Sample records for analysis identifies distinct

  1. Heritability of Nociception IV: Neuropathic pain assays are genetically distinct across methods of peripheral nerve injury

    PubMed Central

    Young, Erin E.; Costigan, Michael; Herbert, Teri A.; Lariviere, William R.

    2013-01-01

    Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified five genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional nine assays of nociception and hypersensitivity to: 1) replicate the previously identified five pain types; 2) test whether any of the newly added pain assays represent novel genetically distinct pain types; 3) test the level of genetic relatedness among nine commonly employed neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the two previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. The four included mechanical hypersensitivity assays are genetically distinct, and do not comprise a single pain type as previously reported. Among the nine neuropathic pain assays including autotomy, chemotherapy, nerve ligation and spared nerve injury assays, at least four genetically distinct types of neuropathic sensory abnormalities were identified, corresponding to differences in nerve injury method. In addition, two itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types. PMID:24071598

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

    PubMed

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

    2002-04-01

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

  3. Analysis of the nucleoprotein gene identifies three distinct lineages of viral haemorrhagic septicemia virus (VHSV) within the European marine environment

    USGS Publications Warehouse

    Snow, M.; Cunningham, C.O.; Melvin, W.T.; Kurath, G.

    1999-01-01

    A ribonuclease (RNase) protection assay (RPA) has been used to detect nucleotide sequence variation within the nucleoprotein gene of 39 viral haemorrhagic septicaemia virus (VHSV) isolates of European marine origin. The classification of VHSV isolates based on RPA cleavage patterns permitted the identification of ten distinct groups of viruses based on differences at the molecular level. The nucleotide sequence of representatives of each of these groupings was determined and subjected to phylogenetic analysis. This revealed grouping of the European marine isolates of VHSV into three genotypes circulating within distinct geographic areas. A fourth genotype was identified comprising isolates originating from North America. Phylogenetic analyses indicated that VHSV isolates recovered from wild caught fish around the British Isles were genetically related to isolates responsible for losses in farmed turbot. Furthermore, a relationship between naturally occurring marine isolates and VHSV isolates causing mortality among rainbow trout in continental Europe was demonstrated. Analysis of the nucleoprotein gene identifies distinct lineages of viral haemorrhagic septicaemia virus within the European marine environment. Virus Res. 63, 35-44. Available from: 

  4. Framing life and death on YouTube: the strategic communication of organ donation messages by organ procurement organizations.

    PubMed

    VanderKnyff, Jeremy; Friedman, Daniela B; Tanner, Andrea

    2015-01-01

    Using a sample of YouTube videos posted on the YouTube channels of organ procurement organizations, a content analysis was conducted to identify the frames used to strategically communicate prodonation messages. A total of 377 videos were coded for general characteristics, format, speaker characteristics, organs discussed, structure, problem definition, and treatment. Principal components analysis identified message frames, and k-means cluster analysis established distinct groupings of videos on the basis of the strength of their relationship to message frames. Analysis of these frames and clusters found that organ procurement organizations present multiple, and sometimes competing, video types and message frames on YouTube. This study serves as important formative research that will inform future studies to measure the effectiveness of the distinct message frames and clusters identified.

  5. Identifying At-Risk Students in General Chemistry via Cluster Analysis of Affective Characteristics

    ERIC Educational Resources Information Center

    Chan, Julia Y. K.; Bauer, Christopher F.

    2014-01-01

    The purpose of this study is to identify academically at-risk students in first-semester general chemistry using affective characteristics via cluster analysis. Through the clustering of six preselected affective variables, three distinct affective groups were identified: low (at-risk), medium, and high. Students in the low affective group…

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

    PubMed

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

    2015-05-01

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

  7. A computational approach to identify cellular heterogeneity and tissue-specific gene regulatory networks.

    PubMed

    Jambusaria, Ankit; Klomp, Jeff; Hong, Zhigang; Rafii, Shahin; Dai, Yang; Malik, Asrar B; Rehman, Jalees

    2018-06-07

    The heterogeneity of cells across tissue types represents a major challenge for studying biological mechanisms as well as for therapeutic targeting of distinct tissues. Computational prediction of tissue-specific gene regulatory networks may provide important insights into the mechanisms underlying the cellular heterogeneity of cells in distinct organs and tissues. Using three pathway analysis techniques, gene set enrichment analysis (GSEA), parametric analysis of gene set enrichment (PGSEA), alongside our novel model (HeteroPath), which assesses heterogeneously upregulated and downregulated genes within the context of pathways, we generated distinct tissue-specific gene regulatory networks. We analyzed gene expression data derived from freshly isolated heart, brain, and lung endothelial cells and populations of neurons in the hippocampus, cingulate cortex, and amygdala. In both datasets, we found that HeteroPath segregated the distinct cellular populations by identifying regulatory pathways that were not identified by GSEA or PGSEA. Using simulated datasets, HeteroPath demonstrated robustness that was comparable to what was seen using existing gene set enrichment methods. Furthermore, we generated tissue-specific gene regulatory networks involved in vascular heterogeneity and neuronal heterogeneity by performing motif enrichment of the heterogeneous genes identified by HeteroPath and linking the enriched motifs to regulatory transcription factors in the ENCODE database. HeteroPath assesses contextual bidirectional gene expression within pathways and thus allows for transcriptomic assessment of cellular heterogeneity. Unraveling tissue-specific heterogeneity of gene expression can lead to a better understanding of the molecular underpinnings of tissue-specific phenotypes.

  8. Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines.

    PubMed

    Brasier, Allan R; Victor, Sundar; Boetticher, Gary; Ju, Hyunsu; Lee, Chang; Bleecker, Eugene R; Castro, Mario; Busse, William W; Calhoun, William J

    2008-01-01

    Asthma is a heterogeneous clinical disorder. Methods for objective identification of disease subtypes will focus on clinical interventions and help identify causative pathways. Few studies have explored phenotypes at a molecular level. We sought to discriminate asthma phenotypes on the basis of cytokine profiles in bronchoalveolar lavage (BAL) samples from patients with mild-moderate and severe asthma. Twenty-five cytokines were measured in BAL samples of 84 patients (41 severe, 43 mild-moderate) using bead-based multiplex immunoassays. The normalized data were subjected to statistical and informatics analysis. Four groups of asthmatic profiles could be identified on the basis of unsupervised analysis (hierarchical clustering) that were independent of treatment. One group, enriched in patients with severe asthma, showed differences in BAL cellular content, reductions in baseline pulmonary function, and enhanced response to methacholine provocation. Ten cytokines were identified that accurately predicted this group. Classification methods for predicting methacholine sensitivity were developed. The best model analysis predicted hyperresponders with 88% accuracy in 10 trials by using a 10-fold cross-validation. The cytokines that contributed to this model were IL-2, IL-4, and IL-5. On the basis of this classifier, 3 distinct hyperresponder classes were identified that varied in BAL eosinophil count and PC20 methacholine. Cytokine expression patterns in BAL can be used to identify distinct types of asthma and identify distinct subsets of methacholine hyperresponders. Further biomarker discovery in BAL may be informative.

  9. A gustatory second-order neuron that connects sucrose-sensitive primary neurons and a distinct region of the gnathal ganglion in the Drosophila brain

    PubMed Central

    Miyazaki, Takaaki; Lin, Tzu-Yang; Ito, Kei; Lee, Chi-Hon; Stopfer, Mark

    2016-01-01

    Although the gustatory system provides animals with sensory cues important for food choice and other critical behaviors, little is known about neural circuitry immediately following gustatory sensory neurons (GSNs). Here, we identify and characterize a bilateral pair of gustatory second-order neurons in Drosophila. Previous studies identified GSNs that relay taste information to distinct subregions of the primary gustatory center (PGC) in the gnathal ganglia (GNG). To identify candidate gustatory second-order neurons (G2Ns) we screened ~5,000 GAL4 driver strains for lines that label neural fibers innervating the PGC. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate G2Ns and the axonal terminals of Gr5a-expressing GSNs, which are known to respond to sucrose. Results of the GRASP analysis, followed by a single cell analysis by FLPout recombination, revealed a pair of neurons that contact Gr5a axon terminals in both brain hemispheres, and send axonal arborizations to a distinct region outside the PGC but within the GNG. To characterize the input and output branches, respectively, we expressed fluorescence-tagged acetylcholine receptor subunit (Dα7) and active-zone marker (Brp) in the G2Ns. We found that G2N input sites overlaid GRASP-labeled synaptic contacts to Gr5a neurons, while presynaptic sites were broadly distributed throughout the neurons’ arborizations. GRASP analysis and further tests with the Syb-GRASP method suggested that the identified G2Ns receive synaptic inputs from Gr5a-expressing GSNs, but not Gr66a-expressing GSNs, which respond to caffeine. The identified G2Ns relay information from Gr5a-expressing GSNs to distinct regions in the GNG, and are distinct from other, recently identified gustatory projection neurons, which relay information about sugars to a brain region called the antennal mechanosensory and motor center (AMMC). Our findings suggest unexpected complexity for taste information processing in the first relay of the gustatory system. PMID:26004543

  10. A gustatory second-order neuron that connects sucrose-sensitive primary neurons and a distinct region of the gnathal ganglion in the Drosophila brain.

    PubMed

    Miyazaki, Takaaki; Lin, Tzu-Yang; Ito, Kei; Lee, Chi-Hon; Stopfer, Mark

    2015-01-01

    Although the gustatory system provides animals with sensory cues important for food choice and other critical behaviors, little is known about neural circuitry immediately following gustatory sensory neurons (GSNs). Here, we identify and characterize a bilateral pair of gustatory second-order neurons (G2Ns) in Drosophila. Previous studies identified GSNs that relay taste information to distinct subregions of the primary gustatory center (PGC) in the gnathal ganglia (GNG). To identify candidate G2Ns, we screened ∼5,000 GAL4 driver strains for lines that label neural fibers innervating the PGC. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate G2Ns and the axonal terminals of Gr5a-expressing GSNs, which are known to respond to sucrose. Results of the GRASP analysis, followed by a single-cell analysis by FLP-out recombination, revealed a pair of neurons that contact Gr5a axon terminals in both brain hemispheres and send axonal arborizations to a distinct region outside the PGC but within the GNG. To characterize the input and output branches, respectively, we expressed fluorescence-tagged acetylcholine receptor subunit (Dα7) and active-zone marker (Brp) in the G2Ns. We found that G2N input sites overlaid GRASP-labeled synaptic contacts to Gr5a neurons, while presynaptic sites were broadly distributed throughout the neurons' arborizations. GRASP analysis and further tests with the Syb-GRASP method suggested that the identified G2Ns receive synaptic inputs from Gr5a-expressing GSNs, but not Gr66a-expressing GSNs, which respond to caffeine. The identified G2Ns relay information from Gr5a-expressing GSNs to distinct regions in the GNG, and are distinct from other, recently identified gustatory projection neurons, which relay information about sugars to a brain region called the antennal mechanosensory and motor center (AMMC). Our findings suggest unexpected complexity for taste information processing in the first relay of the gustatory system.

  11. Microsatellite markers identify three lineages of Phytophthora ramorum in US nurseries, yet single lineages in US forest and European nursery populations.

    PubMed

    Ivors, K; Garbelotto, M; Vries, I D E; Ruyter-Spira, C; Te Hekkert, B; Rosenzweig, N; Bonants, P

    2006-05-01

    Analysis of 12 polymorphic simple sequence repeats identified in the genome sequence of Phytophthora ramorum, causal agent of 'sudden oak death', revealed genotypic diversity to be significantly higher in nurseries (91% of total) than in forests (18% of total). Our analysis identified only two closely related genotypes in US forests, while the genetic structure of populations from European nurseries was of intermediate complexity, including multiple, closely related genotypes. Multilocus analysis determined populations in US forests reproduce clonally and are likely descendants of a single introduced individual. The 151 isolates analysed clustered in three clades. US forest and European nursery isolates clustered into two distinct clades, while one isolate from a US nursery belonged to a third novel clade. The combined microsatellite, sequencing and morphological analyses suggest the three clades represent distinct evolutionary lineages. All three clades were identified in some US nurseries, emphasizing the role of commercial plant trade in the movement of this pathogen.

  12. Use of Parsimony Analysis to Identify Areas of Endemism of Chinese Birds: Implications for Conservation and Biogeography

    PubMed Central

    Huang, Xiao-Lei; Qiao, Ge-Xia; Lei, Fu-Min

    2010-01-01

    Parsimony analysis of endemicity (PAE) was used to identify areas of endemism (AOEs) for Chinese birds at the subregional level. Four AOEs were identified based on a distribution database of 105 endemic species and using 18 avifaunal subregions as the operating geographical units (OGUs). The four AOEs are the Qinghai-Zangnan Subregion, the Southwest Mountainous Subregion, the Hainan Subregion and the Taiwan Subregion. Cladistic analysis of subregions generally supports the division of China’s avifauna into Palaearctic and Oriental realms. Two PAE area trees were produced from two different distribution datasets (year 1976 and 2007). The 1976 topology has four distinct subregional branches; however, the 2007 topology has three distinct branches. Moreover, three Palaearctic subregions in the 1976 tree clustered together with the Oriental subregions in the 2007 tree. Such topological differences may reflect changes in the distribution of bird species through circa three decades. PMID:20559504

  13. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer

    PubMed Central

    Shen, Lanlan; Toyota, Minoru; Kondo, Yutaka; Lin, E; Zhang, Li; Guo, Yi; Hernandez, Natalie Supunpong; Chen, Xinli; Ahmed, Saira; Konishi, Kazuo; Hamilton, Stanley R.; Issa, Jean-Pierre J.

    2007-01-01

    Colon cancer has been viewed as the result of progressive accumulation of genetic and epigenetic abnormalities. However, this view does not fully reflect the molecular heterogeneity of the disease. We have analyzed both genetic (mutations of BRAF, KRAS, and p53 and microsatellite instability) and epigenetic alterations (DNA methylation of 27 CpG island promoter regions) in 97 primary colorectal cancer patients. Two clustering analyses on the basis of either epigenetic profiling or a combination of genetic and epigenetic profiling were performed to identify subclasses with distinct molecular signatures. Unsupervised hierarchical clustering of the DNA methylation data identified three distinct groups of colon cancers named CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. Genetically, these three groups correspond to very distinct profiles. CIMP1 are characterized by MSI (80%) and BRAF mutations (53%) and rare KRAS and p53 mutations (16% and 11%, respectively). CIMP2 is associated with 92% KRAS mutations and rare MSI, BRAF, or p53 mutations (0, 4, and 31% respectively). CIMP-negative cases have a high rate of p53 mutations (71%) and lower rates of MSI (12%) or mutations of BRAF (2%) or KRAS (33%). Clustering based on both genetic and epigenetic parameters also identifies three distinct (and homogeneous) groups that largely overlap with the previous classification. The three groups are independent of age, gender, or stage, but CIMP1 and 2 are more common in proximal tumors. Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease. PMID:18003927

  14. Genetically distinct genogroup IV norovirus strains identified in wastewater.

    PubMed

    Kitajima, Masaaki; Rachmadi, Andri T; Iker, Brandon C; Haramoto, Eiji; Gerba, Charles P

    2016-12-01

    We investigated the prevalence and genetic diversity of genogroup IV norovirus (GIV NoV) strains in wastewater in Arizona, United States, over a 13-month period. Among 50 wastewater samples tested, GIV NoVs were identified in 13 (26 %) of the samples. A total of 47 different GIV NoV strains were identified, which were classified into two genetically distinct clusters: the GIV.1 human cluster and a unique genetic cluster closely related to strains previously identified in Japanese wastewater. The results provide additional evidence of the considerable genetic diversity among GIV NoV strains through the analysis of wastewater containing virus strains shed from all populations.

  15. Managing Complexity in Evidence Analysis: A Worked Example in Pediatric Weight Management.

    PubMed

    Parrott, James Scott; Henry, Beverly; Thompson, Kyle L; Ziegler, Jane; Handu, Deepa

    2018-05-02

    Nutrition interventions are often complex and multicomponent. Typical approaches to meta-analyses that focus on individual causal relationships to provide guideline recommendations are not sufficient to capture this complexity. The objective of this study is to describe the method of meta-analysis used for the Pediatric Weight Management (PWM) Guidelines update and provide a worked example that can be applied in other areas of dietetics practice. The effects of PWM interventions were examined for body mass index (BMI), body mass index z-score (BMIZ), and waist circumference at four different time periods. For intervention-level effects, intervention types were identified empirically using multiple correspondence analysis paired with cluster analysis. Pooled effects of identified types were examined using random effects meta-analysis models. Differences in effects among types were examined using meta-regression. Context-level effects are examined using qualitative comparative analysis. Three distinct types (or families) of PWM interventions were identified: medical nutrition, behavioral, and missing components. Medical nutrition and behavioral types showed statistically significant improvements in BMIZ across all time points. Results were less consistent for BMI and waist circumference, although four distinct patterns of weight status change were identified. These varied by intervention type as well as outcome measure. Meta-regression indicated statistically significant differences between the medical nutrition and behavioral types vs the missing component type for both BMIZ and BMI, although the pattern varied by time period and intervention type. Qualitative comparative analysis identified distinct configurations of context characteristics at each time point that were consistent with positive outcomes among the intervention types. Although analysis of individual causal relationships is invaluable, this approach is inadequate to capture the complexity of dietetics practice. An alternative approach that integrates intervention-level with context-level meta-analyses may provide deeper understanding in the development of practice guidelines. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  16. Temporal analysis and spatial mapping of Lymantria dispar nuclear polyhedrosis virus transcripts and in vitro translation polypeptides

    Treesearch

    James M. Slavicek

    1991-01-01

    Genomic expression of the Lymantriu dispar multinucleocapsid nuclear polyhedrosis virus (LdMNPV) was studied. Viral specific transcripts expressed in cell culture at various times from 2 through 72 h postinfection were identified and their genomic origins mapped through Northern analysis. Sixty-five distinct transcripts were identified in this...

  17. Classification using NMR-based metabolomics of Sophora flavescens grown in Japan and China.

    PubMed

    Suzuki, Ryuichiro; Ikeda, Yuriko; Yamamoto, Akari; Saima, Toyoe; Fujita, Tatsuya; Fukuda, Tatsuo; Fukuda, Eriko; Baba, Masaki; Okada, Yoshihito; Shirataki, Yoshiaki

    2012-11-01

    We demonstrate that NMR-based metabolomics can be used to identify the country of growth (Japan or China) of Sophora flavescens plants. Principle Component Analysis (PCA) conducted on extracts of S. flavescens grown in China provided data distinct from that of extracts of plants grown in Japan. Loading plot analysis showed signals characteristic of Japanese S. flavescens. NMR analyses showed these signals to be due to kurarinol (1) and kushenol H (2). These compounds were confirmed by HPLC analysis to be distinctive markers for Japanese S. flavescens.

  18. REVERSETRANSCIPTION-PCR ASSAYS FOR THE DETECTION OF BOVINE ENTERIC CALICIVIRUSES (BEC) AND ANALYSIS OF THE GENETIC RELATIONSHIPS AMONG BEC AND HUMAN CALICIVIRUSES

    EPA Science Inventory

    Two genetically distinct bovine enteric caliciviruses (BEC) have been identified: the Norwalk-like-viruses (NLV), which are genetically related to human NLV, and the distinct NB-like BEC, which is most closely related to Sapporo-like viruses and lagoviruses, but potentially may ...

  19. Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

    PubMed

    Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

    2011-12-01

    Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent molecular mechanisms in the origins of this disease.

  20. Editing ERTS-1 data to exclude land aids cluster analysis of water targets

    NASA Technical Reports Server (NTRS)

    Erb, R. B. (Principal Investigator)

    1973-01-01

    The author has identified the following significant results. It has been determined that an increase in the number of spectrally distinct coastal water types is achieved when data values over the adjacent land areas are excluded from the processing routine. This finding resulted from an automatic clustering analysis of ERTS-1 system corrected MSS scene 1002-18134 of 25 July 1972 over Monterey Bay, California. When the entire study area data set was submitted to the clustering only two distinct water classes were extracted. However, when the land area data points were removed from the data set and resubmitted to the clustering routine, four distinct groupings of water features were identified. Additionally, unlike the previous separation, the four types could be correlated to features observable in the associated ERTS-1 imagery. This exercise demonstrates that by proper selection of data submitted to the processing routine, based upon the specific application of study, additional information may be extracted from the ERTS-1 MSS data.

  1. The Licensing of Behavior Analysts: Protecting the Profession and the Public

    ERIC Educational Resources Information Center

    Hassert, Derrick L.; Kelly, Amanda N.; Pritchard, Joshua K.; Cautilli, Joseph D.

    2008-01-01

    Applied behavior analysis is a hybrid tradition with roots in many mental health disciplines. Even with these diverse origins, the professional practice of behavior analysis remains distinct and identifiable. Given these factors the professional practice special interest group (SIG) for the Association for Behavior Analysis International has…

  2. An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins.

    PubMed

    Harper, Angela F; Leuthaeuser, Janelle B; Babbitt, Patricia C; Morris, John H; Ferrin, Thomas E; Poole, Leslie B; Fetrow, Jacquelyn S

    2017-02-01

    Peroxiredoxins (Prxs or Prdxs) are a large protein superfamily of antioxidant enzymes that rapidly detoxify damaging peroxides and/or affect signal transduction and, thus, have roles in proliferation, differentiation, and apoptosis. Prx superfamily members are widespread across phylogeny and multiple methods have been developed to classify them. Here we present an updated atlas of the Prx superfamily identified using a novel method called MISST (Multi-level Iterative Sequence Searching Technique). MISST is an iterative search process developed to be both agglomerative, to add sequences containing similar functional site features, and divisive, to split groups when functional site features suggest distinct functionally-relevant clusters. Superfamily members need not be identified initially-MISST begins with a minimal representative set of known structures and searches GenBank iteratively. Further, the method's novelty lies in the manner in which isofunctional groups are selected; rather than use a single or shifting threshold to identify clusters, the groups are deemed isofunctional when they pass a self-identification criterion, such that the group identifies itself and nothing else in a search of GenBank. The method was preliminarily validated on the Prxs, as the Prxs presented challenges of both agglomeration and division. For example, previous sequence analysis clustered the Prx functional families Prx1 and Prx6 into one group. Subsequent expert analysis clearly identified Prx6 as a distinct functionally relevant group. The MISST process distinguishes these two closely related, though functionally distinct, families. Through MISST search iterations, over 38,000 Prx sequences were identified, which the method divided into six isofunctional clusters, consistent with previous expert analysis. The results represent the most complete computational functional analysis of proteins comprising the Prx superfamily. The feasibility of this novel method is demonstrated by the Prx superfamily results, laying the foundation for potential functionally relevant clustering of the universe of protein sequences.

  3. An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins

    PubMed Central

    Babbitt, Patricia C.; Ferrin, Thomas E.

    2017-01-01

    Peroxiredoxins (Prxs or Prdxs) are a large protein superfamily of antioxidant enzymes that rapidly detoxify damaging peroxides and/or affect signal transduction and, thus, have roles in proliferation, differentiation, and apoptosis. Prx superfamily members are widespread across phylogeny and multiple methods have been developed to classify them. Here we present an updated atlas of the Prx superfamily identified using a novel method called MISST (Multi-level Iterative Sequence Searching Technique). MISST is an iterative search process developed to be both agglomerative, to add sequences containing similar functional site features, and divisive, to split groups when functional site features suggest distinct functionally-relevant clusters. Superfamily members need not be identified initially—MISST begins with a minimal representative set of known structures and searches GenBank iteratively. Further, the method’s novelty lies in the manner in which isofunctional groups are selected; rather than use a single or shifting threshold to identify clusters, the groups are deemed isofunctional when they pass a self-identification criterion, such that the group identifies itself and nothing else in a search of GenBank. The method was preliminarily validated on the Prxs, as the Prxs presented challenges of both agglomeration and division. For example, previous sequence analysis clustered the Prx functional families Prx1 and Prx6 into one group. Subsequent expert analysis clearly identified Prx6 as a distinct functionally relevant group. The MISST process distinguishes these two closely related, though functionally distinct, families. Through MISST search iterations, over 38,000 Prx sequences were identified, which the method divided into six isofunctional clusters, consistent with previous expert analysis. The results represent the most complete computational functional analysis of proteins comprising the Prx superfamily. The feasibility of this novel method is demonstrated by the Prx superfamily results, laying the foundation for potential functionally relevant clustering of the universe of protein sequences. PMID:28187133

  4. NREM Arousal Parasomnias and Their Distinction from Nocturnal Frontal Lobe Epilepsy: A Video EEG Analysis

    PubMed Central

    Derry, Christopher P.; Harvey, A. Simon; Walker, Matthew C.; Duncan, John S.; Berkovic, Samuel F.

    2009-01-01

    Study Objectives. To describe the semiological features of NREM arousal parasomnias in detail and identify features that can be used to reliably distinguish parasomnias from nocturnal frontal lobe epilepsy (NFLE). Design. Systematic semiologial evaluation of parasomnias and NFLE seizures recorded on video-EEG monitoring. Patients. 120 events (57 parasomnias, 63 NFLE seizures) from 44 subjects (14 males). Interventions. The presence or absence of 68 elemental clinical features was determined in parasomnias and NFLE seizures. Qualitative analysis of behavior patterns and ictal EEG was undertaken. Statistical analysis was undertaken using established techniques. Results. Elemental clinical features strongly favoring parasomnias included: interactive behavior, failure to wake after event, and indistinct offset (all P < 0.001). Cluster analysis confirmed differences in both the frequency and combination of elemental features in parasomnias and NFLE. A diagnostic decision tree generated from these data correctly classified 94% of events. While sleep stage at onset was discriminatory (82% of seizures occurred during stage 1 or 2 sleep, with 100% of parasomnias occurring from stage 3 or 4 sleep), ictal EEG features were less useful. Video analysis of parasomnias identified three principal behavioral patterns: arousal behavior (92% of events); non-agitated motor behavior (72%); distressed emotional behavior (51%). Conclusions Our results broadly support the concept of confusion arousals, somnambulism and night terrors as prototypical behavior patterns of NREM parasomnias, but as a hierarchical continuum rather than distinct entities. Our observations provide an evidence base to assist in the clinical diagnosis of NREM parasomnias, and their distinction from NFLE seizures, on semiological grounds. Citation: Derry CP; Harvey AS; Walker MC; Duncan JS; Berkovic SF. NREM arousal parasomnias and their distinction from nocturnal frontal lobe epilepsy: a video EEG analysis. SLEEP 2009;32(12):1637-1644. PMID:20041600

  5. Classification and Validation of Behavioral Subtypes of Learning-Disabled Children.

    ERIC Educational Resources Information Center

    Speece, Deborah L.; And Others

    1985-01-01

    Using the Classroom Behavior Inventory, teachers rated the behaviors of 63 school-identified, learning-disabled first and second graders. Hierarchical cluster analysis techniques identified seven distinct behavioral subtypes. Internal validation techniques indicated that the subtypes were replicable and had profile patterns different from a sample…

  6. A Cluster Analytic Study of Clinical Orientations among Chemical Dependency Counselors.

    ERIC Educational Resources Information Center

    Thombs, Dennis L.; Osborn, Cynthia J.

    2001-01-01

    Three distinct clinical orientations were identified in a sample of chemical dependency counselors (N=406). Based on cluster analysis, the largest group, identified and labeled as "uniform counselors," endorsed a simple, moral-disease model with little interest in psychosocial interventions. (Contains 50 references and 4 tables.) (GCP)

  7. Profiles of Reactivity in Cocaine-Exposed Children

    ERIC Educational Resources Information Center

    Schuetze, Pamela; Molnar, Danielle S.; Eiden, Rina D.

    2012-01-01

    This study explored the possibility that specific, theoretically consistent profiles of reactivity could be identified in a sample of cocaine-exposed infants and whether these profiles were associated with a range of infant and/or maternal characteristics. Cluster analysis was used to identify distinct groups of infants based on physiological,…

  8. The Metaphor of the Triangle in Theories of Human Development

    ERIC Educational Resources Information Center

    Zittoun, Tania; Gillespie, Alex; Cornish, Flora; Psaltis, Charis

    2007-01-01

    Developmental psychologists have a long history of using triangle metaphors to conceptualise the social constitution of psychological development. In this paper, we present a genealogy of triadic theories, to clarify their origins, distinctions between them, and to identify key themes for theoretical development. The analysis identifies three core…

  9. Ciência & Saúde Coletiva: scientific production analysis and collaborative research networks.

    PubMed

    Conner, Norma; Provedel, Attilio; Maciel, Ethel Leonor Noia

    2017-03-01

    The purpose of this metric and descriptive study was to identify the most productive authors and their collaborative research networks from articles published in Ciência & Saúde Coletiva between, 2005, and 2014. Authors meeting the cutoff criteria of at least 10 articles were considered the most productive authors. VOSviewer and Network Workbench technologies were applied for visual representations of collaborative research networks involving the most productive authors in the period. Initial analysis recovered 2511 distinct articles, with 8920 total authors with an average of 3.55 authors per article. Author analysis revealed 6288 distinct authors, 24 of these authors were identified as the most productive. These 24 authors generated 287 articles with an average of 4.31 authors per article, and represented 8 separate collaborative partnerships, the largest of which had 14 authors, indicating a significant degree of collaboration among these authors. This analysis provides a visual representation of networks of knowledge development in public health and demonstrates the usefulness of VOSviewer and Network Workbench technologies in future research.

  10. Identifying Patient Attitudinal Clusters Associated with Asthma Control: The European REALISE Survey.

    PubMed

    van der Molen, Thys; Fletcher, Monica; Price, David

    Asthma is a highly heterogeneous disease that can be classified into different clinical phenotypes, and treatment may be tailored accordingly. However, factors beyond purely clinical traits, such as patient attitudes and behaviors, can also have a marked impact on treatment outcomes. The objective of this study was to further analyze data from the REcognise Asthma and LInk to Symptoms and Experience (REALISE) Europe survey, to identify distinct patient groups sharing common attitudes toward asthma and its management. Factor analysis of respondent data (N = 7,930) from the REALISE Europe survey consolidated the 34 attitudinal variables provided by the study population into a set of 8 summary factors. Cluster analyses were used to identify patient clusters that showed similar attitudes and behaviors toward each of the 8 summary factors. Five distinct patient clusters were identified and named according to the key characteristics comprising that cluster: "Confident and self-managing," "Confident and accepting of their asthma," "Confident but dependent on others," "Concerned but confident in their health care professional (HCP)," and "Not confident in themselves or their HCP." Clusters showed clear variability in attributes such as degree of confidence in managing their asthma, use of reliever and preventer medication, and level of asthma control. The 5 patient clusters identified in this analysis displayed distinctly different personal attitudes that would require different approaches in the consultation room certainly for asthma but probably also for other chronic diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Identifying elemental genomic track types and representing them uniformly

    PubMed Central

    2011-01-01

    Background With the recent advances and availability of various high-throughput sequencing technologies, data on many molecular aspects, such as gene regulation, chromatin dynamics, and the three-dimensional organization of DNA, are rapidly being generated in an increasing number of laboratories. The variation in biological context, and the increasingly dispersed mode of data generation, imply a need for precise, interoperable and flexible representations of genomic features through formats that are easy to parse. A host of alternative formats are currently available and in use, complicating analysis and tool development. The issue of whether and how the multitude of formats reflects varying underlying characteristics of data has to our knowledge not previously been systematically treated. Results We here identify intrinsic distinctions between genomic features, and argue that the distinctions imply that a certain variation in the representation of features as genomic tracks is warranted. Four core informational properties of tracks are discussed: gaps, lengths, values and interconnections. From this we delineate fifteen generic track types. Based on the track type distinctions, we characterize major existing representational formats and find that the track types are not adequately supported by any single format. We also find, in contrast to the XML formats, that none of the existing tabular formats are conveniently extendable to support all track types. We thus propose two unified formats for track data, an improved XML format, BioXSD 1.1, and a new tabular format, GTrack 1.0. Conclusions The defined track types are shown to capture relevant distinctions between genomic annotation tracks, resulting in varying representational needs and analysis possibilities. The proposed formats, GTrack 1.0 and BioXSD 1.1, cater to the identified track distinctions and emphasize preciseness, flexibility and parsing convenience. PMID:22208806

  12. Utilization of ACL Injury Biomechanical and Neuromuscular Risk Profile Analysis to Determine the Effectiveness of Neuromuscular Training.

    PubMed

    Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

    2016-12-01

    The widespread use of anterior cruciate ligament (ACL) injury prevention interventions has not been effective in reducing the injury incidence among female athletes who participate in high-risk sports. The purpose of this study was to determine if biomechanical and neuromuscular factors that contribute to the knee abduction moment (KAM), a predictor of future ACL injuries, could be used to characterize athletes by a distinct factor. Specifically, we hypothesized that a priori selected biomechanical and neuromuscular factors would characterize participants into distinct at-risk profiles. Controlled laboratory study. A total of 624 female athletes who participated in jumping, cutting, and pivoting sports underwent testing before their competitive season. During testing, athletes performed drop-jump tasks from which biomechanical measures were captured. Using data from these tasks, latent profile analysis (LPA) was conducted to identify distinct profiles based on preintervention biomechanical and neuromuscular measures. As a validation, we examined whether the profile membership was a significant predictor of the KAM. LPA using 6 preintervention biomechanical measures selected a priori resulted in 3 distinct profiles, including a low (profile 1), moderate (profile 2), and high (profile 3) risk for ACL injuries. Athletes with profiles 2 and 3 had a significantly higher KAM compared with those with profile 1 (P < .05). This is the first study to use LPA of biomechanical landing data to create ACL injury risk profiles. Three distinct risk groups were identified based on differences in the peak KAM. These findings demonstrate the existence of discernable groups of athletes that may benefit from injury prevention interventions. ClinicalTrials.gov NCT identifier: NCT01034527. © 2016 The Author(s).

  13. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods

    PubMed Central

    Reese, Jessica A.; Li, Xiaoning; Hauben, Manfred; Aster, Richard H.; Bougie, Daniel W.; Curtis, Brian R.; George, James N.

    2010-01-01

    Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia. PMID:20530792

  14. A Latent Profile Analysis of University Students' Self-Regulated Learning Strategies

    ERIC Educational Resources Information Center

    Ning, Hoi Kwan; Downing, Kevin

    2015-01-01

    Based on self-reported cognitive, metacognitive, and behavioural strategy measures obtained from 828 final-year students from a university in Hong Kong, latent profile analysis (LPA) identified four distinct types of students with differential self-regulated learning strategy orientations: "competent self-regulated learners",…

  15. Sun Protection Belief Clusters: Analysis of Amazon Mechanical Turk Data.

    PubMed

    Santiago-Rivas, Marimer; Schnur, Julie B; Jandorf, Lina

    2016-12-01

    This study aimed (i) to determine whether people could be differentiated on the basis of their sun protection belief profiles and individual characteristics and (ii) explore the use of a crowdsourcing web service for the assessment of sun protection beliefs. A sample of 500 adults completed an online survey of sun protection belief items using Amazon Mechanical Turk. A two-phased cluster analysis (i.e., hierarchical and non-hierarchical K-means) was utilized to determine clusters of sun protection barriers and facilitators. Results yielded three distinct clusters of sun protection barriers and three distinct clusters of sun protection facilitators. Significant associations between gender, age, sun sensitivity, and cluster membership were identified. Results also showed an association between barrier and facilitator cluster membership. The results of this study provided a potential alternative approach to developing future sun protection promotion initiatives in the population. Findings add to our knowledge regarding individuals who support, oppose, or are ambivalent toward sun protection and inform intervention research by identifying distinct subtypes that may best benefit from (or have a higher need for) skin cancer prevention efforts.

  16. Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in living human brain.

    PubMed

    Ishii, Tatsuya; Kimura, Yasuyuki; Ichise, Masanori; Takahata, Keisuke; Kitamura, Soichiro; Moriguchi, Sho; Kubota, Manabu; Zhang, Ming-Rong; Yamada, Makiko; Higuchi, Makoto; Okubo, Yoshinori; Suhara, Tetsuya

    2017-01-01

    Seven healthy volunteers underwent PET scans with [18F]altanserin and [11C]FLB 457 for 5-HT2A and D2 receptors, respectively. As a measure of receptor density, a binding potential (BP) was calculated from PET data for 76 cerebral cortical regions. A correlation matrix was calculated between the binding potentials of [18F]altanserin and [11C]FLB 457 for those regions. The regional relationships were investigated using a bicluster analysis of the correlation matrix with an iterative signature algorithm. We identified two clusters of regions. The first cluster identified a distinct profile of correlation coefficients between 5-HT2A and D2 receptors, with the former in regions related to sensorimotor integration (supplementary motor area, superior parietal gyrus, and paracentral lobule) and the latter in most cortical regions. The second cluster identified another distinct profile of correlation coefficients between 5-HT2A receptors in the bilateral hippocampi and D2 receptors in most cortical regions. The observation of two distinct clusters in the correlation matrix suggests regional interactions between 5-HT2A and D2 receptors in sensorimotor integration and hippocampal function. A bicluster analysis of the correlation matrix of these neuroreceptors may be beneficial in understanding molecular networks in the human brain.

  17. Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes.

    PubMed

    Kerr, J R; Burke, B; Petty, R; Gough, J; Fear, D; Mattey, D L; Axford, J S; Dalgleish, A G; Nutt, D J

    2008-06-01

    Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. The authors have recently reported a study of gene expression that identified differential expression of 88 human genes in patients with CFS/ME. Clustering of quantitative PCR (qPCR) data from patients with CFS/ME revealed seven distinct subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes and severity. In this study, for each CFS/ME subtype, those genes whose expression differed significantly from that of normal blood donors were identified, and then gene interactions, disease associations and molecular and cellular functions of those gene sets were determined. Genomic analysis was then related to clinical data for each CFS/ME subtype. Genomic analysis revealed some common (neurological, haematological, cancer) and some distinct (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease associations among the subtypes. Subtypes 1, 2 and 7 were the most severe, and subtype 3 was the mildest. Clinical features of each subtype were as follows: subtype 1 (cognitive, musculoskeletal, sleep, anxiety/depression); subtype 2 (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4 (cognitive); subtype 5 (musculoskeletal, gastrointestinal); subtype 6 (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep, neurological, gastrointestinal, neurocognitive, anxiety/depression). It was particularly interesting that in the seven genomically derived subtypes there were distinct clinical syndromes, and that those which were most severe were also those with anxiety/depression, as would be expected in a disease with a biological basis.

  18. The use of LANDSAT imagery in relation to air survey imagery for terrain analysis in northwest Queensland, Australia, volume 1

    NASA Technical Reports Server (NTRS)

    Cole, M. M.; Owen-Jones, E. S. (Principal Investigator)

    1977-01-01

    The author has identified the following significant results. Distinctive spectral signatures discriminated areas underlain by distinctive lithological/stratigraphical units where bedrock either outcrops or is relatively near to surface in the Lady Annie-Mt. Gordon fault zone, the Mary Kathleen, and Dugald River-Naraku areas. Spectral signatures associated with discrete plant communities distinguished different types of superficial deposits over the Cloncurry Plains. Distinctive spectral signatures also revealed the presence and nature of concealed bedrock beneath cover of residuum and superficial deposits where this is relatively thin in the Cloncurry Plains. Major faults were clearly displayed in areas of outcropping and near surface bedrock. Sets of lineaments with preferred orientations were identified in the Lady Annie and Dugald River areas. Known base metal deposits occur along these features.

  19. Automated classification of mouse pup isolation syllables: from cluster analysis to an Excel-based "mouse pup syllable classification calculator".

    PubMed

    Grimsley, Jasmine M S; Gadziola, Marie A; Wenstrup, Jeffrey J

    2012-01-01

    Mouse pups vocalize at high rates when they are cold or isolated from the nest. The proportions of each syllable type produced carry information about disease state and are being used as behavioral markers for the internal state of animals. Manual classifications of these vocalizations identified 10 syllable types based on their spectro-temporal features. However, manual classification of mouse syllables is time consuming and vulnerable to experimenter bias. This study uses an automated cluster analysis to identify acoustically distinct syllable types produced by CBA/CaJ mouse pups, and then compares the results to prior manual classification methods. The cluster analysis identified two syllable types, based on their frequency bands, that have continuous frequency-time structure, and two syllable types featuring abrupt frequency transitions. Although cluster analysis computed fewer syllable types than manual classification, the clusters represented well the probability distributions of the acoustic features within syllables. These probability distributions indicate that some of the manually classified syllable types are not statistically distinct. The characteristics of the four classified clusters were used to generate a Microsoft Excel-based mouse syllable classifier that rapidly categorizes syllables, with over a 90% match, into the syllable types determined by cluster analysis.

  20. Learning and Development Expertise: An Australian Analysis

    ERIC Educational Resources Information Center

    Hodge, Steven; Harvey, Jack

    2015-01-01

    Learning and development (L&D) practitioners draw on a distinctive range of knowledge, skills and techniques in their work. Over the years, there have been attempts to capture this range and identify typical L&D roles. The research presented here was undertaken to identify characteristic areas of expertise (AOEs) of L&D practice in…

  1. Occurrence of different Canine distemper virus lineages in Italian dogs.

    PubMed

    Balboni, Andrea; De Lorenzo Dandola, Giorgia; Scagliarini, Alessandra; Prosperi, Santino; Battilani, Mara

    2014-01-01

    This study describes the sequence analysis of the H gene of 7 Canine distemper virus (CDV) strains identified in dogs in Italy between years 2002-2012. The phylogenetic analysis showed that the CDV strains belonged to 2 clusters: 6 viruses were identified as Arctic-like lineage and 1 as Europe 1 lineage. These data show a considerable prevalence of Arctic-like-CDVs in the analysed dogs. The dogs and the 3 viruses more recently identified showed 4 distinctive amino acid mutations compared to all other Arctic CDVs.

  2. Genome sequence of a distinct watermelon mosaic virus identified from ginseng (Panax ginseng) transcriptome.

    PubMed

    Park, D; Kim, H; Hahn, Y

    Watermelon mosaic virus (WMV) is a member of the genus Potyvirus, which is the largest genus of plant viruses. WMV is a significant pathogen of crop plants, including Cucurbitaceae species. A WMV strain, designated as WMV-Pg, was identified in transcriptome data collected from ginseng (Panax ginseng) root. WMV-Pg showed 84% nucleotide sequence identity and 91% amino acid sequence identity with its closest related virus, WMV-Fr. A phylogenetic analysis of WMV-Pg with other WMVs and soybean mosaic viruses (SMVs) indicated that WMV-Pg is a distinct subtype of the WMV/SMV group of the genus Potyvirus in the family Potyviridae.

  3. Comparative proteomic analysis of Cronobacter sakazakii isolates with different virulences.

    PubMed

    Du, Xin-jun; Han, Ran; Li, Ping; Wang, Shuo

    2015-10-14

    Cronobacter is a genus of widespread, opportunistic, foodborne pathogens that can result in serious illnesses in at-risk infants because of their immature immunity and high dependence on powdered formula, which is one of the foods most often contaminated by this pathogen. However, limited information is available regarding the pathogenesis and the specific virulence factors of this species. In this study, the virulences of 42 Cronobacter sakazakii isolates were analyzed by infecting neonatal SD rats. A comparison of the typing patterns of the isolates enabled groups with close relationships but that exhibited distinct pathogenesis to be identified. Among these groups, 2 strains belonging to the same group but showing distinct virulences were selected, and 2-DE was applied to identify differentially expressed proteins, focusing on virulence-related proteins. A total of 111 protein spots were identified using matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS), and 89 were successfully identified. Further analysis suggested that at least 11 of these proteins may be involved in the pathogenesis of this pathogen. Real-time PCR was carried out to further confirm the differential expression pattern of the genes, and the results indicated that the mRNA expression levels were consistent with the protein expression levels. The virulence factors and pathogenesis of Cronobacter are largely unknown. In combination with animal toxicological experiments and subtyping results of C. sakazakii, comparative proteomics analysis was performed to comprehensively evaluate the differentially expressed proteins of two isolates that exhibited distinct virulence but were closely related. These procedures made it possible to identify the virulence-related of factors of Cronobacter. Among the 89 total identified proteins, at least 11 show virulence-related potential. This work provides comprehensive candidates for the further investigation of the pathogenesis of Cronobacter. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Mining pathway associations for disease-related pathway activity analysis based on gene expression and methylation data.

    PubMed

    Lee, Hyeonjeong; Shin, Miyoung

    2017-01-01

    The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into distinctive associations between pathway activities in case and control samples.

  5. Comparative genome analysis of Pseudomonas genomes including Populus-associated isolates

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

    Jun, Se Ran; Wassenaar, Trudy; Nookaew, Intawat

    The Pseudomonas genus contains a metabolically versatile group of organisms that are known to occupy numerous ecological niches including the rhizosphere and endosphere of many plants influencing phylogenetic diversity and heterogeneity. In this study, comparative genome analysis was performed on over one thousand Pseudomonas genomes, including 21 Pseudomonas strains isolated from the roots of native Populus deltoides. Based on average amino acid identity, genomic clusters were identified within the Pseudomonas genus, which showed agreements with clades by NCBI and cliques by IMG. The P. fluorescens group was organized into 20 distinct genomic clusters, representing enormous diversity and heterogeneity. The speciesmore » P. aeruginosa showed clear distinction in their genomic relatedness compared to other Pseudomonas species groups based on the pan and core genome analysis. The 19 isolates of our 21 Populus-associated isolates formed three distinct subgroups within the P. fluorescens major group, supported by pathway profiles analysis, while two isolates were more closely related to P. chlororaphis and P. putida. The specific genes to Populus-associated subgroups were identified where genes specific to subgroup 1 include several sensory systems such as proteins which act in two-component signal transduction, a TonB-dependent receptor, and a phosphorelay sensor; specific genes to subgroup 2 contain unique hypothetical genes; and genes specific to subgroup 3 organisms have a different hydrolase activity. IMPORTANCE The comparative genome analyses of the genus Pseudomonas that included Populus-associated isolates resulted in novel insights into high diversity of Pseudomonas. Consistent and robust genomic clusters with phylogenetic homogeneity were identified, which resolved species-clades that are not clearly defined by 16S rRNA gene sequence analysis alone. The genomic clusters may be reflective of distinct ecological niches to which the organisms have adapted, but this needs to be experimentally characterized with ecologically relevant phenotype properties. This study justifies the need to sequence multiple isolates, especially from P. fluorescens group in order to study functional capabilities from a pangenomic perspective. This information will prove useful when choosing Pseudomonas strains for use to promote growth and increase disease resistance in plants.« less

  6. Comparative genome analysis of Pseudomonas genomes including Populus-associated isolates

    DOE PAGES

    Jun, Se Ran; Wassenaar, Trudy; Nookaew, Intawat; ...

    2016-01-01

    The Pseudomonas genus contains a metabolically versatile group of organisms that are known to occupy numerous ecological niches including the rhizosphere and endosphere of many plants influencing phylogenetic diversity and heterogeneity. In this study, comparative genome analysis was performed on over one thousand Pseudomonas genomes, including 21 Pseudomonas strains isolated from the roots of native Populus deltoides. Based on average amino acid identity, genomic clusters were identified within the Pseudomonas genus, which showed agreements with clades by NCBI and cliques by IMG. The P. fluorescens group was organized into 20 distinct genomic clusters, representing enormous diversity and heterogeneity. The speciesmore » P. aeruginosa showed clear distinction in their genomic relatedness compared to other Pseudomonas species groups based on the pan and core genome analysis. The 19 isolates of our 21 Populus-associated isolates formed three distinct subgroups within the P. fluorescens major group, supported by pathway profiles analysis, while two isolates were more closely related to P. chlororaphis and P. putida. The specific genes to Populus-associated subgroups were identified where genes specific to subgroup 1 include several sensory systems such as proteins which act in two-component signal transduction, a TonB-dependent receptor, and a phosphorelay sensor; specific genes to subgroup 2 contain unique hypothetical genes; and genes specific to subgroup 3 organisms have a different hydrolase activity. IMPORTANCE The comparative genome analyses of the genus Pseudomonas that included Populus-associated isolates resulted in novel insights into high diversity of Pseudomonas. Consistent and robust genomic clusters with phylogenetic homogeneity were identified, which resolved species-clades that are not clearly defined by 16S rRNA gene sequence analysis alone. The genomic clusters may be reflective of distinct ecological niches to which the organisms have adapted, but this needs to be experimentally characterized with ecologically relevant phenotype properties. This study justifies the need to sequence multiple isolates, especially from P. fluorescens group in order to study functional capabilities from a pangenomic perspective. This information will prove useful when choosing Pseudomonas strains for use to promote growth and increase disease resistance in plants.« less

  7. Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD

    PubMed Central

    Fair, Damien A.; Bathula, Deepti; Nikolas, Molly A.; Nigg, Joel T.

    2012-01-01

    Research and clinical investigations in psychiatry largely rely on the de facto assumption that the diagnostic categories identified in the Diagnostic and Statistical Manual (DSM) represent homogeneous syndromes. However, the mechanistic heterogeneity that potentially underlies the existing classification scheme might limit discovery of etiology for most developmental psychiatric disorders. Another, perhaps less palpable, reality may also be interfering with progress—heterogeneity in typically developing populations. In this report we attempt to clarify neuropsychological heterogeneity in a large dataset of typically developing youth and youth with attention deficit/hyperactivity disorder (ADHD), using graph theory and community detection. We sought to determine whether data-driven neuropsychological subtypes could be discerned in children with and without the disorder. Because individual classification is the sine qua non for eventual clinical translation, we also apply support vector machine-based multivariate pattern analysis to identify how well ADHD status in individual children can be identified as defined by the community detection delineated subtypes. The analysis yielded several unique, but similar subtypes across both populations. Just as importantly, comparing typically developing children with ADHD children within each of these distinct subgroups increased diagnostic accuracy. Two important principles were identified that have the potential to advance our understanding of typical development and developmental neuropsychiatric disorders. The first tenet suggests that typically developing children can be classified into distinct neuropsychological subgroups with high precision. The second tenet proposes that some of the heterogeneity in individuals with ADHD might be “nested” in this normal variation. PMID:22474392

  8. Analysis of Pax6 contiguous gene deletions in the mouse, Mus musculus, identifies regions distinct from Pax6 responsible for extreme small-eye and belly-spotting phenotypes.

    PubMed

    Favor, Jack; Bradley, Alan; Conte, Nathalie; Janik, Dirk; Pretsch, Walter; Reitmeir, Peter; Rosemann, Michael; Schmahl, Wolfgang; Wienberg, Johannes; Zaus, Irmgard

    2009-08-01

    In the mouse Pax6 function is critical in a dose-dependent manner for proper eye development. Pax6 contiguous gene deletions were shown to be homozygous lethal at an early embryonic stage. Heterozygotes express belly spotting and extreme microphthalmia. The eye phenotype is more severe than in heterozygous Pax6 intragenic null mutants, raising the possibility that deletions are functionally different from intragenic null mutations or that a region distinct from Pax6 included in the deletions affects eye phenotype. We recovered and identified the exact regions deleted in three new Pax6 deletions. All are homozygous lethal at an early embryonic stage. None express belly spotting. One expresses extreme microphthalmia and two express the milder eye phenotype similar to Pax6 intragenic null mutants. Analysis of Pax6 expression levels and the major isoforms excluded the hypothesis that the deletions expressing extreme microphthalmia are directly due to the action of Pax6 and functionally different from intragenic null mutations. A region distinct from Pax6 containing eight genes was identified for belly spotting. A second region containing one gene (Rcn1) was identified for the extreme microphthalmia phenotype. Rcn1 is a Ca(+2)-binding protein, resident in the endoplasmic reticulum, participates in the secretory pathway and expressed in the eye. Our results suggest that deletion of Rcn1 directly or indirectly contributes to the eye phenotype in Pax6 contiguous gene deletions.

  9. Substance Use and Abuse Trajectories across Adolescence: A Latent Trajectory Analysis of a Community-Recruited Sample of Girls

    ERIC Educational Resources Information Center

    Marti, C. Nathan; Stice, Eric; Springer, David W.

    2010-01-01

    We used data from a school-based study of 496 adolescent girls to identify qualitatively distinct substance use and substance abuse developmental trajectory groups and tested whether the problematic groups differed from the non-problematic groups on baseline and outcome validation variables. Results identified four substance use groups (late…

  10. An Exploratory Analysis of TPACK Perceptions of Pre-Service Science Teachers: A Regional Australian Perspective

    ERIC Educational Resources Information Center

    Reyes, Vicente Chua, Jr.; Rizk, Nadya; Gregory, Sue; Doyle, Helen

    2016-01-01

    Four distinct constructs were identified from a survey of a sample of pre-service science teachers at a regional Australian University. The constructs emerged after employing Exploratory Factor Analysis (EFA) on respondents' perceptions of pedagogical practices incorporating the use of Information Communication and Technology (ICT). The key…

  11. Psychosocial Costs of Racism to Whites: Exploring Patterns through Cluster Analysis

    ERIC Educational Resources Information Center

    Spanierman, Lisa B.; Poteat, V. Paul; Beer, Amanda M.; Armstrong, Patrick Ian

    2006-01-01

    Participants (230 White college students) completed the Psychosocial Costs of Racism to Whites (PCRW) Scale. Using cluster analysis, we identified 5 distinct cluster groups on the basis of PCRW subscale scores: the unempathic and unaware cluster contained the lowest empathy scores; the insensitive and afraid cluster consisted of low empathy and…

  12. Comparative analysis of Edwardsiella isolates from fish in the eastern United States identifies two distinct genetic taxa amongst organisms phenotypically classified as E. tarda

    USGS Publications Warehouse

    Griffin, Matt J.; Quiniou, Sylvie M.; Cody, Theresa; Tabuchi, Maki; Ware, Cynthia; Cipriano, Rocco C.; Mauel, Michael J.; Soto, Esteban

    2013-01-01

    Edwardsiella tarda, a Gram-negative member of the family Enterobacteriaceae, has been implicated in significant losses in aquaculture facilities worldwide. Here, we assessed the intra-specific variability of E. tarda isolates from 4 different fish species in the eastern United States. Repetitive sequence mediated PCR (rep-PCR) using 4 different primer sets (ERIC I & II, ERIC II, BOX, and GTG5) and multi-locus sequence analysis of 16S SSU rDNA, groEl, gyrA, gyrB, pho, pgi, pgm, and rpoA gene fragments identified two distinct genotypes of E. tarda (DNA group I; DNA group II). Isolates that fell into DNA group II demonstrated more similarity to E. ictaluri than DNA group I, which contained the reference E. tarda strain (ATCC #15947). Conventional PCR analysis using published E. tarda-specific primer sets yielded variable results, with several primer sets producing no observable amplification of target DNA from some isolates. Fluorometric determination of G + C content demonstrated 56.4% G + C content for DNA group I, 60.2% for DNA group II, and 58.4% for E. ictaluri. Surprisingly, these isolates were indistinguishable using conventional biochemical techniques, with all isolates demonstrating phenotypic characteristics consistent with E. tarda. Analysis using two commercial test kits identified multiple phenotypes, although no single metabolic characteristic could reliably discriminate between genetic groups. Additionally, anti-microbial susceptibility and fatty acid profiles did not demonstrate remarkable differences between groups. The significant genetic variation (<90% similarity at gyrA, gyrB, pho, phi and pgm; <40% similarity by rep-PCR) between these groups suggests organisms from DNA group II may represent an unrecognized, genetically distinct taxa of Edwardsiella that is phenotypically indistinguishable from E. tarda.

  13. Sequence determination and analysis of S-adenosyl-L-homocysteine hydrolase from yellow lupine (Lupinus luteus).

    PubMed

    Brzeziński, K; Janowski, R; Podkowiński, J; Jaskólski, M

    2001-01-01

    The coding sequences of two S-adenosyl-L-homocysteine hydrolases (SAHases) were identified in yellow lupine by screenig of a cDNA library. One of them, corresponding to the complete protein, was sequenced and compared with 52 other SAHase sequences. Phylogenetic analysis of these proteins identified three groups of the enzymes. Group A comprises only bacterial sequences. Group B is subdivided into two subgroups, one of which (B1) is formed by animal sequences. Subgroup B2 consist of two distinct clusters, B2a and B2b. Cluster B2b comprises all known plant sequences, including the yellow lupine enzyme, which are distinguished by a 50-residue insert. Group C is heterogeneous and contains SAHases from Archaea as well as a new class of animal enzymes, distinctly different from those in group B1.

  14. Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis.

    PubMed

    Wise, T; Radua, J; Via, E; Cardoner, N; Abe, O; Adams, T M; Amico, F; Cheng, Y; Cole, J H; de Azevedo Marques Périco, C; Dickstein, D P; Farrow, T F D; Frodl, T; Wagner, G; Gotlib, I H; Gruber, O; Ham, B J; Job, D E; Kempton, M J; Kim, M J; Koolschijn, P C M P; Malhi, G S; Mataix-Cols, D; McIntosh, A M; Nugent, A C; O'Brien, J T; Pezzoli, S; Phillips, M L; Sachdev, P S; Salvadore, G; Selvaraj, S; Stanfield, A C; Thomas, A J; van Tol, M J; van der Wee, N J A; Veltman, D J; Young, A H; Fu, C H; Cleare, A J; Arnone, D

    2017-10-01

    Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

  15. Consumer preferences for general practitioner services.

    PubMed

    Morrison, Mark; Murphy, Tom; Nalder, Craig

    2003-01-01

    This study focuses on segmenting the market for General Practitioner services in a regional setting. Using factor analysis, five main service attributes are identified. These are clear communication, ongoing doctor-patient relationship, same gender as the patient, provides advice to the patient, and empowers the patient to make his/her own decisions. These service attributes are used as a basis for market segmentation, using both socio-demographic variables and cluster analysis. Four distinct market segments are identified, with varying degrees of viability in terms of target marketing.

  16. A Method for Populating the Knowledge Base of AFIT’s Domain-Oriented Application Composition System

    DTIC Science & Technology

    1993-12-01

    Analysis ( FODA ). The approach identifies prominent features (similarities) and distinctive features (differences) of software systems within an... analysis approaches we have summarized, the re- searchers described FODA in sufficient detail to use on large domain analysis projects (ones with...Software Technology Center, July 1991. 18. Kang, Kyo C. and others. Feature-Oriented Domain Analysis ( FODA ) Feasibility Study. Technical Report, Software

  17. Distinct Evening Fatigue Profiles in Oncology Outpatients Receiving Chemotherapy

    PubMed Central

    Wright, Fay; Cooper, Bruce A.; Conley, Yvette P.; Hammer, Marilyn J.; Chen, Lee-May; Paul, Steven M.; Levine, Jon D.; Miaskowski, Christine; Kober, Kord M.

    2018-01-01

    Background Fatigue is the most common and debilitating symptom experienced by oncology patients during chemotherapy (CTX). Fatigue severity demonstrates a large amount of inter-individual and diurnal variability. Purpose Study purposes were to evaluate for subgroups of patients with distinct evening fatigue profiles and evaluate how these subgroups differed on demographic, clinical, and symptom characteristics. Methods Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n=1332) completed questionnaires six times over two cycles of CTX. Lee Fatigue Scale (LFS) evaluated evening fatigue severity. Latent profile analysis was used to identify distinct evening fatigue profiles. Results Four distinct evening fatigue classes (i.e., Low (14.0%), Moderate (17.2%), High (36.0%), Very High (32.8%)) were identified. Compared to the Low class, patients in the Very High evening fatigue class were: younger, female, had childcare responsibilities, had more years of education, had a lower functional status, had a higher comorbidity burden, and were diagnosed with breast cancer. Patients in the Very High class reported higher levels of depressive symptoms, sleep disturbance, and evening fatigue at enrollment. Conclusions Findings provide new insights into modifiable risk factors for higher levels of evening fatigue. Clinicians can use this information to identify higher risk patients and plan appropriate interventions. PMID:29725554

  18. Origin of a cryptic lineage in a threatened reptile through isolation and historical hybridization.

    PubMed

    Sovic, M G; Fries, A C; Gibbs, H L

    2016-11-01

    Identifying phylogenetically distinct lineages and understanding the evolutionary processes by which they have arisen are important goals of phylogeography. This information can also help define conservation units in endangered species. Such analyses are being transformed by the availability of genomic-scale data sets and novel analytical approaches for statistically comparing different historical scenarios as causes of phylogeographic patterns. Here, we use genomic-scale restriction-site-associated DNA sequencing (RADseq) data to test for distinct lineages in the endangered Eastern Massasauga Rattlesnake (Sistrurus catenatus). We then use coalescent-based modeling techniques to identify the evolutionary mechanisms responsible for the origin of the lineages in this species. We find equivocal evidence for distinct phylogenetic lineages within S. catenatus east of the Mississippi River, but strong support for a previously unrecognized lineage on the western edge of the range of this snake, represented by populations from Iowa, USA. Snakes from these populations show patterns of genetic admixture with a nearby non-threatened sister species (Sistrurus tergeminus). Tests of historical demographic models support the hypothesis that the genetic distinctiveness of Iowa snakes is due to a combination of isolation and historical introgression between S. catenatus and S. tergeminus. Our work provides an example of how model-based analysis of genomic-scale data can help identify conservation units in rare species.

  19. Making Sense of Sensemaking: Requirements of a Cognitive Analysis to Support C2 Decision Support System Design

    DTIC Science & Technology

    2006-06-01

    heart of a distinction within the CSE community with respect to the differences between Cognitive Task Analysis (CTA) and Cognitive Work Analysis...Wesley. Pirolli, P. and Card, S. (2005). The sensemaking process and leverage points for analyst technology as identified through cognitive task analysis . In...D. D., and Elm, W. C. (2000). Cognitive task analysis as bootstrapping multiple converging techniques. In Schraagen, Chipman, and Shalin (Eds

  20. Māori identity signatures: A latent profile analysis of the types of Māori identity.

    PubMed

    Greaves, Lara M; Houkamau, Carla; Sibley, Chris G

    2015-10-01

    Māori are the indigenous peoples of New Zealand. However, the term 'Māori' can refer to a wide range of people of varying ethnic compositions and cultural identity. We present a statistical model identifying 6 distinct types, or 'Māori Identity Signatures,' and estimate their proportion in the Māori population. The model is tested using a Latent Profile Analysis of a national probability sample of 686 Māori drawn from the New Zealand Attitudes and Values Study. We identify 6 distinct signatures: Traditional Essentialists (22.6%), Traditional Inclusives (16%), High Moderates (31.7%), Low Moderates (18.7%), Spiritually Orientated (4.1%), and Disassociated (6.9%). These distinct Identity Signatures predicted variation in deprivation, age, mixed-ethnic affiliation, and religion. This research presents the first formal statistical model assessing how people's identity as Māori is psychologically structured, documents the relative proportion of these different patterns of structures, and shows that these patterns reliably predict differences in core demographics. We identify a range of patterns of Māori identity far more diverse than has been previously proposed based on qualitative data, and also show that the majority of Māori fit a moderate or traditional identity pattern. The application of our model for studying Māori health and identity development is discussed. (c) 2015 APA, all rights reserved).

  1. SPATIALLY RESOLVED SPECTROSCOPY OF EUROPA: THE DISTINCT SPECTRUM OF LARGE-SCALE CHAOS

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

    Fischer, P. D.; Brown, M. E.; Hand, K. P., E-mail: pfischer@caltech.edu

    2015-11-15

    We present a comprehensive analysis of spatially resolved moderate spectral resolution near-infrared spectra obtained with the adaptive optics system at the Keck Observatory. We identify three compositionally distinct end member regions: the trailing hemisphere bullseye, the leading hemisphere upper latitudes, and a third component associated with leading hemisphere chaos units. We interpret the composition of the three end member regions to be dominated by irradiation products, water ice, and evaporite deposits or salt brines, respectively. The third component is associated with geological features and distinct from the geography of irradiation, suggesting an endogenous identity. Identifying the endogenous composition is ofmore » particular interest for revealing the subsurface composition. However, its spectrum is not consistent with linear mixtures of the salt minerals previously considered relevant to Europa. The spectrum of this component is distinguished by distorted hydration features rather than distinct spectral features, indicating hydrated minerals but making unique identification difficult. In particular, it lacks features common to hydrated sulfate minerals, challenging the traditional view of an endogenous salty component dominated by Mg-sulfates. Chloride evaporite deposits are one possible alternative.« less

  2. Alternative types of molecule-decorated atomic chains in Au–CO–Au single-molecule junctions

    PubMed Central

    Balogh, Zoltán; Makk, Péter

    2015-01-01

    Summary We investigate the formation and evolution of Au–CO single-molecule break junctions. The conductance histogram exhibits two distinct molecular configurations, which are further investigated by a combined statistical analysis. According to conditional histogram and correlation analysis these molecular configurations show strong anticorrelations with each other and with pure Au monoatomic junctions and atomic chains. We identify molecular precursor configurations with somewhat higher conductance, which are formed prior to single-molecule junctions. According to detailed length analysis two distinct types of molecule-affected chain-formation processes are observed, and we compare these results to former theoretical calculations considering bridge- and atop-type molecular configurations where the latter has reduced conductance due to destructive Fano interference. PMID:26199840

  3. Alternative types of molecule-decorated atomic chains in Au-CO-Au single-molecule junctions.

    PubMed

    Balogh, Zoltán; Makk, Péter; Halbritter, András

    2015-01-01

    We investigate the formation and evolution of Au-CO single-molecule break junctions. The conductance histogram exhibits two distinct molecular configurations, which are further investigated by a combined statistical analysis. According to conditional histogram and correlation analysis these molecular configurations show strong anticorrelations with each other and with pure Au monoatomic junctions and atomic chains. We identify molecular precursor configurations with somewhat higher conductance, which are formed prior to single-molecule junctions. According to detailed length analysis two distinct types of molecule-affected chain-formation processes are observed, and we compare these results to former theoretical calculations considering bridge- and atop-type molecular configurations where the latter has reduced conductance due to destructive Fano interference.

  4. A computational study on outliers in world music.

    PubMed

    Panteli, Maria; Benetos, Emmanouil; Dixon, Simon

    2017-01-01

    The comparative analysis of world music cultures has been the focus of several ethnomusicological studies in the last century. With the advances of Music Information Retrieval and the increased accessibility of sound archives, large-scale analysis of world music with computational tools is today feasible. We investigate music similarity in a corpus of 8200 recordings of folk and traditional music from 137 countries around the world. In particular, we aim to identify music recordings that are most distinct compared to the rest of our corpus. We refer to these recordings as 'outliers'. We use signal processing tools to extract music information from audio recordings, data mining to quantify similarity and detect outliers, and spatial statistics to account for geographical correlation. Our findings suggest that Botswana is the country with the most distinct recordings in the corpus and China is the country with the most distinct recordings when considering spatial correlation. Our analysis includes a comparison of musical attributes and styles that contribute to the 'uniqueness' of the music of each country.

  5. A computational study on outliers in world music

    PubMed Central

    Benetos, Emmanouil; Dixon, Simon

    2017-01-01

    The comparative analysis of world music cultures has been the focus of several ethnomusicological studies in the last century. With the advances of Music Information Retrieval and the increased accessibility of sound archives, large-scale analysis of world music with computational tools is today feasible. We investigate music similarity in a corpus of 8200 recordings of folk and traditional music from 137 countries around the world. In particular, we aim to identify music recordings that are most distinct compared to the rest of our corpus. We refer to these recordings as ‘outliers’. We use signal processing tools to extract music information from audio recordings, data mining to quantify similarity and detect outliers, and spatial statistics to account for geographical correlation. Our findings suggest that Botswana is the country with the most distinct recordings in the corpus and China is the country with the most distinct recordings when considering spatial correlation. Our analysis includes a comparison of musical attributes and styles that contribute to the ‘uniqueness’ of the music of each country. PMID:29253027

  6. Dyadic Taxonomy of Delinquent Youth: Exploring Risks and Outcomes Associated With Maternal-Youth Reporting Discrepancies of Delinquent Behavior

    ERIC Educational Resources Information Center

    Reid, Joan A.; Sullivan, Christopher J.

    2016-01-01

    Using latent class analysis (LCA), this study identified a dyadic taxonomy of delinquent youth categorized by varying types of maternal-youth reporting discrepancies (i.e., youth < maternal, youth > maternal) within a sample of 764 14-year-old high-risk youth. Four distinctive subgroups of youth were identified, two of which reported more…

  7. An Analysis of Construction Contractor Performance Evaluation System

    DTIC Science & Technology

    2009-03-01

    65 8. Summary of Determinant and KMO Values for Finalized...principle component analysis output is the KMO and Bartlett‘s Test. KMO or Kaiser-Meyer-Olkin measure of sampling adequacy is used to identify if a...set of variables, when factored together, yield distinct and reliable factors (Field, 2005). KMO statistics vary between values of 0 to 1. Kaiser

  8. Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survival.

    PubMed

    Nicolau, Monica; Levine, Arnold J; Carlsson, Gunnar

    2011-04-26

    High-throughput biological data, whether generated as sequencing, transcriptional microarrays, proteomic, or other means, continues to require analytic methods that address its high dimensional aspects. Because the computational part of data analysis ultimately identifies shape characteristics in the organization of data sets, the mathematics of shape recognition in high dimensions continues to be a crucial part of data analysis. This article introduces a method that extracts information from high-throughput microarray data and, by using topology, provides greater depth of information than current analytic techniques. The method, termed Progression Analysis of Disease (PAD), first identifies robust aspects of cluster analysis, then goes deeper to find a multitude of biologically meaningful shape characteristics in these data. Additionally, because PAD incorporates a visualization tool, it provides a simple picture or graph that can be used to further explore these data. Although PAD can be applied to a wide range of high-throughput data types, it is used here as an example to analyze breast cancer transcriptional data. This identified a unique subgroup of Estrogen Receptor-positive (ER(+)) breast cancers that express high levels of c-MYB and low levels of innate inflammatory genes. These patients exhibit 100% survival and no metastasis. No supervised step beyond distinction between tumor and healthy patients was used to identify this subtype. The group has a clear and distinct, statistically significant molecular signature, it highlights coherent biology but is invisible to cluster methods, and does not fit into the accepted classification of Luminal A/B, Normal-like subtypes of ER(+) breast cancers. We denote the group as c-MYB(+) breast cancer.

  9. From loquacious to reticent: understanding patient health information communication to guide consumer health IT design.

    PubMed

    Valdez, Rupa S; Guterbock, Thomas M; Fitzgibbon, Kara; Williams, Ishan C; Wellbeloved-Stone, Claire A; Bears, Jaime E; Menefee, Hannah K

    2017-07-01

    It is increasingly recognized that some patients self-manage in the context of social networks rather than alone. Consumer health information technology (IT) designed to support socially embedded self-management must be responsive to patients' everyday communication practices. There is an opportunity to improve consumer health IT design by explicating how patients currently leverage social media to support health information communication. The objective of this study was to determine types of health information communication patterns that typify Facebook users with chronic health conditions to guide consumer health IT design. Seven hundred participants with type 2 diabetes were recruited through a commercial survey access panel. Cluster analysis was used to identify distinct approaches to health information communication both on and off Facebook. Analysis of variance (ANOVA) methods were used to identify demographic and behavioral differences among profiles. Secondary analysis of qualitative interviews ( n  = 25) and analysis of open-ended survey questions were conducted to understand participant rationales for each profile. Our analysis yielded 7 distinct health information communication profiles. Five of 7 profiles had consistent patterns both on and off Facebook, while the remaining 2 demonstrated distinct practices, with no health information communication on Facebook but some off Facebook. One profile was distinct from all others in both health information communication practices and demographic composition. Rationales for following specific health information communication practices were categorized under 6 themes: altruism, instrumental support, social support, privacy and stigma, convenience, and Facebook knowledge. Facebook has been widely adopted for health information communication; This study demonstrates that Facebook has been widely adopted for health information communication. It also shows that the ways in which patients communicate health information on and off Facebook are diverse. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Morphological and Genetic Evidence for Multiple Evolutionary Distinct Lineages in the Endangered and Commercially Exploited Red Lined Torpedo Barbs Endemic to the Western Ghats of India

    PubMed Central

    Dahanukar, Neelesh; Anvar Ali, Palakkaparambil Hamsa; Tharian, Josin; Raghavan, Rajeev; Antunes, Agostinho

    2013-01-01

    Red lined torpedo barbs (RLTBs) (Cyprinidae: Puntius) endemic to the Western Ghats Hotspot of India, are popular and highly priced freshwater aquarium fishes. Two decades of indiscriminate exploitation for the pet trade, restricted range, fragmented populations and continuing decline in quality of habitats has resulted in their ‘Endangered’ listing. Here, we tested whether the isolated RLTB populations demonstrated considerable variation qualifying to be considered as distinct conservation targets. Multivariate morphometric analysis using 24 size-adjusted characters delineated all allopatric populations. Similarly, the species-tree highlighted a phylogeny with 12 distinct RLTB lineages corresponding to each of the different riverine populations. However, coalescence-based methods using mitochondrial DNA markers identified only eight evolutionarily distinct lineages. Divergence time analysis points to recent separation of the populations, owing to the geographical isolation, more than 5 million years ago, after the lineages were split into two ancestral stocks in the Paleocene, on north and south of a major geographical gap in the Western Ghats. Our results revealing the existence of eight evolutionarily distinct RLTB lineages calls for the re-determination of conservation targets for these cryptic and endangered taxa. PMID:23894533

  11. Profiles of Reactivity in Cocaine-Exposed Children

    PubMed Central

    Schuetze, Pamela; Molnar, Danielle S.; Eiden, Rina D.

    2012-01-01

    This study explored the possibility that specific, theoretically consistent profiles of reactivity could be identified in a sample of cocaine-exposed infants and whether these profiles were associated with a range of infant and/or maternal characteristics. Cluster analysis was used to identify distinct groups of infants based on physiological, behavioral and maternal reported measures of reactivity. Five replicable clusters were identified which corresponded to 1) Dysregulated/High Maternal Report Reactors, 2) Low Behavioral Reactors, 3) High Reactors, 4) Optimal Reactors and 5) Dysregulated/Low Maternal Report Reactors. These clusters were associated with differences in prenatal cocaine exposure status, birthweight, maternal depressive symptoms, and maternal negative affect during mother-infant interactions. These results support the presence of distinct reactivity profiles among high risk infants recruited on the basis of prenatal cocaine exposure and demographically similar control group infants not exposed to cocaine. PMID:23204615

  12. Molecular classification of gastric cancer: a new paradigm.

    PubMed

    Shah, Manish A; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y; Klimstra, David S; Gerdes, Hans; Kelsen, David P

    2011-05-01

    Gastric cancer may be subdivided into 3 distinct subtypes--proximal, diffuse, and distal gastric cancer--based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. ©2011 AACR.

  13. Molecular Classification of Gastric Cancer: A new paradigm

    PubMed Central

    Shah, Manish A.; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y.; Klimstra, David S.; Gerdes, Hans; Kelsen, David P.

    2011-01-01

    Purpose Gastric cancer may be subdivided into three distinct subtypes –proximal, diffuse, and distal gastric cancer– based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >85% of samples were classified correctly. Gene set analysis with the False Discovery Rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. PMID:21430069

  14. Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology

    PubMed Central

    De Rocco, Daniela; Bottega, Roberta; Cappelli, Enrico; Cavani, Simona; Criscuolo, Maria; Nicchia, Elena; Corsolini, Fabio; Greco, Chiara; Borriello, Adriana; Svahn, Johanna; Pillon, Marta; Mecucci, Cristina; Casazza, Gabriella; Verzegnassi, Federico; Cugno, Chiara; Locasciulli, Anna; Farruggia, Piero; Longoni, Daniela; Ramenghi, Ugo; Barberi, Walter; Tucci, Fabio; Perrotta, Silverio; Grammatico, Paola; Hanenberg, Helmut; Della Ragione, Fulvio; Dufour, Carlo; Savoia, Anna

    2014-01-01

    Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes. PMID:24584348

  15. Cloning and analysis of fetal ovary microRNAs in cattle.

    PubMed

    Tripurani, Swamy K; Xiao, Caide; Salem, Mohamed; Yao, Jianbo

    2010-07-01

    Ovarian folliculogenesis and early embryogenesis are complex processes, which require tightly regulated expression and interaction of a multitude of genes. Small endogenous RNA molecules, termed microRNAs (miRNAs), are involved in the regulation of gene expression during folliculogenesis and early embryonic development. To identify miRNAs in bovine oocytes/ovaries, a bovine fetal ovary miRNA library was constructed. Sequence analysis of random clones from the library identified 679 miRNA sequences, which represent 58 distinct bovine miRNAs. Of these distinct miRNAs, 42 are known bovine miRNAs present in the miRBase database and the remaining 16 miRNAs include 15 new bovine miRNAs that are homologous to miRNAs identified in other species, and one novel miRNA, which does not match any miRNAs in the database. The precursor sequences for 14 of the new 15 miRNAs as well as the novel miRNA were identified from the bovine genome database and their hairpin structures were predicted. Expression analysis of the 58 miRNAs in fetal ovaries in comparison to somatic tissue pools identified 8 miRNAs predominantly expressed in fetal ovaries. Further analysis of the eight miRNAs in germinal vesicle (GV) stage oocytes identified two miRNAs (bta-mir424 and bta-mir-10b), that are highly abundant in GV oocytes. Both miRNAs show similar expression patterns during oocyte maturation and preimplantation development of bovine embryos, being abundant in GV and MII stage oocytes, as well as in early stage embryos (until 16-cell stage). The amount of the novel miRNA is relatively small in oocytes and early cleavage embryos but greater in blastocysts, suggesting a role of this miRNA in blastocyst cell differentiation. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Suicide in the oldest old: an observational study and cluster analysis.

    PubMed

    Sinyor, Mark; Tan, Lynnette Pei Lin; Schaffer, Ayal; Gallagher, Damien; Shulman, Kenneth

    2016-01-01

    The older population are at a high risk for suicide. This study sought to learn more about the characteristics of suicide in the oldest-old and to use a cluster analysis to determine if oldest-old suicide victims assort into clinically meaningful subgroups. Data were collected from a coroner's chart review of suicide victims in Toronto from 1998 to 2011. We compared two age groups (65-79 year olds, n = 335, and 80+ year olds, n = 191) and then conducted a hierarchical agglomerative cluster analysis using Ward's method to identify distinct clusters in the 80+ group. The younger and older age groups differed according to marital status, living circumstances and pattern of stressors. The cluster analysis identified three distinct clusters in the 80+ group. Cluster 1 was the largest (n = 124) and included people who were either married or widowed who had significantly more depression and somewhat more medical health stressors. In contrast, cluster 2 (n = 50) comprised people who were almost all single and living alone with significantly less identified depression and slightly fewer medical health stressors. All members of cluster 3 (n = 17) lived in a retirement residence or nursing home, and this group had the highest rates of depression, dementia, other mental illness and past suicide attempts. This is the first study to use the cluster analysis technique to identify meaningful subgroups among suicide victims in the oldest-old. The results reveal different patterns of suicide in the older population that may be relevant for clinical care. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Risk analysis of autonomous vehicles in mixed traffic streams.

    DOT National Transportation Integrated Search

    2017-05-01

    The objective of this study was to identify the risks associated with the failure of autonomous vehicles in mixed traffic streams and develop strategies to minimize these risks. Three distinct and interconnected phases were used to conduct the risk a...

  18. Spontaneous and natural cytotoxicity receptor-mediated cytotoxicity are effector functions of distinct natural killer subsets in hepatitis C virus-infected chimpanzees.

    PubMed

    Verstrepen, B E; Nieuwenhuis, I G; Mooij, P; Bogers, W M; Boonstra, A; Koopman, G

    2016-07-01

    In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV-infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94(high/dim) CD16(pos) and CD94(low) CD16(pos) subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94(dim) CD16(neg) subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees. © 2016 British Society for Immunology.

  19. Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset.

    PubMed

    Rogers, Angela J; Contrepois, Kévin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B; Matthay, Michael A

    2017-05-01

    There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This "high metabolite" endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS. Copyright © 2017 the American Physiological Society.

  20. Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset

    PubMed Central

    Contrepois, Kévin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B.; Matthay, Michael A.

    2017-01-01

    There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This “high metabolite” endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS. PMID:28258106

  1. Inorganic optical taggant and method of making

    DOEpatents

    Lauf, Robert J.; Anderson, Kimberly K.; Montgomery, Frederick C.

    2005-05-31

    Sintered, translucent ceramic microbeads, preferably alumina, titania, zirconia, yttria, zirconium phosphate, or yttrium aluminum garnet (YAG) are doped with one or more optically active species. The beads may be added to substances such as explosives in order to create a distinctive optical signature that identifies a manufacturer, lot number, etc. in the event of the need for forensic analysis. Because the beads have a generally spherical surface, the radius of curvature provides an additional distinguishing characteristic by which a particular sample may be identified. The beads could also be formulated into paints if needed to create distinctive optical signatures for camouflage, decoys, or other countermeasures and could also be applied as a dust to track the movement of personnel, vehicles, etc.

  2. The mineralogical, chemical, and chronological characteristics of the crystalline Apollo 16 impact melt rocks

    NASA Technical Reports Server (NTRS)

    Reimold, W. U.; Reimold, J. N.

    1984-01-01

    A comparative review of mineralogical, chemical, and chronological data on crystalline Apollo 16 impact melt rocks is presented. The use of such data to identify distinct impact melt complex is discussed, and 22 distinct impact melt bodies are identified. The recently detected group of feldspathic microporphyritic (FM) melt rocks was tested for chemical and isotopic homogeneity; instrumental neutron activation analysis and new Rb-Sr isotopic whole rock data indicate that FMs were probably not derived from a single impact melt sheet, but might be representative of the Descartes basement. Stratigraphical and chronological concepts for the geological development of the landing site are discussed, and a model is presented for the formation of the Cayley Plains and the Descartes formation.

  3. Reduction of Complexity: An Aspect of Network Visualization

    DTIC Science & Technology

    2006-12-01

    research is to identify strategies for the visualization of network information. Distinction can be made between visual communication and visual...exploration (MacEachern 1994). Visual communication deals with how to visualize results of different kinds of analysis, i.e., visualization in the case

  4. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.

    PubMed

    Giustacchini, Alice; Thongjuea, Supat; Barkas, Nikolaos; Woll, Petter S; Povinelli, Benjamin J; Booth, Christopher A G; Sopp, Paul; Norfo, Ruggiero; Rodriguez-Meira, Alba; Ashley, Neil; Jamieson, Lauren; Vyas, Paresh; Anderson, Kristina; Segerstolpe, Åsa; Qian, Hong; Olsson-Strömberg, Ulla; Mustjoki, Satu; Sandberg, Rickard; Jacobsen, Sten Eirik W; Mead, Adam J

    2017-06-01

    Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis.

  5. Characterization of Non-coding DNA Satellites Associated with Sweepoviruses (Genus Begomovirus, Geminiviridae) – Definition of a Distinct Class of Begomovirus-Associated Satellites

    PubMed Central

    Lozano, Gloria; Trenado, Helena P.; Fiallo-Olivé, Elvira; Chirinos, Dorys; Geraud-Pouey, Francis; Briddon, Rob W.; Navas-Castillo, Jesús

    2016-01-01

    Begomoviruses (family Geminiviridae) are whitefly-transmitted, plant-infecting single-stranded DNA viruses that cause crop losses throughout the warmer parts of the World. Sweepoviruses are a phylogenetically distinct group of begomoviruses that infect plants of the family Convolvulaceae, including sweet potato (Ipomoea batatas). Two classes of subviral molecules are often associated with begomoviruses, particularly in the Old World; the betasatellites and the alphasatellites. An analysis of sweet potato and Ipomoea indica samples from Spain and Merremia dissecta samples from Venezuela identified small non-coding subviral molecules in association with several distinct sweepoviruses. The sequences of 18 clones were obtained and found to be structurally similar to tomato leaf curl virus-satellite (ToLCV-sat, the first DNA satellite identified in association with a begomovirus), with a region with significant sequence identity to the conserved region of betasatellites, an A-rich sequence, a predicted stem–loop structure containing the nonanucleotide TAATATTAC, and a second predicted stem–loop. These sweepovirus-associated satellites join an increasing number of ToLCV-sat-like non-coding satellites identified recently. Although sharing some features with betasatellites, evidence is provided to suggest that the ToLCV-sat-like satellites are distinct from betasatellites and should be considered a separate class of satellites, for which the collective name deltasatellites is proposed. PMID:26925037

  6. Origin of a cryptic lineage in a threatened reptile through isolation and historical hybridization

    PubMed Central

    Sovic, M G; Fries, A C; Gibbs, H L

    2016-01-01

    Identifying phylogenetically distinct lineages and understanding the evolutionary processes by which they have arisen are important goals of phylogeography. This information can also help define conservation units in endangered species. Such analyses are being transformed by the availability of genomic-scale data sets and novel analytical approaches for statistically comparing different historical scenarios as causes of phylogeographic patterns. Here, we use genomic-scale restriction-site-associated DNA sequencing (RADseq) data to test for distinct lineages in the endangered Eastern Massasauga Rattlesnake (Sistrurus catenatus). We then use coalescent-based modeling techniques to identify the evolutionary mechanisms responsible for the origin of the lineages in this species. We find equivocal evidence for distinct phylogenetic lineages within S. catenatus east of the Mississippi River, but strong support for a previously unrecognized lineage on the western edge of the range of this snake, represented by populations from Iowa, USA. Snakes from these populations show patterns of genetic admixture with a nearby non-threatened sister species (Sistrurus tergeminus). Tests of historical demographic models support the hypothesis that the genetic distinctiveness of Iowa snakes is due to a combination of isolation and historical introgression between S. catenatus and S. tergeminus. Our work provides an example of how model-based analysis of genomic-scale data can help identify conservation units in rare species. PMID:27460499

  7. A homozygous founder missense variant in arylsulfatase G abolishes its enzymatic activity causing atypical Usher syndrome in humans.

    PubMed

    Khateb, Samer; Kowalewski, Björn; Bedoni, Nicola; Damme, Markus; Pollack, Netta; Saada, Ann; Obolensky, Alexey; Ben-Yosef, Tamar; Gross, Menachem; Dierks, Thomas; Banin, Eyal; Rivolta, Carlo; Sharon, Dror

    2018-01-04

    PurposeWe aimed to identify the cause of disease in patients suffering from a distinctive, atypical form of Usher syndrome.MethodsWhole-exome and genome sequencing were performed in five patients from three families of Yemenite Jewish origin, suffering from distinctive retinal degeneration phenotype and sensorineural hearing loss. Functional analysis of the wild-type and mutant proteins was performed in human fibrosarcoma cells.ResultsWe identified a homozygous founder missense variant, c.133G>T (p.D45Y) in arylsulfatase G (ARSG). All patients shared a distinctive retinal phenotype with ring-shaped atrophy along the arcades engirdling the fovea, resulting in ring scotoma. In addition, patients developed moderate to severe sensorineural hearing loss. Both vision and hearing loss appeared around the age of 40 years. The identified variant affected a fully conserved amino acid that is part of the catalytic site of the enzyme. Functional analysis of the wild-type and mutant proteins showed no basal activity of p.D45Y.ConclusionHomozygosity for ARSG-p.D45Y in humans leads to protein dysfunction, causing an atypical combination of late-onset Usher syndrome. Although there is no evidence for generalized clinical manifestations of lysosomal storage diseases in this set of patients, we cannot rule out the possibility that mild and late-onset symptoms may appear.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.227.

  8. Identification of clinically relevant phenotypes in patients with Ebstein anomaly.

    PubMed

    Cabrera, Rodrigo; Miranda-Fernández, Marta Catalina; Huertas-Quiñones, Victor Manuel; Carreño, Marisol; Pineda, Ivonne; Restrepo, Carlos M; Silva, Claudia Tamar; Quero, Rossi; Cano, Juan David; Manrique, Diana Carolina; Camacho, Camila; Tabares, Sebastián; García, Alberto; Sandoval, Néstor; Moreno Medina, Karen Julieth; Dennis Verano, Rodolfo José

    2018-03-01

    Ebstein anomaly (EA) is a heterogeneous congenital heart defect (CHD), frequently accompanied by diverse cardiac and extracardiac comorbidities, resulting in a wide range of clinical outcomes. Phenotypic characterization of EA patients has the potential to identify variables that influence prognosis and subgroups with distinct contributing factors. A comprehensive cross-sectional phenotypic characterization of 147 EA patients from one of the main referral institutions for CHD in Colombia was carried out. The most prevalent comorbidities and distinct subgroups within the patient cohort were identified through cluster analysis. The most prevalent cardiac comorbidities identified were atrial septal defect (61%), Wolff-Parkinson-White syndrome (WPW; 27%), and right ventricular outflow tract obstruction (25%). Cluster analysis showed that patients can be classified into 2 distinct subgroups with defined phenotypes that determine disease severity and survival. Patients in cluster 1 represented a particularly homogeneous subgroup with a milder spectrum of disease, including only patients with WPW and/or supraventricular tachycardia (SVT). Cluster 2 included patients with more diverse cardiovascular comorbidities. This study represents one of the largest phenotypic characterizations of EA patients reported. The data show that EA is a heterogeneous disease, very frequently associated with cardiovascular and noncardiovascular comorbidities. Patients with WPW and SVT represent a homogeneous subgroup that presents with a less severe spectrum of disease and better survival when adequately managed. This should be considered when searching for genetic causes of EA and in the clinical setting. © 2018 Wiley Periodicals, Inc.

  9. Genetic tracking of the raccoon variant of rabies virus in eastern North America.

    PubMed

    Szanto, Annamaria G; Nadin-Davis, Susan A; Rosatte, Richard C; White, Bradley N

    2011-06-01

    To gain insight into the incursion of the raccoon variant of rabies into the raccoon population in three Canadian provinces, a collection of 192 isolates of the raccoon rabies virus (RRV) strain was acquired from across its North American range and was genetically characterized. A 516-nucleotide segment of the non-coding region between the G and L protein open reading frames, corresponding to the most variable region of the rabies virus genome, was sequenced. This analysis identified 119 different sequences, and phylogenetic analysis of the dataset supports the documented history of RRV spread. Three distinct geographically restricted RRV lineages were identified. Lineage 1 was found in Florida, Alabama and Georgia and appears to form the ancestral lineage of the raccoon variant of rabies. Lineage 2, represented by just two isolates, was found only in Florida, while the third lineage appears broadly distributed throughout the rest of the eastern United States and eastern Canada. In New York State, two distinct spatially segregated variants were identified; the one occupying the western and northern portions of the state was responsible for an incursion of raccoon rabies into the Canadian province of Ontario. Isolates from New Brunswick and Quebec form distinct, separate clusters, consistent with their independent origins from neighboring areas of the United States. The data are consistent with localized northward incursion into these three separate areas with no evidence of east-west viral movement between the three Canadian provinces. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Serum Biochemical Phenotypes in the Domestic Dog

    PubMed Central

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

    2016-01-01

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

  11. Family Satisfaction With Nursing Home Care.

    PubMed

    Shippee, Tetyana P; Henning-Smith, Carrie; Gaugler, Joseph E; Held, Robert; Kane, Robert L

    2017-03-01

    This article explores the factor structure of a new family satisfaction with nursing home care instrument and determines the relationship of resident quality of life (QOL) and facility characteristics with family satisfaction. Data sources include (1) family satisfaction interviews ( n = 16,790 family members), (2) multidimensional survey of resident QOL ( n = 13,433 residents), and (3) facility characteristics ( n = 376 facilities). We used factor analysis to identify domains of family satisfaction and multivariate analyses to identify the role of facility-level characteristics and resident QOL on facility-mean values of family satisfaction. Four distinct domains were identified for family satisfaction: "care," "staff," "environment," and "food." Chain affiliation, higher resident acuity, more deficiencies, and large size were all associated with less family satisfaction, and resident QOL was a significant (albeit weak) predictor of family satisfaction. Results suggest that family member satisfaction is distinct from resident QOL but is associated with resident QOL and facility characteristics.

  12. Distinct phenotype clusters in childhood inflammatory brain diseases: implications for diagnostic evaluation.

    PubMed

    Cellucci, Tania; Tyrrell, Pascal N; Twilt, Marinka; Sheikh, Shehla; Benseler, Susanne M

    2014-03-01

    To identify distinct clusters of children with inflammatory brain diseases based on clinical, laboratory, and imaging features at presentation, to assess which features contribute strongly to the development of clusters, and to compare additional features between the identified clusters. A single-center cohort study was performed with children who had been diagnosed as having an inflammatory brain disease between June 1, 1989 and December 31, 2010. Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis were collected. K-means cluster analysis was performed to identify clusters of patients based on their presenting features. Associations between the clusters and patient variables, such as diagnoses, were determined. A total of 147 children (50% female; median age 8.8 years) were identified: 105 with primary central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other inflammatory brain diseases. Three distinct clusters were identified. Paresis and speech deficits were the most common presenting features in cluster 1. Children in cluster 2 were likely to present with behavior changes, cognitive dysfunction, and seizures, while those in cluster 3 experienced ataxia, vision abnormalities, and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of magnetic resonance imaging were common in all clusters, but unilateral ischemic lesions were more prominent in cluster 1. The clusters were associated with specific diagnoses and diagnostic test results. Children with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted. Copyright © 2014 by the American College of Rheumatology.

  13. Classification and characterization of Japanese consumers' beef preferences by external preference mapping.

    PubMed

    Sasaki, Keisuke; Ooi, Motoki; Nagura, Naoto; Motoyama, Michiyo; Narita, Takumi; Oe, Mika; Nakajima, Ikuyo; Hagi, Tatsuro; Ojima, Koichi; Kobayashi, Miho; Nomura, Masaru; Muroya, Susumu; Hayashi, Takeshi; Akama, Kyoko; Fujikawa, Akira; Hokiyama, Hironao; Kobayashi, Kuniyuki; Nishimura, Takanori

    2017-08-01

    Over the past few decades, beef producers in Japan have improved marbling in their beef products. It was recently reported that marbling is not well correlated with palatability as rated by Japanese consumers. This study sought to identify the consumer segments in Japan that prefer sensory characteristics of beef other than high marbling. Three Wagyu beef, one Holstein beef and two lean imported beef longissimus samples were subjected to a descriptive sensory test, physicochemical analysis and a consumer (n = 307) preference test. According to consumer classification and external preference mapping, four consumer segments were identified as 'gradual high-fat likers', 'moderate-fat and distinctive taste likers', 'Wagyu likers' and 'distinctive texture likers'. Although the major trend of Japanese consumers' beef preference was 'marbling liking', 16.9% of the consumers preferred beef samples that had moderate marbling and distinctive taste. The consumers' attitudes expressed in a questionnaire survey were in good agreement with the preference for marbling among the 'moderate-fat and distinctive taste likers'. These results indicate that moderately marbled beef is a potent category in the Japanese beef market. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  14. Phylogenetic resolution and habitat specificity of members of the Photobacterium phosphoreum species group.

    PubMed

    Ast, Jennifer C; Dunlap, Paul V

    2005-10-01

    Substantial ambiguity exists regarding the phylogenetic status of facultatively psychrophilic luminous bacteria identified as Photobacterium phosphoreum, a species thought to be widely distributed in the world's oceans and believed to be the specific bioluminescent light-organ symbiont of several deep-sea fishes. Members of the P. phosphoreum species group include luminous and non-luminous strains identified phenotypically from a variety of different habitats as well as phylogenetically defined lineages that appear to be evolutionarily distinct. To resolve this ambiguity and to begin developing a meaningful knowledge of the geographic distributions, habitats and symbiotic relationships of bacteria in the P. phosphoreum species group, we carried out a multilocus, fine-scale phylogenetic analysis based on sequences of the 16S rRNA, gyrB and luxABFE genes of many newly isolated luminous strains from symbiotic and saprophytic habitats, together with previously isolated luminous and non-luminous strains identified as P. phosphoreum from these and other habitats. Parsimony analysis unambiguously resolved three evolutionarily distinct clades, phosphoreum, iliopiscarium and kishitanii. The tight phylogenetic clustering within these clades and the distinct separation between them indicates they are different species, P. phosphoreum, Photobacterium iliopiscarium and the newly recognized 'Photobacterium kishitanii'. Previously reported non-luminous strains, which had been identified phenotypically as P. phosphoreum, resolved unambiguously as P. iliopiscarium, and all examined deep-sea fishes (specimens of families Chlorophthalmidae, Macrouridae, Moridae, Trachichthyidae and Acropomatidae) were found to harbour 'P. kishitanii', not P. phosphoreum, in their light organs. This resolution revealed also that 'P. kishitanii' is cosmopolitan in its geographic distribution. Furthermore, the lack of phylogenetic variation within 'P. kishitanii' indicates that this facultatively symbiotic bacterium is not cospeciating with its phylogenetically divergent host fishes. The results of this fine-scale phylogenetic analysis support the emerging view that bacterial species names should designate singular historical entities, i.e. discrete lineages diagnosed by a significant divergence of shared derived nucleotide characters.

  15. Distinct developmental profiles in typical speech acquisition

    PubMed Central

    Campbell, Thomas F.; Shriberg, Lawrence D.; Green, Jordan R.; Abdi, Hervé; Rusiewicz, Heather Leavy; Venkatesh, Lakshmi; Moore, Christopher A.

    2012-01-01

    Three- to five-year-old children produce speech that is characterized by a high level of variability within and across individuals. This variability, which is manifest in speech movements, acoustics, and overt behaviors, can be input to subgroup discovery methods to identify cohesive subgroups of speakers or to reveal distinct developmental pathways or profiles. This investigation characterized three distinct groups of typically developing children and provided normative benchmarks for speech development. These speech development profiles, identified among 63 typically developing preschool-aged speakers (ages 36–59 mo), were derived from the children's performance on multiple measures. These profiles were obtained by submitting to a k-means cluster analysis of 72 measures that composed three levels of speech analysis: behavioral (e.g., task accuracy, percentage of consonants correct), acoustic (e.g., syllable duration, syllable stress), and kinematic (e.g., variability of movements of the upper lip, lower lip, and jaw). Two of the discovered group profiles were distinguished by measures of variability but not by phonemic accuracy; the third group of children was characterized by their relatively low phonemic accuracy but not by an increase in measures of variability. Analyses revealed that of the original 72 measures, 8 key measures were sufficient to best distinguish the 3 profile groups. PMID:22357794

  16. System analysis identifies distinct and common functional networks governed by transcription factor ASCL1, in glioma and small cell lung cancer.

    PubMed

    Donakonda, Sainitin; Sinha, Swati; Dighe, Shrinivas Nivrutti; Rao, Manchanahalli R Satyanarayana

    2017-07-25

    ASCL1 is a basic Helix-Loop-Helix transcription factor (TF), which is involved in various cellular processes like neuronal development and signaling pathways. Transcriptome profiling has shown that ASCL1 overexpression plays an important role in the development of glioma and Small Cell Lung Carcinoma (SCLC), but distinct and common molecular mechanisms regulated by ASCL1 in these cancers are unknown. In order to understand how it drives the cellular functional network in these two tumors, we generated a gene expression profile in a glioma cell line (U87MG) to identify ASCL1 gene targets by an si RNA silencing approach and then compared this with a publicly available dataset of similarly silenced SCLC (NCI-H1618 cells). We constructed TF-TF and gene-gene interactions, as well as protein interaction networks of ASCL1 regulated genes in glioma and SCLC cells. Detailed network analysis uncovered various biological processes governed by ASCL1 target genes in these two tumor cell lines. We find that novel ASCL1 functions related to mitosis and signaling pathways influencing development and tumor growth are affected in both glioma and SCLC cells. In addition, we also observed ASCL1 governed functional networks that are distinct to glioma and SCLC.

  17. Distinct zooplankton regime shift patterns across ecoregions of the U.S. Northeast continental shelf Large Marine Ecosystem

    NASA Astrophysics Data System (ADS)

    Morse, R. E.; Friedland, K. D.; Tommasi, D.; Stock, C.; Nye, J.

    2017-01-01

    We investigated regime shifts in seasonal zooplankton communities of the Northeast continental shelf Large Marine Ecosystem (NES) and its subcomponent ecoregions over a multi-decadal period (1977-2013). Our cross ecoregion analysis shows that regime shifts in different ecoregions often exhibited very distinct characteristics, emphasizing more granular fluctuations in NES plankton communities relative to previous work. Shifts early in the time series generally reflected an increase in abundance levels. The response of zooplankton abundance within fall communities was more similar among ecoregions than for spring communities. The Gulf of Maine exhibited highly distinct patterns from other ecoregions, with regime shifts identified in the early 1980s, early 2000s, and mid-2000s for spring communities. Regime shifts were identified in the early to mid-1990s for the NES, Georges Bank, and the Mid-Atlantic Bight ecoregions, while the fall communities experienced shifts in the early 1990s and late 1980s for the NES and Georges Bank, but in the late 1990s in the Mid-Atlantic Bight. A constrained correspondence analysis of zooplankton community against local and basin-scale climatological indices suggests that water temperature, stratification, and the Atlantic multidecadal oscillation (AMO) were the predominant factors in driving the zooplankton community composition.

  18. Distinct Biological Potential of Streptococcus gordonii and Streptococcus sanguinis Revealed by Comparative Genome Analysis.

    PubMed

    Zheng, Wenning; Tan, Mui Fern; Old, Lesley A; Paterson, Ian C; Jakubovics, Nicholas S; Choo, Siew Woh

    2017-06-07

    Streptococcus gordonii and Streptococcus sanguinis are pioneer colonizers of dental plaque and important agents of bacterial infective endocarditis (IE). To gain a greater understanding of these two closely related species, we performed comparative analyses on 14 new S. gordonii and 5 S. sanguinis strains using various bioinformatics approaches. We revealed S. gordonii and S. sanguinis harbor open pan-genomes and share generally high sequence homology and number of core genes including virulence genes. However, we observed subtle differences in genomic islands and prophages between the species. Comparative pathogenomics analysis identified S. sanguinis strains have genes encoding IgA proteases, mitogenic factor deoxyribonucleases, nickel/cobalt uptake and cobalamin biosynthesis. On the contrary, genomic islands of S. gordonii strains contain additional copies of comCDE quorum-sensing system components involved in genetic competence. Two distinct polysaccharide locus architectures were identified, one of which was exclusively present in S. gordonii strains. The first evidence of genes encoding the CylA and CylB system by the α-haemolytic S. gordonii is presented. This study provides new insights into the genetic distinctions between S. gordonii and S. sanguinis, which yields understanding of tooth surfaces colonization and contributions to dental plaque formation, as well as their potential roles in the pathogenesis of IE.

  19. Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes.

    PubMed

    Pillai, S G; Tang, Y; van den Oord, E; Klotsman, M; Barnes, K; Carlsen, K; Gerritsen, J; Lenney, W; Silverman, M; Sly, P; Sundy, J; Tsanakas, J; von Berg, A; Whyte, M; Ortega, H G; Anderson, W H; Helms, P J

    2008-03-01

    Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the contribution of genes and environments to disease expression. To determine the minimum number of sets of features required to characterize subjects with asthma which will be useful in identifying important genetic and environmental contributors. Methods Probands aged 7-35 years with physician diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families from 11 centres in six countries forming the Genetics of Asthma International Network. Factor analysis was used to identify distinct phenotypes from questionnaire, clinical, and laboratory data, including baseline pulmonary function, allergen skin prick test (SPT). Five distinct factors were identified:(1) baseline pulmonary function measures [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], (2) specific allergen sensitization by SPT, (3) self-reported allergies, (4) symptoms characteristic of rhinitis and (5) symptoms characteristic of asthma. Replication in symptomatic siblings was consistent with shared genetic and/or environmental effects, and was robust across age groups, gender, and centres. Cronbach's alpha ranged from 0.719 to 0.983 suggesting acceptable internal scale consistencies. Derived scales were correlated with serum IgE, methacholine PC(20), age and asthma severity (interrupted sleep). IgE correlated with all three atopy-related factors, the strongest with the SPT factor whereas severity only correlated with baseline lung function, and with symptoms characteristic of rhinitis and of asthma. In children and adolescents with established asthma, five distinct sets of correlated patient characteristics appear to represent important aspects of the disease. Factor scores as quantitative traits may be better phenotypes in epidemiological and genetic analyses than those categories derived from the presence or absence of combinations of +ve SPTs and/or elevated IgE.

  20. Studying Psychosocial Barriers to Drug Treatment Among Chinese Methamphetamine Users Using A 3-Step Latent Class Analysis.

    PubMed

    Wang, Jichuan; Kelly, Brian C; Liu, Tieqiao; Hao, Wei

    2016-03-01

    Given the growth in methamphetamine use in China during the 21st century, we assessed perceived psychosocial barriers to drug treatment among this population. Using a sample of 303 methamphetamine users recruited via Respondent Driven Sampling, we use Latent Class Analysis (LCA) to identify possible distinct latent groups among Chinese methamphetamine users on the basis of their perceptions of psychosocial barriers to drug treatment. After covariates were included to predict latent class membership, the 3-step modeling approach was applied. Our findings indicate that the Chinese methamphetamine using population was heterogeneous on perceptions of drug treatment barriers; four distinct latent classes (subpopulations) were identified--Unsupported Deniers, Deniers, Privacy Anxious, and Low Barriers--and individual characteristics shaped the probability of class membership. Efforts to link Chinese methamphetamine users to treatment may require a multi-faceted approach that attends to differing perceptions about impediments to drug treatment. Copyright © 2015. Published by Elsevier Inc.

  1. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.

    PubMed

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude; Newton, Yulia; Shih, Juliann; Robertson, A Gordon; Hinoue, Toshinori; Hoadley, Katherine A; Gibb, Ewan A; Roszik, Jason; Covington, Kyle R; Wu, Chia-Chin; Shinbrot, Eve; Stransky, Nicolas; Hegde, Apurva; Yang, Ju Dong; Reznik, Ed; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I; Hess, Julian M; Auman, J Todd; Rhie, Suhn K; Bowlby, Reanne; Borad, Mitesh J; Zhu, Andrew X; Stuart, Josh M; Sander, Chris; Akbani, Rehan; Cherniack, Andrew D; Deshpande, Vikram; Mounajjed, Taofic; Foo, Wai Chin; Torbenson, Michael S; Kleiner, David E; Laird, Peter W; Wheeler, David A; McRee, Autumn J; Bathe, Oliver F; Andersen, Jesper B; Bardeesy, Nabeel; Roberts, Lewis R; Kwong, Lawrence N

    2017-03-14

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Recommendations for Review of TRADOC Pam 351-4(T).

    DTIC Science & Technology

    1981-07-08

    demonstrate proficiency in performing task at speed required on the job . Overtrain - Trainee must be trained to a high standard of retention ...20, It different from Report) OI. SUPPLEMENTARY NOTES 1. KEY WORDS (Continue on reveree aide It necessary and Identify by block number) Job Analysis...the analysis effort. The terminology in 351-4 is confusing. For example, no distinction is made between job and task analysis. There are no practical

  3. Two Distinct Clones of Methicillin-Resistant Staphylococcus aureus (MRSA) with the Same USA300 Pulsed-Field Gel Electrophoresis Profile: a Potential Pitfall for Identification of USA300 Community-Associated MRSA▿

    PubMed Central

    Larsen, Anders Rhod; Goering, Richard; Stegger, Marc; Lindsay, Jodi A.; Gould, Katherine A.; Hinds, Jason; Sørum, Marit; Westh, Henrik; Boye, Kit; Skov, Robert

    2009-01-01

    Analysis of methicillin-resistant Staphylococcus aureus (MRSA) characterized as USA300 by pulsed-field gel electrophoresis identified two distinct clones. One was similar to community-associated USA300 MRSA (ST8-IVa, t008, and Panton-Valentine leukocidin positive). The second (ST8-IVa, t024, and PVL negative) had different molecular characteristics and epidemiology, suggesting independent evolution. We recommend spa typing and/or PCR to discriminate between the two clones. PMID:19759225

  4. Subgroups of Chemotherapy Patients With Distinct Morning and Evening Fatigue Trajectories

    PubMed Central

    Kober, Kord M.; Cooper, Bruce A.; Paul, Steven M.; Dunn, Laura B.; Levine, Jon D.; Wright, Fay; Hammer, Marilyn J.; Mastick, Judy; Venook, Alan; Aouizerat, Bradley E.; Miaskowski, Christine

    2017-01-01

    Purpose Purposes of this study were to: identify subgroups of patients with distinct trajectories for morning and evening fatigue; evaluate for differences in demographic and clinical characteristics among these subgroups; and compare and contrast the predictors of subgroup membership for morning and evening fatigue. Methods Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n=582) completed questionnaires a total of six times over two cycles of CTX. Morning and evening fatigue severity were evaluated using the Lee Fatigue Scale. Latent profile analysis (LPA) was used to identify distinct subgroups. Results Three latent classes were identified for morning fatigue (i.e., Low (31.8%), High (51.4%), and Very High (16.8%)) and for evening evening fatigue (i.e., Moderate (20.0%), High (21.8%), and Very High (58.2%)). Most of the disease and treatment characteristics did not distinguish among the morning and evening fatigue classes. Compared to the Low class, patients in the High and Very High morning fatigue class were younger, had a lower functional status and higher level of comorbidity. Compared to the Moderate class, patients in the Very High evening fatigue class were younger, more likely to be female, had child care responsibilities, had a lower functional status, and a higher level of comorbidity. Conclusion LPA allows for the identification of risk factors for more severe fatigue. Since an overlap was not observed across the morning and evening fatigue classes and unique predictors for morning and evening fatigue were identified, these findings suggest that morning and evening fatigue may have distinct underlying mechanisms. PMID:26361758

  5. An observational study identifying obese subgroups among older adults at increased risk of mobility disability: do perceptions of the neighborhood environment matter?

    PubMed

    King, Abby C; Salvo, Deborah; Banda, Jorge A; Ahn, David K; Gill, Thomas M; Miller, Michael; Newman, Anne B; Fielding, Roger A; Siordia, Carlos; Moore, Spencer; Folta, Sara; Spring, Bonnie; Manini, Todd; Pahor, Marco

    2015-12-18

    Obesity is an increasingly prevalent condition among older adults, yet relatively little is known about how built environment variables may be associated with obesity in older age groups. This is particularly the case for more vulnerable older adults already showing functional limitations associated with subsequent disability. The Lifestyle Interventions and Independence for Elders (LIFE) trial dataset (n = 1600) was used to explore the associations between perceived built environment variables and baseline obesity levels. Age-stratified recursive partitioning methods were applied to identify distinct subgroups with varying obesity prevalence. Among participants aged 70-78 years, four distinct subgroups, defined by combinations of perceived environment and race-ethnicity variables, were identified. The subgroups with the lowest obesity prevalence (45.5-59.4%) consisted of participants who reported living in neighborhoods with higher residential density. Among participants aged 79-89 years, the subgroup (of three distinct subgroups identified) with the lowest obesity prevalence (19.4%) consisted of non-African American/Black participants who reported living in neighborhoods with friends or acquaintances similar in demographic characteristics to themselves. Overall support for the partitioned subgroupings was obtained using mixed model regression analysis. The results suggest that, in combination with race/ethnicity, features of the perceived neighborhood built and social environments differentiated distinct groups of vulnerable older adults from different age strata that differed in obesity prevalence. Pending further verification, the results may help to inform subsequent targeting of such subgroups for further investigation. Clinicaltrials.gov Identifier =  NCT01072500.

  6. Molecular subgroups of adult medulloblastoma: a long-term single-institution study.

    PubMed

    Zhao, Fu; Ohgaki, Hiroko; Xu, Lei; Giangaspero, Felice; Li, Chunde; Li, Peng; Yang, Zhijun; Wang, Bo; Wang, Xingchao; Wang, Zhenmin; Ai, Lin; Zhang, Jing; Luo, Lin; Liu, Pinan

    2016-07-01

    Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Morphologic, Pathologic, and Genetic Investigations of Bolbophorus Species Affecting Cultured Channel Catfish in the Mississippi Delta.

    PubMed

    Levy, M G; Flowers, J R; Poore, M F; Mullen, J E; Khoo, L H; Pote, L M; Paperna, I; Dzikowski, R; Litaker, R W

    2006-12-01

    Trematodes belonging to the genus Bolbophorus have recently been reported as the cause of substantial morbidity and mortality in cultured channel catfish Ictalurus punctatus in Mississippi and Louisiana. Previous investigators identified only a single species, B. confusus. In this investigation, genetic techniques were used to identify all stages of the parasite in all of its hosts. The 18s rRNA genes from specimens collected in Mississippi were sequenced and compared; this analysis revealed that there are two distinct species, B. damnificus (previously identified as B. confusus) and another, undescribed species. (Phylogenetic analysis indicated that a third species, B. levantinus, is also closely related to the Mississippi species.) Species-specific polymerase chain reaction assays capable of identifying and differentiating between these two parasites were developed. Both species were found to infect the first intermediate host (the ram's horn snail Planorbella trivolvis) in commercial channel catfish ponds, but only B. damnificus was recovered from the fish themselves. The new, unidentified Bolbophorus species was determined to be highly pathogenic to a number of fish species. The contribution of B. damnificus to disease in cultured channel catfish remains undetermined. Future investigations of these parasites must now take into account the presence of two distinct species.

  8. Morphologic, Pathologic, and Genetic Investigations of Bolbophorus Species Affecting Cultured Channel Catfish in the Mississippi Delta.

    PubMed

    Levy, M G; Flowers, J R; Poore, M F; Mullen, J E; Khoo, L H; Pote, L M; Paperna, I; Dzikowski, R; Litaker, R W

    2002-12-01

    Trematodes belonging to the genus Bolbophorus have recently been reported as the cause of substantial morbidity and mortality in cultured channel catfish Ictalurus punctatus in Mississippi and Louisiana. Previous investigators identified only a single species, B. confusus. In this investigation, genetic techniques were used to identify all stages of the parasite in all of its hosts. The 18s rRNA genes from specimens collected in Mississippi were sequenced and compared; this analysis revealed that there are two distinct species, B. damnificus (previously identified as B. confusus) and another, undescribed species. (Phylogenetic analysis indicated that a third species, B. levantinus, is also closely related to the Mississippi species.) Species-specific polymerase chain reaction assays capable of identifying and differentiating between these two parasites were developed. Both species were found to infect the first intermediate host (the ram's horn snail Planorbella trivolvis) in commercial channel catfish ponds, but only B. damnificus was recovered from the fish themselves. The new, unidentified Bolbophorus species was determined to be highly pathogenic to a number of fish species. The contribution of B. damnificus to disease in cultured channel catfish remains undetermined. Future investigations of these parasites must now take into account the presence of two distinct species.

  9. Tandem mass spectrometry of human tryptic blood peptides calculated by a statistical algorithm and captured by a relational database with exploration by a general statistical analysis system.

    PubMed

    Bowden, Peter; Beavis, Ron; Marshall, John

    2009-11-02

    A goodness of fit test may be used to assign tandem mass spectra of peptides to amino acid sequences and to directly calculate the expected probability of mis-identification. The product of the peptide expectation values directly yields the probability that the parent protein has been mis-identified. A relational database could capture the mass spectral data, the best fit results, and permit subsequent calculations by a general statistical analysis system. The many files of the Hupo blood protein data correlated by X!TANDEM against the proteins of ENSEMBL were collected into a relational database. A redundant set of 247,077 proteins and peptides were correlated by X!TANDEM, and that was collapsed to a set of 34,956 peptides from 13,379 distinct proteins. About 6875 distinct proteins were only represented by a single distinct peptide, 2866 proteins showed 2 distinct peptides, and 3454 proteins showed at least three distinct peptides by X!TANDEM. More than 99% of the peptides were associated with proteins that had cumulative expectation values, i.e. probability of false positive identification, of one in one hundred or less. The distribution of peptides per protein from X!TANDEM was significantly different than those expected from random assignment of peptides.

  10. Unique dietary patterns and chronic disease risk profiles of adult men: the Framingham nutrition studies.

    PubMed

    Millen, Barbara E; Quatromoni, Paula A; Pencina, Michael; Kimokoti, Ruth; Nam, Byung-H O; Cobain, Sonia; Kozak, Waldemar; Appugliese, Danielle P; Ordovas, Jose; D'Agostino, Ralph B

    2005-11-01

    To identify the dietary patterns of adult men and examine their relationships with nutrient intake and chronic disease risk over long-term follow-up. Baseline 145-item food frequency questionnaires from 1,666 Framingham Offspring-Spouse cohort men were used to identify comprehensive dietary patterns. Independent 3-day dietary records at baseline and 8 years later provided estimates of subjects' nutrient intake by dietary pattern. Chronic disease risk factor status was compared at baseline and 16-year follow-up across all male dietary patterns. Cluster analysis was applied to food frequency data to identify non-overlapping male dietary patterns. Analysis of covariance and logistic regression were used to compare nutrient intake, summary nutritional risk scores, and chronic disease risk status at baseline and follow-up by male dietary pattern. Five distinct and comprehensive dietary patterns of Framingham Offspring-Spouse men were identified and ordered according to overall nutritional risk: Transition to Heart Healthy, Higher Starch, Average Male, Lower Variety, and Empty Calories. Nutritional risk was high and varied by dietary pattern; key nutrient contrasts were stable over 8-year follow-up. Chronic disease risk also varied by dietary pattern and specific subgroup differences persisted over 16 years, notably rates of overweight/obesity and smoking. Quantitative cluster analysis applied to food frequency questionnaire data identified five distinct, comprehensive, and stable dietary patterns of adult Framingham Offspring-Spouse cohort men. The close associations between the dietary patterns, nutritional risk, and chronic disease profiles of men emphasize the importance of targeted preventive nutrition interventions to promote health in the male population.

  11. "A Strategy of Distinction" Unfolds: Unsettling the Undergraduate Outbound Mobility Experience

    ERIC Educational Resources Information Center

    Sidhu, Ravinder; Dall'Alba, Gloria

    2017-01-01

    Although short-term mobility programmes are increasingly promoted to university students as sources of competitive advantage, there is little research on academic learnings arising from these initiatives. A "field analysis" of outbound mobility is undertaken to identify convergences and disjunctures between institutional discourses,…

  12. Comparative genomic analysis identifies a Campylobacter clade deficient in selenium metabolism

    USDA-ARS?s Scientific Manuscript database

    The non-thermotolerant Campylobacter species C. fetus, C. hyointestinalis, C. iguaniorum and C. lanienae form a distinct phylogenetic cluster within the genus. These species are primarily isolated from foraging (swine) or grazing (e.g. cattle, sheep) animals and cause sporadic and infrequent human i...

  13. Chemical Engineering Students: A Distinct Group among Engineers

    ERIC Educational Resources Information Center

    Godwin, Allison; Potvin, Geoff

    2013-01-01

    This paper explores differences between chemical engineering students and students of other engineering disciplines, as identified by their intended college major. The data used in this analysis was taken from the nationally representative Sustainability and Gender in Engineering (SaGE) survey. Chemical engineering students differ significantly…

  14. Complete genome sequence analysis identifies a new genotype of brassica yellows virus that infects cabbage and radish in China.

    PubMed

    Zhang, Xiao-Yan; Xiang, Hai-Ying; Zhou, Cui-Ji; Li, Da-Wei; Yu, Jia-Lin; Han, Cheng-Gui

    2014-08-01

    For brassica yellows virus (BrYV), proposed to be a member of a new polerovirus species, two clearly distinct genotypes (BrYV-A and BrYV-B) have been described. In this study, the complete nucleotide sequences of two BrYV isolates from radish and Chinese cabbage were determined. Sequence analysis suggested that these isolates represent a new genotype, referred to here as BrYV-C. The full-length sequences of the two BrYV-C isolates shared 93.4-94.8 % identity with BrYV-A and BrYV-B. Further phylogenetic analysis showed that the BrYV-C isolates formed a subgroup that was distinct from the BrYV-A and BrYV-B isolates based on all of the proteins except P5.

  15. MALDI-TOF MS analysis of bovine and zoonotic Trichophyton verrucosum isolates reveals a distinct peak and cluster formation of a subgroup with Trichophyton benhamiae.

    PubMed

    Bartosch, Theresa; Heydel, Tilo; Uhrlaß, Silke; Nenoff, Pietro; Müller, Hendrik; Baums, Christoph Georg; Schrödl, Wieland

    2018-07-01

    The zoophilic dermatophyte Trichophyton verrucosum is the most important causative agent of bovine dermatophytosis. Additionally, it causes profound and poorly healing skin infections in humans indicating the high zoonotic potential. The objective of this study was to establish differentiation of T. verrucosum from other dermatophytes by mass spectrometry and to identify distinct features of the mass spectra. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was successful for identification of this pathogen only after extension of the database of the manufacturer with spectra from T. verrucosum strains, which were identified as such by sequencing of the internal transcribed spacer (ITS) region. MALDI-TOF MS analysis was conducted with 46 field isolates from cattle, two live vaccine strains, and 10 isolates from humans identified as T. verrucosum by sequence analysis of the ITS region. The results suggest a very good agreement of both methods. Comparison with the mass spectra of 68 strains of other keratinophilic fungi revealed that most T. verrucosum wild-type isolates showed a characteristic peak at 7950-7954 m/z, which was missing in the spectra of other keratinophilic fungi and the live vaccine strains. The spectra of T. verrucosum were most similar to the spectra of T. benhamiae, an emerging zoophilic dermatophyte. In summary, MALDI-TOF MS is a powerful and reliable tool to identify T. verrucosum.

  16. Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia

    PubMed Central

    Lin, Jhih-Rong; Cai, Ying; Zhang, Quanwei; Zhang, Wen; Nogales-Cadenas, Rubén; Zhang, Zhengdong D.

    2016-01-01

    Schizophrenia is a severe mental disorder with a large genetic component. Recent genome-wide association studies (GWAS) have identified many schizophrenia-associated common variants. For most of the reported associations, however, the underlying biological mechanisms are not clear. The critical first step for their elucidation is to identify the most likely disease genes as the source of the association signals. Here, we describe a general computational framework of post-GWAS analysis for complex disease gene prioritization. We identify 132 putative schizophrenia risk genes in 76 risk regions spanning 120 schizophrenia-associated common variants, 78 of which have not been recognized as schizophrenia disease genes by previous GWAS. Even more significantly, 29 of them are outside the risk regions, likely under regulation of transcriptional regulatory elements contained therein. These putative schizophrenia risk genes are transcriptionally active in both brain and the immune system, and highly enriched among cellular pathways, consistent with leading pathophysiological hypotheses about the pathogenesis of schizophrenia. With their involvement in distinct biological processes, these putative schizophrenia risk genes, with different association strengths, show distinctive temporal expression patterns, and play specific biological roles during brain development. PMID:27754856

  17. Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.

    PubMed

    Woll, Petter S; Kjällquist, Una; Chowdhury, Onima; Doolittle, Helen; Wedge, David C; Thongjuea, Supat; Erlandsson, Rikard; Ngara, Mtakai; Anderson, Kristina; Deng, Qiaolin; Mead, Adam J; Stenson, Laura; Giustacchini, Alice; Duarte, Sara; Giannoulatou, Eleni; Taylor, Stephen; Karimi, Mohsen; Scharenberg, Christian; Mortera-Blanco, Teresa; Macaulay, Iain C; Clark, Sally-Ann; Dybedal, Ingunn; Josefsen, Dag; Fenaux, Pierre; Hokland, Peter; Holm, Mette S; Cazzola, Mario; Malcovati, Luca; Tauro, Sudhir; Bowen, David; Boultwood, Jacqueline; Pellagatti, Andrea; Pimanda, John E; Unnikrishnan, Ashwin; Vyas, Paresh; Göhring, Gudrun; Schlegelberger, Brigitte; Tobiasson, Magnus; Kvalheim, Gunnar; Constantinescu, Stefan N; Nerlov, Claus; Nilsson, Lars; Campbell, Peter J; Sandberg, Rickard; Papaemmanuil, Elli; Hellström-Lindberg, Eva; Linnarsson, Sten; Jacobsen, Sten Eirik W

    2014-06-16

    Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which different cancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function in vivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs in vivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Mindfulness and Psychological Health Outcomes: A Latent Profile Analysis among Military Personnel and College Students.

    PubMed

    Bravo, Adrian J; Pearson, Matthew R; Kelley, Michelle L

    2018-02-01

    Previous research on trait mindfulness facets using person-centered analyses (e.g., latent profile analysis [LPA]) has identified four distinct mindfulness profiles among college students: a high mindfulness group (high on all facets of the Five-Factor Mindfulness Questionnaire [FFMQ]), a judgmentally observing group (highest on observing, but low on non-judging of inner experience and acting with awareness), a non-judgmentally aware group (high on non-judging of inner experience and acting with awareness, but very low on observing), and a low mindfulness group (low on all facets of the FFMQ). In the present study, we used LPA to identify distinct mindfulness profiles in a community based sample of U.S. military personnel (majority veterans; n = 407) and non-military college students ( n = 310) and compare these profiles on symptoms of psychological health outcomes (e.g., suicidality, PTSD, anxiety, rumination) and percentage of participants exceeding clinically significant cut-offs for depressive symptoms, substance use, and alcohol use. In the subsample of college students, we replicated previous research and found four distinct mindfulness profiles; however, in the military subsample we found three distinct mindfulness profiles (a combined low mindfulness/judgmentally observing class). In both subsamples, we found that the most adaptive profile was the "high mindfulness" profile (i.e., demonstrated the lowest scores on all psychological symptoms and the lowest probability of exceeding clinical cut-offs). Based on these findings, we purport that the comprehensive examination of an individual's mindfulness profile could help clinicians tailor interventions/treatments that capitalize on individual's specific strengths and work to address their specific deficits.

  19. Differentiation of closely related but biologically distinct cherry isolates of Prunus necrotic ringspot virus by polymerase chain reaction.

    PubMed

    Hammond, R W; Crosslin, J M; Pasini, R; Howell, W E; Mink, G I

    1999-07-01

    Prunus necrotic ringspot ilarvirus (PNRSV) exists as a number of biologically distinct variants which differ in host specificity, serology, and pathology. Previous nucleotide sequence alignment and phylogenetic analysis of cloned reverse transcription-polymerase chain reaction (RT-PCR) products of several biologically distinct sweet cherry isolates revealed correlations between symptom type and the nucleotide and amino acid sequences of the 3a (putative movement protein) and 3b (coat protein) open reading frames. Based upon this analysis, RT-PCR assays have been developed that can identify isolates displaying different symptoms and serotypes. The incorporation of primers in a multiplex PCR protocol permits rapid detection and discrimination among the strains. The results of PCR amplification using type-specific primers that amplify a portion of the coat protein gene demonstrate that the primer-selection procedure developed for PNRSV constitutes a reliable method of viral strain discrimination in cherry for disease control and will also be useful for examining biological diversity within the PNRSV virus group.

  20. Genome-Wide Transcriptome Analysis Reveals Conserved and Distinct Molecular Mechanisms of Al Resistance in Buckwheat (Fagopyrum esculentum Moench) Leaves

    PubMed Central

    Chen, Wei Wei; Xu, Jia Meng; Jin, Jian Feng; Lou, He Qiang; Fan, Wei

    2017-01-01

    Being an Al-accumulating crop, buckwheat detoxifies and tolerates Al not only in roots but also in leaves. While much progress has recently been made toward Al toxicity and resistance mechanisms in roots, little is known about the molecular basis responsible for detoxification and tolerance processes in leaves. Here, we carried out transcriptome analysis of buckwheat leaves in response to Al stress (20 µM, 24 h). We obtained 33,931 unigenes with 26,300 unigenes annotated in the NCBI database, and identified 1063 upregulated and 944 downregulated genes under Al stress. Functional category analysis revealed that genes related to protein translation, processing, degradation and metabolism comprised the biological processes most affected by Al, suggesting that buckwheat leaves maintain flexibility under Al stress by rapidly reprogramming their physiology and metabolism. Analysis of genes related to transcription regulation revealed that a large proportion of chromatin-regulation genes are specifically downregulated by Al stress, whereas transcription factor genes are overwhelmingly upregulated. Furthermore, we identified 78 upregulated and 22 downregulated genes that encode transporters. Intriguingly, only a few genes were overlapped with root Al-regulated transporter genes, which include homologs of AtMATE, ALS1, STAR1, ALS3 and a divalent ion symporter. In addition, we identified a subset of genes involved in development, in which genes associated with flowering regulation were important. Based on these data, it is proposed that buckwheat leaves develop conserved and distinct mechanisms to cope with Al toxicity. PMID:28846612

  1. Genomic analysis of primordial dwarfism reveals novel disease genes.

    PubMed

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S

    2014-02-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.

  2. Genomic analysis of primordial dwarfism reveals novel disease genes

    PubMed Central

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N.; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S.

    2014-01-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis. PMID:24389050

  3. Genome-Wide Transcriptome Analysis Reveals Conserved and Distinct Molecular Mechanisms of Al Resistance in Buckwheat (Fagopyrum esculentum Moench) Leaves.

    PubMed

    Chen, Wei Wei; Xu, Jia Meng; Jin, Jian Feng; Lou, He Qiang; Fan, Wei; Yang, Jian Li

    2017-08-27

    Being an Al-accumulating crop, buckwheat detoxifies and tolerates Al not only in roots but also in leaves. While much progress has recently been made toward Al toxicity and resistance mechanisms in roots, little is known about the molecular basis responsible for detoxification and tolerance processes in leaves. Here, we carried out transcriptome analysis of buckwheat leaves in response to Al stress (20 µM, 24 h). We obtained 33,931 unigenes with 26,300 unigenes annotated in the NCBI database, and identified 1063 upregulated and 944 downregulated genes under Al stress. Functional category analysis revealed that genes related to protein translation, processing, degradation and metabolism comprised the biological processes most affected by Al, suggesting that buckwheat leaves maintain flexibility under Al stress by rapidly reprogramming their physiology and metabolism. Analysis of genes related to transcription regulation revealed that a large proportion of chromatin-regulation genes are specifically downregulated by Al stress, whereas transcription factor genes are overwhelmingly upregulated. Furthermore, we identified 78 upregulated and 22 downregulated genes that encode transporters. Intriguingly, only a few genes were overlapped with root Al-regulated transporter genes, which include homologs of AtMATE , ALS1 , STAR1 , ALS3 and a divalent ion symporter. In addition, we identified a subset of genes involved in development, in which genes associated with flowering regulation were important. Based on these data, it is proposed that buckwheat leaves develop conserved and distinct mechanisms to cope with Al toxicity.

  4. Parental Influences on Adolescent Adjustment: Parenting Styles Versus Parenting Practices

    ERIC Educational Resources Information Center

    Lee, Sang Min; Daniels, M. Harry; Kissinger, Daniel B.

    2006-01-01

    The study identified distinct patterns of parental practices that differentially influence adolescent behavior using the National Educational Longitudinal Survey (NELS:88) database. Following Brenner and Fox's research model (1999), the cluster analysis was used to classify the four types of parental practices. The clusters of parenting practices…

  5. Sensitivity to Landscape Features: A Spatial Analysis of Field Geoscientists on the Move

    ERIC Educational Resources Information Center

    Baker, Kathleen M.; Petcovic, L. Heather

    2016-01-01

    Intelligent behavior in everyday contexts may depend on both ability and an individual's disposition toward using that ability. Research into patterns of thinking has identified three logically distinct components necessary for dispositional behavior: ability, inclination, and sensitivity. Surprisingly, sensitivity appears to be the most common…

  6. Evaluation of new biomarker genes for differentiating Haemophilus influenzae from Haemophilus haemolyticus.

    PubMed

    Theodore, M Jordan; Anderson, Raydel D; Wang, Xin; Katz, Lee S; Vuong, Jeni T; Bell, Melissa E; Juni, Billie A; Lowther, Sara A; Lynfield, Ruth; MacNeil, Jessica R; Mayer, Leonard W

    2012-04-01

    PCR detecting the protein D (hpd) and fuculose kinase (fucK) genes showed high sensitivity and specificity for identifying Haemophilus influenzae and differentiating it from H. haemolyticus. Phylogenetic analysis using the 16S rRNA gene demonstrated two distinct groups for H. influenzae and H. haemolyticus.

  7. Health Lifestyles: Audience Segmentation Analysis for Public Health Interventions.

    ERIC Educational Resources Information Center

    Slater, Michael D.; Flora, June A.

    This paper is concerned with the application of market research techniques to segment large populations into homogeneous units in order to improve the reach, utilization, and effectiveness of health programs. The paper identifies seven distinctive patterns of health attitudes, social influences, and behaviors using cluster analytic techniques in a…

  8. Online Learning: Learner Characteristics and Their Approaches to Managing Learning

    ERIC Educational Resources Information Center

    del Valle, Rodrigo; Duffy, Thomas M.

    2009-01-01

    Using cluster analysis this study investigated the characteristics of learning strategies learners use in online courses with one-on-one mentoring. Three distinct approaches were identified: "Mastery oriented", "Task focused" and "Minimalist in effort". Despite the widespread concern that students will have difficulty managing their time in online…

  9. Exploring the influence of encoding format on subsequent memory.

    PubMed

    Turney, Indira C; Dennis, Nancy A; Maillet, David; Rajah, M Natasha

    2017-05-01

    Distinctive encoding is greatly influenced by gist-based processes and has been shown to suffer when highly similar items are presented in close succession. Thus, elucidating the mechanisms underlying how presentation format affects gist processing is essential in determining the factors that influence these encoding processes. The current study utilised multivariate partial least squares (PLS) analysis to identify encoding networks directly associated with retrieval performance in a blocked and intermixed presentation condition. Subsequent memory analysis for successfully encoded items indicated no significant differences between reaction time and retrieval performance and presentation format. Despite no significant behavioural differences, behaviour PLS revealed differences in brain-behaviour correlations and mean condition activity in brain regions associated with gist-based vs. distinctive encoding. Specifically, the intermixed format encouraged more distinctive encoding, showing increased activation of regions associated with strategy use and visual processing (e.g., frontal and visual cortices, respectively). Alternatively, the blocked format exhibited increased gist-based processes, accompanied by increased activity in the right inferior frontal gyrus. Together, results suggest that the sequence that information is presented during encoding affects the degree to which distinctive encoding is engaged. These findings extend our understanding of the Fuzzy Trace Theory and the role of presentation format on encoding processes.

  10. Typology of patients with fibromyalgia: cluster analysis of duloxetine study patients.

    PubMed

    Lipkovich, Ilya A; Choy, Ernest H; Van Wambeke, Peter; Deberdt, Walter; Sagman, Doron

    2014-12-23

    To identify distinct groups of patients with fibromyalgia (FM) with respect to multiple outcome measures. Data from 631 duloxetine-treated women in 4 randomized, placebo-controlled trials were included in a cluster analysis based on outcomes after up to 12 weeks of treatment. Corresponding classification rules were constructed using a classification tree method. Probabilities for transitioning from baseline to Week 12 category were estimated for placebo and duloxetine patients (Ntotal = 1188) using logistic regression. Five clusters were identified, from "worst" (high pain levels and severe mental/physical impairment) to "best" (low pain levels and nearly normal mental/physical function). For patients with moderate overall severity, mental and physical symptoms were less correlated, resulting in 2 distinct clusters based on these 2 symptom domains. Three key variables with threshold values were identified for classification of patients: Brief Pain Inventory (BPI) pain interference overall scores of <3.29 and <7.14, respectively, a Fibromyalgia Impact Questionnaire (FIQ) interference with work score of <2, and an FIQ depression score of ≥5. Patient characteristics and frequencies per baseline category were similar between treatments; >80% of patients were in the 3 worst categories. Duloxetine patients were significantly more likely to improve after 12 weeks than placebo patients. A sustained effect was seen with continued duloxetine treatment. FM patients are heterogeneous and can be classified into distinct subgroups by simple descriptive rules derived from only 3 variables, which may guide individual patient management. Duloxetine showed higher improvement rates than placebo and had a sustained effect beyond 12 weeks.

  11. Multiple Food-Animal-Borne Route in Transmission of Antibiotic-Resistant Salmonella Newport to Humans

    PubMed Central

    Pan, Hang; Paudyal, Narayan; Li, Xiaoliang; Fang, Weihuan; Yue, Min

    2018-01-01

    Characterization of transmission routes of Salmonella among various food-animal reservoirs and their antibiogram is crucial for appropriate intervention and medical treatment. Here, we analyzed 3728 Salmonella enterica serovar Newport (S. Newport) isolates collected from various food-animals, retail meats and humans in the United States between 1996 and 2015, based on their minimum inhibitory concentration (MIC) toward 27 antibiotics. Random Forest and Hierarchical Clustering statistic was used to group the isolates according to their MICs. Classification and Regression Tree (CART) analysis was used to identify the appropriate antibiotic and its cut-off value between human- and animal-population. Two distinct populations were revealed based on the MICs of individual strain by both methods, with the animal population having significantly higher MICs which correlates to antibiotic-resistance (AR) phenotype. Only ∼9.7% (267/2763) human isolates could be attributed to food–animal origins. Furthermore, the isolates of animal origin had less diverse antibiogram than human isolates (P < 0.001), suggesting multiple sources involved in human infections. CART identified trimethoprim-sulfamethoxazole to be the best classifier for differentiating the animal and human isolates. Additionally, two typical AR patterns, MDR-Amp and Tet-SDR dominant in bovine- or turkey-population, were identified, indicating that distinct food-animal sources could be involved in human infections. The AR analysis suggested fluoroquinolones (i.e., ciprofloxacin), but not extended-spectrum cephalosporins (i.e., ceftriaxone, cefoxitin), is the adaptive choice for empirical therapy. Antibiotic-resistant S. Newport from humans has multiple origins, with distinct food-animal-borne route contributing to a significant proportion of heterogeneous isolates. PMID:29410657

  12. Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia.

    PubMed

    Sun, Heng; Miao, Zhengqiang; Zhang, Xin; Chan, Un In; Su, Sek Man; Guo, Sen; Wong, Chris Koon Ho; Xu, Xiaoling; Deng, Chu-Xia

    2018-06-01

    The mammary gland is very intricately and well organized into distinct tissues, including epithelia, endothelia, adipocytes, and stromal and immune cells. Many mammary gland diseases, such as breast cancer, arise from abnormalities in the mammary epithelium, which is mainly composed of two distinct lineages, the basal and luminal cells. Because of the limitation of traditional transcriptome analysis of bulk mammary cells, the hierarchy and heterogeneity of mammary cells within these two lineages remain unclear. To this end, using single-cell RNA-Seq coupled with FACS analysis and principal component analysis, we determined gene expression profiles of mammary epithelial cells of virgin and pregnant mice. These analyses revealed a much higher heterogeneity among the mammary cells than has been previously reported and enabled cell classification into distinct subgroups according to signature gene markers present in each group. We also identified and verified a rare CDH5 + cell subpopulation within a basal cell lineage as quiescent mammary stem cells (MaSCs). Moreover, using pseudo-temporal analysis, we reconstructed the developmental trajectory of mammary epithelia and uncovered distinct changes in gene expression and in biological functions of mammary cells along the developmental process. In conclusion, our work greatly refines the resolution of the cellular hierarchy in developing mammary tissues. The discovery of CDH5 + cells as MaSCs in these tissues may have implications for our understanding of the initiation, development, and pathogenesis of mammary tumors. © 2018 Sun et al.

  13. Genomic analysis and selected molecular pathways in rare cancers

    NASA Astrophysics Data System (ADS)

    Liu, Stephen V.; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J.; Eng, Cathy; Ramanathan, Ramesh K.; Von Hoff, Daniel D.; Barrett, Michael T.

    2012-12-01

    It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

  14. Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity.

    PubMed

    Azim, Kasum; Angonin, Diane; Marcy, Guillaume; Pieropan, Francesca; Rivera, Andrea; Donega, Vanessa; Cantù, Claudio; Williams, Gareth; Berninger, Benedikt; Butt, Arthur M; Raineteau, Olivier

    2017-03-01

    Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ) is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs) and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells originating from the SVZ. Next, we used a novel in silico genomic analysis, searchable platform-independent expression database/connectivity map (SPIED/CMAP), to generate a catalogue of small molecules that can be used to manipulate SVZ microdomain-specific lineages. Finally, we demonstrate that compounds identified in this analysis promote the generation of specific cell lineages from NSCs in vivo, during postnatal life and adulthood, as well as in regenerative contexts. This study unravels new strategies for using small bioactive molecules to direct germinal activity in the SVZ, which has therapeutic potential in neurodegenerative diseases.

  15. Genomic analysis and selected molecular pathways in rare cancers.

    PubMed

    Liu, Stephen V; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J; Eng, Cathy; Ramanathan, Ramesh K; Von Hoff, Daniel D; Barrett, Michael T

    2012-12-01

    It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

  16. Identifying compromised systems through correlation of suspicious traffic from malware behavioral analysis

    NASA Astrophysics Data System (ADS)

    Camilo, Ana E. F.; Grégio, André; Santos, Rafael D. C.

    2016-05-01

    Malware detection may be accomplished through the analysis of their infection behavior. To do so, dynamic analysis systems run malware samples and extract their operating system activities and network traffic. This traffic may represent malware accessing external systems, either to steal sensitive data from victims or to fetch other malicious artifacts (configuration files, additional modules, commands). In this work, we propose the use of visualization as a tool to identify compromised systems based on correlating malware communications in the form of graphs and finding isomorphisms between them. We produced graphs from over 6 thousand distinct network traffic files captured during malware execution and analyzed the existing relationships among malware samples and IP addresses.

  17. Distinct herpesvirus resistances and immune responses of three gynogenetic clones of gibel carp revealed by comprehensive transcriptomes.

    PubMed

    Gao, Fan-Xiang; Wang, Yang; Zhang, Qi-Ya; Mou, Cheng-Yan; Li, Zhi; Deng, Yuan-Sheng; Zhou, Li; Gui, Jian-Fang

    2017-07-24

    Gibel carp is an important aquaculture species in China, and a herpesvirus, called as Carassius auratus herpesvirus (CaHV), has hampered the aquaculture development. Diverse gynogenetic clones of gibel carp have been identified or created, and some of them have been used as aquaculture varieties, but their resistances to herpesvirus and the underlying mechanism remain unknown. To reveal their susceptibility differences, we firstly performed herpesvirus challenge experiments in three gynogenetic clones of gibel carp, including the leading variety clone A + , candidate variety clone F and wild clone H. Three clones showed distinct resistances to CaHV. Moreover, 8772, 8679 and 10,982 differentially expressed unigenes (DEUs) were identified from comparative transcriptomes between diseased individuals and control individuals of clone A + , F and H, respectively. Comprehensive analysis of the shared DEUs in all three clones displayed common defense pathways to the herpesvirus infection, activating IFN system and suppressing complements. KEGG pathway analysis of specifically changed DEUs in respective clones revealed distinct immune responses to the herpesvirus infection. The DEU numbers identified from clone H in KEGG immune-related pathways, such as "chemokine signaling pathway", "Toll-like receptor signaling pathway" and others, were remarkably much more than those from clone A + and F. Several IFN-related genes, including Mx1, viperin, PKR and others, showed higher increases in the resistant clone H than that in the others. IFNphi3, IFI44-like and Gig2 displayed the highest expression in clone F and IRF1 uniquely increased in susceptible clone A + . In contrast to strong immune defense in resistant clone H, susceptible clone A + showed remarkable up-regulation of genes related to apoptosis or death, indicating that clone A + failed to resist virus offensive and evidently induced apoptosis or death. Our study is the first attempt to screen distinct resistances and immune responses of three gynogenetic gibel carp clones to herpesvirus infection by comprehensive transcriptomes. These differential DEUs, immune-related pathways and IFN system genes identified from susceptible and resistant clones will be beneficial to marker-assisted selection (MAS) breeding or molecular module-based resistance breeding in gibel carp.

  18. Interdisciplinary cognitive task analysis: a strategy to develop a comprehensive endoscopic retrograde cholangiopancreatography protocol for use in fellowship training.

    PubMed

    Canopy, Erin; Evans, Matt; Boehler, Margaret; Roberts, Nicole; Sanfey, Hilary; Mellinger, John

    2015-10-01

    Endoscopic retrograde cholangiopancreatography is a challenging procedure performed by surgeons and gastroenterologists. We employed cognitive task analysis to identify steps and decision points for this procedure. Standardized interviews were conducted with expert gastroenterologists (7) and surgeons (4) from 4 institutions. A procedural step and cognitive decision point protocol was created from audio-taped transcriptions and was refined by 5 additional surgeons. Conceptual elements, sequential actions, and decision points were iterated for 5 tasks: patient preparation, duodenal intubation, selective cannulation, imaging interpretation with related therapeutic intervention, and complication management. A total of 180 steps were identified. Gastroenterologists identified 34 steps not identified by surgeons, and surgeons identified 20 steps not identified by gastroenterologists. The findings suggest that for complex procedures performed by diverse practitioners, more experts may help delineate distinctive emphases differentiated by training background and type of practice. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Histomorphometric analysis of collagen architecture of auricular keloids in an Asian population.

    PubMed

    Chong, Yosep; Park, Tae Hwan; Seo, Sang won; Chang, Choong Hyun

    2015-03-01

    Keloids are a pathologic condition of the reparative process, which present as excessive scar formation that involves various cells and cytokines. Many studies focusing on the histologic feature of keloids, however, have shown discordant results without consideration of architectural aspect of collagen structure. The purpose of this study was to demonstrate a schematic illustration of collagen architecture of keloids, specifically auricular keloids, and to analyze each part on the histomorphologic and morphometric basis. Thirty-nine surgically excised auricular keloids were retrieved from the file of Kangbuk Samsung Hospital. After exhaustive histomorphologic analysis, 3 distinctive structural parts, keloidal collagen, organizing collagen, and proliferating core collagen, were identified and mapped in every case. Cellularity of fibroblasts, blood vessel density, degree of inflammatory cell infiltration, and mast cells counts using Masson trichrome stain, Van Gieson stain, toluidine blue stain, and immunohistochemical stains for CD31 and smooth muscle actin were analyzed in each part of each case. Morphometric analysis on these parameters using ImageJ software was performed using 3 representative images of each part. Three parts were histomorphologically distinct by shape and array of collagen bundles, fibroblasts cellularity, blood vessel density, degree of inflammatory cells, and mast cell infiltration. Morphometric analysis revealed statistically significant difference between each part in fibroblasts cellularity, blood vessel density, degree of inflammatory cell infiltration, and mast cells count. All parameters were exceedingly high in whorling hypercellular fibrous nodules in proliferating core collagen showing simultaneous changes in other parts. Morphologically and morphometrically, 3 distinctive parts were identified in auricular keloids. Mast cell infiltrations, blood vessel density, and fibroblast cellularity are simultaneously increased or decreased according to these parts. Proliferating core collagen might serve as a proliferating center of keloids and might be a key portion for tumor growth and recurrence.

  20. Distinct Host Tropism Protein Signatures to Identify Possible Zoonotic Influenza A Viruses.

    PubMed

    Eng, Christine L P; Tong, Joo Chuan; Tan, Tin Wee

    2016-01-01

    Zoonotic influenza A viruses constantly pose a health threat to humans as novel strains occasionally emerge from the avian population to cause human infections. Many past epidemic as well as pandemic strains have originated from avian species. While most viruses are restricted to their primary hosts, zoonotic strains can sometimes arise from mutations or reassortment, leading them to acquire the capability to escape host species barrier and successfully infect a new host. Phylogenetic analyses and genetic markers are useful in tracing the origins of zoonotic infections, but there are still no effective means to identify high risk strains prior to an outbreak. Here we show that distinct host tropism protein signatures can be used to identify possible zoonotic strains in avian species which have the potential to cause human infections. We have discovered that influenza A viruses can now be classified into avian, human, or zoonotic strains based on their host tropism protein signatures. Analysis of all influenza A viruses with complete proteome using the host tropism prediction system, based on machine learning classifications of avian and human viral proteins has uncovered distinct signatures of zoonotic strains as mosaics of avian and human viral proteins. This is in contrast with typical avian or human strains where they show mostly avian or human viral proteins in their signatures respectively. Moreover, we have found that zoonotic strains from the same influenza outbreaks carry similar host tropism protein signatures characteristic of a common ancestry. Our results demonstrate that the distinct host tropism protein signature in zoonotic strains may prove useful in influenza surveillance to rapidly identify potential high risk strains circulating in avian species, which may grant us the foresight in anticipating an impending influenza outbreak.

  1. Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation

    PubMed Central

    Jha, Prerana; Pia Patric, Irene Rosita; Shukla, Sudhanshu; Pathak, Pankaj; Pal, Jagriti; Sharma, Vikas; Thinagararanjan, Sivaarumugam; Santosh, Vani; Suri, Vaishali; Sharma, Mehar Chand; Arivazhagan, Arimappamagan; Suri, Ashish; Gupta, Deepak; Somasundaram, Kumaravel; Sarkar, Chitra

    2014-01-01

    Background Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Methods Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine–phosphate–guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Results Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine–phosphate–guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Conclusions Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation–specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation. PMID:24997139

  2. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens

    PubMed Central

    Glinsky, Gennadi V.

    2016-01-01

    Abstract Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8–10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P < 0.0001 in all instances). Present analysis supports the idea that phenotypic divergence of Homo sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of creation of divergent sequences of regulatory DNA: (i) recombination-associated exaptation of the highly conserved ancestral regulatory DNA segments; (ii) human-specific insertions of transposable elements. PMID:27503290

  3. Application of Latent Class Analysis to Identify Behavioral Patterns of Response to Behavioral Lifestyle Interventions in Overweight and Obese Adults

    PubMed Central

    Fitzpatrick, Stephanie L.; Coughlin, Janelle W.; Appel, Lawrence J.; Tyson, Crystal; Stevens, Victor J.; Jerome, Gerald J.; Dalcin, Arlene; Brantley, Phillip J.; Hill-Briggs, Felicia

    2016-01-01

    Background Examining responders and non-responders to behavioral lifestyle interventions among overweight/obese adults with additional comorbidities may aid in refining and tailoring obesity treatment. Purpose The purpose of this study is to demonstrate the use of latent class analysis to identify patterns of response to behavioral lifestyle interventions based on adherence to diet and exercise recommendations. Method Repeated measures latent class analysis was applied to two clinical trial datasets, combination of two active interventions in the PREMIER Trial (n=501) and phase 1 of the Weight Loss Maintenance Trial (WLM; n=1685), to identify patterns of response to behavioral lifestyle interventions. Treatment response was based on adherence to daily recommendations for fruit/vegetable, fat, saturated fat, sodium, and exercise at baseline and 6 months. Results In PREMIER, three distinct latent classes emerged: responders (45.9 %), non-responders (23.6 %), and early adherers (30.5 %). Responders and Early Adherers had greater weight loss at 6 and 18 months and were more likely to meet behavioral recommendations at 18 months than Non-responders. For WLM, there were four latent classes: partial responders (16 %), non-responders (40 %), early adherers (2 %), and fruit/veggie only responders (41 %). Non-responders in WLM had significantly less weight loss at 6 months compared to that of the other three latent classes. Conclusion Latent class analysis is a useful method to apply to clinical trial data to identify distinct patterns of response to behavioral interventions. Overweight/ obese participants who respond to behavioral lifestyle treatment (i.e., meet behavioral recommendations) have significantly greater weight loss than that of participants who do not make behavioral changes. PMID:25331853

  4. Application of Latent Class Analysis to Identify Behavioral Patterns of Response to Behavioral Lifestyle Interventions in Overweight and Obese Adults.

    PubMed

    Fitzpatrick, Stephanie L; Coughlin, Janelle W; Appel, Lawrence J; Tyson, Crystal; Stevens, Victor J; Jerome, Gerald J; Dalcin, Arlene; Brantley, Phillip J; Hill-Briggs, Felicia

    2015-08-01

    Examining responders and non-responders to behavioral lifestyle interventions among overweight/obese adults with additional comorbidities may aid in refining and tailoring obesity treatment. The purpose of this study is to demonstrate the use of latent class analysis to identify patterns of response to behavioral lifestyle interventions based on adherence to diet and exercise recommendations. Repeated measures latent class analysis was applied to two clinical trial datasets, combination of two active interventions in the PREMIER Trial (n = 501) and phase 1 of the Weight Loss Maintenance Trial (WLM; n = 1685), to identify patterns of response to behavioral lifestyle interventions. Treatment response was based on adherence to daily recommendations for fruit/vegetable, fat, saturated fat, sodium, and exercise at baseline and 6 months. In PREMIER, three distinct latent classes emerged: responders (45.9%), non-responders (23.6%), and early adherers (30.5%). Responders and Early Adherers had greater weight loss at 6 and 18 months and were more likely to meet behavioral recommendations at 18 months than Non-responders. For WLM, there were four latent classes: partial responders (16%), non-responders (40%), early adherers (2%), and fruit/veggie only responders (41%). Non-responders in WLM had significantly less weight loss at 6 months compared to that of the other three latent classes. Latent class analysis is a useful method to apply to clinical trial data to identify distinct patterns of response to behavioral interventions. Overweight/ obese participants who respond to behavioral lifestyle treatment (i.e., meet behavioral recommendations) have significantly greater weight loss than that of participants who do not make behavioral changes.

  5. Genome-Wide Analysis of Oleosin Gene Family in 22 Tree Species: An Accelerator for Metabolic Engineering of BioFuel Crops and Agrigenomics Industrial Applications?

    PubMed Central

    2015-01-01

    Abstract Trees contribute to enormous plant oil reserves because many trees contain 50%–80% of oil (triacylglycerols, TAGs) in the fruits and kernels. TAGs accumulate in subcellular structures called oil bodies/droplets, in which TAGs are covered by low-molecular-mass hydrophobic proteins called oleosins (OLEs). The OLEs/TAGs ratio determines the size and shape of intracellular oil bodies. There is a lack of comprehensive sequence analysis and structural information of OLEs among diverse trees. The objectives of this study were to identify OLEs from 22 tree species (e.g., tung tree, tea-oil tree, castor bean), perform genome-wide analysis of OLEs, classify OLEs, identify conserved sequence motifs and amino acid residues, and predict secondary and three-dimensional structures in tree OLEs and OLE subfamilies. Data mining identified 65 OLEs with perfect conservation of the “proline knot” motif (PX5SPX3P) from 19 trees. These OLEs contained >40% hydrophobic amino acid residues. They displayed similar properties and amino acid composition. Genome-wide phylogenetic analysis and multiple sequence alignment demonstrated that these proteins could be classified into five OLE subfamilies. There were distinct patterns of sequence conservation among the OLE subfamilies and within individual tree species. Computational modeling indicated that OLEs were composed of at least three α-helixes connected with short coils without any β-strand and that they exhibited distinct 3D structures and ligand binding sites. These analyses provide fundamental information in the similarity and specificity of diverse OLE isoforms within the same subfamily and among the different species, which should facilitate studying the structure-function relationship and identify critical amino acid residues in OLEs for metabolic engineering of tree TAGs. PMID:26258573

  6. Genome-Wide Analysis of Oleosin Gene Family in 22 Tree Species: An Accelerator for Metabolic Engineering of BioFuel Crops and Agrigenomics Industrial Applications?

    PubMed

    Cao, Heping

    2015-09-01

    Trees contribute to enormous plant oil reserves because many trees contain 50%-80% of oil (triacylglycerols, TAGs) in the fruits and kernels. TAGs accumulate in subcellular structures called oil bodies/droplets, in which TAGs are covered by low-molecular-mass hydrophobic proteins called oleosins (OLEs). The OLEs/TAGs ratio determines the size and shape of intracellular oil bodies. There is a lack of comprehensive sequence analysis and structural information of OLEs among diverse trees. The objectives of this study were to identify OLEs from 22 tree species (e.g., tung tree, tea-oil tree, castor bean), perform genome-wide analysis of OLEs, classify OLEs, identify conserved sequence motifs and amino acid residues, and predict secondary and three-dimensional structures in tree OLEs and OLE subfamilies. Data mining identified 65 OLEs with perfect conservation of the "proline knot" motif (PX5SPX3P) from 19 trees. These OLEs contained >40% hydrophobic amino acid residues. They displayed similar properties and amino acid composition. Genome-wide phylogenetic analysis and multiple sequence alignment demonstrated that these proteins could be classified into five OLE subfamilies. There were distinct patterns of sequence conservation among the OLE subfamilies and within individual tree species. Computational modeling indicated that OLEs were composed of at least three α-helixes connected with short coils without any β-strand and that they exhibited distinct 3D structures and ligand binding sites. These analyses provide fundamental information in the similarity and specificity of diverse OLE isoforms within the same subfamily and among the different species, which should facilitate studying the structure-function relationship and identify critical amino acid residues in OLEs for metabolic engineering of tree TAGs.

  7. Massive Analysis of Rice Small RNAs: Mechanistic Implications of Regulated MicroRNAs and Variants for Differential Target RNA Cleavage[W][OA

    PubMed Central

    Jeong, Dong-Hoon; Park, Sunhee; Zhai, Jixian; Gurazada, Sai Guna Ranjan; De Paoli, Emanuele; Meyers, Blake C.; Green, Pamela J.

    2011-01-01

    Small RNAs have a variety of important roles in plant development, stress responses, and other processes. They exert their influence by guiding mRNA cleavage, translational repression, and chromatin modification. To identify previously unknown rice (Oryza sativa) microRNAs (miRNAs) and those regulated by environmental stress, 62 small RNA libraries were constructed from rice plants and used for deep sequencing with Illumina technology. The libraries represent several tissues from control plants and plants subjected to different environmental stress treatments. More than 94 million genome-matched reads were obtained, resulting in more than 16 million distinct small RNA sequences. This allowed an evaluation of ~400 annotated miRNAs with current criteria and the finding that among these, ~150 had small interfering RNA–like characteristics. Seventy-six new miRNAs were found, and miRNAs regulated in response to water stress, nutrient stress, or temperature stress were identified. Among the new examples of miRNA regulation were members of the same miRNA family that were differentially regulated in different organs and had distinct sequences Some of these distinct family members result in differential target cleavage and provide new insight about how an agriculturally important rice phenotype could be regulated in the panicle. This high-resolution analysis of rice miRNAs should be relevant to plant miRNAs in general, particularly in the Poaceae. PMID:22158467

  8. Going coastal: shared evolutionary history between coastal British Columbia and Southeast Alaska wolves (Canis lupus).

    PubMed

    Weckworth, Byron V; Dawson, Natalie G; Talbot, Sandra L; Flamme, Melanie J; Cook, Joseph A

    2011-05-04

    Many coastal species occupying the temperate rainforests of the Pacific Northwest in North America comprise endemic populations genetically and ecologically distinct from interior continental conspecifics. Morphological variation previously identified among wolf populations resulted in recognition of multiple subspecies of wolves in the Pacific Northwest. Recently, separate genetic studies have identified diverged populations of wolves in coastal British Columbia and coastal Southeast Alaska, providing support for hypotheses of distinct coastal subspecies. These two regions are geographically and ecologically contiguous, however, there is no comprehensive analysis across all wolf populations in this coastal rainforest. By combining mitochondrial DNA datasets from throughout the Pacific Northwest, we examined the genetic relationship between coastal British Columbia and Southeast Alaska wolf populations and compared them with adjacent continental populations. Phylogenetic analysis indicates complete overlap in the genetic diversity of coastal British Columbia and Southeast Alaska wolves, but these populations are distinct from interior continental wolves. Analyses of molecular variation support the separation of all coastal wolves in a group divergent from continental populations, as predicted based on hypothesized subspecies designations. Two novel haplotypes also were uncovered in a newly assayed continental population of interior Alaska wolves. We found evidence that coastal wolves endemic to these temperate rainforests are diverged from neighbouring, interior continental wolves; a finding that necessitates new international strategies associated with the management of this species.

  9. Temporomandibular joint formation requires two distinct hedgehog-dependent steps.

    PubMed

    Purcell, Patricia; Joo, Brian W; Hu, Jimmy K; Tran, Pamela V; Calicchio, Monica L; O'Connell, Daniel J; Maas, Richard L; Tabin, Clifford J

    2009-10-27

    We conducted a genetic analysis of the developing temporo-mandibular or temporomandi-bular joint (TMJ), a highly specialized synovial joint that permits movement and function of the mammalian jaw. First, we used laser capture microdissection to perform a genome-wide expression analysis of each of its developing components. The expression patterns of genes identified in this screen were examined in the TMJ and compared with those of other synovial joints, including the shoulder and the hip joints. Striking differences were noted, indicating that the TMJ forms via a distinct molecular program. Several components of the hedgehog (Hh) signaling pathway are among the genes identified in the screen, including Gli2, which is expressed specifically in the condyle and in the disk of the developing TMJ. We found that mice deficient in Gli2 display aberrant TMJ development such that the condyle loses its growth-plate-like cellular organization and no disk is formed. In addition, we used a conditional strategy to remove Smo, a positive effector of the Hh signaling pathway, from chondrocyte progenitors. This cell autonomous loss of Hh signaling allows for disk formation, but the resulting structure fails to separate from the condyle. Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation, and disk-condyle separation and provide a molecular framework for future studies of the TMJ.

  10. Temporomandibular joint formation requires two distinct hedgehog-dependent steps

    PubMed Central

    Purcell, Patricia; Joo, Brian W.; Hu, Jimmy K.; Tran, Pamela V.; Calicchio, Monica L.; O'Connell, Daniel J.; Maas, Richard L.; Tabin, Clifford J.

    2009-01-01

    We conducted a genetic analysis of the developing temporo-mandibular or temporomandi-bular joint (TMJ), a highly specialized synovial joint that permits movement and function of the mammalian jaw. First, we used laser capture microdissection to perform a genome-wide expression analysis of each of its developing components. The expression patterns of genes identified in this screen were examined in the TMJ and compared with those of other synovial joints, including the shoulder and the hip joints. Striking differences were noted, indicating that the TMJ forms via a distinct molecular program. Several components of the hedgehog (Hh) signaling pathway are among the genes identified in the screen, including Gli2, which is expressed specifically in the condyle and in the disk of the developing TMJ. We found that mice deficient in Gli2 display aberrant TMJ development such that the condyle loses its growth-plate-like cellular organization and no disk is formed. In addition, we used a conditional strategy to remove Smo, a positive effector of the Hh signaling pathway, from chondrocyte progenitors. This cell autonomous loss of Hh signaling allows for disk formation, but the resulting structure fails to separate from the condyle. Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation, and disk–condyle separation and provide a molecular framework for future studies of the TMJ. PMID:19815519

  11. Unique glycosignature for intervertebral disc and articular cartilage cells and tissues in immaturity and maturity.

    PubMed

    Collin, E C; Kilcoyne, M; White, S J; Grad, S; Alini, M; Joshi, L; Pandit, A S

    2016-03-11

    In this study, on/off markers for intervertebral disc (IVD) and articular cartilage (AC) cells (chondrocytes) and distinct glycoprofiles of cell and tissue-types were identified from immaturity to maturity. Three and eleven month-old ovine IVD and AC tissues were histochemically profiled with a panel of lectins and antibodies. Relationships between tissue and cell types were analysed by hierarchical clustering. Chondroitin sulfate (CS) composition of annulus fibrosus (AF), nucleus pulposus (NP) and AC tissues was determined by HPLC analysis. Clear on/off cell type markers were identified, which enabled the discrimination of chondrocytes, AF and NP cells. AF and NP cells were distinguishable using MAA, SNA-I, SBA and WFA lectins, which bound to both NP cells and chondrocytes but not AF cells. Chondrocytes were distinguished from NP and AF cells with a specific binding of LTA and PNA lectins to chondrocytes. Each tissue showed a unique CS composition with a distinct switch in sulfation pattern in AF and NP tissues upon disc maturity while cartilage maintained the same sulfation pattern over time. In conclusion, distinct glycoprofiles for cell and tissue-types across age groups were identified in addition to altered CS composition and sulfation patterns for tissue types upon maturity.

  12. Pelagia benovici sp. nov. (Cnidaria, Scyphozoa): a new jellyfish in the Mediterranean Sea.

    PubMed

    Piraino, Stefano; Aglieri, Giorgio; Martell, Luis; Mazzoldi, Carlotta; Melli, Valentina; Milisenda, Giacomo; Scorrano, Simonetta; Boero, Ferdinando

    2014-05-07

    A bloom of an unknown semaestome jellyfish species was recorded in the North Adriatic Sea from September 2013 to early 2014. Morphological analysis of several specimens showed distinct differences from other known semaestome species in the Mediterranean Sea and unquestionably identified them as belonging to a new pelagiid species within genus Pelagia. The new species is morphologically distinct from P. noctiluca, currently the only recognized valid species in the genus, and from other doubtful Pelagia species recorded from other areas of the world. Molecular analyses of mitochondrial cytochrome c oxidase subunit I (COI) and nuclear 28S ribosomal DNA genes corroborate its specific distinction from P. noctiluca and other pelagiid taxa, supporting the monophyly of Pelagiidae. Thus, we describe Pelagia benovici sp. nov. Piraino, Aglieri, Scorrano & Boero.

  13. VARSEDIG: an algorithm for morphometric characters selection and statistical validation in morphological taxonomy.

    PubMed

    Guisande, Cástor; Vari, Richard P; Heine, Jürgen; García-Roselló, Emilio; González-Dacosta, Jacinto; Perez-Schofield, Baltasar J García; González-Vilas, Luis; Pelayo-Villamil, Patricia

    2016-09-12

    We present and discuss VARSEDIG, an algorithm which identifies the morphometric features that significantly discriminate two taxa and validates the morphological distinctness between them via a Monte-Carlo test. VARSEDIG is freely available as a function of the RWizard application PlotsR (http://www.ipez.es/RWizard) and as R package on CRAN. The variables selected by VARSEDIG with the overlap method were very similar to those selected by logistic regression and discriminant analysis, but overcomes some shortcomings of these methods. VARSEDIG is, therefore, a good alternative by comparison to current classical classification methods for identifying morphometric features that significantly discriminate a taxon and for validating its morphological distinctness from other taxa. As a demonstration of the potential of VARSEDIG for this purpose, we analyze morphological discrimination among some species of the Neotropical freshwater family Characidae.

  14. Metabonomics identifies serum metabolite markers of colorectal cancer.

    PubMed

    Tan, Binbin; Qiu, Yunping; Zou, Xia; Chen, Tianlu; Xie, Guoxiang; Cheng, Yu; Dong, Taotao; Zhao, Linjing; Feng, Bo; Hu, Xiaofang; Xu, Lisa X; Zhao, Aihua; Zhang, Menghui; Cai, Guoxiang; Cai, Sanjun; Zhou, Zhanxiang; Zheng, Minhua; Zhang, Yan; Jia, Wei

    2013-06-07

    Recent studies suggest that biofluid-based metabonomics may identify metabolite markers promising for colorectal cancer (CRC) diagnosis. We report here a follow-up replication study, after a previous CRC metabonomics study, aiming to identify a distinct serum metabolic signature of CRC with diagnostic potential. Serum metabolites from newly diagnosed CRC patients (N = 101) and healthy subjects (N = 102) were profiled using gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). Differential metabolites were identified with statistical tests of orthogonal partial least-squares-discriminant analysis (VIP > 1) and the Mann-Whitney U test (p < 0.05). With a total of 249 annotated serum metabolites, we were able to differentiate CRC patients from the healthy controls using an orthogonal partial least-squares-discriminant analysis (OPLS-DA) in a learning sample set of 62 CRC patients and 62 matched healthy controls. This established model was able to correctly assign the rest of the samples to the CRC or control groups in a validation set of 39 CRC patients and 40 healthy controls. Consistent with our findings from the previous study, we observed a distinct metabolic signature in CRC patients including tricarboxylic acid (TCA) cycle, urea cycle, glutamine, fatty acids, and gut flora metabolism. Our results demonstrated that a panel of serum metabolite markers is of great potential as a noninvasive diagnostic method for the detection of CRC.

  15. Distinctive fingerprints of erosional regimes in terrestrial channel networks

    NASA Astrophysics Data System (ADS)

    Grau Galofre, A.; Jellinek, M.

    2017-12-01

    Satellite imagery and digital elevation maps capture the large scale morphology of channel networks attributed to long term erosional processes, such as fluvial, glacial, groundwater sapping and subglacial erosion. Characteristic morphologies associated with each of these styles of erosion have been studied in detail, but there exists a knowledge gap related to their parameterization and quantification. This knowledge gap prevents a rigorous analysis of the dominant processes that shaped a particular landscape, and a comparison across styles of erosion. To address this gap, we use previous morphological descriptions of glaciers, rivers, sapping valleys and tunnel valleys to identify and measure quantitative metrics diagnostic of these distinctive styles of erosion. From digital elevation models, we identify four geometric metrics: The minimum channel width, channel aspect ratio (longest length to channel width at the outlet), presence of undulating longitudinal profiles, and tributary junction angle. We also parameterize channel network complexity in terms of its stream order and fractal dimension. We then perform a statistical classification of the channel networks using a Principal Component Analysis on measurements of these six metrics on a dataset of 70 channelized systems. We show that rivers, glaciers, groundwater seepage and subglacial meltwater erode the landscape in rigorously distinguishable ways. Our methodology can more generally be applied to identify the contributions of different processes involved in carving a channel network. In particular, we are able to identify transitions from fluvial to glaciated landscapes or vice-versa.

  16. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

    PubMed

    Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

    2018-03-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

  17. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

    PubMed Central

    Gray, Alan; Neyton, Lucile P. A.; Barrett, Jeffrey; Stahl, Eli A.; Tenesa, Albert; Andersson, Robin; Brown, J. Ben; Faulkner, Geoffrey J.; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Kawaji, Hideya; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A.; Hacohen, Nir; Freeman, Thomas C.; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Hume, David A.

    2018-01-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits. PMID:29494619

  18. Comparative genomics identifies distinct lineages of S. Enteritidis from Queensland, Australia.

    PubMed

    Graham, Rikki M A; Hiley, Lester; Rathnayake, Irani U; Jennison, Amy V

    2018-01-01

    Salmonella enterica is a major cause of gastroenteritis and foodborne illness in Australia where notification rates in the state of Queensland are the highest in the country. S. Enteritidis is among the five most common serotypes reported in Queensland and it is a priority for epidemiological surveillance due to concerns regarding its emergence in Australia. Using whole genome sequencing, we have analysed the genomic epidemiology of 217 S. Enteritidis isolates from Queensland, and observed that they fall into three distinct clades, which we have differentiated as Clades A, B and C. Phage types and MLST sequence types differed between the clades and comparative genomic analysis has shown that each has a unique profile of prophage and genomic islands. Several of the phage regions present in the S. Enteritidis reference strain P125109 were absent in Clades A and C, and these clades also had difference in the presence of pathogenicity islands, containing complete SPI-6 and SPI-19 regions, while P125109 does not. Antimicrobial resistance markers were found in 39 isolates, all but one of which belonged to Clade B. Phylogenetic analysis of the Queensland isolates in the context of 170 international strains showed that Queensland Clade B isolates group together with the previously identified global clade, while the other two clades are distinct and appear largely restricted to Australia. Locally sourced environmental isolates included in this analysis all belonged to Clades A and C, which is consistent with the theory that these clades are a source of locally acquired infection, while Clade B isolates are mostly travel related.

  19. Family Satisfaction With Nursing Home Care: The Role of Facility Characteristics and Resident Quality-of-Life Scores

    PubMed Central

    Shippee, Tetyana P.; Henning-Smith, Carrie; Gaugler, Joseph E.; Held, Robert; Kane, Robert L.

    2018-01-01

    This article explores the factor structure of a new family satisfaction with nursing home care instrument and determines the relationship of resident quality of life (QOL) and facility characteristics with family satisfaction. Data sources include (1) family satisfaction interviews (n = 16,790 family members), (2) multidimensional survey of resident QOL (n = 13,433 residents), and (3) facility characteristics (n = 376 facilities). We used factor analysis to identify domains of family satisfaction and multivariate analyses to identify the role of facility-level characteristics and resident QOL on facility-mean values of family satisfaction. Four distinct domains were identified for family satisfaction: “care,” “staff,” “environment,” and “food.” Chain affiliation, higher resident acuity, more deficiencies, and large size were all associated with less family satisfaction, and resident QOL was a significant (albeit weak) predictor of family satisfaction. Results suggest that family member satisfaction is distinct from resident QOL but is associated with resident QOL and facility characteristics. PMID:26534835

  20. Identification and Characterization of Inhibitors of West Nile Virus

    PubMed Central

    Puig-Basagoiti, Francesc; Qing, Min; Dong, Hongping; Zhang, Bo; Zou, Gang; Yuan, Zhiming

    2011-01-01

    Although flaviviruses cause significant human diseases, no antiviral therapy is currently available for clinical treatment of these pathogens. To identify flavivirus inhibitors, we performed a high-throughput screening of compound libraries using cells containing luciferase-reporting replicon of West Nile viruses (WNV). Five novel small molecular inhibitors of WNV were identified from libraries containing 96,958 compounds. The inhibitors suppress epidemic strain of WNV in cell culture, with EC50 (50% effective concentration) values of <10 µM and TI (therapeutic index) values of >10. Viral titer reduction assays, using various flaviviruses and nonflaviviruses, showed that the compounds have distinct antiviral spectra. Mode-of-action analysis showed that the inhibitors block distinct steps of WNV replication: four compounds inhibit viral RNA syntheses, while the other compound suppresses both viral translation and RNA syntheses. Biochemical enzyme assays showed that two compounds selectively inhibit viral RNA-dependent RNA polymerase (RdRp), while another compound specifically inhibits both RdRp and methyltransferase. The identified compounds could potentially be developed for treatment of flavivirus infections. PMID:19501258

  1. Nonverbal memory and organizational dysfunctions are related with distinct symptom dimensions in obsessive-compulsive disorder.

    PubMed

    Jang, Joon Hwan; Kim, Hee Sun; Ha, Tae Hyon; Shin, Na Young; Kang, Do-Hyung; Choi, Jung-Seok; Ha, Kyooseob; Kwon, Jun Soo

    2010-12-30

    Recent acceptance that obsessive-compulsive disorder (OCD) represents a heterogeneous phenomenon has underscored the need for dimensional approaches to this disorder. However little is known about the relation between neuropsychological functions and symptom dimensions. The purpose of this study was to identify the cognitive deficits correlated with specific symptom dimensions. Thirteen categories in the Yale-Brown Obsessive Compulsive Scale symptom checklist from 144 patients with OCD were analyzed by principal component analysis. Correlations between identified symptom dimensions and neuropsychological functioning, measured by the Boston Qualitative Scoring System, were analyzed. Five factors or dimensions were identified: contamination/cleaning, hoarding, symmetry/ordering, obsessions/checking, and repeating/counting. Dysfunctions in nonverbal memory and organizational strategies were related to the symmetry/ordering dimension and the obsessions/checking dimension, respectively. The results of the present study support a transculturally stable symptom structure for OCD. They also suggest the possibility that nonverbal memory dysfunction and organizational impairment are mediated by distinct obsessive-compulsive dimensions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Characteristic differences in metabolite profile in male and female plants of dioecious Piper betle L.

    PubMed

    Bajpai, Vikas; Pandey, Renu; Negi, Mahendra Pal Singh; Bindu, K Hima; Kumar, Nikhil; Kumar, Brijesh

    2012-12-01

    Piper betle is a dioecious pan-Asiatic plant having cultural and medicinal uses. It belongs to the family Piperaceae and is a native of the tropics although it is also cultivated in subtropical areas. Flowering in P. betle occurs only in tropical regions. Due to lack of inductive floral cycles the plant remains in its vegetative state in the subtropics. Therefore, due to lack of flowering, gender distinction cannot be made the in the subtropics. Gender distinction in P. betle in vegetative state can be made using Direct Analysis in Real Time Mass Spectroscopy (DARTMS), a robust highthroughput method. DARTMS analysis of leaf samples of two male and six female plants showed characteristic differences in the spectra between male and female plants. Semi-quantitative differences in some of the identified peaks in male and female landraces showed gender-based differences in metabolites. Cluster analysis using the peaks at m/z 151, 193, 235 and 252 showed two distinct clusters of male and female landraces. It appears that male and female plants besides having flowers of different sexes also have characteristic differences in the metabolites representing two metabolic types.

  3. Parental attitudes towards measles vaccination in the canton of Aargau, Switzerland: a latent class analysis.

    PubMed

    Weiss, Carine; Schröpfer, Daniel; Merten, Sonja

    2016-08-11

    Despite the successes of routine national childhood vaccination programmes, measles remains a public health concern. The purpose of this paper is to investigate how patterns of parental attitudes are linked to the decision-making process for or against MMR vaccination. This exploratory study was designed to identify distinct patterns of attitudes towards or against measles vaccination through Latent Class Analysis (LCA) in a sub-sample of mothers living in the canton of Aargau in Switzerland. Parents of young children below 36 months of age were randomly selected through parents' counsellors' registries. Among other questions, respondents were asked to state their agreement in response to 14 belief statements regarding measles vaccination on a 5-point Likert scale. To identify groups of parents showing distinct patterns of attitudes and beliefs regarding measles vaccination, we used Latent Class Analysis (LCA). The LCA showed three classes of parents with different attitudes and believes towards measles vaccination: The biggest group (class 1) are those having positive attitudes towards immunisation, followed by the second biggest group (class 2) which is characterised by having fearful attitudes and by showing uncertainty about immunisation. The third group (class 3) shows distinct patterns of critical attitudes against immunisation. Within this group over 90 % agree or totally agree that immunisation is an artificial intrusion into the natural immune system and therefore want to vaccinate their children only if necessary. We find that parents in the Canton Aargau who hesitate to vaccinate their children against measles, mumps and rubella show distinct opinions and attitudes. Health professionals should be aware of these perceptions to tailor their messages accordingly and positively influence these parents to vaccinate their children. Special attention needs to be given to those parents who are planning to vaccinate their children but are not following the national guidelines.

  4. Seventh Grade Students' Mental Models of the Greenhouse Effect

    ERIC Educational Resources Information Center

    Shepardson, Daniel P.; Choi, Soyoung; Niyogi, Dev; Charusombat, Umarporn

    2011-01-01

    This constructivist study investigates 225 student drawings and explanations from three different schools in the midwest in the US, to identify seventh grade students' mental models of the greenhouse effect. Five distinct mental models were derived from an inductive analysis of the content of the students' drawings and explanations: Model 1, a…

  5. One Policy, Disparate Reactions: Institutional Responses in Florida's Developmental Education Reform

    ERIC Educational Resources Information Center

    Park, Toby J.; Tandberg, David A.; Hu, Shouping; Hankerson, Dava

    2016-01-01

    This paper seeks to better understand how community colleges in Florida planned to implement a new sweeping state policy pertaining to developmental education. Via a cluster analysis, we identify three distinct patterns in the ways in which the colleges responded to the policy: reformers, responders, and resisters. Further, we find that these…

  6. The Funding of Community Colleges: Formulas & Governance

    ERIC Educational Resources Information Center

    Mullin, Christopher M.; Honeyman, David S.

    2008-01-01

    This study identified governing state entities charged with the development of a funding formula for community colleges. Analysis of the data revealed that 40 states utilized a funding formula. Twenty-one states had a "Higher Education" entity with governing control of the formula, 5 states had a "Community College" entity with distinct funding…

  7. The Latent Classes of Subclinical ADHD Symptoms: Convergences of Multiple Informant Reports

    ERIC Educational Resources Information Center

    Kobor, Andrea; Takacs, Adam; Urban, Robert; Csepe, Valeria

    2012-01-01

    The purpose of the present study was to conduct latent class analysis on the Hyperactivity scale of the Strengths and Difficulties Questionnaire in order to identify distinct subgroups of subclinical ADHD in a multi-informant framework. We hypothesized a similar structure between teachers and parents, and differences in symptom severity across…

  8. Visions of Terror: A Q-Methodological Analysis of American Perceptions of International Terrorism.

    ERIC Educational Resources Information Center

    Dowling, Ralph E.; Nitcavic, Richard G.

    A study examined the efficacy of Q-methodology as a tool to explain perceptions of the American public regarding international terrorism, seeking to identify through this methodology distinct views of terrorism and the significant variables characterizing those views. To develop their instrument, researchers interviewed 16 individuals and based…

  9. The Effects of Consequence Manipulation during Functional Analysis of Problem Behavior Maintained by Negative Reinforcement

    ERIC Educational Resources Information Center

    Potoczak, Kathryn; Carr, James E.; Michael, Jack

    2007-01-01

    Two distinct analytic methods have been used to identify the function of problem behavior. The antecedent-behavior-consequence (ABC) method (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) includes the delivery of consequences for problem behavior. The AB method (Carr & Durand, 1985) does not include consequence delivery, instead relying…

  10. Which Emotional Profiles Exhibit the Best Learning Outcomes? A Person-Centered Analysis of Students' Academic Emotions

    ERIC Educational Resources Information Center

    Ganotice, Fraide A., Jr.; Datu, Jesus Alfonso D.; King, Ronnel B.

    2016-01-01

    Previous studies on academic emotions have mostly used variable-centered approaches. Although these studies have elucidated the relationships between academic emotions and key academic outcomes, they cannot identify naturally-occurring groups of students defined by distinct academic emotion profiles. In this study, we adopted a person-centered…

  11. Evaluation of New Biomarker Genes for Differentiating Haemophilus influenzae from Haemophilus haemolyticus

    PubMed Central

    Anderson, Raydel D.; Wang, Xin; Katz, Lee S.; Vuong, Jeni T.; Bell, Melissa E.; Juni, Billie A.; Lowther, Sara A.; Lynfield, Ruth; MacNeil, Jessica R.; Mayer, Leonard W.

    2012-01-01

    PCR detecting the protein D (hpd) and fuculose kinase (fucK) genes showed high sensitivity and specificity for identifying Haemophilus influenzae and differentiating it from H. haemolyticus. Phylogenetic analysis using the 16S rRNA gene demonstrated two distinct groups for H. influenzae and H. haemolyticus. PMID:22301020

  12. Trajectories of Developmental Functioning among Children of Adolescent Mothers: Factors Associated with Risk for Delay

    ERIC Educational Resources Information Center

    Jahromi, Laudan B.; Umaña-Taylor, Adriana J.; Updegraff, Kimberly A.; Zeiders, Katharine H.

    2016-01-01

    Children of adolescent mothers are at risk for developmental delays. Less is known about the heterogeneity in these children's developmental trajectories, and factors associated with different patterns of development. This longitudinal study used latent class growth analysis (LCGA) to identify distinct trajectories in children of Mexican-origin…

  13. The Historical Development of Educational Assessment in Chile: 1810-2014

    ERIC Educational Resources Information Center

    Gysling, Jacqueline

    2016-01-01

    This article examines the historical development of the state's actions in educational assessment in Chile from the nineteenth century to the present day, based on the analysis of governmental decrees and regulations related to assessment, and their variability over time. The research identifies six distinctive periods, each of which expresses a…

  14. All Different or All the Same? Exploring the Diversity of Professional Practices in Portuguese School Psychology

    ERIC Educational Resources Information Center

    Mendes, Sofia A.; Lasser, Jon; Abreu-Lima, Isabel M.; Almeida, Leandro S.

    2017-01-01

    Studies have generally characterized school psychologists as a relative homogenous population. Understanding the differences in professional practices and related variables is important for the development of the profession. Using a sample of 446 Portuguese school psychologists, this study used cluster analysis to identify distinct profiles of…

  15. A Comparison of Classification Approaches for Cyberbullying and Traditional Bullying Using Data from Six European Countries

    ERIC Educational Resources Information Center

    Schultze-Krumbholz, Anja; Göbel, Kristin; Scheithauer, Herbert; Brighi, Antonella; Guarini, Annalisa; Tsorbatzoudis, Haralambos; Barkoukis, Vassilis; Pyzalski, Jacek; Plichta, Piotr; Del Rey, Rosario; Casas, José A.; Thompson, Fran; Smith, Peter K.

    2015-01-01

    In recently published studies on cyberbullying, students are frequently categorized into distinct (cyber)bully and (cyber)victim clusters based on theoretical assumptions and arbitrary cut-off scores adapted from traditional bullying research. The present study identified involvement classes empirically using latent class analysis (LCA), to…

  16. School Organizational Contexts, Teacher Turnover, and Student Achievement: Evidence from Panel Data. Working Paper

    ERIC Educational Resources Information Center

    Kraft, Matthew A.; Marinell, William H.; Yee, Darrick

    2016-01-01

    We study the relationship between school organizational contexts, teacher turnover, and student achievement in New York City (NYC) middle schools. Using factor analysis, we construct measures of four distinct dimensions of school contexts captured on the annual NYC School Survey. We identify credible estimates by isolating variation in…

  17. School Organizational Contexts, Teacher Turnover, and Student Achievement: Evidence From Panel Data

    ERIC Educational Resources Information Center

    Kraft, Matthew A.; Marinell, William H.; Shen-Wei Yee, Darrick

    2016-01-01

    We study the relationship between school organizational contexts, teacher turnover, and student achievement in New York City (NYC) middle schools. Using factor analysis, we construct measures of four distinct dimensions of school climate captured on the annual NYC School Survey. We identify credible estimates by isolating variation in…

  18. A novel approach to identify optimal metabotypes of elongase and desaturase activities in prevention of acute coronary syndrome

    USDA-ARS?s Scientific Manuscript database

    Both metabolomic and genomic approaches are valuable for risk analysis, however typical approaches evaluating differences in means do not model the changes well. Gene polymorphisms that alter function would appear as distinct populations, or metabotypes, from the predominant one, in which case risk...

  19. Chinese American Post-Secondary Achievement and Attainment: A Cultural and Structural Analysis

    ERIC Educational Resources Information Center

    Pearce, Richard R.; Lin, Zeng

    2007-01-01

    In this article, the authors compare Chinese American post-secondary educational attainment with that of White Americans and, in identifying those factors that most strongly account for success, argue that commonalities exist among social structural factors, while distinct differences are evident among cultural capital factors. The article rejects…

  20. Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.

    PubMed

    Stires, Hillary; Heckler, Mary M; Fu, Xiaoyong; Li, Zhao; Grasso, Catherine S; Quist, Michael J; Lewis, Joseph A; Klimach, Uwe; Zwart, Alan; Mahajan, Akanksha; Győrffy, Balázs; Cavalli, Luciane R; Riggins, Rebecca B

    2018-08-15

    Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Breed-specific ancestry studies and genome-wide association analysis highlight an association between the MYH9 gene and heat tolerance in Alaskan sprint racing sled dogs.

    PubMed

    Huson, Heather J; vonHoldt, Bridgett M; Rimbault, Maud; Byers, Alexandra M; Runstadler, Jonathan A; Parker, Heidi G; Ostrander, Elaine A

    2012-02-01

    Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high-performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long-distance racers, and combined that with genome-wide association studies (GWAS) to identify regions that correlate with performance-enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principal components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5-10 and 2.5-3.75 kb, respectively). Furthermore, we identified eight regions with the genomic signal from either a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor-performing sled dogs identified a single region significantly associated with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog.

  2. Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.

    PubMed

    Jurynczyk, Maciej; Probert, Fay; Yeo, Tianrong; Tackley, George; Claridge, Tim D W; Cavey, Ana; Woodhall, Mark R; Arora, Siddharth; Winkler, Torsten; Schiffer, Eric; Vincent, Angela; DeLuca, Gabriele; Sibson, Nicola R; Isabel Leite, M; Waters, Patrick; Anthony, Daniel C; Palace, Jacqueline

    2017-12-06

    The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these conditions are indeed different at a molecular level. The metabolites identified provide a molecular signature of each condition which is independent of antibody titre and EDSS, with potential use for disease monitoring and diagnosis.

  3. Molecular events of apical bud formation in white spruce, Picea glauca.

    PubMed

    El Kayal, Walid; Allen, Carmen C G; Ju, Chelsea J-T; Adams, Eri; King-Jones, Susanne; Zaharia, L Irina; Abrams, Suzanne R; Cooke, Janice E K

    2011-03-01

    Bud formation is an adaptive trait that temperate forest trees have acquired to facilitate seasonal synchronization. We have characterized transcriptome-level changes that occur during bud formation of white spruce [Picea glauca (Moench) Voss], a primarily determinate species in which preformed stem units contained within the apical bud constitute most of next season's growth. Microarray analysis identified 4460 differentially expressed sequences in shoot tips during short day-induced bud formation. Cluster analysis revealed distinct temporal patterns of expression, and functional classification of genes in these clusters implied molecular processes that coincide with anatomical changes occurring in the developing bud. Comparing expression profiles in developing buds under long day and short day conditions identified possible photoperiod-responsive genes that may not be essential for bud development. Several genes putatively associated with hormone signalling were identified, and hormone quantification revealed distinct profiles for abscisic acid (ABA), cytokinins, auxin and their metabolites that can be related to morphological changes to the bud. Comparison of gene expression profiles during bud formation in different tissues revealed 108 genes that are differentially expressed only in developing buds and show greater transcript abundance in developing buds than other tissues. These findings provide a temporal roadmap of bud formation in white spruce. © 2011 Blackwell Publishing Ltd.

  4. Identification and Characterization of Unique Subgroups of Chronic Pain Individuals with Dispositional Personality Traits.

    PubMed

    Mehta, S; Rice, D; McIntyre, A; Getty, H; Speechley, M; Sequeira, K; Shapiro, A P; Morley-Forster, P; Teasell, R W

    2016-01-01

    Objective. The current study attempted to identify and characterize distinct CP subgroups based on their level of dispositional personality traits. The secondary objective was to compare the difference among the subgroups in mood, coping, and disability. Methods. Individuals with chronic pain were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted in order to identify distinct subgroups of patients based on their level of personality traits. Differences in clinical outcomes were compared using the multivariate analysis of variance based on cluster membership. Results. In 229 participants, three clusters were formed. No significant difference was seen among the clusters on patient demographic factors including age, sex, relationship status, duration of pain, and pain intensity. Those with high levels of dispositional personality traits had greater levels of mood impairment compared to the other two groups (p < 0.05). Significant difference in disability was seen between the subgroups. Conclusions. The study identified a high risk group of CP individuals whose level of personality traits significantly correlated with impaired mood and coping. Use of pharmacological treatment alone may not be successful in improving clinical outcomes among these individuals. Instead, a more comprehensive treatment involving psychological treatments may be important in managing the personality traits that interfere with recovery.

  5. TimesVector: a vectorized clustering approach to the analysis of time series transcriptome data from multiple phenotypes.

    PubMed

    Jung, Inuk; Jo, Kyuri; Kang, Hyejin; Ahn, Hongryul; Yu, Youngjae; Kim, Sun

    2017-12-01

    Identifying biologically meaningful gene expression patterns from time series gene expression data is important to understand the underlying biological mechanisms. To identify significantly perturbed gene sets between different phenotypes, analysis of time series transcriptome data requires consideration of time and sample dimensions. Thus, the analysis of such time series data seeks to search gene sets that exhibit similar or different expression patterns between two or more sample conditions, constituting the three-dimensional data, i.e. gene-time-condition. Computational complexity for analyzing such data is very high, compared to the already difficult NP-hard two dimensional biclustering algorithms. Because of this challenge, traditional time series clustering algorithms are designed to capture co-expressed genes with similar expression pattern in two sample conditions. We present a triclustering algorithm, TimesVector, specifically designed for clustering three-dimensional time series data to capture distinctively similar or different gene expression patterns between two or more sample conditions. TimesVector identifies clusters with distinctive expression patterns in three steps: (i) dimension reduction and clustering of time-condition concatenated vectors, (ii) post-processing clusters for detecting similar and distinct expression patterns and (iii) rescuing genes from unclassified clusters. Using four sets of time series gene expression data, generated by both microarray and high throughput sequencing platforms, we demonstrated that TimesVector successfully detected biologically meaningful clusters of high quality. TimesVector improved the clustering quality compared to existing triclustering tools and only TimesVector detected clusters with differential expression patterns across conditions successfully. The TimesVector software is available at http://biohealth.snu.ac.kr/software/TimesVector/. sunkim.bioinfo@snu.ac.kr. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  6. One hundred years of work design research: Looking back and looking forward.

    PubMed

    Parker, Sharon K; Morgeson, Frederick P; Johns, Gary

    2017-03-01

    In this article we take a big picture perspective on work design research. In the first section of the paper we identify influential work design articles and use scientific mapping to identify distinct clusters of research. Pulling this material together, we identify five key work design perspectives that map onto distinct historical developments: (a) sociotechnical systems and autonomous work groups, (b) job characteristics model, (c) job demands-control model, (d) job demands-resources model, and (e) role theory. The grounding of these perspectives in the past is understandable, but we suggest that some of the distinction between clusters is convenient rather than substantive. Thus we also identify contemporary integrative perspectives on work design that build connections across the clusters and we argue that there is scope for further integration. In the second section of the paper, we review the role of Journal of Applied Psychology ( JAP ) in shaping work design research. We conclude that JAP has played a vital role in the advancement of this topic over the last 100 years. Nevertheless, we suspect that to continue to play a leading role in advancing the science and practice of work design, the journal might need to publish research that is broader, more contextualized, and team-oriented. In the third section, we address the impact of work design research on: applied psychology and management, disciplines beyond our own, management thinking, work practice, and national policy agendas. Finally, we draw together observations from our analysis and identify key future directions for the field. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. Trajectories of functional limitation in early rheumatoid arthritis and their association with mortality.

    PubMed

    Norton, Sam; Sacker, Amanda; Dixey, Josh; Done, John; Williams, Peter; Young, Adam

    2013-11-01

    This study aimed to identify subgroups with distinct trajectories of functional (HAQ) progression over 10 years following diagnosis of RA and identify baseline characteristics associated with the trajectories and their prognostic value for mortality. Between 1986 and 1998, 1460 patients with RA symptoms <2 years and prior to disease-modifying treatment (DMARDs) were recruited to an inception cohort (Early RA Study). Standard clinical, functional and laboratory assessments were performed at presentation and annually. Deaths were tracked by the National Health Service Central Register. Growth mixture modelling was used to identify distinct trajectories of HAQ score progression and survival analysis employed to compare all-cause mortality across the trajectory classes. Four HAQ score progression classes were identified: moderate increasing (46%), low stable (6%), moderate stable (28%) and high stable (20%). Only the moderate-increasing class exhibited an accelerated decline in function over normal ageing. Compared with the moderate-increasing class, individuals with high-stable HAQ scores were more likely to be female, have more severe disease and other coexistent conditions. Low-stable class patients were more likely to be male and report less pain. The high-stable class had increased risk of mortality compared with the moderate-increasing class after adjusting for potential confounding factors, whereas low-stable and moderate-stable classes were at reduced mortality risk. The effect of RA on function is set within the first few years and is affected by comorbidity. Identifying distinct groups of patients may help to target those at greater risk of poor functional outcome and mortality.

  8. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis

    PubMed Central

    Erson-Omay, E. Zeynep; Çağlayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S. Bülent; Özduman, Koray; Köksal, Yavuz; Li, Jie; Serin Harmancı, Akdes; Clark, Victoria; Carrión-Grant, Geneive; Baranoski, Jacob; Çağlar, Caner; Barak, Tanyeri; Coşkun, Süleyman; Baran, Burçin; Köse, Doğan; Sun, Jia; Bakırcıoğlu, Mehmet; Moliterno Günel, Jennifer; Pamir, M. Necmettin; Mishra-Gorur, Ketu; Bilguvar, Kaya; Yasuno, Katsuhito; Vortmeyer, Alexander; Huttner, Anita J.; Sander, Chris; Günel, Murat

    2015-01-01

    Background Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. Methods We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. Results We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these “ultramutated” tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. Conclusions We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments. PMID:25740784

  9. Clumpak: a program for identifying clustering modes and packaging population structure inferences across K.

    PubMed

    Kopelman, Naama M; Mayzel, Jonathan; Jakobsson, Mattias; Rosenberg, Noah A; Mayrose, Itay

    2015-09-01

    The identification of the genetic structure of populations from multilocus genotype data has become a central component of modern population-genetic data analysis. Application of model-based clustering programs often entails a number of steps, in which the user considers different modelling assumptions, compares results across different predetermined values of the number of assumed clusters (a parameter typically denoted K), examines multiple independent runs for each fixed value of K, and distinguishes among runs belonging to substantially distinct clustering solutions. Here, we present Clumpak (Cluster Markov Packager Across K), a method that automates the postprocessing of results of model-based population structure analyses. For analysing multiple independent runs at a single K value, Clumpak identifies sets of highly similar runs, separating distinct groups of runs that represent distinct modes in the space of possible solutions. This procedure, which generates a consensus solution for each distinct mode, is performed by the use of a Markov clustering algorithm that relies on a similarity matrix between replicate runs, as computed by the software Clumpp. Next, Clumpak identifies an optimal alignment of inferred clusters across different values of K, extending a similar approach implemented for a fixed K in Clumpp and simplifying the comparison of clustering results across different K values. Clumpak incorporates additional features, such as implementations of methods for choosing K and comparing solutions obtained by different programs, models, or data subsets. Clumpak, available at http://clumpak.tau.ac.il, simplifies the use of model-based analyses of population structure in population genetics and molecular ecology. © 2015 John Wiley & Sons Ltd.

  10. Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci

    PubMed Central

    2013-01-01

    Background Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects — for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD. Results We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, Pempirical = 0.0004) and at chromosome 18 (18q21.2, Pempirical = 0.0005). Conclusions In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHD. PMID:23705960

  11. A distribution-oriented approach to support landscape connectivity for ecologically distinct bird species.

    PubMed

    Herrera, José M; Alagador, Diogo; Salgueiro, Pedro; Mira, António

    2018-01-01

    Managing landscape connectivity is a widely recognized overarching strategy for conserving biodiversity in human-impacted landscapes. However, planning the conservation and management of landscape connectivity of multiple and ecologically distinct species is still challenging. Here we provide a spatially-explicit framework which identifies and prioritizes connectivity conservation and restoration actions for species with distinct habitat affinities. Specifically, our study system comprised three groups of common bird species, forest-specialists, farmland-specialists, and generalists, populating a highly heterogeneous agricultural countryside in the southwestern Iberian Peninsula. We first performed a comprehensive analysis of the environmental variables underlying the distributional patterns of each bird species to reveal generalities in their guild-specific responses to landscape structure. Then, we identified sites which could be considered pivotal in maintaining current levels of landscape connectivity for the three bird guilds simultaneously, as well as the number and location of sites that need to be restored to maximize connectivity levels. Interestingly, we found that a small number of sites defined the shortest connectivity paths for the three bird guilds simultaneously, and were therefore considered key for conservation. Moreover, an even smaller number of sites were identified as critical to expand the landscape connectivity at maximum for the regional bird assemblage as a whole. Our spatially-explicit framework can provide valuable decision-making support to conservation practitioners aiming to identify key connectivity and restoration sites, a particularly urgent task in rapidly changing landscapes such as agroecosystems.

  12. Trajectories of distress, anxiety, and depression among women with breast cancer: Looking beyond the mean.

    PubMed

    Bidstrup, Pernille Envold; Christensen, Jane; Mertz, Birgitte Goldschmidt; Rottmann, Nina; Dalton, Susanne Oksbjerg; Johansen, Christoffer

    2015-05-01

    Little is known about the development of psychological wellbeing over time among women who have been treated for breast cancer. The aim of this study was to identify distinct patterns of distress, anxiety, and depression in such women. We invited 426 consecutive women with newly diagnosed primary breast cancer to participate in this study, and 323 (76%) provided information on distress ('distress thermometer') and on symptoms of anxiety and depression ('hospital anxiety and depression scale'). Semiparametric group-based mixture modeling was used to identify distinct trajectories of distress, anxiety, and depressive symptoms assessed the week before surgery and four and eight months later. Logistic regression analysis was used to evaluate the characteristics of women in the distinct groups. Although no sub-group of women with chronic severe anxiety or depressive symptoms was found, we did identify a sub-group of 8% of the women who experienced continuously severe distress. Young age, having a partner, shorter education, and receiving chemotherapy but not radiotherapy might characterize women whose psychological symptoms remain strong eight months after diagnosis. By looking beyond the mean, we found that 8% of the women experienced chronic severe distress; no sub-groups with chronic severe anxiety or depression were identified. Several socio-demographic and treatment factors characterized the women whose distress level remained severe eight months after diagnosis. The results suggest that support could be focused on relatively small groups of patients most in need.

  13. A distribution-oriented approach to support landscape connectivity for ecologically distinct bird species

    PubMed Central

    Salgueiro, Pedro; Mira, António

    2018-01-01

    Managing landscape connectivity is a widely recognized overarching strategy for conserving biodiversity in human-impacted landscapes. However, planning the conservation and management of landscape connectivity of multiple and ecologically distinct species is still challenging. Here we provide a spatially-explicit framework which identifies and prioritizes connectivity conservation and restoration actions for species with distinct habitat affinities. Specifically, our study system comprised three groups of common bird species, forest-specialists, farmland-specialists, and generalists, populating a highly heterogeneous agricultural countryside in the southwestern Iberian Peninsula. We first performed a comprehensive analysis of the environmental variables underlying the distributional patterns of each bird species to reveal generalities in their guild-specific responses to landscape structure. Then, we identified sites which could be considered pivotal in maintaining current levels of landscape connectivity for the three bird guilds simultaneously, as well as the number and location of sites that need to be restored to maximize connectivity levels. Interestingly, we found that a small number of sites defined the shortest connectivity paths for the three bird guilds simultaneously, and were therefore considered key for conservation. Moreover, an even smaller number of sites were identified as critical to expand the landscape connectivity at maximum for the regional bird assemblage as a whole. Our spatially-explicit framework can provide valuable decision-making support to conservation practitioners aiming to identify key connectivity and restoration sites, a particularly urgent task in rapidly changing landscapes such as agroecosystems. PMID:29641610

  14. Long-Term Exposure to Ozone and Life Expectancy in the United States, 2002 to 2008

    PubMed Central

    Li, Chaoyang; Balluz, Lina S.; Vaidyanathan, Ambarish; Wen, Xiao-Jun; Hao, Yongping; Qualters, Judith R.

    2016-01-01

    Abstract Long-term exposure to ground-level ozone is associated with increased risk of morbidity and mortality. The association remains uncertain between long-term exposure to ozone and life expectancy. We assessed the associations between seasonal mean daily 8-hour maximum (8-hr max) ozone concentrations measured during the ozone monitoring seasons and life expectancy at birth in 3109 counties of the conterminous U.S. during 2002 to 2008. We used latent class growth analysis to identify latent classes of counties that had distinct mean levels and rates of change in ozone concentrations over the 7-year period and used linear regression analysis to determine differences in life expectancy by ozone levels. We identified 3 classes of counties with distinct seasonal mean daily 8-hr max ozone concentrations and rates of change. When compared with the counties with the lowest ozone concentrations, the counties with the highest ozone concentrations had 1.7- and 1.4-year lower mean life expectancy in males and females (both P < 0.0001), respectively. The associations remained statistically significant after controlling for potential confounding effects of seasonal mean PM2.5 concentrations and other selected environmental, demographic, socio-economic, and health-related factors (both P < 0.0001). A 5 ppb higher ozone concentration was associated with 0.25 year lower life expectancy in males (95% CI: −0.30 to −0.19) and 0.21 year in females (95% CI: −0.25 to −0.17). We identified 3 classes of counties with distinct mean levels and rates of change in ozone concentrations. Our findings suggest that long-term exposure to a higher ozone concentration may be associated with a lower life expectancy. PMID:26886595

  15. Binding mechanism investigations guiding the synthesis of novel condensed 1,4-dihydropyridine derivatives with L-/T-type calcium channel blocking activity.

    PubMed

    Schaller, David; Gündüz, Miyase Gözde; Zhang, Fang Xiong; Zamponi, Gerald W; Wolber, Gerhard

    2018-05-23

    Nifedipine and isradipine are prominent examples of calcium channel blockers with a 1,4-dihydropyridine (DHP) scaffold. Although successfully used in clinics since decades for the treatment of hypertension, the binding mechanism to their target, the L-type voltage-gated calcium channel Cav1.2, is still incompletely understood. Recently, novel DHP derivatives with a condensed ring system have been discovered that show distinct selectivity profiles to different calcium channel subtypes. This property renders this DHP class as a promising tool to achieve selectivity towards distinct calcium channel subtypes. In this study, we identified a common binding mode for prominent DHPs nifedipine and isradipine using docking and pharmacophore analysis that is also able to explain the structure-activity relationship of a small subseries of DHP derivatives with a condensed ring system. These findings were used to guide the synthesis of twenty-two novel DHPs. An extensive characterization using 1 H NMR, 13 C NMR, mass spectra and elemental analysis was followed by whole cell patch clamp assays for analyzing activity at Cav1.2 and Cav3.2. Two compounds were identified with significant activity against Cav1.2. Additionally, we identified four compounds active against Cav3.2 of which three were selective over Cav1.2. Novel binding modes were analyzed using docking and pharmacophore analysis as well as molecular dynamics simulations. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Variation in Phytochemical Composition Reveals Distinct Divergence of Aloe vera (L.) Burm.f. From Other Aloe Species: Rationale Behind Selective Preference of Aloe vera in Nutritional and Therapeutic Use

    PubMed Central

    Dey, Priyankar; Dutta, Somit; Chowdhury, Anurag; Das, Abhaya Prasad; Chaudhuri, Tapas Kumar

    2017-01-01

    In the present study, we have phytochemically characterized 5 different abundant Aloe species, including Aloe vera (L.) Burm.f., using silylation followed by Gas Chromatography-Mass Spectrometry technique and compared the data using multivariate statistical analysis. The results demonstrated clear distinction of the overall phytochemical profile of A vera, highlighted by its divergent spatial arrangement in the component plot. Lowest correlation of the phytochemical profiles were found between A vera and A aristata Haw. (−0.626), whereas highest correlation resided between A aristata and A aspera Haw. (0.899). Among the individual phytochemicals, palmitic acid was identified in highest abundance cumulatively, and carboxylic acids were the most predominant phytochemical species in all the Aloe species. Compared to A vera, linear correlation analysis revealed highest and lowest correlation with A aspera (R 2 = 0.9162) and A aristata (R 2 = 0.6745), respectively. Therefore, A vera demonstrated distinct spatial allocation, reflecting its greater phytochemical variability. PMID:29228808

  17. Dipeptide frequency/bias analysis identifies conserved sites of nonrandomness shared by cysteine-rich motifs.

    PubMed

    Campion, S R; Ameen, A S; Lai, L; King, J M; Munzenmaier, T N

    2001-08-15

    This report describes the application of a simple computational tool, AAPAIR.TAB, for the systematic analysis of the cysteine-rich EGF, Sushi, and Laminin motif/sequence families at the two-amino acid level. Automated dipeptide frequency/bias analysis detects preferences in the distribution of amino acids in established protein families, by determining which "ordered dipeptides" occur most frequently in comprehensive motif-specific sequence data sets. Graphic display of the dipeptide frequency/bias data revealed family-specific preferences for certain dipeptides, but more importantly detected a shared preference for employment of the ordered dipeptides Gly-Tyr (GY) and Gly-Phe (GF) in all three protein families. The dipeptide Asn-Gly (NG) also exhibited high-frequency and bias in the EGF and Sushi motif families, whereas Asn-Thr (NT) was distinguished in the Laminin family. Evaluation of the distribution of dipeptides identified by frequency/bias analysis subsequently revealed the highly restricted localization of the G(F/Y) and N(G/T) sequence elements at two separate sites of extreme conservation in the consensus sequence of all three sequence families. The similar employment of the high-frequency/bias dipeptides in three distinct protein sequence families was further correlated with the concurrence of these shared molecular determinants at similar positions within the distinctive scaffolds of three structurally divergent, but similarly employed, motif modules.

  18. Free fatty acid particles in protein formulations, part 1: microspectroscopic identification.

    PubMed

    Cao, Xiaolin; Fesinmeyer, R Matthew; Pierini, Christopher J; Siska, Christine C; Litowski, Jennifer R; Brych, Stephen; Wen, Zai-Qing; Kleemann, Gerd R

    2015-02-01

    We report, for the first time, the identification of fatty acid particles in formulations containing the surfactant polysorbate 20. These fatty acid particles were observed in multiple mAb formulations during their expected shelf life under recommended storage conditions. The fatty acid particles were granular or sand-like in morphology and were several microns in size. They could be identified by distinct IR bands, with additional confirmation from energy-dispersive X-ray spectroscopy analysis. The particles were readily distinguishable from protein particles by these methods. In addition, particles containing a mixture of protein and fatty acids were also identified, suggesting that the particulation pathways for the two particle types may not be distinct. The techniques and observations described will be useful for the correct identification of proteinaceous versus nonproteinaceous particles in pharmaceutical products. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. How to Study the City on Instagram

    PubMed Central

    Uitermark, Justus

    2016-01-01

    We introduce Instagram as a data source for use by scholars in urban studies and neighboring disciplines and propose ways to operationalize key concepts in the study of cities. These data can help shed light on segregation, the formation of subcultures, strategies of distinction, and status hierarchies in the city. Drawing on two datasets of geotagged Instagram posts from Amsterdam and Copenhagen collected over a twelve-week period, we present a proof of concept for how to explore and visualize sociospatial patterns and divisions in these two cities. We take advantage of both the social and the geographic aspects of the data, using network analysis to identify distinct groups of users and metrics of unevenness and diversity to identify socio-spatial divisions. We also discuss some of the limitations of these data and methods and suggest ways in which they can complement established quantitative and qualitative approaches in urban scholarship. PMID:27336728

  20. How to Study the City on Instagram.

    PubMed

    Boy, John D; Uitermark, Justus

    2016-01-01

    We introduce Instagram as a data source for use by scholars in urban studies and neighboring disciplines and propose ways to operationalize key concepts in the study of cities. These data can help shed light on segregation, the formation of subcultures, strategies of distinction, and status hierarchies in the city. Drawing on two datasets of geotagged Instagram posts from Amsterdam and Copenhagen collected over a twelve-week period, we present a proof of concept for how to explore and visualize sociospatial patterns and divisions in these two cities. We take advantage of both the social and the geographic aspects of the data, using network analysis to identify distinct groups of users and metrics of unevenness and diversity to identify socio-spatial divisions. We also discuss some of the limitations of these data and methods and suggest ways in which they can complement established quantitative and qualitative approaches in urban scholarship.

  1. 4-Nitro styrylquinoline is an antimalarial inhibiting multiple stages of Plasmodium falciparum asexual life cycle.

    PubMed

    Roberts, Bracken F; Zheng, Yongsheng; Cleaveleand, Jacob; Lee, Sukjun; Lee, Eunyoung; Ayong, Lawrence; Yuan, Yu; Chakrabarti, Debopam

    2017-04-01

    Drugs against malaria are losing their effectiveness because of emerging drug resistance. This underscores the need for novel therapeutic options for malaria with mechanism of actions distinct from current antimalarials. To identify novel pharmacophores against malaria we have screened compounds containing structural features of natural products that are pharmacologically relevant. This screening has identified a 4-nitro styrylquinoline (SQ) compound with submicromolar antiplasmodial activity and excellent selectivity. SQ exhibits a cellular action distinct from current antimalarials, acting early on malaria parasite's intraerythrocytic life cycle including merozoite invasion. The compound is a fast-acting parasitocidal agent and also exhibits curative property in the rodent malaria model when administered orally. In this report, we describe the synthesis, preliminary structure-function analysis, and the parasite developmental stage specific action of the SQ scaffold. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. The Different Facets of Work Stress: A Latent Profile Analysis of Nurses' Work Demands.

    PubMed

    Jenull, Brigitte B; Wiedermann, Wolfgang

    2015-10-01

    Work-related stress has been identified as a relevant problem leading to negative effects on health and quality of life. Using data from 844 nurses, latent profile analyses (LPA) were applied to identify distinct patterns of work stress. Several sociodemographic variables, including nurses' working and living conditions, as well as nurses' reactions to workload, were considered to predict respondents' profile membership. LPA revealed three distinct profiles that can be distinguished by a low, moderate, and higher stress level. Being financially secure is positively related to the low stress profile, whereas working in an urban area and having low job satisfaction increases the chance of belonging to the higher stress profile. Our results can be used as a basis to develop interventions to create a healthy nursing home environment by supporting the balance between family and work, providing access to job resources and optimizing recovery opportunities. © The Author(s) 2013.

  3. Signatures of cytoplasmic proteins in the exoproteome distinguish community- and hospital-associated methicillin-resistant Staphylococcus aureus USA300 lineages.

    PubMed

    Mekonnen, Solomon A; Palma Medina, Laura M; Glasner, Corinna; Tsompanidou, Eleni; de Jong, Anne; Grasso, Stefano; Schaffer, Marc; Mäder, Ulrike; Larsen, Anders R; Gumpert, Heidi; Westh, Henrik; Völker, Uwe; Otto, Andreas; Becher, Dörte; van Dijl, Jan Maarten

    2017-08-18

    Methicillin-resistant Staphylococcus aureus (MRSA) is the common name for a heterogeneous group of highly drug-resistant staphylococci. Two major MRSA classes are distinguished based on epidemiology, namely community-associated (CA) and hospital-associated (HA) MRSA. Notably, the distinction of CA- and HA-MRSA based on molecular traits remains difficult due to the high genomic plasticity of S. aureus. Here we sought to pinpoint global distinguishing features of CA- and HA-MRSA through a comparative genome and proteome analysis of the notorious MRSA lineage USA300. We show for the first time that CA- and HA-MRSA isolates can be distinguished by 2 distinct extracellular protein abundance clusters that are predictive not only for epidemiologic behavior, but also for their growth and survival within epithelial cells. This 'exoproteome profiling' also groups more distantly related HA-MRSA isolates into the HA exoproteome cluster. Comparative genome analysis suggests that these distinctive features of CA- and HA-MRSA isolates relate predominantly to the accessory genome. Intriguingly, the identified exoproteome clusters differ in the relative abundance of typical cytoplasmic proteins, suggesting that signatures of cytoplasmic proteins in the exoproteome represent a new distinguishing feature of CA- and HA-MRSA. Our comparative genome and proteome analysis focuses attention on potentially distinctive roles of 'liberated' cytoplasmic proteins in the epidemiology and intracellular survival of CA- and HA-MRSA isolates. Such extracellular cytoplasmic proteins were recently invoked in staphylococcal virulence, but their implication in the epidemiology of MRSA is unprecedented.

  4. Microbleeds versus macrobleeds: evidence for distinct entities.

    PubMed

    Greenberg, Steven M; Nandigam, R N Kaveer; Delgado, Pilar; Betensky, Rebecca A; Rosand, Jonathan; Viswanathan, Anand; Frosch, Matthew P; Smith, Eric E

    2009-07-01

    Small, asymptomatic microbleeds commonly accompany larger symptomatic macrobleeds. It is unclear whether microbleeds and macrobleeds represent arbitrary categories within a single continuum versus truly distinct events with separate pathophysiologies. We performed 2 complementary retrospective analyses. In a radiographic analysis, we measured and plotted the volumes of all hemorrhagic lesions detected by gradient-echo MRI among 46 consecutive patients with symptomatic primary lobar intracerebral hemorrhage diagnosed as probable or possible cerebral amyloid angiopathy. In a second neuropathologic analysis, we performed blinded qualitative and quantitative examinations of amyloid-positive vessel segments in 6 autopsied subjects whose MRI scans demonstrated particularly high microbleed counts (>50 microbleeds on MRI, n=3) or low microbleed counts (<3 microbleeds, n=3). Plotted on a logarithmic scale, the volumes of 163 hemorrhagic lesions identified on scans from the 46 subjects fell in a distinctly bimodal distribution with mean volumes for the 2 modes of 0.009 cm(3) and 27.5 cm(3). The optimal cut point for separating the 2 peaks (determined by receiver operating characteristics) corresponded to a lesion diameter of 0.57 cm. On neuropathologic analysis, the high microbleed-count autopsied subjects showed significantly thicker amyloid-positive vessel walls than the low microbleed-count subjects (proportional wall thickness 0.53+/-0.01 versus 0.37+/-0.01; P<0.0001; n=333 vessel segments analyzed). These findings suggest that cerebral amyloid angiopathy-associated microbleeds and macrobleeds comprise distinct entities. Increased vessel wall thickness may predispose to formation of microbleeds relative to macrobleeds.

  5. Microbleeds versus Macrobleeds: Evidence for Distinct Entities

    PubMed Central

    Greenberg, SM; Nandigam, RNK; Delgado, P; Betensky, RA; Rosand, J; Viswanathan, A; Frosch, MP; Smith, EE

    2009-01-01

    Background and Purpose Small, asymptomatic microbleeds commonly accompany larger symptomatic macrobleeds. It is unclear whether microbleeds and macrobleeds represent arbitrary categories within a single continuum versus truly distinct events with separate pathophysiologies. Methods We performed two complementary retrospective analyses. In a radiographic analysis, we measured and plotted the volumes of all hemorrhagic lesions detected by gradient-echo MRI among 46 consecutive patients with symptomatic primary lobar intracerebral hemorrhage diagnosed as probable or possible cerebral amyloid angiopathy (CAA). In a second neuropathologic analysis, we performed blinded qualitative and quantitative examinations of amyloid-positive vessel segments in 6 autopsied subjects whose MRI scans demonstrated particularly high microbleed counts (>50 microbleeds on MRI, n=3) or low microbleed counts (<3 microbleeds, n=3). Results Plotted on a logarithmic scale, the volumes of 163 hemorrhagic lesions identified on scans from the 46 subjects fell in a distinctly bimodal distribution with mean volumes for the two modes of 0.009 cm3 and 27.5 cm3. The optimal cut-point for separating the two peaks (determined by receiver operating characteristics) corresponded to a lesion diameter of 0.57 cm. On neuropathologic analysis, the high microbleed-count autopsied subjects showed significantly thicker amyloid-positive vessel walls than the low microbleed-count subjects (proportional wall thickness 0.53±0.01 versus 0.37±0.01, p<.0001, n=333 vessel segments analyzed). Conclusions These findings suggest that CAA-associated microbleeds and macrobleeds comprise distinct entities. Increased vessel wall thickness may predispose to formation of microbleeds relative to macrobleeds. PMID:19443797

  6. The semiregular variable UU Aurigae ( analysis in adversity?

    NASA Astrophysics Data System (ADS)

    Howarth, J. J.

    2001-06-01

    BAAVSS data for UU Aurigae from 1971 to 1998 are analysed to derive periodicities and to determine the behaviour of the periodic variations in phase and amplitude. Despite the difficulties associated with observing this object, distinct pulsational periods of 439.4 and 233.1 days are identified, and a long-standing phase and amplitude stability is demonstrated.

  7. Opinion: The Two Subject Matters of Behavior Analysis and Early Intervention

    ERIC Educational Resources Information Center

    Greer, R. Douglas

    2004-01-01

    The author argues that the field of behavior intervention has two subject matters that are distinct in several ways. Each is derived from, and contributes to, the foundation science and epistemology associated with behavior selection. The differences that the author wants to describe occurred to him as he sought to identify which of two Spanish…

  8. Development of a Typology of Dual-Earner Couples Caring for Children and Aging Parents

    ERIC Educational Resources Information Center

    Cullen, Jennifer C.; Hammer, Leslie B.; Neal, Margaret B.; Sinclair, Robert R.

    2009-01-01

    Using a national sample of 267 couples, the authors identify distinct profiles of dual-earner couples in the sandwiched generation (i.e., those caring for children and aging parents) using cluster analysis and then assess the relationship between these profiles and work-family conflict. The profiles are defined by characteristics of couples' child…

  9. What Is Successful Writing? An Investigation into the Multiple Ways Writers Can Write Successful Essays

    ERIC Educational Resources Information Center

    Crossley, Scott A.; Roscoe, Rod; McNamara, Danielle S.

    2014-01-01

    This study identifies multiple profiles of successful essays via a cluster analysis approach using linguistic features reported by a variety of natural language processing tools. The findings from the study indicate that there are four profiles of successful writers for the samples analyzed. These four profiles are linguistically distinct from one…

  10. Factor Analysis of the Metropolitan Readiness Test on First-Grade Children.

    ERIC Educational Resources Information Center

    Watkins, Ernest O.; Wiebe, Michael J.

    1984-01-01

    Investigated the factor composition of the Metropolitan Readiness Test, using first-grade subjects (N=1,241). A total battery score was supported, as well as a second factor believed to represent a language dimension of the test. None of the MRT's other content areas or a distinct prereading measure were identified. (Author/JAC)

  11. The Structure of Student Satisfaction with College Services: A Latent Class Model

    ERIC Educational Resources Information Center

    Adwere-Boamah, Joseph

    2011-01-01

    Latent Class Analysis (LCA) was used to identify distinct groups of Community college students based on their self-ratings of satisfaction with student service programs. The programs were counseling, financial aid, health center, student programs and student government. The best fitting model to describe the data was a two Discrete-Factor model…

  12. Moderate Learning Difficulties: Searching for Clarity and Understanding

    ERIC Educational Resources Information Center

    Norwich, Brahm; Ylonen, Annamari; Gwernan-Jones, Ruth

    2014-01-01

    The concept of moderate learning difficulties (MLD) is not clearly understood in its definition and in its general use. Nevertheless, as a distinct area of special educational needs (SEN) this category has constituted about a quarter of all of those pupils identified as having SEN in England. This paper reports the analysis of findings from an…

  13. Combined Patterns of Risk for Problem and Obesogenic Behaviors in Adolescents: A Latent Class Analysis Approach

    ERIC Educational Resources Information Center

    Fleary, Sasha A.

    2017-01-01

    Background: Several studies have used latent class analyses to explore obesogenic behaviors and substance use in adolescents independently. We explored a variety of health risks jointly to identify distinct patterns of risk behaviors among adolescents. Methods: Latent class models were estimated using Youth Risk Behavior Surveillance System…

  14. The Effects of Professional Development Activities on Principals' Perceived Instructional Leadership Practices: Multi-Country Data Analysis Using TALIS 2013

    ERIC Educational Resources Information Center

    Gumus, Emine; Bellibas, Mehmet Sukru

    2016-01-01

    The purpose of this study was to investigate the extent to which professional development predicts principals' instructional leadership in order to identify whether a relationship exists between the duration of principals' participation in distinct professional development activities and their perceived practice of instructional leadership while…

  15. Heterogeneity and phenotypic plasticity of glial cells in the mammalian enteric nervous system.

    PubMed

    Boesmans, Werend; Lasrado, Reena; Vanden Berghe, Pieter; Pachnis, Vassilis

    2015-02-01

    Enteric glial cells are vital for the autonomic control of gastrointestinal homeostasis by the enteric nervous system. Several different functions have been assigned to enteric glial cells but whether these are performed by specialized subtypes with a distinctive phenotype and function remains elusive. We used Mosaic Analysis with Double Markers and inducible lineage tracing to characterize the morphology and dynamic molecular marker expression of enteric GLIA in the myenteric plexus. Functional analysis in individually identified enteric glia was performed by Ca(2+) imaging. Our experiments have identified four morphologically distinct subpopulations of enteric glia in the gastrointestinal tract of adult mice. Marker expression analysis showed that the majority of glia in the myenteric plexus co-express glial fibrillary acidic protein (GFAP), S100β, and Sox10. However, a considerable fraction (up to 80%) of glia outside the myenteric ganglia, did not label for these markers. Lineage tracing experiments suggest that these alternative combinations of markers reflect dynamic gene regulation rather than lineage restrictions. At the functional level, the three myenteric glia subtypes can be distinguished by their differential response to adenosine triphosphate. Together, our studies reveal extensive heterogeneity and phenotypic plasticity of enteric glial cells and set a framework for further investigations aimed at deciphering their role in digestive function and disease. © 2014 Wiley Periodicals, Inc.

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

    The Analysis of Search Results for the Clarification and Identification of Technology Emergence (AR-CITE) computer code examines a scientometric model that tracks the emergence of an identified technology from initial discovery (via original scientific and conference literature), through critical discoveries (via original scientific, conference literature and patents), transitioning through Technology Readiness Levels (TRLs) and ultimately on to commercial currency of citations, collaboration indicators, and on-line news patterns are identified. The combinations of four distinct and separate searchable on-line networked sources (i.e. scholarly publications and citation, world patents, news archives, and on-line mapping networks) are assembled to become one collective networkmore » (a dataset for analysis of relations). This established network becomes the basis from which to quickly analyze the temporal flow of activity (searchable events) for the subject domain to be clarified and identified.« less

  17. Going coastal: Shared evolutionary history between coastal British Columbia and Southeast Alaska wolves (canis lupus)

    USGS Publications Warehouse

    Weckworth, B.V.; Dawson, N.G.; Talbot, S.L.; Flamme, M.J.; Cook, J.A.

    2011-01-01

    Background: Many coastal species occupying the temperate rainforests of the Pacific Northwest in North America comprise endemic populations genetically and ecologically distinct from interior continental conspecifics. Morphological variation previously identified among wolf populations resulted in recognition of multiple subspecies of wolves in the Pacific Northwest. Recently, separate genetic studies have identified diverged populations of wolves in coastal British Columbia and coastal Southeast Alaska, providing support for hypotheses of distinct coastal subspecies. These two regions are geographically and ecologically contiguous, however, there is no comprehensive analysis across all wolf populations in this coastal rainforest. Methodology/Principal Findings: By combining mitochondrial DNA datasets from throughout the Pacific Northwest, we examined the genetic relationship between coastal British Columbia and Southeast Alaska wolf populations and compared them with adjacent continental populations. Phylogenetic analysis indicates complete overlap in the genetic diversity of coastal British Columbia and Southeast Alaska wolves, but these populations are distinct from interior continental wolves. Analyses of molecular variation support the separation of all coastal wolves in a group divergent from continental populations, as predicted based on hypothesized subspecies designations. Two novel haplotypes also were uncovered in a newly assayed continental population of interior Alaska wolves. Conclusions/Significance: We found evidence that coastal wolves endemic to these temperate rainforests are diverged from neighbouring, interior continental wolves; a finding that necessitates new international strategies associated with the management of this species. ?? 2011 This is an open-access article.

  18. Comprehensive Proteomic Analysis of Human Milk-derived Extracellular Vesicles Unveils a Novel Functional Proteome Distinct from Other Milk Components*

    PubMed Central

    van Herwijnen, Martijn J.C.; Zonneveld, Marijke I.; Goerdayal, Soenita; Nolte – 't Hoen, Esther N.M.; Garssen, Johan; Stahl, Bernd; Maarten Altelaar, A.F.; Redegeld, Frank A.; Wauben, Marca H.M.

    2016-01-01

    Breast milk contains several macromolecular components with distinctive functions, whereby milk fat globules and casein micelles mainly provide nutrition to the newborn, and whey contains molecules that can stimulate the newborn's developing immune system and gastrointestinal tract. Although extracellular vesicles (EV) have been identified in breast milk, their physiological function and composition has not been addressed in detail. EV are submicron sized vehicles released by cells for intercellular communication via selectively incorporated lipids, nucleic acids, and proteins. Because of the difficulty in separating EV from other milk components, an in-depth analysis of the proteome of human milk-derived EV is lacking. In this study, an extensive LC-MS/MS proteomic analysis was performed of EV that had been purified from breast milk of seven individual donors using a recently established, optimized density-gradient-based EV isolation protocol. A total of 1963 proteins were identified in milk-derived EV, including EV-associated proteins like CD9, Annexin A5, and Flotillin-1, with a remarkable overlap between the different donors. Interestingly, 198 of the identified proteins are not present in the human EV database Vesiclepedia, indicating that milk-derived EV harbor proteins not yet identified in EV of different origin. Similarly, the proteome of milk-derived EV was compared with that of other milk components. For this, data from 38 published milk proteomic studies were combined in order to construct the total milk proteome, which consists of 2698 unique proteins. Remarkably, 633 proteins identified in milk-derived EV have not yet been identified in human milk to date. Interestingly, these novel proteins include proteins involved in regulation of cell growth and controlling inflammatory signaling pathways, suggesting that milk-derived EVs could support the newborn's developing gastrointestinal tract and immune system. Overall, this study provides an expansion of the whole milk proteome and illustrates that milk-derived EV are macromolecular components with a unique functional proteome. PMID:27601599

  19. Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia

    PubMed Central

    Yang, Quan‐Jun; Zhao, Jiang‐Rong; Hao, Juan; Li, Bin; Huo, Yan; Han, Yong‐Long; Wan, Li‐Li; Li, Jie; Huang, Jinlu; Lu, Jin

    2017-01-01

    Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance‐based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. Methods Eighty‐four cancer cachexia patients, 33 pre‐cachectic patients, 105 weight‐stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. Results Forty‐six cancer cachexia patients, 22 pre‐cachectic patients, 68 weight‐stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre‐cachectic patients, 37 weight‐stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age‐matched and sex‐matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = −400.53 – 481.88 × log(Carnosine) −239.02 × log(Leucine) + 383.92 × log(Phenyl acetate), and the result showed 94.64% accuracy in the validation set. Conclusions This metabolomics study revealed a distinct metabolic profile of cancer cachexia and established and validated a diagnostic model. This research provided a feasible diagnostic tool for identifying at‐risk populations through the detection of serum metabolites. PMID:29152916

  20. BDA: A novel method for identifying defects in body-centered cubic crystals.

    PubMed

    Möller, Johannes J; Bitzek, Erik

    2016-01-01

    The accurate and fast identification of crystallographic defects plays a key role for the analysis of atomistic simulation output data. For face-centered cubic (fcc) metals, most existing structure analysis tools allow for the direct distinction of common defects, such as stacking faults or certain low-index surfaces. For body-centered cubic (bcc) metals, on the other hand, a robust way to identify such defects is currently not easily available. We therefore introduce a new method for analyzing atomistic configurations of bcc metals, the BCC Defect Analysis (BDA). It uses existing structure analysis algorithms and combines their results to uniquely distinguish between typical defects in bcc metals. In essence, the BDA method offers the following features:•Identification of typical defect structures in bcc metals.•Reduction of erroneously identified defects by iterative comparison to the defects in the atom's neighborhood.•Availability as ready-to-use Python script for the widespread visualization tool OVITO [http://ovito.org].

  1. Symptom-Hemodynamic Mismatch and Heart Failure Event Risk

    PubMed Central

    Lee, Christopher S.; Hiatt, Shirin O.; Denfeld, Quin E.; Mudd, James O.; Chien, Christopher; Gelow, Jill M.

    2014-01-01

    Background Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. Objective The goal of this study was to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics, and quantify differences in 180-day event-risk among observed profiles. Methods A secondary analysis of data collected during two prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event-risk (HF emergency visit, hospitalization or death) among profiles. Results The mean age (n=291) was 57±13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified. 17.9% of patients had concordant symptoms and hemodynamics (i.e. moderate physical and psychological symptoms matched the comparatively hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared to those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event-risk (severe symptoms hazards ratio = 3.38, p=0.033; poor hemodynamics hazards ratio = 3.48, p=0.016). Conclusions A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death. PMID:24988323

  2. Population genetics of Vibrio vulnificus: identification of two divisions and a distinct eel-pathogenic clone.

    PubMed

    Gutacker, Michaela; Conza, Nadine; Benagli, Cinzia; Pedroli, Ambra; Bernasconi, Marco Valerio; Permin, Lise; Aznar, Rosa; Piffaretti, Jean-Claude

    2003-06-01

    Genetic relationships among 62 Vibrio vulnificus strains of different geographical and host origins were analyzed by multilocus enzyme electrophoresis (MLEE), random amplification of polymorphic DNA (RAPD), and sequence analyses of the recA and glnA genes. Out of 15 genetic loci analyzed by MLEE, 11 were polymorphic. Cluster analysis identified 43 distinct electrophoretic types (ETs) separating the V. vulnificus population into two divisions (divisions I and II). One ET (ET 35) included all indole-negative isolates from diseased eels worldwide (biotype 2). A second ET (ET 2) marked all of the strains from Israel isolated from patients who handled St. Peter's fish (biotype 3). RAPD analysis of the 62 V. vulnificus isolates identified 26 different profiles separated into two divisions as well. In general, this subdivision was comparable (but not identical) to that observed by MLEE. Phylogenetic analysis of 543 bp of the recA gene and of 402 bp of the glnA gene also separated the V. vulnificus population into two major divisions in a manner similar to that by MLEE and RAPD. Sequence data again indicated the overall subdivision of the V. vulnificus population into different biotypes. In particular, indole-negative eel-pathogenic isolates (biotype 2) on one hand and the Israeli isolates (biotype 3) on the other tended to cluster together in both gene trees. None of the methods showed an association between distinct clones and human clinical manifestations. Furthermore, except for the Israeli strains, only minor clusters comprising geographically related isolates were observed. In conclusion, all three approaches (MLEE, RAPD, and DNA sequencing) generated comparable but not always equivalent results. The significance of the two divisions (divisions I and II) still remains to be clarified, and a reevaluation of the definition of the biotypes is also needed.

  3. Phylogeographic structure and demographic patterns of brown trout in North-West Africa.

    PubMed

    Snoj, Aleš; Marić, Saša; Bajec, Simona Sušnik; Berrebi, Patrick; Janjani, Said; Schöffmann, Johannes

    2011-10-01

    The objectives of the study were to determine the phylogeographic structure of brown trout (Salmo trutta) in Morocco, elucidate their colonization patterns in North-West Africa and identify the mtDNA lineages involved in this process. We also aimed to resolve whether certain brown trout entities are also genetically distinct. Sixty-two brown trout from eleven locations across the Mediterranean and the Atlantic drainages in Morocco were surveyed using sequence analysis of the mtDNA control region and nuclear gene LDH, and by genotyping twelve microsatellite loci. Our study confirms that in Morocco both the Atlantic and Mediterranean basins are populated by Atlantic mtDNA lineage brown trout only, demonstrating that the Atlantic lineage (especially its southern clade) invaded initially not only the western part of the Mediterranean basin in Morocco but also expanded deep into the central area. Atlantic haplotypes identified here sort into three distinct groups suggesting Morocco was colonized in at least three successive waves (1.2, 0.4 and 0.2-0.1 MY ago). This notion becomes more pronounced with the finding of a distinct haplotype in the Dades river system, whose origin appears to coalesce with the nascent stage of the basal mtDNA evolutionary lineages of brown trout. According to our results, Salmo akairos, Salmo pellegrini and "green trout" from Lake Isli do not exhibited any character states that distinctively separate them from the other brown trout populations studied. Therefore, their status as distinct species was not confirmed. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. How We Know It Hurts: Item Analysis of Written Narratives Reveals Distinct Neural Responses to Others' Physical Pain and Emotional Suffering

    PubMed Central

    Bruneau, Emile; Dufour, Nicholas; Saxe, Rebecca

    2013-01-01

    People are often called upon to witness, and to empathize with, the pain and suffering of others. In the current study, we directly compared neural responses to others' physical pain and emotional suffering by presenting participants (n = 41) with 96 verbal stories, each describing a protagonist's physical and/or emotional experience, ranging from neutral to extremely negative. A separate group of participants rated “how much physical pain”, and “how much emotional suffering” the protagonist experienced in each story, as well as how “vivid and movie-like” the story was. Although ratings of Pain, Suffering and Vividness were positively correlated with each other across stories, item-analyses revealed that each scale was correlated with activity in distinct brain regions. Even within regions of the “Shared Pain network” identified using a separate data set, responses to others' physical pain and emotional suffering were distinct. More broadly, item analyses with continuous predictors provided a high-powered method for identifying brain regions associated with specific aspects of complex stimuli – like verbal descriptions of physical and emotional events. PMID:23638181

  5. Breed-Specific Ancestry Studies and Genome-Wide Association Analysis Highlight an Association Between the MYH9 Gene and Heat Tolerance in Alaskan Sprint Racing Sled Dogs

    PubMed Central

    Huson, Heather J.; vonHoldt, Bridgett M.; Rimbault, Maud; Byers, Alexandra M.; Runstadler, Jonathan A.; Parker, Heidi G.; Ostrander, Elaine A.

    2012-01-01

    Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long distance racers, and combined that with genome wide association studies (GWAS) to identify regions correlating with performance enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principle components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5–10 and 2.5–3.75 kb, respectively). Further, we identified eight regions with the genomic signal either from a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor performing sled dogs identified a single region significantly association with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog. PMID:22105876

  6. Symptom clusters and quality of life among patients with advanced heart failure

    PubMed Central

    Yu, Doris SF; Chan, Helen YL; Leung, Doris YP; Hui, Elsie; Sit, Janet WH

    2016-01-01

    Objectives To identify symptom clusters among patients with advanced heart failure (HF) and the independent relationships with their quality of life (QoL). Methods This is the secondary data analysis of a cross-sectional study which interviewed 119 patients with advanced HF in the geriatric unit of a regional hospital in Hong Kong. The symptom profile and QoL were assessed by using the Edmonton Symptom Assessment Scale (ESAS) and the McGill QoL Questionnaire. Exploratory factor analysis was used to identify the symptom clusters. Hierarchical regression analysis was used to examine the independent relationships with their QoL, after adjusting the effects of age, gender, and comorbidities. Results The patients were at an advanced age (82.9 ± 6.5 years). Three distinct symptom clusters were identified: they were the distress cluster (including shortness of breath, anxiety, and depression), the decondition cluster (fatigue, drowsiness, nausea, and reduced appetite), and the discomfort cluster (pain, and sense of generalized discomfort). These three symptom clusters accounted for 63.25% of variance of the patients' symptom experience. The small to moderate correlations between these symptom clusters indicated that they were rather independent of one another. After adjusting the age, gender and comorbidities, the distress (β = −0.635, P < 0.001), the decondition (β = −0.148, P = 0.01), and the discomfort (β = −0.258, P < 0.001) symptom clusters independently predicted their QoL. Conclusions This study identified the distinctive symptom clusters among patients with advanced HF. The results shed light on the need to develop palliative care interventions for optimizing the symptom control for this life-limiting disease. PMID:27403150

  7. Unraveling Appalachian tectonics: domain analysis of topographic lineaments in Pennsylvania

    NASA Astrophysics Data System (ADS)

    Karimi, B.; Schon, K.; Nussbaum, G. W.; Storer, N. D.; McGuire, J. L.; Hardcastle, K.

    2016-12-01

    Litho-tectonic provinces provide different components of a regions' tectonic history, and are identified as spatial entities with common structural elements, or a number of contiguous related elements. The province boundaries are easily identified when geomorphic expressions are distinct, or significant rock exposure allows for little uncertainty. When exposures are limited, locations of boundaries between provinces are uncertain. In such instances, satellite imagery can be quite advantageous, as tectonically sourced features (faults, folds, fractures, and joints) may exert a strong control on topographic patterns by creating pathways for weathering and erosion. Lineament analyses of topography often focus on well-pronounced tectonic features to interpret regional tectonics. We suggest that lineament analyses including all topographic features may include more subtle tectonic features, resulting in the identification of minor heterogeneities within litho-tectonic provinces. Our study focuses on Appalachian tectonics, specifically in Pennsylvania (PA), home to the Appalachian Orocline and 5 distinct tectonic provinces. Using hillshades from a digital elevation model (DEM) of PA, we manually pick all topographic lineaments 1 km or greater, discriminating only against man-made structures. The final lineament coverage of the state is subdivided into smaller areas for which rose diagrams were prepared. The dominant lineament trends were compared and associated with known structural features. Peaks with no known source are marked as possible tectonic features requiring further research. A domain analysis is performed on the lineament data to identify the extent and interplay of swarms, followed by an investigation of their azimuthal compatibility. We present the results of our domain analysis of all topographic lineaments in the context of identifying litho-tectonic provinces associated with Appalachian tectonics in Pennsylvania, and possible heterogeneities within them.

  8. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

    PubMed

    Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun; Hernaez, Ruben; Kim, Lauren J; Palmer, Cameron D; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E; Launer, Lenore J; Nalls, Michael A; Clark, Jeanne M; Mitchell, Braxton D; Shuldiner, Alan R; Butler, Johannah L; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M; O'Donnell, Christopher J; Sahani, Dushyant V; Salomaa, Veikko; Schadt, Eric E; Schwartz, Stephen M; Siscovick, David S; Voight, Benjamin F; Carr, J Jeffrey; Feitosa, Mary F; Harris, Tamara B; Fox, Caroline S; Smith, Albert V; Kao, W H Linda; Hirschhorn, Joel N; Borecki, Ingrid B

    2011-03-01

    Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

  9. Understanding identifiability as a crucial step in uncertainty assessment

    NASA Astrophysics Data System (ADS)

    Jakeman, A. J.; Guillaume, J. H. A.; Hill, M. C.; Seo, L.

    2016-12-01

    The topic of identifiability analysis offers concepts and approaches to identify why unique model parameter values cannot be identified, and can suggest possible responses that either increase uniqueness or help to understand the effect of non-uniqueness on predictions. Identifiability analysis typically involves evaluation of the model equations and the parameter estimation process. Non-identifiability can have a number of undesirable effects. In terms of model parameters these effects include: parameters not being estimated uniquely even with ideal data; wildly different values being returned for different initialisations of a parameter optimisation algorithm; and parameters not being physically meaningful in a model attempting to represent a process. This presentation illustrates some of the drastic consequences of ignoring model identifiability analysis. It argues for a more cogent framework and use of identifiability analysis as a way of understanding model limitations and systematically learning about sources of uncertainty and their importance. The presentation specifically distinguishes between five sources of parameter non-uniqueness (and hence uncertainty) within the modelling process, pragmatically capturing key distinctions within existing identifiability literature. It enumerates many of the various approaches discussed in the literature. Admittedly, improving identifiability is often non-trivial. It requires thorough understanding of the cause of non-identifiability, and the time, knowledge and resources to collect or select new data, modify model structures or objective functions, or improve conditioning. But ignoring these problems is not a viable solution. Even simple approaches such as fixing parameter values or naively using a different model structure may have significant impacts on results which are too often overlooked because identifiability analysis is neglected.

  10. How to Perform an Ethical Risk Analysis (eRA).

    PubMed

    Hansson, Sven Ove

    2018-02-26

    Ethical analysis is often needed in the preparation of policy decisions on risk. A three-step method is proposed for performing an ethical risk analysis (eRA). In the first step, the people concerned are identified and categorized in terms of the distinct but compatible roles of being risk-exposed, a beneficiary, or a decisionmaker. In the second step, a more detailed classification of roles and role combinations is performed, and ethically problematic role combinations are identified. In the third step, further ethical deliberation takes place, with an emphasis on individual risk-benefit weighing, distributional analysis, rights analysis, and power analysis. Ethical issues pertaining to subsidiary risk roles, such as those of experts and journalists, are also treated in this phase. An eRA should supplement, not replace, a traditional risk analysis that puts emphasis on the probabilities and severities of undesirable events but does not cover ethical issues such as agency, interpersonal relationships, and justice. © 2018 Society for Risk Analysis.

  11. Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation.

    PubMed

    Jha, Prerana; Pia Patric, Irene Rosita; Shukla, Sudhanshu; Pathak, Pankaj; Pal, Jagriti; Sharma, Vikas; Thinagararanjan, Sivaarumugam; Santosh, Vani; Suri, Vaishali; Sharma, Mehar Chand; Arivazhagan, Arimappamagan; Suri, Ashish; Gupta, Deepak; Somasundaram, Kumaravel; Sarkar, Chitra

    2014-12-01

    Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

    PubMed

    Glinsky, Gennadi V

    2016-09-19

    Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P < 0.0001 in all instances). Present analysis supports the idea that phenotypic divergence of Homo sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of creation of divergent sequences of regulatory DNA: (i) recombination-associated exaptation of the highly conserved ancestral regulatory DNA segments; (ii) human-specific insertions of transposable elements. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. Discrimination between Bacillus and Alicyclobacillus isolates in apple juice by Fourier transform infrared spectroscopy and multivariate analysis.

    PubMed

    Al-Holy, Murad A; Lin, Mengshi; Alhaj, Omar A; Abu-Goush, Mahmoud H

    2015-02-01

    Alicyclobacillus is a causative agent of spoilage in pasteurized and heat-treated apple juice products. Differentiating between this genus and the closely related Bacillus is crucially important. In this study, Fourier transform infrared spectroscopy (FT-IR) was used to identify and discriminate between 4 Alicyclobacillus strains and 4 Bacillus isolates inoculated individually into apple juice. Loading plots over the range of 1350 and 1700 cm(-1) reflected the most distinctive biochemical features of Bacillus and Alicyclobacillus. Multivariate statistical methods (for example, principal component analysis and soft independent modeling of class analogy) were used to analyze the spectral data. Distinctive separation of spectral samples was observed. This study demonstrates that FT-IR spectroscopy in combination with multivariate analysis could serve as a rapid and effective tool for fruit juice industry to differentiate between Bacillus and Alicyclobacillus and to distinguish between species belonging to these 2 genera. © 2015 Institute of Food Technologists®

  14. Tobacco, Marijuana, and Alcohol Use in University Students: A Cluster Analysis

    PubMed Central

    Primack, Brian A.; Kim, Kevin H.; Shensa, Ariel; Sidani, Jaime E.; Barnett, Tracey E.; Switzer, Galen E.

    2012-01-01

    Objective Segmentation of populations may facilitate development of targeted substance abuse prevention programs. We aimed to partition a national sample of university students according to profiles based on substance use. Participants We used 2008–2009 data from the National College Health Assessment from the American College Health Association. Our sample consisted of 111,245 individuals from 158 institutions. Method We partitioned the sample using cluster analysis according to current substance use behaviors. We examined the association of cluster membership with individual and institutional characteristics. Results Cluster analysis yielded six distinct clusters. Three individual factors—gender, year in school, and fraternity/sorority membership—were the most strongly associated with cluster membership. Conclusions In a large sample of university students, we were able to identify six distinct patterns of substance abuse. It may be valuable to target specific populations of college-aged substance users based on individual factors. However, comprehensive intervention will require a multifaceted approach. PMID:22686360

  15. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    NASA Astrophysics Data System (ADS)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  16. Exploration of Online Culture Through Network Analysis of Wikipedia.

    PubMed

    Park, Sung Joo; Kim, Jong Woo; Lee, Hong Joo; Park, Hyunjung; Han, Deugcheon; Gloor, Peter

    2015-11-01

    Understanding online culture is becoming crucial in the global and connected world. Contrary to conventional attitudinal surveys used in cultural research, this study uses the approach of directly observing culture-specific behavior that emerges from online collaboration on the Internet. The editing data of Wikipedia were analyzed in 12 languages. Distinctive cultural dimensions were identified, including collectivism, extraversion, boldness, and egalitarianism. Using network analysis, the language-framed cultural factors were extracted as an emergent phenomenon in the virtual world.

  17. Unique Transcriptome Patterns of the White and Grey Matter Corroborate Structural and Functional Heterogeneity in the Human Frontal Lobe

    PubMed Central

    Mills, James D.; Kavanagh, Tomas; Kim, Woojin S.; Chen, Bei Jun; Kawahara, Yoshihiro; Halliday, Glenda M.; Janitz, Michael

    2013-01-01

    The human frontal lobe has undergone accelerated evolution, leading to the development of unique human features such as language and self-reflection. Cortical grey matter and underlying white matter reflect distinct cellular compositions in the frontal lobe. Surprisingly little is known about the transcriptomal landscape of these distinct regions. Here, for the first time, we report a detailed transcriptomal profile of the frontal grey (GM) and white matter (WM) with resolution to alternatively spliced isoforms obtained using the RNA-Seq approach. We observed more vigorous transcriptome activity in GM compared to WM, presumably because of the presence of cellular bodies of neurons in the GM and RNA associated with the nucleus and perinuclear space. Among the top differentially expressed genes, we also identified a number of long intergenic non-coding RNAs (lincRNAs), specifically expressed in white matter, such as LINC00162. Furthermore, along with confirmation of expression of known markers for neurons and oligodendrocytes, we identified a number of genes and splicing isoforms that are exclusively expressed in GM or WM with examples of GABRB2 and PAK2 transcripts, respectively. Pathway analysis identified distinct physiological and biochemical processes specific to grey and white matter samples with a prevalence of synaptic processes in GM and myelination regulation and axonogenesis in the WM. Our study also revealed that expression of many genes, for example, the GPR123, is characterized by isoform switching, depending in which structure the gene is expressed. Our report clearly shows that GM and WM have perhaps surprisingly divergent transcriptome profiles, reflecting distinct roles in brain physiology. Further, this study provides the first reference data set for a normal human frontal lobe, which will be useful in comparative transcriptome studies of cerebral disorders, in particular, neurodegenerative diseases. PMID:24194939

  18. Genome-scale analysis of aberrant DNA methylation in colorectal cancer

    PubMed Central

    Hinoue, Toshinori; Weisenberger, Daniel J.; Lange, Christopher P.E.; Shen, Hui; Byun, Hyang-Min; Van Den Berg, David; Malik, Simeen; Pan, Fei; Noushmehr, Houtan; van Dijk, Cornelis M.; Tollenaar, Rob A.E.M.; Laird, Peter W.

    2012-01-01

    Colorectal cancer (CRC) is a heterogeneous disease in which unique subtypes are characterized by distinct genetic and epigenetic alterations. Here we performed comprehensive genome-scale DNA methylation profiling of 125 colorectal tumors and 29 adjacent normal tissues. We identified four DNA methylation–based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic and clinical features, indicating that they represent biologically distinct subgroups. A CIMP-high (CIMP-H) subgroup, which exhibits an exceptionally high frequency of cancer-specific DNA hypermethylation, is strongly associated with MLH1 DNA hypermethylation and the BRAFV600E mutation. A CIMP-low (CIMP-L) subgroup is enriched for KRAS mutations and characterized by DNA hypermethylation of a subset of CIMP-H-associated markers rather than a unique group of CpG islands. Non-CIMP tumors are separated into two distinct clusters. One non-CIMP subgroup is distinguished by a significantly higher frequency of TP53 mutations and frequent occurrence in the distal colon, while the tumors that belong to the fourth group exhibit a low frequency of both cancer-specific DNA hypermethylation and gene mutations and are significantly enriched for rectal tumors. Furthermore, we identified 112 genes that were down-regulated more than twofold in CIMP-H tumors together with promoter DNA hypermethylation. These represent ∼7% of genes that acquired promoter DNA methylation in CIMP-H tumors. Intriguingly, 48/112 genes were also transcriptionally down-regulated in non-CIMP subgroups, but this was not attributable to promoter DNA hypermethylation. Together, we identified four distinct DNA methylation subgroups of CRC and provided novel insight regarding the role of CIMP-specific DNA hypermethylation in gene silencing. PMID:21659424

  19. Comparative genomic analysis of the Lipase3 gene family in five plant species reveals distinct evolutionary origins.

    PubMed

    Wang, Dan; Zhang, Lin; Hu, JunFeng; Gao, Dianshuai; Liu, Xin; Sha, Yan

    2018-04-01

    Lipases are physiologically important and ubiquitous enzymes that share a conserved domain and are classified into eight different families based on their amino acid sequences and fundamental biological properties. The Lipase3 family of lipases was reported to possess a canonical fold typical of α/β hydrolases and a typical catalytic triad, suggesting a distinct evolutionary origin for this family. Genes in the Lipase3 family do not have the same functions, but maintain the conserved Lipase3 domain. There have been extensive studies of Lipase3 structures and functions, but little is known about their evolutionary histories. In this study, all lipases within five plant species were identified, and their phylogenetic relationships and genetic properties were analyzed and used to group them into distinct evolutionary families. Each identified lipase family contained at least one dicot and monocot Lipase3 protein, indicating that the gene family was established before the split of dicots and monocots. Similar intron/exon numbers and predicted protein sequence lengths were found within individual groups. Twenty-four tandem Lipase3 gene duplications were identified, implying that the distinctive function of Lipase3 genes appears to be a consequence of translocation and neofunctionalization after gene duplication. The functional genes EDS1, PAD4, and SAG101 that are reportedly involved in pathogen response were all located in the same group. The nucleotide diversity (Dxy) and the ratio of nonsynonymous to synonymous nucleotide substitutions rates (Ka/Ks) of the three genes were significantly greater than the average across the genomes. We further observed evidence for selection maintaining diversity on three genes in the Toll-Interleukin-1 receptor type of nucleotide binding/leucine-rich repeat immune receptor (TIR-NBS LRR) immunity-response signaling pathway, indicating that they could be vulnerable to pathogen effectors.

  20. Identification of Significant Gene Signatures and Prognostic Biomarkers for Patients With Cervical Cancer by Integrated Bioinformatic Methods

    PubMed Central

    Li, Xiaofang; Tian, Run; Gao, Hugh; Yan, Feng; Ying, Le; Yang, Yongkang; Yang, Pei

    2018-01-01

    Cervical cancer is the leading cause of death with gynecological malignancies. We aimed to explore the molecular mechanism of carcinogenesis and biomarkers for cervical cancer by integrated bioinformatic analysis. We employed RNA-sequencing details of 254 cervical squamous cell carcinomas and 3 normal samples from The Cancer Genome Atlas. To explore the distinct pathways, messenger RNA expression was submitted to a Gene Set Enrichment Analysis. Kyoto Encyclopedia of Genes and Genomes and protein–protein interaction network analysis of differentially expressed genes were performed. Then, we conducted pathway enrichment analysis for modules acquired in protein–protein interaction analysis and obtained a list of pathways in every module. After intersecting the results from the 3 approaches, we evaluated the survival rates of both mutual pathways and genes in the pathway, and 5 survival-related genes were obtained. Finally, Cox hazards ratio analysis of these 5 genes was performed. DNA replication pathway (P < .001; 12 genes included) was suggested to have the strongest association with the prognosis of cervical squamous cancer. In total, 5 of the 12 genes, namely, minichromosome maintenance 2, minichromosome maintenance 4, minichromosome maintenance 5, proliferating cell nuclear antigen, and ribonuclease H2 subunit A were significantly correlated with survival. Minichromosome maintenance 5 was shown as an independent prognostic biomarker for patients with cervical cancer. This study identified a distinct pathway (DNA replication). Five genes which may be prognostic biomarkers and minichromosome maintenance 5 were identified as independent prognostic biomarkers for patients with cervical cancer. PMID:29642758

  1. Knowledge-making distinctions in synthetic biology.

    PubMed

    O'Malley, Maureen A; Powell, Alexander; Davies, Jonathan F; Calvert, Jane

    2008-01-01

    Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. (c) 2007 Wiley Periodicals, Inc.

  2. Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague

    PubMed Central

    Stasulli, Nikolas M.; Eichelberger, Kara R.; Price, Paul A.; Pechous, Roger D.; Montgomery, Stephanie A.; Parker, Joel S.

    2015-01-01

    ABSTRACT During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. PMID:26463167

  3. Pathways to Medical Home Recognition: A Qualitative Comparative Analysis of the PCMH Transformation Process.

    PubMed

    Mendel, Peter; Chen, Emily K; Green, Harold D; Armstrong, Courtney; Timbie, Justin W; Kress, Amii M; Friedberg, Mark W; Kahn, Katherine L

    2017-12-15

    To understand the process of practice transformation by identifying pathways for attaining patient-centered medical home (PCMH) recognition. The CMS Federally Qualified Health Center (FQHC) Advanced Primary Care Practice Demonstration was designed to help FQHCs achieve NCQA Level 3 PCMH recognition and improve patient outcomes. We used a stratified random sample of 20 (out of 503) participating sites for this analysis. We developed a conceptual model of structural, cultural, and implementation factors affecting PCMH transformation based on literature and initial qualitative interview themes. We then used conventional cross-case analysis, followed by qualitative comparative analysis (QCA), a cross-case method based on Boolean logic algorithms, to systematically identify pathways (i.e., combinations of factors) associated with attaining-or not attaining-Level 3 recognition. Site-level indicators were derived from semistructured interviews with site leaders at two points in time (mid- and late-implementation) and administrative data collected prior to and during the demonstration period. The QCA results identified five distinct pathways to attaining PCMH recognition and four distinct pathways to not attaining recognition by the end of the demonstration. Across these pathways, one condition (change leader capacity) was common to all pathways for attaining recognition, and another (previous improvement or recognition experience) was absent in all pathways for not attaining recognition. In general, sites could compensate for deficiencies in one factor with capacity in others, but they needed a threshold of strengths in cultural and implementation factors to attain PCMH recognition. Future efforts at primary care transformation should take into account multiple pathways sites may pursue. Sites should be assessed on key cultural and implementation factors, in addition to structural components, in order to differentiate interventions and technical assistance. © Health Research and Educational Trust.

  4. An exploratory factor analysis of inflammatory and coagulation markers associated with femoral artery atherosclerosis in the San Diego Population Study.

    PubMed

    Egnot, Natalie Suder; Barinas-Mitchell, Emma; Criqui, Michael H; Allison, Matthew A; Ix, Joachim H; Jenny, Nancy S; Wassel, Christina L

    2018-04-01

    Several biomarkers of inflammation and coagulation have been implicated in lower extremity atherosclerosis. We utilized an exploratory factor analysis (EFA) to identify distinct factors derived from circulating inflammatory and coagulation biomarkers then examined the associations of these factors with measures of lower extremity subclinical atherosclerosis, including the ankle-brachial index (ABI), common and superficial femoral intima-media thickness (IMT), and atherosclerotic plaque presence, burden, and characteristics. The San Diego Population Study (SDPS) is a prospective, community-living, multi-ethnic cohort of 1103 men and women averaged age 70. Regression analysis was used to assess cross-sectional associations between the identified groupings of biomarkers (factors) and the ABI and femoral artery atherosclerosis measurements. Two biomarker factors emerged from the factor analysis. Factor 1 consisting of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen was significantly associated with higher odds (OR = 1.99, p < 0.01) of a borderline ABI value (0.91-0.99), while Factor 2 containing D-dimer and pentraxin (PTX)-3 was significantly associated with higher common femoral artery (CFA) IMT (β = 0.23, p < 0.01) and lower ABI (β = -0.03, p < 0.01). Two groupings of biomarkers were identified via EFA of seven circulating biomarkers of inflammation and coagulation. These distinct groups are differentially associated with markers of lower extremity subclinical atherosclerosis. Our findings suggest that high inflammatory and coagulation burden were better markers of more severe lower-extremity disease as indicated by low ABI rather than early atherosclerotic lesion development in the femoral artery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Designing an Information Center: An Analysis of Markets and Delivery Systems. AIR 1986 Annual Forum Paper.

    ERIC Educational Resources Information Center

    Matross, Ronald

    The role of information research centers in institutional research activities was explored, based on 1,040 requests for student data at an information center at the University of Minnesota, Twin Cities, during 1980-1985. Three distinct information center markets were identified and mechanisms for serving each market were recommended. The first was…

  6. Genome-wide analysis of the SPL/miR156 module and its interaction with the AP2/miR172 unit in barley

    USDA-ARS?s Scientific Manuscript database

    The SQUAMOSA-promoter binding like (SPL) gene family encodes transcription factors shown in a number of species to influence plant growth and development, but information about these genes in barley is limited. This study identified 13 barley SPL genes, within five distinct groups, that are ortholog...

  7. Development and application of a multilocus sequence analysis method for the identification of genotypes within genus Bradyrhizobium and for establishing nodule occupancy of soybean (Glycine max L. Merr)

    USDA-ARS?s Scientific Manuscript database

    A Multilocus Sequence Typing (MLST) method based on allelic variation of 7 chromosomal loci was developed for characterizing genotypes within the genus Bradyrhizobium. With the method 29 distinct multilocus genotypes (GTs) were identified among 191 culture collection soybean strains. The occupancy ...

  8. The Social Origins of Students Identified as Gifted and Talented in England: A Geo-Demographic Analysis

    ERIC Educational Resources Information Center

    Campbell, R. J.; Muijs, R. D.; Neelands, J. G. A.; Robinson, W.; Eyre, D.; Hewston, R.

    2007-01-01

    The English education system has been shown over a long period to be catering poorly for the educational needs of gifted and talented students. In the last five years, however, a national policy and an associated strategy have been established, distinctively attempting to embed core provisions for gifted and talented students in the mainstream…

  9. Explaining Cross-State Differences in Elderly Suicide Rates and Identifying State-Level Public Policy Responses that Reduce Rates

    ERIC Educational Resources Information Center

    Giles-Sims, Jean; Lockhart, Charles

    2006-01-01

    Elderly Americans commit suicide at higher rates than other age groups. We contend that macro- and micro-social variables contribute distinct aspects to explanations of this tragic loss: the former focus on circumstances that affect overall rates, the latter reveal why certain individuals succumb to suicide. Our analysis focuses on the…

  10. Land use analysis of US urban areas using high-resolution imagery from Skylab

    NASA Technical Reports Server (NTRS)

    Gallagher, D. B. (Principal Investigator)

    1975-01-01

    The author has identified the following significant results. The S-190B imagery from Skylab 3 permitted the detection of higher levels of land use detail than any satellite imagery previously evaluated using manual interpretation techniques. Resolution approaches that of 1:100,000 scale infrared aircraft photography, especially regarding urban areas. Nonurban areas are less distinct.

  11. Achieving Dramatic School Improvement: An Exploratory Study. A Cross-Site Analysis from the Evaluation of Comprehensive School Reform Program Implementation and Outcomes Study

    ERIC Educational Resources Information Center

    Aladjem, Daniel K.; Birman, Beatrice F.; Orland, Martin; Harr-Robins, Jenifer; Heredia, Alberto; Parrish, Thomas B.; Ruffini, Stephen J.

    2010-01-01

    This exploratory study describes approaches to improving schools through retrospective, in-depth qualitative case studies. To select schools to be examined, the authors sought to identify Comprehensive School Reform (CSR) schools demonstrating two distinctive patterns of improved student achievement between 2000 and 2005, rapid-improvement (i.e.,…

  12. Identifying Academic Skill and Performance Deficits: The Experimental Analysis of Brief Assessments of Academic Skills. General Articles

    ERIC Educational Resources Information Center

    Duhon, Gary J.; Noell, George H.; Witt, Joseph C.; Freeland, Jennifer T.; Dufrene, Brad A.; Gilbertson, Donna N.

    2004-01-01

    This study examined an approach for assessing and intervening with academic concerns that is conceptually derived from the distinction between skill deficits and performance deficits. A class-wide assessment was used to describe the students' functioning in the context of their peers and to help select a target concern for intervention. An…

  13. Single-cell mRNA profiling reveals transcriptional heterogeneity among pancreatic circulating tumour cells.

    PubMed

    Lapin, Morten; Tjensvoll, Kjersti; Oltedal, Satu; Javle, Milind; Smaaland, Rune; Gilje, Bjørnar; Nordgård, Oddmund

    2017-05-31

    Single-cell mRNA profiling of circulating tumour cells may contribute to a better understanding of the biology of these cells and their role in the metastatic process. In addition, such analyses may reveal new knowledge about the mechanisms underlying chemotherapy resistance and tumour progression in patients with cancer. Single circulating tumour cells were isolated from patients with locally advanced or metastatic pancreatic cancer with immuno-magnetic depletion and immuno-fluorescence microscopy. mRNA expression was analysed with single-cell multiplex RT-qPCR. Hierarchical clustering and principal component analysis were performed to identify expression patterns. Circulating tumour cells were detected in 33 of 56 (59%) examined blood samples. Single-cell mRNA profiling of intact isolated circulating tumour cells revealed both epithelial-like and mesenchymal-like subpopulations, which were distinct from leucocytes. The profiled circulating tumour cells also expressed elevated levels of stem cell markers, and the extracellular matrix protein, SPARC. The expression of SPARC might correspond to an epithelial-mesenchymal transition in pancreatic circulating tumour cells. The analysis of single pancreatic circulating tumour cells identified distinct subpopulations and revealed elevated expression of transcripts relevant to the dissemination of circulating tumour cells to distant organ sites.

  14. Passion and intrinsic motivation in digital gaming.

    PubMed

    Wang, Chee Keng John; Khoo, Angeline; Liu, Woon Chia; Divaharan, Shanti

    2008-02-01

    Digital gaming is fast becoming a favorite activity all over the world. Yet very few studies have examined the underlying motivational processes involved in digital gaming. One motivational force that receives little attention in psychology is passion, which could help us understand the motivation of gamers. The purpose of the present study was to identify subgroups of young people with distinctive passion profiles on self-determined regulations, flow dispositions, affect, and engagement time in gaming. One hundred fifty-five students from two secondary schools in Singapore participated in the survey. There were 134 males and 8 females (13 unspecified). The participants completed a questionnaire to measure harmonious passion (HP), obsessive passion (OP), perceived locus of causality, disposition flow, positive and negative affects, and engagement time in gaming. Cluster analysis found three clusters with distinct passion profiles. The first cluster had an average HP/OP profile, the second cluster had a low HP/OP profile, and the third cluster had a high HP/OP profile. The three clusters displayed different levels of cognitive, affective, and behavioral outcomes. Cluster analysis, as this study shows, is useful in identifying groups of gamers with different passion profiles. It has helped us gain a deeper understanding of motivation in digital gaming.

  15. Using Patient-Pathway Analysis to Inform a Differentiated Program Response to Tuberculosis: The Case of Kenya

    PubMed Central

    Masini, Enos; Hanson, Christy; Ogoro, Jeremiah; Brown, Jessie; Ngari, Faith; Mingkwan, Pia; Makayova, Julia; Osberg, Mike

    2017-01-01

    Abstract Background A recent tuberculosis prevalence survey in Kenya found that the country is home to nearly twice as many patients with tuberculosis as previously estimated. Kenya has prioritized identifying and treating the unnotified or missing cases of tuberculosis. This requires a better understanding of patient care seeking and system weaknesses. Methods A patient-pathway analysis (PPA) was completed to assess the alignment between patient care seeking and the availability of tuberculosis diagnostic and treatment services at the national level and for all 47 counties at the subnational level in Kenya. Results It was estimated that more than half of patients initiate care in the public sector. Nationally, just under half of patients encountered tuberculosis diagnostic and treatment capacity where they initiated care. Overall, there was distinct variation in diagnostic and treatment availability across counties and facility levels. Discussion The PPA results emphasized the need for a differentiated approach to tuberculosis care, by county, and the distinct need for better referral systems. The majority of Kenyans actively sought care; improving diagnostic and treatment capacity in the formal and informal private sector, as well as in the public sector, could help identify the majority of missing cases. PMID:29117349

  16. The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes.

    PubMed

    O'Dwyer, David N; Norman, Katy C; Xia, Meng; Huang, Yong; Gurczynski, Stephen J; Ashley, Shanna L; White, Eric S; Flaherty, Kevin R; Martinez, Fernando J; Murray, Susan; Noth, Imre; Arnold, Kelly B; Moore, Bethany B

    2017-04-25

    Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than 1100 proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology.

  17. Clustering of adversity in young adults on disability pension due to mental disorders: a latent class analysis.

    PubMed

    Joensuu, Matti; Mattila-Holappa, Pauliina; Ahola, Kirsi; Ervasti, Jenni; Kivimäki, Mika; Kivekäs, Teija; Koskinen, Aki; Vahtera, Jussi; Virtanen, Marianna

    2016-02-01

    Mental disorders are the leading cause of work disability among young adults. This study examined whether distinct classes could be identified among young adults on the basis of medical history before receiving a disability pension due to a mental disorder. Medical history was obtained from pension applications and attached medical certificates for 1163 individuals aged 18-34 years who, in 2008, received a disability pension due to a mental disorder. Using latent class analysis, 10 clinical and individual adversities and their associations with sex, age and diagnostic category were examined. Three classes were identified: childhood adversity (prevalence, 33%), comorbidity (23%), and undefined (44%). The childhood adversity class was characterized by adverse events and symptoms reported during childhood and it associated with depressive disorders. The comorbidity class was characterized by comorbid mental disorders, suicide attempts and substance abuse and associated with younger age and bipolar disorder. The undefined class formed no distinct profile; individuals in this class had the lowest number of adversities and it associated with psychotic disorders. The identification of subgroups characterized by childhood circumstances and comorbidity may help planning of prevention and support practices for young adults with mental disorders and risk of work disability.

  18. Lifetime Segmented Assimilation Trajectories and Health Outcomes in Latino and Other Community Residents

    PubMed Central

    Marsiglia, Flavio F.; Kulis, Stephen; Kellison, Joshua G.

    2010-01-01

    Objectives. Under an ecodevelopmental framework, we examined lifetime segmented assimilation trajectories (diverging assimilation pathways influenced by prior life conditions) and related them to quality-of-life indicators in a diverse sample of 258 men in the Pheonix, AZ, metropolitan area. Methods. We used a growth mixture model analysis of lifetime changes in socioeconomic status, and used acculturation to identify distinct lifetime segmented assimilation trajectory groups, which we compared on life satisfaction, exercise, and dietary behaviors. We hypothesized that lifetime assimilation change toward mainstream American culture (upward assimilation) would be associated with favorable health outcomes, and downward assimilation change with unfavorable health outcomes. Results. A growth mixture model latent class analysis identified 4 distinct assimilation trajectory groups. In partial support of the study hypotheses, the extreme upward assimilation trajectory group (the most successful of the assimilation pathways) exhibited the highest life satisfaction and the lowest frequency of unhealthy food consumption. Conclusions. Upward segmented assimilation is associated in adulthood with certain positive health outcomes. This may be the first study to model upward and downward lifetime segmented assimilation trajectories, and to associate these with life satisfaction, exercise, and dietary behaviors. PMID:20167890

  19. Metrics and methods for characterizing dairy farm intensification using farm survey data.

    PubMed

    Gonzalez-Mejia, Alejandra; Styles, David; Wilson, Paul; Gibbons, James

    2018-01-01

    Evaluation of agricultural intensification requires comprehensive analysis of trends in farm performance across physical and socio-economic aspects, which may diverge across farm types. Typical reporting of economic indicators at sectorial or the "average farm" level does not represent farm diversity and provides limited insight into the sustainability of specific intensification pathways. Using farm business data from a total of 7281 farm survey observations of English and Welsh dairy farms over a 14-year period we calculate a time series of 16 key performance indicators (KPIs) pertinent to farm structure, environmental and socio-economic aspects of sustainability. We then apply principle component analysis and model-based clustering analysis to identify statistically the number of distinct dairy farm typologies for each year of study, and link these clusters through time using multidimensional scaling. Between 2001 and 2014, dairy farms have largely consolidated and specialized into two distinct clusters: more extensive farms relying predominantly on grass, with lower milk yields but higher labour intensity, and more intensive farms producing more milk per cow with more concentrate and more maize, but lower labour intensity. There is some indication that these clusters are converging as the extensive cluster is intensifying slightly faster than the intensive cluster, in terms of milk yield per cow and use of concentrate feed. In 2014, annual milk yields were 6,835 and 7,500 l/cow for extensive and intensive farm types, respectively, whilst annual concentrate feed use was 1.3 and 1.5 tonnes per cow. For several KPIs such as milk yield the mean trend across all farms differed substantially from the extensive and intensive typologies mean. The indicators and analysis methodology developed allows identification of distinct farm types and industry trends using readily available survey data. The identified groups allow the accurate evaluation of the consequences of the reduction in dairy farm numbers and intensification at national and international scales.

  20. Metrics and methods for characterizing dairy farm intensification using farm survey data

    PubMed Central

    Gonzalez-Mejia, Alejandra; Styles, David; Wilson, Paul

    2018-01-01

    Evaluation of agricultural intensification requires comprehensive analysis of trends in farm performance across physical and socio-economic aspects, which may diverge across farm types. Typical reporting of economic indicators at sectorial or the “average farm” level does not represent farm diversity and provides limited insight into the sustainability of specific intensification pathways. Using farm business data from a total of 7281 farm survey observations of English and Welsh dairy farms over a 14-year period we calculate a time series of 16 key performance indicators (KPIs) pertinent to farm structure, environmental and socio-economic aspects of sustainability. We then apply principle component analysis and model-based clustering analysis to identify statistically the number of distinct dairy farm typologies for each year of study, and link these clusters through time using multidimensional scaling. Between 2001 and 2014, dairy farms have largely consolidated and specialized into two distinct clusters: more extensive farms relying predominantly on grass, with lower milk yields but higher labour intensity, and more intensive farms producing more milk per cow with more concentrate and more maize, but lower labour intensity. There is some indication that these clusters are converging as the extensive cluster is intensifying slightly faster than the intensive cluster, in terms of milk yield per cow and use of concentrate feed. In 2014, annual milk yields were 6,835 and 7,500 l/cow for extensive and intensive farm types, respectively, whilst annual concentrate feed use was 1.3 and 1.5 tonnes per cow. For several KPIs such as milk yield the mean trend across all farms differed substantially from the extensive and intensive typologies mean. The indicators and analysis methodology developed allows identification of distinct farm types and industry trends using readily available survey data. The identified groups allow the accurate evaluation of the consequences of the reduction in dairy farm numbers and intensification at national and international scales. PMID:29742166

  1. Walking-age analyzer for healthcare applications.

    PubMed

    Jin, Bo; Thu, Tran Hoai; Baek, Eunhye; Sakong, SungHwan; Xiao, Jin; Mondal, Tapas; Deen, M Jamal

    2014-05-01

    This paper describes a walking-age pattern analysis and identification system using a 3-D accelerometer and a gyroscope. First, a walking pattern database from 79 volunteers of ages ranging from 10 to 83 years is constructed. Second, using feature extraction and clustering, three distinct walking-age groups, children of ages 10 and below, adults in 20-60s, and elders in 70s and 80s, were identified. For this study, low-pass filtering, empirical mode decomposition, and K-means were used to process and analyze the experimental results. Analysis shows that volunteers' walking-ages can be categorized into distinct groups based on simple walking pattern signals. This grouping can then be used to detect persons with walking patterns outside their age groups. If the walking pattern puts an individual in a higher "walking age" grouping, then this could be an indicator of potential health/walking problems, such as weak joints, poor musculoskeletal support system or a tendency to fall.

  2. Perceived demands during modern military operations.

    PubMed

    Boermans, Sylvie M; Kamphuis, Wim; Kamhuis, Wim; Delahaij, Roos; Korteling, J E Hans; Euwema, Martin C

    2013-07-01

    Using a cross-sectional design, this study explored operational demands during the International Security Assistance Force for Afghanistan (2009-2010) across distinct military units. A total of 1,413 Dutch soldiers, nested within four types of units (i.e., combat, combat support, service support, and command support units) filled out a 23-item self-survey in which they were asked to evaluate the extent to which they experienced operational characteristics as demanding. Exploratory factor analysis identified six underlying dimensions of demands. Multivariate analysis of variance revealed that distinct units are characterized by their own unique constellation of perceived demands, even after controlling for previous deployment experience. Most notable findings were found when comparing combat units to other types of units. These insights can be used to better prepare different types of military units for deployment, and support them in the specific demands they face during deployment. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

  3. New arrows in the quiver for targeting care management: high-risk versus high-opportunity case identification.

    PubMed

    Bernstein, Richard H

    2007-01-01

    "Care management" purposefully obscures the distinctions between disease and case management and stresses their common features: action in the present to prevent adverse future outcomes and costs. It includes identifying a high-need population by referrals, screening, or data analysis, assessing those likely to benefit from interventions, intervening, evaluating the intervention, and adjusting interventions when needed. High-risk individuals can be identified using at least 9 techniques, from referrals and questionnaires to retrospective claims analysis and predictive models. Other than referrals, software based on the risk-adjustment methodology that we have adapted can incorporate all these methodologies. Because the risk adjustment employs extensive case mix and severity adjustment, it provides care managers with 3 innovative ways to identify not only high-risk individuals but also high-opportunity cases.

  4. Multiscale Feature Analysis of Salivary Gland Branching Morphogenesis

    PubMed Central

    Baydil, Banu; Daley, William P.; Larsen, Melinda; Yener, Bülent

    2012-01-01

    Pattern formation in developing tissues involves dynamic spatio-temporal changes in cellular organization and subsequent evolution of functional adult structures. Branching morphogenesis is a developmental mechanism by which patterns are generated in many developing organs, which is controlled by underlying molecular pathways. Understanding the relationship between molecular signaling, cellular behavior and resulting morphological change requires quantification and categorization of the cellular behavior. In this study, tissue-level and cellular changes in developing salivary gland in response to disruption of ROCK-mediated signaling by are modeled by building cell-graphs to compute mathematical features capturing structural properties at multiple scales. These features were used to generate multiscale cell-graph signatures of untreated and ROCK signaling disrupted salivary gland organ explants. From confocal images of mouse submandibular salivary gland organ explants in which epithelial and mesenchymal nuclei were marked, a multiscale feature set capturing global structural properties, local structural properties, spectral, and morphological properties of the tissues was derived. Six feature selection algorithms and multiway modeling of the data was performed to identify distinct subsets of cell graph features that can uniquely classify and differentiate between different cell populations. Multiscale cell-graph analysis was most effective in classification of the tissue state. Cellular and tissue organization, as defined by a multiscale subset of cell-graph features, are both quantitatively distinct in epithelial and mesenchymal cell types both in the presence and absence of ROCK inhibitors. Whereas tensor analysis demonstrate that epithelial tissue was affected the most by inhibition of ROCK signaling, significant multiscale changes in mesenchymal tissue organization were identified with this analysis that were not identified in previous biological studies. We here show how to define and calculate a multiscale feature set as an effective computational approach to identify and quantify changes at multiple biological scales and to distinguish between different states in developing tissues. PMID:22403724

  5. A Comparative Analysis of Industrial Escherichia coli K–12 and B Strains in High-Glucose Batch Cultivations on Process-, Transcriptome- and Proteome Level

    PubMed Central

    Marisch, Karoline; Bayer, Karl; Scharl, Theresa; Mairhofer, Juergen; Krempl, Peter M.; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Striedner, Gerald

    2013-01-01

    Escherichia coli K–12 and B strains are among the most frequently used bacterial hosts for production of recombinant proteins on an industrial scale. To improve existing processes and to accelerate bioprocess development, we performed a detailed host analysis. We investigated the different behaviors of the E. coli production strains BL21, RV308, and HMS174 in response to high-glucose concentrations. Tightly controlled cultivations were conducted under defined environmental conditions for the in-depth analysis of physiological behavior. In addition to acquisition of standard process parameters, we also used DNA microarray analysis and differential gel electrophoresis (EttanTM DIGE). Batch cultivations showed different yields of the distinct strains for cell dry mass and growth rate, which were highest for BL21. In addition, production of acetate, triggered by excess glucose supply, was much higher for the K–12 strains compared to the B strain. Analysis of transcriptome data showed significant alteration in 347 of 3882 genes common among all three hosts. These differentially expressed genes included, for example, those involved in transport, iron acquisition, and motility. The investigation of proteome patterns additionally revealed a high number of differentially expressed proteins among the investigated hosts. The subsequently selected 38 spots included proteins involved in transport and motility. The results of this comprehensive analysis delivered a full genomic picture of the three investigated strains. Differentially expressed groups for targeted host modification were identified like glucose transport or iron acquisition, enabling potential optimization of strains to improve yield and process quality. Dissimilar growth profiles of the strains confirm different genotypes. Furthermore, distinct transcriptome patterns support differential regulation at the genome level. The identified proteins showed high agreement with the transcriptome data and suggest similar regulation within a host at both levels for the identified groups. Such host attributes need to be considered in future process design and operation. PMID:23950949

  6. A comparative analysis of industrial Escherichia coli K-12 and B strains in high-glucose batch cultivations on process-, transcriptome- and proteome level.

    PubMed

    Marisch, Karoline; Bayer, Karl; Scharl, Theresa; Mairhofer, Juergen; Krempl, Peter M; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Striedner, Gerald

    2013-01-01

    Escherichia coli K-12 and B strains are among the most frequently used bacterial hosts for production of recombinant proteins on an industrial scale. To improve existing processes and to accelerate bioprocess development, we performed a detailed host analysis. We investigated the different behaviors of the E. coli production strains BL21, RV308, and HMS174 in response to high-glucose concentrations. Tightly controlled cultivations were conducted under defined environmental conditions for the in-depth analysis of physiological behavior. In addition to acquisition of standard process parameters, we also used DNA microarray analysis and differential gel electrophoresis (Ettan(TM) DIGE). Batch cultivations showed different yields of the distinct strains for cell dry mass and growth rate, which were highest for BL21. In addition, production of acetate, triggered by excess glucose supply, was much higher for the K-12 strains compared to the B strain. Analysis of transcriptome data showed significant alteration in 347 of 3882 genes common among all three hosts. These differentially expressed genes included, for example, those involved in transport, iron acquisition, and motility. The investigation of proteome patterns additionally revealed a high number of differentially expressed proteins among the investigated hosts. The subsequently selected 38 spots included proteins involved in transport and motility. The results of this comprehensive analysis delivered a full genomic picture of the three investigated strains. Differentially expressed groups for targeted host modification were identified like glucose transport or iron acquisition, enabling potential optimization of strains to improve yield and process quality. Dissimilar growth profiles of the strains confirm different genotypes. Furthermore, distinct transcriptome patterns support differential regulation at the genome level. The identified proteins showed high agreement with the transcriptome data and suggest similar regulation within a host at both levels for the identified groups. Such host attributes need to be considered in future process design and operation.

  7. Host switch during evolution of a genetically distinct hantavirus in the American shrew mole (Neurotrichus gibbsii)

    PubMed Central

    Kang, Hae Ji; Bennett, Shannon N.; Dizney, Laurie; Sumibcay, Laarni; Arai, Satoru; Ruedas, Luis A.; Song, Jin-Won; Yanagihara, Richard

    2009-01-01

    A genetically distinct hantavirus, designated Oxbow virus (OXBV), was detected in tissues of an American shrew mole (Neurotrichus gibbsii), captured in Gresham, Oregon, in September 2003. Pairwise analysis of full-length S- and M- and partial L-segment nucleotide and amino acid sequences of OXBV indicated low sequence similarity with rodent-borne hantaviruses. Phylogenetic analyses using maximum-likelihood and Bayesian methods, and host-parasite evolutionary comparisons, showed that OXBV and Asama virus, a hantavirus recently identified from the Japanese shrew mole (Urotrichus talpoides), were related to soricine shrew-borne hantaviruses from North America and Eurasia, respectively, suggesting parallel evolution associated with cross-species transmission. PMID:19394994

  8. Simulation of the recharge area for Frederick Springs, Dane County, Wisconsin

    USGS Publications Warehouse

    Hunt, R.J.; Steuer, J.J.

    2000-01-01

    Analysis of samples from the springs and a nearby municipal well identified large contrasts in chemistry, even for springs within 50 feet of one another. The differences were stable over time, were present in both ion and isotope analyses, and showed a distinct gradation from high nitrate, high calcium, Ordovician-carbonate dominated water in western spring vents to low nitrate, lower calcium, Cambrian-sandstone influenced water in eastern spring vents. The difference in chemistry was attributed to distinctive bedrock geology as demonstrated by overlaying the 50 percent probability capture zone over a bedrock geology map for the area. This finding gives additional confidence to the capture zone calculated by the ground-water flow model.

  9. Biochemical and Structural Analysis of an Eis Family Aminoglycoside Acetyltransferase from Bacillus anthracis

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

    Green, Keith D.; Biswas, Tapan; Chang, Changsoo

    Proteins from the enhanced intracellular survival (Eis) family are versatile acetyltransferases that acetylate amines at multiple positions of several aminoglycosides (AGs). Their upregulation confers drug resistance. Homologues of Eis are present in diverse bacteria, including many pathogens. Eis from Mycobacterium tuberculosis (Eis_Mtb) has been well characterized. In this study, we explored the AG specificity and catalytic efficiency of the Eis family protein from Bacillus anthracis (Eis_Ban). Kinetic analysis of specificity and catalytic efficiency of acetylation of six AGs indicates that Eis_Ban displays significant differences from Eis_Mtb in both substrate binding and catalytic efficiency. The number of acetylated amines was alsomore » different for several AGs, indicating a distinct regiospecificity of Eis_Ban. Furthermore, most recently identified inhibitors of Eis_Mtb did not inhibit Eis_Ban, underscoring the differences between these two enzymes. To explain these differences, we determined an Eis_Ban crystal structure. The comparison of the crystal structures of Eis_Ban and Eis_Mtb demonstrates that critical residues lining their respective substrate binding pockets differ substantially, explaining their distinct specificities. Our results suggest that acetyltransferases of the Eis family evolved divergently to garner distinct specificities while conserving catalytic efficiency, possibly to counter distinct chemical challenges. The unique specificity features of these enzymes can be utilized as tools for developing AGs with novel modifications and help guide specific AG treatments to avoid Eis-mediated resistance.« less

  10. Pattern of calbindin-D28k and calretinin immunoreactivity in the brain of Xenopus laevis during embryonic and larval development.

    PubMed

    Morona, Ruth; González, Agustín

    2013-01-01

    The present study represents a detailed spatiotemporal analysis of the localization of calbindin-D28k (CB) and calretinin (CR) immunoreactive structures in the brain of Xenopus laevis throughout development, conducted with the aim to correlate the onset of the immunoreactivity with the development of compartmentalization of distinct subdivisions recently identified in the brain of adult amphibians and primarily highlighted when analyzed within a segmental paradigm. CR and CB are expressed early in the brain and showed a progressively increasing expression throughout development, although transient expression in some neuronal subpopulations was also noted. Common and distinct characteristics in Xenopus, as compared with reported features during development in the brain of mammals, were observed. The development of specific regions in the forebrain such as the olfactory bulbs, the components of the basal ganglia and the amygdaloid complex, the alar and basal hypothalamic regions, and the distinct diencephalic neuromeres could be analyzed on the basis of the distinct expression of CB and CR in subregions. Similarly, the compartments of the mesencephalon and the main rhombencephalic regions, including the cerebellum, were differently highlighted by their specific content in CB and CR throughout development. Our results show the usefulness of the analysis of the distribution of these proteins as a tool in neuroanatomy to interpret developmental aspects of many brain regions. Copyright © 2012 Wiley Periodicals, Inc.

  11. Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma.

    PubMed

    Jusakul, Apinya; Cutcutache, Ioana; Yong, Chern Han; Lim, Jing Quan; Huang, Mi Ni; Padmanabhan, Nisha; Nellore, Vishwa; Kongpetch, Sarinya; Ng, Alvin Wei Tian; Ng, Ley Moy; Choo, Su Pin; Myint, Swe Swe; Thanan, Raynoo; Nagarajan, Sanjanaa; Lim, Weng Khong; Ng, Cedric Chuan Young; Boot, Arnoud; Liu, Mo; Ong, Choon Kiat; Rajasegaran, Vikneswari; Lie, Stefanus; Lim, Alvin Soon Tiong; Lim, Tse Hui; Tan, Jing; Loh, Jia Liang; McPherson, John R; Khuntikeo, Narong; Bhudhisawasdi, Vajaraphongsa; Yongvanit, Puangrat; Wongkham, Sopit; Totoki, Yasushi; Nakamura, Hiromi; Arai, Yasuhito; Yamasaki, Satoshi; Chow, Pierce Kah-Hoe; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Dima, Simona; Duda, Dan G; Popescu, Irinel; Broet, Philippe; Hsieh, Sen-Yung; Yu, Ming-Chin; Scarpa, Aldo; Lai, Jiaming; Luo, Di-Xian; Carvalho, André Lopes; Vettore, André Luiz; Rhee, Hyungjin; Park, Young Nyun; Alexandrov, Ludmil B; Gordân, Raluca; Rozen, Steven G; Shibata, Tatsuhiro; Pairojkul, Chawalit; Teh, Bin Tean; Tan, Patrick

    2017-10-01

    Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1 / PD-L2 expression, or epigenetic mutations ( IDH1/2, BAP1 ) and FGFR / PRKA -related gene rearrangements. Whole-genome analysis highlighted FGFR2 3' untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores-mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer. Significance: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes. Cancer Discov; 7(10); 1116-35. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1047 . ©2017 American Association for Cancer Research.

  12. Heteroduplex analysis can increase the informativeness of PCR-amplified VNTR markers: Application using a marker tightly linked to the COL2A1 gene

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

    Wilkin, D.J.; Cohn, D.H.; Koprivnikar, K.E.

    1993-02-01

    Variable number of tandem repeat (VNTR) polymorphism provide a high degree of informativeness in linkage studies. Whether performed by standard methods or by polymerase chain reaction (PCR), analysis of these markers involves assessment of the length of each allele. VNTR alleles usually differ in the number of tandem repeats. During PCR amplification of a VNTR closely linked to the type II collagen gene (COL2A1), we identified allelic microheterogeneity through the analysis of unique heteroduplexes between amplified strands of the two alleles. In one large pedigree, heteroduplex analysis identified only three distinct alleles. The identification of these heteroduplexes allowed the determinationmore » of the COL2A1 inheritance pattern in the family, which otherwise would have been noninformative. 26 refs., 3 figs.« less

  13. Co-circulation of genetically distinct human metapneumovirus and human bocavirus strains in young children with respiratory tract infections in Italy.

    PubMed

    Zappa, Alessandra; Canuti, Marta; Frati, Elena; Pariani, Elena; Perin, Silvana; Ruzza, Maria Lorena; Farina, Claudio; Podestà, Alberto; Zanetti, Alessandro; Amendola, Antonella; Tanzi, Elisabetta

    2011-01-01

    The discovery of human Metapneumovirus (hMPV) and human Bocavirus (hBoV) identified the etiological causes of several cases of acute respiratory tract infections in children. This report describes the molecular epidemiology of hMPV and hBoV infections observed following viral surveillance of children hospitalized for acute respiratory tract infections in Milan, Italy. Pharyngeal swabs were collected from 240 children ≤3 years of age (130 males, 110 females; median age, 5.0 months; IQR, 2.0-12.5 months) and tested for respiratory viruses, including hMPV and hBoV, by molecular methods. hMPV-RNA and hBoV-DNA positive samples were characterized molecularly and a phylogenetical analysis was performed. PCR analysis identified 131/240 (54.6%) samples positive for at least one virus. The frequency of hMPV and hBoV infections was similar (8.3% and 12.1%, respectively). Both infections were associated with lower respiratory tract infections: hMPV was present as a single infectious agent in 7.2% of children with bronchiolitis, hBoV was associated with 18.5% of pediatric pneumonias and identified frequently as a single etiological agent. Genetically distinct hMPV and hBoV strains were identified in children examined with respiratory tract infections. Phylogenetic analysis showed an increased prevalence of hMPV genotype A (A2b sublineage) compared to genotype B (80% vs. 20%, respectively) and of the hBoV genotype St2 compared to genotype St1 (71.4% vs. 28.6%, respectively). Interestingly, a shift in hMPV infections resulting from A2 strains has been observed in recent years. In addition, the occurrence of recombination events between two hBoV strains with a breakpoint located in the VP1/VP2 region was identified. © 2010 Wiley-Liss, Inc.

  14. Meta-analysis identifies gene-by-environment interactions as demonstrated in a study of 4,965 mice.

    PubMed

    Kang, Eun Yong; Han, Buhm; Furlotte, Nicholas; Joo, Jong Wha J; Shih, Diana; Davis, Richard C; Lusis, Aldons J; Eskin, Eleazar

    2014-01-01

    Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study.

  15. Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice

    PubMed Central

    Joo, Jong Wha J.; Shih, Diana; Davis, Richard C.; Lusis, Aldons J.; Eskin, Eleazar

    2014-01-01

    Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study. PMID:24415945

  16. A Guideline to Family-Wide Comparative State-of-the-Art Quantitative RT-PCR Analysis Exemplified with a Brassicaceae Cross-Species Seed Germination Case Study[W][OA

    PubMed Central

    Graeber, Kai; Linkies, Ada; Wood, Andrew T.A.; Leubner-Metzger, Gerhard

    2011-01-01

    Comparative biology includes the comparison of transcriptome and quantitative real-time RT-PCR (qRT-PCR) data sets in a range of species to detect evolutionarily conserved and divergent processes. Transcript abundance analysis of target genes by qRT-PCR requires a highly accurate and robust workflow. This includes reference genes with high expression stability (i.e., low intersample transcript abundance variation) for correct target gene normalization. Cross-species qRT-PCR for proper comparative transcript quantification requires reference genes suitable for different species. We addressed this issue using tissue-specific transcriptome data sets of germinating Lepidium sativum seeds to identify new candidate reference genes. We investigated their expression stability in germinating seeds of L. sativum and Arabidopsis thaliana by qRT-PCR, combined with in silico analysis of Arabidopsis and Brassica napus microarray data sets. This revealed that reference gene expression stability is higher for a given developmental process between distinct species than for distinct developmental processes within a given single species. The identified superior cross-species reference genes may be used for family-wide comparative qRT-PCR analysis of Brassicaceae seed germination. Furthermore, using germinating seeds, we exemplify optimization of the qRT-PCR workflow for challenging tissues regarding RNA quality, transcript stability, and tissue abundance. Our work therefore can serve as a guideline for moving beyond Arabidopsis by establishing high-quality cross-species qRT-PCR. PMID:21666000

  17. A discourse analysis of the construction of mental illness in two UK newspapers from 1985-2000.

    PubMed

    Paterson, Brodie

    2007-10-01

    This study explored the discourse of mental illness contained within two UK newspapers over a 15-year period, excluding those stories that mentioned any reference to a diagnosis. Using frame analysis, a form of discourse analysis, ten distinct frames were identified and classified into "stories." These ten stories were categorized as: foreign, legal, drug, feature, trauma, tragedy, community care tragedy, social policy, inquiry report, and sports/celebrity stories. Each frame is described and the potential influence of such frames on both social policy and nursing practice is discussed.

  18. Sleep quality subtypes and obesity.

    PubMed

    Magee, Christopher A; Reddy, Prasuna; Robinson, Laura; McGregor, Alisha

    2016-12-01

    Poor sleep quality could be a risk factor for obesity. This article utilized a person-centered approach to investigate whether distinct sleep quality subtypes were associated with obesity directly, and indirectly via physical activity. The sample included 8,932 Australian employees who participated in the Household, Income and Labor Dynamics in Australia Survey. Structured interviews and self-report questionnaires collected information on sleep quality, obesity, and relevant demographic, health, and work-related variables. Latent class analysis identified distinct subtypes of sleep quality. General linear modeling examined the associations of sleep quality subtypes with body mass index (BMI) and waist circumference. Multicategorical mediation models examined indirect paths linking sleep quality classes with obesity via physical activity. Five distinct sleep quality subtypes were identified: Poor Sleepers (20.0%), Frequent Sleep Disturbances (19.2%), Minor Sleep Disturbances (24.5%), Long Sleepers (9.6%), and Good Sleepers (26.7%). BMI, waist circumference, and physical activity differed among the sleep quality subtypes, with similar results observed for males and females. For example, Poor Sleepers had the highest BMIs, followed by Frequent Sleep Disturbances and Minor Sleep Disturbances; Long Sleepers and Good Sleepers had the lowest BMIs. Mediation analyses indicated that low levels of physical activity linked the Poor Sleep, Frequent Sleep Disturbance, and Long Sleep classes with higher BMI. These results provide new insights into the nature of sleep quality in employees. In particular, distinct sleep quality patterns had differing associations with measures of obesity, suggesting the need for tailored workplace interventions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  19. Taxonomic distinctness and richness of helminth parasite assemblages of freshwater fishes in Mexican hydrological basins.

    PubMed

    Quiroz-Martínez, Benjamín; Salgado-Maldonado, Guillermo

    2013-01-01

    In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes with respect to the main hydrological basins of Mexico. We use the taxonomic distinctness and the variation in taxonomic distinctness to explore patterns of parasite diversity and how these patterns change between zoogeographical regions. We address questions about the factors that determine the variation of observed diversity of helminths between basins. We also investigate patterns of richness, taxonomic distinctness and distance decay of similarity amongst basins. Our analyses suggest that the evolution of the fauna of helminth parasites in Mexico is mostly dominated by independent host colonization events and that intra--host speciation could be a minor factor explaining the origin of this diversity. This paper points out a clear separation between the helminth faunas of northern--nearctic and southern--neotropical components in Mexican continental waters, suggesting the availability of two distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies Mexican drainage basins as unities inhabited by freshwater fishes, hosting a mixture of neotropical and nearctic species, in addition, data confirms neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico are host to a richest and more diversified helminth fauna, including more families, genera and species, compared to the less rich and less diverse helminth fauna in the nearctic basins. The present analysis confirms distance--decay as one of the important factors contributing to the patterns of diversity observed. The hypothesis that helminth diversity could be explained by the ichthyological diversity of the basin received no support from present analysis.

  20. Taxonomic Distinctness and Richness of Helminth Parasite Assemblages of Freshwater Fishes in Mexican Hydrological Basins

    PubMed Central

    Quiroz-Martínez, Benjamín; Salgado-Maldonado, Guillermo

    2013-01-01

    In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes with respect to the main hydrological basins of Mexico. We use the taxonomic distinctness and the variation in taxonomic distinctness to explore patterns of parasite diversity and how these patterns change between zoogeographical regions. We address questions about the factors that determine the variation of observed diversity of helminths between basins. We also investigate patterns of richness, taxonomic distinctness and distance decay of similarity amongst basins. Our analyses suggest that the evolution of the fauna of helminth parasites in Mexico is mostly dominated by independent host colonization events and that intra - host speciation could be a minor factor explaining the origin of this diversity. This paper points out a clear separation between the helminth faunas of northern - nearctic and southern - neotropical components in Mexican continental waters, suggesting the availability of two distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies Mexican drainage basins as unities inhabited by freshwater fishes, hosting a mixture of neotropical and nearctic species, in addition, data confirms neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico are host to a richest and more diversified helminth fauna, including more families, genera and species, compared to the less rich and less diverse helminth fauna in the nearctic basins. The present analysis confirms distance - decay as one of the important factors contributing to the patterns of diversity observed. The hypothesis that helminth diversity could be explained by the ichthyological diversity of the basin received no support from present analysis. PMID:24086342

  1. Principal component analysis and analysis of variance on the effects of Entellan New on the Raman spectra of fibers.

    PubMed

    Yu, Marcia M L; Sandercock, P Mark L

    2012-01-01

    During the forensic examination of textile fibers, fibers are usually mounted on glass slides for visual inspection and identification under the microscope. One method that has the capability to accurately identify single textile fibers without subsequent demounting is Raman microspectroscopy. The effect of the mountant Entellan New on the Raman spectra of fibers was investigated to determine if it is suitable for fiber analysis. Raman spectra of synthetic fibers mounted in three different ways were collected and subjected to multivariate analysis. Principal component analysis score plots revealed that while spectra from different fiber classes formed distinct groups, fibers of the same class formed a single group regardless of the mounting method. The spectra of bare fibers and those mounted in Entellan New were found to be statistically indistinguishable by analysis of variance calculations. These results demonstrate that fibers mounted in Entellan New may be identified directly by Raman microspectroscopy without further sample preparation. © 2011 American Academy of Forensic Sciences.

  2. Molecular complexity of successive bacterial epidemics deconvoluted by comparative pathogenomics.

    PubMed

    Beres, Stephen B; Carroll, Ronan K; Shea, Patrick R; Sitkiewicz, Izabela; Martinez-Gutierrez, Juan Carlos; Low, Donald E; McGeer, Allison; Willey, Barbara M; Green, Karen; Tyrrell, Gregory J; Goldman, Thomas D; Feldgarden, Michael; Birren, Bruce W; Fofanov, Yuriy; Boos, John; Wheaton, William D; Honisch, Christiane; Musser, James M

    2010-03-02

    Understanding the fine-structure molecular architecture of bacterial epidemics has been a long-sought goal of infectious disease research. We used short-read-length DNA sequencing coupled with mass spectroscopy analysis of SNPs to study the molecular pathogenomics of three successive epidemics of invasive infections involving 344 serotype M3 group A Streptococcus in Ontario, Canada. Sequencing the genome of 95 strains from the three epidemics, coupled with analysis of 280 biallelic SNPs in all 344 strains, revealed an unexpectedly complex population structure composed of a dynamic mixture of distinct clonally related complexes. We discovered that each epidemic is dominated by micro- and macrobursts of multiple emergent clones, some with distinct strain genotype-patient phenotype relationships. On average, strains were differentiated from one another by only 49 SNPs and 11 insertion-deletion events (indels) in the core genome. Ten percent of SNPs are strain specific; that is, each strain has a unique genome sequence. We identified nonrandom temporal-spatial patterns of strain distribution within and between the epidemic peaks. The extensive full-genome data permitted us to identify genes with significantly increased rates of nonsynonymous (amino acid-altering) nucleotide polymorphisms, thereby providing clues about selective forces operative in the host. Comparative expression microarray analysis revealed that closely related strains differentiated by seemingly modest genetic changes can have significantly divergent transcriptomes. We conclude that enhanced understanding of bacterial epidemics requires a deep-sequencing, geographically centric, comparative pathogenomics strategy.

  3. Is there Complex Trauma Experience typology for Australian's experiencing extreme social disadvantage and low housing stability?

    PubMed

    Keane, Carol A; Magee, Christopher A; Kelly, Peter J

    2016-11-01

    Traumatic childhood experiences predict many adverse outcomes in adulthood including Complex-PTSD. Understanding complex trauma within socially disadvantaged populations has important implications for policy development and intervention implementation. This paper examined the nature of complex trauma experienced by disadvantaged individuals using a latent class analysis (LCA) approach. Data were collected through the large-scale Journeys Home Study (N=1682), utilising a representative sample of individuals experiencing low housing stability. Data on adverse childhood experiences, adulthood interpersonal trauma and relevant covariates were collected through interviews at baseline (Wave 1). Latent class analysis (LCA) was conducted to identify distinct classes of childhood trauma history, which included physical assault, neglect, and sexual abuse. Multinomial logistic regression investigated childhood relevant factors associated with class membership such as biological relationship of primary carer at age 14 years and number of times in foster care. Of the total sample (N=1682), 99% reported traumatic adverse childhood experiences. The most common included witnessing of violence, threat/experience of physical abuse, and sexual assault. LCA identified six distinct childhood trauma history classes including high violence and multiple traumas. Significant covariate differences between classes included: gender, biological relationship of primary carer at age 14 years, and time in foster care. Identification of six distinct childhood trauma history profiles suggests there might be unique treatment implications for individuals living in extreme social disadvantage. Further research is required to examine the relationship between these classes of experience, consequent impact on adulthood engagement, and future transitions though homelessness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of Patients with Severe Asthma.

    PubMed

    Konno, Satoshi; Taniguchi, Natsuko; Makita, Hironi; Nakamaru, Yuji; Shimizu, Kaoruko; Shijubo, Noriharu; Fuke, Satoshi; Takeyabu, Kimihiro; Oguri, Mitsuru; Kimura, Hirokazu; Maeda, Yukiko; Suzuki, Masaru; Nagai, Katsura; Ito, Yoichi M; Wenzel, Sally E; Nishimura, Masaharu

    2015-12-01

    Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).

  5. Estimating connectivity in marine populations: an empirical evaluation of assignment tests and parentage analysis under different gene flow scenarios.

    PubMed

    Saenz-Agudelo, P; Jones, G P; Thorrold, S R; Planes, S

    2009-04-01

    The application of spatially explicit models of population dynamics to fisheries management and the design marine reserve network systems has been limited due to a lack of empirical estimates of larval dispersal. Here we compared assignment tests and parentage analysis for examining larval retention and connectivity under two different gene flow scenarios using panda clownfish (Amphiprion polymnus) in Papua New Guinea. A metapopulation of panda clownfish in Bootless Bay with little or no genetic differentiation among five spatially discrete locations separated by 2-6 km provided the high gene flow scenario. The low gene flow scenario compared the Bootless Bay metapopulation with a genetically distinct population (F(ST )= 0.1) located at Schumann Island, New Britain, 1500 km to the northeast. We used assignment tests and parentage analysis based on microsatellite DNA data to identify natal origins of 177 juveniles in Bootless Bay and 73 juveniles at Schumann Island. At low rates of gene flow, assignment tests correctly classified juveniles to their source population. On the other hand, parentage analysis led to an overestimate of self-recruitment within the two populations due to the significant deviation from panmixia when both populations were pooled. At high gene flow (within Bootless Bay), assignment tests underestimated self-recruitment and connectivity among subpopulations, and grossly overestimated self-recruitment within the overall metapopulation. However, the assignment tests did identify immigrants from distant (genetically distinct) populations. Parentage analysis clearly provided the most accurate estimates of connectivity in situations of high gene flow.

  6. Towards a typology of business process management professionals: identifying patterns of competences through latent semantic analysis

    NASA Astrophysics Data System (ADS)

    Müller, Oliver; Schmiedel, Theresa; Gorbacheva, Elena; vom Brocke, Jan

    2016-01-01

    While researchers have analysed the organisational competences that are required for successful Business Process Management (BPM) initiatives, individual BPM competences have not yet been studied in detail. In this study, latent semantic analysis is used to examine a collection of 1507 BPM-related job advertisements in order to develop a typology of BPM professionals. This empirical analysis reveals distinct ideal types and profiles of BPM professionals on several levels of abstraction. A closer look at these ideal types and profiles confirms that BPM is a boundary-spanning field that requires interdisciplinary sets of competence that range from technical competences to business and systems competences. Based on the study's findings, it is posited that individual and organisational alignment with the identified ideal types and profiles is likely to result in high employability and organisational BPM success.

  7. Investigating incidents of EHR failures in China: analysis of search engine reports.

    PubMed

    Lei, Jianbo; Guan, Pengcheng; Gao, Kaihua; Lu, Xueqing; Sittig, Dean

    2013-01-01

    As the healthcare industry becomes increasingly dependent on information technology (IT), the failure of computerized systems could cause catastrophic effects on patient safety. We conducted an empirical study to analyze news articles available on the internet using Baidu and Google. 116 distinct EHR outage news reports were identified. We examined characteristics, potential causes, and possible preventive strategies. Risk management strategies based are discussed.

  8. Identifying Solution Paths in Cognitive Diagnosis.

    DTIC Science & Technology

    1985-03-01

    the clinical tradi- tion. Psychoanalysis gets its distinctive flavor to a large extent from the various diagnostic techniques pioneered by Freud and...his disciples: free association, dream analysis, and pro- jective tests. These methods are content-oriented, and aim at a detailed description of the...Also, Psychoanalysis shares with Test Psychology the ambition to find out about stable properties of the individual, properties of his mental life

  9. A Discriminant Analysis of Majors in the College Business and Public Administration at the University of North Dakota. North Dakota Economics Studies, Number 52.

    ERIC Educational Resources Information Center

    Tedefalk, Rolf K.

    Researchers have demonstrated that particular careers attract individuals with distinct identifiable personality profiles and learning styles, and this idea is extended to the selection of majors within the College of Business and Public Administration (BPA) at the University of North Dakota. The Myers-Briggs Type Indicator (MBTI) was used both to…

  10. Trajectories of Diurnal Cortisol in Mothers of Children with Autism and Other Developmental Disabilities: Relations to Health and Mental Health

    ERIC Educational Resources Information Center

    Dykens, Elisabeth M.; Lambert, Warren

    2013-01-01

    This study used a stress biomarker, diurnal cortisol, to identify how elevated stress in mothers of children and adults with autism and other disabilities relates to their health and mental health. Based on semi-parametric, group-based trajectory analysis of 91 mothers, two distinctive cortisol trajectories emerged: blunted (63%) or steep (37%).…

  11. Public access to New Hampshire state waters: a comparison of three cohorts of residents across three distinct geographic

    Treesearch

    Kim Pawlawski; Robert A. Robertson; Laura Pfister

    2003-01-01

    This study was intended to provide New Hampshire agencies with a better understanding of public access-related demand information. Through an analysis of three groups of New Hampshire residents based upon geographic location and length of residency, important issues and attitudes were identified from all over the State. The results of this study will assist in policy-...

  12. Parental Perceptions of the Outcome and Meaning of Normalization

    PubMed Central

    Knafl, Kathleen A.; Darney, Blair G.; Gallo, Agatha M.; Angst, Denise B.

    2010-01-01

    The purpose of this secondary analysis was to identify the meaning of normalization for parents of a child with a chronic genetic condition. The sample was comprised of 28 families (48 parents), selected to reflect two groups: Normalization Present (NP) and Normalization Absent (NA). Constant comparison analysis was used to identify themes characterizing parents' perceptions of the meaning of normalization. The meanings parents attributed to normalization reflected their evaluation of condition management, parenting role, and condition impact, with parents in the NP and NA groups demonstrating distinct patterns of meaning. These meaning patterns are discussed as an outcome of normalization. Providers can play a pivotal role in helping families achieve normalization by providing guidance on how to balance condition management with normal family life. PMID:20108258

  13. Coats' disease and congenital retinoschisis in a single eye: a case report and DNA analysis.

    PubMed

    Berinstein, D M; Hiraoka, M; Trese, M T; Shastry, B S

    2001-01-01

    The clinical features of Coats' disease and congenital retinoschisis (RS) are distinctly different. Therefore, finding changes consistent with Coats' disease and congenital RS in a single eye is an unusual occurrence. The following report describes two cases with a Coats' telangiectatic lesion in one region of the retina separated by normal retina and the presence of central and peripheral congenital RS. Molecular genetic analysis of the Norrie disease and RS genes failed to identify disease-causing or polymorphic mutations in either of the genes, suggesting that the above condition is clinically and genetically a different disorder. Further studies are needed to identify the genes responsible for the above disorder and associated ocular manifestations. Copyright 2001 S. Karger AG, Basel.

  14. The Role of Religiousness/Spirituality in Health-Related Quality of Life Among Adolescents with HIV: A Latent Profile Analysis

    PubMed Central

    Kimmel, Allison L.; Cheng, Yao Iris; Wang, Jichuan

    2016-01-01

    The purpose of this study was to determine whether distinct latent profiles of religiousness/spirituality exist for ALWH, and if so, are latent profile memberships associated with health-related quality of life (HRQoL). Latent profile analysis of religiosity identified four profiles/groups. Compared to the other three groups, higher levels of emotional well-being were found among young perinatally infected adolescents who attended religious services, but who did not pray privately, feel God's presence or identify as religious or spiritual. Social HRQoL was significantly higher among the highest overall religious/spiritual group. Understanding adolescent profiles of religiousness/spirituality on HRQoL could inform faith-based interventions. PMID:27071797

  15. The Role of Religiousness/Spirituality in Health-Related Quality of Life Among Adolescents with HIV: A Latent Profile Analysis.

    PubMed

    Lyon, Maureen E; Kimmel, Allison L; Cheng, Yao Iris; Wang, Jichuan

    2016-10-01

    The purpose of this study was to determine whether distinct latent profiles of religiousness/spirituality exist for ALWH, and if so, are latent profile memberships associated with health-related quality of life (HRQoL). Latent profile analysis of religiosity identified four profiles/groups. Compared to the other three groups, higher levels of emotional well-being were found among young perinatally infected adolescents who attended religious services, but who did not pray privately, feel God's presence or identify as religious or spiritual. Social HRQoL was significantly higher among the highest overall religious/spiritual group. Understanding adolescent profiles of religiousness/spirituality on HRQoL could inform faith-based interventions. Trial registration NCT01289444.

  16. 76 FR 25590 - Endangered and Threatened Wildlife and Plants; Reissuance of Final Rule To Identify the Northern...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-05

    ...; Reissuance of Final Rule To Identify the Northern Rocky Mountain Population of Gray Wolf as a Distinct..., that identified the Northern Rocky Mountain population of gray wolf (Canis lupus) as a distinct... gray wolves in the DPS. This rule complies with that directive. DATES: This action is effective May 5...

  17. A Comprehensive Analysis of RALF Proteins in Green Plants Suggests There Are Two Distinct Functional Groups

    PubMed Central

    Campbell, Liam; Turner, Simon R.

    2017-01-01

    Rapid Alkalinization Factors (RALFs) are small, cysteine-rich peptides known to be involved in various aspects of plant development and growth. Although RALF peptides have been identified within many species, a single wide-ranging phylogenetic analysis of the family across the plant kingdom has not yet been undertaken. Here, we identified RALF proteins from 51 plant species that represent a variety of land plant lineages. The inferred evolutionary history of the 795 identified RALFs suggests that the family has diverged into four major clades. We found that much of the variation across the family exists within the mature peptide region, suggesting clade-specific functional diversification. Clades I, II, and III contain the features that have been identified as important for RALF activity, including the RRXL cleavage site and the YISY motif required for receptor binding. In contrast, members of clades IV that represent a third of the total dataset, is highly diverged and lacks these features that are typical of RALFs. Members of clade IV also exhibit distinct expression patterns and physico-chemical properties. These differences suggest a functional divergence of clades and consequently, we propose that the peptides within clade IV are not true RALFs, but are more accurately described as RALF-related peptides. Expansion of this RALF–related clade in the Brassicaceae is responsible for the large number of RALF genes that have been previously described in Arabidopsis thaliana. Future experimental work will help to establish the nature of the relationship between the true RALFs and the RALF-related peptides, and whether they function in a similar manner. PMID:28174582

  18. Remote sensor digital image data analysis using the General Electric Image 100 analysis system (a study of analysis speed, cost, and performance)

    NASA Technical Reports Server (NTRS)

    Mcmurtry, G. J.; Petersen, G. W. (Principal Investigator)

    1975-01-01

    The author has identified the following significant results. It was found that the high speed man machine interaction capability is a distinct advantage of the image 100; however, the small size of the digital computer in the system is a definite limitation. The system can be highly useful in an analysis mode in which it complements a large general purpose computer. The image 100 was found to be extremely valuable in the analysis of aircraft MSS data where the spatial resolution begins to approach photographic quality and the analyst can exercise interpretation judgements and readily interact with the machine.

  19. Ants regulate colony spatial organization using multiple chemical road-signs

    PubMed Central

    Heyman, Yael; Shental, Noam; Brandis, Alexander; Hefetz, Abraham; Feinerman, Ofer

    2017-01-01

    Communication provides the basis for social life. In ant colonies, the prevalence of local, often chemically mediated, interactions introduces strong links between communication networks and the spatial distribution of ants. It is, however, unknown how ants identify and maintain nest chambers with distinct functions. Here, we combine individual tracking, chemical analysis and machine learning to decipher the chemical signatures present on multiple nest surfaces. We present evidence for several distinct chemical ‘road-signs' that guide the ants' movements within the dark nest. These chemical signatures can be used to classify nest chambers with different functional roles. Using behavioural manipulations, we demonstrate that at least three of these chemical signatures are functionally meaningful and allow ants from different task groups to identify their specific nest destinations, thus facilitating colony coordination and stabilization. The use of multiple chemicals that assist spatiotemporal guidance, segregation and pattern formation is abundant in multi-cellular organisms. Here, we provide a rare example for the use of these principles in the ant colony. PMID:28569746

  20. Molecular Epidemiological Analysis of Dengue Fever in Bolivia from 1998 to 2008

    PubMed Central

    Roca, Yelin; Baronti, Cécile; Revollo, Roberto Jimmy; Cook, Shelley; Loayza, Roxana; Ninove, Laetitia; Fernandez, Roberto Torrez; Flores, Jorge Vargas; Herve, Jean-Pierre; de Lamballerie, Xavier

    2012-01-01

    Dengue fever was first recognized in Bolivia in 1931. However, very limited information was available to date regarding the genetic characterization and epidemiology of Bolivian dengue virus strains. Here, we performed genetic characterization of the full-length envelope gene of 64 Bolivian isolates from 1998 to 2008 and investigated their origin and evolution to determine whether strains circulated simultaneously or alternatively, and whether or not multiple introductions of distinct viral variants had occurred during the period studied. We determined that, during the last decade, closely related viruses circulated during several consecutive years (5, 6, and 6 years for DENV-1, DENV-2, and DENV-3, respectively) and the co-circulation of two or even three serotypes was observed. Emergence of new variants (distinct from those identified during the previous episodes) was identified in the case of DENV-1 (2007 outbreak) and DENV-2 (2001 outbreak). In all cases, it is likely that the viruses originated from neighboring countries. PMID:19505253

  1. Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity.

    PubMed

    Nguyen, Quy H; Pervolarakis, Nicholas; Blake, Kerrigan; Ma, Dennis; Davis, Ryan Tevia; James, Nathan; Phung, Anh T; Willey, Elizabeth; Kumar, Raj; Jabart, Eric; Driver, Ian; Rock, Jason; Goga, Andrei; Khan, Seema A; Lawson, Devon A; Werb, Zena; Kessenbrock, Kai

    2018-05-23

    Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we use single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone-responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produces one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides insights into the cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer.

  2. Ants regulate colony spatial organization using multiple chemical road-signs.

    PubMed

    Heyman, Yael; Shental, Noam; Brandis, Alexander; Hefetz, Abraham; Feinerman, Ofer

    2017-06-01

    Communication provides the basis for social life. In ant colonies, the prevalence of local, often chemically mediated, interactions introduces strong links between communication networks and the spatial distribution of ants. It is, however, unknown how ants identify and maintain nest chambers with distinct functions. Here, we combine individual tracking, chemical analysis and machine learning to decipher the chemical signatures present on multiple nest surfaces. We present evidence for several distinct chemical 'road-signs' that guide the ants' movements within the dark nest. These chemical signatures can be used to classify nest chambers with different functional roles. Using behavioural manipulations, we demonstrate that at least three of these chemical signatures are functionally meaningful and allow ants from different task groups to identify their specific nest destinations, thus facilitating colony coordination and stabilization. The use of multiple chemicals that assist spatiotemporal guidance, segregation and pattern formation is abundant in multi-cellular organisms. Here, we provide a rare example for the use of these principles in the ant colony.

  3. Genome organization of Tobacco leaf curl Zimbabwe virus, a new, distinct monopartite begomovirus associated with subgenomic defective DNA molecules.

    PubMed

    Paximadis, M; Rey, M E

    2001-12-01

    The complete DNA A of the begomovirus Tobacco leaf curl Zimbabwe virus (TbLCZWV) was sequenced: it comprises 2767 nucleotides with six major open reading frames encoding proteins with molecular masses greater than 9 kDa. Full-length TbLCZWV DNA A tandem dimers, cloned in binary vectors (pBin19 and pBI121) and transformed into Agrobacterium tumefaciens, were systemically infectious upon agroinoculation of tobacco and tomato. Efforts to identify a DNA B component were unsuccessful. These findings suggest that TbLCZWV is a new member of the monopartite group of begomoviruses. Phylogenetic analysis identified TbLCZWV as a distinct begomovirus with its closest relative being Chayote mosaic virus. Abutting primer PCR amplified ca. 1300 bp molecules, and cloning and sequencing of two of these molecules revealed them to be subgenomic defective DNA molecules originating from TbLCZWV DNA A. Variable symptom severity associated with tobacco leaf curl disease and TbLCZWV is discussed.

  4. Distinction of broken cellular wall Ganoderma lucidum spores and G. lucidum spores using FTIR microspectroscopy

    NASA Astrophysics Data System (ADS)

    Chen, Xianliang; Liu, Xingcun; Sheng, Daping; Huang, Dake; Li, Weizu; Wang, Xin

    2012-11-01

    In this paper, FTIR microspectroscopy was used to identify broken cellular wall Ganoderma lucidum spores and G. lucidum spores. For IR spectra, broken cellular wall G. lucidum spores and G. lucidum spores were mainly different in the regions of 3000-2800, 1660-1600, 1400-1200 and 1100-1000 cm-1. For curve fitting, the results showed the differences in the protein secondary structures and the polysaccharide structures/content between broken cellular wall G. lucidum spores and G. lucidum spores. Moreover, the value of A1078/A1741 might be a potentially useful factor to distinguish broken cellular wall G. lucidum spores from G. lucidum spores. Additionally, FTIR microspectroscopy could identify broken cellular wall G. lucidum spores and G. lucidum spores accurately when it was combined with hierarchical cluster analysis. The result suggests FTIR microspectroscopy is very simple and efficient for distinction of broken cellular wall G. lucidum spores and G. lucidum spores. The result also indicates FTIR microspectroscopy may be useful for TCM identification.

  5. Patterns of productive activity engagement as a longitudinal predictor of depressive symptoms among older adults in urban China.

    PubMed

    Liu, Huiying; Lou, Vivian W Q

    2017-11-01

    Using two waves of panel data from the China Health and Retirement Longitudinal Study, this study prospectively assessed whether four distinct patterns of productive activity engagement would predict depressive symptoms among older adults in urban China two years later. A sample of urban residents aged 60 or above at Wave 1 and who were interviewed in both waves (N = 2398) was used. Latent class analysis (LCA) was conducted to identify distinct patterns of productive activity engagement that occurred within the Wave 1 data. Next, the generalized estimating equations were used to assess whether identified patterns predicted the levels of depressive symptoms measured at Wave 2. Our use of LCA confirmed the existence of four distinct patterns of productive activity engagement among the study sample: Informal Helper/Carer, Working-Caring Engager, Civic Contributor, and Low/Spousal Carer. All of these three patterns exhibited significantly lower levels of depressive symptoms than that of Low/Spousal Carer two years later. Our use of individual-based categorization of productive engagement better captured the reality of older adults performing various productive activities than summative scales of productive activities did and, therefore, provided a more valid clarification of differential well-being outcomes among older adults.

  6. Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity

    PubMed Central

    Walrad, Pegine B.; Hang, Saiyu; Joseph, Genevieve S.; Salas, Julia

    2010-01-01

    Runx proteins play vital roles in regulating transcription in numerous developmental pathways throughout the animal kingdom. Two Runx protein hallmarks are the DNA-binding Runt domain and a C-terminal VWRPY motif that mediates interaction with TLE/Gro corepressor proteins. A phylogenetic analysis of Runt, the founding Runx family member, identifies four distinct regions C-terminal to the Runt domain that are conserved in Drosophila and other insects. We used a series of previously described ectopic expression assays to investigate the functions of these different conserved regions in regulating gene expression during embryogenesis and in controlling axonal projections in the developing eye. The results indicate each conserved region is required for a different subset of activities and identify distinct regions that participate in the transcriptional activation and repression of the segmentation gene sloppy-paired-1 (slp1). Interestingly, the C-terminal VWRPY-containing region is not required for repression but instead plays a role in slp1 activation. Genetic experiments indicating that Groucho (Gro) does not participate in slp1 regulation further suggest that Runt's conserved C-terminus interacts with other factors to promote transcriptional activation. These results provide a foundation for further studies on the molecular interactions that contribute to the context-dependent properties of Runx proteins as developmental regulators. PMID:20462957

  7. Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis.

    PubMed

    Kale, Shiv D; Ayubi, Tariq; Chung, Dawoon; Tubau-Juni, Nuria; Leber, Andrew; Dang, Ha X; Karyala, Saikumar; Hontecillas, Raquel; Lawrence, Christopher B; Cramer, Robert A; Bassaganya-Riera, Josep

    2017-12-06

    Incidences of invasive pulmonary aspergillosis, an infection caused predominantly by Aspergillus fumigatus, have increased due to the growing number of immunocompromised individuals. While A. fumigatus is reliant upon deficiencies in the host to facilitate invasive disease, the distinct mechanisms that govern the host-pathogen interaction remain enigmatic, particularly in the context of distinct immune modulating therapies. To gain insights into these mechanisms, RNA-Seq technology was utilized to sequence RNA derived from lungs of 2 clinically relevant, but immunologically distinct murine models of IPA on days 2 and 3 post inoculation when infection is established and active disease present. Our findings identify notable differences in host gene expression between the chemotherapeutic and steroid models at the interface of immunity and metabolism. RT-qPCR verified model specific and nonspecific expression of 23 immune-associated genes. Deep sequencing facilitated identification of highly expressed fungal genes. We utilized sequence similarity and gene expression to categorize the A. fumigatus putative in vivo secretome. RT-qPCR suggests model specific gene expression for nine putative fungal secreted proteins. Our analysis identifies contrasting responses by the host and fungus from day 2 to 3 between the two models. These differences may help tailor the identification, development, and deployment of host- and/or fungal-targeted therapeutics.

  8. Human germline and pan-cancer variomes and their distinct functional profiles

    PubMed Central

    Pan, Yang; Karagiannis, Konstantinos; Zhang, Haichen; Dingerdissen, Hayley; Shamsaddini, Amirhossein; Wan, Quan; Simonyan, Vahan; Mazumder, Raja

    2014-01-01

    Identification of non-synonymous single nucleotide variations (nsSNVs) has exponentially increased due to advances in Next-Generation Sequencing technologies. The functional impacts of these variations have been difficult to ascertain because the corresponding knowledge about sequence functional sites is quite fragmented. It is clear that mapping of variations to sequence functional features can help us better understand the pathophysiological role of variations. In this study, we investigated the effect of nsSNVs on more than 17 common types of post-translational modification (PTM) sites, active sites and binding sites. Out of 1 705 285 distinct nsSNVs on 259 216 functional sites we identified 38 549 variations that significantly affect 10 major functional sites. Furthermore, we found distinct patterns of site disruptions due to germline and somatic nsSNVs. Pan-cancer analysis across 12 different cancer types led to the identification of 51 genes with 106 nsSNV affected functional sites found in 3 or more cancer types. 13 of the 51 genes overlap with previously identified Significantly Mutated Genes (Nature. 2013 Oct 17;502(7471)). 62 mutations in these 13 genes affecting functional sites such as DNA, ATP binding and various PTM sites occur across several cancers and can be prioritized for additional validation and investigations. PMID:25232094

  9. Three perspectives on the mismatch between measures of material poverty.

    PubMed

    Hick, Rod

    2015-03-01

    The two most prominent measures of material poverty within contemporary European poverty analysis are low income and material deprivation. However, it is by now well-known that these measures identify substantially different people as being poor. In this research note, I seek to demonstrate that there are at least three ways to understand the mismatch between low income and material deprivation, relating to three different forms of identification: identifying poor households, identifying groups at risk of poverty and identifying trends in material poverty over time. Drawing on data from the British Household Panel Survey, I show that while low income and material deprivation identify very different households as being poor, and display distinct trends over time, in many cases they identify the same groups at being at risk of material poverty. © London School of Economics and Political Science 2014.

  10. Two stable variants of Burkholderia pseudomallei strain MSHR5848 express broadly divergent in vitro phenotypes associated with their virulence differences.

    PubMed

    Shea, A A; Bernhards, R C; Cote, C K; Chase, C J; Koehler, J W; Klimko, C P; Ladner, J T; Rozak, D A; Wolcott, M J; Fetterer, D P; Kern, S J; Koroleva, G I; Lovett, S P; Palacios, G F; Toothman, R G; Bozue, J A; Worsham, P L; Welkos, S L

    2017-01-01

    Burkholderia pseudomallei (Bp), the agent of melioidosis, causes disease ranging from acute and rapidly fatal to protracted and chronic. Bp is highly infectious by aerosol, can cause severe disease with nonspecific symptoms, and is naturally resistant to multiple antibiotics. However, no vaccine exists. Unlike many Bp strains, which exhibit random variability in traits such as colony morphology, Bp strain MSHR5848 exhibited two distinct and relatively stable colony morphologies on sheep blood agar plates: a smooth, glossy, pale yellow colony and a flat, rough, white colony. Passage of the two variants, designated "Smooth" and "Rough", under standard laboratory conditions produced cultures composed of > 99.9% of the single corresponding type; however, both could switch to the other type at different frequencies when incubated in certain nutritionally stringent or stressful growth conditions. These MSHR5848 derivatives were extensively characterized to identify variant-associated differences. Microscopic and colony morphology differences on six differential media were observed and only the Rough variant metabolized sugars in selective agar. Antimicrobial susceptibilities and lipopolysaccharide (LPS) features were characterized and phenotype microarray profiles revealed distinct metabolic and susceptibility disparities between the variants. Results using the phenotype microarray system narrowed the 1,920 substrates to a subset which differentiated the two variants. Smooth grew more rapidly in vitro than Rough, yet the latter exhibited a nearly 10-fold lower lethal dose for mice than Smooth. Finally, the Smooth variant was phagocytosed and replicated to a greater extent and was more cytotoxic than Rough in macrophages. In contrast, multiple locus sequence type (MLST) analysis, ribotyping, and whole genome sequence analysis demonstrated the variants' genetic conservation; only a single consistent genetic difference between the two was identified for further study. These distinct differences shown by two variants of a Bp strain will be leveraged to better understand the mechanism of Bp phenotypic variability and to possibly identify in vitro markers of infection.

  11. Mapping remote and multidisciplinary learning barriers: lessons from challenge-based innovation at CERN

    NASA Astrophysics Data System (ADS)

    Jensen, Matilde Bisballe; Utriainen, Tuuli Maria; Steinert, Martin

    2018-01-01

    This paper presents the experienced difficulties of students participating in the multidisciplinary, remote collaborating engineering design course challenge-based innovation at CERN. This is with the aim to identify learning barriers and improve future learning experiences. We statistically analyse the rated differences between distinct design activities, educational background and remote vs. co-located collaboration. The analysis is based on a quantitative and qualitative questionnaire (N = 37). Our analysis found significant ranking differences between remote and co-located activities. This questions whether the remote factor might be a barrier for the originally intended learning goals. Further a correlation between analytical and converging design phases was identified. Hence, future facilitators are suggested to help students in the transition from one design phase to the next rather than only teaching methods in the individual design phases. Finally, we discuss how educators address the identified learning barriers when designing future courses including multidisciplinary or remote collaboration.

  12. Using cluster analysis to identify phenotypes and validation of mortality in men with COPD.

    PubMed

    Chen, Chiung-Zuei; Wang, Liang-Yi; Ou, Chih-Ying; Lee, Cheng-Hung; Lin, Chien-Chung; Hsiue, Tzuen-Ren

    2014-12-01

    Cluster analysis has been proposed to examine phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). The aim of this study was to use cluster analysis to define COPD phenotypes and validate them by assessing their relationship with mortality. Male subjects with COPD were recruited to identify and validate COPD phenotypes. Seven variables were assessed for their relevance to COPD, age, FEV(1) % predicted, BMI, history of severe exacerbations, mMRC, SpO(2), and Charlson index. COPD groups were identified by cluster analysis and validated prospectively against mortality during a 4-year follow-up. Analysis of 332 COPD subjects identified five clusters from cluster A to cluster E. Assessment of the predictive validity of these clusters of COPD showed that cluster E patients had higher all cause mortality (HR 18.3, p < 0.0001), and respiratory cause mortality (HR 21.5, p < 0.0001) than those in the other four groups. Cluster E patients also had higher all cause mortality (HR 14.3, p = 0.0002) and respiratory cause mortality (HR 10.1, p = 0.0013) than patients in cluster D alone. COPD patient with severe airflow limitation, many symptoms, and a history of frequent severe exacerbations was a novel and distinct clinical phenotype predicting mortality in men with COPD.

  13. Connectedness in the context of patient-provider relationships: a concept analysis.

    PubMed

    Phillips-Salimi, Celeste R; Haase, Joan E; Kooken, Wendy Carter

    2012-01-01

    This paper is a report of an analysis of the concept of connectedness. Previous attempts to conceptualize patient-provider relationships were limited in explaining how such relationships are fostered and maintained, and how they influence patient outcomes. Connectedness is a concept that may provide insights into the advantages of patient-provider relationships; however, the usefulness of this concept in health care is limited by its conceptual ambiguity. Although connectedness is widely used to describe other social relationships, little consistency exists among its definitions and measures. Sources identified through CINAHL, OVID, PubMed and PsychINFO databases and references lists of selected articles between 1983 and 2010. A hybrid concept analysis approach was used, involving a combination of traditional concept analysis strategies that included: describing historical conceptualizations, identifying attributes, critiquing existing definitions, examining boundaries and identifying antecedents and consequences. Using five distinct historical perspectives, seven attributes of connectedness were identified: intimacy, sense of belonging, caring, empathy, respect, trust and reciprocity. A broad definition of connectedness, which can be used in the context of patient-provider relationships, was developed. A preliminary theoretical framework of connectedness was derived from the identified antecedents, attributes and consequences. Research efforts to advance the concept of connectedness in patient-provider relationships have been hampered by a lack of conceptual clarity. This concept analysis offers a clearer understanding of connectedness, provides recommendations for future research and suggests practice implications. © 2011 Blackwell Publishing Ltd.

  14. Machine-learning phenotypic classification of bicuspid aortopathy.

    PubMed

    Wojnarski, Charles M; Roselli, Eric E; Idrees, Jay J; Zhu, Yuanjia; Carnes, Theresa A; Lowry, Ashley M; Collier, Patrick H; Griffin, Brian; Ehrlinger, John; Blackstone, Eugene H; Svensson, Lars G; Lytle, Bruce W

    2018-02-01

    Bicuspid aortic valves (BAV) are associated with incompletely characterized aortopathy. Our objectives were to identify distinct patterns of aortopathy using machine-learning methods and characterize their association with valve morphology and patient characteristics. We analyzed preoperative 3-dimensional computed tomography reconstructions for 656 patients with BAV undergoing ascending aorta surgery between January 2002 and January 2014. Unsupervised partitioning around medoids was used to cluster aortic dimensions. Group differences were identified using polytomous random forest analysis. Three distinct aneurysm phenotypes were identified: root (n = 83; 13%), with predominant dilatation at sinuses of Valsalva; ascending (n = 364; 55%), with supracoronary enlargement rarely extending past the brachiocephalic artery; and arch (n = 209; 32%), with aortic arch dilatation. The arch phenotype had the greatest association with right-noncoronary cusp fusion: 29%, versus 13% for ascending and 15% for root phenotypes (P < .0001). Severe valve regurgitation was most prevalent in root phenotype (57%), followed by ascending (34%) and arch phenotypes (25%; P < .0001). Aortic stenosis was most prevalent in arch phenotype (62%), followed by ascending (50%) and root phenotypes (28%; P < .0001). Patient age increased as the extent of aneurysm became more distal (root, 49 years; ascending, 53 years; arch, 57 years; P < .0001), and root phenotype was associated with greater male predominance compared with ascending and arch phenotypes (94%, 76%, and 70%, respectively; P < .0001). Phenotypes were visually recognizable with 94% accuracy. Three distinct phenotypes of bicuspid valve-associated aortopathy were identified using machine-learning methodology. Patient characteristics and valvular dysfunction vary by phenotype, suggesting that the location of aortic pathology may be related to the underlying pathophysiology of this disease. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  15. G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

    PubMed Central

    2013-01-01

    Background Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Results Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Conclusions Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways is a secondary benefit to identifying differential GPCR expression patterns in medulloblastoma tumors. PMID:24252460

  16. Phylogenetic analysis of the lux operon distinguishes two evolutionarily distinct clades of Photobacterium leiognathi.

    PubMed

    Ast, Jennifer C; Dunlap, Paul V

    2004-05-01

    The luminous marine bacterium Photobacterium mandapamensis was synonymized several years ago with Photobacterium leiognathi based on a high degree of phenotypic and genetic similarity. To test the possibility that P. leiognathi as now formulated, however, actually contains two distinct bacterial groups reflecting the earlier identification of P. mandapamensis and P. leiognathi as separate species, we compared P. leiognathi strains isolated from light-organ symbiosis with leiognathid fishes (i.e., ATCC 25521(T), ATCC 25587, lequu.1.1 and lleuc.1.1) with strains from seawater originally described as P. mandapamensis and later synonymized as P. leiognathi (i.e., ATCC 27561(T) and ATCC 33981) and certain strains initially identified as P. leiognathi (i.e., PL-721, PL-741, 554). Analysis of the 16S rRNA and gyrB genes did not resolve distinct clades, affirming a close relationship among these strains. However, strains ATCC 27561(T), ATCC 33981, PL-721, PL-741 and 554 were found to bear a luxF gene in the lux operon ( luxABFE), whereas ATCC 25521(T), ATCC 25587, lequu.1.1 and lleuc.1.1 lack this gene ( luxABE). Phylogenetic analysis of the luxAB(F)E region confirmed this distinction. Furthermore, ATCC 27561(T), ATCC 33981, PL-721, PL-741 and 554 all produced a higher level of luminescence on high-salt medium, as previously described for PL-721, whereas ATCC 25521(T), ATCC 25587, lequu.1.1 and lleuc.1.1 all produced a higher level of luminescence on low-salt medium, a characteristic of P. leiognathi from leiognathid fish light organs. These results demonstrate that P. leiognathi contains two evolutionarily and phenotypically distinct clades, P. leiognathi subsp. leiognathi (strains ATCC 25521(T), ATCC 25587, lequu.1.1 and lleuc.1.1), and P. leiognathi subsp. mandapamensis (strains ATCC 27561(T), ATCC 33981, PL-721, PL-741 and 554).

  17. Proteomics and Deep Sequencing Comparison of Seasonally Active Venom Glands in the Platypus Reveals Novel Venom Peptides and Distinct Expression Profiles*

    PubMed Central

    Wong, Emily S. W.; Morgenstern, David; Mofiz, Ehtesham; Gombert, Sara; Morris, Katrina M.; Temple-Smith, Peter; Renfree, Marilyn B.; Whittington, Camilla M.; King, Glenn F.; Warren, Wesley C.; Papenfuss, Anthony T.; Belov, Katherine

    2012-01-01

    The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution. PMID:22899769

  18. Proteomics and deep sequencing comparison of seasonally active venom glands in the platypus reveals novel venom peptides and distinct expression profiles.

    PubMed

    Wong, Emily S W; Morgenstern, David; Mofiz, Ehtesham; Gombert, Sara; Morris, Katrina M; Temple-Smith, Peter; Renfree, Marilyn B; Whittington, Camilla M; King, Glenn F; Warren, Wesley C; Papenfuss, Anthony T; Belov, Katherine

    2012-11-01

    The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution.

  19. Integrative Analysis of Response to Tamoxifen Treatment in ER-Positive Breast Cancer Using GWAS Information and Transcription Profiling.

    PubMed

    Hicks, Chindo; Kumar, Ranjit; Pannuti, Antonio; Miele, Lucio

    2012-01-01

    Variable response and resistance to tamoxifen treatment in breast cancer patients remains a major clinical problem. To determine whether genes and biological pathways containing SNPs associated with risk for breast cancer are dysregulated in response to tamoxifen treatment, we performed analysis combining information from 43 genome-wide association studies with gene expression data from 298 ER(+) breast cancer patients treated with tamoxifen and 125 ER(+) controls. We identified 95 genes which distinguished tamoxifen treated patients from controls. Additionally, we identified 54 genes which stratified tamoxifen treated patients into two distinct groups. We identified biological pathways containing SNPs associated with risk for breast cancer, which were dysregulated in response to tamoxifen treatment. Key pathways identified included the apoptosis, P53, NFkB, DNA repair and cell cycle pathways. Combining GWAS with transcription profiling provides a unified approach for associating GWAS findings with response to drug treatment and identification of potential drug targets.

  20. Toward Biological Subtyping of Papillary Renal Cell Carcinoma With Clinical Implications Through Histologic, Immunohistochemical, and Molecular Analysis.

    PubMed

    Saleeb, Rola M; Brimo, Fadi; Farag, Mina; Rompré-Brodeur, Alexis; Rotondo, Fabio; Beharry, Vidya; Wala, Samantha; Plant, Pamela; Downes, Michelle R; Pace, Kenneth; Evans, Andrew; Bjarnason, Georg; Bartlett, John M S; Yousef, George M

    2017-12-01

    Papillary renal cell carcinoma (PRCC) has 2 histologic subtypes. Almost half of the cases fail to meet all morphologic criteria for either type, hence are characterized as PRCC not otherwise specified (NOS). There are yet no markers to resolve the PRCC NOS category. Accurate classification can better guide the management of these patients. In our previous PRCC study we identified markers that can distinguish between the subtypes. A PRCC patient cohort of 108 cases was selected for the current study. A panel of potentially distinguishing markers was chosen from our previous genomic analysis, and assessed by immunohistochemistry. The panel exhibited distinct staining patterns between the 2 classic PRCC subtypes; and successfully reclassified the NOS (45%) cases. Moreover, these immunomarkers revealed a third subtype, PRCC3 (35% of the cohort). Molecular testing using miRNA expression and copy number variation analysis confirmed the presence of 3 distinct molecular signatures corresponding to the 3 subtypes. Disease-free survival was significantly enhanced in PRCC1 versus 2 and 3 (P=0.047) on univariate analysis. The subtypes stratification was also significant on multivariate analysis (P=0.025; hazard ratio, 6; 95% confidence interval, 1.25-32.2). We propose a new classification system of PRCC integrating morphologic, immunophenotypical, and molecular analysis. The newly described PRCC3 has overlapping morphology between PRCC1 and PRCC2, hence would be subtyped as NOS in the current classification. Molecularly PRCC3 has a distinct signature and clinically it behaves similar to PRCC2. The new classification stratifies PRCC patients into clinically relevant subgroups and has significant implications on the management of PRCC.

  1. Mineral exploration potential of ERTS-1 data. [porphyry copper deposits in Arizona

    NASA Technical Reports Server (NTRS)

    Brewer, W. A. (Principal Investigator); Erskine, M. C., Jr.; Prindle, R. O.; Haenggi, W. T.

    1974-01-01

    The author has identified the following significant results. ERTS-1 imagery of an area approximately 15,000 square miles in Arizona was interpreted for regional structure and tectonic units. Eight fault systems were identified by trend, of which two, northeast and northwest, are considered to be related to porphyry copper mineralization. Nine tectonic units can be identified on the imagery as distinct geological identities. The boundaries between these units can be correlated with theoretical shear directions related to the San Andreas stress system. Fourier analysis of the N 50 W fault trend indicates a fundamental spacing between Fourier energy maxima that can be related to distances between copper deposits.

  2. Global analysis of gully composition using manual and automated exploration of CRISM imagery

    NASA Astrophysics Data System (ADS)

    Allender, Elyse; Stepinski, Tomasz F.

    2018-03-01

    Gully formations on Mars have been the focus of many morphological and mineralogical studies aimed at inferring the mechanisms of their formation and evolution. In this paper we have analyzed 354 globally distributed gully-bearing Full Resolution Targeted (FRT) Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) images. The primary goal of the analysis was to identify all spectrally distinct deposits in these images (if any) and to classify them into hydrated and non-hydrated categories using only CRISM summary parameters (Viviano-Beck et al., 2014). Such approach makes possible to analyze a very large set of all distinct deposits in 354 images. We found that 68% of these images lack any distinct deposits, 8% of images contain non-hydrated deposits which coincide with the gullies and 24% of images contain hydrated deposits which coincide with the gullies. These results are compared with the recent analysis of 110 CRISM images by Nuñez et al. (2016) who also found that most gullies coincide with indistinct deposits, but, contrary to our findings, they found a predominance of non-hydrated minerals among distinct deposits. We attribute this discrepancy in part to their smaller and geographically biased sample of images, and in part to differing protocols of categorizing images. The discrepancy between the two surveys is further increased if we count all deposits in FRT gully-bearing images, not just deposits directly coinciding with the gullies, obtaining 44% indistinct, 15% non-hydrated, and 41% hydrated images. The secondary goal of this study was to perform the same image survey using a recently developed automated method in order to assess its accuracy and thus its feasibility for performing future surveys. We found the overall accuracy of the auto-mapper to be 76.2% but its accuracy for discovering distinct deposits, and in particular, distinct hydrated deposits was lower. We attributed the deficiencies of the auto-mapper primarily to its sensitivity to presence of noise in images and especially to presence of speckle noise. It is however worth noting that qualitatively both manual and automatic surveys arrived at the same overall conclusion.

  3. Palus Somni - Anomalies in the correlation of Al/Si X-ray fluorescence intensity ratios and broad-spectrum visible albedos. [lunar surface mineralogy

    NASA Technical Reports Server (NTRS)

    Clark, P. E.; Andre, C. G.; Adler, I.; Weidner, J.; Podwysocki, M.

    1976-01-01

    The positive correlation between Al/Si X-ray fluorescence intensity ratios determined during the Apollo 15 lunar mission and a broad-spectrum visible albedo of the moon is quantitatively established. Linear regression analysis performed on 246 1 degree geographic cells of X-ray fluorescence intensity and visible albedo data points produced a statistically significant correlation coefficient of .78. Three distinct distributions of data were identified as (1) within one standard deviation of the regression line, (2) greater than one standard deviation below the line, and (3) greater than one standard deviation above the line. The latter two distributions of data were found to occupy distinct geographic areas in the Palus Somni region.

  4. Comprehensive Proteomic Analysis of Human Milk-derived Extracellular Vesicles Unveils a Novel Functional Proteome Distinct from Other Milk Components.

    PubMed

    van Herwijnen, Martijn J C; Zonneveld, Marijke I; Goerdayal, Soenita; Nolte-'t Hoen, Esther N M; Garssen, Johan; Stahl, Bernd; Maarten Altelaar, A F; Redegeld, Frank A; Wauben, Marca H M

    2016-11-01

    Breast milk contains several macromolecular components with distinctive functions, whereby milk fat globules and casein micelles mainly provide nutrition to the newborn, and whey contains molecules that can stimulate the newborn's developing immune system and gastrointestinal tract. Although extracellular vesicles (EV) have been identified in breast milk, their physiological function and composition has not been addressed in detail. EV are submicron sized vehicles released by cells for intercellular communication via selectively incorporated lipids, nucleic acids, and proteins. Because of the difficulty in separating EV from other milk components, an in-depth analysis of the proteome of human milk-derived EV is lacking. In this study, an extensive LC-MS/MS proteomic analysis was performed of EV that had been purified from breast milk of seven individual donors using a recently established, optimized density-gradient-based EV isolation protocol. A total of 1963 proteins were identified in milk-derived EV, including EV-associated proteins like CD9, Annexin A5, and Flotillin-1, with a remarkable overlap between the different donors. Interestingly, 198 of the identified proteins are not present in the human EV database Vesiclepedia, indicating that milk-derived EV harbor proteins not yet identified in EV of different origin. Similarly, the proteome of milk-derived EV was compared with that of other milk components. For this, data from 38 published milk proteomic studies were combined in order to construct the total milk proteome, which consists of 2698 unique proteins. Remarkably, 633 proteins identified in milk-derived EV have not yet been identified in human milk to date. Interestingly, these novel proteins include proteins involved in regulation of cell growth and controlling inflammatory signaling pathways, suggesting that milk-derived EVs could support the newborn's developing gastrointestinal tract and immune system. Overall, this study provides an expansion of the whole milk proteome and illustrates that milk-derived EV are macromolecular components with a unique functional proteome. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Genome-wide characterization and analysis of bZIP transcription factor gene family related to abiotic stress in cassava.

    PubMed

    Hu, Wei; Yang, Hubiao; Yan, Yan; Wei, Yunxie; Tie, Weiwei; Ding, Zehong; Zuo, Jiao; Peng, Ming; Li, Kaimian

    2016-03-07

    The basic leucine zipper (bZIP) transcription factor family plays crucial roles in various aspects of biological processes. Currently, no information is available regarding the bZIP family in the important tropical crop cassava. Herein, 77 bZIP genes were identified from cassava. Evolutionary analysis indicated that MebZIPs could be divided into 10 subfamilies, which was further supported by conserved motif and gene structure analyses. Global expression analysis suggested that MebZIPs showed similar or distinct expression patterns in different tissues between cultivated variety and wild subspecies. Transcriptome analysis of three cassava genotypes revealed that many MebZIP genes were activated by drought in the root of W14 subspecies, indicating the involvement of these genes in the strong resistance of cassava to drought. Expression analysis of selected MebZIP genes in response to osmotic, salt, cold, ABA, and H2O2 suggested that they might participate in distinct signaling pathways. Our systematic analysis of MebZIPs reveals constitutive, tissue-specific and abiotic stress-responsive candidate MebZIP genes for further functional characterization in planta, yields new insights into transcriptional regulation of MebZIP genes, and lays a foundation for understanding of bZIP-mediated abiotic stress response.

  6. The Promise of Multi-Omics and Clinical Data Integration to Identify and Target Personalized Healthcare Approaches in Autism Spectrum Disorders

    PubMed Central

    Higdon, Roger; Earl, Rachel K.; Stanberry, Larissa; Hudac, Caitlin M.; Montague, Elizabeth; Stewart, Elizabeth; Janko, Imre; Choiniere, John; Broomall, William; Kolker, Natali

    2015-01-01

    Abstract Complex diseases are caused by a combination of genetic and environmental factors, creating a difficult challenge for diagnosis and defining subtypes. This review article describes how distinct disease subtypes can be identified through integration and analysis of clinical and multi-omics data. A broad shift toward molecular subtyping of disease using genetic and omics data has yielded successful results in cancer and other complex diseases. To determine molecular subtypes, patients are first classified by applying clustering methods to different types of omics data, then these results are integrated with clinical data to characterize distinct disease subtypes. An example of this molecular-data-first approach is in research on Autism Spectrum Disorder (ASD), a spectrum of social communication disorders marked by tremendous etiological and phenotypic heterogeneity. In the case of ASD, omics data such as exome sequences and gene and protein expression data are combined with clinical data such as psychometric testing and imaging to enable subtype identification. Novel ASD subtypes have been proposed, such as CHD8, using this molecular subtyping approach. Broader use of molecular subtyping in complex disease research is impeded by data heterogeneity, diversity of standards, and ineffective analysis tools. The future of molecular subtyping for ASD and other complex diseases calls for an integrated resource to identify disease mechanisms, classify new patients, and inform effective treatment options. This in turn will empower and accelerate precision medicine and personalized healthcare. PMID:25831060

  7. Multivariate inference of pathway activity in host immunity and response to therapeutics

    PubMed Central

    Goel, Gautam; Conway, Kara L.; Jaeger, Martin; Netea, Mihai G.; Xavier, Ramnik J.

    2014-01-01

    Developing a quantitative view of how biological pathways are regulated in response to environmental factors is central for understanding of disease phenotypes. We present a computational framework, named Multivariate Inference of Pathway Activity (MIPA), which quantifies degree of activity induced in a biological pathway by computing five distinct measures from transcriptomic profiles of its member genes. Statistical significance of inferred activity is examined using multiple independent self-contained tests followed by a competitive analysis. The method incorporates a new algorithm to identify a subset of genes that may regulate the extent of activity induced in a pathway. We present an in-depth evaluation of specificity, robustness, and reproducibility of our method. We benchmarked MIPA's false positive rate at less than 1%. Using transcriptomic profiles representing distinct physiological and disease states, we illustrate applicability of our method in (i) identifying gene–gene interactions in autophagy-dependent response to Salmonella infection, (ii) uncovering gene–environment interactions in host response to bacterial and viral pathogens and (iii) identifying driver genes and processes that contribute to wound healing and response to anti-TNFα therapy. We provide relevant experimental validation that corroborates the accuracy and advantage of our method. PMID:25147207

  8. Pathways to adolescent childbearing among Kaqchikel women in Guatemala.

    PubMed

    Lemon, Emily; Hennink, Monique; Can Saquic, Nely Amparo

    2017-10-01

    One-in-five children in Guatemala is born to a mother aged 15-19 years, which poses social, economic and health risks to both mother and child. In Guatemala, adolescent childbearing is directly associated with education, ethnicity and poverty, which increases vulnerability among Indigenous young women living in poverty. This study examines the context and experiences of adolescent childbearing from the perspectives of young mothers in the Kaqchikel Indigenous ethnic group of Sololá, Guatemala. Data were collected in 19 qualitative in-depth interviews with women who had given birth to one or more children when aged 15 to 19 years. Grounded theory and narrative analysis were used to develop a conceptual framework of the process and influences on childbearing. Four distinct pathways were identified, which were influenced by gender expectations, limited communication about sex and stigma around sex. The study identifies key sociocultural influences that lead to adolescent childbearing and reveals variability within these. Identifying distinct pathways to early childbearing and their influences enables a clearer understanding of potential opportunities to interrupt these pathways with culturally relevant policies and programmes, in particular those that promote gender equality and intergenerational communication about sex.

  9. Phylogenetic evidence of noteworthy microflora from the subsurface of the former Homestake gold mine, Lead, South Dakota

    PubMed Central

    Waddell, Evan J.; Elliott, Terran J.; Sani, Rajesh K.; Vahrenkamp, Jefferey M.; Roggenthen, William M.; Anderson, Cynthia M.; Bang, Sookie S.

    2013-01-01

    Molecular characterization of subsurface microbial communities in the former Homestake gold mine, South Dakota, was carried out by 16S rDNA sequence analysis using a water sample and a weathered soil–like sample. Geochemical analyses indicated that both samples were high in sulfur, rich in nitrogen and salt, but with significantly different metal concentrations. Microbial diversity comparisons unexpectedly revealed three distinct operational taxonomic units (OTUs) belonging to the archaeal phylum Thaumarchaeota typically identified from marine environments, and one OTU to a potentially novel phylum that falls sister to Thaumarchaeota. To our knowledge this is only the second report of Thaumarchaeota in a terrestrial environment. The majority of the clones from Archaea sequence libraries fell into two closely related OTUs and grouped most closely to an ammonia–oxidizing, carbon–fixing and halophilic thaumarchaeote genus, Nitrosopumilus. The two samples showed neither Euryarchaeota nor Crenarchaeota members that were often identified from other subsurface terrestrial ecosystems. Bacteria OTUs containing the highest percentage of sequences were related to sulfur-oxidizing bacteria of the orders Chromatiales and Thiotrichales. Community members of Bacteria from individual Homestake ecosystems were heterogeneous and distinctive to each community with unique phylotypes identified within each sample. PMID:20662386

  10. A Method for Identification and Analysis of Non-Overlapping Myeloid Immunophenotypes in Humans

    PubMed Central

    Gustafson, Michael P.; Lin, Yi; Maas, Mary L.; Van Keulen, Virginia P.; Johnston, Patrick B.; Peikert, Tobias; Gastineau, Dennis A.; Dietz, Allan B.

    2015-01-01

    The development of flow cytometric biomarkers in human studies and clinical trials has been slowed by inconsistent sample processing, use of cell surface markers, and reporting of immunophenotypes. Additionally, the function(s) of distinct cell types as biomarkers cannot be accurately defined without the proper identification of homogeneous populations. As such, we developed a method for the identification and analysis of human leukocyte populations by the use of eight 10-color flow cytometric protocols in combination with novel software analyses. This method utilizes un-manipulated biological sample preparation that allows for the direct quantitation of leukocytes and non-overlapping immunophenotypes. We specifically designed myeloid protocols that enable us to define distinct phenotypes that include mature monocytes, granulocytes, circulating dendritic cells, immature myeloid cells, and myeloid derived suppressor cells (MDSCs). We also identified CD123 as an additional distinguishing marker for the phenotypic characterization of immature LIN-CD33+HLA-DR- MDSCs. Our approach permits the comprehensive analysis of all peripheral blood leukocytes and yields data that is highly amenable for standardization across inter-laboratory comparisons for human studies. PMID:25799053

  11. Investigation of the aroma of commercial peach (Prunus persica L. Batsch) types by Proton Transfer Reaction-Mass Spectrometry (PTR-MS) and sensory analysis.

    PubMed

    Bianchi, Tiago; Weesepoel, Yannick; Koot, Alex; Iglesias, Ignasi; Eduardo, Iban; Gratacós-Cubarsí, Marta; Guerrero, Luis; Hortós, Maria; van Ruth, Saskia

    2017-09-01

    The aim of this study was to investigate the aroma and sensory profiles of various types of peaches (Prunus persica L. Batsch.). Forty-three commercial cultivars comprising peaches, flat peaches, nectarines, and canning peaches (pavías) were grown over two consecutive harvest years. Fruits were assessed for chemical aroma and sensory profiles. Chemical aroma profile was obtained by proton transfer reaction-mass spectrometry (PTR-MS) and spectral masses were tentatively identified with PTR-Time of Flight-MS (PTR-Tof-MS). Sensory analysis was performed at commercial maturity considering seven aroma/flavor attributes. The four types of peaches showed both distinct chemical aroma and sensory profiles. Flat peaches and canning peaches showed most distinct patterns according to discriminant analysis. The sensory data were related to the volatile compounds by partial least square regression. γ-Hexalactone, γ-octalactone, hotrienol, acetic acid and ethyl acetate correlated positively, and benzeneacetaldehyde, trimethylbenzene and acetaldehyde negatively to the intensities of aroma and ripe fruit sensory scores. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Reactive and proactive aggression as meaningful distinctions at the variable and person level in primary school-aged children.

    PubMed

    Carroll, Annemaree; McCarthy, Molly; Houghton, Stephen; Sanders O'Connor, Emma; Zadow, Corinne

    2018-04-24

    Reactive and proactive aggression is a dichotomous classification of aggression in adults and children. This distinction has been supported by a number of variable-based and factor analytic studies. Due to high inter-correlations, however, the reactive-proactive aggression distinction may not be entirely useful for understanding how group or individual aggressive behavior varies in children and adolescents. Drawing on a sample of primary school-aged children (N = 242) aged 7-12 years, this study sought to determine whether reactive and proactive aggression could be distinguished at the variable-level and the person-level in children. Exploratory Factor Analysis of data from an aggression instrument measuring both functions and forms of aggression, found a two-factor construct of aggression constituted by a reactive and proactive aggression factor. A person-based analysis was then conducted after classifying children according to the presence of reactive and/or proactive aggression. Discriminant function analysis was used to discern whether classifications on the basis of aggression function produced meaningful distinctions in terms of antisocial traits and emotional valence and intensity measures. Two functions were identified which distinguished children with different combinations of reactive and proactive aggression. Reactive-only aggressive children were defined primarily by high levels of impulsivity, while proactive-only children were defined primarily by higher levels of antisocial traits. Children high in both types of aggression exhibited both the presence of antisocial traits and impulsivity. Contrary to recent findings, this suggests that differences in aggression functions remain meaningful at the person level in children. Implications for interventions are discussed. © 2018 Wiley Periodicals, Inc.

  13. OD (Organization Development) Interventions that Enhance Equal Opportunity.

    DTIC Science & Technology

    1983-09-01

    aide to aaesam mod Identify by week nim obe) Socialization process Socialization model Self-esteem Organization form and structure Equal Opportunity...itself speaks to the way individuals are socialized into the Navy or a perceived lack of socialization . 7 pi ’..7 ’ .. . . 7 Today the Equal ... equal opportunity. Analysis of five different dimensions of the socialization process can be thought of as distinct "tactics" which managers (agents

  14. Occurrence and molecular analysis of Balantidium coli in mountain gorilla (Gorilla beringei beringei) in the Volcanoes National Park, Rwanda.

    PubMed

    Hassell, James M; Blake, Damer P; Cranfield, Michael R; Ramer, Jan; Hogan, Jennifer N; Noheli, Jean Bosco; Waters, Michael; Hermosilla, Carlos

    2013-10-01

    Cysts morphologically resembling Balantidium coli were identified in the feces of a mountain gorilla (Gorilla beringei beringei). Confirmatory PCR and sequencing revealed two distinct B. coli-specific sequences (ITS-1, sub-types A0 and B1). This represents the first report of B. coli in this species, raising the possibility of infection from a reservoir host.

  15. Authentication of commercial spices based on the similarities between gas chromatographic fingerprints.

    PubMed

    Matsushita, Takaya; Zhao, Jing Jing; Igura, Noriyuki; Shimoda, Mitsuya

    2018-06-01

    A simple and solvent-free method was developed for the authentication of commercial spices. The similarities between gas chromatographic fingerprints were measured using similarity indices and multivariate data analyses, as morphological differentiation between dried powders and small spice particles was challenging. The volatile compounds present in 11 spices (i.e. allspice, anise, black pepper, caraway, clove, coriander, cumin, dill, fennel, star anise, and white pepper) were extracted by headspace solid-phase microextraction, and analysed by gas chromatography-mass spectrometry. The largest 10 peaks were selected from each total ion chromatogram, and a total of 65 volatiles were tentatively identified. The similarity indices (i.e. the congruence coefficients) were calculated using the data matrices of the identified compound relative peak areas to differentiate between two sets of fingerprints. Where pairs of similar fingerprints produced high congruence coefficients (>0.80), distinctive volatile markers were employed to distinguish between these samples. In addition, hierarchical cluster analysis and principal component analysis were performed to visualise the similarity among fingerprints, and the analysed spices were grouped and characterised according to their distinctive major components. This method is suitable for screening unknown spices, and can therefore be employed to evaluate the quality and authenticity of various spices. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  16. Distribution and abundance of phytobenthic communities: Implications for connectivity and ecosystem functioning in a Black Sea Marine Protected Area

    NASA Astrophysics Data System (ADS)

    Berov, Dimitar; Todorova, Valentina; Dimitrov, Lubomir; Rinde, Eli; Karamfilov, Ventzislav

    2018-01-01

    The distribution and abundance of macroalgal communities in a Marine Protected Area (MPA) along the Bulgarian Black Sea coast were mapped and quantified, with particular focus on the previously unstudied P. crispa lower-infralittoral communities on Ostrea edulis biogenic reefs. Data from high resolution geophysical substrate mapping were combined with benthic community observations from georeferenced benthic photographic surveys and sampling. Multivariate analysis identified four distinct assemblages of lower-infralittoral macroalgal communities at depths between 10 and 17 m, dominated by Phyllophora crispa, Apoglossum ruscifoluim, Zanardinia typus and Gelidium spp. Maxent software analysis showed distinct preferences of the identified communities to areas with specific ranges of depth, inclination and curvature, with P. crispa more frequently occurring on vertical oyster biogenic reef structures. By combining production rates from literature, biomass measurements and the produced habitat maps, the highest proportion of primary production and DOC release was shown for the upper infralittoral Cystoseira barbata and Cystoseira bosphorica, followed by the production of the lower-infralittoral macroalgae. The observed distribution of P. crispa within the studied MPA was related to the network of Natura 2000 maritime MPAs along the Bulgarian Black Sea coast, which indicated that the connectivity of the populations of the species within the established network is insufficient within this cell of ecosystem functioning.

  17. Using Patient-Pathway Analysis to Inform a Differentiated Program Response to Tuberculosis: The Case of Kenya.

    PubMed

    Masini, Enos; Hanson, Christy; Ogoro, Jeremiah; Brown, Jessie; Ngari, Faith; Mingkwan, Pia; Makayova, Julia; Osberg, Mike

    2017-11-06

    A recent tuberculosis prevalence survey in Kenya found that the country is home to nearly twice as many patients with tuberculosis as previously estimated. Kenya has prioritized identifying and treating the unnotified or missing cases of tuberculosis. This requires a better understanding of patient care seeking and system weaknesses. A patient-pathway analysis (PPA) was completed to assess the alignment between patient care seeking and the availability of tuberculosis diagnostic and treatment services at the national level and for all 47 counties at the subnational level in Kenya. It was estimated that more than half of patients initiate care in the public sector. Nationally, just under half of patients encountered tuberculosis diagnostic and treatment capacity where they initiated care. Overall, there was distinct variation in diagnostic and treatment availability across counties and facility levels. The PPA results emphasized the need for a differentiated approach to tuberculosis care, by county, and the distinct need for better referral systems. The majority of Kenyans actively sought care; improving diagnostic and treatment capacity in the formal and informal private sector, as well as in the public sector, could help identify the majority of missing cases. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  18. Profiles of Community Violence Exposure Among African American Youth: An Examination of Desensitization to Violence Using Latent Class Analysis.

    PubMed

    Gaylord-Harden, Noni K; Dickson, Daniel; Pierre, Cynthia

    2016-07-01

    The current study employed latent class analysis (LCA) to identify distinct profiles of community violence exposure and their associations to desensitization outcomes in 241 African American early adolescents (M age = 12.86, SD = 1.28) in the sixth through eighth grade from under-resourced urban communities. Participants self-reported on their exposure to community violence, as well as on depressive and anxiety symptoms. The LCA revealed three distinct classes: a class exposed to low levels of violence (low exposure class), a class exposed to moderately high levels of victimization (victimization class), and a class exposed to high levels of all types of violence (high exposure class). Consistent with predictions, the high exposure class showed the lowest levels of depressive symptoms, suggesting a desensitization outcome. Gender and age were also examined in relation to the classes, and age was significantly associated with an increased risk of being a member of the high exposure class relative to the low exposure class. Using person-based analyses to examine desensitization outcomes provides useful information for prevention and intervention efforts, as it helps to identify a specific subgroup of youth that may be more likely to show desensitization outcomes in the context of community violence. © The Author(s) 2015.

  19. Are clusters of dietary patterns and cluster membership stable over time? Results of a longitudinal cluster analysis study.

    PubMed

    Walthouwer, Michel Jean Louis; Oenema, Anke; Soetens, Katja; Lechner, Lilian; de Vries, Hein

    2014-11-01

    Developing nutrition education interventions based on clusters of dietary patterns can only be done adequately when it is clear if distinctive clusters of dietary patterns can be derived and reproduced over time, if cluster membership is stable, and if it is predictable which type of people belong to a certain cluster. Hence, this study aimed to: (1) identify clusters of dietary patterns among Dutch adults, (2) test the reproducibility of these clusters and stability of cluster membership over time, and (3) identify sociodemographic predictors of cluster membership and cluster transition. This study had a longitudinal design with online measurements at baseline (N=483) and 6 months follow-up (N=379). Dietary intake was assessed with a validated food frequency questionnaire. A hierarchical cluster analysis was performed, followed by a K-means cluster analysis. Multinomial logistic regression analyses were conducted to identify the sociodemographic predictors of cluster membership and cluster transition. At baseline and follow-up, a comparable three-cluster solution was derived, distinguishing a healthy, moderately healthy, and unhealthy dietary pattern. Male and lower educated participants were significantly more likely to have a less healthy dietary pattern. Further, 251 (66.2%) participants remained in the same cluster, 45 (11.9%) participants changed to an unhealthier cluster, and 83 (21.9%) participants shifted to a healthier cluster. Men and people living alone were significantly more likely to shift toward a less healthy dietary pattern. Distinctive clusters of dietary patterns can be derived. Yet, cluster membership is unstable and only few sociodemographic factors were associated with cluster membership and cluster transition. These findings imply that clusters based on dietary intake may not be suitable as a basis for nutrition education interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Analysis of Strengths, Weaknesses, Opportunities, and Threats as a Tool for Translating Evidence into Individualized Medical Strategies (I-SWOT)

    PubMed Central

    von Kodolitsch, Yskert; Bernhardt, Alexander M.; Robinson, Peter N.; Kölbel, Tilo; Reichenspurner, Hermann; Debus, Sebastian; Detter, Christian

    2015-01-01

    Background It is the physicians’ task to translate evidence and guidelines into medical strategies for individual patients. Until today, however, there is no formal tool that is instrumental to perform this translation. Methods We introduce the analysis of strengths (S) and weaknesses (W) related to therapy with opportunities (O) and threats (T) related to individual patients as a tool to establish an individualized (I) medical strategy (I-SWOT). The I-SWOT matrix identifies four fundamental types of strategy. These comprise “SO” maximizing strengths and opportunities, “WT” minimizing weaknesses and threats, “WO” minimizing weaknesses and maximizing opportunities, and “ST” maximizing strengths and minimizing threats. Each distinct type of strategy may be considered for individualized medical strategies. Results We describe four steps of I-SWOT to establish an individualized medical strategy to treat aortic disease. In the first step, we define the goal of therapy and identify all evidence-based therapeutic options. In a second step, we assess strengths and weaknesses of each therapeutic option in a SW matrix form. In a third step, we assess opportunities and threats related to the individual patient, and in a final step, we use the I-SWOT matrix to establish an individualized medical strategy through matching “SW” with “OT”. As an example we present two 30-year-old patients with Marfan syndrome with identical medical history and aortic pathology. As a result of I-SWOT analysis of their individual opportunities and threats, we identified two distinct medical strategies in these patients. Conclusion I-SWOT is a formal but easy to use tool to translate medical evidence into individualized medical strategies. PMID:27069939

  1. Analysis of Strengths, Weaknesses, Opportunities, and Threats as a Tool for Translating Evidence into Individualized Medical Strategies (I-SWOT).

    PubMed

    von Kodolitsch, Yskert; Bernhardt, Alexander M; Robinson, Peter N; Kölbel, Tilo; Reichenspurner, Hermann; Debus, Sebastian; Detter, Christian

    2015-06-01

    It is the physicians' task to translate evidence and guidelines into medical strategies for individual patients. Until today, however, there is no formal tool that is instrumental to perform this translation. We introduce the analysis of strengths (S) and weaknesses (W) related to therapy with opportunities (O) and threats (T) related to individual patients as a tool to establish an individualized (I) medical strategy (I-SWOT). The I-SWOT matrix identifies four fundamental types of strategy. These comprise "SO" maximizing strengths and opportunities, "WT" minimizing weaknesses and threats, "WO" minimizing weaknesses and maximizing opportunities, and "ST" maximizing strengths and minimizing threats. Each distinct type of strategy may be considered for individualized medical strategies. We describe four steps of I-SWOT to establish an individualized medical strategy to treat aortic disease. In the first step, we define the goal of therapy and identify all evidence-based therapeutic options. In a second step, we assess strengths and weaknesses of each therapeutic option in a SW matrix form. In a third step, we assess opportunities and threats related to the individual patient, and in a final step, we use the I-SWOT matrix to establish an individualized medical strategy through matching "SW" with "OT". As an example we present two 30-year-old patients with Marfan syndrome with identical medical history and aortic pathology. As a result of I-SWOT analysis of their individual opportunities and threats, we identified two distinct medical strategies in these patients. I-SWOT is a formal but easy to use tool to translate medical evidence into individualized medical strategies.

  2. Classification of Neuropsychiatric Symptoms Requiring Antipsychotic Treatment in Patients with Alzheimer's Disease: Analysis of the CATIE-AD Study.

    PubMed

    Nagata, Tomoyuki; Shinagawa, Shunichiro; Nakajima, Shinichiro; Plitman, Eric; Mihashi, Yukiko; Hayashi, Shogo; Mimura, Masaru; Nakayama, Kazuhiko

    2016-01-01

    The Neuropsychiatric Inventory (NPI) comprises 12 items, which were conventionally determined by psychopathological symptoms of patients with dementia. The clinical rating scales with structured questionnaires have been useful to evaluate neuropsychiatric symptoms (NPSs) of patients with dementia over the past twenty year. The aim of this study was to classify the conventional NPSs in patients with Alzheimer's disease (AD) requiring antipsychotic treatment for their NPSs into distinct clusters to simplify assessment of these numerous symptoms. Twelve items scores (product of severity and frequency of each symptom) in the NPI taken from the baseline visit were classified into subgroups by principle component analysis using data from 421 outpatients with AD enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Phase 1. Chi square tests were conducted to examine the co-occurrence of the subgroups. We found four distinct clusters: aggressiveness (agitation and irritabilities), apathy and eating problems (apathy and appetite/eating disturbance), psychosis (delusions and hallucinations), and emotion and disinhibition (depression, euphoria, and disinhibition). Anxiety, aberrant motor behavior, and sleep disturbance were not included by these clusters. Apathy and eating problems, and emotion and disinhibition co-occurred (p = 0.002), whereas aggressiveness and psychosis occurred independent of the other clusters. Four distinct category clusters were identified from NPSs in patients with AD requiring antipsychotic treatment. Future studies should investigate psychosocial backgrounds or risk factors of each distinct cluster, in addition to their longitudinal course over treatment intervention.

  3. Phase diagram and electrical behavior of silicon-rich iridium silicide compounds

    NASA Technical Reports Server (NTRS)

    Allevato, C. E.; Vining, Cronin B.

    1992-01-01

    The iridium-silicon phase diagram on the silicon-rich side was investigated by means of X-ray powder diffraction, density, differential thermal analysis, metalography, microprobe analysis, and electrical resistivity. Attempts were made to prepare eight previously reported silicon-rich iridium silicide compounds by arc melting and Bridgman-like growth. However, microprobe analysis identified only four distinct compositions: IrSi, Ir3Si4, Ir3Si5 and IrSi sub about 3. The existence of Ir4Si5 could not be confirmed in this study, even though the crystal structure has been previously reported. Differential thermal analysis (DTA) in conjunction with X-ray powder diffraction confirm polymorphism in IrSi sub about 3, determined to have orthorhombic and monoclinic unit cells in the high and low temperature forms. A eutectic composition alloy of 83 +/- 1 atomic percent silicon was observed between IrSi sub about 3 and silicon. Ir3Si4 exhibits distinct metallic behavior while Ir3Si5 is semiconducting. Both and IrSi and IrSi sub about 3 exhibit nearly temperature independent electrical resistivities on the order of 5-10 x 10 exp -6 ohms-m.

  4. Genetic relatedness between oral and intestinal isolates of Porphyromonas endodontalis by analysis of random amplified polymorphic DNA.

    PubMed

    Gonçalves, R B; Väisänen, M L; Van Steenbergen, T J; Sundqvist, G; Mouton, C

    1999-01-01

    Genomic fingerprints from the DNA of 27 strains of Porphyromonas endodontalis from diverse clinical and geographic origins were generated as random amplified polymorphic DNA (RAPD) using the technique of PCR amplification with a single primer of arbitrary sequence. Cluster analysis of the combined RAPD data obtained with three selected 9- or 10-mer-long primers identified 25 distinct RAPD types which clustered as three main groups identifying three genogroups. Genogroups I and II included exclusively P. endodontalis isolates of oral origin, while 7/9 human intestinal strains of genogroup III which linked at a similarity level of 52% constituted the most homogeneous group in our study. Genotypic diversity within P. endodontalis, as shown by RAPD analysis, suggests that the taxon is composed of two oral genogroups and one intestinal genogroup. This hypothesis remains to be confirmed.

  5. Distinct Cortical Pathways for Music and Speech Revealed by Hypothesis-Free Voxel Decomposition

    PubMed Central

    Norman-Haignere, Sam

    2015-01-01

    SUMMARY The organization of human auditory cortex remains unresolved, due in part to the small stimulus sets common to fMRI studies and the overlap of neural populations within voxels. To address these challenges, we measured fMRI responses to 165 natural sounds and inferred canonical response profiles (“components”) whose weighted combinations explained voxel responses throughout auditory cortex. This analysis revealed six components, each with interpretable response characteristics despite being unconstrained by prior functional hypotheses. Four components embodied selectivity for particular acoustic features (frequency, spectrotemporal modulation, pitch). Two others exhibited pronounced selectivity for music and speech, respectively, and were not explainable by standard acoustic features. Anatomically, music and speech selectivity concentrated in distinct regions of non-primary auditory cortex. However, music selectivity was weak in raw voxel responses, and its detection required a decomposition method. Voxel decomposition identifies primary dimensions of response variation across natural sounds, revealing distinct cortical pathways for music and speech. PMID:26687225

  6. Distinct Cortical Pathways for Music and Speech Revealed by Hypothesis-Free Voxel Decomposition.

    PubMed

    Norman-Haignere, Sam; Kanwisher, Nancy G; McDermott, Josh H

    2015-12-16

    The organization of human auditory cortex remains unresolved, due in part to the small stimulus sets common to fMRI studies and the overlap of neural populations within voxels. To address these challenges, we measured fMRI responses to 165 natural sounds and inferred canonical response profiles ("components") whose weighted combinations explained voxel responses throughout auditory cortex. This analysis revealed six components, each with interpretable response characteristics despite being unconstrained by prior functional hypotheses. Four components embodied selectivity for particular acoustic features (frequency, spectrotemporal modulation, pitch). Two others exhibited pronounced selectivity for music and speech, respectively, and were not explainable by standard acoustic features. Anatomically, music and speech selectivity concentrated in distinct regions of non-primary auditory cortex. However, music selectivity was weak in raw voxel responses, and its detection required a decomposition method. Voxel decomposition identifies primary dimensions of response variation across natural sounds, revealing distinct cortical pathways for music and speech. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Repetition priming influences distinct brain systems: evidence from task-evoked data and resting-state correlations.

    PubMed

    Wig, Gagan S; Buckner, Randy L; Schacter, Daniel L

    2009-05-01

    Behavioral dissociations suggest that a single experience can separately influence multiple processing components. Here we used a repetition priming functional magnetic resonance imaging paradigm that directly contrasted the effects of stimulus and decision changes to identify the underlying brain systems. Direct repetition of stimulus features caused marked reductions in posterior regions of the inferior temporal lobe that were insensitive to whether the decision was held constant or changed between study and test. By contrast, prefrontal cortex showed repetition effects that were sensitive to the exact stimulus-to-decision mapping. Analysis of resting-state functional connectivity revealed that the dissociated repetition effects are embedded within distinct brain systems. Regions that were sensitive to changes in the stimulus correlated with perceptual cortices, whereas the decision changes attenuated activity in regions correlated with middle-temporal regions and a frontoparietal control system. These results thus explain the long-known dissociation between perceptual and conceptual components of priming by revealing how a single experience can separately influence distinct, concurrently active brain systems.

  8. Anogenital warts contain several distinct species of human papillomavirus.

    PubMed Central

    Krzyzek, R A; Watts, S L; Anderson, D L; Faras, A J; Pass, F

    1980-01-01

    Anogenital warts from 26 patients were examined for the presence of human papillomavirus (HPV). Although no whole, intact virus could be identified, varying amounts of nonintegrated HPV DNA were detected in 18 tissue specimens (70%) by employing both an agarose gel-ethidium bromide staining method and the Southern blot hybridization procedure. When hybridization analysis was performed under stringent conditions, six anogenital warts were observed to contain HPV genomic sequences related to either of the cutaneous viruses HPV type 1 (HPV-1) or HPV-2. In 12 tissue samples lacking sequence homology to either HPV-1 or HPV-2 under stringent conditions, HPV-related sequences were detected when the hybridization was performed under less stringent conditions, indicating that an HPV distinct from both HPV-1 and HPV-2 is also associated with these lesions. This anogenital HPV also appeared to be distinct from the other characterized types of HPV. These data indicate that at least three HPVs are associated with anogenital wart disease. Images PMID:6255208

  9. Intrinsic Network Connectivity Patterns Underlying Specific Dimensions of Impulsiveness in Healthy Young Adults.

    PubMed

    Kubera, Katharina M; Hirjak, Dusan; Wolf, Nadine D; Sambataro, Fabio; Thomann, Philipp A; Wolf, R Christian

    2018-05-01

    Impulsiveness is a central human personality trait and of high relevance for the development of several mental disorders. Impulsiveness is a multidimensional construct, yet little is known about dimension-specific neural correlates. Here, we address the question whether motor, attentional and non-planning components, as measured by the Barratt Impulsiveness Scale (BIS-11), are associated with distinct or overlapping neural network activity. In this study, we investigated brain activity at rest and its relationship to distinct dimensions of impulsiveness in 30 healthy young adults (m/f = 13/17; age mean/SD = 26.4/2.6 years) using resting-state functional magnetic resonance imaging at 3T. A spatial independent component analysis and a multivariate model selection strategy were used to identify systems loading on distinct impulsivity domains. We first identified eight networks for which we had a-priori hypotheses. These networks included basal ganglia, cortical motor, cingulate and lateral prefrontal systems. From the eight networks, three were associated with impulsiveness measures (p < 0.05, FDR corrected). There were significant relationships between right frontoparietal network function and all three BIS domains. Striatal and midcingulate network activity was associated with motor impulsiveness only. Within the networks regionally confined effects of age and gender were found. These data suggest distinct and overlapping patterns of neural activity underlying specific dimensions of impulsiveness. Motor impulsiveness appears to be specifically related to striatal and midcingulate network activity, in contrast to a domain-unspecific right frontoparietal system. Effects of age and gender have to be considered in young healthy samples.

  10. Identifying patterns of motor performance, executive functioning, and verbal ability in preschool children: A latent profile analysis.

    PubMed

    Houwen, Suzanne; Kamphorst, Erica; van der Veer, Gerda; Cantell, Marja

    2018-04-30

    A relationship between motor performance and cognitive functioning is increasingly being recognized. Yet, little is known about the precise nature of the relationship between both domains, especially in early childhood. To identify distinct constellations of motor performance, executive functioning (EF), and verbal ability in preschool aged children; and to explore how individual and contextual variables are related to profile membership. The sample consisted of 119 3- to 4-year old children (62 boys; 52%). The home based assessments consisted of a standardized motor test (Movement Assessment Battery for Children - 2), five performance-based EF tasks measuring inhibition and working memory, and the Receptive Vocabulary subtest from the Wechsler Preschool and Primary Scale of Intelligence Third Edition. Parents filled out the Behavior Rating Inventory of Executive Function - Preschool version. Latent profile analysis (LPA) was used to delineate profiles of motor performance, EF, and verbal ability. Chi-square statistics and multinomial logistic regression analysis were used to examine whether profile membership was predicted by age, gender, risk of motor coordination difficulties, ADHD symptomatology, language problems, and socioeconomic status (SES). LPA yielded three profiles with qualitatively distinct response patterns of motor performance, EF, and verbal ability. Quantitatively, the profiles showed most pronounced differences with regard to parent ratings and performance-based tests of EF, as well as verbal ability. Risk of motor coordination difficulties and ADHD symptomatology were associated with profile membership, whereas age, gender, language problems, and SES were not. Our results indicate that there are distinct subpopulations of children who show differential relations with regard to motor performance, EF, and verbal ability. The fact that we found both quantitative as well as qualitative differences between the three patterns of profiles underscores the need for a person-centered approach with a focus on patterns of individual characteristics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Cluster analysis of the national weight control registry to identify distinct subgroups maintaining successful weight loss.

    PubMed

    Ogden, Lorraine G; Stroebele, Nanette; Wyatt, Holly R; Catenacci, Victoria A; Peters, John C; Stuht, Jennifer; Wing, Rena R; Hill, James O

    2012-10-01

    The National Weight Control Registry (NWCR) is the largest ongoing study of individuals successful at maintaining weight loss; the registry enrolls individuals maintaining a weight loss of at least 13.6 kg (30 lb) for a minimum of 1 year. The current report uses multivariate latent class cluster analysis to identify unique clusters of individuals within the NWCR that have distinct experiences, strategies, and attitudes with respect to weight loss and weight loss maintenance. The cluster analysis considers weight and health history, weight control behaviors and strategies, effort and satisfaction with maintaining weight, and psychological and demographic characteristics. The analysis includes 2,228 participants enrolled between 1998 and 2002. Cluster 1 (50.5%) represents a weight-stable, healthy, exercise conscious group who are very satisfied with their current weight. Cluster 2 (26.9%) has continuously struggled with weight since childhood; they rely on the greatest number of resources and strategies to lose and maintain weight, and report higher levels of stress and depression. Cluster 3 (12.7%) represents a group successful at weight reduction on the first attempt; they were least likely to be overweight as children, are maintaining the longest duration of weight loss, and report the least difficulty maintaining weight. Cluster 4 (9.9%) represents a group less likely to use exercise to control weight; they tend to be older, eat fewer meals, and report more health problems. Further exploration of the unique characteristics of these clusters could be useful for tailoring future weight loss and weight maintenance programs to the specific characteristics of an individual.

  12. Comprehensive analysis of the optical Kerr coefficient of graphene

    DOE PAGES

    Soh, Daniel B. S.; Hamerly, Ryan; Mabuchi, Hideo

    2016-08-25

    We present a comprehensive analysis of the nonlinear optical Kerr effect in graphene. We directly solve the S-matrix element to calculate the absorption rate, utilizing the Volkov-Keldysh-type crystal wave functions. We then convert to the nonlinear refractive index coefficients through the Kramers-Kronig relation. In this formalism, the source of Kerr nonlinearity is the interplay of optical fields that cooperatively drive the transition from valence to conduction band. This formalism makes it possible to identify and compute the rates of distinct nonlinear processes that contribute to the Kerr nonlinear refractive index coefficient. The four identified mechanisms are two-photon absorption, Raman transition,more » self-coupling, and quadratic ac Stark effect. As a result, we present a comparison of our theory with recent experimental and theoretical results.« less

  13. A Computational Approach to Qualitative Analysis in Large Textual Datasets

    PubMed Central

    Evans, Michael S.

    2014-01-01

    In this paper I introduce computational techniques to extend qualitative analysis into the study of large textual datasets. I demonstrate these techniques by using probabilistic topic modeling to analyze a broad sample of 14,952 documents published in major American newspapers from 1980 through 2012. I show how computational data mining techniques can identify and evaluate the significance of qualitatively distinct subjects of discussion across a wide range of public discourse. I also show how examining large textual datasets with computational methods can overcome methodological limitations of conventional qualitative methods, such as how to measure the impact of particular cases on broader discourse, how to validate substantive inferences from small samples of textual data, and how to determine if identified cases are part of a consistent temporal pattern. PMID:24498398

  14. Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits

    PubMed Central

    Palmer, Cameron D.; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E.; Launer, Lenore J.; Nalls, Michael A.; Clark, Jeanne M.; Mitchell, Braxton D.; Shuldiner, Alan R.; Butler, Johannah L.; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M.; O'Donnell, Christopher J.; Sahani, Dushyant V.; Salomaa, Veikko; Schadt, Eric E.; Schwartz, Stephen M.; Siscovick, David S.; Voight, Benjamin F.; Carr, J. Jeffrey; Feitosa, Mary F.; Harris, Tamara B.; Fox, Caroline S.

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%–27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10−8) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT–assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits. PMID:21423719

  15. Different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis.

    PubMed

    Akar, Servet; Solmaz, Dilek; Kasifoglu, Timucin; Bilge, Sule Yasar; Sari, Ismail; Gumus, Zeynep Zehra; Tunca, Mehmet

    2016-02-01

    The aim of this study was to evaluate whether there are clinical subgroups that may have different prognoses among FMF patients. The cumulative clinical features of a large group of FMF patients [1168 patients, 593 (50.8%) male, mean age 35.3 years (s.d. 12.4)] were studied. To analyse our data and identify groups of FMF patients with similar clinical characteristics, a two-step cluster analysis using log-likelihood distance measures was performed. For clustering the FMF patients, we evaluated the following variables: gender, current age, age at symptom onset, age at diagnosis, presence of major clinical features, variables related with therapy and family history for FMF, renal failure and carriage of M694V. Three distinct groups of FMF patients were identified. Cluster 1 was characterized by a high prevalence of arthritis, pleuritis, erysipelas-like erythema (ELE) and febrile myalgia. The dosage of colchicine and the frequency of amyloidosis were lower in cluster 1. Patients in cluster 2 had an earlier age of disease onset and diagnosis. M694V carriage and amyloidosis prevalence were the highest in cluster 2. This group of patients was using the highest dose of colchicine. Patients in cluster 3 had the lowest prevalence of arthritis, ELE and febrile myalgia. The frequencies of M694V carriage and amyloidosis were lower in cluster 3 than the overall FMF patients. Non-response to colchicine was also slightly lower in cluster 3. Patients with FMF can be clustered into distinct patterns of clinical and genetic manifestations and these patterns may have different prognostic significance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Top-down and bottom-up attention-to-memory: mapping functional connectivity in two distinct networks that underlie cued and uncued recognition memory.

    PubMed

    Burianová, Hana; Ciaramelli, Elisa; Grady, Cheryl L; Moscovitch, Morris

    2012-11-15

    The objective of this study was to examine the functional connectivity of brain regions active during cued and uncued recognition memory to test the idea that distinct networks would underlie these memory processes, as predicted by the attention-to-memory (AtoM) hypothesis. The AtoM hypothesis suggests that dorsal parietal cortex (DPC) allocates effortful top-down attention to memory retrieval during cued retrieval, whereas ventral parietal cortex (VPC) mediates spontaneous bottom-up capture of attention by memory during uncued retrieval. To identify networks associated with these two processes, we conducted a functional connectivity analysis of a left DPC and a left VPC region, both identified by a previous analysis of task-related regional activations. We hypothesized that the two parietal regions would be functionally connected with distinct neural networks, reflecting their engagement in the differential mnemonic processes. We found two spatially dissociated networks that overlapped only in the precuneus. During cued trials, DPC was functionally connected with dorsal attention areas, including the superior parietal lobules, right precuneus, and premotor cortex, as well as relevant memory areas, such as the left hippocampus and the middle frontal gyri. During uncued trials, VPC was functionally connected with ventral attention areas, including the supramarginal gyrus, cuneus, and right fusiform gyrus, as well as the parahippocampal gyrus. In addition, activity in the DPC network was associated with faster response times for cued retrieval. This is the first study to show a dissociation of the functional connectivity of posterior parietal regions during episodic memory retrieval, characterized by a top-down AtoM network involving DPC and a bottom-up AtoM network involving VPC. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Identification of a reference gene for the quantification of mRNA and miRNA expression during skin wound healing.

    PubMed

    Etich, Julia; Bergmeier, Vera; Pitzler, Lena; Brachvogel, Bent

    2017-03-01

    Wound healing is a coordinated process to restore tissue homeostasis and reestablish the protective barrier of the skin. miRNAs may modulate the expression of target genes to contribute to repair processes, but due to the complexity of the tissue it is challenging to quantify gene expression during the distinct phases of wound repair. Here, we aimed to identify a common reference gene to quantify changes in miRNA and mRNA expression during skin wound healing. Quantitative real-time PCR and bioinformatic analysis tools were used to identify suitable reference genes during skin repair and their reliability was tested by studying the expression of mRNAs and miRNAs. Morphological assessment of wounds showed that the injury model recapitulates the distinct phases of skin repair. Non-degraded RNA could be isolated from skin and wounds and used to study the expression of non-coding small nuclear RNAs during wound healing. Among those, RNU6B was most constantly expressed during skin repair. Using this reference gene we could confirm the transient upregulation of IL-1β and PTPRC/CD45 during the early phase as well as the increased expression of collagen type I at later stages of repair and validate the differential expression of miR-204, miR-205, and miR-31 in skin wounds. In contrast to Gapdh the normalization to multiple reference genes gave a similar outcome. RNU6B is an accurate alternative normalizer to quantify mRNA and miRNA expression during the distinct phases of skin wound healing when analysis of multiple reference genes is not feasible.

  18. Characterizing the course of back pain after osteoporotic vertebral fracture: a hierarchical cluster analysis of a prospective cohort study.

    PubMed

    Toyoda, Hiromitsu; Takahashi, Shinji; Hoshino, Masatoshi; Takayama, Kazushi; Iseki, Kazumichi; Sasaoka, Ryuichi; Tsujio, Tadao; Yasuda, Hiroyuki; Sasaki, Takeharu; Kanematsu, Fumiaki; Kono, Hiroshi; Nakamura, Hiroaki

    2017-09-23

    This study demonstrated four distinct patterns in the course of back pain after osteoporotic vertebral fracture (OVF). Greater angular instability in the first 6 months after the baseline was one factor affecting back pain after OVF. Understanding the natural course of symptomatic acute OVF is important in deciding the optimal treatment strategy. We used latent class analysis to classify the course of back pain after OVF and identify the risk factors associated with persistent pain. This multicenter cohort study included 218 consecutive patients with ≤ 2-week-old OVFs who were enrolled at 11 institutions. Dynamic x-rays and back pain assessment with a visual analog scale (VAS) were obtained at enrollment and at 1-, 3-, and 6-month follow-ups. The VAS scores were used to characterize patient groups, using hierarchical cluster analysis. VAS for 128 patients was used for hierarchical cluster analysis. Analysis yielded four clusters representing different patterns of back pain progression. Cluster 1 patients (50.8%) had stable, mild pain. Cluster 2 patients (21.1%) started with moderate pain and progressed quickly to very low pain. Patients in cluster 3 (10.9%) had moderate pain that initially improved but worsened after 3 months. Cluster 4 patients (17.2%) had persistent severe pain. Patients in cluster 4 showed significant high baseline pain intensity, higher degree of angular instability, and higher number of previous OVFs, and tended to lack regular exercise. In contrast, patients in cluster 2 had significantly lower baseline VAS and less angular instability. We identified four distinct groups of OVF patients with different patterns of back pain progression. Understanding the course of back pain after OVF may help in its management and contribute to future treatment trials.

  19. Phylogenetic analysis of Mycobacterium massiliense strains having recombinant rpoB gene laterally transferred from Mycobacterium abscessus.

    PubMed

    Kim, Byoung-Jun; Kim, Ga-Na; Kim, Bo-Ram; Shim, Tae-Sun; Kook, Yoon-Hoh; Kim, Bum-Joon

    2017-01-01

    Recent multi locus sequence typing (MLST) and genome based studies indicate that lateral gene transfer (LGT) events in the rpoB gene are prevalent between Mycobacterium abscessus complex strains. To check the prevalence of the M. massiliense strains subject to rpoB LGT (Rec-mas), we applied rpoB typing (711 bp) to 106 Korean strains of M. massiliense infection that had already been identified by hsp65 sequence analysis (603 bp). The analysis indicated 6 smooth strains in M. massiliense Type I (10.0%, 6/60) genotypes but no strains in M. massiliense Type II genotypes (0%, 0/46), showing a discrepancy between the 2 typing methods. Further MLST analysis based on the partial sequencing of seven housekeeping genes, argH, cya, glpK, gnd, murC, pta and purH, as well as erm(41) PCR proved that these 6 Rec-mas strains consisted of two distinct genotypes belonging to M. massiliense and not M. abscessus. The complete rpoB sequencing analysis showed that these 6 Rec-mas strains have an identical hybrid rpoB gene, of which a 478 bp partial rpoB fragment may be laterally transferred from M. abscessus. Notably, five of the 6 Rec-mas strains showed complete identical sequences in a total of nine genes, including the seven MLST genes, hsp65, and rpoB, suggesting their clonal propagation in South Korea. In conclusion, we identified 6 M. massiliense smooth strains of 2 phylogenetically distinct genotypes with a specific hybrid rpoB gene laterally transferred from M. abscessus from Korean patients. Their clinical relevance and bacteriological traits remain to be elucidated.

  20. Phylogenetic analysis of Mycobacterium massiliense strains having recombinant rpoB gene laterally transferred from Mycobacterium abscessus

    PubMed Central

    Kim, Byoung-Jun; Kim, Ga-Na; Kim, Bo-Ram; Shim, Tae-Sun; Kook, Yoon-Hoh

    2017-01-01

    Recent multi locus sequence typing (MLST) and genome based studies indicate that lateral gene transfer (LGT) events in the rpoB gene are prevalent between Mycobacterium abscessus complex strains. To check the prevalence of the M. massiliense strains subject to rpoB LGT (Rec-mas), we applied rpoB typing (711 bp) to 106 Korean strains of M. massiliense infection that had already been identified by hsp65 sequence analysis (603 bp). The analysis indicated 6 smooth strains in M. massiliense Type I (10.0%, 6/60) genotypes but no strains in M. massiliense Type II genotypes (0%, 0/46), showing a discrepancy between the 2 typing methods. Further MLST analysis based on the partial sequencing of seven housekeeping genes, argH, cya, glpK, gnd, murC, pta and purH, as well as erm(41) PCR proved that these 6 Rec-mas strains consisted of two distinct genotypes belonging to M. massiliense and not M. abscessus. The complete rpoB sequencing analysis showed that these 6 Rec-mas strains have an identical hybrid rpoB gene, of which a 478 bp partial rpoB fragment may be laterally transferred from M. abscessus. Notably, five of the 6 Rec-mas strains showed complete identical sequences in a total of nine genes, including the seven MLST genes, hsp65, and rpoB, suggesting their clonal propagation in South Korea. In conclusion, we identified 6 M. massiliense smooth strains of 2 phylogenetically distinct genotypes with a specific hybrid rpoB gene laterally transferred from M. abscessus from Korean patients. Their clinical relevance and bacteriological traits remain to be elucidated. PMID:28604829

  1. Functional Status, Quality of Life, and Costs Associated With Fibromyalgia Subgroups: A Latent Profile Analysis.

    PubMed

    Luciano, Juan V; Forero, Carlos G; Cerdà-Lafont, Marta; Peñarrubia-María, María Teresa; Fernández-Vergel, Rita; Cuesta-Vargas, Antonio I; Ruíz, José M; Rozadilla-Sacanell, Antoni; Sirvent-Alierta, Elena; Santo-Panero, Pilar; García-Campayo, Javier; Serrano-Blanco, Antoni; Pérez-Aranda, Adrián; Rubio-Valera, María

    2016-10-01

    Although fibromyalgia syndrome (FM) is considered a heterogeneous condition, there is no generally accepted subgroup typology. We used hierarchical cluster analysis and latent profile analysis to replicate Giesecke's classification in Spanish FM patients. The second aim was to examine whether the subgroups differed in sociodemographic characteristics, functional status, quality of life, and in direct and indirect costs. A total of 160 FM patients completed the following measures for cluster derivation: the Center for Epidemiological Studies-Depression Scale, the Trait Anxiety Inventory, the Pain Catastrophizing Scale, and the Control over Pain subscale. Pain threshold was measured with a sphygmomanometer. In addition, the Fibromyalgia Impact Questionnaire-Revised, the EuroQoL-5D-3L, and the Client Service Receipt Inventory were administered for cluster validation. Two distinct clusters were identified using hierarchical cluster analysis ("hypersensitive" group, 69.8% and "functional" group, 30.2%). In contrast, the latent profile analysis goodness-of-fit indices supported the existence of 3 FM patient profiles: (1) a "functional" profile (28.1%) defined as moderate tenderness, distress, and pain catastrophizing; (2) a "dysfunctional" profile (45.6%) defined by elevated tenderness, distress, and pain catastrophizing; and (3) a "highly dysfunctional and distressed" profile (26.3%) characterized by elevated tenderness and extremely high distress and catastrophizing. We did not find significant differences in sociodemographic characteristics between the 2 clusters or among the 3 profiles. The functional profile was associated with less impairment, greater quality of life, and lower health care costs. We identified 3 distinct profiles which accounted for the heterogeneity of FM patients. Our findings might help to design tailored interventions for FM patients.

  2. Genotyping-by-sequencing highlights original diversity patterns within a European collection of 1191 maize flint lines, as compared to the maize USDA genebank.

    PubMed

    Gouesnard, Brigitte; Negro, Sandra; Laffray, Amélie; Glaubitz, Jeff; Melchinger, Albrecht; Revilla, Pedro; Moreno-Gonzalez, Jesus; Madur, Delphine; Combes, Valérie; Tollon-Cordet, Christine; Laborde, Jacques; Kermarrec, Dominique; Bauland, Cyril; Moreau, Laurence; Charcosset, Alain; Nicolas, Stéphane

    2017-10-01

    Genotyping by sequencing is suitable for analysis of global diversity in maize. We showed the distinctiveness of flint maize inbred lines of interest to enrich the diversity of breeding programs. Genotyping-by-sequencing (GBS) is a highly cost-effective procedure that permits the analysis of large collections of inbred lines. We used it to characterize diversity in 1191 maize flint inbred lines from the INRA collection, the European Cornfed association panel, and lines recently derived from landraces. We analyzed the properties of GBS data obtained with different imputation methods, through comparison with a 50 K SNP array. We identified seven ancestral groups within the Flint collection (dent, Northern flint, Italy, Pyrenees-Galicia, Argentina, Lacaune, Popcorn) in agreement with breeding knowledge. Analysis highlighted many crosses between different origins and the improvement of flint germplasm with dent germplasm. We performed association studies on different agronomic traits, revealing SNPs associated with cob color, kernel color, and male flowering time variation. We compared the diversity of both our collection and the USDA collection which has been previously analyzed by GBS. The population structure of the 4001 inbred lines confirmed the influence of the historical inbred lines (B73, A632, Oh43, Mo17, W182E, PH207, and Wf9) within the dent group. It showed distinctly different tropical and popcorn groups, a sweet-Northern flint group and a flint group sub-structured in Italian and European flint (Pyrenees-Galicia and Lacaune) groups. Interestingly, we identified several selective sweeps between dent, flint, and tropical inbred lines that co-localized with SNPs associated with flowering time variation. The joint analysis of collections by GBS offers opportunities for a global diversity analysis of maize inbred lines.

  3. Linking Spatial Variations in Water Quality with Water and Land Management using Multivariate Techniques.

    PubMed

    Wan, Yongshan; Qian, Yun; Migliaccio, Kati White; Li, Yuncong; Conrad, Cecilia

    2014-03-01

    Most studies using multivariate techniques for pollution source evaluation are conducted in free-flowing rivers with distinct point and nonpoint sources. This study expanded on previous research to a managed "canal" system discharging into the Indian River Lagoon, Florida, where water and land management is the single most important anthropogenic factor influencing water quality. Hydrometric and land use data of four drainage basins were uniquely integrated into the analysis of 25 yr of monthly water quality data collected at seven stations to determine the impact of water and land management on the spatial variability of water quality. Cluster analysis (CA) classified seven monitoring stations into four groups (CA groups). All water quality parameters identified by discriminant analysis showed distinct spatial patterns among the four CA groups. Two-step principal component analysis/factor analysis (PCA/FA) was conducted with (i) water quality data alone and (ii) water quality data in conjunction with rainfall, flow, and land use data. The results indicated that PCA/FA of water quality data alone was unable to identify factors associated with management activities. The addition of hydrometric and land use data into PCA/FA revealed close associations of nutrients and color with land management and storm-water retention in pasture and citrus lands; total suspended solids, turbidity, and NO + NO with flow and Lake Okeechobee releases; specific conductivity with supplemental irrigation supply; and dissolved O with wetland preservation. The practical implication emphasizes the importance of basin-specific land and water management for ongoing pollutant loading reduction and ecosystem restoration programs. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  4. Apple miRNAs and tasiRNAs with novel regulatory networks

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) and their regulatory functions have been extensively characterized in model species but whether apple has evolved similar or unique regulatory features remains unknown. Results We performed deep small RNA-seq and identified 23 conserved, 10 less-conserved and 42 apple-specific miRNAs or families with distinct expression patterns. The identified miRNAs target 118 genes representing a wide range of enzymatic and regulatory activities. Apple also conserves two TAS gene families with similar but unique trans-acting small interfering RNA (tasiRNA) biogenesis profiles and target specificities. Importantly, we found that miR159, miR828 and miR858 can collectively target up to 81 MYB genes potentially involved in diverse aspects of plant growth and development. These miRNA target sites are differentially conserved among MYBs, which is largely influenced by the location and conservation of the encoded amino acid residues in MYB factors. Finally, we found that 10 of the 19 miR828-targeted MYBs undergo small interfering RNA (siRNA) biogenesis at the 3' cleaved, highly divergent transcript regions, generating over 100 sequence-distinct siRNAs that potentially target over 70 diverse genes as confirmed by degradome analysis. Conclusions Our work identified and characterized apple miRNAs, their expression patterns, targets and regulatory functions. We also discovered that three miRNAs and the ensuing siRNAs exploit both conserved and divergent sequence features of MYB genes to initiate distinct regulatory networks targeting a multitude of genes inside and outside the MYB family. PMID:22704043

  5. A profile of four patterns of vulnerability to functional decline in older general medicine patients in Victoria, Australia: a cross sectional survey.

    PubMed

    Beddoes-Ley, Lenore; Khaw, Damien; Duke, Maxine; Botti, Mari

    2016-08-05

    There are limited published data reporting Australian hospitalized elders' vulnerability to functional decline to guide best practice interventions. The objectives of this study were to describe the prevalence of vulnerability to functional decline and explore profiles of vulnerability related to the performance of physical activity in a representative group of elders in a single centre in Victoria, Australia. A cross-sectional survey of patients aged ≥ 70 years (Mean age 82.4, SD 7 years) admitted to a general medical ward of an Australian tertiary-referral metropolitan public hospital from March 2010 to March 2011 (n = 526). Patients were screened using the Vulnerable Elders Survey (VES-13). Distinct typologies of physical difficulties were identified using latent class analysis. Most elders scored ≥3/10 on the VES-13 and were rated vulnerable to functional decline (n = 480, 89.5 %). Four distinct classes of physical difficulty were identified: 1) Elders with higher physical functioning (n = 114, 21.7 %); 2) Ambulant elders with diminished strength (n = 24, 4.6 %); 3) Elders with impaired mobility, strength and ability to stoop (n = 267, 50.8 %) and 4) Elders with extensive physical impairment (n = 121, 23 %) Vulnerable elders were distributed through all classes. Older general medicine patients in Victoria, Australia, are highly vulnerable to functional decline. We identified four distinct patterns of physical difficulties associated with vulnerability to functional decline that can inform health service planning, delivery and education.

  6. Evidence of two distinct phylogenetic lineages of dog rabies virus circulating in Cambodia.

    PubMed

    Mey, Channa; Metlin, Artem; Duong, Veasna; Ong, Sivuth; In, Sotheary; Horwood, Paul F; Reynes, Jean-Marc; Bourhy, Hervé; Tarantola, Arnaud; Buchy, Philippe

    2016-03-01

    This first extensive retrospective study of the molecular epidemiology of dog rabies in Cambodia included 149 rabies virus (RABV) entire nucleoprotein sequences obtained from 1998-2011. The sequences were analyzed in conjunction with RABVs from other Asian countries. Phylogenetic reconstruction confirmed the South-East Asian phylogenetic clade comprising viruses from Cambodia, Vietnam, Thailand, Laos and Myanmar. The present study represents the first attempt to classify the phylogenetic lineages inside this clade, resulting in the confirmation that all the Cambodian viruses belonged to the South-East Asian (SEA) clade. Three distinct phylogenetic lineages in the region were established with the majority of viruses from Cambodia closely related to viruses from Thailand, Laos and Vietnam, forming the geographically widespread phylogenetic lineage SEA1. A South-East Asian lineage SEA2 comprised two viruses from Cambodia was identified, which shared a common ancestor with RABVs originating from Laos. Viruses from Myanmar formed separate phylogenetic lineages within the major SEA clade. Bayesian molecular clock analysis suggested that the time to most recent common ancestor (TMRCA) of all Cambodian RABVs dated to around 1950. The TMRCA of the Cambodian SEA1 lineage was around 1964 and that of the SEA2 lineage was around 1953. The results identified three phylogenetically distinct and geographically separated lineages inside the earlier identified major SEA clade, covering at least five countries in the region. A greater understanding of the molecular epidemiology of rabies in South-East Asia is an important step to monitor progress on the efforts to control canine rabies in the region. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Anticancer Properties of Distinct Antimalarial Drug Classes

    PubMed Central

    Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

    2013-01-01

    We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

  8. Emergence and global spread of epidemic healthcare-associated Clostridium difficile

    PubMed Central

    He, Miao; Miyajima, Fabio; Roberts, Paul; Ellison, Louise; Pickard, Derek J.; Martin, Melissa J.; Connor, Thomas R.; Harris, Simon R.; Fairley, Derek; Bamford, Kathleen B.; D’Arc, Stephanie; Brazier, Jon; Brown, Derek; Coia, John E.; Douce, Gill; Gerding, Dale; Kim, Hee Jung; Koh, Tse Hsien; Kato, Haru; Senoh, Mitsutoshi; Louie, Tom; Michell, Stephen; Butt, Emma; Peacock, Sharon J.; Brown, Nick M.; Riley, Tom; Songer, Glen; Wilcox, Mark; Pirmohamed, Munir; Kuijper, Ed; Hawkey, Peter; Wren, Brendan W.; Dougan, Gordon; Parkhill, Julian; Lawley, Trevor D.

    2012-01-01

    Epidemic Clostridium difficile (027/BI/NAP1) rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key moments in the evolutionary history leading to its emergence and subsequent patterns of global spread remain unknown. Here we define the global population structure of C. difficile 027/BI/NAP1 based on whole-genome sequencing and phylogenetic analysis. We demonstrate that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance mutation and a highly-related conjugative transposon. The two epidemic lineages displayed distinct patterns of global spread, and the FQR2 lineage spread more widely leading to healthcare outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid trans-continental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system. PMID:23222960

  9. Genome-wide Functional Analysis of CREB/Long-Term Memory-Dependent Transcription Reveals Distinct Basal and Memory Gene Expression Programs

    PubMed Central

    Lakhina, Vanisha; Arey, Rachel N.; Kaletsky, Rachel; Kauffman, Amanda; Stein, Geneva; Keyes, William; Xu, Daniel; Murphy, Coleen T.

    2014-01-01

    SUMMARY Induced CREB activity is a hallmark of long-term memory, but the full repertoire of CREB transcriptional targets required specifically for memory is not known in any system. To obtain a more complete picture of the mechanisms involved in memory, we combined memory training with genome-wide transcriptional analysis of C. elegans CREB mutants. This approach identified 757 significant CREB/memory-induced targets and confirmed the involvement of known memory genes from other organisms, but also suggested new mechanisms and novel components that may be conserved through mammals. CREB mediates distinct basal and memory transcriptional programs at least partially through spatial restriction of CREB activity: basal targets are regulated primarily in nonneuronal tissues, while memory targets are enriched for neuronal expression, emanating from CREB activity in AIM neurons. This suite of novel memory-associated genes will provide a platform for the discovery of orthologous mammalian long-term memory components. PMID:25611510

  10. Spatio-temporal distribution and natural variation of metabolites in citrus fruits.

    PubMed

    Wang, Shouchuang; Tu, Hong; Wan, Jian; Chen, Wei; Liu, Xianqing; Luo, Jie; Xu, Juan; Zhang, Hongyan

    2016-05-15

    To study the natural variation and spatio-temporal accumulation of citrus metabolites, liquid chromatography tandem mass spectrometry (LC-MS) based metabolome analysis was performed on four fruit tissues (flavedo, albedo, segment membrane and juice sacs) and different Citrus species (lemon, pummelo and grapefruit, sweet orange and mandarin). Using a non-targeted metabolomics approach, more than 2000 metabolite signals were detected, from which more than 54 metabolites, including amino acids, flavonoids and limonoids, were identified/annotated. Differential accumulation patterns of both primary metabolites and secondary metabolites in various tissues and species were revealed by our study. Further investigation indicated that flavedo accumulates more flavonoids while juice sacs contain more amino acids. Besides this, cluster analysis based on the levels of metabolites detected in 47 individual Citrus accessions clearly grouped them into four distinct clusters: pummelos and grapefruits, lemons, sweet oranges and mandarins, while the cluster of pummelos and grapefruits lay distinctly apart from the other three species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Elucidating distinct ion channel populations on the surface of hippocampal neurons via single-particle tracking recurrence analysis

    NASA Astrophysics Data System (ADS)

    Sikora, Grzegorz; Wyłomańska, Agnieszka; Gajda, Janusz; Solé, Laura; Akin, Elizabeth J.; Tamkun, Michael M.; Krapf, Diego

    2017-12-01

    Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface. We specifically study the dynamics of the K+ channel Kv1.4 and the Na+ channel Nav1.6 on the surface of cultured hippocampal neurons at the single-molecule level. We find that both these molecules are expressed in two different forms with distinct kinetics with regards to surface interactions, emphasizing the complex proteomic landscape of the neuronal surface. Further, the tools presented in this work provide new methods for the analysis of membrane nanodomains, transient confinement, and identification of populations within single-particle trajectories.

  12. Integrating single-cell transcriptomic data across different conditions, technologies, and species.

    PubMed

    Butler, Andrew; Hoffman, Paul; Smibert, Peter; Papalexi, Efthymia; Satija, Rahul

    2018-06-01

    Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. However, identifying subpopulations of cells that are present across multiple data sets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq data sets based on common sources of variation, enabling the identification of shared populations across data sets and downstream comparative analysis. We apply this approach, implemented in our R toolkit Seurat (http://satijalab.org/seurat/), to align scRNA-seq data sets of peripheral blood mononuclear cells under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across data sets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq data sets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution.

  13. Domestic Property Violence: A Distinct and Damaging Form of Parent Abuse.

    PubMed

    Murphy-Edwards, Latesha; van Heugten, Kate

    2018-02-01

    This article reports on the qualitative phase of mixed method research conducted in a medium-size city in New Zealand, which examined 14 parents' experiences of child- and youth-perpetrated domestic property violence (DPV). The research used semi-structured interviews and interpretative phenomenological analysis, enabling parents' perceptions of the causes and impacts of this form of family violence to be explored in depth. Three superordinate themes were identified in the analysis: damage done, the various impacts of DPV; staying safe and sane; and making sense of DPV, parents' perspectives. An ecological meaning-making theory emerged from the data and provided an overarching interpretative framework for considering the themes both separately and together. The findings showed that DPV is a distinct form of parent abuse and one that can have serious impacts of a financial, emotional, and relational nature. The theoretical and practical implications of the findings are discussed along with ideas for further research into this problem.

  14. A social cybernetic analysis of simulation-based, remotely delivered medical skills training in an austere environment: developing a test bed for spaceflight medicine.

    PubMed

    Musson, David M; Doyle, Thomas E

    2012-01-01

    This paper describes analysis of medical skills training exercises that were conducted at an arctic research station. These were conducted as part of an ongoing effort to establish high fidelity medical simulation test bed capabilities in remote and extreme "space analogue" environments for the purpose studying medical care in spaceflight. The methodological orientation followed by the authors is that of "second order cybernetics," or the science of studying human systems where the observer is involved within the system in question. Analyses presented include the identification of three distinct phases of the training activity, and two distinct levels of work groups-- termed "first-order teams" and "second-order teams." Depending on the phase of activity, first-order and second-order teams are identified, each having it own unique structure, composition, communications, goals, and challenges. Several specific teams are highlighted as case examples. Limitations of this approach are discussed, as are potential benefits to ongoing and planned research activity in this area.

  15. Two distinct phenotypes of asthma in elite athletes identified by latent class analysis.

    PubMed

    Couto, Mariana; Stang, Julie; Horta, Luís; Stensrud, Trine; Severo, Milton; Mowinckel, Petter; Silva, Diana; Delgado, Luís; Moreira, André; Carlsen, Kai-Håkon

    2015-01-01

    Clusters of asthma in athletes have been insufficiently studied. Therefore, the present study aimed to characterize asthma phenotypes in elite athletes using latent class analysis (LCA) and to evaluate its association with the type of sport practiced. In the present cross-sectional study, an analysis of athletes' records was carried out in databases of the Portuguese National Anti-Doping Committee and the Norwegian School of Sport Sciences. Athletes with asthma, diagnosed according to criteria given by the International Olympic Committee, were included for LCA. Sports practiced were categorized into water, winter and other sports. Of 324 files screened, 150 files belonged to asthmatic athletes (91 Portuguese; 59 Norwegian). LCA retrieved two clusters: "atopic asthma" defined by allergic sensitization, rhinitis and allergic co-morbidities and increased exhaled nitric oxide levels; and "sports asthma", defined by exercise-induced respiratory symptoms and airway hyperesponsiveness without allergic features. The risk of developing the phenotype "sports asthma" was significantly increased in athletes practicing water (OR = 2.87; 95% CI [1.82-4.51]) and winter (OR = 8.65; 95% CI [2.67-28.03]) sports, when compared with other athletes. Two asthma phenotypes were identified in elite athletes: "atopic asthma" and "sports asthma". The type of sport practiced was associated with different phenotypes: water and winter sport athletes had three- and ninefold increased risk of "sports asthma". Recognizing different phenotypes is clinically relevant as it would lead to distinct targeted treatments.

  16. Classification of Forefoot Plantar Pressure Distribution in Persons with Diabetes: A Novel Perspective for the Mechanical Management of Diabetic Foot?

    PubMed Central

    Deschamps, Kevin; Matricali, Giovanni Arnoldo; Roosen, Philip; Desloovere, Kaat; Bruyninckx, Herman; Spaepen, Pieter; Nobels, Frank; Tits, Jos; Flour, Mieke; Staes, Filip

    2013-01-01

    Background The aim of this study was to identify groups of subjects with similar patterns of forefoot loading and verify if specific groups of patients with diabetes could be isolated from non-diabetics. Methodology/Principal Findings Ninety-seven patients with diabetes and 33 control participants between 45 and 70 years were prospectively recruited in two Belgian Diabetic Foot Clinics. Barefoot plantar pressure measurements were recorded and subsequently analysed using a semi-automatic total mapping technique. Kmeans cluster analysis was applied on relative regional impulses of six forefoot segments in order to pursue a classification for the control group separately, the diabetic group separately and both groups together. Cluster analysis led to identification of three distinct groups when considering only the control group. For the diabetic group, and the computation considering both groups together, four distinct groups were isolated. Compared to the cluster analysis of the control group an additional forefoot loading pattern was identified. This group comprised diabetic feet only. The relevance of the reported clusters was supported by ANOVA statistics indicating significant differences between different regions of interest and different clusters. Conclusion/s Significance There seems to emerge a new era in diabetic foot medicine which embraces the classification of diabetic patients according to their biomechanical profile. Classification of the plantar pressure distribution has the potential to provide a means to determine mechanical interventions for the prevention and/or treatment of the diabetic foot. PMID:24278219

  17. A Comprehensive Reanalysis of the Distal Iliotibial Band: Quantitative Anatomy, Radiographic Markers, and Biomechanical Properties.

    PubMed

    Godin, Jonathan A; Chahla, Jorge; Moatshe, Gilbert; Kruckeberg, Bradley M; Muckenhirn, Kyle J; Vap, Alexander R; Geeslin, Andrew G; LaPrade, Robert F

    2017-09-01

    The qualitative anatomy of the distal iliotibial band (ITB) has previously been described. However, a comprehensive characterization of the quantitative anatomic, radiographic, and biomechanical properties of the Kaplan fibers of the deep distal ITB has not yet been established. It is paramount to delineate these characteristics to fully understand the distal ITB's contribution to rotational knee stability. Purpose/Hypothesis: There were 2 distinct purposes for this study: (1) to perform a quantitative anatomic and radiographic evaluation of the distal ITB's attachment sites and their relationships to pertinent osseous and soft tissue landmarks, and (2) to quantify the biomechanical properties of the deep (Kaplan) fibers of the distal ITB. It was hypothesized that the distal ITB has definable parameters concerning its anatomic attachments and consistent relationships to surgically pertinent landmarks with correlating plain radiographic findings. In addition, it was hypothesized that the biomechanical properties of the Kaplan fibers would support their role as important restraints against internal rotation. Descriptive laboratory study. Ten nonpaired, fresh-frozen human cadaveric knees (mean age, 61.1 years; range, 54-65 years) were dissected for anatomic and radiographic purposes. A coordinate measuring device quantified the attachment areas of the distal ITB to the distal femur, patella, and proximal tibia and their relationships to pertinent bony landmarks. A radiographic analysis was performed by inserting pins into the attachment sites of relevant anatomic structures to assess their location relative to pertinent bony landmarks with fluoroscopic guidance. A further biomechanical assessment of 10 cadaveric knees quantified the load to failure and stiffness of the Kaplan fibers' insertion on the distal femur after a preconditioning protocol. Two separate deep (Kaplan) fiber bundles were identified with attachments to 2 newly identified femoral bony prominences (ridges). The proximal and distal bundles inserted on the distal femur 53.6 mm (95% CI, 50.7-56.6 mm) and 31.4 mm (95% CI, 27.3-35.5 mm) proximal to the lateral epicondyle, respectively. The centers of the bundle insertions were 22.5 mm (95% CI, 19.1-25.9 mm) apart. The total insertion area of the distal ITB on the proximal tibia was 429.1 mm 2 (95% CI, 349.2-509.1 mm 2 ). A distinct capsulo-osseous layer of the distal ITB was also identified that was intimately related to the lateral knee capsule. Its origin was in close proximity to the lateral gastrocnemius tubercle, and it inserted on the proximal tibia at the lateral tibial tubercle between the fibular head and the Gerdy tubercle. Radiographic analysis supported the quantitative anatomic findings. The mean maximum load during pull-to-failure testing was 71.3 N (95% CI, 41.2-101.4 N) and 170.2 N (95% CI, 123.6-216.8 N) for the proximal and distal Kaplan bundles, respectively. The most important finding of this study was that 2 distinct deep bundles (Kaplan fibers) of the distal ITB were identified. Each bundle of the deep layer of the ITB was associated with a newly identified distinct bony ridge. Radiographic analysis confirmed the measurements previously recorded and established reproducible landmarks for the newly described structures. Biomechanical testing revealed that the Kaplan fibers had a strong attachment to the distal femur, thereby supporting a role in rotational knee stability. The identification of 2 distinct deep fiber (Kaplan) attachments clarifies the function of the ITB more definitively. The results also support the role of the ITB in rotatory knee stability because of the fibers' vectors and their identified maximum loads. These findings provide the anatomic and biomechanical foundation needed for the development of reconstruction or repair techniques to anatomically address these deficiencies in knee ligament injuries.

  18. Overlap and distinction between measures of insight and self-stigma.

    PubMed

    Hasson-Ohayon, Ilanit

    2018-05-24

    Multiple studies on insight into one's illness and self-stigma among patients with serious mental illness and their relatives have shown that these constructs are related to one another and that they affect outcome. However, a critical exploration of the items used to assess both constructs raises questions with regard to the possible overlapping and centrality of items. The current study used five different samples to explore the possible overlap and distinction between insight and self-stigma, and to identify central items, via network analyses and principal component factor analysis. Findings from the network analyses showed overlap between insight and self-stigma exist with a relatively clearer observational distinction between the constructs among the two parent samples in comparison to the patient samples. Principal component factor analysis constrained to two factors showed that a relatively high percentage of items were not loaded on either factor, and in a few datasets, several insight items were loaded on the self-stigma scale and vice versa. The author discusses implications for research and calls for rethinking the way insight is assessed. Clinical implications are also discussed in reference to central items of social isolation, future worries and stereotype endorsement among the different study groups. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Evolutionary Novelty in a Butterfly Wing Pattern through Enhancer Shuffling

    PubMed Central

    Pardo-Diaz, Carolina; Hanly, Joseph J.; Martin, Simon H.; Mallet, James; Dasmahapatra, Kanchon K.; Salazar, Camilo; Joron, Mathieu; Nadeau, Nicola; McMillan, W. Owen; Jiggins, Chris D.

    2016-01-01

    An important goal in evolutionary biology is to understand the genetic changes underlying novel morphological structures. We investigated the origins of a complex wing pattern found among Amazonian Heliconius butterflies. Genome sequence data from 142 individuals across 17 species identified narrow regions associated with two distinct red colour pattern elements, dennis and ray. We hypothesise that these modules in non-coding sequence represent distinct cis-regulatory loci that control expression of the transcription factor optix, which in turn controls red pattern variation across Heliconius. Phylogenetic analysis of the two elements demonstrated that they have distinct evolutionary histories and that novel adaptive morphological variation was created by shuffling these cis-regulatory modules through recombination between divergent lineages. In addition, recombination of modules into different combinations within species further contributes to diversity. Analysis of the timing of diversification in these two regions supports the hypothesis of introgression moving regulatory modules between species, rather than shared ancestral variation. The dennis phenotype introgressed into Heliconius melpomene at about the same time that ray originated in this group, while ray introgressed back into H. elevatus much more recently. We show that shuffling of existing enhancer elements both within and between species provides a mechanism for rapid diversification and generation of novel morphological combinations during adaptive radiation. PMID:26771987

  20. Evolutionary Novelty in a Butterfly Wing Pattern through Enhancer Shuffling.

    PubMed

    Wallbank, Richard W R; Baxter, Simon W; Pardo-Diaz, Carolina; Hanly, Joseph J; Martin, Simon H; Mallet, James; Dasmahapatra, Kanchon K; Salazar, Camilo; Joron, Mathieu; Nadeau, Nicola; McMillan, W Owen; Jiggins, Chris D

    2016-01-01

    An important goal in evolutionary biology is to understand the genetic changes underlying novel morphological structures. We investigated the origins of a complex wing pattern found among Amazonian Heliconius butterflies. Genome sequence data from 142 individuals across 17 species identified narrow regions associated with two distinct red colour pattern elements, dennis and ray. We hypothesise that these modules in non-coding sequence represent distinct cis-regulatory loci that control expression of the transcription factor optix, which in turn controls red pattern variation across Heliconius. Phylogenetic analysis of the two elements demonstrated that they have distinct evolutionary histories and that novel adaptive morphological variation was created by shuffling these cis-regulatory modules through recombination between divergent lineages. In addition, recombination of modules into different combinations within species further contributes to diversity. Analysis of the timing of diversification in these two regions supports the hypothesis of introgression moving regulatory modules between species, rather than shared ancestral variation. The dennis phenotype introgressed into Heliconius melpomene at about the same time that ray originated in this group, while ray introgressed back into H. elevatus much more recently. We show that shuffling of existing enhancer elements both within and between species provides a mechanism for rapid diversification and generation of novel morphological combinations during adaptive radiation.

  1. Phylogenetic analysis and protein structure modelling identifies distinct Ca(2+)/Cation antiporters and conservation of gene family structure within Arabidopsis and rice species.

    PubMed

    Pittman, Jon K; Hirschi, Kendal D

    2016-12-01

    The Ca(2+)/Cation Antiporter (CaCA) superfamily is an ancient and widespread family of ion-coupled cation transporters found in nearly all kingdoms of life. In animals, K(+)-dependent and K(+)-indendent Na(+)/Ca(2+) exchangers (NCKX and NCX) are important CaCA members. Recently it was proposed that all rice and Arabidopsis CaCA proteins should be classified as NCX proteins. Here we performed phylogenetic analysis of CaCA genes and protein structure homology modelling to further characterise members of this transporter superfamily. Phylogenetic analysis of rice and Arabidopsis CaCAs in comparison with selected CaCA members from non-plant species demonstrated that these genes form clearly distinct families, with the H(+)/Cation exchanger (CAX) and cation/Ca(2+) exchanger (CCX) families dominant in higher plants but the NCKX and NCX families absent. NCX-related Mg(2+)/H(+) exchanger (MHX) and CAX-related Na(+)/Ca(2+) exchanger-like (NCL) proteins are instead present. Analysis of genomes of ten closely-related rice species and four Arabidopsis-related species found that CaCA gene family structures are highly conserved within related plants, apart from minor variation. Protein structures were modelled for OsCAX1a and OsMHX1. Despite exhibiting broad structural conservation, there are clear structural differences observed between the different CaCA types. Members of the CaCA superfamily form clearly distinct families with different phylogenetic, structural and functional characteristics, and therefore should not be simply classified as NCX proteins, which should remain as a separate gene family.

  2. Genome-Wide Analysis of bZIP-Encoding Genes in Maize

    PubMed Central

    Wei, Kaifa; Chen, Juan; Wang, Yanmei; Chen, Yanhui; Chen, Shaoxiang; Lin, Yina; Pan, Si; Zhong, Xiaojun; Xie, Daoxin

    2012-01-01

    In plants, basic leucine zipper (bZIP) proteins regulate numerous biological processes such as seed maturation, flower and vascular development, stress signalling and pathogen defence. We have carried out a genome-wide identification and analysis of 125 bZIP genes that exist in the maize genome, encoding 170 distinct bZIP proteins. This family can be divided into 11 groups according to the phylogenetic relationship among the maize bZIP proteins and those in Arabidopsis and rice. Six kinds of intron patterns (a–f) within the basic and hinge regions are defined. The additional conserved motifs have been identified and present the group specificity. Detailed three-dimensional structure analysis has been done to display the sequence conservation and potential distribution of the bZIP domain. Further, we predict the DNA-binding pattern and the dimerization property on the basis of the characteristic features in the basic and hinge regions and the leucine zipper, respectively, which supports our classification greatly and helps to classify 26 distinct subfamilies. The chromosome distribution and the genetic analysis reveal that 58 ZmbZIP genes are located in the segmental duplicate regions in the maize genome, suggesting that the segment chromosomal duplications contribute greatly to the expansion of the maize bZIP family. Across the 60 different developmental stages of 11 organs, three apparent clusters formed represent three kinds of different expression patterns among the ZmbZIP gene family in maize development. A similar but slightly different expression pattern of bZIPs in two inbred lines displays that 22 detected ZmbZIP genes might be involved in drought stress. Thirteen pairs and 143 pairs of ZmbZIP genes show strongly negative and positive correlations in the four distinct fungal infections, respectively, based on the expression profile and Pearson's correlation coefficient analysis. PMID:23103471

  3. Analysis of epitope information related to Bacillus anthracis and Clostridium botulinum

    PubMed Central

    Zarebski, Laura M; Vaughan, Kerrie; Sidney, John; Peters, Bjoern; Grey, Howard; Janda, Kim D; Casadevall, Arturo

    2012-01-01

    We have reviewed the information about epitopes of immunological interest from Clostridium botulinum and Bacillus anthracis, by mining the Immune Epitope Database and Analysis Resource. For both pathogens, the vast majority of epitopes reported to date are derived from a single protein: the protective antigen of B. anthracis and the neurotoxin type A of C. botulinum. A detailed analysis of the data was performed to characterize the function, localization and conservancy of epitopes identified as neutralizing and/or protective. In order to broaden the scope of this analysis, we have also included data describing immune responses against defined fragments (over 50 amino acids long) of the relevant antigens. The scarce information on T-cell determinants and on epitopes from other antigens besides the toxins, highlights a gap in our knowledge and identifies areas for future research. Despite this, several distinct structures at the epitope and fragment level are described herein, which could be potential additions to future vaccines or targets of novel immunotherapeutics and diagnostic reagents. PMID:18251694

  4. Motif-based analysis of large nucleotide data sets using MEME-ChIP

    PubMed Central

    Ma, Wenxiu; Noble, William S; Bailey, Timothy L

    2014-01-01

    MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets. It can analyze peak regions identified by ChIP-seq, cross-linking sites identified by cLIP-seq and related assays, as well as sets of genomic regions selected using other criteria. MEME-ChIP performs de novo motif discovery, motif enrichment analysis, motif location analysis and motif clustering, providing a comprehensive picture of the DNA or RNA motifs that are enriched in the input sequences. MEME-ChIP performs two complementary types of de novo motif discovery: weight matrix–based discovery for high accuracy; and word-based discovery for high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human, mouse, worm, fly and other model organisms provides even greater sensitivity. MEME-ChIP’s interactive HTML output groups and aligns significant motifs to ease interpretation. this protocol takes less than 3 h, and it provides motif discovery approaches that are distinct and complementary to other online methods. PMID:24853928

  5. Partial Least Squares Based Gene Expression Analysis in EBV- Positive and EBV-Negative Posttransplant Lymphoproliferative Disorders.

    PubMed

    Wu, Sa; Zhang, Xin; Li, Zhi-Ming; Shi, Yan-Xia; Huang, Jia-Jia; Xia, Yi; Yang, Hang; Jiang, Wen-Qi

    2013-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

  6. Phosphoproteomic analysis of the non-seed vascular plant model Selaginella moellendorffii

    PubMed Central

    2014-01-01

    Background Selaginella (Selaginella moellendorffii) is a lycophyte which diverged from other vascular plants approximately 410 million years ago. As the first reported non-seed vascular plant genome, Selaginella genome data allow comparative analysis of genetic changes that may be associated with land plant evolution. Proteomics investigations on this lycophyte model have not been extensively reported. Phosphorylation represents the most common post-translational modifications and it is a ubiquitous regulatory mechanism controlling the functional expression of proteins inside living organisms. Results In this study, polyethylene glycol fractionation and immobilized metal ion affinity chromatography were employed to isolate phosphopeptides from wild-growing Selaginella. Using liquid chromatography-tandem mass spectrometry analysis, 1593 unique phosphopeptides spanning 1104 non-redundant phosphosites with confirmed localization on 716 phosphoproteins were identified. Analysis of the Selaginella dataset revealed features that are consistent with other plant phosphoproteomes, such as the relative proportions of phosphorylated Ser, Thr, and Tyr residues, the highest occurrence of phosphosites in the C-terminal regions of proteins, and the localization of phosphorylation events outside protein domains. In addition, a total of 97 highly conserved phosphosites in evolutionary conserved proteins were identified, indicating the conservation of phosphorylation-dependent regulatory mechanisms in phylogenetically distinct plant species. On the other hand, close examination of proteins involved in photosynthesis revealed phosphorylation events which may be unique to Selaginella evolution. Furthermore, phosphorylation motif analyses identified Pro-directed, acidic, and basic signatures which are recognized by typical protein kinases in plants. A group of Selaginella-specific phosphoproteins were found to be enriched in the Pro-directed motif class. Conclusions Our work provides the first large-scale atlas of phosphoproteins in Selaginella which occupies a unique position in the evolution of terrestrial plants. Future research into the functional roles of Selaginella-specific phosphorylation events in photosynthesis and other processes may offer insight into the molecular mechanisms leading to the distinct evolution of lycophytes. PMID:24628833

  7. Analysis of Iran’s Political Leadership,

    DTIC Science & Technology

    1982-01-01

    interest groups . As a group lay politicans are even less cohesive than are their clerical counter- parts. Nevertheless, it is possible to identify at least... group . While Ayatollah Sayyid RUhOllah al-lusavi Khomeini is the supreme political leader among the clergy, he is not condidered to be infallible and in...major source of controversey within the Sh’i clergy, dividing the entire religious establisiment into at least two distinct groups . Essentially, Khomeini

  8. Genetic Identification of Rickettsial Isolates from Fatal Cases of Brazilian Spotted Fever and Comparison with Rickettsia rickettsii Isolates from the American Continents

    PubMed Central

    Santos, Fabiana C. P.; Ogrzewalska, Maria; Nascimento, Elvira M. M.; Colombo, Silvia; Marcili, Arlei; Angerami, Rodrigo N.

    2014-01-01

    Fifteen bacterial isolates from spotted fever group rickettsiosis in Brazil were genetically identified as Rickettsia rickettsii. In a phylogenetic analysis with other R. rickettsii isolates from GenBank, the Central/South American isolates showed low polymorphism and formed a clade distinct from two North American clades, with the North American clades having greater in-branch polymorphism. PMID:25078908

  9. Phylogenetic analysis of feline immunodeficiency virus in feral and companion domestic cats of New Zealand.

    PubMed

    Hayward, Jessica J; Taylor, John; Rodrigo, Allen G

    2007-03-01

    Nested PCR was used to amplify envelope V3-V6 gene fragments of feline immunodeficiency virus (FIV) from New Zealand cats. Phylogenetic analyses established that subtypes A and C predominate among New Zealand cats, with clear evidence of intersubtype recombination. In addition, 17 sequences were identified that were distinct from all known FIV clades, and we tentatively suggest these belong to a novel subtype.

  10. Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses

    PubMed Central

    Rucevic, Marijana; Kourjian, Georgio; Boucau, Julie; Blatnik, Renata; Garcia Bertran, Wilfredo; Berberich, Matthew J.; Walker, Bruce D.; Riemer, Angelika B.

    2016-01-01

    ABSTRACT Despite the critical role of epitope presentation for immune recognition, we still lack a comprehensive definition of HIV peptides presented by HIV-infected cells. Here we identified 107 major histocompatibility complex (MHC)-bound HIV peptides directly from the surface of live HIV-transfected 293T cells, HIV-infected B cells, and primary CD4 T cells expressing a variety of HLAs. The majority of peptides were 8 to 12 amino acids (aa) long and mostly derived from Gag and Pol. The analysis of the total MHC-peptidome and of HLA-A02-bound peptides identified new noncanonical HIV peptides of up to 16 aa that could not be predicted by HLA anchor scanning and revealed an heterogeneous surface peptidome. Nested sets of surface HIV peptides included optimal and extended HIV epitopes and peptides partly overlapping or distinct from known epitopes, revealing new immune responses in HIV-infected persons. Surprisingly, in all three cell types, a majority of Gag peptides derived from p15 rather than from the most immunogenic p24. The cytosolic degradation of peptide precursors in corresponding cells confirmed the generation of identified surface-nested peptides. Cytosolic degradation revealed peptides commonly produced in all cell types and displayed by various HLAs, peptides commonly produced in all cell types and selectively displayed by specific HLAs, and peptides produced in only one cell type. Importantly, we identified areas of proteins leading to common presentations of noncanonical peptides by several cell types with distinct HLAs. These peptides may benefit the design of immunogens, focusing T cell responses on relevant markers of HIV infection in the context of HLA diversity. IMPORTANCE The recognition of HIV-infected cells by immune T cells relies on the presentation of HIV-derived peptides by diverse HLA molecules at the surface of cells. The landscape of HIV peptides displayed by HIV-infected cells is not well defined. Considering the diversity of HLA molecules in the human population, it is critical for vaccine design to identify HIV peptides that may be displayed despite the HLA diversity. We identified 107 HIV peptides directly from the surface of three cell types infected with HIV. They corresponded to nested sets of HIV peptides of canonical and novel noncanonical lengths not predictable by the presence of HLA anchors. Importantly, we identified areas of HIV proteins leading to presentation of noncanonical peptides by several cell types with distinct HLAs. Including such peptides in vaccine immunogen may help to focus immune responses on common markers of HIV infection in the context of HLA diversity. PMID:27440904

  11. Cluster analysis in phenotyping a Portuguese population.

    PubMed

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

    2015-09-03

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

  12. Biomass digestibility is predominantly affected by three factors of wall polymer features distinctive in wheat accessions and rice mutants

    PubMed Central

    2013-01-01

    Background Wheat and rice are important food crops with enormous biomass residues for biofuels. However, lignocellulosic recalcitrance becomes a crucial factor on biomass process. Plant cell walls greatly determine biomass recalcitrance, thus it is essential to identify their key factors on lignocellulose saccharification. Despite it has been reported about cell wall factors on biomass digestions, little is known in wheat and rice. In this study, we analyzed nine typical pairs of wheat and rice samples that exhibited distinct cell wall compositions, and identified three major factors of wall polymer features that affected biomass digestibility. Results Based on cell wall compositions, ten wheat accessions and three rice mutants were classified into three distinct groups each with three typical pairs. In terms of group I that displayed single wall polymer alternations in wheat, we found that three wall polymer levels (cellulose, hemicelluloses and lignin) each had a negative effect on biomass digestibility at similar rates under pretreatments of NaOH and H2SO4 with three concentrations. However, analysis of six pairs of wheat and rice samples in groups II and III that each exhibited a similar cell wall composition, indicated that three wall polymer levels were not the major factors on biomass saccharification. Furthermore, in-depth detection of the wall polymer features distinctive in rice mutants, demonstrated that biomass digestibility was remarkably affected either negatively by cellulose crystallinity (CrI) of raw biomass materials, or positively by both Ara substitution degree of non-KOH-extractable hemicelluloses (reverse Xyl/Ara) and p-coumaryl alcohol relative proportion of KOH-extractable lignin (H/G). Correlation analysis indicated that Ara substitution degree and H/G ratio negatively affected cellulose crystallinity for high biomass enzymatic digestion. It was also suggested to determine whether Ara and H monomer have an interlinking with cellulose chains in the future. Conclusions Using nine typical pairs of wheat and rice samples having distinct cell wall compositions and wide biomass saccharification, Ara substitution degree and monolignin H proportion have been revealed to be the dominant factors positively determining biomass digestibility upon various chemical pretreatments. The results demonstrated the potential of genetic modification of plant cell walls for high biomass saccharification in bioenergy crops. PMID:24341349

  13. Molecular Systematics of the Cape Parrot (Poicephalus robustus): Implications for Taxonomy and Conservation

    PubMed Central

    Coetzer, Willem G.; Downs, Colleen T.; Perrin, Mike R.; Willows-Munro, Sandi

    2015-01-01

    The taxonomic position of the Cape Parrot (Poicephalus robustus robustus) has been the focus of much debate. A number of authors suggest that the Cape Parrot should be viewed as a distinct species separate from the other two P. robustus subspecies (P. r. fuscicollis and P. r. suahelicus). These recommendations were based on morphological, ecological, and behavioural assessments. In this study we investigated the validity of these recommendations using multilocus DNA analyses. We genotyped 138 specimens from five Poicephalus species (P. cryptoxanthus, P. gulielmi, P. meyeri, P. robustus, and P. rueppellii) using 11 microsatellite loci. Additionally, two mitochondrial (cytochrome oxidase I gene and 16S ribosomal RNA) and one nuclear intron (intron 7 of the β-fibrinogen gene) markers were amplified and sequenced. Bayesian clustering analysis and pairwise FST analysis of microsatellite data identified P. r. robustus as genetically distinct from the other P. robustus subspecies. Phylogenetic and molecular clock analyses on sequence data also supported the microsatellite analyses, placing P. r. robustus in a distinct clade separate from the other P. robustus subspecies. Molecular clock analysis places the most recent common ancestor between P. r. robustus and P. r. fuscicollis / P. r. suahelicus at 2.13 to 2.67 million years ago. Our results all support previous recommendations to elevate the Cape Parrot to species level. This will facilitate better planning and implementation of international and local conservation management strategies for the Cape Parrot. PMID:26267261

  14. Characterisation of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains

    PubMed Central

    Maratou, Klio; Behmoaras, Jacques; Fewings, Chris; Srivastava, Prashant; D’Souza, Zelpha; Smith, Jennifer; Game, Laurence; Cook, Terence; Aitman, Tim

    2010-01-01

    Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity. PMID:21179115

  15. Constituents and functional implications of the rat default mode network.

    PubMed

    Hsu, Li-Ming; Liang, Xia; Gu, Hong; Brynildsen, Julia K; Stark, Jennifer A; Ash, Jessica A; Lin, Ching-Po; Lu, Hanbing; Rapp, Peter R; Stein, Elliot A; Yang, Yihong

    2016-08-02

    The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation within the network. Because preclinical models can inform translational studies of neuropsychiatric disorders, partitioning of the DMN in nonhuman species, which has previously not been reported, may inform both physiology and pathophysiology of the human DMN. In this study, we sought to identify constituents of the rat DMN using resting-state functional MRI (rs-fMRI) and diffusion tensor imaging. After identifying DMN using a group-level independent-component analysis on the rs-fMRI data, modularity analyses fractionated the DMN into an anterior and a posterior subsystem, which were further segregated into five modules. Diffusion tensor imaging tractography demonstrates a close relationship between fiber density and the functional connectivity between DMN regions, and provides anatomical evidence to support the detected DMN subsystems. Finally, distinct modulation was seen within and between these DMN subcomponents using a neurocognitive aging model. Taken together, these results suggest that, like the human DMN, the rat DMN can be partitioned into several subcomponents that may support distinct functions. These data encourage further investigation into the neurobiological mechanisms of DMN processing in preclinical models of both normal and disease states.

  16. Understanding women's experiences of distress during pregnancy in Dar es Salaam, Tanzania.

    PubMed

    Kaaya, S F; Mbwambo, J K; Fawzi, M C Smith; Van Den Borne, H; Schaalma, H; Leshabari, M T

    2010-01-01

    Several studies show depression is common during pregnancy. However, there is limited information in Tanzania on the magnitude of perceived distress during pregnancy and meanings ascribed to such distress. A descriptive survey collected data using unstructured interviews from 12 traditional practitioners and 10 peri-urban women with previous pregnancy related mental health concerns identified using a depression vignette. The objectives were to describe the sources and characteristics of distress during pregnancy, and idioms of distress that could inform cultural adaptation of depression screening tools. Narrative analysis showed an emergent category of "problematic pregnancies" framed women's recollections of prolonged periods of sadness. This experience was qualified using various idioms of distress that were differentially emphasized depending on informant's perceived causes of health concern. The idiom kusononeka was consistently used to describe extreme sadness across causal categories and clustered with at least two typical features of major depression. This suggested existence of a construct with similarities to biomedical criteria for depression. "Thinking too much" emerged as a distinctive expression associated with prolonged sadness. Distinctive expressions of social functioning impairments were identified that can inform depression severity assessments. In conclusion, contextual inquiry into experiences of psychological distress showed distinct local idioms that clustered in patterns similar to symptoms of biomedical depressive episodes. Further studies to assess the utility of local idioms of distress and distress related functional impairment in depression assessment tools are warranted.

  17. Identification and discrimination of oral asaccharolytic Eubacterium spp. by pyrolysis mass spectrometry and artificial neural networks.

    PubMed

    Goodacre, R; Hiom, S J; Cheeseman, S L; Murdoch, D; Weightman, A J; Wade, W G

    1996-02-01

    Curie-point pyrolysis mass spectra were obtained from 29 oral asaccharolytic Eubacterium strains and 6 abscess isolates previously identified as Peptostreptococcus heliotrinreducens. Pyrolysis mass spectrometry (PyMS) with cluster analysis was able to clarify the taxonomic position of this group of organisms. Artificial neural networks (ANNS) were then trained by supervised learning (with the back-propagation algorithm) to recognize the strains from their pyrolysis mass spectra; all Eubacterium strains were correctly identified, and the abscess isolates were identified as un-named Eubacterium taxon C2 and were distinct from the type strain of P. heliotrinreducens. These results demonstrate that the combination of PyMS and ANNs provides a rapid and accurate identification technique.

  18. Global warming's five Germanys: A typology of Germans' views on climate change and patterns of media use and information.

    PubMed

    Metag, Julia; Füchslin, Tobias; Schäfer, Mike S

    2017-05-01

    People's attitudes toward climate change differ, and these differences may correspond to distinct patterns of media use and information seeking. However, studies extending analyses of attitude types and their specific media diets to countries beyond the United States are lacking. We use a secondary analysis of survey data from Germany to identify attitudes toward climate change among the German public and specify those segments of the population based on their media use and information seeking. Similar to the Global Warming's Six Americas study, we find distinct attitudes (Global Warming's Five Germanys) that differ in climate change-related perceptions as well as in media use and communicative behavior. These findings can help tailor communication campaigns regarding climate change to specific audiences.

  19. 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.

  20. Genotypic and Phenotypic Characterization of “Streptococcus milleri” Group Isolates from a Veterans Administration Hospital Population

    PubMed Central

    Clarridge, Jill E.; Osting, Cheryl; Jalali, Mehri; Osborne, Janet; Waddington, Michael

    1999-01-01

    Because identification of the species within the “Streptococcus milleri” group is difficult for the clinical laboratory as the species share overlapping phenotypic characteristics, we wished to confirm biochemical identification with identification by 16S rRNA gene sequence analysis. Ninety-four clinical isolates previously identified as the “Streptococcus milleri” group were reclassified as S. anginosus, S. constellatus, or S. intermedius with the API 20 Strep system (bioMerieux Vikek, Hazelton, Mo.) and the Fluo-card (Key Scientific, Round Rock, Tex.). In addition, we determined the Lancefield group, hemolysis, colony size, colony texture, repetitive extragenic palindromic PCR (rep-PCR) pattern, and cellular fatty acid (CFA) profile (MIDI, Newark, Del.). 16S rRNA gene sequence analysis with 40 selected representative strains showed three distinct groups, with S. constellatus and S. intermedius found to be more closely related to each other than to S. anginosus, and further distinguished a biochemically distinct group of urogenital isolates within the S. anginosus group of isolates. Except for strains unreactive with the Fluo-card (8%), all S. anginosus and S. intermedius strains identified by sequencing were similarly identified by biochemical testing. However, 23% of the selected S. constellatus isolates identified by sequencing (9% of all S. constellatus isolates) would have been identified as S. anginosus or S. intermedius by biochemical tests. Although most S. anginosus strains formed one unique cluster by CFA analysis and most S. constellatus strains showed similar rep-PCR patterns, neither method was sufficiently dependable for identification. Whereas Lancefield group or lactose fermentation did not correspond to sequence or biochemical type, S. constellatus was most likely to be beta-hemolytic and S. intermedius was most likely to have a dry colony type. The most frequent isolate in our population was S. constellatus, followed by S. anginosus. There was an association of S. anginosus with a gastrointestinal or urogenital source, and there was an association of S. constellatus and S. intermedius with both the respiratory tract and upper-body abscesses. PMID:10523574

  1. Teenage Drinking, Symbolic Capital and Distinction

    ERIC Educational Resources Information Center

    Jarvinen, Margaretha; Gundelach, Peter

    2007-01-01

    This article analyses alcohol-related lifestyles among Danish teenagers. Building on Bourdieu's reasoning on symbolic capital and distinction, we analyse three interrelated themes. First, we show that alcohol-related variables (drinking patterns, drinking debut, experience of intoxication, etc.) can be used to identify some very distinctive life…

  2. Terahertz spectral unmixing based method for identifying gastric cancer

    NASA Astrophysics Data System (ADS)

    Cao, Yuqi; Huang, Pingjie; Li, Xian; Ge, Weiting; Hou, Dibo; Zhang, Guangxin

    2018-02-01

    At present, many researchers are exploring biological tissue inspection using terahertz time-domain spectroscopy (THz-TDS) techniques. In this study, based on a modified hard modeling factor analysis method, terahertz spectral unmixing was applied to investigate the relationships between the absorption spectra in THz-TDS and certain biomarkers of gastric cancer in order to systematically identify gastric cancer. A probability distribution and box plot were used to extract the distinctive peaks that indicate carcinogenesis, and the corresponding weight distributions were used to discriminate the tissue types. The results of this work indicate that terahertz techniques have the potential to detect different levels of cancer, including benign tumors and polyps.

  3. Identification of binding domains in the herpes simplex virus type 1 small capsid protein pUL35 (VP26).

    PubMed

    Apcarian, Arin; Cunningham, Anthony L; Diefenbach, Russell J

    2010-11-01

    In this study, fragments of the small capsid protein pUL35 (VP26) from herpes simplex virus type 1 (HSV-1) were generated to identify binding domains for a number of known ligands. Analysis of the binding of dynein light chain subunits, DYNLT1 and DYNLT3, as well the HSV-1 structural proteins pUL19 (VP5) and pUL37 was then undertaken using the LexA yeast two-hybrid assay. The N-terminal half of pUL35, in particular residues 30-43, was identified as a common region for the binding of DYNLT1 and DYNLT3. Additional distinct regions in the C terminus of pUL35 also contribute to the binding of DYNLT1 and DYNLT3. In contrast, only the C-terminal half of pUL35 was found to mediate the binding of pUL19 and pUL37 through distinct regions. The relevance of this information to the role of pUL35 in viral transport and assembly is discussed.

  4. Adolescent accounts of the UK National Lottery and scratchcards: an analysis using Q-sorts.

    PubMed

    Wood, Richard T A; Griffiths, Mark D; Derevensky, Jeffrey L; Gupta, Rina

    2002-01-01

    The study examined adolescents' accounts of the UK National Lottery and scratchcards. Q-sorts were used to examine the views of 62 participants aged between 11 and 15 years of age. Findings identified four distinct accounts in relation to the National Lottery (Moral Opposition, Luck Seeking, Rationalist, & Uncertainty), and four distinct accounts in relation to scratchcards (Scepticism, Thrill-Seeking, Rationalist, & Libertarian). Some of the accounts identified described the UK National Lottery and scratchcards as bona fide forms of gambling. Reports indicated that adolescents were pessimistic about the chances of winning large sums of money, while other accounts demonstrated gambling misperceptions particularly in relation to their belief in luck and the laws of probability. It is argued that to fully understand why adolescents take part in these activities it is important to consider the diverse ways that adolescents represent these activities. These differing representations will have consequences for measures aimed at reducing, preventing, or treating adolescent problem gambling. The utility of Q-sorts as a technique for examining the views of problem and non-problem gamblers is also discussed.

  5. Phylogenetic analysis and survey of Apis cerana strain of Sacbrood virus (AcSBV) in Taiwan suggests a recent introduction.

    PubMed

    Huang, Wei-Fone; Mehmood, Shahid; Huang, Shaokang; Chen, Yue-Wen; Ko, Chong-Yu; Su, Songkun

    2017-06-01

    The Sacbrood virus (SBV) is widely distributed in European honey bees, Apis mellifera. AcSBV, a distinct SBV strain in Asian honey bees (A. cerana) causes larva death before pupation and often depopulates colonies, leading to collapse. It is the most severe disease in A. cerana beekeeping. AcSBV infects A. cerana in most natural habitats, yet occurrences were not reported in Taiwan before 2015 and were not a concern for local beekeepers. However, in 2016, A. cerana beekeepers in central Taiwan reported SBV-like symptoms. We screened samples of larvae using RT-PCR and surveyed asymptomatic apiaries in north Taiwan. Phylogenetic analyses suggested that AcSBV isolates from central Taiwan were introduced; all isolates had high similarity in sequences to AcSBV genomes identified in mainland China, Vietnam, and Korea and distinct differences to SBV sequence identified in Taiwan. The overall prevalence in symptomatic colonies was low. No latent infections were detected in asymptomatic colonies. The AcSBV epizootic may not yet have reached its highest potential. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The genome of the endophytic bacterium H. frisingense GSF30(T) identifies diverse strategies in the Herbaspirillum genus to interact with plants.

    PubMed

    Straub, Daniel; Rothballer, Michael; Hartmann, Anton; Ludewig, Uwe

    2013-01-01

    The diazotrophic, bacterial endophyte Herbaspirillum frisingense GSF30(T) has been identified in biomass grasses grown in temperate climate, including the highly nitrogen-efficient grass Miscanthus. Its genome was annotated and compared with related Herbaspirillum species from diverse habitats, including H. seropedicae, and further well-characterized endophytes. The analysis revealed that Herbaspirillum frisingense lacks a type III secretion system that is present in some related Herbaspirillum grass endophytes. Together with the lack of components of the type II secretion system, the genomic inventory indicates distinct interaction scenarios of endophytic Herbaspirillum strains with plants. Differences in respiration, carbon, nitrogen and cell wall metabolism among Herbaspirillum isolates partially correlate with their different habitats. Herbaspirillum frisingense is closely related to strains isolated from the rhizosphere of phragmites and from well water, but these lack nitrogen fixation and metabolism genes. Within grass endophytes, the high diversity in their genomic inventory suggests that even individual plant species provide distinct, highly diverse metabolic niches for successful endophyte-plant associations.

  7. The genome of the endophytic bacterium H. frisingense GSF30T identifies diverse strategies in the Herbaspirillum genus to interact with plants

    PubMed Central

    Straub, Daniel; Rothballer, Michael; Hartmann, Anton; Ludewig, Uwe

    2013-01-01

    The diazotrophic, bacterial endophyte Herbaspirillum frisingense GSF30T has been identified in biomass grasses grown in temperate climate, including the highly nitrogen-efficient grass Miscanthus. Its genome was annotated and compared with related Herbaspirillum species from diverse habitats, including H. seropedicae, and further well-characterized endophytes. The analysis revealed that Herbaspirillum frisingense lacks a type III secretion system that is present in some related Herbaspirillum grass endophytes. Together with the lack of components of the type II secretion system, the genomic inventory indicates distinct interaction scenarios of endophytic Herbaspirillum strains with plants. Differences in respiration, carbon, nitrogen and cell wall metabolism among Herbaspirillum isolates partially correlate with their different habitats. Herbaspirillum frisingense is closely related to strains isolated from the rhizosphere of phragmites and from well water, but these lack nitrogen fixation and metabolism genes. Within grass endophytes, the high diversity in their genomic inventory suggests that even individual plant species provide distinct, highly diverse metabolic niches for successful endophyte-plant associations. PMID:23825472

  8. Distinction of broken cellular wall Ganoderma lucidum spores and G. lucidum spores using FTIR microspectroscopy.

    PubMed

    Chen, Xianliang; Liu, Xingcun; Sheng, Daping; Huang, Dake; Li, Weizu; Wang, Xin

    2012-11-01

    In this paper, FTIR microspectroscopy was used to identify broken cellular wall Ganoderma lucidum spores and G. lucidum spores. For IR spectra, broken cellular wall G. lucidum spores and G. lucidum spores were mainly different in the regions of 3000-2800, 1660-1600, 1400-1200 and 1100-1000 cm(-1). For curve fitting, the results showed the differences in the protein secondary structures and the polysaccharide structures/content between broken cellular wall G. lucidum spores and G. lucidum spores. Moreover, the value of A1078/A1741 might be a potentially useful factor to distinguish broken cellular wall G. lucidum spores from G. lucidum spores. Additionally, FTIR microspectroscopy could identify broken cellular wall G. lucidum spores and G. lucidum spores accurately when it was combined with hierarchical cluster analysis. The result suggests FTIR microspectroscopy is very simple and efficient for distinction of broken cellular wall G. lucidum spores and G. lucidum spores. The result also indicates FTIR microspectroscopy may be useful for TCM identification. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. A further case of a Prader-Willi syndrome phenotype in a patient with Angelman syndrome molecular defect.

    PubMed

    De Molfetta, Greice Andreotti; Felix, Temis Maria; Riegel, Mariluce; Ferraz, Victor Evangelista de Faria; de Pina Neto, João Monteiro

    2002-12-01

    Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are distinct human neurogenetic disorders; however, a clinical overlap between AS and PWS has been identified. We report on a further case of a patient showing the PWS phenotype with the AS molecular defect. Despite the PWS phenotype, the DNA methylation analysis of SNRPN revealed an AS pattern. Cytogenetic and FISH analysis showed normal chromosomes 15 and microsatellite analysis showed heterozygous loci inside and outside the 15q11-13 region. The presence of these atypical cases could be more frequent than previously expected and we reinforce that the DNA methylation analysis is important for the correct diagnosis of severe mental deficiency, congenital hypotonia and obesity.

  10. Dietary patterns, insulin sensitivity and adiposity in the multi-ethnic Insulin Resistance Atherosclerosis Study population.

    PubMed

    Liese, Angela D; Schulz, Mandy; Moore, Charity G; Mayer-Davis, Elizabeth J

    2004-12-01

    Epidemiological investigations increasingly employ dietary-pattern techniques to fully integrate dietary data. The present study evaluated the relationship of dietary patterns identified by cluster analysis with measures of insulin sensitivity (SI) and adiposity in the multi-ethnic, multi-centre Insulin Resistance Atherosclerosis Study (IRAS, 1992-94). Cross-sectional data from 980 middle-aged adults, of whom 67 % had normal and 33 % had impaired glucose tolerance, were analysed. Usual dietary intake was obtained by an interviewer-administered, validated food-frequency questionnaire. Outcomes included SI, fasting insulin (FI), BMI and waist circumference. The relationship of dietary patterns to log(SI+1), log(FI), BMI and waist circumference was modelled with multivariable linear regressions. Cluster analysis identified six distinct diet patterns--'dark bread', 'wine', 'fruits', 'low-frequency eaters', 'fries' and 'white bread'. The 'white bread' and the 'fries' patterns over-represented the Hispanic IRAS population predominantly from two centres, while the 'wine' and 'dark bread' groups were dominated by non-Hispanic whites. The dietary patterns were associated significantly with each of the outcomes first at the crude, clinical level (P<0.001). Furthermore, they were significantly associated with FI, BMI and waist circumference independent of age, sex, race or ethnicity, clinic, family history of diabetes, smoking and activity (P<0.004), whereas significance was lost for SI. Studying the total dietary behaviour via a pattern approach allowed us to focus both on the qualitative and quantitative dimensions of diet. The present study identified highly consistent associations of distinct dietary patterns with measures of insulin resistance and adiposity, which are risk factors for diabetes and heart disease.

  11. Time course of neck-shoulder pain among workers: A longitudinal latent class growth analysis.

    PubMed

    Hallman, David M; Rasmussen, Charlotte D Nørregaard; Jørgensen, Marie Birk; Holtermann, Andreas

    2018-01-01

    Objectives The aims of this study were to (i) identify trajectories of neck-shoulder pain (NSP) over one year in an occupational population and (ii) determine whether these trajectories are predicted by NSP characteristics as well as personal and occupational factors at baseline. Methods This longitudinal study was conducted among Danish workers (N=748) from 2012-2014. Text messages were used to collect frequent data on NSP over one year (14 waves in total). Peak NSP intensity in the past month was rated on a 0-10 numeric scale. A baseline questionnaire covered NSP characteristics (pain intensity, duration, comorbidity, pain medication, and pain interference) as well as personal (age, gender, body mass index) and occupational (seniority, work type, physical strain at work) factors. Latent class growth analysis was used to distinguish trajectories of NSP. Multivariate regression models with odds ratios (OR) were constructed to predict trajectories of NSP. Results Six distinct trajectories of NSP were identified (asymptomatic 11%, very low NSP 10%, low recovering NSP 18%, moderate recovering NSP 28%, strong fluctuating NSP 24% and severe persistent NSP 9% of the workers). Female gender, age, physical strain at work, NSP intensity and duration, pain medication, and pain interference in daily work at baseline were positively associated with severe persistent NSP and strong fluctuating NSP (all P<0.05). Altogether, personal and occupational factors accounted for 14% of the variance, while NSP characteristics accounted for 54%. Conclusions In an occupational sample, six distinct trajectories of NSP were identified. Physical strain at work appears to be a pertinent occupational factor predicting strong fluctuating and severe persistent NSP.

  12. An Assessment of Concerns Regarding New Regulatory Guidance for Combination Products: A Review of the Submissions Made to the FDA Regarding Their Proposed Draft New Guidance on Human Factors Studies for a Combination Product in an Abbreviated New Drug Application.

    PubMed

    Lance, Philip T; Greenaway, Ruth V; Edwards, Brian

    2018-01-01

    The US Food and Drug Administration (FDA) put out a call for comments on new draft guidance for industry "Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA." This call for comments elicited 7 submissions from various organizations in the field of health care products. This article reports on a review conducted on these 7 submissions. The purpose of this review was to identify any commonalities across the different submissions and determine if there was consensus on any point or aspect of the draft guidance. To identify any commonalities, a heat map plotting the lines of the draft guidance that had raised a comment/suggestion was produced. Also, a thematic analysis was conducted on the comments/suggestions. In total the 7 submissions produced 137 suggestions. The heat map revealed that these suggestions did not focus on any single part of the guidance but were spread throughout the guidance. The thematic analysis conducted on the suggestions found a number of distinct trends. These trends were grouped into 10 primary themes, each with a number of subthemes. It was concluded that guidance from the FDA on this matter is warranted and would be appreciated. However, it was also concluded that based on the distinct trends identified in the suggestions, there are issues that the FDA may wish to consider before publishing their final guidance.

  13. Brain mediators of the effects of noxious heat on pain

    PubMed Central

    Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.

    2014-01-01

    Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572

  14. Influences of Plant Species, Season and Location on Leaf Endophytic Bacterial Communities of Non-Cultivated Plants

    PubMed Central

    Ding, Tao; Melcher, Ulrich

    2016-01-01

    Bacteria are known to be associated endophytically with plants. Research on endophytic bacteria has identified their importance in food safety, agricultural production and phytoremediation. However, the diversity of endophytic bacterial communities and the forces that shape their compositions in non-cultivated plants are largely uncharacterized. In this study, we explored the diversity, community structure, and dynamics of endophytic bacteria in different plant species in the Tallgrass Prairie Preserve of northern Oklahoma, USA. High throughput sequencing of amplified segments of bacterial rDNA from 81 samples collected at four sampling times from five plant species at four locations identified 335 distinct OTUs at 97% sequence similarity, representing 16 phyla. Proteobacteria was the dominant phylum in the communities, followed by the phyla Bacteriodetes and Actinobacteria. Bacteria from four classes of Proteobacteria were detected with Alphaproteobacteria as the dominant class. Analysis of molecular variance revealed that host plant species and collecting date had significant influences on the compositions of the leaf endophytic bacterial communities. The proportion of Alphaproteobacteria was much higher in the communities from Asclepias viridis than from other plant species and differed from month to month. The most dominant bacterial groups identified in LDA Effect Size analysis showed host-specific patterns, indicating mutual selection between host plants and endophytic bacteria and that leaf endophytic bacterial compositions were dynamic, varying with the host plant’s growing season in three distinct patterns. In summary, next generation sequencing has revealed variations in the taxonomic compositions of leaf endophytic bacterial communities dependent primarily on the nature of the plant host species. PMID:26974817

  15. DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors.

    PubMed

    Amatruda, James F; Ross, Julie A; Christensen, Brock; Fustino, Nicholas J; Chen, Kenneth S; Hooten, Anthony J; Nelson, Heather; Kuriger, Jacquelyn K; Rakheja, Dinesh; Frazier, A Lindsay; Poynter, Jenny N

    2013-06-27

    Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy.

  16. Four distinct types of E.C. 1.2.1.30 enzymes can catalyze the reduction of carboxylic acids to aldehydes.

    PubMed

    Stolterfoht, Holly; Schwendenwein, Daniel; Sensen, Christoph W; Rudroff, Florian; Winkler, Margit

    2017-09-10

    Increasing demand for chemicals from renewable resources calls for the development of new biotechnological methods for the reduction of oxidized bio-based compounds. Enzymatic carboxylate reduction is highly selective, both in terms of chemo- and product selectivity, but not many carboxylate reductase enzymes (CARs) have been identified on the sequence level to date. Thus far, their phylogeny is unexplored and very little is known about their structure-function-relationship. CARs minimally contain an adenylation domain, a phosphopantetheinylation domain and a reductase domain. We have recently identified new enzymes of fungal origin, using similarity searches against genomic sequences from organisms in which aldehydes were detected upon incubation with carboxylic acids. Analysis of sequences with known CAR functionality and CAR enzymes recently identified in our laboratory suggests that the three-domain architecture mentioned above is modular. The construction of a distance tree with a subsequent 1000-replicate bootstrap analysis showed that the CAR sequences included in our study fall into four distinct subgroups (one of bacterial origin and three of fungal origin, respectively), each with a bootstrap value of 100%. The multiple sequence alignment of all experimentally confirmed CAR protein sequences revealed fingerprint sequences of residues which are likely to be involved in substrate and co-substrate binding and one of the three catalytic substeps, respectively. The fingerprint sequences broaden our understanding of the amino acids that might be essential for the reduction of organic acids to the corresponding aldehydes in CAR proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Influences of Plant Species, Season and Location on Leaf Endophytic Bacterial Communities of Non-Cultivated Plants.

    PubMed

    Ding, Tao; Melcher, Ulrich

    2016-01-01

    Bacteria are known to be associated endophytically with plants. Research on endophytic bacteria has identified their importance in food safety, agricultural production and phytoremediation. However, the diversity of endophytic bacterial communities and the forces that shape their compositions in non-cultivated plants are largely uncharacterized. In this study, we explored the diversity, community structure, and dynamics of endophytic bacteria in different plant species in the Tallgrass Prairie Preserve of northern Oklahoma, USA. High throughput sequencing of amplified segments of bacterial rDNA from 81 samples collected at four sampling times from five plant species at four locations identified 335 distinct OTUs at 97% sequence similarity, representing 16 phyla. Proteobacteria was the dominant phylum in the communities, followed by the phyla Bacteriodetes and Actinobacteria. Bacteria from four classes of Proteobacteria were detected with Alphaproteobacteria as the dominant class. Analysis of molecular variance revealed that host plant species and collecting date had significant influences on the compositions of the leaf endophytic bacterial communities. The proportion of Alphaproteobacteria was much higher in the communities from Asclepias viridis than from other plant species and differed from month to month. The most dominant bacterial groups identified in LDA Effect Size analysis showed host-specific patterns, indicating mutual selection between host plants and endophytic bacteria and that leaf endophytic bacterial compositions were dynamic, varying with the host plant's growing season in three distinct patterns. In summary, next generation sequencing has revealed variations in the taxonomic compositions of leaf endophytic bacterial communities dependent primarily on the nature of the plant host species.

  18. Targeted mass spectrometric analysis of N-terminally truncated isoforms generated via alternative translation initiation.

    PubMed

    Kobayashi, Ryuji; Patenia, Rebecca; Ashizawa, Satoshi; Vykoukal, Jody

    2009-07-21

    Alternative translation initiation is a mechanism whereby functionally altered proteins are produced from a single mRNA. Internal initiation of translation generates N-terminally truncated protein isoforms, but such isoforms observed in immunoblot analysis are often overlooked or dismissed as degradation products. We identified an N-terminally truncated isoform of human Dok-1 with N-terminal acetylation as seen in the wild-type. This Dok-1 isoform exhibited distinct perinuclear localization whereas the wild-type protein was distributed throughout the cytoplasm. Targeted analysis of blocked N-terminal peptides provides rapid identification of protein isoforms and could be widely applied for the general evaluation of perplexing immunoblot bands.

  19. Motor current signature analysis method for diagnosing motor operated devices

    DOEpatents

    Haynes, Howard D.; Eissenberg, David M.

    1990-01-01

    A motor current noise signature analysis method and apparatus for remotely monitoring the operating characteristics of an electric motor-operated device such as a motor-operated valve. Frequency domain signal analysis techniques are applied to a conditioned motor current signal to distinctly identify various operating parameters of the motor driven device from the motor current signature. The signature may be recorded and compared with subsequent signatures to detect operating abnormalities and degradation of the device. This diagnostic method does not require special equipment to be installed on the motor-operated device, and the current sensing may be performed at remote control locations, e.g., where the motor-operated devices are used in accessible or hostile environments.

  20. Phylogeographic analysis reveals high genetic structure with uniform phenotypes in the paper wasp Protonectarina sylveirae (Hymenoptera: Vespidae).

    PubMed

    da Silva, Marjorie; Noll, Fernando Barbosa; E Castro, Adriana C Morales-Corrêa

    2018-01-01

    Swarm-founding wasps are endemic and common representatives of neotropical fauna and compose an interesting social tribe of vespids, presenting both complex social characteristics and uncommon traits for a eusocial group, such as the absence of castes with distinct morphology. The paper wasp Protonectarina sylveirae (Saussure) presents a broad distribution from Brazil, Argentina and Paraguay, occurring widespread in the Atlantic rainforest and arboreal Caatinga, being absent in the Amazon region. Given the peculiar distribution among swarm-founding wasps, an integrative approach to reconstruct the evolutionary history of P. sylveirae in a spatial-temporal framework was performed to investigate: the presence of genetic structure and its relationship with the geography, the evolution of distinct morphologic lineages and the possible historical event(s) in Neotropical region, which could explain the observed phylogeographic pattern. Individuals of P. sylveirae were obtained from populations of 16 areas throughout its distribution for DNA extraction and amplification of mitochondrial genes 12S, 16S and COI. Analysis of genetic diversity, construction of haplotype net, analysis of population structure and dating analysis of divergence time were performed. A morphometric analysis was also performed using 8 measures of the body of the adult (workers) to test if there are morphological distinction among populations. Thirty-five haplotypes were identified, most of them exclusively of a group and a high population structure was found. The possibility of genetic divergence because of isolation by distance was rejected. Morphological analysis pointed to a great uniformity in phenotypes, with only a small degree of differentiation between populations of south and the remaining. Divergence time analysis showed a Middle/Late Miocene origin, a period where an extensive marine ingression occurred in South America. Divergence of haplogroups began from the Plio/Pleistocene boundary and the last glacial maximum most likely modeled the current distribution of species, even though it was not the cause of genetic breaks.

  1. Phylogeographic analysis reveals high genetic structure with uniform phenotypes in the paper wasp Protonectarina sylveirae (Hymenoptera: Vespidae)

    PubMed Central

    2018-01-01

    Swarm-founding wasps are endemic and common representatives of neotropical fauna and compose an interesting social tribe of vespids, presenting both complex social characteristics and uncommon traits for a eusocial group, such as the absence of castes with distinct morphology. The paper wasp Protonectarina sylveirae (Saussure) presents a broad distribution from Brazil, Argentina and Paraguay, occurring widespread in the Atlantic rainforest and arboreal Caatinga, being absent in the Amazon region. Given the peculiar distribution among swarm-founding wasps, an integrative approach to reconstruct the evolutionary history of P. sylveirae in a spatial-temporal framework was performed to investigate: the presence of genetic structure and its relationship with the geography, the evolution of distinct morphologic lineages and the possible historical event(s) in Neotropical region, which could explain the observed phylogeographic pattern. Individuals of P. sylveirae were obtained from populations of 16 areas throughout its distribution for DNA extraction and amplification of mitochondrial genes 12S, 16S and COI. Analysis of genetic diversity, construction of haplotype net, analysis of population structure and dating analysis of divergence time were performed. A morphometric analysis was also performed using 8 measures of the body of the adult (workers) to test if there are morphological distinction among populations. Thirty-five haplotypes were identified, most of them exclusively of a group and a high population structure was found. The possibility of genetic divergence because of isolation by distance was rejected. Morphological analysis pointed to a great uniformity in phenotypes, with only a small degree of differentiation between populations of south and the remaining. Divergence time analysis showed a Middle/Late Miocene origin, a period where an extensive marine ingression occurred in South America. Divergence of haplogroups began from the Plio/Pleistocene boundary and the last glacial maximum most likely modeled the current distribution of species, even though it was not the cause of genetic breaks. PMID:29538451

  2. The Comparative Genomics and Phylogenomics of Leishmania amazonensis Parasite.

    PubMed

    Tschoeke, Diogo A; Nunes, Gisele L; Jardim, Rodrigo; Lima, Joana; Dumaresq, Aline Sr; Gomes, Monete R; de Mattos Pereira, Leandro; Loureiro, Daniel R; Stoco, Patricia H; de Matos Guedes, Herbert Leonel; de Miranda, Antonio Basilio; Ruiz, Jeronimo; Pitaluga, André; Silva, Floriano P; Probst, Christian M; Dickens, Nicholas J; Mottram, Jeremy C; Grisard, Edmundo C; Dávila, Alberto Mr

    2014-01-01

    Leishmaniasis is an infectious disease caused by Leishmania species. Leishmania amazonensis is a New World Leishmania species belonging to the Mexicana complex, which is able to cause all types of leishmaniasis infections. The L. amazonensis reference strain MHOM/BR/1973/M2269 was sequenced identifying 8,802 codifying sequences (CDS), most of them of hypothetical function. Comparative analysis using six Leishmania species showed a core set of 7,016 orthologs. L. amazonensis and Leishmania mexicana share the largest number of distinct orthologs, while Leishmania braziliensis presented the largest number of inparalogs. Additionally, phylogenomic analysis confirmed the taxonomic position for L. amazonensis within the "Mexicana complex", reinforcing understanding of the split of New and Old World Leishmania. Potential non-homologous isofunctional enzymes (NISE) were identified between L. amazonensis and Homo sapiens that could provide new drug targets for development.

  3. The Comparative Genomics and Phylogenomics of Leishmania amazonensis Parasite

    PubMed Central

    Tschoeke, Diogo A; Nunes, Gisele L; Jardim, Rodrigo; Lima, Joana; Dumaresq, Aline SR; Gomes, Monete R; de Mattos Pereira, Leandro; Loureiro, Daniel R; Stoco, Patricia H; de Matos Guedes, Herbert Leonel; de Miranda, Antonio Basilio; Ruiz, Jeronimo; Pitaluga, André; Silva, Floriano P; Probst, Christian M; Dickens, Nicholas J; Mottram, Jeremy C; Grisard, Edmundo C; Dávila, Alberto MR

    2014-01-01

    Leishmaniasis is an infectious disease caused by Leishmania species. Leishmania amazonensis is a New World Leishmania species belonging to the Mexicana complex, which is able to cause all types of leishmaniasis infections. The L. amazonensis reference strain MHOM/BR/1973/M2269 was sequenced identifying 8,802 codifying sequences (CDS), most of them of hypothetical function. Comparative analysis using six Leishmania species showed a core set of 7,016 orthologs. L. amazonensis and Leishmania mexicana share the largest number of distinct orthologs, while Leishmania braziliensis presented the largest number of inparalogs. Additionally, phylogenomic analysis confirmed the taxonomic position for L. amazonensis within the “Mexicana complex”, reinforcing understanding of the split of New and Old World Leishmania. Potential non-homologous isofunctional enzymes (NISE) were identified between L. amazonensis and Homo sapiens that could provide new drug targets for development. PMID:25336895

  4. Global priorities for conserving the evolutionary history of sharks, rays and chimaeras.

    PubMed

    Stein, R William; Mull, Christopher G; Kuhn, Tyler S; Aschliman, Neil C; Davidson, Lindsay N K; Joy, Jeffrey B; Smith, Gordon J; Dulvy, Nicholas K; Mooers, Arne O

    2018-02-01

    In an era of accelerated biodiversity loss and limited conservation resources, systematic prioritization of species and places is essential. In terrestrial vertebrates, evolutionary distinctness has been used to identify species and locations that embody the greatest share of evolutionary history. We estimate evolutionary distinctness for a large marine vertebrate radiation on a dated taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic constraints. Chondrichthyans are by far the most evolutionarily distinct of all major radiations of jawed vertebrates-the average species embodies 26 million years of unique evolutionary history. With this metric, we identify 21 countries with the highest richness, endemism and evolutionary distinctness of threatened species as targets for conservation prioritization. On average, threatened chondrichthyans are more evolutionarily distinct-further motivating improved conservation, fisheries management and trade regulation to avoid significant pruning of the chondrichthyan tree of life.

  5. Micro-Raman spectroscopy and chemometrical analysis for the distinction of copper phthalocyanine polymorphs in paint layers.

    PubMed

    Defeyt, C; Van Pevenage, J; Moens, L; Strivay, D; Vandenabeele, P

    2013-11-01

    In art analysis, copper phthalocyanine (CuPc) is often identified as an important pigment (PB15) in 20th century artworks. Raman spectroscopy is a very valuable technique for the detection of this pigment in paint systems. However, PB15 is used in different polymorphic forms and identification of the polymorph could retrieve information on the production process of the pigment at the moment. Raman spectroscopy, being a molecular spectroscopic method of analysis, is able to discriminate between polymorphs of crystals. However, in the case of PB15, spectral interpretation is not straightforward, and Raman data treatment requires some improvements concerning the PB15 polymorphic discrimination in paints. Here, Raman spectroscopy is combined with chemometrical analysis in order to develop a procedure allowing us to identify the PB15 crystalline structure in painted layers and in artworks. The results obtained by Linear Discriminant Analysis (LDA), using intensity ratios as variables, demonstrate the ability of this procedure to predict the crystalline structure of a PB15 pigment in unknown paint samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Online discourse on fibromyalgia: text-mining to identify clinical distinction and patient concerns.

    PubMed

    Park, Jungsik; Ryu, Young Uk

    2014-10-07

    The purpose of this study was to evaluate the possibility of using text-mining to identify clinical distinctions and patient concerns in online memoires posted by patients with fibromyalgia (FM). A total of 399 memoirs were collected from an FM group website. The unstructured data of memoirs associated with FM were collected through a crawling process and converted into structured data with a concordance, parts of speech tagging, and word frequency. We also conducted a lexical analysis and phrase pattern identification. After examining the data, a set of FM-related keywords were obtained and phrase net relationships were set through a web-based visualization tool. The clinical distinction of FM was verified. Pain is the biggest issue to the FM patients. The pains were affecting body parts including 'muscles,' 'leg,' 'neck,' 'back,' 'joints,' and 'shoulders' with accompanying symptoms such as 'spasms,' 'stiffness,' and 'aching,' and were described as 'sever,' 'chronic,' and 'constant.' This study also demonstrated that it was possible to understand the interests and concerns of FM patients through text-mining. FM patients wanted to escape from the pain and symptoms, so they were interested in medical treatment and help. Also, they seemed to have interest in their work and occupation, and hope to continue to live life through the relationships with the people around them. This research shows the potential for extracting keywords to confirm the clinical distinction of a certain disease, and text-mining can help objectively understand the concerns of patients by generalizing their large number of subjective illness experiences. However, it is believed that there are limitations to the processes and methods for organizing and classifying large amounts of text, so these limits have to be considered when analyzing the results. The development of research methodology to overcome these limitations is greatly needed.

  7. Paraduodenal Pancreatitis: Imaging and Pathologic Correlation of 47 Cases Elucidates Distinct Subtypes and the Factors Involved in its Etiopathogenesis.

    PubMed

    Muraki, Takashi; Kim, Grace E; Reid, Michelle D; Mittal, Pardeep; Bedolla, Gabriela; Memis, Bahar; Pehlivanoglu, Burcin; Freedman, Alexa; Erbarut Seven, Ipek; Choi, Hyejeong; Kooby, David; Maithel, Shishir K; Sarmiento, Juan M; Krasinskas, Alyssa; Adsay, Volkan

    2017-10-01

    Clinicopathologic characteristics of paraduodenal (groove) pancreatitis (PDP) remain to be fully unraveled. In this study, 47 PDPs with preoperative enhanced images available were subjected to detailed comparative analysis in conjunction with pathologic findings. PDP were predominantly in males (3:1) with a mean age of 50 years, and 60% had a preoperative diagnosis of cancer. Mean lesional size was 3.1 cm. Three distinct subtypes were identified by imaging. Solid-tumoral (type-1) with groove-predominant (type-1A, 36%) forming a distinct solid band between the duodenum and pancreas often with histologic microabscesses (69% vs. 33% in others), and pancreas-involving (type-1B, 19%) forming a pseudotumoral mass spanning into the head-groove area, always diagnosed preoperatively as "cancer," but often lacked parenchymal atrophy of the body (44% vs. 92%). Cyst-forming (type-2) had groove-predominant (type-2A, 15%), often accompanied by Brunner gland hyperplasia, and pancreas-predominant (type-2B, 15%) were in younger (mean: 44 y) females (57% vs. 18%) and had less alcohol/tobacco abuse (50/33% vs. 81/69%). Ill-defined (type-3; 15%) often had main pancreatic duct dilatation (mean: 5.6 vs. 2.8 mm). The capricious presentations of PDP could be attributed to variable effects of different mechanistic and precipitative etiopathogenetic factors such as disturbed accessory duct outflow (dilated Santorini duct, 87%), aggravated by alcohol (77%) with superimposed stasis in the main ampulla (previous cholecystectomy, 47%; choledocholithiasis, 9%), strictured Wirsung duct (68%), and some likely exacerbated by ischemia (hypertension [59%], tobacco abuse [64%], arteriosclerosis in the tissue [23%]). In conclusion, our study identified 3 distinct types of PDP and each may reflect different pathogenetic contributing factors.

  8. A practical guideline for identifying research intent with projects that collect private, identifiable health information.

    PubMed

    Amdur, Robert J; Speers, Marjorie A

    2003-06-01

    Radiation oncologists frequently engage in activities that involve the collection and analysis of data from medical records. Access to health information is an ethical issue because, if not done according to appropriate guidelines, it constitutes an invasion of privacy or breach in confidentiality. To protect patients for the social harm that may result from medical record review, our society has established laws and regulations that apply to projects that require medical record review. A major branch point in the guidelines for such projects is whether private information will be collected for research or nonresearch purposes. However, a problem with discussing privacy protection in terms of a research versus nonresearch model is that it is difficult to make this distinction for many kinds of projects. The purpose of this paper is to establish a practical guideline that can be used to decide if a project that involves analysis of private, identifiable medical information should be considered research from the regulatory standpoint.

  9. The proteomic landscape of triple-negative breast cancer.

    PubMed

    Lawrence, Robert T; Perez, Elizabeth M; Hernández, Daniel; Miller, Chris P; Haas, Kelsey M; Irie, Hanna Y; Lee, Su-In; Blau, C Anthony; Villén, Judit

    2015-04-28

    Triple-negative breast cancer is a heterogeneous disease characterized by poor clinical outcomes and a shortage of targeted treatment options. To discover molecular features of triple-negative breast cancer, we performed quantitative proteomics analysis of twenty human-derived breast cell lines and four primary breast tumors to a depth of more than 12,000 distinct proteins. We used this data to identify breast cancer subtypes at the protein level and demonstrate the precise quantification of biomarkers, signaling proteins, and biological pathways by mass spectrometry. We integrated proteomics data with exome sequence resources to identify genomic aberrations that affect protein expression. We performed a high-throughput drug screen to identify protein markers of drug sensitivity and understand the mechanisms of drug resistance. The genome and proteome provide complementary information that, when combined, yield a powerful engine for therapeutic discovery. This resource is available to the cancer research community to catalyze further analysis and investigation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Comprehensive proteomic analysis of the human spliceosome

    NASA Astrophysics Data System (ADS)

    Zhou, Zhaolan; Licklider, Lawrence J.; Gygi, Steven P.; Reed, Robin

    2002-09-01

    The precise excision of introns from pre-messenger RNA is performed by the spliceosome, a macromolecular machine containing five small nuclear RNAs and numerous proteins. Much has been learned about the protein components of the spliceosome from analysis of individual purified small nuclear ribonucleoproteins and salt-stable spliceosome `core' particles. However, the complete set of proteins that constitutes intact functional spliceosomes has yet to be identified. Here we use maltose-binding protein affinity chromatography to isolate spliceosomes in highly purified and functional form. Using nanoscale microcapillary liquid chromatography tandem mass spectrometry, we identify ~145 distinct spliceosomal proteins, making the spliceosome the most complex cellular machine so far characterized. Our spliceosomes comprise all previously known splicing factors and 58 newly identified components. The spliceosome contains at least 30 proteins with known or putative roles in gene expression steps other than splicing. This complexity may be required not only for splicing multi-intronic metazoan pre-messenger RNAs, but also for mediating the extensive coupling between splicing and other steps in gene expression.

  11. Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators.

    PubMed

    Silberstein, Lev; Goncalves, Kevin A; Kharchenko, Peter V; Turcotte, Raphael; Kfoury, Youmna; Mercier, Francois; Baryawno, Ninib; Severe, Nicolas; Bachand, Jacqueline; Spencer, Joel A; Papazian, Ani; Lee, Dongjun; Chitteti, Brahmananda Reddy; Srour, Edward F; Hoggatt, Jonathan; Tate, Tiffany; Lo Celso, Cristina; Ono, Noriaki; Nutt, Stephen; Heino, Jyrki; Sipilä, Kalle; Shioda, Toshihiro; Osawa, Masatake; Lin, Charles P; Hu, Guo-Fu; Scadden, David T

    2016-10-06

    Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology-the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin-and discovered that all of these factors are HSPC quiescence regulators. Therefore, our proximity-based differential single-cell approach reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance the understanding of microenvironmental regulation of stem cell function. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Trajectories of fathers' psychological distress across the early parenting period: Implications for parenting.

    PubMed

    Giallo, Rebecca; Cooklin, Amanda; Brown, Stephanie; Christensen, Daniel; Kingston, Dawn; Liu, Cindy H; Wade, Catherine; Nicholson, Jan M

    2015-10-01

    Fathers' parenting behavior is a likely key mechanism underlying the consistent associations between paternal mental health difficulties and poor emotional-behavioral outcomes for children. This study investigates the association between fathers' mental health trajectories and key parenting behaviors (warmth, hostility, consistency) spanning the first 8-9 years postpartum. Secondary analyses of 5 waves of data from 2,662 fathers participating in the Longitudinal Study of Australian Children were conducted. Latent growth class analysis was used to identify distinct trajectories of fathers' distress (Kessler-6; Kessler et al., 2003), and latent growth models estimated parenting warmth, hostility, and consistency. Multiple group analyses were conducted to describe and compare the course of parenting behaviors for fathers assigned to the distress trajectories identified. Two distinct classes of fathers were identified based on the trajectories of distress: minimal distress (92%) and persistent and increasing distress (8%). The latter group reported significantly lower parenting warmth when their children were 8-9 years and lower consistency and higher hostility across all study intervals. The postnatal and early parenting period is a critical time for the development of parenting behaviors that are important for children's development. Engagement and support for fathers around well-being and parenting is vital for promoting optimal family and child developmental outcomes. (c) 2015 APA, all rights reserved).

  13. In cell mutational interference mapping experiment (in cell MIME) identifies the 5' polyadenylation signal as a dual regulator of HIV-1 genomic RNA production and packaging.

    PubMed

    Smyth, Redmond P; Smith, Maureen R; Jousset, Anne-Caroline; Despons, Laurence; Laumond, Géraldine; Decoville, Thomas; Cattenoz, Pierre; Moog, Christiane; Jossinet, Fabrice; Mougel, Marylène; Paillart, Jean-Christophe; von Kleist, Max; Marquet, Roland

    2018-05-18

    Non-coding RNA regulatory elements are important for viral replication, making them promising targets for therapeutic intervention. However, regulatory RNA is challenging to detect and characterise using classical structure-function assays. Here, we present in cell Mutational Interference Mapping Experiment (in cell MIME) as a way to define RNA regulatory landscapes at single nucleotide resolution under native conditions. In cell MIME is based on (i) random mutation of an RNA target, (ii) expression of mutated RNA in cells, (iii) physical separation of RNA into functional and non-functional populations, and (iv) high-throughput sequencing to identify mutations affecting function. We used in cell MIME to define RNA elements within the 5' region of the HIV-1 genomic RNA (gRNA) that are important for viral replication in cells. We identified three distinct RNA motifs controlling intracellular gRNA production, and two distinct motifs required for gRNA packaging into virions. Our analysis reveals the 73AAUAAA78 polyadenylation motif within the 5' PolyA domain as a dual regulator of gRNA production and gRNA packaging, and demonstrates that a functional polyadenylation signal is required for viral packaging even though it negatively affects gRNA production.

  14. In cell mutational interference mapping experiment (in cell MIME) identifies the 5′ polyadenylation signal as a dual regulator of HIV-1 genomic RNA production and packaging

    PubMed Central

    Smith, Maureen R; Jousset, Anne-Caroline; Despons, Laurence; Laumond, Géraldine; Decoville, Thomas; Cattenoz, Pierre; Moog, Christiane; Jossinet, Fabrice; Mougel, Marylène; Paillart, Jean-Christophe

    2018-01-01

    Abstract Non-coding RNA regulatory elements are important for viral replication, making them promising targets for therapeutic intervention. However, regulatory RNA is challenging to detect and characterise using classical structure-function assays. Here, we present in cell Mutational Interference Mapping Experiment (in cell MIME) as a way to define RNA regulatory landscapes at single nucleotide resolution under native conditions. In cell MIME is based on (i) random mutation of an RNA target, (ii) expression of mutated RNA in cells, (iii) physical separation of RNA into functional and non-functional populations, and (iv) high-throughput sequencing to identify mutations affecting function. We used in cell MIME to define RNA elements within the 5′ region of the HIV-1 genomic RNA (gRNA) that are important for viral replication in cells. We identified three distinct RNA motifs controlling intracellular gRNA production, and two distinct motifs required for gRNA packaging into virions. Our analysis reveals the 73AAUAAA78 polyadenylation motif within the 5′ PolyA domain as a dual regulator of gRNA production and gRNA packaging, and demonstrates that a functional polyadenylation signal is required for viral packaging even though it negatively affects gRNA production. PMID:29514260

  15. Guanine nucleotide-binding protein α subunit hypofunction in children with short stature and disproportionate shortening of the 4th and 5th metacarpals.

    PubMed

    Inta, Ioana Monica; Choukair, Daniela; Bender, Sebastian; Kneppo, Carolin; Knauer-Fischer, Sabine; Meyenburg, Kahina; Ivandic, Boris; Pfister, Stefan M; Bettendorf, Markus

    2014-01-01

    GNAS encodes the α subunit of the stimulatory G protein (Gsα). Maternal inherited Gsα mutations cause pseudohypoparathyroidism type Ia (PHP-Ia), associated with shortening of the 4th and 5th metacarpals. Here we investigated the Gsα pathway in short patients with distinct shortening of the 4th and 5th metacarpals. In 571 children with short stature and 4 patients with PHP-Ia metacarpal bone lengths were measured. In identified patients we analysed the Gsα protein function in platelets, performed GNAS sequencing, and epigenetic analysis of four significant differentially methylated regions. In 51 patients (8.9%) shortening of the 4th and 5th metacarpals was more pronounced than their height deficit. No GNAS coding mutations were identified in 20 analysed patients, except in 2 PHP-Ia patients. Gsα activity was reduced in all PHP-Ia patients and in 25% of the analysed patients. No significant methylation changes were identified. Our findings suggest that patients with short stature and distinct metacarpal bone shortening could be part of the wide variety of PHP/PPHP, therefore it was worthwhile analysing the Gsα protein function and GNAS gene in these patients in order to further elucidate the phenotype and genotype of Gsα dysfunction.

  16. Genome-wide analysis identifies chickpea (Cicer arietinum) heat stress transcription factors (Hsfs) responsive to heat stress at the pod development stage.

    PubMed

    Chidambaranathan, Parameswaran; Jagannadham, Prasanth Tej Kumar; Satheesh, Viswanathan; Kohli, Deshika; Basavarajappa, Santosh Halasabala; Chellapilla, Bharadwaj; Kumar, Jitendra; Jain, Pradeep Kumar; Srinivasan, R

    2018-05-01

    The heat stress transcription factors (Hsfs) play a prominent role in thermotolerance and eliciting the heat stress response in plants. Identification and expression analysis of Hsfs gene family members in chickpea would provide valuable information on heat stress responsive Hsfs. A genome-wide analysis of Hsfs gene family resulted in the identification of 22 Hsf genes in chickpea in both desi and kabuli genome. Phylogenetic analysis distinctly separated 12 A, 9 B, and 1 C class Hsfs, respectively. An analysis of cis-regulatory elements in the upstream region of the genes identified many stress responsive elements such as heat stress elements (HSE), abscisic acid responsive element (ABRE) etc. In silico expression analysis showed nine and three Hsfs were also expressed in drought and salinity stresses, respectively. Q-PCR expression analysis of Hsfs under heat stress at pod development and at 15 days old seedling stage showed that CarHsfA2, A6, and B2 were significantly upregulated in both the stages of crop growth and other four Hsfs (CarHsfA2, A6a, A6c, B2a) showed early transcriptional upregulation for heat stress at seedling stage of chickpea. These subclasses of Hsfs identified in this study can be further evaluated as candidate genes in the characterization of heat stress response in chickpea.

  17. HealthStyles: a new psychographic segmentation system for health care marketers.

    PubMed

    Endresen, K W; Wintz, J C

    1988-01-01

    HealthStyles is a new psychographic segmentation system specifically designed for the health care industry. This segmentation system goes beyond traditional geographic and demographic analysis and examines health-related consumer attitudes and behaviors. Four statistically distinct "styles" of consumer health care preferences have been identified. The profiles of the four groups have substantial marketing implications in terms of design and promotion of products and services. Each segment of consumers also has differing expectations of physician behavior.

  18. Ethical issues in public health surveillance: a systematic qualitative review.

    PubMed

    Klingler, Corinna; Silva, Diego Steven; Schuermann, Christopher; Reis, Andreas Alois; Saxena, Abha; Strech, Daniel

    2017-04-04

    Public health surveillance is not ethically neutral and yet, ethics guidance and training for surveillance programmes is sparse. Development of ethics guidance should be based on comprehensive and transparently derived overviews of ethical issues and arguments. However, existing overviews on surveillance ethics are limited in scope and in how transparently they derived their results. Our objective was accordingly to provide an overview of ethical issues in public health surveillance; in addition, to list the arguments put forward with regards to arguably the most contested issue in surveillance, that is whether to obtain informed consent. Ethical issues were defined based on principlism. We assumed an ethical issue to arise in surveillance when a relevant normative principle is not adequately considered or two principles come into conflict. We searched Pubmed and Google Books for relevant publications. We analysed and synthesized the data using qualitative content analysis. Our search strategy retrieved 525 references of which 83 were included in the analysis. We identified 86 distinct ethical issues arising in the different phases of the surveillance life-cycle. We further identified 20 distinct conditions that make it more or less justifiable to forego informed consent procedures. This is the first systematic qualitative review of ethical issues in public health surveillance resulting in a comprehensive ethics matrix that can inform guidelines, reports, strategy papers, and educational material and raise awareness among practitioners.

  19. Common and distinct neural targets of treatment: changing brain function in substance addiction.

    PubMed

    Konova, Anna B; Moeller, Scott J; Goldstein, Rita Z

    2013-12-01

    Neuroimaging offers an opportunity to examine the neurobiological effects of therapeutic interventions for human drug addiction. Using activation likelihood estimation, the aim of the current meta-analysis was to quantitatively summarize functional neuroimaging studies of pharmacological and cognitive-based interventions for drug addiction, with an emphasis on their common and distinct neural targets. More exploratory analyses also contrasted subgroups of studies based on specific study and sample characteristics. The ventral striatum, a region implicated in reward, motivation, and craving, and the inferior frontal gyrus and orbitofrontal cortex, regions involved in inhibitory control and goal-directed behavior, were identified as common targets of pharmacological and cognitive-based interventions; these regions were observed when the analysis was limited to only studies that used established or efficacious interventions, and across imaging paradigms and types of addictions. Consistent with theoretical models, cognitive-based interventions were additionally more likely to activate the anterior cingulate cortex, middle frontal gyrus, and precuneus, implicated in self-referential processing, cognitive control, and attention. These results suggest that therapeutic interventions for addiction may target the brain structures that are altered across addictions and identify potential neurobiological mechanisms by which the tandem use of pharmacological and cognitive-based interventions may yield synergistic or complementary effects. These findings could inform the selection of novel functional targets in future treatment development for this difficult-to-treat disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Common and distinct neural targets of treatment: changing brain function in substance addiction

    PubMed Central

    Konova, Anna B.; Moeller, Scott J.; Goldstein, Rita Z.

    2013-01-01

    Neuroimaging offers an opportunity to examine the neurobiological effects of therapeutic interventions for human drug addiction. Using activation likelihood estimation, the aim of the current meta-analysis was to quantitatively summarize functional neuroimaging studies of pharmacological and cognitive-based interventions for drug addiction, with an emphasis on their common and distinct neural targets. More exploratory analyses also contrasted subgroups of studies based on specific study and sample characteristics. The ventral striatum, a region implicated in reward, motivation, and craving, and the inferior frontal gyrus and orbitofrontal cortex, regions involved in inhibitory control goal-directed behavior, were identified as common targets of pharmacological and cognitive-based interventions; these regions were observed when the analysis was limited to only studies that used established or efficacious interventions, and across imaging paradigms and types of addictions. Consistent with theoretical models, cognitive-based interventions were additionally more likely to activate the anterior cingulate cortex, middle frontal gyrus, and precuneus, implicated in self-referential processing, cognitive control, and attention. These results suggest that therapeutic interventions for addiction may target the brain structures that are altered across addictions and identify potential neurobiological mechanisms by which the tandem use of pharmacological and cognitive-based interventions may yield synergistic or complementary effects. These findings could inform the selection of novel functional targets in future treatment development for this difficult-to-treat disorder. PMID:24140399

  1. Exploring student learning profiles in algebra-based studio physics: A person-centered approach

    NASA Astrophysics Data System (ADS)

    Pond, Jarrad W. T.; Chini, Jacquelyn J.

    2017-06-01

    In this study, we explore the strategic self-regulatory and motivational characteristics of students in studio-mode physics courses at three universities with varying student populations and varying levels of success in their studio-mode courses. We survey students using questions compiled from several existing questionnaires designed to measure students' study strategies, attitudes toward and motivations for learning physics, organization of scientific knowledge, experiences outside the classroom, and demographics. Using a person-centered approach, we utilize cluster analysis methods to group students into learning profiles based on their individual responses to better understand the strategies and motives of algebra-based studio physics students. Previous studies have identified five distinct learning profiles across several student populations using similar methods. We present results from first-semester and second-semester studio-mode introductory physics courses across three universities. We identify these five distinct learning profiles found in previous studies to be present within our population of introductory physics students. In addition, we investigate interactions between these learning profiles and student demographics. We find significant interactions between a student's learning profile and their experience with high school physics, major, gender, grade expectation, and institution. Ultimately, we aim to use this method of analysis to take the characteristics of students into account in the investigation of successful strategies for using studio methods of physics instruction within and across institutions.

  2. Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design

    PubMed Central

    Andreae, Clio A.; Sessions, Richard B.; Virji, Mumtaz

    2018-01-01

    Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis. PMID:29547646

  3. Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design.

    PubMed

    Andreae, Clio A; Sessions, Richard B; Virji, Mumtaz; Hill, Darryl J

    2018-01-01

    Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis.

  4. Structure of the effector-binding domain of the arabinose repressor AraR from Bacillus subtilis

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

    Procházková, Kateřina; Čermáková, Kateřina; Pachl, Petr

    2012-02-01

    The crystal structure of the effector-binding domain of the transcriptional repressor AraR from B. subtilis in complex with the effector molecule (l-arabinose) was determined at 2.2 Å resolution. A detailed analysis of the crystal identified a dimer organization that is distinctive from that of other members of the GalR/LacI family. In Bacillus subtilis, the arabinose repressor AraR negatively controls the expression of genes in the metabolic pathway of arabinose-containing polysaccharides. The protein is composed of two domains of different phylogenetic origin and function: an N-terminal DNA-binding domain belonging to the GntR family and a C-terminal effector-binding domain that shows similaritymore » to members of the GalR/LacI family. The crystal structure of the C-terminal effector-binding domain of AraR in complex with the effector l-arabinose has been determined at 2.2 Å resolution. The l-arabinose binding affinity was characterized by isothermal titration calorimetry and differential scanning fluorimetry; the K{sub d} value was 8.4 ± 0.4 µM. The effect of l-arabinose on the protein oligomeric state was investigated in solution and detailed analysis of the crystal identified a dimer organization which is distinctive from that of other members of the GalR/LacI family.« less

  5. Distinct Trajectories in the Transition to Adulthood: Are Children of Immigrants Advantaged?

    ERIC Educational Resources Information Center

    Hao, Lingxin; Woo, Han S.

    2012-01-01

    Studies on children of immigrants have generally ignored distinct developmental trajectories during adolescence and their role in the transition to adulthood. This study identifies distinct trajectories in cognitive, sociobehavioral, and psychological domains and estimates their consequences for young adults. Drawing data from a nationally…

  6. Cluster analysis reveals seasonal variation of sperm subpopulations in extended boar semen

    PubMed Central

    IBĂNESCU, Iulian; LEIDING, Claus; BOLLWEIN, Heinrich

    2017-01-01

    This study aimed to identify motile sperm subpopulations in extended boar semen and to observe the presumptive seasonal variation in their distribution. Data from 4837 boar ejaculates collected over a two-year period were analyzed in terms of kinematic parameters by Computer Assisted Sperm Analysis (CASA). Individual sperm data were used to determine subgroups of motile sperm within the ejaculates using cluster analysis. Four motile sperm subpopulations (SP) were identified, with distinct movement patterns: SP1 sperm with high velocity and high linearity; SP2 sperm with high velocity but low linearity; SP3 sperm with low velocity but high linearity; and SP4 sperm with low velocity and low linearity. SP1 constituted the least overall proportion within the ejaculates (P < 0.05). Season of semen collection significantly influenced the different proportions of sperm subpopulations. Spring was characterized by similar proportions of SP1 and SP4 (NS) and higher proportions of SP3. Summer brought a decrease in both subgroups containing fast sperm (SP1 and SP2) (P < 0.05). During autumn, increases in SP2 and SP4 were recorded. Winter substantially affected the proportions of all sperm subpopulations (P < 0.05) and SP2 became the most represented subgroup, while SP1 (fast and linear) reached its highest proportion compared to other seasons. In conclusion, extended boar semen is structured in distinct motile sperm subpopulations whose proportions vary according to the season of collection. Summer and autumn seem to have a negative impact on the fast and linear subpopulation. Cluster analysis can be useful in revealing differences in semen quality that are not normally detected by classical evaluation based on mean values. PMID:29081440

  7. Identifying Neural Patterns of Functional Dyspepsia Using Multivariate Pattern Analysis: A Resting-State fMRI Study

    PubMed Central

    Liu, Peng; Qin, Wei; Wang, Jingjing; Zeng, Fang; Zhou, Guangyu; Wen, Haixia; von Deneen, Karen M.; Liang, Fanrong; Gong, Qiyong; Tian, Jie

    2013-01-01

    Background Previous imaging studies on functional dyspepsia (FD) have focused on abnormal brain functions during special tasks, while few studies concentrated on the resting-state abnormalities of FD patients, which might be potentially valuable to provide us with direct information about the neural basis of FD. The main purpose of the current study was thereby to characterize the distinct patterns of resting-state function between FD patients and healthy controls (HCs). Methodology/Principal Findings Thirty FD patients and thirty HCs were enrolled and experienced 5-mintue resting-state scanning. Based on the support vector machine (SVM), we applied multivariate pattern analysis (MVPA) to investigate the differences of resting-state function mapped by regional homogeneity (ReHo). A classifier was designed by using the principal component analysis and the linear SVM. Permutation test was then employed to identify the significant contribution to the final discrimination. The results displayed that the mean classifier accuracy was 86.67%, and highly discriminative brain regions mainly included the prefrontal cortex (PFC), orbitofrontal cortex (OFC), supplementary motor area (SMA), temporal pole (TP), insula, anterior/middle cingulate cortex (ACC/MCC), thalamus, hippocampus (HIPP)/parahippocamus (ParaHIPP) and cerebellum. Correlation analysis revealed significant correlations between ReHo values in certain regions of interest (ROI) and the FD symptom severity and/or duration, including the positive correlations between the dmPFC, pACC and the symptom severity; whereas, the positive correlations between the MCC, OFC, insula, TP and FD duration. Conclusions These findings indicated that significantly distinct patterns existed between FD patients and HCs during the resting-state, which could expand our understanding of the neural basis of FD. Meanwhile, our results possibly showed potential feasibility of functional magnetic resonance imaging diagnostic assay for FD. PMID:23874543

  8. Genome-wide organization and expression profiling of the R2R3-MYB transcription factor family in pineapple (Ananas comosus).

    PubMed

    Liu, Chaoyang; Xie, Tao; Chen, Chenjie; Luan, Aiping; Long, Jianmei; Li, Chuhao; Ding, Yaqi; He, Yehua

    2017-07-01

    The MYB proteins comprise one of the largest families of plant transcription factors, which are involved in various plant physiological and biochemical processes. Pineapple (Ananas comosus) is one of three most important tropical fruits worldwide. The completion of pineapple genome sequencing provides a great opportunity to investigate the organization and evolutionary traits of pineapple MYB genes at the genome-wide level. In the present study, a total of 94 pineapple R2R3-MYB genes were identified and further phylogenetically classified into 26 subfamilies, as supported by the conserved gene structures and motif composition. Collinearity analysis indicated that the segmental duplication events played a crucial role in the expansion of pineapple MYB gene family. Further comparative phylogenetic analysis suggested that there have been functional divergences of MYB gene family during plant evolution. RNA-seq data from different tissues and developmental stages revealed distinct temporal and spatial expression profiles of the AcMYB genes. Further quantitative expression analysis showed the specific expression patterns of the selected putative stress-related AcMYB genes in response to distinct abiotic stress and hormonal treatments. The comprehensive expression analysis of the pineapple MYB genes, especially the tissue-preferential and stress-responsive genes, could provide valuable clues for further function characterization. In this work, we systematically identified AcMYB genes by analyzing the pineapple genome sequence using a set of bioinformatics approaches. Our findings provide a global insight into the organization, phylogeny and expression patterns of the pineapple R2R3-MYB genes, and hence contribute to the greater understanding of their biological roles in pineapple.

  9. Self-efficacy difference among patients with cancer with different socioeconomic status: application of latent class analysis and standardization and decomposition analysis.

    PubMed

    Yuan, Changrong; Wei, Chunlan; Wang, Jichuan; Qian, Huijuan; Ye, Xianghong; Liu, Yingyan; Hinds, Pamela S

    2014-06-01

    Although the relationship between partial socioeconomic status (SES) and self-efficacy has been studied in previous studies, few research have examined self-efficacy difference among patients with cancer with different SES. A cross-sectional survey involving 764 patients with cancer was completed. Latent class analysis (LCA) was applied to identify distinct groups of patients with cancer using four SES indicators (education, income, employment status and health insurance status). Standardization and decomposition analysis (SDA) was then used to examine differences in patients' self-efficacy among SES groups and the components of the differences attributed to confounding factors, such as gender, age, anxiety, depression and social support. Participants were classified into four distinctive SES groups via using LCA method, and the observed self-efficacy level significantly varied by SES groups; as theorized, higher self-efficacy was associated with higher SES. The self-efficacy differences by SES groups were decomposed into "real" group differences and factor component effects that are attributed to group differences in confounding factor compositions. Self-efficacy significantly varies by SES. Social support significantly confounded the observed differences in self-efficacy between different SES groups among Chinese patients with cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Ownership reform and the changing manufacturing landscape in Chinese cities: The case of Wuxi.

    PubMed

    Zhou, Lei; Yang, Shan; Wang, Shuguang; Xiong, Liyang

    2017-01-01

    Since the economic transition, manufacturing in China has undergone profound changes not only in number of enterprises, but also in ownership structure and intra-urban spatial distribution. Investigating the changing manufacturing landscape from the perspective of ownership structure is critical to a deep understanding of the changing role of market and government in re-shaping manufacturing location behavior. Through a case study of Wuxi, a city experiencing comprehensive ownership reform, this paper presents a detailed analysis of the intra-urban spatial shift of manufacturing, identifies the location discrepancies, and examines the underlying forces responsible for the geographical differentiations. Through zone- and district-based analysis, a distinctive trend of decentralization and suburbanization, as well as an uneven distribution of manufacturing, is unveiled. The results of Location Quotient analysis show that the distribution of manufacturing by ownership exhibits distinctive spatial patterns, which is characterized by a historically-based, market-led, and institutionally-created spatial variation. By employing Hot Spot analysis, the role of development zones in attracting manufacturing enterprises of different ownerships is established. Overall, the location behavior of the diversified manufacturing has been increasingly based on the forces of market since the land marketization began. A proactive role played by local governments has also guided the enterprise location decision through spatial planning and regulatory policies.

  11. Ownership reform and the changing manufacturing landscape in Chinese cities: The case of Wuxi

    PubMed Central

    Zhou, Lei; Yang, Shan; Wang, Shuguang

    2017-01-01

    Since the economic transition, manufacturing in China has undergone profound changes not only in number of enterprises, but also in ownership structure and intra-urban spatial distribution. Investigating the changing manufacturing landscape from the perspective of ownership structure is critical to a deep understanding of the changing role of market and government in re-shaping manufacturing location behavior. Through a case study of Wuxi, a city experiencing comprehensive ownership reform, this paper presents a detailed analysis of the intra-urban spatial shift of manufacturing, identifies the location discrepancies, and examines the underlying forces responsible for the geographical differentiations. Through zone- and district-based analysis, a distinctive trend of decentralization and suburbanization, as well as an uneven distribution of manufacturing, is unveiled. The results of Location Quotient analysis show that the distribution of manufacturing by ownership exhibits distinctive spatial patterns, which is characterized by a historically-based, market-led, and institutionally-created spatial variation. By employing Hot Spot analysis, the role of development zones in attracting manufacturing enterprises of different ownerships is established. Overall, the location behavior of the diversified manufacturing has been increasingly based on the forces of market since the land marketization began. A proactive role played by local governments has also guided the enterprise location decision through spatial planning and regulatory policies. PMID:28278284

  12. Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor.

    PubMed

    Haller, Florian; Zhang, Jitao David; Moskalev, Evgeny A; Braun, Alexander; Otto, Claudia; Geddert, Helene; Riazalhosseini, Yasser; Ward, Aoife; Balwierz, Aleksandra; Schaefer, Inga-Marie; Cameron, Silke; Ghadimi, B Michael; Agaimy, Abbas; Fletcher, Jonathan A; Hoheisel, Jörg; Hartmann, Arndt; Werner, Martin; Wiemann, Stefan; Sahin, Ozgür

    2015-03-01

    Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to localization, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer-related genes in a cohort of 76 GISTs, combined with genome-wide mRNA expression analysis in 22 GISTs, to identify signatures associated with clinicopathological parameters and prognosis. Principal component analysis revealed distinct DNA methylation patterns associated with anatomical localization, genotype, mitotic counts and clinical follow-up. Methylation of a single CpG dinucleotide in the non-CpG island promoter of SPP1 was significantly correlated with shorter disease-free survival. Hypomethylation of this CpG was an independent prognostic parameter in a multivariate analysis compared to anatomical localization, genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical follow-up. The epigenetic regulation of SPP1 was confirmed in vitro, and the functional impact of SPP1 protein on tumorigenesis-related signaling pathways was demonstrated. In summary, SPP1 promoter methylation is a novel and independent prognostic parameter in GISTs, and might be helpful in estimating the aggressiveness of GISTs from the intermediate-risk category. © 2014 UICC.

  13. Nitrogen economics of root foraging: Transitive closure of the nitrate–cytokinin relay and distinct systemic signaling for N supply vs. demand

    PubMed Central

    Ruffel, Sandrine; Krouk, Gabriel; Ristova, Daniela; Shasha, Dennis; Birnbaum, Kenneth D.; Coruzzi, Gloria M.

    2011-01-01

    As sessile organisms, root plasticity enables plants to forage for and acquire nutrients in a fluctuating underground environment. Here, we use genetic and genomic approaches in a “split-root” framework—in which physically isolated root systems of the same plant are challenged with different nitrogen (N) environments—to investigate how systemic signaling affects genome-wide reprogramming and root development. The integration of transcriptome and root phenotypes enables us to identify distinct mechanisms underlying “N economy” (i.e., N supply and demand) of plants as a system. Under nitrate-limited conditions, plant roots adopt an “active-foraging strategy”, characterized by lateral root outgrowth and a shared pattern of transcriptome reprogramming, in response to either local or distal nitrate deprivation. By contrast, in nitrate-replete conditions, plant roots adopt a “dormant strategy”, characterized by a repression of lateral root outgrowth and a shared pattern of transcriptome reprogramming, in response to either local or distal nitrate supply. Sentinel genes responding to systemic N signaling identified by genome-wide comparisons of heterogeneous vs. homogeneous split-root N treatments were used to probe systemic N responses in Arabidopsis mutants impaired in nitrate reduction and hormone synthesis and also in decapitated plants. This combined analysis identified genetically distinct systemic signaling underlying plant N economy: (i) N supply, corresponding to a long-distance systemic signaling triggered by nitrate sensing; and (ii) N demand, experimental support for the transitive closure of a previously inferred nitrate–cytokinin shoot–root relay system that reports the nitrate demand of the whole plant, promoting a compensatory root growth in nitrate-rich patches of heterogeneous soil. PMID:22025711

  14. Two distinct major QTL for resistance to fire blight co-localize on linkage group 12 in apple genotypes 'Evereste' and Malus floribunda clone 821.

    PubMed

    Durel, C-E; Denancé, C; Brisset, M-N

    2009-02-01

    Fire blight, caused by the bacterium Erwinia amylovora, is one of the most destructive diseases of apple (Malus xdomestica) worldwide. No major, qualitative gene for resistance to this disease has been identified so far in apple. A quantitative trait locus (QTL) analysis was performed in two F1 progenies derived from two controled crosses: one between the susceptible rootstock cultivar 'MM106' and the resistant ornamental cultivar 'Evereste' and the other one between the moderately susceptible cultivar 'Golden Delicious' and the wild apple Malus floribunda clone 821, with unknown level of fire blight resistance. Both progenies were inoculated in the greenhouse with the same reference strain of E. amylovora. The length of stem necrosis was scored 7 and 14 days after inoculation. A strong QTL effect was identified in both 'Evereste' and M. floribunda 821 at a similar position on the distal region of linkage group 12 of the apple genome. From 50% to 70% of the phenotypic variation was explained by the QTL in 'Evereste' progeny according to the scored trait. More than 40% of the phenotypic variation was explained by the M. floribunda QTL in the second progeny. It was shown that 'Evereste' and M. floribunda 821 carried distinct QTL alleles at that genomic position. A small additional QTL was identified in 'Evereste' on linkage group 15, which explained about 6% of the phenotypic variation. Although it was not possible to confirm whether or not 'Evereste' and M. floribunda QTL belonged to the same locus or two distinct closely related loci, these QTL can be valuable targets in marker-assisted selection to obtain fire blight resistant apple cultivars and form a starting point for discovering the function of the genes controlling apple fire blight resistance.

  15. Epigenome overlap measure (EPOM) for comparing tissue/cell types based on chromatin states.

    PubMed

    Li, Wei Vivian; Razaee, Zahra S; Li, Jingyi Jessica

    2016-01-11

    The dynamics of epigenomic marks in their relevant chromatin states regulate distinct gene expression patterns, biological functions and phenotypic variations in biological processes. The availability of high-throughput epigenomic data generated by next-generation sequencing technologies allows a data-driven approach to evaluate the similarities and differences of diverse tissue and cell types in terms of epigenomic features. While ChromImpute has allowed for the imputation of large-scale epigenomic information to yield more robust data to capture meaningful relationships between biological samples, widely used methods such as hierarchical clustering and correlation analysis cannot adequately utilize epigenomic data to accurately reveal the distinction and grouping of different tissue and cell types. We utilize a three-step testing procedure-ANOVA, t test and overlap test to identify tissue/cell-type- associated enhancers and promoters and to calculate a newly defined Epigenomic Overlap Measure (EPOM). EPOM results in a clear correspondence map of biological samples from different tissue and cell types through comparison of epigenomic marks evaluated in their relevant chromatin states. Correspondence maps by EPOM show strong capability in distinguishing and grouping different tissue and cell types and reveal biologically meaningful similarities between Heart and Muscle, Blood & T-cell and HSC & B-cell, Brain and Neurosphere, etc. The gene ontology enrichment analysis both supports and explains the discoveries made by EPOM and suggests that the associated enhancers and promoters demonstrate distinguishable functions across tissue and cell types. Moreover, the tissue/cell-type-associated enhancers and promoters show enrichment in the disease-related SNPs that are also associated with the corresponding tissue or cell types. This agreement suggests the potential of identifying causal genetic variants relevant to cell-type-specific diseases from our identified associated enhancers and promoters. The proposed EPOM measure demonstrates superior capability in grouping and finding a clear correspondence map of biological samples from different tissue and cell types. The identified associated enhancers and promoters provide a comprehensive catalog to study distinct biological processes and disease variants in different tissue and cell types. Our results also find that the associated promoters exhibit more cell-type-specific functions than the associated enhancers do, suggesting that the non-associated promoters have more housekeeping functions than the non-associated enhancers.

  16. Distinct Neural-Functional Effects of Treatments With Selective Serotonin Reuptake Inhibitors, Electroconvulsive Therapy, and Transcranial Magnetic Stimulation and Their Relations to Regional Brain Function in Major Depression: A Meta-analysis.

    PubMed

    Chau, David T; Fogelman, Phoebe; Nordanskog, Pia; Drevets, Wayne C; Hamilton, J Paul

    2017-05-01

    Functional neuroimaging studies have examined the neural substrates of treatments for major depressive disorder (MDD). Low sample size and methodological heterogeneity, however, undermine the generalizability of findings from individual studies. We conducted a meta-analysis to identify reliable neural changes resulting from different modes of treatment for MDD and compared them with each other and with reliable neural functional abnormalities observed in depressed versus control samples. We conducted a meta-analysis of studies reporting changes in brain activity (e.g., as indexed by positron emission tomography) following treatments with selective serotonin reuptake inhibitors (SSRIs), electroconvulsive therapy (ECT), or transcranial magnetic stimulation. Additionally, we examined the statistical reliability of overlap among thresholded meta-analytic SSRI, ECT, and transcranial magnetic stimulation maps as well as a map of abnormal neural function in MDD. Our meta-analysis revealed that 1) SSRIs decrease activity in the anterior insula, 2) ECT decreases activity in central nodes of the default mode network, 3) transcranial magnetic stimulation does not result in reliable neural changes, and 4) regional effects of these modes of treatment do not significantly overlap with each other or with regions showing reliable functional abnormality in MDD. SSRIs and ECT produce neurally distinct effects relative to each other and to the functional abnormalities implicated in depression. These treatments therefore may exert antidepressant effects by diminishing neural functions not implicated in depression but that nonetheless impact mood. We discuss how the distinct neural changes resulting from SSRIs and ECT can account for both treatment effects and side effects from these therapies as well as how to individualize these treatments. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Development of endosperm transfer cells in barley.

    PubMed

    Thiel, Johannes

    2014-01-01

    Endosperm transfer cells (ETCs) are positioned at the intersection of maternal and filial tissues in seeds of cereals and represent a bottleneck for apoplasmic transport of assimilates into the endosperm. Endosperm cellularization starts at the maternal-filial boundary and generates the highly specialized ETCs. During differentiation barley ETCs develop characteristic flange-like wall ingrowths to facilitate effective nutrient transfer. A comprehensive morphological analysis depicted distinct developmental time points in establishment of transfer cell (TC) morphology and revealed intracellular changes possibly associated with cell wall metabolism. Embedded inside the grain, ETCs are barely accessible by manual preparation. To get tissue-specific information about ETC specification and differentiation, laser microdissection (LM)-based methods were used for transcript and metabolite profiling. Transcriptome analysis of ETCs at different developmental stages by microarrays indicated activated gene expression programs related to control of cell proliferation and cell shape, cell wall and carbohydrate metabolism reflecting the morphological changes during early ETC development. Transporter genes reveal distinct expression patterns suggesting a switch from active to passive modes of nutrient uptake with the onset of grain filling. Tissue-specific RNA-seq of the differentiating ETC region from the syncytial stage until functionality in nutrient transfer identified a high number of novel transcripts putatively involved in ETC differentiation. An essential role for two-component signaling (TCS) pathways in ETC development of barley emerged from this analysis. Correlative data provide evidence for abscisic acid and ethylene influences on ETC differentiation and hint at a crosstalk between hormone signal transduction and TCS phosphorelays. Collectively, the data expose a comprehensive view on ETC development, associated pathways and identified candidate genes for ETC specification.

  18. Development of endosperm transfer cells in barley

    PubMed Central

    Thiel, Johannes

    2014-01-01

    Endosperm transfer cells (ETCs) are positioned at the intersection of maternal and filial tissues in seeds of cereals and represent a bottleneck for apoplasmic transport of assimilates into the endosperm. Endosperm cellularization starts at the maternal-filial boundary and generates the highly specialized ETCs. During differentiation barley ETCs develop characteristic flange-like wall ingrowths to facilitate effective nutrient transfer. A comprehensive morphological analysis depicted distinct developmental time points in establishment of transfer cell (TC) morphology and revealed intracellular changes possibly associated with cell wall metabolism. Embedded inside the grain, ETCs are barely accessible by manual preparation. To get tissue-specific information about ETC specification and differentiation, laser microdissection (LM)-based methods were used for transcript and metabolite profiling. Transcriptome analysis of ETCs at different developmental stages by microarrays indicated activated gene expression programs related to control of cell proliferation and cell shape, cell wall and carbohydrate metabolism reflecting the morphological changes during early ETC development. Transporter genes reveal distinct expression patterns suggesting a switch from active to passive modes of nutrient uptake with the onset of grain filling. Tissue-specific RNA-seq of the differentiating ETC region from the syncytial stage until functionality in nutrient transfer identified a high number of novel transcripts putatively involved in ETC differentiation. An essential role for two-component signaling (TCS) pathways in ETC development of barley emerged from this analysis. Correlative data provide evidence for abscisic acid and ethylene influences on ETC differentiation and hint at a crosstalk between hormone signal transduction and TCS phosphorelays. Collectively, the data expose a comprehensive view on ETC development, associated pathways and identified candidate genes for ETC specification. PMID:24723929

  19. Antibody-based analysis reveals “filamentous vs. non-filamentous” and “cytoplasmic vs. nuclear” crosstalk of cytoskeletal proteins

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

    Kumeta, Masahiro, E-mail: kumeta@lif.kyoto-u.ac.jp; Hirai, Yuya; Yoshimura, Shige H.

    2013-12-10

    To uncover the molecular composition and dynamics of the functional scaffold for the nucleus, three fractions of biochemically-stable nuclear protein complexes were extracted and used as immunogens to produce a variety of monoclonal antibodies. Many helix-based cytoskeletal proteins were identified as antigens, suggesting their dynamic contribution to nuclear architecture and function. Interestingly, sets of antibodies distinguished distinct subcellular localization of a single isoform of certain cytoskeletal proteins; distinct molecular forms of keratin and actinin were found in the nucleus. Their nuclear shuttling properties were verified by the apparent nuclear accumulations under inhibition of CRM1-dependent nuclear export. Nuclear keratins do notmore » take an obvious filamentous structure, as was revealed by non-filamentous cytoplasmic keratin-specific monoclonal antibody. These results suggest the distinct roles of the helix-based cytoskeletal proteins in the nucleus. - Highlights: • A set of monoclonal antibodies were raised against nuclear scaffold proteins. • Helix-based cytoskeletal proteins were involved in nuclear scaffold. • Many cytoskeletal components shuttle into the nucleus in a CRM1-dependent manner. • Sets of antibodies distinguished distinct subcellular localization of a single isoform. • Nuclear keratin is soluble and does not form an obvious filamentous structure.« less

  20. SOX2 expression levels distinguish between neural progenitor populations of the developing dorsal telencephalon.

    PubMed

    Hutton, Scott R; Pevny, Larysa H

    2011-04-01

    The HMG-Box transcription factor SOX2 is expressed in neural progenitor populations throughout the developing and adult central nervous system and is necessary to maintain their progenitor identity. However, it is unclear whether SOX2 levels are uniformly expressed across all neural progenitor populations. In the developing dorsal telencephalon, two distinct populations of neural progenitors, radial glia and intermediate progenitor cells, are responsible for generating a majority of excitatory neurons found in the adult neocortex. Here we demonstrate, using both cellular and molecular analyses, that SOX2 is differentially expressed between radial glial and intermediate progenitor populations. Moreover, utilizing a SOX2(EGFP) mouse line, we show that this differential expression can be used to prospectively isolate distinct, viable populations of radial glia and intermediate cells for in vitro analysis. Given the limited repertoire of cell-surface markers currently available for neural progenitor cells, this provides an invaluable tool for prospectively identifying and isolating distinct classes of neural progenitor cells from the central nervous system. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. What is your patient’s cognitive profile? Three distinct subgroups of cognitive function in persons with heart failure

    PubMed Central

    Hawkins, Misty A.W.; Schaefer, Julie T.; Gunstad, John; Dolansky, Mary A.; Redle, Joseph D.; Josephson, Richard; Moore, Shirley M.; Hughes, Joel W.

    2014-01-01

    Purpose To determine whether patients with heart failure (HF) have distinct profiles of cognitive impairment. Background Cognitive impairment is common in HF. Recent work found three cognitive profiles in HF patients— (1) intact, (2) impaired, and (3) memory-impaired. We examined the reproducibility of these profiles and clarified mechanisms. Methods HF patients (68.6±9.7years; N=329) completed neuropsychological testing. Composite scores were created for cognitive domains and used to identify clusters via agglomerative-hierarchical cluster analysis. Results A 3-cluster solution emerged. Cluster 1 (n=109) had intact cognition. Cluster 2 (n=123) was impaired across all domains. Cluster 3 (n=97) had impaired memory only. Clusters differed in age, race, education, SES, IQ, BMI, and diabetes (ps ≤.026) but not in mood, anxiety, cardiovascular, or pulmonary disease (ps≥.118). Conclusions We replicated three distinct patterns of cognitive function in persons with HF. These profiles may help providers offer tailored care to patients with different cognitive and clinical needs. PMID:25510559

  2. The use of ERTS/LANDSAT imagery in relation to airborne remote sensing for terrain analysis in western Queensland, Australia

    NASA Technical Reports Server (NTRS)

    Cole, M. M. (Principal Investigator); Owen-Jones, S.

    1976-01-01

    The author has identified the following significant results. Distinctive spectral signatures were found associated with areas of near surface bedrock with covered ground east of Dugald River and along the Thorntonia River valley west of Lady Annie. Linears identified in the Dugald River area on LANDSAT 2 imagery taken in March and July 1975 over the Cloncurry-Dobbyn area, displayed preferred orientation. A linear group with NE-SW orientation was identified in the Lady Annie area. In this area, the copper mineralization in the Mt. Kelly area occurs along a well marked linear with NNW/SSE direction apparent on images for March, September, and November 1975. Geobotanical anomalies provided surface expression of the copper deposits in Mt. Kelley.

  3. On Sinking and Swimming: The Dialectic of Hope, Hopelessness, and Acceptance in Terminal Cancer

    PubMed Central

    Sachs, Emily; Kolva, Elissa; Pessin, Hayley; Rosenfeld, Barry; Breitbart, William

    2016-01-01

    For terminally ill cancer patients, hope and hopelessness are constructs that significantly impact the quality of life. The aim of this study was to examine the relationship between hope and hopelessness in advanced cancer and to identify factors that maintain hope and increase vulnerability to hopelessness. Semistructured interviews were conducted with 22 terminally ill cancer patients. Interview transcripts were analyzed using thematic content analysis to identify patient definitions of these terms and associated cognitions and emotions. Hope and hopelessness were identified as distinct, often co-occurring, and dialectically interacting constructs. The relationship between hope and hopelessness often balanced on acceptance, perceived as diametrically opposed to hopelessness, and conducive to redirecting hope toward new goals. Positive interpersonal relationships enhanced hope, and uncontrolled physical pain increased vulnerability to hopelessness. PMID:22556280

  4. Proteomic analysis of papaya (Carica papaya L.) displaying typical sticky disease symptoms.

    PubMed

    Rodrigues, Silas P; Ventura, José A; Aguilar, Clemente; Nakayasu, Ernesto S; Almeida, Igor C; Fernandes, Patricia M B; Zingali, Russolina B

    2011-07-01

    Papaya (Carica papaya L.) hosts the only described laticifer-infecting virus (Papaya meleira virus, PMeV), which is the causal agent of papaya sticky disease. To understand the systemic effects of PMeV in papaya, we conducted a comprehensive proteomic analysis of leaf samples from healthy and diseased plants grown under field conditions. First, a reference 2-DE map was established for proteins from healthy samples. A total of 486 reproducible spots were identified, and MALDI-TOF-MS/MS data identified 275 proteins accounting for 159 distinct proteins from 231 spots that were annotated. Second, the differential expression of proteins from healthy and diseased leaves was determined through parallel experiments, using 2-DE and DIGE followed by MALDI-TOF-MS/MS and LC-IonTrap-MS/MS, respectively. Conventional 2-DE analysis revealed 75 differentially expressed proteins. Of those, 48 proteins were identified, with 26 being upregulated (U) and 22 downregulated (D). In general, metabolism-related proteins were downregulated, and stress-responsive proteins were upregulated. This expression pattern was corroborated by the results of the DIGE analysis, which identified 79 differentially expressed proteins, with 23 identified (17 U and 6 D). Calreticulin and the proteasome subunits 20S and RPT5a were shown to be upregulated during infection by both 2-DE and DIGE analyses. These data may help shed light on plant responses against stresses and viral infections. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

    PubMed

    Hoefnagel, Juliette J; Dijkman, Remco; Basso, Katia; Jansen, Patty M; Hallermann, Christian; Willemze, Rein; Tensen, Cornelis P; Vermeer, Maarten H

    2005-05-01

    In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

  6. Analyzing the presentation and the stigma of schizophrenia in French newspapers.

    PubMed

    Lampropoulos, Dimitrios; Wolman, Angelika; Apostolidis, Thémis

    2017-12-01

    It has been suggested that the stigmatizing presentation of people with schizophrenia by newspapers is an example of structural stigma. In this study, we explore how French newspapers contribute to the stigma of people with schizophrenia. All the articles of eight major newspapers (four national and four regional) that include the term schizophr* and that were published in 2015 were therefore analyzed using a coding scheme that we developed inductively. This analysis showed that among the identified themes, 40.4% of the articles used the term schizophrenia metaphorically and 28.3% referred to dangerousness. The first concerned mostly national newspapers, while the second were mostly published by regional newspapers. A more selective analysis was also carried out on these major themes in order to investigate how the "us" against "them" distinction is created and how negative stereotypes are associated with this distinction. In the case of the metaphorical use of the term, schizophrenia was presented as a "split personality" disorder and the label used in order to devalue the political opposition. Schizophrenia was presented either as a deterministic cause of dangerousness or as a potential cause of crime. In either case, the question of control was clearly present in these articles. These results are discussed in terms of the "us" against "them" distinction as a double process of stigmatization of people with schizophrenia and of reinforcement of one's own identity and security.

  7. Consumer preferences for mild cheddar cheese flavors.

    PubMed

    Drake, S L; Gerard, P D; Drake, M A

    2008-11-01

    Flavor is an important factor in consumer selection of cheeses. Mild Cheddar cheese is the classification used to describe Cheddar cheese that is not aged extensively and has a "mild" flavor. However, there is no legal definition or age limit for Cheddar cheese to be labeled mild, medium, or sharp, nor are the flavor profiles or flavor expectations of these cheeses specifically defined. The objectives of this study were to document the distinct flavor profiles among commercially labeled mild Cheddar cheeses, and to characterize if consumer preferences existed for specific mild Cheddar cheese flavors or flavor profiles. Flavor descriptive sensory profiles of a representative array of commercial Cheddar cheeses labeled as mild (n= 22) were determined using a trained sensory panel and an established cheese flavor sensory language. Nine representative Cheddar cheeses were selected for consumer testing. Consumers (n= 215) assessed the cheeses for overall liking and other consumer liking attributes. Internal preference mapping, cluster analysis, and discriminant analysis were conducted. Mild Cheddar cheeses were diverse in flavor with many displaying flavors typically associated with more age. Four distinct consumer clusters were identified. The key drivers of liking for mild Cheddar cheese were: color, cooked/milky, whey and brothy flavors, and sour taste. Consumers have distinct flavor and color preferences for mild Cheddar cheese. These results can help manufacturers understand consumer preferences for mild Cheddar cheese.

  8. Cassava (Manihot esculenta Krantz) genome harbors KNOX genes differentially expressed during storage root development.

    PubMed

    Guo, D; Li, H L; Tang, X; Peng, S Q

    2014-12-18

    In plants, homeodomain proteins play a critical role in regulating various aspects of plant growth and development. KNOX proteins are members of the homeodomain protein family. The KNOX transcription factors have been reported from Arabidopsis, rice, and other higher plants. The recent publication of the draft genome sequence of cassava (Manihot esculenta Krantz) has allowed a genome-wide search for M. esculenta KNOX (MeKNOX) transcription factors and the comparison of these positively identified proteins with their homologs in model plants. In the present study, we identified 12 MeKNOX genes in the cassava genome and grouped them into two distinct subfamilies based on their domain composition and phylogenetic analysis. Furthermore, semi-quantitative reverse transcription polymerase chain reaction analysis was performed to elucidate the expression profiles of these genes in different tissues and during various stages of root development. The analysis of MeKNOX expression profiles of indicated that 12 MeKNOX genes display differential expressions either in their transcript abundance or expression patterns.

  9. Characterisation of lab in typical Salento Pecorino cheese.

    PubMed

    Cappello, M S; Laddomada, B; Poltronieri, P; Zacheo, G

    2001-01-01

    Twenty-nine strains of Lactic Acid Bacteria isolated from the typical Pecorino cheese of the Salento area of Italy, were identified and grouped according to their genetic similarity. A preliminary characterisation of the strains was conducted by means of morphological and biochemical analysis, but molecular approaches were necessary for the clear identification of the species. For the species detection, the amplification and sequencing of the 16S rDNA gene was employed In addition, restriction analysis of amplified rDNA (ARDRA) and PCR and AFLP fingerprinting enabled inter- and intra-specific variation to be estimated UPGMA cluster analysis was used to divide the strains into distinct clusters which corresponded with the species delineation obtained by molecular identification. The data obtained show that the community of lactobacilli responsible for the fermentation and aging of Pecorino cheese is composed of a limited number of species. The main identified strains were Lactobacillus brevis, L. plantarum, L. casei, L. sakei, L. pentosus, L. farciminis and Leuconostoc mesenteroides.

  10. Comparing sugar components of cereal and pseudocereal flour by GC-MS analysis.

    PubMed

    Ačanski, Marijana M; Vujić, Djura N

    2014-02-15

    Gas chromatography with mass spectrometry was used for carrying out a qualitative analysis of the ethanol soluble flour extract of different types of cereals bread wheat and spelt and pseudocereals (amaranth and buckwheat). TMSI (trimethylsilylimidazole) was used as a reagent for the derivatisation of carbohydrates into trimethylsilyl ethers. All samples were first defatted with hexane. (In our earlier investigations, hexane extracts were used for the analysis of fatty acid of lipid components.) Many components of pentoses, hexoses and disaccharides were identified using 73 and 217 Da mass and the Wiley Online Library search. The aim of this paper is not to identify and find new components, but to compare sugar components of tested samples of flour of cereals bread wheat and spelt and pseudocereals (amarnath and buckwheat). Results were analysed using descriptive statistics (dendrograms and PCA). The results show that this method can be used for making a distinction among different types of flour. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays

    PubMed Central

    Augustin, Regina; Lichtenthaler, Stefan F.; Greeff, Michael; Hansen, Jens; Wurst, Wolfgang; Trümbach, Dietrich

    2011-01-01

    The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD) pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases. PMID:21559189

  12. Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects.

    PubMed

    McCallin, Shawna; Alam Sarker, Shafiqul; Barretto, Caroline; Sultana, Shamima; Berger, Bernard; Huq, Sayeda; Krause, Lutz; Bibiloni, Rodrigo; Schmitt, Bertrand; Reuteler, Gloria; Brüssow, Harald

    2013-09-01

    Phage therapy has a long tradition in Eastern Europe, where preparations are comprised of complex phage cocktails whose compositions have not been described. We investigated the composition of a phage cocktail from the Russian pharmaceutical company Microgen targeting Escherichia coli/Proteus infections. Electron microscopy identified six phage types, with numerically T7-like phages dominating over T4-like phages. A metagenomic approach using taxonomical classification, reference mapping and de novo assembly identified 18 distinct phage types, including 7 genera of Podoviridae, 2 established and 2 proposed genera of Myoviridae, and 2 genera of Siphoviridae. De novo assembly yielded 7 contigs greater than 30 kb, including a 147-kb Myovirus genome and a 42-kb genome of a potentially new phage. Bioinformatic analysis did not reveal undesired genes and a small human volunteer trial did not associate adverse effects with oral phage exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Characteristics of cyclist crashes in Italy using latent class analysis and association rule mining

    PubMed Central

    De Angelis, Marco; Marín Puchades, Víctor; Fraboni, Federico; Pietrantoni, Luca

    2017-01-01

    The factors associated with severity of the bicycle crashes may differ across different bicycle crash patterns. Therefore, it is important to identify distinct bicycle crash patterns with homogeneous attributes. The current study aimed at identifying subgroups of bicycle crashes in Italy and analyzing separately the different bicycle crash types. The present study focused on bicycle crashes that occurred in Italy during the period between 2011 and 2013. We analyzed categorical indicators corresponding to the characteristics of infrastructure (road type, road signage, and location type), road user (i.e., opponent vehicle and cyclist’s maneuver, type of collision, age and gender of the cyclist), vehicle (type of opponent vehicle), and the environmental and time period variables (time of the day, day of the week, season, pavement condition, and weather). To identify homogenous subgroups of bicycle crashes, we used latent class analysis. Using latent class analysis, the bicycle crash data set was segmented into 19 classes, which represents 19 different bicycle crash types. Logistic regression analysis was used to identify the association between class membership and severity of the bicycle crashes. Finally, association rules were conducted for each of the latent classes to uncover the factors associated with an increased likelihood of severity. Association rules highlighted different crash characteristics associated with an increased likelihood of severity for each of the 19 bicycle crash types. PMID:28158296

  14. An Integrated Strategy to Qualitatively Differentiate Components of Raw and Processed Viticis Fructus Based on NIR, HPLC and UPLC-MS Analysis.

    PubMed

    Diao, Jiayin; Xu, Can; Zheng, Huiting; He, Siyi; Wang, Shumei

    2018-06-21

    Viticis Fructus is a traditional Chinese herbal drug processed by various methods to achieve different clinical purposes. Thermal treatment potentially alters chemical composition, which may impact on effectiveness and toxicity. In order to interpret the constituent discrepancies of raw versus processed (stir-fried) Viticis Fructus, a multivariate detection method (NIR, HPLC, and UPLC-MS) based on metabonomics and chemometrics was developed. Firstly, synergy interval partial least squares and partial least squares-discriminant analysis were employed to screen the distinctive wavebands (4319 - 5459 cm -1 ) based on preprocessed near-infrared spectra. Then, HPLC with principal component analysis was performed to characterize the distinction. Subsequently, a total of 49 compounds were identified by UPLC-MS, among which 42 compounds were eventually characterized as having a significant change during processing via the semiquantitative volcano plot analysis. Moreover, based on the partial least squares-discriminant analysis, 16 compounds were chosen as characteristic markers that could be in close correlation with the discriminatory near-infrared wavebands. Together, all of these characterization techniques effectively discriminated raw and processed products of Viticis Fructus. In general, our work provides an integrated way of classifying Viticis Fructus, and a strategy to explore discriminatory chemical markers for other traditional Chinese herbs, thus ensuring safety and efficacy for consumers. Georg Thieme Verlag KG Stuttgart · New York.

  15. Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

    PubMed Central

    Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

    2014-01-01

    Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

  16. [From synthetic biology to synthetic humankind].

    PubMed

    Nouvel, Pascal

    2015-01-01

    In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  17. Dynamics of body time, social time and life history at adolescence.

    PubMed

    Worthman, Carol M; Trang, Kathy

    2018-02-21

    Recent opposing trends towards earlier physical maturation and later social maturation present a conundrum of apparent biological-social mismatch. Here we use life history analysis from evolutionary ecology to identify forces that drive these shifts. Together with findings in developmental science, our life history analysis indicates that adolescence is a distinctive period for biological embedding of culture. Ethnographic evidence shows that mass education is a novel feature of the globalizing cultural configurations of adolescence, which are driven by transformations in labour, livelihood and lifestyle. Evaluation of the life history trade-offs and sociocultural ecologies that are experienced by adolescents may offer a practical basis for enhancing their development.

  18. Dynamics of body time, social time and life history at adolescence

    NASA Astrophysics Data System (ADS)

    Worthman, Carol M.; Trang, Kathy

    2018-02-01

    Recent opposing trends towards earlier physical maturation and later social maturation present a conundrum of apparent biological-social mismatch. Here we use life history analysis from evolutionary ecology to identify forces that drive these shifts. Together with findings in developmental science, our life history analysis indicates that adolescence is a distinctive period for biological embedding of culture. Ethnographic evidence shows that mass education is a novel feature of the globalizing cultural configurations of adolescence, which are driven by transformations in labour, livelihood and lifestyle. Evaluation of the life history trade-offs and sociocultural ecologies that are experienced by adolescents may offer a practical basis for enhancing their development.

  19. Co-fuse: a new class discovery analysis tool to identify and prioritize recurrent fusion genes from RNA-sequencing data.

    PubMed

    Paisitkriangkrai, Sakrapee; Quek, Kelly; Nievergall, Eva; Jabbour, Anissa; Zannettino, Andrew; Kok, Chung Hoow

    2018-06-07

    Recurrent oncogenic fusion genes play a critical role in the development of various cancers and diseases and provide, in some cases, excellent therapeutic targets. To date, analysis tools that can identify and compare recurrent fusion genes across multiple samples have not been available to researchers. To address this deficiency, we developed Co-occurrence Fusion (Co-fuse), a new and easy to use software tool that enables biologists to merge RNA-seq information, allowing them to identify recurrent fusion genes, without the need for exhaustive data processing. Notably, Co-fuse is based on pattern mining and statistical analysis which enables the identification of hidden patterns of recurrent fusion genes. In this report, we show that Co-fuse can be used to identify 2 distinct groups within a set of 49 leukemic cell lines based on their recurrent fusion genes: a multiple myeloma (MM) samples-enriched cluster and an acute myeloid leukemia (AML) samples-enriched cluster. Our experimental results further demonstrate that Co-fuse can identify known driver fusion genes (e.g., IGH-MYC, IGH-WHSC1) in MM, when compared to AML samples, indicating the potential of Co-fuse to aid the discovery of yet unknown driver fusion genes through cohort comparisons. Additionally, using a 272 primary glioma sample RNA-seq dataset, Co-fuse was able to validate recurrent fusion genes, further demonstrating the power of this analysis tool to identify recurrent fusion genes. Taken together, Co-fuse is a powerful new analysis tool that can be readily applied to large RNA-seq datasets, and may lead to the discovery of new disease subgroups and potentially new driver genes, for which, targeted therapies could be developed. The Co-fuse R source code is publicly available at https://github.com/sakrapee/co-fuse .

  20. A genomic investigation of ecological differentiation between free-living and Drosophila-associated bacteria.

    PubMed

    Winans, Nathan J; Walter, Alec; Chouaia, Bessem; Chaston, John M; Douglas, Angela E; Newell, Peter D

    2017-09-01

    Various bacterial taxa have been identified both in association with animals and in the external environment, but the extent to which related bacteria from the two habitat types are ecologically and evolutionarily distinct is largely unknown. This study investigated the scale and pattern of genetic differentiation between bacteria of the family Acetobacteraceae isolated from the guts of Drosophila fruit flies, plant material and industrial fermentations. Genome-scale analysis of the phylogenetic relationships and predicted functions was conducted on 44 Acetobacteraceae isolates, including newly sequenced genomes from 18 isolates from wild and laboratory Drosophila. Isolates from the external environment and Drosophila could not be assigned to distinct phylogenetic groups, nor are their genomes enriched for any different sets of genes or category of predicted gene functions. In contrast, analysis of bacteria from laboratory Drosophila showed they were genetically distinct in their universal capacity to degrade uric acid (a major nitrogenous waste product of Drosophila) and absence of flagellar motility, while these traits vary among wild Drosophila isolates. Analysis of the competitive fitness of Acetobacter discordant for these traits revealed a significant fitness deficit for bacteria that cannot degrade uric acid in culture with Drosophila. We propose that, for wild populations, frequent cycling of Acetobacter between Drosophila and the external environment prevents genetic differentiation by maintaining selection for traits adaptive in both the gut and external habitats. However, laboratory isolates bear the signs of adaptation to persistent association with the Drosophila host under tightly defined environmental conditions. © 2017 John Wiley & Sons Ltd.

  1. Differences in transcriptional effects of 1α,25 dihydroxyvitamin D3 on fibroblasts associated to breast carcinomas and from paired normal breast tissues.

    PubMed

    Campos, Laura Tojeiro; Brentani, Helena; Roela, Rosimeire Aparecida; Katayama, Maria Lucia Hirata; Lima, Leandro; Rolim, Cíntia Flores; Milani, Cíntia; Folgueira, Maria Aparecida Azevedo Koike; Brentani, Maria Mitzi

    2013-01-01

    The effects of 1α,25 dihydroxyvitamin D3 (1,25D) on breast carcinoma associated fibroblasts (CAFs) are still unknown. This study aimed to identify genes whose expression was altered after 1,25D treatment in CAFs and matched adjacent normal mammary associated fibroblasts (NAFs). CAFs and NAFs (from 5 patients) were cultured with or without (control) 1,25D 100 nM. Both CAF and NAF expressed vitamin D receptor (VDR) and 1,25D induction of the genomic pathway was detected through up-regulation of the target gene CYP24A1. Microarray analysis showed that despite presenting 50% of overlapping genes, CAFs and NAFs exhibited distinct transcriptional profiles after 1,25D treatment (FDR<0.05). Functional analysis revealed that in CAFs, genes associated with proliferation (NRG1, WNT5A, PDGFC) were down regulated and those involved in immune modulation (NFKBIA, TREM-1) were up regulated, consistent with anti tumor activities of 1,25D in breast cancer. In NAFs, a distinct subset of genes was induced by 1,25D, involved in anti apoptosis, detoxification, antibacterial defense system and protection against oxidative stress, which may limit carcinogenesis. Co-expression network and interactome analysis of genes commonly regulated by 1,25D in NAFs and CAFs revealed differences in their co-expression values, suggesting that 1,25D effects in NAFs are distinct from those triggered in CAFs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Clonal T-Cell Receptor γ-Chain Gene Rearrangements in Differential Diagnosis of Lymphomatoid Papulosis From Skin Metastasis of Nodal Anaplastic Large-Cell Lymphoma

    PubMed Central

    Akilov, Oleg E.; Pillai, Raju K.; Grandinetti, Lisa M.; Kant, Jeffrey A.; Geskin, Larisa

    2012-01-01

    Background In patients with a history of nodal anaplastic large-cell lymphoma (ALCL), differentiation of type C lymphomatoid papulosis from cutaneous involvement of systemic ALCL may be challenging because the 2 entities may exhibit identical histologic features. Although metastatic ALCL generally carries the same clone as the primary lymphoma, expression of a distinct clone likely represents a distinct process. Observations A 54-year-old white man had a history of anaplastic lymphoma kinase 1–negative ALCL in the right inguinal lymph node 6 years ago. A complete response was achieved after 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone administered in 21-day cycles) and radiation therapy. After 3½ years, the patient observed waxing and waning papules and nodules. Examination of the biopsy specimen revealed a dense CD30+ lymphocytic infiltrate; no evidence of systemic malignancy was evident on positron emission tomography. Although clinically the presentation was consistent with lymphomatoid papulosis, metastatic ALCL had to be excluded. Polymerase chain reaction analysis with T-cell receptor γ-chain gene rearrangement (TCR-γR) was performed on the original lymph node and new skin lesions. Results of the TCR-γR analysis were positive for clonality in both lesions. However, separate clonal processes were identified. The identification of distinct clones supported the clinical impression of lymphomatoid papulosis. Conclusion Polymerase chain reaction analysis of TCR-γR is a useful method for distinguishing different clonal processes and is recommended when differentiation of primary and secondary lymphoproliferative disorders is required. PMID:21844453

  3. Genetic and Modeling Approaches Reveal Distinct Components of Impulsive Behavior

    PubMed Central

    Nautiyal, Katherine M; Wall, Melanie M; Wang, Shuai; Magalong, Valerie M; Ahmari, Susanne E; Balsam, Peter D; Blanco, Carlos; Hen, René

    2017-01-01

    Impulsivity is an endophenotype found in many psychiatric disorders including substance use disorders, pathological gambling, and attention deficit hyperactivity disorder. Two behavioral features often considered in impulsive behavior are behavioral inhibition (impulsive action) and delayed gratification (impulsive choice). However, the extent to which these behavioral constructs represent distinct facets of behavior with discrete biological bases is unclear. To test the hypothesis that impulsive action and impulsive choice represent statistically independent behavioral constructs in mice, we collected behavioral measures of impulsivity in a single cohort of mice using well-validated operant behavioral paradigms. Mice with manipulation of serotonin 1B receptor (5-HT1BR) expression were included as a model of disordered impulsivity. A factor analysis was used to characterize correlations between the measures of impulsivity and to identify covariates. Using two approaches, we dissociated impulsive action from impulsive choice. First, the absence of 5-HT1BRs caused increased impulsive action, but not impulsive choice. Second, based on an exploratory factor analysis, a two-factor model described the data well, with measures of impulsive action and choice separating into two independent factors. A multiple-indicator multiple-causes analysis showed that 5-HT1BR expression and sex were significant covariates of impulsivity. Males displayed increased impulsivity in both dimensions, whereas 5-HT1BR expression was a predictor of increased impulsive action only. These data support the conclusion that impulsive action and impulsive choice are distinct behavioral phenotypes with dissociable biological influences that can be modeled in mice. Our work may help inform better classification, diagnosis, and treatment of psychiatric disorders, which present with disordered impulsivity. PMID:27976680

  4. Genetic Diversity Among Botulinum Neurotoxin Producing Clostridial Strains

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

    Hill, K K; Smith, T J; Helma, C H

    2006-07-06

    Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore forming rod-shaped bacteria which have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and even death in humans and various other animal species. A collection of 174 C. botulinum strains were examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT A-G). Analysis of the16S rRNA sequences confirmed earliermore » reports of at least four distinct genomic backgrounds (Groups I-IV) each of which has independently acquired one or more BoNT serotypes through horizontal gene transfer. AFLP analysis provided higher resolution, and can be used to further subdivide the four groups into sub-groups. Sequencing of the BoNT genes from serotypes A, B and E in multiple strains confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes, and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven serotypes of BoNT were compared and show varying degrees of interrelatedness and recombination as has been previously noted for the NTNH gene which is linked to BoNT. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for treatment of botulism.« less

  5. Characterization of bacterial community dynamics in a full-scale drinking water treatment plant.

    PubMed

    Li, Cuiping; Ling, Fangqiong; Zhang, Minglu; Liu, Wen-Tso; Li, Yuxian; Liu, Wenjun

    2017-01-01

    Understanding the spatial and temporal dynamics of microbial communities in drinking water systems is vital to securing the microbial safety of drinking water. The objective of this study was to comprehensively characterize the dynamics of microbial biomass and bacterial communities at each step of a full-scale drinking water treatment plant in Beijing, China. Both bulk water and biofilm samples on granular activated carbon (GAC) were collected over 9months. The proportion of cultivable cells decreased during the treatment processes, and this proportion was higher in warm season than cool season, suggesting that treatment processes and water temperature probably had considerable impact on the R2A cultivability of total bacteria. 16s rRNA gene based 454 pyrosequencing analysis of the bacterial community revealed that Proteobacteria predominated in all samples. The GAC biofilm harbored a distinct population with a much higher relative abundance of Acidobacteria than water samples. Principle coordinate analysis and one-way analysis of similarity indicated that the dynamics of the microbial communities in bulk water and biofilm samples were better explained by the treatment processes rather than by sampling time, and distinctive changes of the microbial communities in water occurred after GAC filtration. Furthermore, 20 distinct OTUs contributing most to the dissimilarity among samples of different sampling locations and 6 persistent OTUs present in the entire treatment process flow were identified. Overall, our findings demonstrate the significant effects that treatment processes have on the microbial biomass and community fluctuation and provide implications for further targeted investigation on particular bacteria populations. Copyright © 2016. Published by Elsevier B.V.

  6. Compositional studies of Mare Moscoviense: New perspectives from Chandrayaan-1 VIS-NIR data

    NASA Astrophysics Data System (ADS)

    Bhatt, Megha; Wöhler, Christian; Dhingra, Deepak; Thangjam, Guneshwar; Rommel, Daniela; Mall, Urs; Bhardwaj, Anil; Grumpe, Arne

    2018-03-01

    Moscoviense is one of the prominent mare-filled basin on the lunar far side holding key insights about volcanic activity on the far side. Here, we present spectral and elemental maps of mare Moscoviense, using the Moon Mineralogy Mapper (M3) and Infrared Spectrometer-2 (SIR-2) data-sets. The different mare units are mapped based on their spectral properties analyzing both quantitatively (band center, band depth) and qualitatively (Integrated Band Depth composite images), and also using their elemental compositions. We find a total of five distinct spectral units from the basin floor based on the spectral properties. Our analysis suggests that the northern part which was mapped as Iltm unit (Imbrian low Ti, low Fe) by earlier researchers is actually a distinct unit, which is different in composition and age, named as Ivltm unit (Imbrian very low Ti and very low Fe). We obtain the absolute model age of 3.2 Ga with uncertainties of +0.2/ -0.5 Ga for the unit Ivltm. The newly identified basalt unit Ivltm is compositionally intermediate to the units Im and Iltm in FeO and TiO2 abundances. We find a total of five distinct spectral units from the basin floor based on the spectral properties. The units Im (Imbrian very low Ti) from southern and northern regions of the basin floor are spectrally distinct in terms of band center position and corresponding band depths but considered a single unit based on the elemental abundance analysis. The units Ivltm and Im are consistent with a high-Al basalt composition. Our detailed analysis of the entire Moscoviense basin indicates that the concentrations of orthopyroxene, olivine, and Mg-rich spinel, named as OOS rock family are widespread and dominant at the western and southern side of the middle ring of the basin with one isolated area found on the northern side of the peak ring.

  7. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.

    PubMed

    Gormley, Padhraig; Anttila, Verneri; Winsvold, Bendik S; Palta, Priit; Esko, Tonu; Pers, Tune H; Farh, Kai-How; Cuenca-Leon, Ester; Muona, Mikko; Furlotte, Nicholas A; Kurth, Tobias; Ingason, Andres; McMahon, George; Ligthart, Lannie; Terwindt, Gisela M; Kallela, Mikko; Freilinger, Tobias M; Ran, Caroline; Gordon, Scott G; Stam, Anine H; Steinberg, Stacy; Borck, Guntram; Koiranen, Markku; Quaye, Lydia; Adams, Hieab H H; Lehtimäki, Terho; Sarin, Antti-Pekka; Wedenoja, Juho; Hinds, David A; Buring, Julie E; Schürks, Markus; Ridker, Paul M; Hrafnsdottir, Maria Gudlaug; Stefansson, Hreinn; Ring, Susan M; Hottenga, Jouke-Jan; Penninx, Brenda W J H; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Malik, Rainer; Heath, Andrew C; Madden, Pamela A F; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Kals, Mart; Mägi, Reedik; Pärn, Kalle; Hämäläinen, Eija; Huang, Hailiang; Byrnes, Andrea E; Franke, Lude; Huang, Jie; Stergiakouli, Evie; Lee, Phil H; Sandor, Cynthia; Webber, Caleb; Cader, Zameel; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Eriksson, Johan G; Salomaa, Veikko; Heikkilä, Kauko; Loehrer, Elizabeth; Uitterlinden, Andre G; Hofman, Albert; van Duijn, Cornelia M; Cherkas, Lynn; Pedersen, Linda M; Stubhaug, Audun; Nielsen, Christopher S; Männikkö, Minna; Mihailov, Evelin; Milani, Lili; Göbel, Hartmut; Esserlind, Ann-Louise; Christensen, Anne Francke; Hansen, Thomas Folkmann; Werge, Thomas; Kaprio, Jaakko; Aromaa, Arpo J; Raitakari, Olli; Ikram, M Arfan; Spector, Tim; Järvelin, Marjo-Riitta; Metspalu, Andres; Kubisch, Christian; Strachan, David P; Ferrari, Michel D; Belin, Andrea C; Dichgans, Martin; Wessman, Maija; van den Maagdenberg, Arn M J M; Zwart, John-Anker; Boomsma, Dorret I; Smith, George Davey; Stefansson, Kari; Eriksson, Nicholas; Daly, Mark J; Neale, Benjamin M; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Palotie, Aarno

    2016-08-01

    Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.

  8. Genetic identification of rickettsial isolates from fatal cases of Brazilian spotted fever and comparison with Rickettsia rickettsii isolates from the American continents.

    PubMed

    Labruna, Marcelo B; Santos, Fabiana C P; Ogrzewalska, Maria; Nascimento, Elvira M M; Colombo, Silvia; Marcili, Arlei; Angerami, Rodrigo N

    2014-10-01

    Fifteen bacterial isolates from spotted fever group rickettsiosis in Brazil were genetically identified as Rickettsia rickettsii. In a phylogenetic analysis with other R. rickettsii isolates from GenBank, the Central/South American isolates showed low polymorphism and formed a clade distinct from two North American clades, with the North American clades having greater in-branch polymorphism. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  9. Analysis of ERTS-1 imagery of Wyoming and its application to evaluation of Wyoming's natural resources

    NASA Technical Reports Server (NTRS)

    Marrs, R. W.; Breckenridge, R. M.

    1973-01-01

    The author has identified the following significant results. The Wyoming investigation has progressed according to schedule during the Jan. - Feb., 1973 report period. A map of the maximum extent of Pleistocene glaciation was compiled for northwest Wyoming from interpretations of glacial features seen on ERTS-1 imagery. Using isodensitometry as a tool for image enhancement, techniques were developed which allowed accurate delineation of small urban areas and provided distinction of broad classifications within these small urban centers.

  10. Spectroscopy of γ Doradus stars

    NASA Astrophysics Data System (ADS)

    Brunsden, E.; Pollard, K. R.; Cottrell, P. L.; Wright, D. J.; De Cat, P.; Kilmartin, P. M.

    2014-02-01

    The musician programme at the University of Canterbury has been successfully identifying pulsation modes in many γ Doradus stars using hundreds of ground-based spectroscopic observations. This paper describes some of the successful mode identifications and emerging patterns of the programme. The hybrid γ Doradus/δ Scuti star HD 49434 remains an enigma, despite the analysis of more than 1700 multi-site high-resolution spectra. A new result for this star is apparently distinct line-profile variations for the γ Doradus and δ Scuti frequencies.

  11. The somatic POLE P286R mutation defines a unique subclass of colorectal cancer featuring hypermutation, representing a potential genomic biomarker for immunotherapy

    PubMed Central

    Kim, Jihun; Kim, Deokhoon; Chun, Sung-Min; Kim, Jiyun; Kim, Tae Won; Park, Inja; Yu, Chang-Sik; Jang, Se Jin

    2016-01-01

    Early-onset colorectal cancers (EOCRCs) may have biological or genomic features distinct from late-onset CRCs (LOCRCs). Previous studies have mostly focused on the germline predisposition conditions of EOCRCs, but we hypothesized that EOCRCs may have distinct somatic aberrations that accelerate cancer development. To identify the somatic aberrations that accelerate cancer development at an early age, we conducted whole exome sequencing for 28 polyposis-unrelated, microsatellite stable (MSS) EOCRCs with no known germline predisposition conditions. Surprisingly, we found two distinct groups in the context of mutational burden: 6 hypermutated cases with 2325 to 10973 mutations and 22 nonhypermutated cases with 47 to 154 mutations. Further analysis revealed that four of the six hypermutated cases had the same POLE P286R mutation. We validated this finding in 83 MSS EOCRCs and 27 MSS LOCRCs, which revealed that 7.2% of EOCRCs (6/83) had the POLE P286R mutation, which was not found in LOCRCs. Clinicopathologically, EOCRCs with POLE mutations occurred far more frequently in the right colon than in the left colon, affecting men more frequently than women. In summary, we have identified a unique subclass of colon cancer characterized by a hypermutation associated with the POLE mutation. The acquisition of the POLE mutation leading to hypermutation can accelerate cancer development. Clinically, this subset with hypermutation may be susceptible to immune checkpoint blockade. PMID:27612425

  12. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities.

    PubMed

    Skoulidis, Ferdinandos; Byers, Lauren A; Diao, Lixia; Papadimitrakopoulou, Vassiliki A; Tong, Pan; Izzo, Julie; Behrens, Carmen; Kadara, Humam; Parra, Edwin R; Canales, Jaime Rodriguez; Zhang, Jianjun; Giri, Uma; Gudikote, Jayanthi; Cortez, Maria A; Yang, Chao; Fan, Youhong; Peyton, Michael; Girard, Luc; Coombes, Kevin R; Toniatti, Carlo; Heffernan, Timothy P; Choi, Murim; Frampton, Garrett M; Miller, Vincent; Weinstein, John N; Herbst, Roy S; Wong, Kwok-Kin; Zhang, Jianhua; Sharma, Padmanee; Mills, Gordon B; Hong, Waun K; Minna, John D; Allison, James P; Futreal, Andrew; Wang, Jing; Wistuba, Ignacio I; Heymach, John V

    2015-08-01

    The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma are poorly characterized. We performed an integrative analysis of genomic, transcriptomic, and proteomic data from early-stage and chemorefractory lung adenocarcinoma and identified three robust subsets of KRAS-mutant lung adenocarcinoma dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP), and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further revealed biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules, and improved relapse-free survival. Differences in drug sensitivity patterns were also observed; notably, KL cells showed increased vulnerability to HSP90-inhibitor therapy. This work provides evidence that co-occurring genomic alterations identify subgroups of KRAS-mutant lung adenocarcinoma with distinct biology and therapeutic vulnerabilities. Co-occurring genetic alterations in STK11/LKB1, TP53, and CDKN2A/B-the latter coupled with low TTF1 expression-define three major subgroups of KRAS-mutant lung adenocarcinoma with distinct biology, patterns of immune-system engagement, and therapeutic vulnerabilities. ©2015 American Association for Cancer Research.

  13. Mutations in SNX14 Cause a Distinctive Autosomal-Recessive Cerebellar Ataxia and Intellectual Disability Syndrome

    PubMed Central

    Thomas, Anna C.; Williams, Hywel; Setó-Salvia, Núria; Bacchelli, Chiara; Jenkins, Dagan; O’Sullivan, Mary; Mengrelis, Konstantinos; Ishida, Miho; Ocaka, Louise; Chanudet, Estelle; James, Chela; Lescai, Francesco; Anderson, Glenn; Morrogh, Deborah; Ryten, Mina; Duncan, Andrew J.; Pai, Yun Jin; Saraiva, Jorge M.; Ramos, Fabiana; Farren, Bernadette; Saunders, Dawn; Vernay, Bertrand; Gissen, Paul; Straatmaan-Iwanowska, Anna; Baas, Frank; Wood, Nicholas W.; Hersheson, Joshua; Houlden, Henry; Hurst, Jane; Scott, Richard; Bitner-Glindzicz, Maria; Moore, Gudrun E.; Sousa, Sérgio B.; Stanier, Philip

    2014-01-01

    Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum. PMID:25439728

  14. Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome.

    PubMed

    Thomas, Anna C; Williams, Hywel; Setó-Salvia, Núria; Bacchelli, Chiara; Jenkins, Dagan; O'Sullivan, Mary; Mengrelis, Konstantinos; Ishida, Miho; Ocaka, Louise; Chanudet, Estelle; James, Chela; Lescai, Francesco; Anderson, Glenn; Morrogh, Deborah; Ryten, Mina; Duncan, Andrew J; Pai, Yun Jin; Saraiva, Jorge M; Ramos, Fabiana; Farren, Bernadette; Saunders, Dawn; Vernay, Bertrand; Gissen, Paul; Straatmaan-Iwanowska, Anna; Baas, Frank; Wood, Nicholas W; Hersheson, Joshua; Houlden, Henry; Hurst, Jane; Scott, Richard; Bitner-Glindzicz, Maria; Moore, Gudrun E; Sousa, Sérgio B; Stanier, Philip

    2014-11-06

    Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Cytokinin-dependent secondary growth determines root biomass in radish (Raphanus sativus L.)

    PubMed Central

    Jang, Geupil; Lee, Jung-Hun; Rastogi, Khushboo; Park, Suhyoung; Oh, Sang-Hun; Lee, Ji-Young

    2015-01-01

    The root serves as an essential organ in plant growth by taking up nutrients and water from the soil and supporting the rest of the plant body. Some plant species utilize roots as storage organs. Sweet potatoes (Ipomoea batatas), cassava (Manihot esculenta), and radish (Raphanus sativus), for example, are important root crops. However, how their root growth is regulated remains unknown. In this study, we characterized the relationship between cambium and radial root growth in radish. Through a comparative analysis with Arabidopsis root expression data, we identified putative cambium-enriched transcription factors in radish and analysed their expression in representative inbred lines featuring distinctive radial growth. We found that cell proliferation activities in the cambium positively correlated with radial growth and final yields of radish roots. Expression analysis of candidate transcription factor genes revealed that some genes are differentially expressed between inbred lines and that the difference is due to the distinct cytokinin response. Taken together, we have demonstrated for the first time, to the best of our knowledge, that cytokinin-dependent radial growth plays a key role in the yields of root crops. PMID:25979997

  16. Magnetic resonance imaging patterns of muscle involvement in genetic muscle diseases: a systematic review.

    PubMed

    Leung, Doris G

    2017-07-01

    A growing body of the literature supports the use of magnetic resonance imaging as a potential biomarker for disease severity in the hereditary myopathies. We performed a systematic review of the medical literature to evaluate patterns of fat infiltration observed in magnetic resonance imaging studies of muscular dystrophy and congenital myopathy. Searches were performed using MEDLINE, EMBASE, and grey literature databases. Studies that described fat infiltration of muscles in patients with muscular dystrophy or congenital myopathy were selected for full-length review. Data on preferentially involved or spared muscles were extracted for analysis. A total of 2172 titles and abstracts were screened, and 70 publications met our criteria for inclusion in the systematic review. There were 23 distinct genetic disorders represented in this analysis. In most studies, preferential involvement and sparing of specific muscles were reported. We conclude that magnetic resonance imaging studies can be used to identify distinct patterns of muscle involvement in the hereditary myopathies. However, larger studies and standardized methods of reporting are needed to develop imaging as a diagnostic tool in these diseases.

  17. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    PubMed Central

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

  18. Coexposure of dioxin-like polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins and dibenzofurans in free-range hens and implications derived from congener profile analysis.

    PubMed

    Lin, Chingju; Hsu, Jing-Fang; Liao, Pao-Chi

    2012-02-29

    The consumption of free-range eggs is becoming more popular worldwide. We analyzed the levels of 12 dioxin-like polychlorinated biphenyls (dl-PCBs) and their congener profiles from 6 free-range and 12 caged egg samples. The mean levels of dl-PCBs in the free-range samples were 5.4 times higher than those in caged eggs. All egg samples exhibited at least two characteristic dl-PCB congener patterns, which reflected distinctive contamination sources. Additionally, for the first time, we demonstrated that the dl-PCB levels in the free-range eggs were highly correlated with elevated levels of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) (r = 0.986; p < 0.001), indicating a coexposure scenario in free-range hens. Cluster analysis of congener patterns implied that this coexposure scenario could be attributed to distinct dl-PCB and PCDD/F sources. This congener profile information provides insights from a different perspective for further identifying potential dl-PCB and PCDD/F sources in the polluted free-range eggs.

  19. Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007.

    PubMed

    Riehm, Julia M; Projahn, Michaela; Vogler, Amy J; Rajerison, Minoaerisoa; Andersen, Genevieve; Hall, Carina M; Zimmermann, Thomas; Soanandrasana, Rahelinirina; Andrianaivoarimanana, Voahangy; Straubinger, Reinhard K; Nottingham, Roxanne; Keim, Paul; Wagner, David M; Scholz, Holger C

    2015-06-01

    Yersinia pestis is the causative agent of human plague and is endemic in various African, Asian and American countries. In Madagascar, the disease represents a significant public health problem with hundreds of human cases a year. Unfortunately, poor infrastructure makes outbreak investigations challenging. DNA was extracted directly from 93 clinical samples from patients with a clinical diagnosis of plague in Madagascar in 2007. The extracted DNAs were then genotyped using three molecular genotyping methods, including, single nucleotide polymorphism (SNP) typing, multi-locus variable-number tandem repeat analysis (MLVA), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) analysis. These methods provided increasing resolution, respectively. The results of these analyses revealed that, in 2007, ten molecular groups, two newly described here and eight previously identified, were responsible for causing human plague in geographically distinct areas of Madagascar. Plague in Madagascar is caused by numerous distinct types of Y. pestis. Genotyping method choice should be based upon the discriminatory power needed, expense, and available data for any desired comparisons. We conclude that genotyping should be a standard tool used in epidemiological investigations of plague outbreaks.

  20. Windowed multitaper correlation analysis of multimodal brain monitoring parameters.

    PubMed

    Faltermeier, Rupert; Proescholdt, Martin A; Bele, Sylvia; Brawanski, Alexander

    2015-01-01

    Although multimodal monitoring sets the standard in daily practice of neurocritical care, problem-oriented analysis tools to interpret the huge amount of data are lacking. Recently a mathematical model was presented that simulates the cerebral perfusion and oxygen supply in case of a severe head trauma, predicting the appearance of distinct correlations between arterial blood pressure and intracranial pressure. In this study we present a set of mathematical tools that reliably detect the predicted correlations in data recorded at a neurocritical care unit. The time resolved correlations will be identified by a windowing technique combined with Fourier-based coherence calculations. The phasing of the data is detected by means of Hilbert phase difference within the above mentioned windows. A statistical testing method is introduced that allows tuning the parameters of the windowing method in such a way that a predefined accuracy is reached. With this method the data of fifteen patients were examined in which we found the predicted correlation in each patient. Additionally it could be shown that the occurrence of a distinct correlation parameter, called scp, represents a predictive value of high quality for the patients outcome.

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