given a caries risk status based on analysis of defined clinical and social criteria before implementing a tailored preventive plan. Improve documentation of caries risk assessment (CRA) in a general dental practice setting, using a systems-based approach to quality improvement methods. Investigate the impact of quality improvement efforts on subsequent design and delivery of preventive care. Identify barriers to delivery of CRA and provision of preventive care. Data for patients aged 0-16 years was collected over two cycles using standard audit methodology. The first cycle was a retrospective analysis (n = 400) using random sampling. The second cycle a prospective analysis (n = 513) using consecutive sampling over a 15-week period. Five staff meetings with feedback occurred between cycles. In cycle one, no specific CRA system was identified. CRA status was not stated widely, risk factors were not analysed and there was variation with respect to the prescription and delivery of preventive strategies. These discrepancies were demonstrable for all four participating dentists and at all ages. In cycle two, 100% recorded CRA. All risk factors were analysed and individual caries risk was correctly annotated. There was 100% compliance with the protocol for preventive plans. The use of CRA improved documentation of caries risk status. This has improved subsequent prescription of age specific evidence-based preventive care appropriate to the risk status of that individual. Barriers were identified to the delivery of CRA and the provision of comprehensive preventive care by the dentists and other healthcare professionals.
Growth and stress response mechanisms underlying post-feeding regenerative organ growth in the Burmese python.

PubMed

Andrew, Audra L; Perry, Blair W; Card, Daren C; Schield, Drew R; Ruggiero, Robert P; McGaugh, Suzanne E; Choudhary, Amit; Secor, Stephen M; Castoe, Todd A

2017-05-02

Previous studies examining post-feeding organ regeneration in the Burmese python (Python molurus bivittatus) have identified thousands of genes that are significantly differentially regulated during this process. However, substantial gaps remain in our understanding of coherent mechanisms and specific growth pathways that underlie these rapid and extensive shifts in organ form and function. Here we addressed these gaps by comparing gene expression in the Burmese python heart, liver, kidney, and small intestine across pre- and post-feeding time points (fasted, one day post-feeding, and four days post-feeding), and by conducting detailed analyses of molecular pathways and predictions of upstream regulatory molecules across these organ systems. Identified enriched canonical pathways and upstream regulators indicate that while downstream transcriptional responses are fairly tissue specific, a suite of core pathways and upstream regulator molecules are shared among responsive tissues. Pathways such as mTOR signaling, PPAR/LXR/RXR signaling, and NRF2-mediated oxidative stress response are significantly differentially regulated in multiple tissues, indicative of cell growth and proliferation along with coordinated cell-protective stress responses. Upstream regulatory molecule analyses identify multiple growth factors, kinase receptors, and transmembrane receptors, both within individual organs and across separate tissues. Downstream transcription factors MYC and SREBF are induced in all tissues. These results suggest that largely divergent patterns of post-feeding gene regulation across tissues are mediated by a core set of higher-level signaling molecules. Consistent enrichment of the NRF2-mediated oxidative stress response indicates this pathway may be particularly important in mediating cellular stress during such extreme regenerative growth.
Gastrointestinal symptoms predictors of health-related quality of life in pediatric patients with functional gastrointestinal disorders.

PubMed

Varni, James W; Shulman, Robert J; Self, Mariella M; Nurko, Samuel; Saps, Miguel; Saeed, Shehzad A; Patel, Ashish S; Dark, Chelsea Vaughan; Bendo, Cristiane B; Pohl, John F

2017-04-01

To investigate the patient-reported multidimensional gastrointestinal symptoms predictors of generic health-related quality of life (HRQOL) in pediatric patients with functional gastrointestinal disorders (FGIDs). The Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and PedsQL™ 4.0 Generic Core Scales were completed in a 9-site study by 259 pediatric patients with functional constipation, functional abdominal pain (FAP), or irritable bowel syndrome (IBS). Gastrointestinal Symptoms Scales measuring stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood in poop, and diarrhea were identified as clinically important symptom differentiators from healthy controls based on prior findings, and subsequently tested for bivariate and multivariate linear associations with overall HRQOL. Gastrointestinal symptoms were differentially associated with decreased HRQOL in bivariate analyses for the three FGIDs. In predictive models utilizing hierarchical multiple regression analyses controlling for age, gender, and race/ethnicity, gastrointestinal symptoms differentially accounted for an additional 47, 40, and 60 % of the variance in patient-reported HRQOL for functional constipation, FAP, and IBS, respectively, reflecting large effect sizes. Significant individual gastrointestinal symptoms predictors were identified after controlling for the other gastrointestinal symptoms in the FGID-specific predictive models. Gastrointestinal symptoms represent potentially modifiable predictors of generic HRQOL in pediatric patients with FGIDs. Identifying the condition-specific gastrointestinal symptoms that are the most important predictors from the patient perspective facilitates a patient-centered approach to targeted interventions designed to ameliorate impaired overall HRQOL.
Characterization of Residential Pesticide Use and Chemical Formulations through Self-Report and Household Inventory: The Northern California Childhood Leukemia Study

PubMed Central

Guha, Neela; Ward, Mary H.; Gunier, Robert; Colt, Joanne S.; Lea, C. Suzanne; Buffler, Patricia A.

2012-01-01

Background: Home and garden pesticide use has been linked to cancer and other health outcomes in numerous epidemiological studies. Exposure has generally been self-reported, so the assessment is potentially limited by recall bias and lack of information on specific chemicals. Objectives: As part of an integrated assessment of residential pesticide exposure, we identified active ingredients and described patterns of storage and use. Methods: During a home interview of 500 residentially stable households enrolled in the Northern California Childhood Leukemia Study during 2001–2006, trained interviewers inventoried residential pesticide products and queried participants about their storage and use. U.S. Environmental Protection Agency registration numbers, recorded from pesticide product labels, and pesticide chemical codes were matched to public databases to obtain information on active ingredients and chemical class. Poisson regression was used to identify independent predictors of pesticide storage. Analyses were restricted to 259 participating control households. Results: Ninety-five percent (246 of 259) of the control households stored at least one pesticide product (median, 4). Indicators of higher sociodemographic status predicted more products in storage. We identified the most common characteristics: storage areas (garage, 40%; kitchen, 20%), pests treated (ants, 33%; weeds, 20%), pesticide types (insecticides, 46%; herbicides, 24%), chemical classes (pyrethroids, 77%; botanicals, 50%), active ingredients (pyrethrins, 43%) and synergists (piperonyl butoxide, 42%). Products could contain multiple active ingredients. Conclusions: Our data on specific active ingredients and patterns of storage and use will inform future etiologic analyses of residential pesticide exposures from self-reported data, particularly among households with young children. PMID:23110983
Real-space analysis of radiation-induced specific changes with independent component analysis

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

Borek, Dominika; Bromberg, Raquel; Hattne, Johan

A method of analysis is presented that allows for the separation of specific radiation-induced changes into distinct components in real space. The method relies on independent component analysis (ICA) and can be effectively applied to electron density maps and other types of maps, provided that they can be represented as sets of numbers on a grid. Here, for glucose isomerase crystals, ICA was used in a proof-of-concept analysis to separate temperature-dependent and temperature-independent components of specific radiation-induced changes for data sets acquired from multiple crystals across multiple temperatures. ICA identified two components, with the temperature-independent component being responsible for themore » majority of specific radiation-induced changes at temperatures below 130 K. The patterns of specific temperature-independent radiation-induced changes suggest a contribution from the tunnelling of electron holes as a possible explanation. In the second case, where a group of 22 data sets was collected on a single thaumatin crystal, ICA was used in another type of analysis to separate specific radiation-induced effects happening on different exposure-level scales. Here, ICA identified two components of specific radiation-induced changes that likely result from radiation-induced chemical reactions progressing with different rates at different locations in the structure. In addition, ICA unexpectedly identified the radiation-damage state corresponding to reduced disulfide bridges rather than the zero-dose extrapolated state as the highest contrast structure. The application of ICA to the analysis of specific radiation-induced changes in real space and the data pre-processing for ICA that relies on singular value decomposition, which was used previously in data space to validate a two-component physical model of X-ray radiation-induced changes, are discussed in detail. This work lays a foundation for a better understanding of protein-specific radiation chemistries and provides a framework for analysing effects of specific radiation damage in crystallographic and cryo-EM experiments.« less
Use of multicriteria analysis (MCA) for sustainable hydropower planning and management.

PubMed

Vassoney, Erica; Mammoliti Mochet, Andrea; Comoglio, Claudio

2017-07-01

Multicriteria analysis (MCA) is a decision-making tool applied to a wide range of environmental management problems, including renewable energy planning and management. An interesting field of application of MCA is the evaluation and analysis of the conflicting aspects of hydropower (HP) exploitation, affecting the three pillars of sustainability and involving several different stakeholders. The present study was aimed at reviewing the state of the art of MCA applications to sustainable hydropower production and related decision-making problems, based on a detailed analysis of the scientific papers published over the last 15 years on this topic. The papers were analysed and compared, focusing on the specific features of the MCA methods applied in the described case studies, highlighting the general aspects of the MCA application (purpose, spatial scale, software used, stakeholders, etc.) and the specific operational/technical features of the selected MCA technique (methodology, criteria, evaluation, approach, sensitivity, etc.). Some specific limitations of the analysed case studies were identified and a set of "quality indexes" of an exhaustive MCA application were suggested as potential improvements for more effectively support decision-making processes in sustainable HP planning and management problems. Copyright © 2017 Elsevier Ltd. All rights reserved.
Determining the composition and benefit of the pre-hospital medical response team in the conflict setting.

PubMed

Davis, P R; Rickards, A C; Ollerton, J E

2007-12-01

To determine the optimal composition o f the pre-hospital medical response team (MERT) and the value of pre-hospital critical care interventions in a military setting, and specifically to determine both the benefit of including a doctor in the pre-hospital response team and the relevance of the time and distance to definitive care. A comprehensive review of the literature incorporating a range of electronic search engines and hand searches of key journals. There was no level 1 evidence on which to base conclusions. The 15 most relevant articles were analysed in detail. There was one randomized controlled trial (level 2 evidence) that supports the inclusion of a doctor on MERT. Several cohort studies were identified that analysed the benefits of specific critical care interventions in the pre-hospital setting. A doctor with critical care skills deployed on the MERT is associated with improved survival in victims of major trauma. Specific critical care interventions including emergency endotracheal intubation and ventilation, and intercostal drainage are associated with improved survival and functional recovery in certain patients. These benefits appear to be more easily demonstrated for the rural and remote setting than for the urban setting.
A systematic analysis of commonly used antibodies in cancer diagnostics.

PubMed

Gremel, Gabriela; Bergman, Julia; Djureinovic, Dijana; Edqvist, Per-Henrik; Maindad, Vikas; Bharambe, Bhavana M; Khan, Wasif Ali Z A; Navani, Sanjay; Elebro, Jacob; Jirström, Karin; Hellberg, Dan; Uhlén, Mathias; Micke, Patrick; Pontén, Fredrik

2014-01-01

Immunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. A tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. The results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer. © 2013 John Wiley & Sons Ltd.
Analysis of worldwide research in the field of cybernetics during 1997-2011.

PubMed

Singh, Virender; Perdigones, Alicia; García, José Luis; Cañas-Guerrero, Ignacio; Mazarrón, Fernando R

2014-12-01

The study provides an overview of the research activity carried out in the field of cybernetics. To do so, all research papers from 1997 to 2011 (16,445 research papers) under the category of "Computer Science, Cybernetics" of Web of Science have been processed using our in-house software which is developed specifically for this purpose. Among its multiple capabilities, this software analyses individual and compound keywords, quantifies productivity taking into account the work distribution, estimates the impact of each article and determines the collaborations established at different scales. Keywords analysis identifies the evolution of the most important research topics in the field of cybernetics and their specificity in biological aspects, as well as the research topics with lesser interest. The analysis of productivity, impact and collaborations provides a framework to assess research activity in a specific and realistic context. The geographical and institutional distribution of publications reveals the leading countries and research centres, analysing their relation to main research journals. Moreover, collaborations analysis reveals great differences in terms of internationalization and complexity of research networks. The results of this study may be very useful for the characterization and the decisions made by research in the field of cybernetics.
Influence of toroidal magnetic field in multiaccreting tori

NASA Astrophysics Data System (ADS)

Pugliese, D.; Montani, G.

2018-06-01

We analysed the effects of a toroidal magnetic field in the formation of several magnetized accretion tori, dubbed as ringed accretion discs (RADs), orbiting around one central Kerr supermassive black hole (SMBH) in active galactic nuclei (AGNs), where both corotating and counterotating discs are considered. Constraints on tori formation and emergence of RADs instabilities, accretion on to the central attractor and tori collision emergence, are investigated. The results of this analysis show that the role of the central BH spin-mass ratio, the magnetic field and the relative fluid rotation and tori rotation with respect the central BH, are crucial elements in determining the accretion tori features, providing ultimately evidence of a strict correlation between SMBH spin, fluid rotation, and magnetic fields in RADs formation and evolution. More specifically, we proved that magnetic field and discs rotation are in fact strongly constrained, as tori formation and evolution in RADs depend on the toroidal magnetic fields parameters. Eventually, this analysis identifies specific classes of tori, for restrict ranges of magnetic field parameter, that can be observed around some specific SMBHs identified by their dimensionless spin.
Subtractive cloning of cDNA from Aspergillus oryzae differentially regulated between solid-state culture and liquid (submerged) culture.

PubMed

Akao, Takeshi; Gomi, Katsuya; Goto, Kuniyasu; Okazaki, Naoto; Akita, Osamu

2002-07-01

In solid-state cultures (SC), Aspergillus oryzae shows characteristics such as high-level production and secretion of enzymes and hyphal differentiation with asexual development which are absent in liquid (submerged) culture (LC). It was predicted that many of the genes involved in the characteristics of A. oryzae in SC are differentially expressed between SC and LC. We generated two subtracted cDNA libraries with bi-directional cDNA subtractive hybridizations to isolate and identify such genes. Among them, we identified genes upregulated in or specific to SC, such as the AOS ( A. oryzae SC-specific gene) series, and those downregulated or not expressed in SC, such as the AOL ( A. oryzae LC-specific) series. Sequencing analyses revealed that the AOS series and the AOL series contain genes encoding extra- and intracellular enzymes and transport proteins. However, half were functionally unclassified by nucleotide sequences. Also, by expression profile, the AOS series comprised two groups. These gene products' molecular functions and physiological roles in SC await further investigation.
Comparison of synovial fluid culture and 16S rRNA PCR in dogs with suspected septic arthritis.

PubMed

Scharf, V F; Lewis, D D; Wellehan, J F; Wamsley, H L; Richardson, R

2015-06-01

To prospectively compare the sensitivity and specificity of 16S rRNA PCR with culture for identifying the causative organism in synovial fluid obtained from dogs with suspected septic arthritis. Synovial fluid cytology, PCR analysis and aerobic, anaerobic and Mycoplasma culture of samples from the affected joints of 18 dogs presenting with suspected septic arthritis were performed. Synovial fluid samples from the corresponding contralateral joints of 7 dogs were also analysed as negative controls. There was no significant difference between the sensitivity of bacterial detection via culture (63.2%) versus PCR (73.7%) of synovial fluid (P=0.728) or between culture and combined PCR and culture (89.5%) of synovial fluid (P=0.124). The specificity of PCR (42.9%) was significantly lower than culture specificity (100%) (P=0.07). Although 16S PCR may hold potential as an ancillary diagnostic test for identifying the causative organism in dogs with septic arthritis, our study failed to demonstrate improved accuracy compared with traditional synovial fluid culture. © 2015 Australian Veterinary Association.

Surveillance of construction worker injuries: the utility of trade-specific analysis.

PubMed

Hunting, K L; Welch, L S; Nessel-Stephens, L; Anderson, J; Mawudeku, A

1999-07-01

Construction is a dangerous industry, with high rates of both fatal and nonfatal injuries. To learn more about the causes of nonfatal construction worker injuries, and to identify injury cases for further work site-based investigations or prevention programs, we established an emergency department-based surveillance program in November 1990. This article describes circumstances of injury, diagnoses, and demographic characteristics of injured construction workers for 2,791 cases identified through mid-August, 1997. Lacerations and strains and sprains were the most frequent diagnoses; cutting and piercing objects were the leading causes of injury among all construction workers, followed by falls and overexertion. Because of the variety of work performed in this industry, more detailed injury descriptions, by trade, are most useful for thinking about injury prevention. To illustrate this, we profile injury patterns among workers from four specific trades: carpenters, electricians, plumbers, and ironworkers. Areas of concern highlighted by the trade-specific analyses include eye injuries among plumbers; falls from ladders among electricians and plumbers; slips, trips, and falls on the same level among ironworkers; electrical exposure among electricians; and, amputations among carpenters.
Investigation of cancer mortality inequalities between rural and urban areas in South Korea.

PubMed

Choi, Kyung-Mee

2016-02-01

Little is known about rural-urban cancer disparities, particularly in South Korea, and this study is to identify cancer-specific mortality inequalities between the rural and urban areas of the country. For 11 specific cancer sites, age-standardised mortality rates were analysed for the rural and urban administrative districts of South Korea during 2006-2011. The Poisson log linear regression models were employed to estimate cancer-specific mortality rates, and Bonferroni comparison method was used to identify rural-urban disparities. There were significant rural-urban disparities observed for all cancer sites except prostate, pancreas and leukaemia. The mortality rates of lung, liver and stomach cancers, the three most common cancers in the country, were observed to be significantly higher in rural areas than in metropolitan areas. In contrast, the reverse relationship was observed for the reproductive system (breast and uterus) and colon cancers. Central nervous system cancer mortality was observed to be significantly higher in rural areas than in non-metro urban areas. For the first time ever, significant rural-urban disparity patterns in cancer mortality rates in South Korea have been identified in this paper. Future investigations on cancer risk factors for the country should address these disparity patterns. © 2015 National Rural Health Alliance Inc.
Species-specific serine-threonine protein kinase Pkb2 of Bifidobacterium longum subsp. longum: Genetic environment and substrate specificity.

PubMed

Nezametdinova, V Z; Mavletova, D A; Alekseeva, M G; Chekalina, M S; Zakharevich, N V; Danilenko, V N

2018-06-01

The objective of this study was to determine for phosphorylated substrates of the species-specific serine-threonine protein kinase (STPK) Pkb2 from Bifidobacterium longum subsp. longum GT15. Two approaches were employed: analyses of phosphorylated membrane vesicles protein spectra following kinase reactions and analyses of the genes surrounding pkb2. A bioinformatics analysis of the genes surrounding pkb2 found a species-specific gene cluster PFNA in the genomes of 34 different bifidobacterial species. The identified cluster consisted of 5-8 genes depending on the species. The first five genes are characteristic for all considered species. These are the following genes encoding serine-threonine protein kinase (pkb2), fibronectin type III domain-containing protein (fn3), AAA-ATPase (aaa-atp), hypothetical protein with DUF58 domain (duf58) and transglutaminase (tgm). The sixth (protein phosphatase, prpC), seventh (hypothetical protein, BLGT_RS02790), and eighth (FHA domain-containing protein, fha) genes are included in this cluster, but they are not found in all species. The operon organization of the PFNA gene cluster was confirmed with transcriptional analysis. AAA-ATPase, which is encoded by a gene of the PFNA gene cluster, was found to be a substrate of the STPK Pkb2. Fourteen AAA-ATPase sites (seven serine, six threonine, and one tyrosine) phosphorylated by STPK Pkb2 were revealed. Analysis of the spectra of phosphorylated membrane vesicles proteins allowed us to identify eleven proteins that were considered as possible Pkb2 substrates. They belong to several functional classes: proteins involved in transcription and translation; proteins of the F1-domain of the FoF1-ATPase; ABC-transporters; molecular chaperone GroEL; and glutamine synthase, GlnA1. All identified proteins were considered moonlighting proteins. Three out of 11 proteins (glutamine synthetase GlnA1 and FoF1-ATPase alpha and beta subunits) were selected for further in vitro phosphorylation assays and were shown to be phosphorylated by Pkb2. Four phosphorylated substrates of the species-specific STPK Pkb2 from B. longum subsp. longum GT15 were identified for the first time. They included the moonlighting protein glutamine synthase GlnA, FoF1-ATPase alpha and beta subunits, and the chaperone MoxR family of AAA-ATPase. The ability of bifidobacterial STPK to phosphorylate the substrate on serine, threonine, and tyrosine residues was shown for the first time. Copyright © 2018 Elsevier Ltd. All rights reserved.
Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of Stevia for Diterpenoid Production.

PubMed

Kim, Mi Jung; Jin, Jingjing; Zheng, Junshi; Wong, Limsoon; Chua, Nam-Hai; Jang, In-Cheol

2015-12-01

Stevia (Stevia rebaudiana) produces not only a group of diterpenoid glycosides known as steviol glycosides (SGs), but also other labdane-type diterpenoids that may be spatially separated from SGs. However, their biosynthetic routes and spatial distribution in leaf tissues have not yet been elucidated. Here, we integrate metabolome and transcriptome analyses of Stevia to explore the biosynthetic capacity of leaf tissues for diterpenoid metabolism. Tissue-specific chemical analyses confirmed that SGs were accumulated in leaf cells but not in trichomes. On the other hand, Stevia leaf trichomes stored other labdane-type diterpenoids such as oxomanoyl oxide and agatholic acid. RNA sequencing analyses from two different tissues of Stevia provided a comprehensive overview of dynamic metabolic activities in trichomes and leaf without trichomes. These metabolite-guided transcriptomics and phylogenetic and gene expression analyses clearly identified specific gene members encoding enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate pathway and the biosynthesis of steviol or other labdane-type diterpenoids. Additionally, our RNA sequencing analysis uncovered copalyl diphosphate synthase (SrCPS) and kaurene synthase1 (SrKS1) homologs, SrCPS2 and KS-like (SrKSL), which were specifically expressed in trichomes. In vitro and in planta assays showed that unlike SrCPS and SrKS1, SrCPS2 synthesized labda-13-en-8-ol diphosphate and successively catalyzed the formation of manoyl oxide and epi-manoyl oxide in combination with SrKSL. Our findings suggest that Stevia may have evolved to use distinct metabolic pathways to avoid metabolic interferences in leaf tissues for efficient production of diverse secondary metabolites. © 2015 American Society of Plant Biologists. All Rights Reserved.
Ground- and Surface-Water Chemistry of Handcart Gulch, Park County, Colorado, 2003-2006

USGS Publications Warehouse

Verplanck, Philip L.; Manning, Andrew H.; Kimball, Briant A.; McCleskey, R. Blaine; Runkel, Robert L.; Caine, Jonathan S.; Adams, Monique; Gemery-Hill, Pamela A.; Fey, David L.

2008-01-01

As part of a multidisciplinary project to determine the processes that control ground-water chemistry and flow in mineralized alpine environments, ground- and surface-water samples from Handcart Gulch, Colorado were collected for analysis of inorganic solutes and water and dissolved sulfate stable isotopes in selected samples. The primary aim of this study was to document variations in ground-water chemistry in Handcart Gulch and to identify changes in water chemistry along the receiving stream of Handcart Gulch. Water analyses are reported for ground-water samples collected from 12 wells in Handcart Gulch, Colorado. Samples were collected between August 2003 and October 2005. Water analyses for surface-water samples are reported for 50 samples collected from Handcart Gulch and its inflows during a low-flow tracer injection on August 6, 2003. In addition, water analyses are reported for three other Handcart Gulch stream samples collected in September 2005 and March 2006. Reported analyses include field parameters (pH, specific conductance, temperature, dissolved oxygen, and Eh), major and trace constituents, oxygen and hydrogen isotopic composition of water and oxygen and sulfur isotopic composition of dissolved sulfate. Ground-water samples from this study are Ca-SO4 type and range in pH from 2.5 to 6.8. Most of the samples (75 percent) have pH values between 3.3 and 4.3. Surface water samples are also Ca-SO4 type and have a narrower range in pH (2.7?4.0). Ground- and surface-water samples vary from relatively dilute (specific conductance of 68 ?S/cm) to concentrated (specific conductance of 2,000 ?S/cm).
The current status of theory evaluation in nursing.

PubMed

Im, Eun-Ok

2015-10-01

To identify the current status of theory evaluation in nursing and provide directions for theory evaluation for future development of theoretical bases of nursing discipline. Theory evaluation is an essential component in development of nursing knowledge, which is a critical element in development of nursing discipline. Despite earlier significant efforts for theory evaluation in nursing, a recent decline in the number of theory evaluation articles was noted and there have been few updates on theory evaluation in nursing. Discussion paper. A total of 58 articles published from 2003-2014 were retrieved through searches using the PUBMED, PsyInfo and CINAHL. The articles were sorted by the area of evaluation and analysed to identify themes reflecting the theory evaluation process. Diverse ways of theory evaluation need to be continuously used in future theory evaluation efforts. Six themes reflecting the theory evaluation process were identified: (a) rarely using existing theory evaluation criteria; (b) evaluating specifics; (c) using various statistical analysis methods; (d) developing instruments; (e) adopting in practice and education; and (f) evaluating mainly middle-range theories and situation-specific theories. © 2015 John Wiley & Sons Ltd.
Identifying hearing loss by means of iridology.

PubMed

Stearn, Natalie; Swanepoel, De Wet

2006-11-13

Isolated reports of hearing loss presenting as markings on the iris exist, but to date the effectiveness of iridology to identify hearing loss has not been investigated. This study therefore aimed to determine the efficacy of iridological analysis in the identification of moderate to profound sensorineural hearing loss in adolescents. A controlled trial was conducted with an iridologist, blind to the actual hearing status of participants, analyzing the irises of participants with and without hearing loss. Fifty hearing impaired and fifty normal hearing subjects, between the ages of 15 and 19 years, controlled for gender, participated in the study. An experienced iridologist analyzed the randomised set of participants' irises. A 70% correct identification of hearing status was obtained by iridological analyses with a false negative rate of 41% compared to a 19% false positive rate. The respective sensitivity and specificity rates therefore came to 59% and 81%. Iridological analysis of hearing status indicated a statistically significant relationship to actual hearing status (P < 0.05). Although statistically significant sensitivity and specificity rates for identifying hearing loss by iridology were not comparable to those of traditional audiological screening procedures.
Identifying substance misuse in primary care: TAPS Tool compared to the WHO ASSIST.

PubMed

Schwartz, R P; McNeely, J; Wu, L T; Sharma, G; Wahle, A; Cushing, C; Nordeck, C D; Sharma, A; O'Grady, K E; Gryczynski, J; Mitchell, S G; Ali, R L; Marsden, J; Subramaniam, G A

2017-05-01

There is a need for screening and brief assessment instruments to identify primary care patients with substance use problems. This study's aim was to examine the performance of a two-step screening and brief assessment instrument, the TAPS Tool, compared to the WHO ASSIST. Two thousand adult primary care patients recruited from five primary care clinics in four Eastern US states completed the TAPS Tool followed by the ASSIST. The ability of the TAPS Tool to identify moderate- and high-risk use scores on the ASSIST was examined using sensitivity and specificity analyses. The interviewer and self-administered computer tablet versions of the TAPS Tool generated similar results. The interviewer-administered version (at cut-off of 2), had acceptable sensitivity and specificity for high-risk tobacco (0.90 and 0.77) and alcohol (0.87 and 0.80) use. For illicit drugs, sensitivities were >0.82 and specificities >0.92. The TAPS (at a cut-off of 1) had good sensitivity and specificity for moderate-risk tobacco use (0.83 and 0.97) and alcohol (0.83 and 0.74). Among illicit drugs, sensitivity was acceptable for moderate-risk of marijuana (0.71), while it was low for all other illicit drugs and non-medical use of prescription medications. Specificities were 0.97 or higher for all illicit drugs and prescription medications. The TAPS Tool identified adult primary care patients with high-risk ASSIST scores for all substances as well moderate-risk users of tobacco, alcohol, and marijuana, although it did not perform well in identifying patients with moderate-risk use of other drugs or non-medical use of prescription medications. The advantages of the TAPS Tool over the ASSIST are its more limited number of items and focus solely on substance use in the past 3months. Copyright © 2017 Elsevier Inc. All rights reserved.
A decade of individual participant data meta-analyses: A review of current practice.

PubMed

Simmonds, Mark; Stewart, Gavin; Stewart, Lesley

2015-11-01

Individual participant data (IPD) systematic reviews and meta-analyses are often considered to be the gold standard for meta-analysis. In the ten years since the first review into the methodology and reporting practice of IPD reviews was published much has changed in the field. This paper investigates current reporting and statistical practice in IPD systematic reviews. A systematic review was performed to identify systematic reviews that collected and analysed IPD. Data were extracted from each included publication on a variety of issues related to the reporting of IPD review process, and the statistical methods used. There has been considerable growth in the use of "one-stage" methods to perform IPD meta-analyses. The majority of reviews consider at least one covariate other than the primary intervention, either using subgroup analysis or including covariates in one-stage regression models. Random-effects analyses, however, are not often used. Reporting of review methods was often limited, with few reviews presenting a risk-of-bias assessment. Details on issues specific to the use of IPD were little reported, including how IPD were obtained; how data was managed and checked for consistency and errors; and for how many studies and participants IPD were sought and obtained. While the last ten years have seen substantial changes in how IPD meta-analyses are performed there remains considerable scope for improving the quality of reporting for both the process of IPD systematic reviews, and the statistical methods employed in them. It is to be hoped that the publication of the PRISMA-IPD guidelines specific to IPD reviews will improve reporting in this area. Copyright © 2015 Elsevier Inc. All rights reserved.
Comparative transcriptomics reveals similarities and differences between astrocytoma grades.

PubMed

Seifert, Michael; Garbe, Martin; Friedrich, Betty; Mittelbronn, Michel; Klink, Barbara

2015-12-16

Astrocytomas are the most common primary brain tumors distinguished into four histological grades. Molecular analyses of individual astrocytoma grades have revealed detailed insights into genetic, transcriptomic and epigenetic alterations. This provides an excellent basis to identify similarities and differences between astrocytoma grades. We utilized public omics data of all four astrocytoma grades focusing on pilocytic astrocytomas (PA I), diffuse astrocytomas (AS II), anaplastic astrocytomas (AS III) and glioblastomas (GBM IV) to identify similarities and differences using well-established bioinformatics and systems biology approaches. We further validated the expression and localization of Ang2 involved in angiogenesis using immunohistochemistry. Our analyses show similarities and differences between astrocytoma grades at the level of individual genes, signaling pathways and regulatory networks. We identified many differentially expressed genes that were either exclusively observed in a specific astrocytoma grade or commonly affected in specific subsets of astrocytoma grades in comparison to normal brain. Further, the number of differentially expressed genes generally increased with the astrocytoma grade with one major exception. The cytokine receptor pathway showed nearly the same number of differentially expressed genes in PA I and GBM IV and was further characterized by a significant overlap of commonly altered genes and an exclusive enrichment of overexpressed cancer genes in GBM IV. Additional analyses revealed a strong exclusive overexpression of CX3CL1 (fractalkine) and its receptor CX3CR1 in PA I possibly contributing to the absence of invasive growth. We further found that PA I was significantly associated with the mesenchymal subtype typically observed for very aggressive GBM IV. Expression of endothelial and mesenchymal markers (ANGPT2, CHI3L1) indicated a stronger contribution of the micro-environment to the manifestation of the mesenchymal subtype than the tumor biology itself. We further inferred a transcriptional regulatory network associated with specific expression differences distinguishing PA I from AS II, AS III and GBM IV. Major central transcriptional regulators were involved in brain development, cell cycle control, proliferation, apoptosis, chromatin remodeling or DNA methylation. Many of these regulators showed directly underlying DNA methylation changes in PA I or gene copy number mutations in AS II, AS III and GBM IV. This computational study characterizes similarities and differences between all four astrocytoma grades confirming known and revealing novel insights into astrocytoma biology. Our findings represent a valuable resource for future computational and experimental studies.
Comparative transcriptome analyses on silk glands of six silkmoths imply the genetic basis of silk structure and coloration.

PubMed

Dong, Yang; Dai, Fangyin; Ren, Yandong; Liu, Hui; Chen, Lei; Yang, Pengcheng; Liu, Yanqun; Li, Xin; Wang, Wen; Xiang, Hui

2015-03-17

Silk has numerous unique properties that make it a staple of textile manufacturing for several thousand years. However, wider applications of silk in modern have been stalled due to limitations of traditional silk produced by Bombyx mori. While silk is commonly produced by B. mori, several wild non-mulberry silkmoths--especially members of family Saturniidae--produce silk with superior properties that may be useful for wider applications. Further utilization of such silks is hampered by the non-domestication status or limited culturing population of wild silkworms. To date there is insufficient basic genomic or transcriptomic data on these organisms or their silk production. We sequenced and compared the transcriptomes of silk glands of six Saturniidae wild silkmoth species through next-generation sequencing technology, identifying 37758 ~ 51734 silkmoth unigenes, at least 36.3% of which are annotated with an e-value less than 10(-5). Sequence analyses of these unigenes identified a batch of genes specific to Saturniidae that are enriched in growth and development. Analyses of silk proteins including fibroin and sericin indicate intra-genus conservation and inter-genus diversification of silk protein features among the wild silkmoths, e.g., isoelectric points, hydrophilicity profile and amino acid composition in motifs of silk H-fibroin. Interestingly, we identified p25 in two of the silkmoths, which were previously predicted to be absent in Saturniidae. There are rapid evolutionary changes in sericin proteins, which might account for the highly heterogeneity of sericin in Saturniidae silkmoths. Within the six sikmoths, both colored-cocoon silkmoth specific transcripts and differentially expressed genes between the colored-cocoon and non-colored-cocoon silkmoths are significantly enriched in catalytic activity, especially transferase activity, suggesting potentially viable targets for future gene mining or genetic manipulation. Our results characterize novel and potentially valuable gene resources of saturniid silkmoths that may facilitate future genetic improvement and modification of mulberry silkworms. Our results suggest that the disparate features of silk--coloration, retention, strength, etc. --are likely not only due to silk proteins, but also to the environment of silk assembly, and more specifically, that stable silk coloration exhibited by some Saturniidae silkmoths may be attributable to active catalytic progress in pigmentation.
Giardia duodenalis genotypes in domestic and wild animals from Romania identified by PCR-RFLP targeting the gdh gene.

PubMed

Adriana, Gyӧrke; Zsuzsa, Kalmár; Mirabela Oana, Dumitrache; Mircea, Gherman Călin; Viorica, Mircean

2016-02-15

Sixty Giardia duodenalis isolates from domestic (n=49) and wild (n=11) animals (dogs, cats, deers, wolves, raccoon dog and muskrat) were analysed by PCR-RFLP at glutamate dehydrogenase locus (gdh). The isolates were obtained from positive feces samples for Giardia cysts analysed by flotation technique with saturated sodium chloride solution (specific gravity 1.28). Three G. duodenalis genotypes were identified: C (10/60; 16.7%); D (42/60; 70.0%); and E (7/60; 11.7%). In dogs all three genotypes were found, with the following prevalences: 76.9% genotype D (30/39); 23.1% C (9/39); 2.6% genotype E (1/39). One dog was co-infected with C and D genotypes. In cats we identified only G. duodenalis genotype D. Wolves and raccoon dog harbored infection with G. duodenalis genotype D, deers with E type and muskrat C type. This is the first study regarding genotyping of G. duodenalis in cats and wild animals from Romania. To the best of our knowledge, this is the first report of assemblages E in roe deers; assemblage C in wolves and muskrat; and assemblage D in raccoon dog. Copyright © 2016. Published by Elsevier B.V.
Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

PubMed

Savage, Jeanne E; Jansen, Philip R; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien; de Leeuw, Christiaan A; Nagel, Mats; Awasthi, Swapnil; Barr, Peter B; Coleman, Jonathan R I; Grasby, Katrina L; Hammerschlag, Anke R; Kaminski, Jakob A; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A; Trampush, Joey W; Young, Hannah; Zabaneh, Delilah; Hägg, Sara; Hansell, Narelle K; Karlsson, Ida K; Linnarsson, Sten; Montgomery, Grant W; Muñoz-Manchado, Ana B; Quinlan, Erin B; Schumann, Gunter; Skene, Nathan G; Webb, Bradley T; White, Tonya; Arking, Dan E; Avramopoulos, Dimitrios; Bilder, Robert M; Bitsios, Panos; Burdick, Katherine E; Cannon, Tyrone D; Chiba-Falek, Ornit; Christoforou, Andrea; Cirulli, Elizabeth T; Congdon, Eliza; Corvin, Aiden; Davies, Gail; Deary, Ian J; DeRosse, Pamela; Dickinson, Dwight; Djurovic, Srdjan; Donohoe, Gary; Conley, Emily Drabant; Eriksson, Johan G; Espeseth, Thomas; Freimer, Nelson A; Giakoumaki, Stella; Giegling, Ina; Gill, Michael; Glahn, David C; Hariri, Ahmad R; Hatzimanolis, Alex; Keller, Matthew C; Knowles, Emma; Koltai, Deborah; Konte, Bettina; Lahti, Jari; Le Hellard, Stephanie; Lencz, Todd; Liewald, David C; London, Edythe; Lundervold, Astri J; Malhotra, Anil K; Melle, Ingrid; Morris, Derek; Need, Anna C; Ollier, William; Palotie, Aarno; Payton, Antony; Pendleton, Neil; Poldrack, Russell A; Räikkönen, Katri; Reinvang, Ivar; Roussos, Panos; Rujescu, Dan; Sabb, Fred W; Scult, Matthew A; Smeland, Olav B; Smyrnis, Nikolaos; Starr, John M; Steen, Vidar M; Stefanis, Nikos C; Straub, Richard E; Sundet, Kjetil; Tiemeier, Henning; Voineskos, Aristotle N; Weinberger, Daniel R; Widen, Elisabeth; Yu, Jin; Abecasis, Goncalo; Andreassen, Ole A; Breen, Gerome; Christiansen, Lene; Debrabant, Birgit; Dick, Danielle M; Heinz, Andreas; Hjerling-Leffler, Jens; Ikram, M Arfan; Kendler, Kenneth S; Martin, Nicholas G; Medland, Sarah E; Pedersen, Nancy L; Plomin, Robert; Polderman, Tinca J C; Ripke, Stephan; van der Sluis, Sophie; Sullivan, Patrick F; Vrieze, Scott I; Wright, Margaret J; Posthuma, Danielle

2018-06-25

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Pathway Analysis in Attention Deficit Hyperactivity Disorder: An Ensemble Approach

PubMed Central

Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth

2016-01-01

Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. PMID:27004716
The Survey of Treatment Entry Pressures (STEP): identifying client's reasons for entering substance abuse treatment.

PubMed

Dugosh, Karen Leggett; Festinger, David S; Lynch, Kevin G; Marlowe, Douglas B

2014-10-01

Systematically identifying reasons that clients enter substance abuse treatment may allow clinicians to immediately focus on issues of greatest relevance to the individual and enhance treatment engagement. We developed the Survey of Treatment Entry Pressures (STEP) to identify the specific factors that precipitated an individual's treatment entry. The instrument contains 121 items from 6 psychosocial domains (i.e., family, financial, social, medical, psychiatric, legal). The current study examined the STEP's psychometric properties. A total of 761 participants from various treatment settings and modalities completed the STEP prior to treatment admission and 4-7 days later. Analyses were performed to examine the instrument's psychometric properties including item response rates, test-retest reliability, internal consistency, and factor structure. The items displayed adequate test-retest reliability and internal consistency within each psychosocial domain. Generally, results from exploratory and confirmatory factor analyses support a 2-factor structure reflecting type of reinforcement schedule. The study provides preliminary support for the psychometric properties of the STEP. The STEP may provide a reliable way for clinicians to characterize and capitalize on a client's treatment motivation early on which may serve to improve treatment retention and therapeutic outcomes. © 2014 Wiley Periodicals, Inc.
Brachypodium distachyon as a new model system for understanding iron homeostasis in grasses: phylogenetic and expression analysis of Yellow Stripe-Like (YSL) transporters

PubMed Central

Yordem, Burcu K.; Conte, Sarah S.; Ma, Jian Feng; Yokosho, Kengo; Vasques, Kenneth A.; Gopalsamy, Srinivasa N.; Walker, Elsbeth L.

2011-01-01

Background and Aims Brachypodium distachyon is a temperate grass with a small stature, rapid life cycle and completely sequenced genome that has great promise as a model system to study grass-specific traits for crop improvement. Under iron (Fe)-deficient conditions, grasses synthesize and secrete Fe(III)-chelating agents called phytosiderophores (PS). In Zea mays, Yellow Stripe1 (ZmYS1) is the transporter responsible for the uptake of Fe(III)–PS complexes from the soil. Some members of the family of related proteins called Yellow Stripe-Like (YSL) have roles in internal Fe translocation of plants, while the function of other members remains uninvestigated. The aim of this study is to establish brachypodium as a model system to study Fe homeostasis in grasses, identify YSL proteins in brachypodium and maize, and analyse their expression profiles in brachypodium in response to Fe deficiency. Methods The YSL family of proteins in brachypodium and maize were identified based on sequence similarity to ZmYS1. Expression patterns of the brachypodium YSL genes (BdYSL genes) were determined by quantitative RT–PCR under Fe-deficient and Fe-sufficient conditions. The types of PS secreted, and secretion pattern of PS in brachypodium were analysed by high-performance liquid chromatography. Key Results Eighteen YSL family members in maize and 19 members in brachypodium were identified. Phylogenetic analysis revealed that some YSLs group into a grass-specific clade. The Fe status of the plant can regulate expression of brachypodium YSL genes in both shoots and roots. 3-Hydroxy-2′-deoxymugineic acid (HDMA) is the dominant type of PS secreted by brachypodium, and its secretion is diurnally regulated. Conclusions PS secretion by brachypodium parallels that of related crop species such as barley and wheat. A single grass species-specific YSL clade is present, and expression of the BdYSL members of this clade could not be detected in shoots or roots, suggesting grass-specific functions in reproductive tissues. Finally, the Fe-responsive expression profiles of several YSLs suggest roles in Fe homeostasis. PMID:21831857
The trucker strain monitor: an occupation-specific questionnaire measuring psychological job strain.

PubMed

De Croon, E M; Blonk, R W; Van der Beek, J; Frings-Dresen, M H

2001-08-01

To develop and validate a short and user-friendly questionnaire measuring psychological job strain in truck drivers. In cooperation with an occupational physician in the Dutch road transport industry we developed items on the basis of face validity and information of existing questionnaires on the subject. These items were pilot-tested, by means of interviews, in 15 truck drivers. Study I examined the factorial structure of the initial 30-item trucker strain monitor (TSM) in a sample of 153 truck drivers. Subsequently, number of items per factor was reduced on the basis of reliability analyses (Cronbach's alpha). Study II examined construct and criterion validity of the TSM in a randomly selected group of 2,000 truck drivers, of whom 1,111 participated (adjusted response = 63%). Additionally, sensitivity and specificity were assessed by examining the ability of the TSM to identify truck drivers with or without self-reported sickness absence in the past 12 months because of psychological complaints. Factor analyses of the initial 30-item TSM revealed a two-factor solution. Item reduction resulted in a six-item work-related fatigue scale and four-item sleeping problems scale with high internal consistency. Results of study II confirmed the internal consistency of the TSM scales and provided support for construct and criterion validity. The composite, work-related fatigue, and sleeping problems scale had a sensitivity of 83%, 80% and 71% respectively, in identifying truck drivers with prior sickness absence because of psychological complaints. Specificity rates were 72%, 73% and 72% respectively. Despite methodological limitations, the results suggest that the TSM is a reliable and valid indicator of psychological job strain in truck drivers. In particular, the composite and work-related fatigue scale identified drivers with prior absenteeism because of psychological complaints, quite accurately. Future longitudinal research in specific sub-groups of truck drivers including both self-reported and objective psychological health measures should evidence whether (1) the distinction between two indicators of psychological job strain is useful, and whether (2) the TSM can be used in screening out truck drivers at risk of developing psychological health problems.
Does Treatment of the Tibia Matter in Bipolar Chondral Defects of the Knee? Clinical Outcomes with Greater Than 2 Years Follow-up.

PubMed

Hannon, Charles P; Weber, Alexander E; Gitelis, Matthew; Meyer, Maximillian A; Yanke, Adam B; Cole, Brian J

2018-04-01

To compare the osteochondral allograft (OCA) outcomes of bipolar defects with isolated femoral defects and to investigate the optimal treatment of bipolar defects by comparing femoral OCA with tibial debridement to femoral OCA and tibial microfracture. A series of patients with 2-year follow-up from March 2004 to September 2015 after femoral OCA for bipolar chondral defects was identified. Group 1 contained patients with tibial defects treated with debridement and group 2 contained patients with microfractured tibial defects. A third group (group 3) with isolated femoral defects treated with OCA was identified and matched by gender, body mass index (BMI), laterality, and OCA size to groups 1 and 2. Patient-specific, defect-specific, intraoperative, and postoperative data including patient-reported outcomes were collected on all patients. The study groups were compared using analyses of variance, paired sample t tests, and χ-square analyses. Thirty-six patients who had femoral OCA for bipolar lesions were identified with 20 patients in group 1 and 16 patients in group 2. Group 3 had 20 patients. There were no differences between the 3 groups in terms of gender (P = .616), BMI (P = .271), number of previous surgeries (P = .451), femoral or tibial defect size (P = .296), and OCA size (P = .981). Preoperative to postoperative patient-reported clinical outcomes (PROs) revealed statistical and clinically meaningful improvement in all 3 groups, but did not differ between groups. Patient-specific and defect-specific factors did not correlate with PROs. The graft survivorship for group 1 was 85% at 4.5 years, 100% for group 2 at 2.5 years, and 95% for group 3 at 3.8 years. Regardless of tibial treatment, patients with bipolar defects treated with femoral OCA have clinically meaningful improvements in PROs and excellent graft survivorship comparable to isolated femoral OCAs at more than 2 years. Level III, case-control study. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
QA/QC in the laboratory

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

Hood, F.C.

1992-05-01

Quality assurance and quality control (QA/QC) of analytical chemistry laboratory activities are essential to the validity and usefulness of resultant data. However, in themselves, conventional QA/QC measures will not always ensure that fraudulent data are not generated. Conventional QA/QC measures are based on the assumption that work will be done in good faith; to assure against fraudulent practices, QA/QC measures must be tailored to specific analyses protocols in anticipation of intentional misapplication of those protocols. Application of specific QA/QC measures to ensure against fraudulent practices result in an increased administrative burden being placed on the analytical process; accordingly, in keepingmore » with graded QA philosophy, data quality objectives must be used to identify specific points of concern for special control to minimize the administrative impact.« less
QA/QC in the laboratory. Session F

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

Hood, F.C.

1992-05-01

Quality assurance and quality control (QA/QC) of analytical chemistry laboratory activities are essential to the validity and usefulness of resultant data. However, in themselves, conventional QA/QC measures will not always ensure that fraudulent data are not generated. Conventional QA/QC measures are based on the assumption that work will be done in good faith; to assure against fraudulent practices, QA/QC measures must be tailored to specific analyses protocols in anticipation of intentional misapplication of those protocols. Application of specific QA/QC measures to ensure against fraudulent practices result in an increased administrative burden being placed on the analytical process; accordingly, in keepingmore » with graded QA philosophy, data quality objectives must be used to identify specific points of concern for special control to minimize the administrative impact.« less

Trans-Homolog Interactions Facilitating Paramutation in Maize

PubMed Central

2015-01-01

Paramutations represent locus-specific trans-homolog interactions affecting the heritable silencing properties of endogenous alleles. Although examples of paramutation are well studied in maize (Zea mays), the responsible mechanisms remain unclear. Genetic analyses indicate roles for plant-specific DNA-dependent RNA polymerases that generate small RNAs, and current working models hypothesize that these small RNAs direct heritable changes at sequences often acting as transcriptional enhancers. Several studies have defined specific sequences that mediate paramutation behaviors, and recent results identify a diversity of DNA-dependent RNA polymerase complexes operating in maize. Other reports ascribe broader roles for some of these complexes in normal genome function. This review highlights recent research to understand the molecular mechanisms of paramutation and examines evidence relevant to small RNA-based modes of transgenerational epigenetic inheritance. PMID:26149572
Applicability of IHE/Continua components for PHR systems: learning from experiences.

PubMed

Urbauer, Philipp; Sauermann, Stefan; Frohner, Matthias; Forjan, Mathias; Pohn, Birgit; Mense, Alexander

2015-04-01

Capturing personal health data using smartphones, PCs or other devices, and the reuse of the data in personal health records (PHR) is becoming more and more attractive for modern health-conscious populations. This paper analyses interoperability specifications targeting standards-based communication of computer systems and personal health devices (e.g. blood pressure monitor) in healthcare from initiatives like Integrating the Healthcare Enterprise (IHE) and Continua Health Alliance driven by industry and healthcare professionals. Furthermore it identifies certain contradictions and gaps in the specifications and suggests possible solutions. Despite these shortcomings, the specifications allow fully functional implementations of PHR systems. Henceforth, both big business and small and medium-sized enterprises (SMEs) can actively contribute to the widespread use of large-scale interoperable PHR systems. Copyright © 2013 Elsevier Ltd. All rights reserved.
Biochemical phenotypes to discriminate microbial subpopulations and improve outbreak detection.

PubMed

Galar, Alicia; Kulldorff, Martin; Rudnick, Wallis; O'Brien, Thomas F; Stelling, John

2013-01-01

Clinical microbiology laboratories worldwide constitute an invaluable resource for monitoring emerging threats and the spread of antimicrobial resistance. We studied the growing number of biochemical tests routinely performed on clinical isolates to explore their value as epidemiological markers. Microbiology laboratory results from January 2009 through December 2011 from a 793-bed hospital stored in WHONET were examined. Variables included patient location, collection date, organism, and 47 biochemical and 17 antimicrobial susceptibility test results reported by Vitek 2. To identify biochemical tests that were particularly valuable (stable with repeat testing, but good variability across the species) or problematic (inconsistent results with repeat testing), three types of variance analyses were performed on isolates of K. pneumonia: descriptive analysis of discordant biochemical results in same-day isolates, an average within-patient variance index, and generalized linear mixed model variance component analysis. 4,200 isolates of K. pneumoniae were identified from 2,485 patients, 32% of whom had multiple isolates. The first two variance analyses highlighted SUCT, TyrA, GlyA, and GGT as "nuisance" biochemicals for which discordant within-patient test results impacted a high proportion of patient results, while dTAG had relatively good within-patient stability with good heterogeneity across the species. Variance component analyses confirmed the relative stability of dTAG, and identified additional biochemicals such as PHOS with a large between patient to within patient variance ratio. A reduced subset of biochemicals improved the robustness of strain definition for carbapenem-resistant K. pneumoniae. Surveillance analyses suggest that the reduced biochemical profile could improve the timeliness and specificity of outbreak detection algorithms. The statistical approaches explored can improve the robust recognition of microbial subpopulations with routinely available biochemical test results, of value in the timely detection of outbreak clones and evolutionarily important genetic events.
Spatial variation of volcanic rock geochemistry in the Virunga Volcanic Province: Statistical analysis of an integrated database

NASA Astrophysics Data System (ADS)

Barette, Florian; Poppe, Sam; Smets, Benoît; Benbakkar, Mhammed; Kervyn, Matthieu

2017-10-01

We present an integrated, spatially-explicit database of existing geochemical major-element analyses available from (post-) colonial scientific reports, PhD Theses and international publications for the Virunga Volcanic Province, located in the western branch of the East African Rift System. This volcanic province is characterised by alkaline volcanism, including silica-undersaturated, alkaline and potassic lavas. The database contains a total of 908 geochemical analyses of eruptive rocks for the entire volcanic province with a localisation for most samples. A preliminary analysis of the overall consistency of the database, using statistical techniques on sets of geochemical analyses with contrasted analytical methods or dates, demonstrates that the database is consistent. We applied a principal component analysis and cluster analysis on whole-rock major element compositions included in the database to study the spatial variation of the chemical composition of eruptive products in the Virunga Volcanic Province. These statistical analyses identify spatially distributed clusters of eruptive products. The known geochemical contrasts are highlighted by the spatial analysis, such as the unique geochemical signature of Nyiragongo lavas compared to other Virunga lavas, the geochemical heterogeneity of the Bulengo area, and the trachyte flows of Karisimbi volcano. Most importantly, we identified separate clusters of eruptive products which originate from primitive magmatic sources. These lavas of primitive composition are preferentially located along NE-SW inherited rift structures, often at distance from the central Virunga volcanoes. Our results illustrate the relevance of a spatial analysis on integrated geochemical data for a volcanic province, as a complement to classical petrological investigations. This approach indeed helps to characterise geochemical variations within a complex of magmatic systems and to identify specific petrologic and geochemical investigations that should be tackled within a study area.
Sensitivity and specificity of the American College of Rheumatology 1987 criteria for the diagnosis of rheumatoid arthritis according to disease duration: a systematic literature review and meta-analysis.

PubMed

Banal, F; Dougados, M; Combescure, C; Gossec, L

2009-07-01

To evaluate the ability of the widely used ACR set of criteria (both list and tree format) to diagnose RA compared with expert opinion according to disease duration. A systematic literature review was conducted in PubMed and Embase databases. All articles reporting the prevalence of RA according to ACR criteria and expert opinion in cohorts of early (<1 year duration) or established (>1 year) arthritis were analysed to calculate the sensitivity and specificity of ACR 1987 criteria against the "gold standard" (expert opinion). A meta-analysis using a summary receiver operating characteristic (SROC) curve was performed and pooled sensitivity and specificity were calculated with confidence intervals. Of 138 publications initially identified, 19 were analysable (total 7438 patients, 3883 RA). In early arthritis, pooled sensitivity and specificity of the ACR set of criteria were 77% (68% to 84%) and 77% (68% to 84%) in the list format versus 80% (72% to 88%) and 33% (24% to 43%) in the tree format. In established arthritis, sensitivity and specificity were respectively 79% (71% to 85%) and 90% (84% to 94%) versus 80% (71% to 85%) and 93% (86% to 97%). The SROC meta-analysis confirmed the statistically significant differences, suggesting that diagnostic performances of ACR list criteria are better in established arthritis. The specificity of ACR 1987 criteria in early RA is low, and these criteria should not be used as diagnostic tools. Sensitivity and specificity in established RA are higher, which reflects their use as classification criteria gold standard.
Evidence for localised HIV related micro-epidemics associated with the decentralised provision of antiretroviral treatment in rural South Africa: a spatio-temporal analysis of changing mortality patterns (2007-2010).

PubMed

Mee, Paul; Collinson, Mark A; Madhavan, Sangeetha; Root, Elisabeth Dowling; Tollman, Stephen M; Byass, Peter; Kahn, Kathleen

2014-06-01

In this study we analysed the spatial and temporal changes in patterns of mortality over a period when antiretroviral therapy (ART) was rolled out in a rural region of north-eastern South Africa. Previous studies have identified localised concentrated HIV related sub-epidemics and recommended that micro-level analyses be carried out in order to direct focused interventions. Data from an ongoing health and socio-demographic surveillance study was used in the analysis. The follow-up was divided into two periods, 2007-2008 and 2009-2010, representing the times immediately before and after the effects on mortality of the decentralised ART provision from a newly established local health centre would be expected to be evident. The study population at the start of the analysis was approximately 73 000 individuals. Data were aggregated by village and also using a 2 × 2 km grid. We identified villages, grid squares and regions in the site where mortality rates within each time period or rate ratios between the periods differed significantly from the overall trends. We used clustering techniques to identify cause-specific mortality hotspots. Comparing the two periods, there was a 30% decrease in age and gender standardised adult HIV-related and TB (HIV/TB) mortality with no change in mortality due to other causes. There was considerable spatial heterogeneity in the mortality patterns. Areas separated by 2 to 4 km with very different epidemic trajectories were identified. There was evidence that the impact of ART in reducing HIV/TB mortality was greatest in communities with higher mortality rates in the earlier period. This study shows the value of conducting high resolution spatial analyses in order to understand how local micro-epidemics contribute to changes seen over a wider area. Such analyses can support targeted interventions.
Investigation of the mechanical behaviour of the foot skin.

PubMed

Fontanella, C G; Carniel, E L; Forestiero, A; Natali, A N

2014-11-01

The aim of this work was to provide computational tools for the characterization of the actual mechanical behaviour of foot skin, accounting for results from experimental testing and histological investigation. Such results show the typical features of skin mechanics, such as anisotropic configuration, almost incompressible behaviour, material and geometrical non linearity. The anisotropic behaviour is mainly determined by the distribution of collagen fibres along specific directions, usually identified as cleavage lines. To evaluate the biomechanical response of foot skin, a refined numerical model of the foot is developed. The overall mechanical behaviour of the skin is interpreted by a fibre-reinforced hyperelastic constitutive model and the orientation of the cleavage lines is implemented by a specific procedure. Numerical analyses that interpret typical loading conditions of the foot are performed. The influence of fibres orientation and distribution on skin mechanics is outlined also by a comparison with results using an isotropic scheme. A specific constitutive formulation is provided to characterize the mechanical behaviour of foot skin. The formulation is applied within a numerical model of the foot to investigate the skin functionality during typical foot movements. Numerical analyses developed accounting for the actual anisotropic configuration of the skin show lower maximum principal stress fields than results from isotropic analyses. The developed computational models provide reliable tools for the investigation of foot tissues functionality. Furthermore, the comparison between numerical results from anisotropic and isotropic models shows the optimal configuration of foot skin. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Comprehensive Logic Based Analyses of Toll-Like Receptor 4 Signal Transduction Pathway

PubMed Central

Padwal, Mahesh Kumar; Sarma, Uddipan; Saha, Bhaskar

2014-01-01

Among the 13 TLRs in the vertebrate systems, only TLR4 utilizes both Myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adapter interferon-β-inducing Factor (TRIF) adaptors to transduce signals triggering host-protective immune responses. Earlier studies on the pathway combined various experimental data in the form of one comprehensive map of TLR signaling. But in the absence of adequate kinetic parameters quantitative mathematical models that reveal emerging systems level properties and dynamic inter-regulation among the kinases/phosphatases of the TLR4 network are not yet available. So, here we used reaction stoichiometry-based and parameter independent logical modeling formalism to build the TLR4 signaling network model that captured the feedback regulations, interdependencies between signaling kinases and phosphatases and the outcome of simulated infections. The analyses of the TLR4 signaling network revealed 360 feedback loops, 157 negative and 203 positive; of which, 334 loops had the phosphatase PP1 as an essential component. The network elements' interdependency (positive or negative dependencies) in perturbation conditions such as the phosphatase knockout conditions revealed interdependencies between the dual-specific phosphatases MKP-1 and MKP-3 and the kinases in MAPK modules and the role of PP2A in the auto-regulation of Calmodulin kinase-II. Our simulations under the specific kinase or phosphatase gene-deficiency or inhibition conditions corroborated with several previously reported experimental data. The simulations to mimic Yersinia pestis and E. coli infections identified the key perturbation in the network and potential drug targets. Thus, our analyses of TLR4 signaling highlights the role of phosphatases as key regulatory factors in determining the global interdependencies among the network elements; uncovers novel signaling connections; identifies potential drug targets for infections. PMID:24699232
Defining Chronic Cough: A Systematic Review of the Epidemiological Literature

PubMed Central

Song, Woo-Jung; Chang, Yoon-Seok; Faruqi, Shoaib; Kang, Min-Koo; Kim, Ju-Young; Kang, Min-Gyu; Kim, Sujeong; Jo, Eun-Jung; Lee, Seung-Eun; Kim, Min-Hye; Plevkova, Jana; Park, Heung-Woo

2016-01-01

Purpose Recent evidence suggests a global burden of chronic cough in general populations. However, the definitions vary greatly among epidemiological studies, and none have been validated for clinical relevance. We aimed to examine previous epidemiological definitions in detail and explore the operational characteristics. Methods A systematic review was conducted for epidemiological surveys that reported the prevalence of chronic cough in general adult populations during the years 1980 to 2013. A literature search was performed on Pubmed and Embase without language restriction. Epidemiological definitions for chronic cough were classified according to their components, such as cutoff duration. Meta-analyses were performed for the male-to-female ratio of chronic cough prevalence to explore operational characteristics of epidemiological definitions. Results A total of 70 studies were included in the systematic review. The most common epidemiological definition was identified as 'cough ≥3 months' duration without specification of phlegm (n=50); however, it conflicted with the cutoff duration in current clinical guidelines (cough ≥8 weeks). Meta-analyses were performed for the male-to-female ratio of chronic cough among 28 studies that reported sex-specific prevalence using the most common definition. The pooled male-to-female odds ratio was 1.26 (95% confidence interval 0.92-1.73) with significant heterogeneity (I2=96%, P<0.001), which was in contrast to clinical observations of female predominance from specialist clinics. Subgroup analyses did not reverse the ratio or reduce the heterogeneity. Conclusions This study identified major issues in defining chronic cough in future epidemiological studies. The conflict between epidemiological and clinical diagnostic criteria needs to be resolved. The unexpected difference in the gender predominance between the community and clinics warrants further studies. Clinical validation of the existing definition is required. PMID:26739408
External validity of a hierarchical dimensional model of child and adolescent psychopathology: Tests using confirmatory factor analyses and multivariate behavior genetic analyses.

PubMed

Waldman, Irwin D; Poore, Holly E; van Hulle, Carol; Rathouz, Paul J; Lahey, Benjamin B

2016-11-01

Several recent studies of the hierarchical phenotypic structure of psychopathology have identified a General psychopathology factor in addition to the more expected specific Externalizing and Internalizing dimensions in both youth and adult samples and some have found relevant unique external correlates of this General factor. We used data from 1,568 twin pairs (599 MZ & 969 DZ) age 9 to 17 to test hypotheses for the underlying structure of youth psychopathology and the external validity of the higher-order factors. Psychopathology symptoms were assessed via structured interviews of caretakers and youth. We conducted phenotypic analyses of competing structural models using Confirmatory Factor Analysis and used Structural Equation Modeling and multivariate behavior genetic analyses to understand the etiology of the higher-order factors and their external validity. We found that both a General factor and specific Externalizing and Internalizing dimensions are necessary for characterizing youth psychopathology at both the phenotypic and etiologic levels, and that the 3 higher-order factors differed substantially in the magnitudes of their underlying genetic and environmental influences. Phenotypically, the specific Externalizing and Internalizing dimensions were slightly negatively correlated when a General factor was included, which reflected a significant inverse correlation between the nonshared environmental (but not genetic) influences on Internalizing and Externalizing. We estimated heritability of the general factor of psychopathology for the first time. Its moderate heritability suggests that it is not merely an artifact of measurement error but a valid construct. The General, Externalizing, and Internalizing factors differed in their relations with 3 external validity criteria: mother's smoking during pregnancy, parent's harsh discipline, and the youth's association with delinquent peers. Multivariate behavior genetic analyses supported the external validity of the 3 higher-order factors by suggesting that the General, Externalizing, and Internalizing factors were correlated with peer delinquency and parent's harsh discipline for different etiologic reasons. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Aspirin in the Treatment of Cancer: Reductions in Metastatic Spread and in Mortality: A Systematic Review and Meta-Analyses of Published Studies

PubMed Central

Elwood, Peter C.

2016-01-01

Background Low-dose aspirin has been shown to reduce the incidence of cancer, but its role in the treatment of cancer is uncertain. Objectives We conducted a systematic search of the scientific literature on aspirin taken by patients following a diagnosis of cancer, together with appropriate meta-analyses. Methods Searches were completed in Medline and Embase in December 2015 using a pre-defined search strategy. References and abstracts of all the selected papers were scanned and expert colleagues were contacted for additional studies. Two reviewers applied pre-determined eligibility criteria (cross-sectional, cohort and controlled studies, and aspirin taken after a diagnosis of cancer), assessed study quality and extracted data on cancer cause-specific deaths, overall mortality and incidence of metastases. Random effects meta-analyses and planned sub-group analyses were completed separately for observational and experimental studies. Heterogeneity and publication bias were assessed in sensitivity analyses and appropriate omissions made. Papers were examined for any reference to bleeding and authors of the papers were contacted and questioned. Results Five reports of randomised trials were identified, together with forty two observational studies: sixteen on colorectal cancer, ten on breast and ten on prostate cancer mortality. Pooling of eleven observational reports of the effect of aspirin on cause-specific mortality from colon cancer, after the omission of one report identified on the basis of sensitivity analyses, gave a hazard ratio (HR) of 0.76 (95% CI 0.66, 0.88) with reduced heterogeneity (P = 0.04). The cause specific mortality in five reports of patients with breast cancer showed significant heterogeneity (P<0.0005) but the omission of one outlying study reduced heterogeneity (P = 0.19) and led to an HR = 0.87 (95% CI 0.69, 1.09). Heterogeneity between nine studies of prostate cancer was significant, but again, the omission of one study led to acceptable homogeneity (P = 0.26) and an overall HR = 0.89 (95% CI 0.79–0.99). Six single studies of other cancers suggested reductions in cause specific mortality by aspirin, and in five the effect is statistically significant. There were no significant differences between the pooled HRs for the three main cancers and after the omission of three reports already identified in sensitivity analyses heterogeneity was removed and revealed an overall HR of 0.83 (95% CI 0.76–0.90). A mutation of PIK3CA was present in about 20% of patients, and appeared to explain most of the reduction in colon cancer mortality by aspirin. Data were not adequate to examine the importance of this or any other marker in the effect of aspirin in the other cancers. On bleeding attributable to aspirin two reports stated that there had been no side effect or bleeding attributable to aspirin. Authors on the other reports were written to and 21 replied stating that no data on bleeding were available. Conclusions and Implications The study highlights the need for randomised trials of aspirin treatment in a variety of cancers. While these are awaited there is an urgent need for evidence from observational studies of aspirin and the less common cancers, and for more evidence of the relevance of possible bio-markers of the aspirin effect on a wide variety of cancers. In the meantime it is urged that patients in whom a cancer is diagnosed should be given details of this research, together with its limitations, to enable each to make an informed decision as to whether or not to take low-dose aspirin. Systematic Review Protocol Number CRD42015014145 PMID:27096951
Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

PubMed Central

Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

2016-01-01

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465
Identifying at-risk children at school entry: the usefulness of multibehavioral problem profiles.

PubMed

Flanagan, Kelly S; Bierman, Karen L; Kam, Chi-Ming

2003-09-01

Found that 1st-grade teacher ratings of aggressive, hyperactive-inattentive, and low levels of prosocial behaviors made unique contributions to the prediction of school outcomes (measured 2 years later) for 755 children. Person-oriented analyses compared the predictive utility of 5 screening strategies based on child problem profiles to identify children at risk for school problems. A broad screening strategy, in which children with elevations in any 1 of the 3 behavior problem dimensions were identified as "at-risk," showed lower specificity but superior sensitivity, odds ratios, and overall accuracy in the prediction of school outcomes than the other screening strategies that were more narrowly focused or were based on a total problem score. Results are discussed in terms of implications for the screening and design of preventive interventions.
Domestic violence and employment: a qualitative study.

PubMed

Swanberg, Jennifer E; Logan, T K

2005-01-01

This exploratory study sought to gather detailed information about how domestic violence affects women's employment, specifically to identify the types of job interference tactics used by abusers and their consequences on women's job performance; identify and understand the context associated with disclosure about victimization to employers and coworkers; and identify the supports offered to employees after disclosure. Qualitative analyses, guided by grounded theory, revealed that perpetrators exhibited job interference behaviors before, during, and after work. Abuser tactics reduced women's job performance as measured by absenteeism, tardiness, job leavings, and terminations. Among women who disclosed victimization to employers, informal and formal job supports were offered. Workplace supports led to short-term job retention, but fear and safety issues mitigated employers' attempts to retain workers. ((c) 2005 APA, all rights reserved).
A genome-wide association study of corneal astigmatism: The CREAM Consortium

PubMed Central

Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W.V.; Hysi, Pirro G.; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R.; Jonas, Jost B.; Mitchell, Paul; Hammond, Christopher J.; Höhn, René; Baird, Paul N.; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A.; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C.W.; Bailey-Wilson, Joan E.

2018-01-01

Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism. PMID:29422769
Advanced 3-V semiconductor technology assessment. [space communications

NASA Technical Reports Server (NTRS)

Nowogrodzki, M.

1983-01-01

Against a background of an extensive survey of the present state of the art in the field of III-V semiconductors for operation at microwave frequencies (or gigabit rate speeds), likely requirements of future space communications systems are identified, competing technologies and physical device limitations are discussed, and difficulties in implementing emerging technologies are projected. On the basis of these analyses, specific research and development programs required for the development of future systems components are recommended.
A Framework for Integrating Environmental Justice in Regulatory Analysis

PubMed Central

Nweke, Onyemaechi C.

2011-01-01

With increased interest in integrating environmental justice into the process for developing environmental regulations in the United States, analysts and decision makers are confronted with the question of what methods and data can be used to assess disproportionate environmental health impacts. However, as a first step to identifying data and methods, it is important that analysts understand what information on equity impacts is needed for decision making. Such knowledge originates from clearly stated equity objectives and the reflection of those objectives throughout the analytical activities that characterize Regulatory Impact Analysis (RIA), a process that is traditionally used to inform decision making. The framework proposed in this paper advocates structuring analyses to explicitly provide pre-defined output on equity impacts. Specifically, the proposed framework emphasizes: (a) defining equity objectives for the proposed regulatory action at the onset of the regulatory process, (b) identifying specific and related sub-objectives for key analytical steps in the RIA process, and (c) developing explicit analytical/research questions to assure that stated sub-objectives and objectives are met. In proposing this framework, it is envisioned that information on equity impacts informs decision-making in regulatory development, and that this is achieved through a systematic and consistent approach that assures linkages between stated equity objectives, regulatory analyses, selection of policy options, and the design of compliance and enforcement activities. PMID:21776235
Sperm flagella protein components: Human meichroacidin constructed by the membrane occupation and recognition nexus motif

PubMed Central

MATSUOKA, YASUHIRO; NISHIMURA, HIROMI; NUMAZAWA, KAHORI; TSUCHIDA, JUNJI; MIYAGAWA, YASUSHI; TSUJIMURA, AKIRA; MATSUMIYA, KIYOMI; OKUYAMA, AKIHIKO; NISHIMUNE, YOSHITAKE

2005-01-01

Background and Aims: In a previous study, the authors of the present study cloned mouse meichroacidin (MCA), which is expressed in stages of spermatogenesis from pachytene spermatocytes through round spermatid germ cells. MCA protein contains the membrane occupation and recognition nexus (MORN) motif and localizes to a male meiotic metaphase chromosome. Recently, a MCA homolog of carp (Cyprinus carpio), MORN motif‐containing sperm‐specific axonemal protein (MSAP), was reportedly identified and localized in sperm flagella. Present knowledge of human spermiogenesis requires the identification of proteins in human sperm. The present study identified the human orthologue of MCA. Methods: Colony hybridization using a human testis plasmid cDNA library was carried out to clone human MCA (h‐MCA) cDNA. Northern blot, Western blot, and immunohistochemical analyses were carried out. Results: h‐MCA was found to be specifically expressed in the testes. The h‐MCA amino acid sequence shared 79.8% identity with mouse MCA and contained MORN motifs. h‐MCA localized in the sperm flagellum and basal body, as does MSAP in carp. Conclusion: Expression and localization analyses showed that h‐MCA is a component of the sperm flagellum and basal body and might play an important role in the development of the sperm flagellum in humans. (Reprod Med Biol 2005; 4: 213–219) PMID:29699225
A Modified ABCDE Model of Flowering in Orchids Based on Gene Expression Profiling Studies of the Moth Orchid Phalaenopsis aphrodite

PubMed Central

Lee, Ann-Ying; Chen, Chun-Yi; Chang, Yao-Chien Alex; Chao, Ya-Ting; Shih, Ming-Che

2013-01-01

Previously we developed genomic resources for orchids, including transcriptomic analyses using next-generation sequencing techniques and construction of a web-based orchid genomic database. Here, we report a modified molecular model of flower development in the Orchidaceae based on functional analysis of gene expression profiles in Phalaenopsis aphrodite (a moth orchid) that revealed novel roles for the transcription factors involved in floral organ pattern formation. Phalaenopsis orchid floral organ-specific genes were identified by microarray analysis. Several critical transcription factors including AP3, PI, AP1 and AGL6, displayed distinct spatial distribution patterns. Phylogenetic analysis of orchid MADS box genes was conducted to infer the evolutionary relationship among floral organ-specific genes. The results suggest that gene duplication MADS box genes in orchid may have resulted in their gaining novel functions during evolution. Based on these analyses, a modified model of orchid flowering was proposed. Comparison of the expression profiles of flowers of a peloric mutant and wild-type Phalaenopsis orchid further identified genes associated with lip morphology and peloric effects. Large scale investigation of gene expression profiles revealed that homeotic genes from the ABCDE model of flower development classes A and B in the Phalaenopsis orchid have novel functions due to evolutionary diversification, and display differential expression patterns. PMID:24265826
Identification of New and Distinctive Exposures from Little Cigars

PubMed Central

Klupinski, Theodore P.; Strozier, Erich D.; Friedenberg, David A.; Brinkman, Marielle C.; Gordon, Sydney M.; Clark, Pamela I.

2016-01-01

Little cigar mainstream smoke is less well-characterized than cigarette mainstream smoke in terms of chemical composition. This study compared four popular little cigar products against four popular cigarette products to determine compounds that are either unique to or more abundant in little cigars. These compounds are categorized as new or distinctive exposures, respectively. Total particulate matter samples collected from machine-generated mainstream smoke were extracted with methylene chloride, and the extracts were analyzed using two-dimensional gas chromatography–time-of-flight mass spectrometry. The data were evaluated using novel data-processing algorithms that account for characteristics specific to the selected analytical technique and variability associated with replicate sample analyses. Among more than 25 000 components detected across the complete data set, ambrox was confirmed as a new exposure, and 3-methylbutanenitrile and 4-methylimidazole were confirmed as distinctive exposures. Concentrations of these compounds for the little cigar mainstream smoke were estimated at approximately 0.4, 0.7, and 12 μg/rod, respectively. In achieving these results, this study has demonstrated the capability of a powerful analytical approach to identify previously uncharacterized tobacco-related exposures from little cigars. The same approach could also be applied to other samples to characterize constituents associated with tobacco product classes or specific tobacco products of interest. Such analyses are critical in identifying tobacco-related exposures that may affect public health. PMID:26605856

High-throughput single-molecule telomere characterization.

PubMed

McCaffrey, Jennifer; Young, Eleanor; Lassahn, Katy; Sibert, Justin; Pastor, Steven; Riethman, Harold; Xiao, Ming

2017-11-01

We have developed a novel method that enables global subtelomere and haplotype-resolved analysis of telomere lengths at the single-molecule level. An in vitro CRISPR/Cas9 RNA-directed nickase system directs the specific labeling of human (TTAGGG)n DNA tracts in genomes that have also been barcoded using a separate nickase enzyme that recognizes a 7-bp motif genome-wide. High-throughput imaging and analysis of large DNA single molecules from genomes labeled in this fashion using a nanochannel array system permits mapping through subtelomere repeat element (SRE) regions to unique chromosomal DNA while simultaneously measuring the (TTAGGG)n tract length at the end of each large telomere-terminal DNA segment. The methodology also permits subtelomere and haplotype-resolved analyses of SRE organization and variation, providing a window into the population dynamics and potential functions of these complex and structurally variant telomere-adjacent DNA regions. At its current stage of development, the assay can be used to identify and characterize telomere length distributions of 30-35 discrete telomeres simultaneously and accurately. The assay's utility is demonstrated using early versus late passage and senescent human diploid fibroblasts, documenting the anticipated telomere attrition on a global telomere-by-telomere basis as well as identifying subtelomere-specific biases for critically short telomeres. Similarly, we present the first global single-telomere-resolved analyses of two cancer cell lines. © 2017 McCaffrey et al.; Published by Cold Spring Harbor Laboratory Press.
Modelling the Cost Effectiveness of Disease-Modifying Treatments for Multiple Sclerosis

PubMed Central

Thompson, Joel P.; Abdolahi, Amir; Noyes, Katia

2013-01-01

Several cost-effectiveness models of disease-modifying treatments (DMTs) for multiple sclerosis (MS) have been developed for different populations and different countries. Vast differences in the approaches and discrepancies in the results give rise to heated discussions and limit the use of these models. Our main objective is to discuss the methodological challenges in modelling the cost effectiveness of treatments for MS. We conducted a review of published models to describe the approaches taken to date, to identify the key parameters that influence the cost effectiveness of DMTs, and to point out major areas of weakness and uncertainty. Thirty-six published models and analyses were identified. The greatest source of uncertainty is the absence of head-to-head randomized clinical trials. Modellers have used various techniques to compensate, including utilizing extension trials. The use of large observational cohorts in recent studies aids in identifying population-based, ‘real-world’ treatment effects. Major drivers of results include the time horizon modelled and DMT acquisition costs. Model endpoints must target either policy makers (using cost-utility analysis) or clinicians (conducting cost-effectiveness analyses). Lastly, the cost effectiveness of DMTs outside North America and Europe is currently unknown, with the lack of country-specific data as the major limiting factor. We suggest that limited data should not preclude analyses, as models may be built and updated in the future as data become available. Disclosure of modelling methods and assumptions could improve the transferability and applicability of models designed to reflect different healthcare systems. PMID:23640103
How accurately does the Brief Job Stress Questionnaire identify workers with or without potential psychological distress?

PubMed

Tsutsumi, Akizumi; Inoue, Akiomi; Eguchi, Hisashi

2017-07-27

The manual for the Japanese Stress Check Program recommends use of the Brief Job Stress Questionnaire (BJSQ) from among the program's instruments and proposes criteria for defining "high-stress" workers. This study aimed to examine how accurately the BJSQ identifies workers with or without potential psychological distress. We used an online survey to administer the BJSQ with a psychological distress scale (K6) to randomly selected workers (n=1,650). We conducted receiver operating characteristics curve analyses to estimate the screening performance of the cutoff points that the Stress Check Program manual recommends for the BJSQ. Prevalence of workers with potential psychological distress defined as K6 score ≥13 was 13%. Prevalence of "high-risk" workers defined using criteria recommended by the program manual was 16.7% for the original version of the BJSQ. The estimated values were as follows: sensitivity, 60.5%; specificity, 88.9%; Youden index, 0.504; positive predictive value, 47.3%; negative predictive value, 93.8%; positive likelihood ratio, 6.0; and negative likelihood ratio, 0.4. Analyses based on the simplified BJSQ indicated lower sensitivity compared with the original version, although we expected roughly the same screening performance for the best scenario using the original version. Our analyses in which psychological distress measured by K6 was set as the target condition indicate less than half of the identified "high-stress" workers warrant consideration for secondary screening for psychological distress.
Event-related fMRI studies of false memory: An Activation Likelihood Estimation meta-analysis.

PubMed

Kurkela, Kyle A; Dennis, Nancy A

2016-01-29

Over the last two decades, a wealth of research in the domain of episodic memory has focused on understanding the neural correlates mediating false memories, or memories for events that never happened. While several recent qualitative reviews have attempted to synthesize this literature, methodological differences amongst the empirical studies and a focus on only a sub-set of the findings has limited broader conclusions regarding the neural mechanisms underlying false memories. The current study performed a voxel-wise quantitative meta-analysis using activation likelihood estimation to investigate commonalities within the functional magnetic resonance imaging (fMRI) literature studying false memory. The results were broken down by memory phase (encoding, retrieval), as well as sub-analyses looking at differences in baseline (hit, correct rejection), memoranda (verbal, semantic), and experimental paradigm (e.g., semantic relatedness and perceptual relatedness) within retrieval. Concordance maps identified significant overlap across studies for each analysis. Several regions were identified in the general false retrieval analysis as well as multiple sub-analyses, indicating their ubiquitous, yet critical role in false retrieval (medial superior frontal gyrus, left precentral gyrus, left inferior parietal cortex). Additionally, several regions showed baseline- and paradigm-specific effects (hit/perceptual relatedness: inferior and middle occipital gyrus; CRs: bilateral inferior parietal cortex, precuneus, left caudate). With respect to encoding, analyses showed common activity in the left middle temporal gyrus and anterior cingulate cortex. No analysis identified a common cluster of activation in the medial temporal lobe. Copyright © 2015 Elsevier Ltd. All rights reserved.
Molecular signatures and phylogenomic analysis of the genus Burkholderia: proposal for division of this genus into the emended genus Burkholderia containing pathogenic organisms and a new genus Paraburkholderia gen. nov. harboring environmental species

PubMed Central

Sawana, Amandeep; Adeolu, Mobolaji; Gupta, Radhey S.

2014-01-01

The genus Burkholderia contains large number of diverse species which include many clinically important organisms, phytopathogens, as well as environmental species. However, currently, there is a paucity of biochemical or molecular characteristics which can reliably distinguish different groups of Burkholderia species. We report here the results of detailed phylogenetic and comparative genomic analyses of 45 sequenced species of the genus Burkholderia. In phylogenetic trees based upon concatenated sequences for 21 conserved proteins as well as 16S rRNA gene sequence based trees, members of the genus Burkholderia grouped into two major clades. Within these main clades a number of smaller clades including those corresponding to the clinically important Burkholderia cepacia complex (BCC) and the Burkholderia pseudomallei groups were also clearly distinguished. Our comparative analysis of protein sequences from Burkholderia spp. has identified 42 highly specific molecular markers in the form of conserved sequence indels (CSIs) that are uniquely found in a number of well-defined groups of Burkholderia spp. Six of these CSIs are specific for a group of Burkholderia spp. (referred to as Clade I in this work) which contains all clinically relevant members of the genus (viz. the BCC and the B. pseudomallei group) as well as the phytopathogenic Burkholderia spp. The second main clade (Clade II), which is composed of environmental Burkholderia species, is also distinguished by 2 identified CSIs that are specific for this group. Additionally, our work has also identified multiple CSIs that serve to clearly demarcate a number of smaller groups of Burkholderia spp. including 3 CSIs that are specific for the B. cepacia complex, 4 CSIs that are uniquely found in the B. pseudomallei group, 5 CSIs that are specific for the phytopathogenic Burkholderia spp. and 22 other CSI that distinguish two groups within Clade II. The described molecular markers provide highly specific means for the demarcation of different groups of Burkholderia spp. and they also offer novel and useful targets for the development of diagnostic assays for the clinically important members of the BCC or the pseudomallei groups. Based upon the results of phylogenetic analyses, the identified CSIs and the pathogenicity profile of Burkholderia species, we are proposing a division of the genus Burkholderia into two genera. In this new proposal, the emended genus Burkholderia will correspond to the Clade I and it will contain only the clinically relevant and phytopathogenic Burkholderia species. All other Burkholderia spp., which are primarily environmental, will be transferred to a new genus Paraburkholderia gen. nov. PMID:25566316
Monitoring the southwestern Wyoming landscape—A foundation for management and science

USGS Publications Warehouse

Manier, Daniel J.; Anderson, Patrick J.; Assal, Timothy J.; Chong, Geneva W.; Melcher, Cynthia P.

2017-08-29

Natural resource monitoring involves repeated collections of resource condition data and analyses to detect possible changes and identify underlying causes of changes. For natural resource agencies, monitoring provides the foundation for management and science. Specifically, analyses of monitoring data allow managers to better understand effects of land-use and other changes on important natural resources and to achieve their conservation and management goals. Examples of natural resources monitored on public lands include wildlife habitats, plant productivity, animal movements and population trends, soil chemistry, and water quality and quantity. Broader definitions of monitoring also recognize the need for scientifically valid data to help support planning efforts and informed decisions, to develop adaptive management strategies, and to provide the means for evaluating management outcomes.
Deaf college students' mathematical skills relative to morphological knowledge, reading level, and language proficiency.

PubMed

Kelly, Ronald R; Gaustad, Martha G

2007-01-01

This study of deaf college students examined specific relationships between their mathematics performance and their assessed skills in reading, language, and English morphology. Simple regression analyses showed that deaf college students' language proficiency scores, reading grade level, and morphological knowledge regarding word segmentation and meaning were all significantly correlated with both the ACT Mathematics Subtest and National Technical Institute for the Deaf (NTID) Mathematics Placement Test scores. Multiple regression analyses identified the best combination from among these potential independent predictors of students' performance on both the ACT and NTID mathematics tests. Additionally, the participating deaf students' grades in their college mathematics courses were significantly and positively associated with their reading grade level and their knowledge of morphological components of words.
Biochemical and transcriptomic analyses reveal different metabolite biosynthesis profiles among three color and developmental stages in 'Anji Baicha' (Camellia sinensis).

PubMed

Li, Chun-Fang; Xu, Yan-Xia; Ma, Jian-Qiang; Jin, Ji-Qiang; Huang, Dan-Juan; Yao, Ming-Zhe; Ma, Chun-Lei; Chen, Liang

2016-09-08

The new shoots of the albino tea cultivar 'Anji Baicha' are yellow or white at low temperatures and turn green as the environmental temperatures increase during the early spring. 'Anji Baicha' metabolite profiles exhibit considerable variability over three color and developmental stages, especially regarding the carotenoid, chlorophyll, and theanine concentrations. Previous studies focused on physiological characteristics, gene expression differences, and variations in metabolite abundances in albino tea plant leaves at specific growth stages. However, the molecular mechanisms regulating metabolite biosynthesis in various color and developmental stages in albino tea leaves have not been fully characterized. We used RNA-sequencing to analyze 'Anji Baicha' leaves at the yellow-green, albescent, and re-greening stages. The leaf transcriptomes differed considerably among the three stages. Functional classifications based on Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that differentially expressed unigenes were mainly related to metabolic pathways, biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, and carbon fixation in photosynthetic organisms. Chemical analyses revealed higher β-carotene and theanine levels, but lower chlorophyll a levels, in the albescent stage than in the green stage. Furthermore, unigenes involved in carotenoid, chlorophyll, and theanine biosyntheses were identified, and the expression patterns of the differentially expressed unigenes in these biosynthesis pathways were characterized. Through co-expression analyses, we identified the key genes in these pathways. These genes may be responsible for the metabolite biosynthesis differences among the different leaf color and developmental stages of 'Anji Baicha' tea plants. Our study presents the results of transcriptomic and biochemical analyses of 'Anji Baicha' tea plants at various stages. The distinct transcriptome profiles for each color and developmental stage enabled us to identify changes to biosynthesis pathways and revealed the contributions of such variations to the albino phenotype of tea plants. Furthermore, comparisons of the transcriptomes and related metabolites helped clarify the molecular regulatory mechanisms underlying the secondary metabolic pathways in different stages.
Human Lineage-Specific Transcriptional Regulation through GA-Binding Protein Transcription Factor Alpha (GABPa)

PubMed Central

Perdomo-Sabogal, Alvaro; Nowick, Katja; Piccini, Ilaria; Sudbrak, Ralf; Lehrach, Hans; Yaspo, Marie-Laure; Warnatz, Hans-Jörg; Querfurth, Robert

2016-01-01

A substantial fraction of phenotypic differences between closely related species are likely caused by differences in gene regulation. While this has already been postulated over 30 years ago, only few examples of evolutionary changes in gene regulation have been verified. Here, we identified and investigated binding sites of the transcription factor GA-binding protein alpha (GABPa) aiming to discover cis-regulatory adaptations on the human lineage. By performing chromatin immunoprecipitation-sequencing experiments in a human cell line, we found 11,619 putative GABPa binding sites. Through sequence comparisons of the human GABPa binding regions with orthologous sequences from 34 mammals, we identified substitutions that have resulted in 224 putative human-specific GABPa binding sites. To experimentally assess the transcriptional impact of those substitutions, we selected four promoters for promoter-reporter gene assays using human and African green monkey cells. We compared the activities of wild-type promoters to mutated forms, where we have introduced one or more substitutions to mimic the ancestral state devoid of the GABPa consensus binding sequence. Similarly, we introduced the human-specific substitutions into chimpanzee and macaque promoter backgrounds. Our results demonstrate that the identified substitutions are functional, both in human and nonhuman promoters. In addition, we performed GABPa knock-down experiments and found 1,215 genes as strong candidates for primary targets. Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes. Thus, we propose that differences in GABPa binding sites played important roles in the evolution of human-specific phenotypes. PMID:26814189
Reflex Cough and Disease Duration as Predictors of Swallowing Dysfunction in Parkinson's Disease.

PubMed

Troche, Michelle S; Schumann, Beate; Brandimore, Alexandra E; Okun, Michael S; Hegland, Karen W

2016-12-01

Patients with Parkinson's disease (PD) have progressive and pervasive disorders of airway protection. Recent work has highlighted the relationship between reflex and voluntary cough and swallowing safety. The goal of this study was to test the sensitivity and specificity of several airway protective and disease-specific factors for predicting swallowing safety outcomes in PD. Sixty-four participants (44 males) completed measures of voluntary and reflex cough, and swallowing safety. Clinical predictors included disease severity and duration, and cough airflow and sensitivity measures. ROC and Chi-square analyses identified predictors of swallowing safety (penetration-aspiration score) in PD. Disease duration significantly discriminated between patients with normal and abnormal swallowing safety (p = 0.027, sensitivity: 71 %, specificity: 55.4 %). Cough reflex sensitivity significantly discriminated between patients who penetrated above the level of the vocal folds and those with more severe penetration/aspiration (p = 0.021, sensitivity: 71.0 %, specificity 57.6 %). Urge-to-cough sensitivity (log-log linear slope) was the only variable which significantly discriminated between patients with penetration versus aspiration (p = 0.017, sensitivity: 85.7 %, specificity 73.2 %). It is important to identify the factors which influence airway protective outcomes in PD especially given that aspiration pneumonia is a leading cause of death. Results from this study highlight the ecological validity of reflex cough in the study of airway protection and this study further identifies important factors to consider in the screening of airway protective deficits in PD.
Defining robustness protocols: a method to include and evaluate robustness in clinical plans

NASA Astrophysics Data System (ADS)

McGowan, S. E.; Albertini, F.; Thomas, S. J.; Lomax, A. J.

2015-04-01

We aim to define a site-specific robustness protocol to be used during the clinical plan evaluation process. Plan robustness of 16 skull base IMPT plans to systematic range and random set-up errors have been retrospectively and systematically analysed. This was determined by calculating the error-bar dose distribution (ebDD) for all the plans and by defining some metrics used to define protocols aiding the plan assessment. Additionally, an example of how to clinically use the defined robustness database is given whereby a plan with sub-optimal brainstem robustness was identified. The advantage of using different beam arrangements to improve the plan robustness was analysed. Using the ebDD it was found range errors had a smaller effect on dose distribution than the corresponding set-up error in a single fraction, and that organs at risk were most robust to the range errors, whereas the target was more robust to set-up errors. A database was created to aid planners in terms of plan robustness aims in these volumes. This resulted in the definition of site-specific robustness protocols. The use of robustness constraints allowed for the identification of a specific patient that may have benefited from a treatment of greater individuality. A new beam arrangement showed to be preferential when balancing conformality and robustness for this case. The ebDD and error-bar volume histogram proved effective in analysing plan robustness. The process of retrospective analysis could be used to establish site-specific robustness planning protocols in proton therapy. These protocols allow the planner to determine plans that, although delivering a dosimetrically adequate dose distribution, have resulted in sub-optimal robustness to these uncertainties. For these cases the use of different beam start conditions may improve the plan robustness to set-up and range uncertainties.
Initial proteome analysis of caffeine-induced proteins in Aspergillus tamarii using two-dimensional fluorescence difference gel electrophoresis.

PubMed

Gutiérrez-Sánchez, Gerardo; Atwood, James; Kolli, V S Kumar; Roussos, Sévastianos; Augur, Christopher

2012-04-01

Caffeine is toxic to most microorganisms. However, some filamentous fungi, such as Aspergillus tamarii, are able to metabolize this alkaloid when fed caffeine as the sole nitrogen source. The aim of the present work was to identify intracellular A. tamarii proteins, regulated by caffeine, using fluorescence difference two-dimensional gel electrophoresis. Specific proteins from two culture media of A. tamarii grown either on ammonium sulfate or caffeine as the sole nitrogen source were analysed by mass spectrometry. Thirteen out of a total of 85 differentially expressed spots were identified after database search. Identified up-regulated proteins include phosphoglycerate kinase, malate dehydrogenase, dyp-type peroxidase family protein, heat shock protein, Cu, Zn superoxidase dismutase and xanthine dehydrogenase. Some of the proteins identified in this study are involved in the caffeine degradation pathway as well as in stress response, suggesting that stress proteins could be involved in caffeine metabolism in filamentous fungi.
Whole exome sequence-based association analyses of plasma amyloid-β in African and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive Study.

PubMed

Simino, Jeannette; Wang, Zhiying; Bressler, Jan; Chouraki, Vincent; Yang, Qiong; Younkin, Steven G; Seshadri, Sudha; Fornage, Myriam; Boerwinkle, Eric; Mosley, Thomas H

2017-01-01

We performed single-variant and gene-based association analyses of plasma amyloid-β (aβ) concentrations using whole exome sequence from 1,414 African and European Americans. Our goal was to identify genes that influence plasma aβ42 concentrations and aβ42:aβ40 ratios in late middle age (mean = 59 years), old age (mean = 77 years), or change over time (mean = 18 years). Plasma aβ measures were linearly regressed onto age, gender, APOE ε4 carrier status, and time elapsed between visits (fold-changes only) separately by race. Following inverse normal transformation of the residuals, seqMeta was used to conduct race-specific single-variant and gene-based association tests while adjusting for population structure. Linear regression models were fit on autosomal variants with minor allele frequencies (MAF)≥1%. T5 burden and Sequence Kernel Association (SKAT) gene-based tests assessed functional variants with MAF≤5%. Cross-race fixed effects meta-analyses were Bonferroni-corrected for the number of variants or genes tested. Seven genes were associated with aβ in late middle age or change over time; no associations were identified in old age. Single variants in KLKB1 (rs3733402; p = 4.33x10-10) and F12 (rs1801020; p = 3.89x10-8) were significantly associated with midlife aβ42 levels through cross-race meta-analysis; the KLKB1 variant replicated internally using 1,014 additional participants with exome chip. ITPRIP, PLIN2, and TSPAN18 were associated with the midlife aβ42:aβ40 ratio via the T5 test; TSPAN18 was significant via the cross-race meta-analysis, whereas ITPRIP and PLIN2 were European American-specific. NCOA1 and NT5C3B were associated with the midlife aβ42:aβ40 ratio and the fold-change in aβ42, respectively, via SKAT in African Americans. No associations replicated externally (N = 725). We discovered age-dependent genetic effects, established associations between vascular-related genes (KLKB1, F12, PLIN2) and midlife plasma aβ levels, and identified a plausible Alzheimer's Disease candidate gene (ITPRIP) influencing cell death. Plasma aβ concentrations may have dynamic biological determinants across the lifespan; plasma aβ study designs or analyses must consider age.
Lessons on RNA Silencing Mechanisms in Plants from Eukaryotic Argonaute Structures[W

PubMed Central

Poulsen, Christian; Vaucheret, Hervé; Brodersen, Peter

2013-01-01

RNA silencing refers to a collection of gene regulatory mechanisms that use small RNAs for sequence specific repression. These mechanisms rely on ARGONAUTE (AGO) proteins that directly bind small RNAs and thereby constitute the central component of the RNA-induced silencing complex (RISC). AGO protein function has been probed extensively by mutational analyses, particularly in plants where large allelic series of several AGO proteins have been isolated. Structures of entire human and yeast AGO proteins have only very recently been obtained, and they allow more precise analyses of functional consequences of mutations obtained by forward genetics. To a large extent, these analyses support current models of regions of particular functional importance of AGO proteins. Interestingly, they also identify previously unrecognized parts of AGO proteins with profound structural and functional importance and provide the first hints at structural elements that have important functions specific to individual AGO family members. A particularly important outcome of the analysis concerns the evidence for existence of Gly-Trp (GW) repeat interactors of AGO proteins acting in the plant microRNA pathway. The parallel analysis of AGO structures and plant AGO mutations also suggests that such interactions with GW proteins may be a determinant of whether an endonucleolytically competent RISC is formed. PMID:23303917
Lessons on RNA silencing mechanisms in plants from eukaryotic argonaute structures.

PubMed

Poulsen, Christian; Vaucheret, Hervé; Brodersen, Peter

2013-01-01

RNA silencing refers to a collection of gene regulatory mechanisms that use small RNAs for sequence specific repression. These mechanisms rely on ARGONAUTE (AGO) proteins that directly bind small RNAs and thereby constitute the central component of the RNA-induced silencing complex (RISC). AGO protein function has been probed extensively by mutational analyses, particularly in plants where large allelic series of several AGO proteins have been isolated. Structures of entire human and yeast AGO proteins have only very recently been obtained, and they allow more precise analyses of functional consequences of mutations obtained by forward genetics. To a large extent, these analyses support current models of regions of particular functional importance of AGO proteins. Interestingly, they also identify previously unrecognized parts of AGO proteins with profound structural and functional importance and provide the first hints at structural elements that have important functions specific to individual AGO family members. A particularly important outcome of the analysis concerns the evidence for existence of Gly-Trp (GW) repeat interactors of AGO proteins acting in the plant microRNA pathway. The parallel analysis of AGO structures and plant AGO mutations also suggests that such interactions with GW proteins may be a determinant of whether an endonucleolytically competent RISC is formed.
No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.

PubMed

Loley, Christina; Alver, Maris; Assimes, Themistocles L; Bjonnes, Andrew; Goel, Anuj; Gustafsson, Stefan; Hernesniemi, Jussi; Hopewell, Jemma C; Kanoni, Stavroula; Kleber, Marcus E; Lau, King Wai; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Nelson, Christopher P; Nikpay, Majid; Qu, Liming; Salfati, Elias; Scholz, Markus; Tukiainen, Taru; Willenborg, Christina; Won, Hong-Hee; Zeng, Lingyao; Zhang, Weihua; Anand, Sonia S; Beutner, Frank; Bottinger, Erwin P; Clarke, Robert; Dedoussis, George; Do, Ron; Esko, Tõnu; Eskola, Markku; Farrall, Martin; Gauguier, Dominique; Giedraitis, Vilmantas; Granger, Christopher B; Hall, Alistair S; Hamsten, Anders; Hazen, Stanley L; Huang, Jie; Kähönen, Mika; Kyriakou, Theodosios; Laaksonen, Reijo; Lind, Lars; Lindgren, Cecilia; Magnusson, Patrik K E; Marouli, Eirini; Mihailov, Evelin; Morris, Andrew P; Nikus, Kjell; Pedersen, Nancy; Rallidis, Loukianos; Salomaa, Veikko; Shah, Svati H; Stewart, Alexandre F R; Thompson, John R; Zalloua, Pierre A; Chambers, John C; Collins, Rory; Ingelsson, Erik; Iribarren, Carlos; Karhunen, Pekka J; Kooner, Jaspal S; Lehtimäki, Terho; Loos, Ruth J F; März, Winfried; McPherson, Ruth; Metspalu, Andres; Reilly, Muredach P; Ripatti, Samuli; Sanghera, Dharambir K; Thiery, Joachim; Watkins, Hugh; Deloukas, Panos; Kathiresan, Sekar; Samani, Nilesh J; Schunkert, Heribert; Erdmann, Jeanette; König, Inke R

2016-10-12

In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.
Transcriptome analyses reveal genotype- and developmental stage-specific molecular responses to drought and salinity stresses in chickpea

PubMed Central

Garg, Rohini; Shankar, Rama; Thakkar, Bijal; Kudapa, Himabindu; Krishnamurthy, Lakshmanan; Mantri, Nitin; Varshney, Rajeev K.; Bhatia, Sabhyata; Jain, Mukesh

2016-01-01

Drought and salinity are the major factors that limit chickpea production worldwide. We performed whole transcriptome analyses of chickpea genotypes to investigate the molecular basis of drought and salinity stress response/adaptation. Phenotypic analyses confirmed the contrasting responses of the chickpea genotypes to drought or salinity stress. RNA-seq of the roots of drought and salinity related genotypes was carried out under control and stress conditions at vegetative and/or reproductive stages. Comparative analysis of the transcriptomes revealed divergent gene expression in the chickpea genotypes at different developmental stages. We identified a total of 4954 and 5545 genes exclusively regulated in drought-tolerant and salinity-tolerant genotypes, respectively. A significant fraction (~47%) of the transcription factor encoding genes showed differential expression under stress. The key enzymes involved in metabolic pathways, such as carbohydrate metabolism, photosynthesis, lipid metabolism, generation of precursor metabolites/energy, protein modification, redox homeostasis and cell wall component biogenesis, were affected by drought and/or salinity stresses. Interestingly, transcript isoforms showed expression specificity across the chickpea genotypes and/or developmental stages as illustrated by the AP2-EREBP family members. Our findings provide insights into the transcriptome dynamics and components of regulatory network associated with drought and salinity stress responses in chickpea. PMID:26759178
Verbal and non-verbal memory and hippocampal volumes in a memory clinic population.

PubMed

Bonner-Jackson, Aaron; Mahmoud, Shamseldeen; Miller, Justin; Banks, Sarah J

2015-10-15

Better characterization of the relationship between episodic memory and hippocampal volumes is crucial in early detection of neurodegenerative disease. We examined these relationships in a memory clinic population. Participants (n = 226) underwent structural magnetic resonance imaging and tests of verbal (Hopkins Verbal Learning Test-Revised, HVLT-R) and non-verbal (Brief Visuospatial Memory Test-Revised, BVMT-R) memory. Correlational analyses were performed, and analyses on clinical subgroups (i.e., amnestic Mild Cognitive Impairment, non-amnestic Mild Cognitive Impairment, probable Alzheimer's disease, intact memory) were conducted. Positive associations were identified between bilateral hippocampal volumes and both memory measures, and BVMT-R learning slope was more strongly positively associated with hippocampal volumes than HVLT-R learning slope. Amnestic Mild Cognitive Impairment (aMCI) participants showed specific positive associations between BVMT-R performance and hippocampal volumes bilaterally. Additionally, analyses of the aMCI group showed trend-level evidence of material-specific lateralization, such that retention of verbal information was positively associated with left hippocampal volume, whereas learning curve and retention of non-verbal information was positively associated with right hippocampal volume. Findings support the link between episodic memory and hippocampal volumes in a memory clinic population. Non-verbal memory measures also may have higher diagnostic value, particularly in individuals at elevated risk for Alzheimer's disease.
Gene expression atlas of pigeonpea and its application to gain insights into genes associated with pollen fertility implicated in seed formation.

PubMed

Pazhamala, Lekha T; Purohit, Shilp; Saxena, Rachit K; Garg, Vanika; Krishnamurthy, L; Verdier, Jerome; Varshney, Rajeev K

2017-04-01

Pigeonpea (Cajanus cajan) is an important grain legume of the semi-arid tropics, mainly used for its protein rich seeds. To link the genome sequence information with agronomic traits resulting from specific developmental processes, a Cajanus cajan gene expression atlas (CcGEA) was developed using the Asha genotype. Thirty tissues/organs representing developmental stages from germination to senescence were used to generate 590.84 million paired-end RNA-Seq data. The CcGEA revealed a compendium of 28 793 genes with differential, specific, spatio-temporal and constitutive expression during various stages of development in different tissues. As an example to demonstrate the application of the CcGEA, a network of 28 flower-related genes analysed for cis-regulatory elements and splicing variants has been identified. In addition, expression analysis of these candidate genes in male sterile and male fertile genotypes suggested their critical role in normal pollen development leading to seed formation. Gene network analysis also identified two regulatory genes, a pollen-specific SF3 and a sucrose-proton symporter, that could have implications for improvement of agronomic traits such as seed production and yield. In conclusion, the CcGEA provides a valuable resource for pigeonpea to identify candidate genes involved in specific developmental processes and to understand the well-orchestrated growth and developmental process in this resilient crop. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Developing an Experiential Definition of Recovery: Participatory Research with Recovering Substance Abusers from Multiple Pathways

PubMed Central

Borkman, Thomasina J.; Stunz, Aina; Kaskutas, Lee Ann

2016-01-01

Background The What is Recovery? (WIR) study identified specific elements of a recovery definition that people in substance abuse recovery from multiple pathways would endorse. Objectives To explain how participatory research contributed to the development of a comprehensive pool of items defining recovery; and to identify the commonality between the specific items endorsed by participants as defining recovery and the abstract components of recovery found in four important broad recovery definitions Methods A four-step, mixed-methods, iterative process was used to develop and pretest items (August 2010 to February 2012). Online survey recruitment (n=238) was done via email lists of individuals in recovery and electronic advertisements; 54 were selected for in-depth telephone interviews. Analyses using experientially-based and survey research criteria resulted in a revised item pool of 47 refined and specific items. The WIR items were matched with the components of four important definitions. Results Recovering participants (1) proposed and validated new items; (2) developed an alternative response category to the Likert; (3) suggested criteria for eliminating items irrelevant to recovery. The matching of WIR items with the components of important abstract definitions revealed extensive commonality. Conclusions, importance The WIR items define recovery as ways of being, as a growth and learning process involving internal values and self-awareness with moral dimensions. This is the first wide-scale research identifying specific items defining recovery, which can be used to guide service provision in Recovery-Oriented Systems of Care. PMID:27159851

Developing an Experiential Definition of Recovery: Participatory Research With Recovering Substance Abusers From Multiple Pathways.

PubMed

Borkman, Thomasina Jo; Stunz, Aina; Kaskutas, Lee Ann

2016-07-28

The What is Recovery? (WIR) study identified specific elements of a recovery definition that people in substance abuse recovery from multiple pathways would endorse. To explain how participatory research contributed to the development of a comprehensive pool of items defining recovery; and to identify the commonality between the specific items endorsed by participants as defining recovery and the abstract components of recovery found in four important broad recovery definitions. A four-step, mixed-methods, iterative process was used to develop and pretest items (August 2010 to February 2012). Online survey recruitment (n = 238) was done via email lists of individuals in recovery and electronic advertisements; 54 were selected for in-depth telephone interviews. Analyses using experientially-based and survey research criteria resulted in a revised item pool of 47 refined and specific items. The WIR items were matched with the components of four important definitions. Recovering participants (1) proposed and validated new items; (2) developed an alternative response category to the Likert; (3) suggested criteria for eliminating items irrelevant to recovery. The matching of WIR items with the components of important abstract definitions revealed extensive commonality. The WIR items define recovery as ways of being, as a growth and learning process involving internal values and self-awareness with moral dimensions. This is the first wide-scale research identifying specific items defining recovery, which can be used to guide service provision in Recovery-Oriented Systems of Care.
Fungal microbiota dysbiosis in IBD

PubMed Central

Sokol, Harry; Leducq, Valentin; Aschard, Hugues; Pham, Hang-Phuong; Jegou, Sarah; Landman, Cecilia; Cohen, David; Liguori, Giuseppina; Bourrier, Anne; Nion-Larmurier, Isabelle; Cosnes, Jacques; Seksik, Philippe; Langella, Philippe; Skurnik, David; Richard, Mathias L; Beaugerie, Laurent

2017-01-01

Objective The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Design Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. Results We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Conclusions Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis. PMID:26843508
76 FR 24831 - Site-Specific Analyses for Demonstrating Compliance With Subpart C Performance Objectives

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... available under ADAMS accession number ML111040419, and the ``Technical Analysis Supporting Definition of... NUCLEAR REGULATORY COMMISSION 10 CFR Part 61 RIN 3150-AI92 [NRC-2011-0012] Site-Specific Analyses...-level radioactive waste disposal facilities to conduct site-specific analyses to demonstrate compliance...
Development of the Veritas plot and its application in cardiac surgery: an evidence-synthesis graphic tool for the clinician to assess multiple meta-analyses reporting on a common outcome.

PubMed

Panesar, Sukhmeet S; Rao, Christopher; Vecht, Joshua A; Mirza, Saqeb B; Netuveli, Gopalakrishnan; Morris, Richard; Rosenthal, Joe; Darzi, Ara; Athanasiou, Thanos

2009-10-01

Meta-analyses may be prone to generating misleading results because of a paucity of experimental studies (especially in surgery); publication bias; and heterogeneity in study design, intervention and the patient population of included studies. When investigating a specific clinical or scientific question on which several relevant meta-analyses may have been published, value judgments must be applied to determine which analysis represents the most robust evidence. These value judgments should be specifically acknowledged. We designed the Veritas plot to explicitly explore important elements of quality and to facilitate decision-making by highlighting specific areas in which meta-analyses are found to be deficient. Furthermore, as a graphic tool, it may be more intuitive than when similar data are presented in a tabular or text format. The Veritas plot is an adaption of the radar plot, a graphic tool for the description of multiattribute data. Key elements of meta-analytical quality such as heterogeneity, publication bias and study design are assessed. Existing qualitative methods such as the Assessment of Multiple Systematic Reviews (AMSTAR) tool have been incorporated in addition to important considerations when interpreting surgical meta-analyses such as the year of publication and population characteristics. To demonstrate the potential of the Veritas plot to inform clinical practice, we apply the Veritas plot to the meta-analytical literature comparing the incidence of 30-day stroke in off-pump coronary artery bypass surgery and conventional coronary artery bypass surgery. We demonstrate that a visually-stimulating and practical evidence-synthesis tool can direct the clinician and scientist to a particular meta-analytical study to inform clinical practice. The Veritas plot is also cumulative and allowed us to assess the quality of evidence over time. We have presented a practical graphic application for scientists and clinicians to identify and interpret variability in meta-analyses. Although further validation of the Veritas plot is required, it may have the potential to contribute to the implementation of evidence-based practice.
DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatakeyama, Hiroto; Wu, Sherry Y.; Lyons, Yasmin A.

Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene signatures and the differences in response to hyperthermia between hyperthermia-sensitive and -resistant cancer cells identified CTGF as a key regulator of sensitivity. CTGF silencing sensitized resistant cells to hyperthermia. CTGF small interfering RNA (siRNA) treatment also sensitized resistant cancers to localized hyperthermia induced by copper sulfide nanoparticles and near-infrared laser in orthotopic ovarian cancer models. Lastly, CTGF silencingmore » aggravated energy stress induced by hyperthermia and enhanced apoptosis of hyperthermia-resistant cancers.« less
Identification of male-specific chiral compound from the sugarcane weevil Sphenophorus levis.

PubMed

Zarbin, Paulo H G; Arrigoni, Enrico de Beni; Reckziegel, Aurélia; Moreira, Jardel A; Baraldi, Patrícia T; Vieira, Paulo C

2003-02-01

Comparative gas chromatographic analyses of airborne volatiles produced by males and females of the sugarcane weevil Sphenophorus levis, showed one male-specific compound. Gas chromatography-mass spectrometry data indicated an aliphatic alcohol that was identified as 2-methyl-4-octanol. Both optical isomers were synthesized in five steps by employing commercially available (R)- and (S)-2.2-dimethyl-1,3-dioxolane-4-methanol as starting material. Enantiomeric resolution by gas chromatography with a chiral column demonstrated that the natural alcohol possessed the S configuration. Preliminary indoor observations suggested that the alcohol elicited aggregation behavior among adults. The same compound has been previously described as an aggregation pheromone in several other curculionid species.
Fatal Case of Deer Tick Virus Encephalitis

PubMed Central

Tavakoli, Norma P.; Wang, Heng; Dupuis, Michelle; Hull, Rene; Ebel, Gregory D.; Gilmore, Emily J.; Faust, Phyllis L.

2010-01-01

SUMMARY Deer tick virus is related to Powassan virus, a tickborne encephalitis virus. A 62-year-old man presented with a meningoencephalitis syndrome and eventually died. Analyses of tissue samples obtained during surgery and at autopsy revealed a widespread necrotizing meningoencephalitis. Nucleic acid was extracted from formalin-fixed tissue, and the presence of deer tick virus was verified on a flavivirus-specific polymerase-chain-reaction (PCR) assay, followed by sequence confirmation. Immunohistochemical analysis with antisera specific for deer tick virus identified numerous immunoreactive neurons, with prominent involvement of large neurons in the brain stem, cerebellum, basal ganglia, thalamus, and spinal cord. This case demonstrates that deer tick virus can be a cause of fatal encephalitis. PMID:19439744
Fatal case of deer tick virus encephalitis.

PubMed

Tavakoli, Norma P; Wang, Heng; Dupuis, Michelle; Hull, Rene; Ebel, Gregory D; Gilmore, Emily J; Faust, Phyllis L

2009-05-14

Deer tick virus is related to Powassan virus, a tickborne encephalitis virus. A 62-year-old man presented with a meningoencephalitis syndrome and eventually died. Analyses of tissue samples obtained during surgery and at autopsy revealed a widespread necrotizing meningoencephalitis. Nucleic acid was extracted from formalin-fixed tissue, and the presence of deer tick virus was verified on a flavivirus-specific polymerase-chain-reaction (PCR) assay, followed by sequence confirmation. Immunohistochemical analysis with antisera specific for deer tick virus identified numerous immunoreactive neurons, with prominent involvement of large neurons in the brain stem, cerebellum, basal ganglia, thalamus, and spinal cord. This case demonstrates that deer tick virus can be a cause of fatal encephalitis. 2009 Massachusetts Medical Society
Space Station Food System

NASA Technical Reports Server (NTRS)

Thurmond, Beverly A.; Gillan, Douglas J.; Perchonok, Michele G.; Marcus, Beth A.; Bourland, Charles T.

1986-01-01

A team of engineers and food scientists from NASA, the aerospace industry, food companies, and academia are defining the Space Station Food System. The team identified the system requirements based on an analysis of past and current space food systems, food systems from isolated environment communities that resemble Space Station, and the projected Space Station parameters. The team is resolving conflicts among requirements through the use of trade-off analyses. The requirements will give rise to a set of specifications which, in turn, will be used to produce concepts. Concept verification will include testing of prototypes, both in 1-g and microgravity. The end-item specification provides an overall guide for assembling a functional food system for Space Station.
Evidence for wild waterfowl origin of H7N3 influenza A virus detected in captive-reared New Jersey pheasants

USGS Publications Warehouse

Ramey, Andrew M.; Kim Torchetti, Mia; Poulson, Rebecca L.; Carter, Deborah L.; Reeves, Andrew B.; Link, Paul; Walther, Patrick; Lebarbenchon, Camille; Stallknecht, David E.

2016-01-01

In August 2014, a low-pathogenic H7N3 influenza A virus was isolated from pheasants at a New Jersey gamebird farm and hunting preserve. In this study, we use phylogenetic analyses and calculations of genetic similarity to gain inference into the genetic ancestry of this virus and to identify potential routes of transmission. Results of maximum-likelihood (ML) and maximum-clade-credibility (MCC) phylogenetic analyses provide evidence that A/pheasant/New Jersey/26996-2/2014 (H7N3) had closely related H7 hemagglutinin (HA) and N3 neuraminidase (NA) gene segments as compared to influenza A viruses circulating among wild waterfowl in the central and eastern USA. The estimated time of the most recent common ancestry (TMRCA) between the pheasant virus and those most closely related from wild waterfowl was early 2013 for both the H7 HA and N3 NA gene segments. None of the viruses from waterfowl identified as being most closely related to A/pheasant/New Jersey/26996-2/2014 at the HA and NA gene segments in ML and MCC phylogenetic analyses shared ≥99 % nucleotide sequence identity for internal gene segment sequences. This result indicates that specific viral strains identified in this study as being closely related to the HA and NA gene segments of A/pheasant/New Jersey/26996-2/2014 were not the direct predecessors of the etiological agent identified during the New Jersey outbreak. However, the recent common ancestry of the H7 and N3 gene segments of waterfowl-origin viruses and the virus isolated from pheasants suggests that viral diversity maintained in wild waterfowl likely played an important role in the emergence of A/pheasant/New Jersey/26996-2/2014.
HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

PubMed Central

Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Luscombe, Christopher J; Cheng, KK; Zeegers, Maurice P; James, Nicholas D; Gommersall, Lyndon M; Fryer, Anthony A

2018-01-01

Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease. PMID:29343995
Phylogeny and evolution of plant cyclic nucleotide-gated ion channel (CNGC) gene family and functional analyses of tomato CNGCs

PubMed Central

Saand, Mumtaz Ali; Xu, You-Ping; Munyampundu, Jean-Pierre; Li, Wen; Zhang, Xuan-Rui; Cai, Xin-Zhong

2015-01-01

Cyclic nucleotide-gated ion channels (CNGCs) are calcium-permeable channels that are involved in various biological functions. Nevertheless, phylogeny and function of plant CNGCs are not well understood. In this study, 333 CNGC genes from 15 plant species were identified using comprehensive bioinformatics approaches. Extensive bioinformatics analyses demonstrated that CNGCs of Group IVa were distinct to those of other groups in gene structure and amino acid sequence of cyclic nucleotide-binding domain. A CNGC-specific motif that recognizes all identified plant CNGCs was generated. Phylogenetic analysis indicated that CNGC proteins of flowering plant species formed five groups. However, CNGCs of the non-vascular plant Physcomitrella patens clustered only in two groups (IVa and IVb), while those of the vascular non-flowering plant Selaginella moellendorffii gathered in four (IVa, IVb, I and II). These data suggest that Group IV CNGCs are most ancient and Group III CNGCs are most recently evolved in flowering plants. Furthermore, silencing analyses revealed that a set of CNGC genes might be involved in disease resistance and abiotic stress responses in tomato and function of SlCNGCs does not correlate with the group that they are belonging to. Our results indicate that Group IVa CNGCs are structurally but not functionally unique among plant CNGCs. PMID:26546226
Phylogenetic Analyses of Shigella and Enteroinvasive Escherichia coli for the Identification of Molecular Epidemiological Markers: Whole-Genome Comparative Analysis Does Not Support Distinct Genera Designation

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

Pettengill, Emily A.; Pettengill, James B.; Binet, Rachel

As a leading cause of bacterial dysentery, Shigella represents a significant threat to public health and food safety. Related, but often overlooked, enteroinvasive Escherichia coli (EIEC) can also cause dysentery. Current typing methods have limited ability to identify and differentiate between these pathogens despite the need for rapid and accurate identification of pathogens for clinical treatment and outbreak response. We present a comprehensive phylogeny of Shigella and EIEC using whole genome sequencing of 169 samples, constituting unparalleled strain diversity, and observe a lack of monophyly between Shigella and EIEC and among Shigella taxonomic groups. The evolutionary relationships in the phylogenymore » are supported by analyses of population structure and hierarchical clustering patterns of translated gene homolog abundance. Lastly, we identified a panel of 404 single nucleotide polymorphism (SNP) markers specific to each phylogenetic cluster for more accurate identification of Shigella and EIEC. Our findings show that Shigella and EIEC are not distinct evolutionary groups within the E. coli genus and, thus, EIEC as a group is not the ancestor to Shigella. The multiple analyses presented provide evidence for reconsidering the taxonomic placement of Shigella. The SNP markers offer more discriminatory power to molecular epidemiological typing methods involving these bacterial pathogens.« less
Phylogenetic Analyses of Shigella and Enteroinvasive Escherichia coli for the Identification of Molecular Epidemiological Markers: Whole-Genome Comparative Analysis Does Not Support Distinct Genera Designation

DOE PAGES

Pettengill, Emily A.; Pettengill, James B.; Binet, Rachel

2016-01-19

As a leading cause of bacterial dysentery, Shigella represents a significant threat to public health and food safety. Related, but often overlooked, enteroinvasive Escherichia coli (EIEC) can also cause dysentery. Current typing methods have limited ability to identify and differentiate between these pathogens despite the need for rapid and accurate identification of pathogens for clinical treatment and outbreak response. We present a comprehensive phylogeny of Shigella and EIEC using whole genome sequencing of 169 samples, constituting unparalleled strain diversity, and observe a lack of monophyly between Shigella and EIEC and among Shigella taxonomic groups. The evolutionary relationships in the phylogenymore » are supported by analyses of population structure and hierarchical clustering patterns of translated gene homolog abundance. Lastly, we identified a panel of 404 single nucleotide polymorphism (SNP) markers specific to each phylogenetic cluster for more accurate identification of Shigella and EIEC. Our findings show that Shigella and EIEC are not distinct evolutionary groups within the E. coli genus and, thus, EIEC as a group is not the ancestor to Shigella. The multiple analyses presented provide evidence for reconsidering the taxonomic placement of Shigella. The SNP markers offer more discriminatory power to molecular epidemiological typing methods involving these bacterial pathogens.« less
Serial analysis of gene expression in a rat lung model of asthma.

PubMed

Yin, Lei-Miao; Jiang, Gong-Hao; Wang, Yu; Wang, Yan; Liu, Yan-Yan; Jin, Wei-Rong; Zhang, Zen; Xu, Yu-Dong; Yang, Yong-Qing

2008-11-01

The pathogenesis and molecular mechanism underlying asthma remain undetermined. The purpose of this study was to identify genes and pathways involved in the early airway response (EAR) phase of asthma by using serial analysis of gene expression (SAGE). Two SAGE tag libraries of lung tissues derived from a rat model of asthma and controls were generated. Bioinformatic analyses were carried out using the Database for Annotation, Visualization and IntegratedDiscovery Functional Annotation Tool, Gene Ontology (GO) TreeMachine and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A total of 26 552 SAGE tags of asthmatic rat lung were obtained, of which 12 221 were unique tags. Of the unique tags, 55.5% were matched with known genes. By comparison of the two libraries, 186 differentially expressed tags (P < 0.05) were identified, of which 103 were upregulated and 83 were downregulated. Using the bioinformatic tools these genes were classified into 23 functional groups, 15 KEGG pathways and 37 enriched GO categories. The bioinformatic analyses of gene distribution, enriched categories and the involvement of specific pathways in the SAGE libraries have provided information on regulatory networks of the EAR phase of asthma. Analyses of the regulated genes of interest may inform new hypotheses, increase our understanding of the disease and provide a foundation for future research.
The Influence of Metabolic Syndrome and Sex on the DNA Methylome in Schizophrenia

PubMed Central

Lines, Brittany N.

2018-01-01

Introduction The mechanism by which metabolic syndrome occurs in schizophrenia is not completely known; however, previous work suggests that changes in DNA methylation may be involved which is further influenced by sex. Within this study, the DNA methylome was profiled to identify altered methylation associated with metabolic syndrome in a schizophrenia population on atypical antipsychotics. Methods Peripheral blood from schizophrenia subjects was utilized for DNA methylation analyses. Discovery analyses (n = 96) were performed using an epigenome-wide analysis on the Illumina HumanMethylation450K BeadChip based on metabolic syndrome diagnosis. A secondary discovery analysis was conducted based on sex. The top hits from the discovery analyses were assessed in an additional validation set (n = 166) using site-specific methylation pyrosequencing. Results A significant increase in CDH22 gene methylation in subjects with metabolic syndrome was identified in the overall sample. Additionally, differential methylation was found within the MAP3K13 gene in females and the CCDC8 gene within males. Significant differences in methylation were again observed for the CDH22 and MAP3K13 genes, but not CCDC8, in the validation sample set. Conclusions This study provides preliminary evidence that DNA methylation may be associated with metabolic syndrome and sex in schizophrenia. PMID:29850476
Integrating microarray analysis and the soybean genome to understand the soybeans iron deficiency response

PubMed Central

2009-01-01

Background Soybeans grown in the upper Midwestern United States often suffer from iron deficiency chlorosis, which results in yield loss at the end of the season. To better understand the effect of iron availability on soybean yield, we identified genes in two near isogenic lines with changes in expression patterns when plants were grown in iron sufficient and iron deficient conditions. Results Transcriptional profiles of soybean (Glycine max, L. Merr) near isogenic lines Clark (PI548553, iron efficient) and IsoClark (PI547430, iron inefficient) grown under Fe-sufficient and Fe-limited conditions were analyzed and compared using the Affymetrix® GeneChip® Soybean Genome Array. There were 835 candidate genes in the Clark (PI548553) genotype and 200 candidate genes in the IsoClark (PI547430) genotype putatively involved in soybean's iron stress response. Of these candidate genes, fifty-eight genes in the Clark genotype were identified with a genetic location within known iron efficiency QTL and 21 in the IsoClark genotype. The arrays also identified 170 single feature polymorphisms (SFPs) specific to either Clark or IsoClark. A sliding window analysis of the microarray data and the 7X genome assembly coupled with an iterative model of the data showed the candidate genes are clustered in the genome. An analysis of 5' untranslated regions in the promoter of candidate genes identified 11 conserved motifs in 248 differentially expressed genes, all from the Clark genotype, representing 129 clusters identified earlier, confirming the cluster analysis results. Conclusion These analyses have identified the first genes with expression patterns that are affected by iron stress and are located within QTL specific to iron deficiency stress. The genetic location and promoter motif analysis results support the hypothesis that the differentially expressed genes are co-regulated. The combined results of all analyses lead us to postulate iron inefficiency in soybean is a result of a mutation in a transcription factor(s), which controls the expression of genes required in inducing an iron stress response. PMID:19678937
DNA barcodes reveal species-specific mercury levels in tuna sushi that pose a health risk to consumers

PubMed Central

Lowenstein, Jacob H.; Burger, Joanna; Jeitner, Christian W.; Amato, George; Kolokotronis, Sergios-Orestis; Gochfeld, Michael

2010-01-01

Excessive ingestion of mercury—a health hazard associated with consuming predatory fishes—damages neurological, sensory-motor and cardiovascular functioning. The mercury levels found in Bigeye Tuna (Thunnus obesus) and bluefin tuna species (Thunnus maccoyii, Thunnus orientalis, and Thunnus thynnus), exceed or approach levels permissible by Canada, the European Union, Japan, the US, and the World Health Organization. We used DNA barcodes to identify tuna sushi samples analysed for mercury and demonstrate that the ability to identify cryptic samples in the market place allows regulatory agencies to more accurately measure the risk faced by fish consumers and enact policies that better safeguard their health. PMID:20410032
Extending Data Worth Analyses to Select Multiple Observations Targeting Multiple Forecasts.

PubMed

Vilhelmsen, Troels N; Ferré, Ty P A

2018-05-01

Hydrological models are often set up to provide specific forecasts of interest. Owing to the inherent uncertainty in data used to derive model structure and used to constrain parameter variations, the model forecasts will be uncertain. Additional data collection is often performed to minimize this forecast uncertainty. Given our common financial restrictions, it is critical that we identify data with maximal information content with respect to forecast of interest. In practice, this often devolves to qualitative decisions based on expert opinion. However, there is no assurance that this will lead to optimal design, especially for complex hydrogeological problems. Specifically, these complexities include considerations of multiple forecasts, shared information among potential observations, information content of existing data, and the assumptions and simplifications underlying model construction. In the present study, we extend previous data worth analyses to include: simultaneous selection of multiple new measurements and consideration of multiple forecasts of interest. We show how the suggested approach can be used to optimize data collection. This can be used in a manner that suggests specific measurement sets or that produces probability maps indicating areas likely to be informative for specific forecasts. Moreover, we provide examples documenting that sequential measurement election approaches often lead to suboptimal designs and that estimates of data covariance should be included when selecting future measurement sets. © 2017, National Ground Water Association.
Dissection of stromal and cancer cell-derived signals in melanoma xenografts before and after treatment with DMXAA

PubMed Central

Henare, K; Wang, L; Wang, L-Cs; Thomsen, L; Tijono, S; Chen, C-Jj; Winkler, S; Dunbar, P R; Print, C; Ching, L-M

2012-01-01

Background: The non-malignant cells of the tumour stroma have a critical role in tumour biology. Studies dissecting the interplay between cancer cells and stromal cells are required to further our understanding of tumour progression and methods of intervention. For proof-of-principle of a multi-modal approach to dissect the differential effects of treatment on cancer cells and stromal cells, we analysed the effects of the stromal-targeting agent 5,6-dimethylxanthenone-4-acetic acid on melanoma xenografts. Methods: Flow cytometry and multi-colour immunofluorescence staining was used to analyse leukocyte numbers in xenografts. Murine-specific and human-specific multiplex cytokine panels were used to quantitate cytokines produced by stromal and melanoma cells, respectively. Human and mouse Affymetrix microarrays were used to separately identify melanoma cell-specific and stromal cell-specific gene expression. Results: 5,6-Dimethylxanthenone-4-acetic acid activated pro-inflammatory signalling pathways and cytokine expression from both stromal and cancer cells, leading to neutrophil accumulation and haemorrhagic necrosis and a delay in tumour re-growth of 26 days in A375 melanoma xenografts. Conclusion: 5,6-Dimethylxanthenone-4-acetic acid and related analogues may potentially have utility in the treatment of melanoma. The experimental platform used allowed distinction between cancer cells and stromal cells and can be applied to investigate other tumour models and anti-cancer agents. PMID:22415295

Multivariate analyses of individual variation in soccer skill as a tool for talent identification and development: utilising evolutionary theory in sports science.

PubMed

Wilson, Robbie S; James, Rob S; David, Gwendolyn; Hermann, Ecki; Morgan, Oliver J; Niehaus, Amanda C; Hunter, Andrew; Thake, Doug; Smith, Michelle D

2016-11-01

The development of a comprehensive protocol for quantifying soccer-specific skill could markedly improve both talent identification and development. Surprisingly, most protocols for talent identification in soccer still focus on the more generic athletic attributes of team sports, such as speed, strength, agility and endurance, rather than on a player's technical skills. We used a multivariate methodology borrowed from evolutionary analyses of adaptation to develop our quantitative assessment of individual soccer-specific skill. We tested the performance of 40 individual academy-level players in eight different soccer-specific tasks across an age range of 13-18 years old. We first quantified the repeatability of each skill performance then explored the effects of age on soccer-specific skill, correlations between each of the pairs of skill tasks independent of age, and finally developed an individual metric of overall skill performance that could be easily used by coaches. All of our measured traits were highly repeatable when assessed over a short period and we found that an individual's overall skill - as well as their performance in their best task - was strongly positively correlated with age. Most importantly, our study established a simple but comprehensive methodology for assessing skill performance in soccer players, thus allowing coaches to rapidly assess the relative abilities of their players, identify promising youths and work on eliminating skill deficits in players.
An Org-1-Tup transcriptional cascade reveals different types of alary muscles connecting internal organs in Drosophila.

PubMed

Boukhatmi, Hadi; Schaub, Christoph; Bataillé, Laetitia; Reim, Ingolf; Frendo, Jean-Louis; Frasch, Manfred; Vincent, Alain

2014-10-01

The T-box transcription factor Tbx1 and the LIM-homeodomain transcription factor Islet1 are key components in regulatory circuits that generate myogenic and cardiogenic lineage diversity in chordates. We show here that Org-1 and Tup, the Drosophila orthologs of Tbx1 and Islet1, are co-expressed and required for formation of the heart-associated alary muscles (AMs) in the abdomen. The same holds true for lineage-related muscles in the thorax that have not been described previously, which we name thoracic alary-related muscles (TARMs). Lineage analyses identified the progenitor cell for each AM and TARM. Three-dimensional high-resolution analyses indicate that AMs and TARMs connect the exoskeleton to the aorta/heart and to different regions of the midgut, respectively, and surround-specific tracheal branches, pointing to an architectural role in the internal anatomy of the larva. Org-1 controls tup expression in the AM/TARM lineage by direct binding to two regulatory sites within an AM/TARM-specific cis-regulatory module, tupAME. The contributions of Org-1 and Tup to the specification of Drosophila AMs and TARMs provide new insights into the transcriptional control of Drosophila larval muscle diversification and highlight new parallels with gene regulatory networks involved in the specification of cardiopharyngeal mesodermal derivatives in chordates. © 2014. Published by The Company of Biologists Ltd.
In-depth analyses of paleolithic pigments in cave climatic conditions

NASA Astrophysics Data System (ADS)

Touron, Stéphanie; Trichereau, Barbara; Syvilay, Delphine

2017-07-01

Painted caves are a specific environment which preservation needs multidisciplinary studies carried out within the different actors. The actions set-up must follow national and European ethics and treaties and be as less invasive as possible to preserve the integrity of the site. Studying colorants in caves should meet these expectations and take into account on-field conditions: high humidity rate, reduced access to electricity, etc. Therefore, non-invasive analyses should be preferred. However, their limits restrict the field of application and sometimes sampling and laboratory analyses must be used to answer the problematic. It is especially true when the pigment is covered by calcite. For this purpose, the Laser-Induced Breakdown Spectroscopy (LIBS) has been assessed to identify the composition with stratigraphic analyses. This study carries out in-depth profile on laboratory samples in conditions close to the ones meet in caves. Samples were prepared on a calcareous substrate using three pigments: red ochre, manganese black and carbon black and two binding media: water and saliva. All samples have been covered by calcite. Four sets of measurements have then been done using the LIBS instrument. The in-depth profiles were obtained using the Standard Normal Variate (SNV) normalization. For all the samples, the pigment layer was identified in the second or third shot, the calcite layer being quite thin. However, the results remain promising with the carbon black pigment but not really conclusive, the carbon being generally quite difficult to quantify.
Comprehensive high-resolution genomic profiling and cytogenetics of human chondrocyte cultures by GTG-banding, locus-specific FISH, SKY and SNP array.

PubMed

Wallenborn, M; Petters, O; Rudolf, D; Hantmann, H; Richter, M; Ahnert, P; Rohani, L; Smink, J J; Bulwin, G C; Krupp, W; Schulz, R M; Holland, H

2018-04-23

In the development of cell-based medicinal products, it is crucial to guarantee that the application of such an advanced therapy medicinal product (ATMP) is safe for the patients. The consensus of the European regulatory authorities is: "In conclusion, on the basis of the state of art, conventional karyotyping can be considered a valuable and useful technique to analyse chromosomal stability during preclinical studies". 408 chondrocyte samples (84 monolayers and 324 spheroids) from six patients were analysed using trypsin-Giemsa staining, spectral karyotyping and fluorescence in situ hybridisation, to evaluate the genetic stability of chondrocyte samples from non-clinical studies. Single nucleotide polymorphism (SNP) array analysis was performed on chondrocyte spheroids from five of the six donors. Applying this combination of techniques, the genetic analyses performed revealed no significant genetic instability until passage 3 in monolayer cells and interphase cells from spheroid cultures at different time points. Clonal occurrence of polyploid metaphases and endoreduplications were identified associated with prolonged cultivation time. Also, gonosomal losses were observed in chondrocyte spheroids, with increasing passage and duration of the differentiation phase. Interestingly, in one of the donors, chromosomal aberrations that are also described in extraskeletal myxoid chondrosarcoma were identified. The SNP array analysis exhibited chromosomal aberrations in two donors and copy neutral losses of heterozygosity regions in four donors. This study showed the necessity of combined genetic analyses at defined cultivation time points in quality studies within the field of cell therapy.
Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes

PubMed Central

Winnard, Paul T.; Zhang, Chi; Vesuna, Farhad; Kang, Jeon Woong; Garry, Jonah; Dasari, Ramachandra Rao; Barman, Ishan; Raman, Venu

2017-01-01

Molecular characterization of organ-specific metastatic lesions, which distinguish them from the primary tumor, will provide a better understanding of tissue specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cell lines directly from organ explants that are phenotypically distinct from the primary tumor cell line. Label-free Raman spectroscopy was used and informative spectral bands were ascertained as differentiators of organ-specific metastases as opposed to the presence of a single universal marker. Decision algorithms derived from the Raman spectra unambiguously identified these isogenic cell lines as unique biological entities – a finding reinforced through metabolomic analyses that indicated tissue of origin metabolite distinctions between the cell lines. Notably, complementarity of the metabolomics and Raman datasets was found. Our findings provide evidence that metastatic spread generates tissue-specific adaptations at the molecular level within cancer cells, which can be differentiated with Raman spectroscopy. PMID:28145887
Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes.

PubMed

Winnard, Paul T; Zhang, Chi; Vesuna, Farhad; Kang, Jeon Woong; Garry, Jonah; Dasari, Ramachandra Rao; Barman, Ishan; Raman, Venu

2017-03-21

Molecular characterization of organ-specific metastatic lesions, which distinguish them from the primary tumor, will provide a better understanding of tissue specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cell lines directly from organ explants that are phenotypically distinct from the primary tumor cell line. Label-free Raman spectroscopy was used and informative spectral bands were ascertained as differentiators of organ-specific metastases as opposed to the presence of a single universal marker. Decision algorithms derived from the Raman spectra unambiguously identified these isogenic cell lines as unique biological entities - a finding reinforced through metabolomic analyses that indicated tissue of origin metabolite distinctions between the cell lines. Notably, complementarity of the metabolomics and Raman datasets was found. Our findings provide evidence that metastatic spread generates tissue-specific adaptations at the molecular level within cancer cells, which can be differentiated with Raman spectroscopy.
Sensitivity and Specificity of Suspected Case Definition Used during West Africa Ebola Epidemic

PubMed Central

Champaloux, Steven W.; Keïta, Sakoba; Martel, Lise; Bilivogui, Pepe; Knust, Barbara; McCollum, Andrea M.

2018-01-01

Rapid early detection and control of Ebola virus disease (EVD) is contingent on accurate case definitions. Using an epidemic surveillance dataset from Guinea, we analyzed an EVD case definition developed by the World Health Organization (WHO) and used in Guinea. We used the surveillance dataset (March–October 2014; n = 2,847 persons) to identify patients who satisfied or did not satisfy case definition criteria. Laboratory confirmation determined cases from noncases, and we calculated sensitivity, specificity and predictive values. The sensitivity of the defintion was 68.9%, and the specificity of the definition was 49.6%. The presence of epidemiologic risk factors (i.e., recent contact with a known or suspected EVD case-patient) had the highest sensitivity (74.7%), and unexplained deaths had the highest specificity (92.8%). Results for case definition analyses were statistically significant (p<0.05 by χ2 test). Multiple components of the EVD case definition used in Guinea contributed to improved overall sensitivity and specificity. PMID:29260687
Final technical report

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

Edward DeLong

2011-10-07

Our overarching goals in this project were to: Develop and improve high-throughput sequencing methods and analytical approaches for quantitative analyses of microbial gene expression at the Hawaii Ocean Time Series Station and the Bermuda Atlantic Time Series Station; Conduct field analyses following gene expression patterns in picoplankton microbial communities in general, and Prochlorococcus flow sorted from that community, as they respond to different environmental variables (light, macronutrients, dissolved organic carbon), that are predicted to influence activity, productivity, and carbon cycling; Use the expression analyses of flow sorted Prochlorococcus to identify horizontally transferred genes and gene products, in particular those thatmore » are located in genomic islands and likely to confer habitat-specific fitness advantages; Use the microbial community gene expression data that we generate to gain insights, and test hypotheses, about the variability, genomic context, activity and function of as yet uncharacterized gene products, that appear highly expressed in the environment. We achieved the above goals, and even more over the course of the project. This includes a number of novel methodological developments, as well as the standardization of microbial community gene expression analyses in both field surveys, and experimental modalities. The availability of these methods, tools and approaches is changing current practice in microbial community analyses.« less
Siemens Immulite Aspergillus-specific IgG assay for chronic pulmonary aspergillosis diagnosis.

PubMed

Page, Iain D; Richardson, Malcolm D; Denning, David W

2018-05-14

Chronic pulmonary aspergillosis (CPA) complicates underlying lung disease, including treated tuberculosis. Measurement of Aspergillus-specific immunoglobulin G (IgG) is a key diagnostic step. Cutoffs have been proposed based on receiver operating characteristic (ROC) curve analyses comparing CPA cases to healthy controls, but performance in at-risk populations with underlying lung disease is unclear. We evaluated optimal cutoffs for the Siemens Immulite Aspergillus-specific IgG assay for CPA diagnosis in relation to large groups of healthy and diseased controls with treated pulmonary tuberculosis. Sera from 241 patients with CPA attending the UK National Aspergillosis Centre, 299 Ugandan blood donors (healthy controls), and 398 Ugandans with treated pulmonary tuberculosis (diseased controls) were tested. Radiological screening removed potential CPA cases from diseased controls (234 screened diseased controls). ROC curve analyses were performed and optimal cutoffs identified by Youden J statistic. CPA versus control ROC area under curve (AUC) results were: healthy controls 0.984 (95% confidence interval 0.972-0.997), diseased controls 0.972 (0.959-0.985), screened diseased controls 0.979 (0.967-0.992). Optimal cutoffs were: healthy controls 15 mg/l (94.6% sensitivity, 98% specificity), unscreened diseased controls 15 mg/l (94.6% sensitivity, 94.5% specificity), screened diseased controls 25 mg/l (92.9% sensitivity, 98.7% specificity). Results were similar in healthy and diseased controls. We advocate a cutoff of 20 mg/l as this is the midpoint of the range of optimal cutoffs. Cutoffs calculated in relation to healthy controls for other assays are likely to remain valid for use in a treated tuberculosis population.
The cleavage specificity of the aspartic protease of cocoa beans involved in the generation of the cocoa-specific aroma precursors.

PubMed

Janek, Katharina; Niewienda, Agathe; Wöstemeyer, Johannes; Voigt, Jürgen

2016-11-15

Particular peptides generated from the vicilin-class(7S) globulin of the cocoa beans by acid-induced proteolysis during cocoa fermentation are essential precursors of the cocoa-specific aroma notes. As revealed by in vitro studies, the formation of the cocoa-specific aroma precursors depends on the particular cleavage specificity of the cocoa aspartic protease, which cannot be substituted by pepsin. Therefore, we have investigated the effects of aspartic protease inhibitors on both enzymes and comparatively studied their cleavage specificities using different protein substrates and MALDI-TOF mass spectrometric analyses of the generated oligopeptides. Three classes of cleavage sites have been identified and characterized: (I) sequences exclusively cleaved by the cocoa enzyme, (II) sequences cleaved by both pepsin and the cocoa enzyme, and (III) those cleaved exclusively by pepsin. In contrast to most aspartic proteases from other origins, basic amino acid residues, particularly lysine, were found to be abundant in the specific cleavage sites of the cocoa enzyme. Copyright © 2016 Elsevier Ltd. All rights reserved.
Resilience and Happiness After Spinal Cord Injury: A Qualitative Study

PubMed Central

Duggan, Colette; Wilson, Catherine; DiPonio, Lisa; Trumpower, Brad

2016-01-01

Objective: The purpose of this study was to identify factors associated with resilience among individuals with spinal cord injury (SCI). Methods: Qualitative analyses were conducted of the written comments that were completed as part of a cross-sectional survey of individuals with SCI living in the community. More than 1,800 mail surveys were distributed to individuals identified as having a traumatic SCI through the records and/or membership lists of 4 organizations. Four hundred and seventy-five individuals completed and returned the survey, with approximately half (48.6%; n = 231) of respondents answering the open-ended question “Is there anything else you would like to tell us about your resilience or ability to ‘bounce back’ when you face a challenge?” Results: Analyses of these responses identified both specific resources and cognitive perspectives that are associated with perceived happiness. Responses fell within 8 general categories: resilience, general outlook on life, social support and social relationships, religion or faith in a higher power, mood, physical health and functioning (including pain), social comparisons, and resources. Nuanced themes within these categories were identified and were generally concordant with self-reported level of happiness. Conclusion: A majority of respondents with SCI identified themselves as happy and explained their adjustment and resilience as related to personality, good social support, and a spiritual connection. In contrast, pain and physical challenges appeared to be associated with limited ability to bounce back. PMID:29339852
Validation of PDE9A Gene Identified in GWAS Showing Strong Association with Milk Production Traits in Chinese Holstein.

PubMed

Yang, Shao-Hua; Bi, Xiao-Jun; Xie, Yan; Li, Cong; Zhang, Sheng-Li; Zhang, Qin; Sun, Dong-Xiao

2015-11-05

Phosphodiesterase9A (PDE9A) is a cyclic guanosine monophosphate (cGMP)-specific enzyme widely expressed among the tissues, which is important in activating cGMP-dependent signaling pathways. In our previous genome-wide association study, a single nucleotide polymorphism (SNP) (BTA-55340-no-rs(b)) located in the intron 14 of PDE9A, was found to be significantly associated with protein yield. In addition, we found that PDE9A was highly expressed in mammary gland by analyzing its mRNA expression in different tissues. The objectives of this study were to identify genetic polymorphisms of PDE9A and to determine the effects of these variants on milk production traits in dairy cattle. DNA sequencing identified 11 single nucleotide polymorphisms (SNPs) and six SNPs in 5' regulatory region were genotyped to test for the subsequent association analyses. After Bonferroni correction for multiple testing, all these identified SNPs were statistically significant for one or more milk production traits (p < 0.0001~0.0077). Interestingly, haplotype-based association analysis revealed similar effects on milk production traits (p < 0.01). In follow-up RNA expression analyses, two SNPs (c.-1376 G>A, c.-724 A>G) were involved in the regulation of gene expression. Consequently, our findings provide confirmatory evidences for associations of PDE9A variants with milk production traits and these identified SNPs may serve as genetic markers to accelerate Chinese Holstein breeding program.
Trafficking in persons and victim health in Australia.

PubMed

Schloenhardt, Andreas; Klug, Benjamin

2011-12-01

This article explores the health problems experienced by victims of trafficking in persons in Australia and analyses the domestic support schemes established to assist these victims. It focuses specifically on the health of adult, female victims who constitute the majority of identified victims, and who are the principal recipients of government support services. Domestic experiences and support schemes are reviewed in the light of international law and best practice guidelines. Recommendations are made to improve the health services available to victims of trafficking in persons in Australia.
Improving Care for Veterans with PTSD: Comparing Risks and Benefits of Antipsychotics Versus Other Medications to Augment First-Line Pharmacologic Therapy

DTIC Science & Technology

2017-10-01

for all project Aims. Timeline- months 3-6. Status: completed. Task 6: Complete primary analyses and hypothesis testing for Aim 2, including...glucose. For each of these lab tests , each VA site can name them something different and can change names over times. Labs should be linked to Logical...Observation Identifiers Names (LOINC) codes, an international standard system that assigns a numeric code to specific lab tests . However, VA data
Can Automated Facial Expression Analysis Show Differences Between Autism and Typical Functioning?

PubMed

Borsos, Zsófia; Gyori, Miklos

2017-01-01

Exploratory analyses of emotional expressions using a commercially available facial expression recognition software are reported, from the context of a serious game for screening purposes. Our results are based on a comparative analysis of two matched groups of kindergarten-age children (high-functioning children with autism spectrum condition: n=13; typically developing children: n=13). Results indicate that this technology has the potential to identify autism-specific emotion expression features, and may play a role in affective diagnostic and assistive technologies.
Board on Earth Sciences and Resources and its Activities

NASA Technical Reports Server (NTRS)

Schiffries, Craig M.

1997-01-01

The Board will provide oversight of the earth science and resource activities within the National Research Council, provide a review of research and public activities in the solid-earth sciences, and provide analyses and recommendations relevant to the supply, delivery, and associated impacts of and issues related to hydrocarbon, metallic, and non-metallic mineral resources. The Board will monitor the status of the earth sciences, assess the health of the disciplines, and identify research opportunities, and will respond to specific agency requests.
40 CFR 279.72 - On-specification used oil fuel.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of § 279.11 by performing analyses or obtaining copies of analyses or other information documenting...-specification used oil fuel. (a) Analysis of used oil fuel. A generator, transporter, processor/re-refiner, or... meets the specifications for used oil fuel under § 279.11, must keep copies of analyses of the used oil...
Students' Attitudes to Information in the Press: Critical Reading of a Newspaper Article With Scientific Content

NASA Astrophysics Data System (ADS)

Oliveras, B.; Márquez, C.; Sanmartí, N.

2014-08-01

This research analyses what happens when a critical reading activity based on a press article dealing with an energy-related problem is implemented with two groups of students of 13-14 years old and 16-17 years old in the same school (a total of 117 students). Specifically, the research analyses the students' profiles from the standpoint of their attitudes to the information given in the news story and the use they make of it when writing an argumentative text. It also analyses the difficulties the students have when it comes to applying their knowledge about energy in a real-life context. Lastly, some strategies are suggested for helping students to critically analyse the scientific content of a newspaper article. Three reader profiles were identified (the credulous reader, the ideological reader and the critical reader). No significant differences were found in reading profiles in terms of age or scientific knowledge. The findings show that the activity helped to link science learning in school with facts relating to an actual context, particularly in the case of students with more science knowledge.
Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii

PubMed Central

Mahamad Maifiah, Mohd Hafidz; Cheah, Soon-Ee; Johnson, Matthew D.; Han, Mei-Ling; Boyce, John D.; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S.; Hertzog, Paul; Purcell, Anthony W.; Song, Jiangning; Velkov, Tony; Creek, Darren J.; Li, Jian

2016-01-01

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii. PMID:26924392
Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

PubMed

Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

2016-02-29

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

Peptidome analysis of amniotic fluid from pregnancies with preeclampsia.

PubMed

Qian, Yating; Zhang, Lei; Rui, Can; Ding, Hongjuan; Mao, Pengyuan; Ruan, Hongjie; Jia, Ruizhe

2017-11-01

Preeclampsia (PE), a life‑threatening, complicated pregnancy‑associated disease, has recently become a research focus in obstetrics. However, the peptidome of the amniotic fluid in PE patients has rarely been investigated. The present study used peptidomic profiling to perform a comparative analysis of human amniotic fluid between normal and PE pregnancies. Centrifugal ultraﬁltration and liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) was combined with isotopomeric dimethyl labels to gain a deeper understanding of the role of proteins and the peptidome in the onset of PE. Following ultrafiltration and LC‑MS/MS, 352 peptides were identified. Of these, 23 peptides were observed to be significantly differentially expressed (6 downregulated and 17 upregulated; P<0.05). Using Gene Ontology and Blastp analyses, the functions and biological activities of these 23 peptides were identified and revealed to include autophagy, signal transduction, receptor activity, enzymatic activity and nucleic acid binding. In addition, a bibliographic search revealed that some of the identified peptides, including Titin, are crucial to the pathogenesis underlying PE. The present study identified 23 peptides expressed at significantly different levels in the amniotic fluid of PE and normal pregnancies. A comprehensive peptidome analysis is more efficient than a simple biomarker analysis at revealing deficiencies and improving the detection rate in diseases. These analyses therefore provide a substantial advantage in applications aimed at the discovery of disease‑specific biomarkers.
Allogeneic T cell responses are regulated by a specific miRNA-mRNA network

PubMed Central

Sun, Yaping; Tawara, Isao; Zhao, Meng; Qin, Zhaohui S.; Toubai, Tomomi; Mathewson, Nathan; Tamaki, Hiroya; Nieves, Evelyn; Chinnaiyan, Arul M.; Reddy, Pavan

2013-01-01

Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses and their direct mRNA targets. We identified a unique expression pattern of miRs and mRNAs following the allostimulation of T cells and a high correlation between the expression of the identified miRs and a reduction of their mRNA targets. miRs and mRNAs that were predicted to be differentially regulated in allogeneic T cells compared with nonspecifically stimulated T cells were validated in vitro. These analyses identified wings apart-like homolog (Wapal) and synaptojanin 1 (Synj1) as potential regulators of allogeneic T cell responses. The expression of these molecular targets in vivo was confirmed in MHC-mismatched experimental BMT. Targeted silencing of either Wapal or Synj1 prevented the development of GVH response, confirming a role for these regulators in allogeneic T cell responses. Thus, this genome-wide analysis of miRNA-mRNA interactions identifies previously unrecognized molecular regulators of T cell responses. PMID:24216511
Genomic Variation by Whole-Genome SNP Mapping Arrays Predicts Time-to-Event Outcome in Patients with Chronic Lymphocytic Leukemia

PubMed Central

Schweighofer, Carmen D.; Coombes, Kevin R.; Majewski, Tadeusz; Barron, Lynn L.; Lerner, Susan; Sargent, Rachel L.; O'Brien, Susan; Ferrajoli, Alessandra; Wierda, William G.; Czerniak, Bogdan A.; Medeiros, L. Jeffrey; Keating, Michael J.; Abruzzo, Lynne V.

2013-01-01

Genomic abnormalities, such as deletions in 11q22 or 17p13, are associated with poorer prognosis in patients with chronic lymphocytic leukemia (CLL). We hypothesized that unknown regions of copy number variation (CNV) affect clinical outcome and can be detected by array-based single-nucleotide polymorphism (SNP) genotyping. We compared SNP genotypes from 168 untreated patients with CLL with genotypes from 73 white HapMap controls. We identified 322 regions of recurrent CNV, 82 of which occurred significantly more often in CLL than in HapMap (CLL-specific CNV), including regions typically aberrant in CLL: deletions in 6q21, 11q22, 13q14, and 17p13 and trisomy 12. In univariate analyses, 35 of total and 11 of CLL-specific CNVs were associated with unfavorable time-to-event outcomes, including gains or losses in chromosomes 2p, 4p, 4q, 6p, 6q, 7q, 11p, 11q, and 17p. In multivariate analyses, six CNVs (ie, CLL-specific variations in 11p15.1-15.4 or 6q27) predicted time-to-treatment or overall survival independently of established markers of prognosis. Moreover, genotypic complexity (ie, the number of independent CNVs per patient) significantly predicted prognosis, with a median time-to-treatment of 64 months versus 23 months in patients with zero to one versus two or more CNVs, respectively (P = 3.3 × 10−8). In summary, a comparison of SNP genotypes from patients with CLL with HapMap controls allowed us to identify known and unknown recurrent CNVs and to determine regions and rates of CNV that predict poorer prognosis in patients with CLL. PMID:23273604
Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn.

PubMed

Dong, Yongbin; Wang, Qilei; Zhang, Long; Du, Chunguang; Xiong, Wenwei; Chen, Xinjian; Deng, Fei; Ma, Zhiyan; Qiao, Dahe; Hu, Chunhui; Ren, Yangliu; Li, Yuling

2015-01-01

The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize.
Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn

PubMed Central

Du, Chunguang; Xiong, Wenwei; Chen, Xinjian; Deng, Fei; Ma, Zhiyan; Qiao, Dahe; Hu, Chunhui; Ren, Yangliu; Li, Yuling

2015-01-01

The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize. PMID:26587848
Identification of Brucella melitensis Rev.1 vaccine-strain genetic markers: Towards understanding the molecular mechanism behind virulence attenuation.

PubMed

Issa, Mohammad Nouh; Ashhab, Yaqoub

2016-09-22

Brucella melitensis Rev.1 is an avirulent strain that is widely used as a live vaccine to control brucellosis in small ruminants. Although an assembled draft version of Rev.1 genome has been available since 2009, this genome has not been investigated to characterize this important vaccine. In the present work, we used the draft genome of Rev.1 to perform a thorough genomic comparison and sequence analysis to identify and characterize the panel of its unique genetic markers. The draft genome of Rev.1 was compared with genome sequences of 36 different Brucella melitensis strains from the Brucella project of the Broad Institute of MIT and Harvard. The comparative analyses revealed 32 genetic alterations (30 SNPs, 1 single-bp insertion and 1 single-bp deletion) that are exclusively present in the Rev.1 genome. In silico analyses showed that 9 out of the 17 non-synonymous mutations are deleterious. Three ABC transporters are among the disrupted genes that can be linked to virulence attenuation. Out of the 32 mutations, 11 Rev.1 specific markers were selected to test their potential to discriminate Rev.1 using a bi-directional allele-specific PCR assay. Six markers were able to distinguish between Rev.1 and a set of control strains. We succeeded in identifying a panel of 32 genome-specific markers of the B. melitensis Rev.1 vaccine strain. Extensive in silico analysis showed that a considerable number of these mutations could severely affect the function of the associated genes. In addition, some of the discovered markers were able to discriminate Rev.1 strain from a group of control strains using practical PCR tests that can be applied in resource-limited settings. Copyright © 2016 Elsevier Ltd. All rights reserved.
Phthalate esters and childhood asthma: A systematic review and congener-specific meta-analysis.

PubMed

Li, Ming-Chieh; Chen, Chi-Hsien; Guo, Yue Leon

2017-10-01

Exposure to phthalate esters (PAEs) has been associated with childhood asthma, but the congener-specific effects of PAEs on childhood asthma were unclear. We aimed to systematically review and meta-analyze observational studies on the associations between specific effects of PAEs and the risk of childhood asthma. Relevant studies were identified by searching three databases up to October 20, 2016. The reference lists of the retrieved articles were also reviewed. We included observational studies that reported risk estimates with 95% confidence intervals (CIs) for the associations between phthalate exposure and the risk of childhood asthma. Fixed-effects models were generally applied to calculate pooled risk estimates. When heterogeneity was present, random-effects models were applied. A total of nine studies featuring 43 data points were included in our final meta-analyses. Results indicated that the benzyl butyl phthalate (BBzP) exposure had a significant association with the risk of childhood asthma. The Odd Ratios (ORs) were from 1.39 to 1.41 for different combination strategies. Subgroup analyses by different exposure period or samples used showed that prenatal exposure to BBzP had a stronger association with the risk of childhood asthma (OR = 1.38, 95% CI = 1.09-1.75), compared to those with postnatal exposure. Besides, the association was evident when the phthalate exposure was measured from dust samples. The OR for the associations between di-2-ethylhexyl phthalate (DEHP) in dust and childhood asthma was 2.71 (95% CI = 1.39-5.28), and 2.08 (95% CI = 1.10-3.92) for BBzP. Our study suggested a positive association between DEHP and BBzP exposure and childhood asthma. Future studies are warranted to identify the underlying mechanisms of the association. Copyright © 2017 Elsevier Ltd. All rights reserved.
Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora

PubMed Central

Steige, Kim A.; Laenen, Benjamin; Reimegård, Johan; Slotte, Tanja

2017-01-01

Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora. We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species. PMID:28096395
Retrospective evaluation of all recorded horse race starts in Switzerland during a four year period focusing on discipline-specific risk factors for clinical events.

PubMed

Schweizer, C; Ramseyer, A; Gerber, V; Christen, G; Burger, D; Wohlfender, F D

2016-11-01

Racetrack injuries are of welfare concern and the prevention of injuries is an important goal in many racing jurisdictions. Over the years this has led to more detailed recording of clinical events on racecourses. However, risk factor analyses of clinical events at race meetings have not been previously reported for Switzerland. To identify discipline-specific factors that influence the occurrence of clinical events during race meetings with the ultimate aim of improving the monitoring and safety of racetracks in Switzerland and optimising racehorse welfare. Retrospective study of horse race data collected by the Swiss horse racing association. All race starts (n = 17,670, including 6198 flat, 1257 obstacle and 10,215 trot race starts) recorded over a period of 4 years (2009-2012) were analysed in multivariable mixed effect logistic regression models including horse and racecourse related data. The models were designed to identify discipline-specific factors influencing the occurrence of clinical events on racecourses in Switzerland. Factors influencing the risk of clinical events during races were different for each discipline. The risk of a clinical event in trot racing was lower for racing on a Porphyre sand track than on grass tracks. Horses whose driver was also their trainer had an approximately 2-fold higher risk for clinical events. In obstacle races, longer distances (2401-3300 m and 3301-5400 m, respectively) had a protective effect compared with racing over shorter distances. In flat racing, 5 racecourses reported significantly fewer clinical events. In all 3 disciplines, finishing 8th place or later was associated with clinical events. Changes in management that aim to improve the safety and welfare of racehorses, such as racetrack adaptations, need to be individualised for each discipline. © 2015 EVJ Ltd.
The Adequate Corpus Luteum: miR-96 Promotes Luteal Cell Survival and Progesterone Production.

PubMed

Mohammed, Bushra T; Sontakke, Sadanand D; Ioannidis, Jason; Duncan, W Colin; Donadeu, F Xavier

2017-07-01

Inadequate progesterone production from the corpus luteum is associated with pregnancy loss. Data available in model species suggest important roles of microRNAs (miRNAs) in luteal development and maintenance. To comprehensively investigate the involvement of miRNAs during the ovarian follicle-luteal transition. The effects of specific miRNAs on survival and steroid production by human luteinized granulosa cells (hLGCs) were tested using specific miRNA inhibitors. Candidate miRNAs were identified through microarray analyses of follicular and luteal tissues in a bovine model. An academic institution in the United Kingdom associated with a teaching hospital. hLGCs were obtained by standard transvaginal follicular-fluid aspiration from 35 women undergoing assisted conception. Inhibition of candidate miRNAs in vitro. Levels of miRNAs, mRNAs, FOXO1 protein, apoptosis, and steroids were measured in tissues and/or cultured cells. Two specific miRNA clusters, miR-183-96-182 and miR-212-132, were dramatically increased in luteal relative to follicular tissues. miR-96 and miR-132 were the most upregulated miRNAs within each cluster. Database analyses identified FOXO1 as a putative target of both these miRNAs. In cultured hLGCs, inhibition of miR-96 increased apoptosis and FOXO1 protein levels, and decreased progesterone production. These effects were prevented by small interfering RNA-mediated downregulation of FOXO1. In bovine luteal cells, miR-96 inhibition also led to increases in apoptosis and FOXO1 protein levels. miR-96 targets FOXO1 to regulate luteal development through effects on cell survival and steroid production. The miR-183-96-182 cluster could provide a novel target for the manipulation of luteal function. Copyright © 2017 Endocrine Society
Diversity Arrays Technology (DArT) for Pan-Genomic Evolutionary Studies of Non-Model Organisms

PubMed Central

James, Karen E.; Schneider, Harald; Ansell, Stephen W.; Evers, Margaret; Robba, Lavinia; Uszynski, Grzegorz; Pedersen, Niklas; Newton, Angela E.; Russell, Stephen J.; Vogel, Johannes C.; Kilian, Andrzej

2008-01-01

Background High-throughput tools for pan-genomic study, especially the DNA microarray platform, have sparked a remarkable increase in data production and enabled a shift in the scale at which biological investigation is possible. The use of microarrays to examine evolutionary relationships and processes, however, is predominantly restricted to model or near-model organisms. Methodology/Principal Findings This study explores the utility of Diversity Arrays Technology (DArT) in evolutionary studies of non-model organisms. DArT is a hybridization-based genotyping method that uses microarray technology to identify and type DNA polymorphism. Theoretically applicable to any organism (even one for which no prior genetic data are available), DArT has not yet been explored in exclusively wild sample sets, nor extensively examined in a phylogenetic framework. DArT recovered 1349 markers of largely low copy-number loci in two lineages of seed-free land plants: the diploid fern Asplenium viride and the haploid moss Garovaglia elegans. Direct sequencing of 148 of these DArT markers identified 30 putative loci including four routinely sequenced for evolutionary studies in plants. Phylogenetic analyses of DArT genotypes reveal phylogeographic and substrate specificity patterns in A. viride, a lack of phylogeographic pattern in Australian G. elegans, and additive variation in hybrid or mixed samples. Conclusions/Significance These results enable methodological recommendations including procedures for detecting and analysing DArT markers tailored specifically to evolutionary investigations and practical factors informing the decision to use DArT, and raise evolutionary hypotheses concerning substrate specificity and biogeographic patterns. Thus DArT is a demonstrably valuable addition to the set of existing molecular approaches used to infer biological phenomena such as adaptive radiations, population dynamics, hybridization, introgression, ecological differentiation and phylogeography. PMID:18301759
A theoretical and empirical framework for constructing culture-specific stigma instruments for Chile

PubMed Central

Yang, Lawrence H.; Valencia, Elie; Alvarado, Ruben; Link, Bruce; Huynh, Nina; Nguyen, Kristy; Morita, Kara; Saavedra, Mariella; Wong, Chak; Galea, Sandro; Susser, Ezra

2013-01-01

Different cultural contexts contribute to substantial variation in the stigma faced by people with psychosis globally. We propose a new formulation of how culture affects stigma to create psychometrically-validated tools to assess stigma’s culture-specific effects. We propose to construct culture-specific stigma measures for the Chilean context via: 1) open-ended administration of ‘universal’ stigma scales to a sample of individuals with psychosis, relatives, and community respondents; 2) qualitative analyses to identify how culture shapes stigma and to derive initial ‘culture-specific’ stigma items; 3) construction and pilot-testing of final ‘culture-specific’ stigma measures; 4) initial psychometric validation among a sample of individuals with psychosis. We identify initial hypotheses for how stigma might threaten the capacities to participate in fundamental activities that ‘matter most’ in the Chilean context. These include mental illness stigma threatening the man’s ability to protect the honor of the family, and the woman’s ability to be a ‘holy and pure’ mother. Mental illness stigma may further endanger the ability of the family to uphold reciprocal obligations within their social network. Developing such measures promises to aid efforts to address culture-specific forms of stigma, and to facilitate implementation of community mental health services, in Chile and other Latin American contexts. PMID:23990755
Flow cytometric purification of Colletotrichum higginsianum biotrophic hyphae from Arabidopsis leaves for stage-specific transcriptome analysis.

PubMed

Takahara, Hiroyuki; Dolf, Andreas; Endl, Elmar; O'Connell, Richard

2009-08-01

Generation of stage-specific cDNA libraries is a powerful approach to identify pathogen genes that are differentially expressed during plant infection. Biotrophic pathogens develop specialized infection structures inside living plant cells, but sampling the transcriptome of these structures is problematic due to the low ratio of fungal to plant RNA, and the lack of efficient methods to isolate them from infected plants. Here we established a method, based on fluorescence-activated cell sorting (FACS), to purify the intracellular biotrophic hyphae of Colletotrichum higginsianum from homogenates of infected Arabidopsis leaves. Specific selection of viable hyphae using a fluorescent vital marker provided intact RNA for cDNA library construction. Pilot-scale sequencing showed that the library was enriched with plant-induced and pathogenicity-related fungal genes, including some encoding small, soluble secreted proteins that represent candidate fungal effectors. The high purity of the hyphae (94%) prevented contamination of the library by sequences derived from host cells or other fungal cell types. RT-PCR confirmed that genes identified in the FACS-purified hyphae were also expressed in planta. The method has wide applicability for isolating the infection structures of other plant pathogens, and will facilitate cell-specific transcriptome analysis via deep sequencing and microarray hybridization, as well as proteomic analyses.
Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.).

PubMed

Yin, Tao; Wu, Hanying; Zhang, Shanglong; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming; Liu, Jingmei

2009-01-01

A 1.8 kb 5'-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from -986 to -959 and from -472 to -424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative beta-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were approximately 10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves.
Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.)

PubMed Central

Yin, Tao; Wu, Hanying; Zhang, Shanglong; Liu, Jingmei; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming

2009-01-01

A 1.8 kb 5′-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from –986 to –959 and from –472 to –424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative β-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were ∼10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves. PMID:19073962
Glypican1 identifies cancer exosomes and facilitates early detection of cancer

PubMed Central

Melo, Sonia A.; Luecke, Linda B.; Kahlert, Christoph; Fernandez, Agustin F.; Gammon, Seth T.; Kaye, Judith; LeBleu, Valerie S.; Mittendorf, Elizabeth A.; Weitz, Juergen; Rahbari, Nuh; Reissfelder, Christoph; Pilarsky, Christian; Fraga, Mario F.; Piwnica-Worms, David; Kalluri, Raghu

2016-01-01

Summary Exosomes are lipid bilayer-enclosed extracellular vesicles (EVs) that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer cell-derived exosomes in circulation is currently lacking. Using mass spectrometry analyses, we identified a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer cell-derived exosomes. GPC1+ circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of cancer patients and mice with cancer. GPC1+ crExos were detected in the serum of patients with pancreas cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreas disease from patients with early and late stage pancreas cancer. Levels of GPC1+ crExos correlate with tumor burden and survival in patients pre- and post-surgical tumor resection. GPC1+ crExos from patients and from mice with spontaneous pancreas tumors driven by oncogenic KRAS contained RNA with specific KRAS mutation, and it emerges as a reliable biomarker for the detection of PanIN lesions despite negative signal by MRI in mice. GPC1+ crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreas cancer to facilitate possible curative surgical therapy. PMID:26106858
Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

PubMed Central

Fedrigo, Olivier; Babbitt, Courtney C.; Wortham, Matthew; Tewari, Alok K.; London, Darin; Song, Lingyun; Lee, Bum-Kyu; Iyer, Vishwanath R.; Parker, Stephen C. J.; Margulies, Elliott H.; Wray, Gregory A.; Furey, Terrence S.; Crawford, Gregory E.

2012-01-01

Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species. PMID:22761590
Genetic neuroscience of mammalian learning and memory.

PubMed Central

Tonegawa, Susumu; Nakazawa, Kazu; Wilson, Matthew A

2003-01-01

Our primary research interest is to understand the molecular and cellular mechanisms on neuronal circuitry underlying the acquisition, consolidation and retrieval of hippocampus-dependent memory in rodents. We study these problems by producing genetically engineered (i.e. spatially targeted and/or temporally restricted) mice and analysing these mice by multifaceted methods including molecular and cellular biology, in vitro and in vivo physiology and behavioural studies. We attempt to identify deficits at each of the multiple levels of complexity in specific brain areas or cell types and deduce those deficits that underlie specific learning or memory. We will review our recent studies on the acquisition, consolidation and recall of memories that have been conducted with mouse strains in which genetic manipulations were targeted to specific types of cells in the hippocampus or forebrain of young adult mice. PMID:12740125
Molecular identification and phylogenetic analysis of important medicinal plant species in genus Paeonia based on rDNA-ITS, matK, and rbcL DNA barcode sequences.

PubMed

Kim, W J; Ji, Y; Choi, G; Kang, Y M; Yang, S; Moon, B C

2016-08-05

This study was performed to identify and analyze the phylogenetic relationship among four herbaceous species of the genus Paeonia, P. lactiflora, P. japonica, P. veitchii, and P. suffruticosa, using DNA barcodes. These four species, which are commonly used in traditional medicine as Paeoniae Radix and Moutan Radicis Cortex, are pharmaceutically defined in different ways in the national pharmacopoeias in Korea, Japan, and China. To authenticate the different species used in these medicines, we evaluated rDNA-internal transcribed spacers (ITS), matK and rbcL regions, which provide information capable of effectively distinguishing each species from one another. Seventeen samples were collected from different geographic regions in Korea and China, and DNA barcode regions were amplified using universal primers. Comparative analyses of these DNA barcode sequences revealed species-specific nucleotide sequences capable of discriminating the four Paeonia species. Among the entire sequences of three barcodes, marker nucleotides were identified at three positions in P. lactiflora, eleven in P. japonica, five in P. veitchii, and 25 in P. suffruticosa. Phylogenetic analyses also revealed four distinct clusters showing homogeneous clades with high resolution at the species level. The results demonstrate that the analysis of these three DNA barcode sequences is a reliable method for identifying the four Paeonia species and can be used to authenticate Paeoniae Radix and Moutan Radicis Cortex at the species level. Furthermore, based on the assessment of amplicon sizes, inter/intra-specific distances, marker nucleotides, and phylogenetic analysis, rDNA-ITS was the most suitable DNA barcode for identification of these species.
UHPLC/PDA-ESI/MS analysis of the main berry and leaf flavonol glycosides from different Carpathian Hippophaë rhamnoides L. varieties.

PubMed

Pop, Raluca Maria; Socaciu, Carmen; Pintea, Adela; Buzoianu, Anca Dana; Sanders, Mark Gerardus; Gruppen, Harry; Vincken, Jean-Paul

2013-01-01

Sea buckthorn (Hippophaë rhamnoides L.) is known to be rich in many bioactive compounds (such as vitamins, phenolics, carotenoids) important for human health and nutrition. Among the phenolics, berries and leaves contain a wide range of flavonols that are good quality and authenticity biomarkers. To compare the composition of the main flavonols of Romanian sea buckthorn berry and leaf varieties and to identify the specific biomarkers that contribute to sample differentiation among varieties. Six varieties of cultivated sea buckthorn (ssp. Carpatica) berries and leaves were analysed by UHPLC/PDA-ESI/MS. Berries and leaves contained mainly isorhamnetin (I) glycosides in different ratios. Whereas I-3-neohesperidoside, I-3-glucoside, I-3-rhamnosylglucoside, I-3-sophoroside-7-rhamnoside and free isorhamnetin were predominant for berries (out of 17 compounds identified), I-3-rhamnosylglucoside, I-3-neohesperidoside, I-3-glucoside, quercetin-3-pentoside, kaempferol-3-rutinoside, and quercetin-3-glucoside were predominant in leaves (out of 19 compounds identified). Berries contained, on average, 917 mg/100 g DW flavonol glycosides. Leaves had higher content of flavonol glycosides than berries, on average 1118 mg/100 g DW. The variation of the quantitative dataset analysed using principal component analysis accounted for 91% of the total variance in the case of berries and 73% in case of leaves, demonstrating a good discrimination among samples. Based on quantitative analysis, by principal component analysis, the flavonol derivatives can be considered as biomarkers to discriminate among varieties and to recognise specifically the berry versus leaf composition. Copyright © 2013 John Wiley & Sons, Ltd.

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